PALLADIUM MEDIATED SYNTHESIS OF METALLODENDRIMERS BASED ON DIAZINE AND TRIAZINE
M. PHIL THESIS
SUBMITTED IN THE PARTIAL FULFILMENT OF THE
REQUIREMENT FOR THE DEGREE OF MASTER OF PHILOSOPHY
(M. PHIL) IN CHEMISTRY
Submitted by--
MD. SAYEDUL ISLAM
Student No.: 0413033112 F
Registration No.: 0413033112
Session: April, 2013
ORGANIC CHEMISTRY RESEARCH LABORATORY
DEPARTMENT OF CHEMISTRY
BANGLADESH UNIVERSITY OF ENGINEERING AND TECHNOLOGY
(BUET)
DHAKA-1000, BANGLADESH
MAY, 2016
DEDICATED
TO
MY PARENTS
DEPARTMENT OF CHEMISTRY
BANGLADESH UNIVERSITY OF ENGINEERING AND TECHNOLOGY
(BUET)
DHAKA-1000, BANGLADESH
Candidate’s Declaration
It is hereby declared that this thesis or any part of it has not been submitted
elsewhere for the award of any degree or diploma.
Date: 25/05/2016
Signature of the Student
Sayedul
(Md. Sayedul Islam)
Student No.: 0413033112 F
Reg. No.: 0413033112
Session: April, 2013
Acknowledgment
All praise and admiration for almighty Allah, the most kind and merciful who has enabled me
in carrying out the research work presented in this dissertation.
I am extremely delighted to express my deepest gratitude and sincere thanks to my respected
advisor & supervisor Dr. Md. Wahab Khan, Professor, Department of Chemistry, BUET,
Dhaka for his scholastic supervision, friendly co-operation, valuable suggestions and
constructive criticisms in the entire period of this research work.
I feel myself very much fortunate to express my gratitude and thanks to all of my respected
teachers of the Chemistry department, BUET: Dr. Md. Rafique Ullah, Dr. Md. Nazrul Islam,
Dr. Md. Abdur Rashid, Dr. Nazrul Islam, Dr. Shakila Rahman, Dr. Md. Manwarul Islam, Dr.
Md. Shakhawat Hossain Firoz, Mrs. Dina Nasrin, Dr. Abu Bin Imran, Mr. Md. Elius Hossain
and Mr. Md. Abu Hasan Howlader for their whole-hearted co-operation and plentiful help at
the different stages of my research work.
I desire to offer my pleasant thanks to BUET for economical support to take NMR, Mass, SEM
and EDX of my synthesized compounds.
I would like to extend thanks to my senior lab mates Md. Ashraful Alam, Shakir, Laila,
Dilruba, Tazine, Nixon, Shohag and Ismail for their co-operation in the laboratory. I convey my
thanks to all of staffs of the chemistry dept., BUET for their kind co-operation.
Finally, I would like to extend my special thanks to my father Md. Akhtar Hossain and
relatives for their untiring inspiration and contribution in my entire career.
Author
(Md. Sayedul Islam)
Contents
Pages
Abstract of research work
i
Abbreviations
ii-iii
Chapter 1: Introduction
1-38
1.1
Dendrimers: an overview
1
1.2
Historical perspective
3
1.3
Synthetic Strategies
4
1.4
General Characteristics
6
1.5.1 Dendrimers Synthesized by a Divergent Strategy
7
1.5.2 Dendrimers Synthesized by a Convergent Strategy
9
1.5.3 Applications and Recent Trends
12
1.5.4 Dendrimer Templates
14
1.6
17
Metallodendrimer
1.6.1 Structure
17
1.7
31-38
Aplication of metallodendrimer
Chapter 2: Results and Discussion
2.
39-68
Present work: Synthesis & characterization of Palladium mediated metallodendrimer
compounds based on diazine and triazine.
2.1
Rationale
39
2.2.1 Synthesis of 2,4,6-Tris (di-amido)-1,3,5-triazine Palladium(II) chloride 8-12
with tables.
40-42
2.2.2 Synthesis of 2,4,6-Tris (di-amido)-1,5-triazine Palladium(II) chloride 13-17
with tables.
2.3
Mechanism of the reactions
46
2.4
Characterization
2.4.1 Characterization of 2,4,6-Tris (di-4-methylbenzamido)-1,3,5-triazine palladium(II)
Chloride 8
2.4.2
Characterization
47
of
2,4,6-Tris(di-4-chlorobenzamido)-1,3,5-triazine
chloride 9
palladium(II)
48
2.4.3 Characterization of 2,4,6-Tris(di-4-methoxybenzamido)-1,3,5-triazine palladium(II)
chloride 10
49
2.4.4 Characterization of 2,4,6-Tris(di-4-benzamido)-1,3,5-triazine palladium(II) chloride 11
50
2.4.5
Characterization
of
2,4,6-Tris(di-4-nitrobenzamido)-1,3,5-triazine
chloride 12
2.4.6
Characterization
palladium(II)
51
of
2,4,6-Tris
(di-4-methylbenzamido)-1,5-diazine
chloride 13
Palladium(II)
52
2.4.7 Characterization of 2,4,6-Tris (di-4-chlorobenzamido)-1,5-diazine Palladium(II) chloride
14
53
2.4.8 Characterization of 2,4,6-Tris (di-4-methoxybenzamido)-1,5-diazine Palladium(II)
Chloride 15
54
2.4.9 Characterization of 2,4,6-Tris (di -benzamido)-1,5-diazine palladium(II)
chloride 16
55
2.4.10 Characterization of 2,4,6-Tris (di-4-nitrobenzamido)-1,5-diazine palladium(II)
2.5
Chloride 17
56
Scanning Electron Microscopic (SEM) and EDX analysis
57-68
2.5.1 SEM images and EDX spectrum of compound 2,4,6-Tris(di-4-methylbenzamido)-1,3,5triazine palladium(II) chloride 8
58-59
2.5.1 SEM images and EDX of compound of 2,4,6-Tris(di-4-chlorobenzamido)-1,3,5triazine palladium(II) chloride 9
60-62
2.5.3 SEM images of compound of 2,4,6-Tris(di-4 methylbenzamido)-1,5-diazine palladium(II)
chloride 13
63-64
2.5.4 SEM images and EDX of compound 2,4,6-Tris(di-4 chlorobenzamido)-1,5-diazine
palladium(II) chloride 14
65-68
Chapter 3: Experimental Data
69-79
3.
69
3.1
General Experimental
Synthesis of 2,4,6-Tris(di-4-methylbenzamido)-1,3,5-triazine palladium(II) chloride 8
69
3.2 Synthesis of 2,4,6-Tris(di-4-chlorobenzamido)-1,3,5-triazine palladium(II) chloride 9
71
3.3 Synthesis of 2,4,6-Tris(4-methoxybenzamido)-1,3,5-triazine palladium(II) chloride 10
72
3.4 Synthesis of 2,4,6-Tris(di-benzamido)-1,3,5-triazine palladium(II) chloride 11 73
3.5 Synthesis of 2,4,6-Tris(di-4-nitrobenzamido)-1,3,5-triazine palladium(II) chloride 12
74
3.6 Synthesis of 2,4,6-Tris(di-4-methylbenzamido)-1,5-diazine Palladium(II) chloride 13
75
3.7 Synthesis of 2,4,6-Tris(di-4-chlorobenzamido)-1,5-diazine Palladium(II) chloride 14
76
3.8 Synthesis of 2,4,6-Tris(4-methoxybenzamido)-1,5-diazine palladium(II) chloride 15
77
3.9
Synthesis of 2,4,6-Tris(di-benzamido)-1,5-diazine palladium(II) chloride 16
78
3.10 Synthesis of 2,4,6-Tris(di-4-nitrobenzamido)-1,5-diazine palladium(II) chloride 17
79
Chapter 4: Different spectra of synthesized compounds
80-95
Conclusion
96
References
97-103
Abstract
In the light of past and recent developments, there is precedence for the development of new
bioorganometallic metallodendrimers. Dendrimers and Metallodendrimers are highly branched,
globular, multivalent, monodisperse molecules with synthetic versatility and many possible
applications ranging from catalysis to electronics and drug delivery. Due to versatile applications
it was planned to develop a method to synthesis palladium mediated metallodendrimer molecules
based on Triazine and Diazine.
Firstly, a convenient method for the synthesis of metallodendrimer compounds 8-17 was
developed from the reaction of triazine (melamine) and diazine (pyrimidine) with different
aroylchlorides 3-7 in the presence of (Ph3P)2PdCl2 at room temperature as shown in Scheme1.
Cl
Pd
O
NH2
O
R
C R
C
N
H2 N
N
1-2
N
(Ph3P)2PdCl2
X
Cl
RCOCl
NH2
3--7
DMF / DMSO / Neat
r.t, 6-7 h
N
R
C
O
Cl
Pd
R
X
N
N
C
O
C
O
N
C
O
Cl
Scheme 1
Cl
Pd
Cl
R
R
8-12, 13-17
1, 8-12, X=N; 2, 13-17, X=CH; 3, 8, 13, R= C6H4CH3(p); 4, 9, 14, R= C6H4Cl(p); 5, 10, 15, R=
C6H5; 6, 11, 16, R= C6H4OCH3(p); 7, 12, 17, R= C6H4NO2(p)
All the synthesized compounds were characterized by analytical data obtained from IR spectra,
1
H NMR, 13C NMR and Mass spectrophotometry to establish the structure. The SEM was taken
for the analysis of surface morphology of the synthesized compounds. EDX was also taken for
metal investigation as well as elemental analysis. The compounds were found having a
homogeneous as well as non-homogeneous morphology with the particle size range from 100
µm to 500 nm.
I
LIST OF ABBREVIATIONS
Ac
acetyl
aq.
Aqueous
b.p.
Boiling point
br
broad
d
doublet
dec.
Decomposition
DMF
N, N-dimethyl formamide
equiv.
Equivalent
Et
ethyl
Et2O
diethyl ether
EDX
Energy Dispersive X-ray spectroscopy
EtOAc
ethyl acetate
h
hour
hv
light
Hz
hertz
IR
infrared (spectrum)
J
coupling constant
m
multiplet or medium
M
mass or metal
min
minutes
mmol
mili mole
mol
mole
mol %
mole percent
m. p.
Melting point
NMR
nuclear magnetic resonance
OAc
acetate
Ph
phenyl
II
PhH
benzene
ppm
parts per million
quin.
Quintet
r.t.
Room temperature
SEM
Scanning Electron Microscope
s
singlet/ strong/ second
t
triplet
T
temperature
TLC
thin layer chromatography
TMS
trimethylsilane
UV
ultra-violet
W
weak
Δ
heat/ reflux
δH/ δc
chemical shift
λmax
ultraviolet absorption in nm
νmax
infrared absorption in cm-1
III
Introduction:
1.1 Dendrimers: an overview:
Dendrimers (from the Greek, dendron: tree, branch, meros: part) are defined as highly branched
monodispersed three dimensional macromolecules obtained by an iterative sequence of reaction
steps1a-f. Large dendrimers tend to adopt a globular shape1g-j. Chemists' attraction towards
dendrimers is attributed to the precisely defined molecular and almost perfect structures they
exhibit when compared to conventional polymers. In addition, dendrimers and linear polymers
present considerable differences in their physical properties2, 3. For example, dendrimers have
demonstrated a different solubility pattern when compared with their linear counter parts
2, 4-7
.
Convention a linear polymers are two dimensional, randomly coiled chains typically containing
two reactive chain ends. Dendrimers feature a large number of functional groups at the periphery
and internal cavities that can host guests of different sizes 8 a, c.
Dendritic and metallodendritic polymers are unique “ball shaped” polymeric substance, whose
molecular architecture consists of an initial core and repeating units with branching and terminal
groups. Each repeating units bears a branching point to which two or several new repeating units
are attached. Owing to their unique properties such as solubility in water, well defined molecular
architecture, and spherical shape, dendrimers and metallodendrimers have found numerous
applications in chemical, physical and biological processes.9-11
Recently, metallodendrimers have been widely investigated in different fields, such as molecular
light harvesting, catalysts, liquid crystals, molecular encapsulation, and drug delivery.12 In the case
of poly(amidoamine) (PAMAM) dendrimers the initiator core is an ammonia or ethylenediamine
(EDA) molecule. Ammonia has three and EDA has four possible binding sites for amidoamine
repeating units. The primary amino groups are on the surface of molecule two new branches may
be attached to each of them13.
Metallodendrimer compounds have been prepared via click chemistry, employing,14 thiolene
reactions15 and azide-alkyne reactions.16-18 Compounds containing S-triazine and dendrimers based
on triazine have received a remarkable attention owing to their potential applications and have
shown molecular recognition and self-assembly properties.19 Dendrimers are a class of regularly
branched mono-dispersed polymer having 5-10 nanometers in diameter with unique structural and
1
topological features whose properties are attracting considerable interest from both scientists and
technologists.20 Dendrimers are just in between molecular chemistry and polymer chemistry. They
pertain to the molecular chemistry world by virtue of their step by step controlled synthesis, and
they pertain to the polymer world because of their repetitive structure made of monomers. Unlike
classical polymers, dendrimers have a high degree of molecular uniformity, narrow molecular
weight distribution, specific size and shape characteristics, and a highly-functionalized terminal
surface. Dendrimer oligonucleotide are representative of a new segment of polymer science, often
been referred to as the “Polymers of the 21st century”.21
Dendrimers are precisely defined, synthetic nonmaterial‟s that are approximately 5-10 nanometers
in diameter. Dendritic polymers or dendrimers provide a route to create very well-defined
nanostructures suitable for drug solubilization applications, delivery of DNA and oligonucletide,
targeting drug at specific receptor site, and ability to act as carrier for the development of drug
delivery system.
Dendrimers are core-shell nanostructures with precise architecture and low polydispersity, which
are synthesized in a layer-by-layer fashion (expressed in „generations‟) around a core unit,
resulting in high level of control over size, branching points and surface functionality. The ability
to tailor dendrimer properties to therapeutic needs makes them ideal carriers for small molecule
drugs and biomolecules. Dendrimers are being considered as additives in several routes of
administration, including intravenous, oral, transdermal, pulmonary and ocular.22
Metallodendrimers,23 i.e. dendrimers that contain metal atoms or cations, constitute a special class
of dendrimer whose redox
24
, catalytic25, ion recognition26, sensor
27
, and light harvesting
28,
properties are well documented. Other advantages of these dendritic catalysts have been
demonstrated and are described in the review by ven Leeuwen29. Dendritic encapsulation of
functional molecules allows for the isolation of the active site, a structure that mimics that of
active sites in biomaterials.30, 31, 32 Also, it is possible to make dendrimers water soluble, unlike
most polymers, by functionalizing their outer shell with charged species or other hydrophilic
groups. Other controllable properties of dendrimers include toxicity, crystallinity, tecto-dendrimer
formation, and chirality. The active catalytic centre in a metallodendrimer can be situated in three
different areas: (a) metal atom as the dendrimer core, (b) metal atoms in the dendrimer branches
2
(c) metal atoms in the periphery. Diazine and Triazine core is more electrons withdrawing and
possesses a larger nucleophilic susceptibility than the benzene core. These cores might also have
interesting physical properties. The symmetry and electronic properties of the diazine core and the
triazine core have made them valuable molecular skeleton for exploring a wide range of
interesting applications such as antitumor agent and catalytic supports
33
. But the facile and
efficient methods for the synthesis of metallodendrimer still remain scarce.
1.2 Historical perspective:
As depicted in the book of Newkome, Moorefield and Vogtle34, Dendrimers
and
Dendron‟s:
Concepts, Syntheses, Applications, the development of the dendrimer Chemistry can be broken
down into three different periods. The first can be defined as roughly from the late 1880's to the
early 1940's. At that time it was believed that Branched structures lead to in soluble and intractable
materials. However, means of separation as well as characterization were too primitive to lead to
relevant conclusions. Nonetheless, Zincke35 and Friedel and Crafts36 (1885) were already
speculating on Polymers adopting non-linear or branched connectivity. In 1922, Ingold and
Nickolls37 reported the preparation of the branched "methanetetraacetic acid". This work is still
considered as the earliest case of deliberately constructed dendritic structure.
The second period covers four decades, from the early 1940's to the late 1970's. This period is
defined by the incredible amount of work generated to prepare branched structures .The main
piece of work covering this subject is attributed to Flory38 who introduced an alternative approach
to polymer synthesis in 1952. Macromolecules generated using this synthetic strategy, were
anticipated to be highly branched, entanglement-free and non-crystalline, with broad molecular
weight distributions. He reported the preparation of a highly branched polymer, employing an
AB2-type monomer, without "insoluble gel formation". The third period began in the late 1970's
and still continues. however, much of the work in this area only began to build
momentum in the mid-1980s. A chronology of the key developments in dendritic polymers is
provided in the following table
3
Year
Type
Authors
Cascade growth and dendrimers
1978
Vögtle39
1982
Maciejewski40
1983
de Gennes41
1985
Tomalia,42 Newkome43
1990
Fréchet/Hawker,44 Miller/Neenan45
Random hyperbranched polymers
Odian/Tomalia46
1988
1990
47
Kim/Webster
Fréchet/Hawker48
1991
Dendrigraft polymers
1991
49
Möller,
Gauthier,50Hedstrand/Ferritto, Tomalia51
1.3 Synthetic Strategies:
The strictly controlled structure of ideal dendrimers results from the layered assembly of branch
cells surrounding the core, which is attained through sequential reaction cycles. This can be
achieved in two different ways, namely by divergent (core-first) or convergent (arm-first/corelast) methods.
The divergent approach begins with a multifunctional core onto which polyfunctional monomers
of the ABn-type are added. Dendrimers result when the branching multiplicity (subscriptn) of the
monomer unit is at least 2. Following the addition of these small molecule building blocks, the
4
subsequent
layer can be added after deprotection of the end groups
and
another
monomer
condensation reaction. The structure resulting after the first addition cycle is known as a
generation-1(G1) dendrimer. Further reaction cycles are employed to prepare dendrimers of the
desired generation, size, or molecular weight.
The convergent approach uses monomers similar to the divergent strategy and provides branched
molecules with the same characteristics and predictability; however, wedge like dendrons are first
synthesized and subsequently anchored on a core to complet the dendritic structure. The number
of dendrons that can be coupled with a core is governe by the core functionality. Convergent
growth of the dendron occurs through selective protection of one of the functional groups
followed
by
a
condensation
reaction, resulting in
directional
growth.
The
dendron
unit is interesting in itself, and it has been investigated as its own entity, but deprotection
and coupling with a multifunctional “anchor” core is required to complete the dendrimer structure.
Scheme 1.1 Synthesis of a G2 dendrimer by (a) divergent and (b) convergent strategies.
The divergent synthesis (Scheme 1.1a) begins with an unprotected trifunctional
initiating
core
(Nc=3). The G0 core can be coupled with a partially protected monomer, BA2(P)2, having a
branching multiplicity(Nb) of 2. The G1 dendrimer results after removal of the protecting group
on the A functionality(-PA). Coupling of this substrate with the protected monomer yields what is
referred to as a half-generation dendrimer(G1.5), and the G2 dendrimer is obtained upon
deprotection. The convergent synthesis starts by coupling a partially protected monomer, B(P)A2,
with a complementary protected monomer, BA2(P)2, to yield a dendron. Deprotection of the B
5
group(-PB) at the focal point of the dendron allows selective coupling with the G0 core(A3) to
obtain the G1.5 dendrimer. Deprotection of the terminal a functionalities provides the G2
dendrimer.
1.4 General Characteristics:
A graphical comparison of the structure of dendrons, dendrimers, hyperbranched polymers, and
dendrigraft polymers is provided in Figure 1.1.
Figure 1.1 Structure of four types of dendritic polymers: (a) Dendron, (b) dendrimer,
(c) hyperbranched polymer, and (d) dendrigraft polymer.
Each color in Figure 1.1 represents the branching levels derived from building blocks introduced
in
successive
generations,
these
being small molecules for dendrons,
dendrimers,
and
hyperbranched polymers (Figure 1.1( a – c), and polymeric segments for the dendrigraft polymers
(Figure 1.1d). The size, shape, and molecular weight of a dendrimer depend on the molecular
weight
and
the
branching
multiplicity of the monomer,
as well as its generation number.
Molecular weights can range from the hundreds or thousands for low generations, to over 105
g/mol for generations 10 and above the corresponding diameterof these structures ranges from ca.1
to above 10 nm. Different generations of dendrimers derived from a trifunctional core are
compared in Scheme 1.2.
Scheme 1.2 Dendrimer generations derived from a trifunctional core and a monomer with a
branching multiplicity of 2
6
The three-dimensional topology of dendrimers displays a transition from ellipsoidal to spherical
for increasing generations.52 The onset of the morphogenesis is reliant on the core multiplicity and
the synthetic strategy (divergent or convergent) used. Increased core multiplicity (Nc = 3 or 4 vs.
Nc = 2) forces a shape change at least one generation earlier. The convergent method has a similar
effect due to the more perfect structure (increased crowding) attained for a particular generation.
The most significant transformations occur between generations 3 and 5, after which the dendritic
species adopt either spheroidal or slightly ellipsoidal geometries. An increase in generation
number also brings enhanced surface group congestion, until a maximum known as
the dense packing state is reached. Beyond this point only a fraction of the end-groups can
participate in the next cycle of monomer addition. Targeting a specific molecular weight and
number of functional groups in dendrimer synthesis is relatively easy due to the uniform structure
of the molecules, in as much as complete reactions are possible.
1.5 Common Structures:
1.5.1 Dendrimers Synthesized by a Divergent Strategy
The
concept
of branched macromolecules
derived from repetitive reaction cycles of
multifunctional small molecules was first introduced in 1978.53 Vögtle thus reported a cascadetype divergent synthesis for low molecular weight polypropylenimine by the cyanoethylation of
various amines cited in Reference 53, using acrylonitrile in glacial acetic acid at reflux for 24 h.
Subsequent reduction of the cyanofunctionalities with cobalt(II) chloride hexahydrate and NaBH4
in methanol converted the terminal cyanoethyl groups to primary propylamine functionalities,
which were subjected to further cyanoethylation and reduction reactions to obtain the upper
generation cascade polymers.
The yield of the cyanoethylation and reduction reactions in Vögtle‟ s work was less than ideal,
varying from 76 % for the zeroth generation to 35 % for the G1 product. These low yields resulted
in ill-defined structures and prevented the synthesis of the upper generation structures. This
procedure was nevertheless improved upon in the early 1990s after optimizing the cyanoethylation
and hydrogenation reactions, by working in aqueous solutions at 80°C and through hydrogenation
with Raney cobalt, respectively.54, 55 In this case diaminobutane (DAB) served as multifunctional
core to generate DAB-dendr-(CN)x and DAB dendr-(NH2)x dendrimers after the cyanoethylation
7
and hydrogenation reactions respectively. Their action sequence for the divergent synthesis of
poly-propylenimine dendrimers is shown in Scheme 1.3
Scheme 1.3 Preparation of polypropylenimine dendrimers
Polyamidoamine (PAMAM) dendrimers, synthesized subsequently, are likely the most widely
investigated and used dendritic polymers to date. The first dendrimers commercialized in that
family were the Starburst® systems. These species were developed in the mid1980s by Tomalia,56
at about the same time when Newkome developed similar dendritic architectures named
Arborols.57 A major incentive for development of these molecules was the creation of covalently
bonded (unimolecular) micelles comparable to the well-known multi-or intermolecular micellar
systems.
PAMAM dendrimers are versatile in that their terminal groups can be easily modified for targeted
functionality or reactivity. These compounds are synthesized by the condensation of amines and
acrylates. An initiating core containing one or more amine functionalities is first reacted with an
excess of methyl acrylate, resulting in an alkyl ester branch addition at each amino hydrogen. This
ester-terminated product is referred to as the G0.5 dendrimer. Amidation of the ester with
ethylenediamine (EDA) causes branch extension with terminal amino groups. This amineterminated dendrimer is referred to as a G1 PAMAM dendrimer. Repetitive cycles of Michael
addition of the acrylate ester and amidation with EDA leads to successive generations of
dendrimers. Functional group modification chemistry can also be performed on the terminal ester
or amine groups. Thus treatment of the half-generation (ester-terminated) PAMAM dendrimers
with alkali metal hydroxides yields carboxylate functionalities
8
Scheme 1.4 Divergent PAMAM dendrimer synthesis starting from a diamine (EDA) core.
1.5.2 Dendrimers Synthesized by a Convergent Strategy
Hawker
and Fréchet made a major contribution to the dendritic polymer chemistry field by
developing
a
convergent approach to dendrimer synthesis in 1990.58
Dendritic fragments
(dendrons) of benzylether were thus created by coupling phenols with benzylic halides. This
approach represents a surface-to-core method, where the monomers are assembled from the
peripheral units towards the core. Benzyl bromide was first coupled with dihydroxybenzyl
alcohol (DHBA) in the presence of potassium carbonate and 18-crown-6 as a phase transfer
catalyst in acetone as shown in scheme 1.5
9
Scheme 1.5 Synthesis of a Fréchet benzyl ether dendrimer by a convergent approach
Following isolation and purification of the product, the G1 dendritic benzyl alcohol was converted
to a benzylic bromide by treatment with carbon tetrabromide and triphenyl phosphine. Further
cycles of DHBA monomer coupling were performed to obtain subsequent dendron generations. To
obtain a symmetrical dendrimer, the dendritic wedges carrying a bromide functionality at their
focal point can be coupled with a polyfunctional core such as l,l,l-tris (4′-hydroxypheny1) ethane.
A
convergent strategy such as this, with only one final coupling step for the dendron
wedge
facilitates high yield reactions leading to well-defined structures. The symmetry of the molecules
can be controlled through the functionality of the anchoring core.
10
In
fact Newkome was really the first one to report a convergent dendron synthesis for
preparation
of
arborols,
but the generation number and the molecular weight attained
the
were
limited.59 The synthesis of arborols started from a trifunctional branch cell formed by treating an
alkyl halide with triethyl sodium methanetricarboxylate. Subsequent reduction of the ester with
LiAlH4 yielded a triol. The formation of the second tier through another cycle of esterification was
attempted
by
tosylation
with
tosyl
chloride
in
pyridine
and treatment
with
the
methylsodiumtriester, but the yield was very low due to inefficient nucleophilic attack at the three
terminal sites as a result of steric crowding. To solve this issue, extension of the ester was
performed prior to tosylation and coupling with the methylsodium trimester to afford the
nonaester. The third generation of this cascade molecule, obtained through amide functionalization
with tris (hydroxyl methyl) aminomethane was completely water-soluble. The reaction scheme for
Newkome‟ s synthesis of a 27-arm arborol is shown in Scheme 1.6
Scheme 1.6 Arborol synthesis according to Newkome
11
1.5.3 Applications and Recent Trends:
Considering the extensive control achieved over the size, shape, and surface functionality of
dendrimers, it is not surprising that these molecules have a wide range of potential applications.
Upon examination of the structural features of a dendrimer, one can visualize sector specific uses
as shown in Figure 1.5.3A.
Figure 1.2 Structural features and potential uses of dendrimers.60
The first application examined, and one of the primary motivations for dendrimer syntheses, was
asunimolecular micelles. In contrast to common micellar structures formed through intermolecular
association or aggregation, dendrimers are covalently bonded structures unaffected by their
surrounding environment. Consequently, the ability of amphiphilic dendrimers to encapsulate
guest compounds should be independent of changes in concentration, solvent, and pH, among
others. A strong incentive for dendrimer micelles is in catalysis. Considering the structure and
functionality control attained, catalytic sites can be introduced specifically within the core, on the
periphery of dendrimers, or both, as illustrated in Figure 1.3
Figure 1.3 Internal (a) and peripheral (b) dendrimer functionalization
12
The preparation of metallodendrimers, incorporating metallic species within their structure is a
relatively facile process given the ease and versatility of dendrimer functionalization which can be
tailored for metal coordination. For example, the PAMAM dendrimers discussed earlier can
coordinate different transition metals through their nitrogen atoms. Metals able to coordinate with
the PAMAM structure include among others Cu,
61, 62
Au,
63
Pd,64 Pt,65 Ag,66 Co,67 as well as
bimetallic systems such as Pd-Au68 and Pt-Ru.69 Dendritic catalyst selectivity, activity, and
stability can vary on the basis of steric effects, the location of the catalyst, and the architecture of
the dendritic support.70, 71
Coronal
functionalization of the dendrimers with metals is typically performed by a
divergent
approach, i.e. with the metal binding process occurring in the final step. Catalysis on the periphery
of dendrimers provides easily accessible sites; however, steric crowding of the reactants can
influence
the
activity
level
observed. In theory, such a system should have a
performance
comparable to homogeneous (non-supported) systems.72, 73
Examples of peripherally functionalized catalysts include carbosilane dendrimers with Ni at their
peripheral functional sites serving in the Kharasch addition of polyhalogenoalkanes to terminal
carbon-carbon double bonds, which displayed regioselectivity.74 Polypropyl enimine dendrimers
have likewise been end-functionalized with palladium, rhodium, iridium, and Pd-Ni bimetallic
catalysts for use in the Heck reaction and hydro formylation.75 Polyamidoamine dendrimers
supported on silica were complexed with rhodium for heterogeneous catalysis in the
hydroformylation of styrene and various other olefins. The highly active catalyst yielded branched
chain aldehydes with high selectivity from aryl olefins and vinyl esters. The catalyst was easily
recovered, and no significant loss in selectivity or activity was observed upon reuse.76
Core-functionalized metallodendrimer catalysts are sometimes referred to as
dendrizymes‟
by
analogy to biological systems and due to the observed influence of the generation number on
selectivity. Ferrocenyldiphosphine core-functionalized carbosilane dendrimers have thus been
prepared as Pd ligands for the homogeneous catalysis of allylic alkylation reactions, and displayed
variations in product selectivity for the largest dendrimers investigated.77 Fréchet-type polyether
dendrons were complexed with Pt for use as SO2 sensor, and with Ni for the Kharasch addition of
CCl4 to methyl methacrylate.78 The Dendron wedges, when functionalized at their focal point,
13
displayed adequate catalytic activity with easy recovery and good stability. Mimicking
biological species is a major investigation area for dendrimers, particularly for PAMAM-based
structures due to their similarities in size, shape, and chemical make-up with globular proteins.
Thus the immunodiagnostic capabilities of dendrimers have been investigated79 as well as in vitro
and in vivo gene delivery80 and gene expression.81 These species possess an exterior barrier
controlled through end-group functionalization, as well as void spaces within their interior, much
like liposomes. The tailored unimoleular micelle characteristics of dendrimers, with an open
interior (in contrast to typical micelles), allows them to entrap guest molecules of various sizes
and to selectively release them under certain conditions.82 These characteristics have led to the
development of macromolecular drug delivery systems from dendrimers. In analogy to other
complexation processes, drug molecules can be loaded inside or attached at the periphery of the
molecules, to form dendrimer-drug conjugates. In the latter category, it has been demonstrated that
PAMAM dendrimer palatinate conjugates have anti-tumor activity.83 More recently, it was shown
that the encapsulation or complexation of camptothecin (a plant alkaloid known for its anti-cancer
potency) with PAMAM dendrimers increased its solubility, which represents a step towards the
effective delivery of this drug to cancerous cells.84 PAMAM dendrimer–glucosamine conjugates
have even been shown to prevent scar tissue formation.85 Lastly, dendrimers have been
investigated for light-harvesting applications.86
1.5.4 Dendrimer Templates
Polyamidoamine(PAMAM) dendrimers were among the first dendritic macromolecules
synthesized and are likely the most widely used dendritic molecules to this day.87,
88
PAMAM
dendrimers offer ample opportunities for chemical functionalization given the reactivity of the
amine-based building blocks used in their synthesis. Illustrated in Figure 1.4 is the branched
architecture of a generation (G1) PAMAM dendrimer containing various amine and oxygen
functionalities available for the coordination of various metal loading of PAMAM molecules with
metals has been accomplished by various researchers, some of which will be described herein.
This includes PAMAM dendrimers functionalized with different functional groups, or coupled
with polymer segments to create larger templates.
14
Figure 1.4 Illustration of G1 PAMAM architecture and sites available for meta coordination.
Crooks89 and Tomalia90 both investigated the loading and reduction of copper salt within PAMAM
dendrimer
scaffolds. Crooks loaded both amine-
and hydroxyl-terminated
(G4)
PAMAM
dendrimers (G4-NH2 and G4-OH respectively) with Cu2+ using CuSO4, and reduced the salt to
Cu0 with NaBH4. It was observed that aqueous solutions of Cu-loaded G4- OH were stable in the
absence of oxygen, showing no agglomeration or precipitation. The size of the Cu nanoparticles
was dependent on the template characteristics. As binding only occurred within the dendrimer
core,
91
the copper nanoclusters were well shielded from each other and from the aqueous
environment, resulting in soluble unmolecular micelles.
TEM analysis and UV-Vis spectroscopy both revealed ultra-fine copper particles less than 2 nm in
diameter. Intradendrimer copper clusters larger than 5 nm should exhibit a Mieplasmon resonance
peak around 590 nm in UV-Vis analysis,
92
but this was not observed for the G4-OH Cu0 system.
For the loaded G4-NH2 template, in contrast, a plasmon peak was evident after Cu2+ reduction.
This was attributed to copper complexation with the NH2-functionalized corona of the dendrimers
and Cu0 agglomeration into larger clusters on the exterior of the dendrimer after reduction.
Tomalia found similar results in his work: Extremely stable copper-loaded PAMAM dendrimers
were obtained in both aqueous and methanolic environments. Specifically, Tomalia examined
copper(II)-acetate loading and its reduction with hydrazine in PAMAM dendrimers capped with
TRIS[tris-(2-hydroxymethyl)
methyl, (CH2OH)3], amino (NH2), or
pivalate
[NHCOC(CH3)3]
functionalities. Most samples lacked plasmon resonance in the 590 nm region, with the exception
of the TRIS-capped dendrimers for which a small increase in plasmon resonance was observed
after21 h.The PAMAM structure is not limited to copper loading, as many metallic
nanoparticles
have been successfully templated including Au,93 Pd,94 Pt,95 Ag,96 Co,97 and bimetallic particles of
Pd-Au,98 and Pt-Ru.99 The images shown in Figure 1.5.4B are typical for the size, shape, and
distribution of metal within dendrimer templates. PAMAM dendrimers can be loaded at various
15
levels relative to the number of coordinating amine sites, which depends on the 6th generation
number of the dendrimer used. Thus Figure 1.5 corresponds to a G4 PAMAM dendrimer endfunctionalized with hydroxyl groups and loaded with either 40 or 60 atoms per dendrimer (Figure
1.5(a) and Figure 1.5(b), respectively). The diameter of these nanoparticles was reported to be 1.4
± 0.2 nm and 1.6 ± 0.2 nm, respectively. Figure 1.5(c) depicts dendrimers loaded with 40 atoms
of Pd, having a diameter of 1.3 ± 0.2 nm.
Figure 1.5 TEM images for G4 PAMAM-OH loaded with (a) 40 atoms of Pt, (b) 60 atoms of Pt,
and (c) 40 atoms of Pd.68
PAMAM dendrimers can also serve as precursors for the synthesis of much larger
and higher
molecular weight polymers by using the terminal end groups on the periphery of the dendrimers
for coupling reactions. For example, vinylsulfonyl(VS) end-functionalized poly(ethylene glycol),
PEG-VS,
was
coupled with PAMAM dendrimers having amine end
groups
via
Michael
addition.100 The star-branched dendrimer-linear polymer hybrid obtained has a core-shell
morphology and the ability to house materials within its core, while the polymer chains in the
corona helped to stabilize the molecules in solvents. Metal loading into PAMAM-PEG dendrimerstar polymers was illustrated by the same group.101 The dendrimer core was thus used to template
the deposition of Cd(NO2)3·4H2O in methanol before its reaction with Na2S·9H2O. Zero-valent
gold was also formed within the core of these dendrimer hybrids by loading HAuCl4·H2O and
reduction with NaBH4 in aqueous solution. The synthesis of the hybrid dendrimers and metal
loading within their core is shown in Scheme 1.7
Scheme 1.7 Synthesis and metal loading of PAMAM-PEG dendrimer-star polymer
16
1.6 Metallodendrimer
A Metallodendrimer is a type of dendrimer with incorporated metal atoms. The development of
this type of material is actively pursued in academia.102, 103, 104
Figure 1.6: Ferrocene containing dendrimer
1.6.1 Structure
The metal can be situated in the repeat unit, the core or at the extremities as end-group. Elements
often encountered are palladium and platinum. These metals can form octahedral six-coordinate
M(IV) linking units from organic dihalides and the corresponding 4-coordinate M(II) monomers.
Ferrocene-containing dendrimers and dendrimers with cobaltocene and arylchromiumtricarbonyl
units have been reported in end-functional dendrimers. Metallodendrimers can form as metal
complexes with dendritic counter ions for example by hydrolysis of ester terminated PAMAM
dendrimers with sodium hydroxide.
More recently, a number of dendrimers based on metal complexes have been synthesized105. Metal
complexes are characterized by a precise molecular geometry related to the characteristic
17
coordination number of the metal ion and can exhibit valuable properties such as absorption of
visible light, luminescence andreduction and oxidation at low potentials. By using metal
complexes it is possible to incorporate in the dendritic structure specific pieces of information‟
that, when placed in suitable sites of the array, can be used to perform valuable functions. From a
structural view point, most of the metal-containing dendrimers can be classified according to four
categories:
(i) dendrimers built around a metal complex as a core;
(ii) dendrimers containing metal complexes as peripheral units;
(iii) dendrimers containing metal complexes in the branches;
(iv) dendrimers based on metals as branching centers106;
Exmples
of dendrimers synthesized by Balzani and coworkers
107
, shows in some case some
complexes assembly architectures containing polypyridine metal complexes like Ru and Os. The
design of such plynuclear metal complexes capable of exhibiting interesting photo physical and
electrochemical
properties.
Using polypyridine
ligands like 2,3-dpp and 2,5-dpp as bridging
ligands(dpp=bis(2-pyridyl)pyrazine), Ru(II) and Os(II) as metal centers, complexes-as-metals and
complexes-as-ligands synthetic strategy107,108, Balzani has prepared a series of homo- and
heterometallicdi-109, tri-110, tetra-111,112, hexa-113,114, hepta-115, deca-116, trideca-117, and
docosanuclear118
complexes. Such complexes, which have a dendrimer-type structure
are very
interesting because depending on the number and location of the metal and the ligand components,
predetermined energy migration (Fig I-36 right) and redox patterns (Fig I.6a) can be obtained119.
The use of this kind of dendrimers as molecular-level antennas to harvest sunlight has been
recently reviewed 120.
18
Fig 1.7
Schematic view of the structure of a decanuclear complex containing Ru and Os
ions
2,2’:6’,2”-terpyridine complexes
The 2,2´:6´,2´´terpyridine ligands have very
Interesting chemical properties due to the possible
linearfonctionalisation at the 4´-position121,127.
In the course to synthesise
are
scale,
potential
the
molecules
molecular-wire
useful
of
which
at
nano
4´-substituted
tpy ligand is a great interest
because
the
bridging spacer formed after
complexing with transition metal can have a linear geometry. However that is not the case with the
2,2´-bipyridine ligands which have
geometries,
several problems when used for devices with well-defined
and after complexation and formation of heteroleptic
complexes,
the
problem
ofenantiomer formation appears. Octahedral complexes [M(tpy)3] 2+ are achiral and the
substitution
in 4´- position does not generates enantiomers
According
the definition
of
Constable,128 metallostars are first generation metallodendrimers and it is convenient to consider
19
them
as a separate class
128
because the majority of
compounds
of
this
class
have
been specifically prepared as first-generation species without the structural development of the
ligands that would be required for the separation of a dendrimer. In the literature, the distinction
between metallostars and metallodendrimers is not usually clearly made series of heptanuclear
metallostars based upon central {M(bpy)3} motifs and bearing pendant {M‟(tpy)2} units has been
prepared by Constable and co-workers making extensive use of the reactions of coordinated
bpy and tpy ligands. In a convergent approach, the complex (Fig I.6b) was obtained by the
reaction of 4, 4‟-(HO)2 bpy with [Ru(tpy)(tpy-Cl)]2+.
Fig 1.8 Geometrical representation of dinuclear complexes containing bpy ligand and tpy
ligand
The inherent chirality of the {M(bpy)3} motif is a disadvantage when it comes to multinuclear
compounds
are
used
as these will be formed as mixtures of diastereoisomers unless special conditions
to
optimize stereospecificity. In contrast, {M(tpy)2} units linked through the 4´-
position are achiral and are an ideal motif for the linear extension of achiral metallostars
Fig 1.9 Octadecanuclear Ru(II) terpyridine based metallostar129, 130.
20
Multiinuclear oligopyridine complexes are important in metallosupramolecular chemistry and
species such as rods or wires, helicates and dendrimers are well established. The investigation of
photo induced energy- and electron-transfer (Metal-to-Ligand) in geometrically well defined ploynuclear
systems allows the electronic and nuclear factors governing these
investigated.
processee to
The exploitation of the spectroscopic (particularly luminescence)
be
properties of
transition metal-oligopyridine complexes for ion sensing, light harvesting or energy collection
using high-nuclearity dendrimers is of intense current interest 131,132
131, 132
Fig 1.10 Photoinduced energy transfer through a Ru-Os Y shaped metallostar
1,4,8,11-Tetraazacyclotetradecane (cyclam), which is one of the most extensively investigated
ligands in coordination chemistry, in its protonated forms can play the role of host towards cyanide
metal complexes. Balzani and Vögtle133 have investigated the acid-driven adducts formed in
acetonitrile dichloromethane solution between [Ru(bpy)(CN)4]2- and 1,4,8,11-tetrakis (naphthyl
methyl) cyclam and a dendrimer consisting of a cyclam core appended with 1,2,3,5 dimethoxy
benzene and 16 naphtyl unit (Fig 1.11)-[Ru(bpy)(CN)4]2-, with the two cyclamic ligands exhibiting
characteristic absorption and emission bands that are strongly affected by addition of acid.
21
2-
Fig 1.11 Structure of [Ru(bpy)(CN)4] complex and of two cyclam-cored dendrimers
Schem 1.8 Representation of the formation of the [Ru(bpy)(CN)4]2-(Cyclam) adduct
22
1.7 Aplication of metallodendrimer
1.7.1 Aplication of metallodendrimer with focus on Cancer:
Cancer
is a class of disease characterized by uncontrolled cell proliferation (i.e. undergoing
cell
division
beyond
and
the
normal limits) and the ability of these cells to invade adjacent tissue,
sometimes spreading to other locations of the body via blood or lymph. The main types of cancers
(based on mortality rate) are lung, stomach, colorectal, liver and breast cancer. These cancers can be
treated by several methods such as surgery, radiotherapy and most importantly chemotherapy, which
is the main treatment of this disease. Chemotherapy is the treatment of cancer with anticancer drugs
that target and destroy cancer cells. In the last decade, a revolution in cancer treatment has been
presented by organometallic chemists.134, 135
1.7.1a The Use of Metals as Therapeutic Agents
Forthe last 25 years medicinal inorganic chemistry was a new and unexplored field.However, research
has flourished following the success of platinum-based anticancer agents.136 In addition to metalbased therapies, the efficacy of organic drugs can be improved by combining them with metals.136
1.7.1b Platinum Anticancer Agents
The therapeutic properties of cis-diamminedichloridoplatinum(II)(cis-[Pt(NH3)2Cl2, cisplatin) was
accidently discovered by Barnett Rosenberg,137,
138
in the late 1960s, whilst he was investigating the
influence of an electric field on the growth of Escherichia coli bacteria. Cisplatin was in fact first
synthesized by Michele Peyrone139 in 1844 and was known as Peyrone‟s chloride. More than a
century later it became the first metal-containing anticancer drug.Today, cisplatin is FDA approved,
and is used in the treatment of a wide range of tumors,140 in particular ovarian141,
142
and testicular
cancers.143, 144 Cisplatin is also used in combination therapy of many other solid tumors, such as head,
neck, bladder and small cell lung cancers.145 Analogs of cisplatin (i.e. carboplatin and oxaliplatin),
have shown great effectiveness as second-generation drugs.146 Oxaliplatin is currently a „billiondollar‟ drug, primarily used to treat colorectal cancer.147
23
Farrell and co-workers synthesized a Pt-based trinuclear complex with the general formula [trans,
trans, trans-(NH3)2-Pt(Cl)(CH2)6NH2Pt(NH3)2NH2(CH2)6NH2Pt-(NH3)2(Cl)][NO3]4 (BBR3464, Figure
1.12) which showed potent in vitro toxicity over cisplatin and its mononuclear analog.148 BBR3464
was claimed as the first platinum-based drug with a DNA binding mode different to cisplatin.149
Though Phase II trials of BBR3464 were not pursued further,149 the concept of multinuclearity
may assist in the improvement of the activity of potential therapeutic agents.
Figure 1.12 Structure of the trinuclear Pt-based anticancer agent, BBR3464.148
The clinical successes of platinum-based therapies tend to be overlooked due to the severe toxic sideeffects and drug-resistance of these complexes.149, 150 To overcome these limitations researchers have
moved their attention to compounds incorporating other metals.136
1.7.1c Titanium Anticancer Agents
There have been two TiIV complexes explored as anticancer agents, both entered clinical trials in the
1990s. The first is a tris-acetylacetonate derivative called Budotitane (Figure 1.13)151 and the second,
titanocene dichloride [(η5-C5H5)2TiCl2].152 Both complexes are similar in structure to cisplatin, with
both containing two labile chloride ligands. Though the rate hydrolysis of these Ti-complexes is much
faster than cisplatin, it did however lead to complications. Bound water is more acidic, which lead
to the formation of hydroxo-bridged species, which in turn lead to toxic TiO2 and hence did not
complete Phase I clinical trials.153,
154
Titanocene dichloride had more success than Budotitane,
with the completion of Phase I and II clinical trials; however it was abandoned.155
24
Titanocene dichloride was not approved for clinical use since it did not show significant advantages
over current drugs on the market. The poor water solubility and low hydrolytic stability hampered its
development.153, 154
Figure 1.13 Structures of Ti-based anticancer agents: Budotitane
Toaid in stability of the Ti-based complexes, ansa derivatives of titanocene dichloride were developed
(Figure 1.14)153 and some complexes were active against 36 human tumor cell lines.157 However, he
hydrolytic stability of the complexes remained a problem, hence an alternative approach was taken.
The dichloride ligands of the ansa derivatives were replaced with an oxalate ligand, generating bis[(pmethoxybenzyl)cyclopentadienyl]-titanium(IV)
oxalate (oxali
titanocene
Y,
Figure
1.14)
which was found to be twice as potent as cisplatin towards pig kidney epithelial (LLC-PK) cells158
and demonstrated favorable pharmacokinetic properties.
Fig.1.14 Structures of dichloride titanocene derivative (left) and oxalititanocene Y (right).156, 158
25
1.7.1d Gallium Anticancer Agents
There are only a handful of gallium-based complexes used as anticancer agents,159 namely Ganite®
(galliumnitrate complex),159 KP46 [tris(8-quinlinolato)gallium (III)]160 and GaM (galliummaltolate),
tris(3-hydroxy-2-methyl-4H-pyran-4onato)gallium)161 (Figure1.15). Ganite® is FDA approved, and
used to treat cancer-related hypercalcemia, however the drug has poor bioavailability.159 KP46 is an
orally bioavailable drug, which has been through Phase I clinical trials for the treatment of solid
tumors via S-phase cell cycle and apoptosis.160 Though not redox active under biological conditions,
Ga(III) has similar chemistry to Fe(III) and can be transported to cells via the Fe(III) transport system
(bound to serum protein transferrin).162
Figure 1.15 Structures of KP46 (left) and GaM (right).160, 161
1.7.1e Tin Anticancer Agents
SnIVcomplexes have become very attractive as therapeutic agents because of their attractive properties
such as, increased water solubility, lower general toxicity than Pt-based drugs, better body clearance,
fewer side-effects163 and most importantly does not develop drug resistance.164, 165
Recently, a tributyl complex tri-n-butyltin(IV)lupinylsulfide hydrogen flumarate (IST-FE 35, Figure
1.16), displayed inhibition of the implanted tumors (p388 myelomonocytic leukemia and B16-F10
melanoma) in BDF1 mice.166, 167 Following a single dose of the drug, IST-FE 168 reduced the tumor
volume by 96 % at day 11.166, 167
26
Figure 1.17 Structure of SnIV anticancer complex, IST-FS 35.166, 167
Other examples of a Sn-based antitumor agents, are the trigonal-bipyrimidal anionic tin(IV)
complexes recently synthesized by Kaluderovic,168 namely, triphenyltin(IV) chlorides containing Nphthaloyl-L-glycine(P-Gly), N-phthaloyl-L-alanine(P-AlaH), and 1, 2, 4-benzenetricarboxylic 1, 2anhydride(BTCH), were tested against a series of cancer cell lines. The Sn-based complexes displayed
high activity in the cancer cell lines, with some of the complexes displaying IC50 values lower
than cisplatin. The most active complex of the series (50 times more potent than cisplatin) was the
organotin complex, triethylammonium(N-phthaloylglycinato)triphenyltin(IV) chloride [SnPh3(PGly)Cl] and was found to induce apoptosis via extrinsic pathways on DLD-1 cancer cells.168 Other
metals have been used in the pursuit of potential therapeutic agents, such as gold169 arsenic,170
copper,171 zinc,172 bismuth,173 molybdenum.174 However, ruthenium-based complexes have shown the
most promise as anticancer agents.175
1.7.1f Ruthenium(III) Anticancer Agents
Soon after the discovery of the cytotoxic effects of platinum-based drugs, ruthenium compounds were
investigated as potential therapeutic agents. As an alternative to platinum, ruthenium has shown
favorable
properties
and conditions to form the basis for anticancer drug
design.13
Moreover
ruthenium is less toxic than platinum, with its biological activity attributed to its ability to mimic the
behavior of iron, and bind to biomolecules, such as human serum albumin and transferrin.176 Two
inorganic Ru(III) complexes, [ImH][transRu(DMSO)(Im)Cl4] (NAMI-A, where Im=imidazole )177-179
and [IndH][trans-Ru(Ind)2Cl4](KP1019, where Ind=indazole)180-182 (Figure 1.18) are currently
undergoing Phase II clinical trials.
27
Figure1.18
Ru(III)-anticancer compounds, NAMI-A (left) and KP1019 (right), currently
undergoing clinical trials.
NAMI-A, synthesized by Gianni Sava, is a tetrachlorido imidazole/DMSO-Ru(III) compound,
and
was the first of the two RuIII complexes to enter clinical trials. NAMI-A, was found to be inactive
during initial in vitro testing. However, in vivo testing showed that the drug inhibits matrix metalloproteinases and prevents metastases (tumor growth)179 with little impact on primary tumors in animal
models.178
KP1019, developed by Bernhard Keppler, is administered intravenously and hence binds initially to
proteins in the blood stream. In fact, following cellular uptake of KP1019, it was primarily found
bound to proteins (i.e. albumin and transferrin) and on DNA in peripheral leukocytes.181 The sideeffects seen with platinum-based anticancer agents were related to their binding to serum proteins,
while KP1019 binds to transferrin, an important step in its mode of action, as it aids in the transport
into the cell via the transition pathway.180, 183, 184
In recent years the focus on Ru(III) complexes has shifted towards the development of Ru(II)
complexes, as in both cases (i.e. NAMI-A and KP1019) the active drug is considered a Ru(II) species.
Moreover, the Ru(III)
agents are
activated‟ upon entering the cancerous cell, by
reduction
to
the Ru(II) species which coordinate more rapidly to biomolecules. 185, 186
28
1.7.1g Ruthenium(II) Compounds as Anticancer Agents
Ru(III)-based anticancer drugs such as NAMI-A, KP1019 and their derivatives, pioneered as
alternatives
to Pt-based
therapeutic agents. However, with the +2 oxidation state proposed as
the
active ruthenium species, several investigations into the development of Ru (II) compounds as
anticancer agents have been pursued.187-189
1.7.1h Organometallic Ruthenium-Based Antitumor Compounds
In organometallic complexes, it is the metal-carbon bond which endows these coordination complexes
with
their
unique
properties. The lability of the metal-ligand bond can greatly be
by the presence of metal-carbon
bonds,
as
these complexes have high trans-effects
influenced
and
trans-
influences. Moreover, the π-bonded arene and cyclopentadienyl (Cp) ligands can act as both electron
donors and π-acceptors.
Similarly to Ru(III) complexes, Ru(II) complexes have been extensively studied as anticancer
agents.187-189 The most widely studied organoruthenium compounds are the ruthenium-arene and
ruthenium-cyclopentadienyl half-sandwich compounds, also referred to as „piano-stool‟ complexes.190
The term „piano-stool‟ is derived from
the
orientation
of the coordinating
ligands
around
the metal centre. All these pseudo-octahedral complexes have either a Cp (η5) or arene (η6) ring
(i.e. the „seat‟ of the „piano-stool‟), and coordinating ligands (i.e. the „legs‟
of the
„piano-stool‟).
There are three forms of binding in which the coordinating ligands can coordinate around the d6 metal
[Ru(II), Os(II), Ir(III) or Rh(III)].
Depending
on the nature of the ligand, binding can occur in a monodentate (Z), bidentate(X-Y)
or
tridentate (X-Y-Z) manner, in-turn generating neutral or charged (isolated as salts) complexes. The
different types of coordinating ligands (X, Y, Z and arene/Cp) dictate the reactivity (labile or inert) of
the complexes. The π-donor ability of the arene/Cp ligand protect the metal centre from oxidation.1
The first half-sandwich organoruthenium antitumor agent was 1-β hydroxyethyl-2-methyl-5-nitro
imidazole (metronidazole) coordinated to a
ruthenium(II)-benzene
dichlorido moiety.
The
Ru-
complex is more active in vitro than its base-ligand, metronidazole.191
29
1.7.1i Multinuclear Ruthenium-Arene Compounds as Anticancer Agents
The trinuclear Pt-based anticancer agent, BBR3464, is 2-6 orders of magnitude more active
than
cisplatin in cisplatin-resistant cell lines.192 Hence, the use of multinuclear complexes as potential
therapeutic agents has since been considered.
In order to improve the activity of the ruthenium-arene complexes, Keppler and co-workers,
synthesized water-soluble dinuclear ruthenium-arene complexes, based on 3-hydroxy-2- methyl
pyridinone with varied alkyl spacers (Figure 1.19).193 The dinuclear ruthenium-arene complexes were
compared against Pt-based antitumor agents (i.e. cisplatin, carboplatin and oxaliplatin), in a series
of human tumor cell lines.193 In particular, one of the dinuclear complexes has similar activity to
oxaliplatin, with the mononuclear derivative (Figure 1.19) inactive in the same cell line.
Figure 1.19
complexes
dinuclear (with varying
spacer lengths, right)
ruthenium-arene
antitumor
193
Stringer et al. prepared a series of mononuclear and dinuclear ruthenium-arene complexes based on
benzaldehydethiosemicarbazone (Figure 1.20).194 The thiosemicarbazone moiety is known for its
potent enzyme inhibition (in particular ribonucleotide reductase) and is capable of interrupting DNA
replication.195 The dinuclear complex showed enhanced biological activity (IC50=8.96 μM) in the
oesophageal cancer cell line (WHCO1), over its mononuclear derivative (IC50 >200 μM,
WHCO1).194
30
Figure 1.20 Ruthenium-arene thiosemicarbazone-based antitumor agents, mononuclear and
dinuclear.194
A tetranuclear ruthenium-arene complex with general formula [(p-cymene)4Ru4 (R1)Cl6]Cl2 (where
R1=1,2-bis(di-N-methylimidazol-2-ylphosphine)ethane) was prepared by Noffke and
co-workers
(Figure 1.21).196 However, the cytotoxicity of the complexes are poor in several cancer cell lines
(Hct116, Huh7, H411E and A2780 cells).
Figure 1.21 novel tetranuclear ruthenium-arene complex synthesized by Noffke et al.196
31
1.7.1j Ferrocene in Cancer Research
Ferrocene was first discovered in 1951,197,198 however the structure was elucidated afterwards
independently by Wilkinson, Fischer and Pfab.199,
200
The benzene inspired
name
„ferrocene‟
was coined by Woodword and co-workers in 1952.201 Scientists wasted no time in developing new
strategies in synthesizing ferrocene and its derivatives.202 Owing to its ease of functionalization
and favorable electronic properties, a wide range applications for these sandwich complexes were
explored.203 Stability of ferrocene in aqueous and aerobic media, the large variety of
derivatives and the favorable electronic properties made ferrocene and its derivatives attractive as
potential biological agents.204,205
1.7.1k Ferrocene in Medicine: With Focus on Ferrocenyl-Based Derivatives asTherapeutic Agents
Many ferrocenyl compounds display good in vivo or in vitro activity as antitumor,206, antimalarial,207
antifungal208 and antiretroviral (ARV)209 agents, and show DNA-cleavage activity.210 Brynes et al.
reported the first ferrocene-based anticancer complex in the late 1970s, with the compounds bearing
amine or amide groups tested against leukemia P-388 cells.210 The ferrocenyl-derived compounds
were administered to mice and the activity of these complexes were low but showed an improvement
compared to the starting ligand.211 This report clearly suggests, the incorporation of ferrocene into an
appropriate biomolecule or
carrier
molecule,
could provide
the
compound
with
enhanced
anticancer activity.
Jaouen and co-workers developed a series of ferrocenyl derivatives and studied their activity in cancer
cells.212 The ferrocenyl derivatives, called ferrocifens (Figure 1.22), were derived from the anticancer
drug tamoxifen (Figure 1.22), where one of the phenyl rings was replaced with ferrocene moiety.
Derivatives of the active metabolite, hydroxytamoxifen (Figure 1.22) were also synthesized and
the antiproliferative activity of these ferrocenyl derivatives investigated against breast cancer cells
(MCF-7, hormone independent and MDA-MB231, hormone dependent).213 The ferrocifens exhibited
strong biological activity in both cell lines, though some were comparable to hydroxyl-tamoxifen,
others were slightly better. The authors attribute the activity to the greater lipophilicity of
ferrocifens and the cytotoxicity induced by the redox-active ferrocene moiety. Furthermore, these
results show that ferrocifens are the first molecules to show activity in both hormone-dependent and
hormone-independent human breast cancer lines.214
32
Figure 1.22
Structures of parent drugs tamoxifen and hydroxytamoxifen
ferrocenyl-based derivatives, ferrocifens (right).
(left)
and
the
213, 214
The extended π-system plays an important role on the mode of action of the ferrocenyl-derived
anticancer agents, with authors reporting a correlation between cytotoxicity and electron transfer
capacity of these complexes.215 The mode of action is said to originate from a series of redox
processes on the ferrocenyl moiety, which results in the generation of reactive oxygen species
(ROS).215
It has been shown that tethering the ferrocenyl moiety onto biologically active compounds increases
their potency. The increase in activity has been attributed to the combined action of the organic drug
and the Fenton chemistry of the Fe centre.216
1.7.1l Heterometallic and Multinuclear Ferrocenyl-Derived Anticancer Agents
Ferrocene has been linked to both platinum121-124 gold125 and ruthenium126, 127 in an effort to achieve a
synergistic effect between the two biologically active centres. Nieto and co-workers synthesized a
series of heterometallic Pt(II) compounds with β-aminoethylferrocenes. The compounds were tested
against four cancer cell lines (HBL-100 (breast), HeLa (cervix), SW1573 (lung), WiDr (colon)). One
of the β-aminoethylferrocenes-Pt(II) compounds (Figure 1.23) displayed good cytotoxicity in all four
cell lines (IC50=1.7 - 2.3 μM), with activity in the colon cancer cell line better than the benchmark
drug (cisplatin).
33
Figure 1.23 Structure of heterometallic Pt(II)-compound with β aminoethylferrocenes.123
Recently, Dyson and co-workers prepared heterometallicphosphinoferroceneamino conjugates,
incorporating
show
the biologically active ruthenium-arene moiety (Figure 1.24).126
moderate to good in vitro antitumor activity towards both the sensitive
These systems
and
cisplatin
126
resistanthuman ovarian cancer cell lines (A2780, IC50=4.1 μM; A2780cisR, IC50 = 6.9 μM).
Figure
1.24
conjugate.126
Structure
of heterometallic ruthenium-arene
phosphinoferroceneamino
1.7.2 Metallodendrimers: Metal Decorated Dendrimers for Oncology
The term metallodendrimers is derived from the name given to metal functionalized highly branched
macromolecules known as dendrimers. The term dendrimer is built from the Greek words “dendros”
meaning tree, and “meros” meaning part. These complex macromolecules have well defined shape,
are highly branched and are built from a central core.178 compared to linear polymers, dendrimers can
be synthesized reproducibly with low polydispersity, which is a highly discernible feature for drug
delivery agents. A wide range of functionalities can be included throughout the dendritic framework
(on the periphery, at the core or interspersed which give them a wide range of applications in
medicinal chemistry, 179, 180 host-guest chemistry181, 182.
34
1.7.3 Applications of Metallodendrimers: With Focus on Nanomedicine
The well-defined and ordered molecular structure of dendrimers and their unique properties such as
the high density and highly flexible design, the reactivity of the functional groups on the periphery, as
well as the possible aqueous solubility and low toxicity offers dendrimer applications in a variety of
fields. These fields include catalysis,183-185 biosensors,196,
imaging,199 and nanomedicine.179,
180
197
adhesives,198 magnetic resonance
Moreover in catalysis, the catalytically active complex can be
located throughout the dendritc framework.178 The multinuclearity approach affords greater
activity and efficiency of the the concept of multinuclearity could lead to improved activity of
metallodrugs. Hence, another application of metallodendrimers is the delivery of drugs. Several
approaches have been used:
i. physical encapsulation of the drugs into the void spaces (drawbacks, fast and
uncontrolled
delivery of drugs)
ii. electrostatic binding between the ionic peripheral groups of the dendrimer and the drug
iii. hydrogen bonding between the peripheral functional groups and the drug
iv. and covalent linkage of the drug to the dendritic periphery or surface
(known as the pro-drug approach)
Notably, in nanomedicine, the concept of multinuclearity can be applied to improve the
potency
of
chemotherapeutic drugs. By exploiting the enhanced permeability and retention effect (EPR effect)
dendrimers can be used to selectively target drug-targets.
The EPR effect is a phenomenon in which macromolecules (such as metallodendrimers), can exploit
the physiological patterns of solid tumors (Figure 1.25). Metallodendrimers can accumulate at the
tumor site due to an increase in blood vessel permeability (porous endothelial layer) within the
cancerous cells over healthy tissues.203, 204. The healthy endothelial layer surrounding blood vessels,
restricts the size of molecules that can diffuse from the blood stream into the cells. In contrast, the
endothelial layer of cancerous tissues is more porous, providing access to the surrounding tissue.
Furthermore, diseased tissues have an impaired lymphatic drainage system, thus once macromolecules
have entered the cancerous site they are retained for longer periods (increase in bio-availability). A
tetraruthenium cluster is highly active against the polio virus, without effecting healthy cells.
35
Figure
1.25
Illustration showing the
diffusion
of
explained by the phenomenon known as the EPR effect.
The use
metallodendrimer into the tumor site,
203, 204
of dendrimers in the field of medicine is highly developed, with a number of
dendrimer
conjugates reported.205-207 However, the use of metallodrugs conjugated to dendritic frameworks is
sparse, with only a handful of reports as antitumor agents 180, 187 or antimalarial agents.208
Following the successes of cisplatin and its analogs, in particular the trinuclear Pt-based complex
(BBR3464) mentioned earlier.15 Researchers have pursued the idea of functionalizing metallodrugs
onto dendritic scaffolds in an effort to improve the activity of the metallodrug. There are only a
handful of metallodendrimer specifically developed to target cancerous cells and are highlighted in
a recent review.180
It should come to no surprise that the first metallodendrimer synthesized to target cancer cells, was a
tetranuclear Pt-based compound..209 The platinum-functionalized metallodendrimer DAB(PA-tPt-Cl)4
(where DAB=diaminobutane, PA=polyamine) is based on the first-generation poly(propylene) (PPI)
dendritic scaffold.
The Pt-metallodendrimer was synthesized to overcome problems associated with cisplatin resistance
in cancer cells:
i. Deactivation of the Pt-species by intracellular thiolates and
ii. Improved repair of crosslinks with DNA.
36
With the severe side-effects of platinum-based drugs,
17
researchers shifted their attention to other
metals. Hence, Zhao and co-workers synthesized tetranuclear (Pt-based) and hexanuclear (Cu-based)
PAMAM
(Figure 1.26), with the biological
metallodendrimers
activity of
these
complexes
investigated (in cisplatin-sensitive, MOLT-4, and cisplatin-resistant, MCF-7, breast cancer cells).210
Figure 1.26 Structure of G1tetranuclearPt-(left) and Cu-functionalized (right)
metallodendrimer. 210
The ligands showed no activity against the cancer cells, whilst the multinuclear complexes
showed
enhanced activity over their mononuclear derivatives. Moreover, the copper analogs displayed greater
activity to their platinum analogs, with the authors attributing the low toxicity of the Pt-complexes
to poor
solubility in the
testing medium
and ability of the
complexes to self-assemble
(seen
through SEM experiments).210
Stability of anticancer agents in solution is a key aspect before consideration for biological
clinical
applications.
Rodrigues and co-workers monitored the degradation and stability
and
of low
generation ruthenium-based poly (alkylideneamine)-nitrile metallodendrimers (Figure 1.27) by
31
P-
NMR spectroscopy. The metallodendrimers containing the [Ru (Cp)(PPh3)2]+ moiety was unstable at
physiological
temperature,
as
there
is
a release of the Ru half-
sandwich. However,
the
metallodendrimer containing the [Ru (dppe)2Cl]+ is stable over 4 h in solution, revealing the potential
of the complexes for biological applications.
37
Figure 1.27 Structure of poly(alkylideneamine)-nitrile metallodendrimer functionalized with
[Ru(dppe)2Cl]+ or [Ru(Cp)(PPh3)2]+.211
Metallodendrimers have also shown promise as potential photodynamic therapy (PDT)agents,
with the synthesis of a 32-armed rutheniumpolypyridyl functionalized PAMAM metallodendrimer,
by Velders and co-workers.212 The positively charged derivative shows promise as a PDT agent,
whilst the negatively charged derivative shows promise for diagnostic fluorescence assays
Figure 1.28 A positively and negatively charged PAMAM polypyridylruthenium metallo
dendrimer.212
38
2. Present work: Synthesis & characterization of Palladium mediated metallodendrimer
compounds based on diazine and triazine.
2.1 Rationale:
Dendrimers, which are highly branched macromolecules that emanate from a central core with a welldefined
structure, have attracted considerable attention from a
fundamental viewpoint and
their
development is rapidly expanding in many applications (e.g., OLEDs, sensors, and lasers).
The incorporation of transition metals or lanthanides into dendritic macromolecules leads to a new
class of materials called “metallodendrimers”.
The active catalytic centre in a metallodendrimer can be situated in three different areas: (i) metal
atom as the dendrimer core; (ii) metal atoms in the dendrimer branches; (iii) metal atoms in the
periphery. The synthesis of the third type of metallodendrimer may be envisaged by two strategies.
Firstly, it is possible to build the dendrimer and then incorporate the metal atoms in the final stage or,
secondly, the metal atoms can be incorporated within the molecular fragments used to build the
dendrimer. Regardless of the choice of route, it is necessary to obtain appropriate dendrons that have
the ability to coordinate the catalytically active metal atom.
Research
on metallodendrimers has received significant attention in recent years owing,
in part, to
their potential applications in homogenous catalysis, sensing and light harvesting.
Metallodendrimer compounds have been prepared via click chemistry, employing Diels-Alder
reactions, thiol-ene reactions and azide-alkyne reactions. Compounds containing S-triazine and
dendrimers based on triazine have received a remarkable attention owing to their potential
applications and have shown molecular recognition and self-assembly properties.
In view of remarkable importance of dendrimer and metallodendrimer compounds in the field of
biological and medicinal chemistry and metal mediated approaches still remain scarce for their
synthesis. The aim of the present study was to synthesize dendrimer and metallodendrimer based on
diazine and triazine. It is planned to develop a simple and efficient method for the synthesis of
metallodendrimer compounds from the reaction of triazine and diazine with different aroylchlorides at
variable temperatures in presence of bis-triphenylphosphine palladium(II) chloride. It is expected that
the synthesized compounds would be biologically active and they might be used as an intermediate
products and catalyst for the synthesis of heterocyclic compounds as well as drugs. It might also be
applicable in chemical, physical and biological processes.
39
2.2 Results and Discussion:
2.2.1 Synthesis of 2,4,6-Tris (di-amido)-1,3,5-triazine Palladium(II) chloride 8-12
The compounds, 8-12 were synthesized by treating melamine with different aroylchlorides in
the presence of (Ph3P)2PdCl2 in different solvents at room temperature for 6-7 hours as shown
in Scheme 2.1 and Table 1
Cl
Pd
O
NH2
O
R
C R
C
N
H2 N
N
N
(Ph3P)2PdCl2
N
Cl
RCOCl
NH2
3-7
DMF / DMSO / Neat
r.t, 6-7 h
1
N
R
C
O
Cl
Pd
Cl
R
N
O
N
N
C
8-12
R
C
O
C
O
N
Cl
Pd
Cl
R
3-7
3, 8 R= C6H4CH3(p)
4, 9 R= C6H4Cl(p)
5, 10 R= C6H4OCH3(p)
6, 11 R= C6H5
7, 12 R= C6H4NO2(p)
40
Table 1:
Sl.
No
Substrate
Reagents and
conditions
Products
(8-12)
Cl
1
NH2
N
N
H 3C
O
Cl
328330
CH3
Yield
%
90
O
C
CH3
C
N
H 3C
NH2
N
H2N
Pd
p-CH3C6H4COCl,
DMSO
r.t, 6-7 h
m. p.
( °C )
N
(Ph3P)2PdCl2
N
C
1
O
Cl
Pd
N
N
C
O
C
O
Cl
Pd
N
C
Cl
O
Cl
CH3
CH3
8
2
N
N
Cl
p-ClC6H4COCl,
DMSO
r.t, 6 h
NH2
Pd
Cl
O
NH2
N
Cl
310312
90
320322
95
O
Cl
C
H2N
Cl
C
N
(Ph3P)2PdCl2
Cl
N
1
N
C
O
Cl
Pd
N
N
Cl
C
O
C
O
Pd
N
C
Cl
O
Cl
Cl
Cl
9
3
N
N
Cl
p-CH3 OC6H4COCl,
DMSO
r.t, 6 h
NH2
Pd
H3CO
O
Cl
OCH3
O
C
OCH3
C
N
H2N
N
NH2
(Ph3P)2PdCl2
H3CO
N
1
N
C
O
Cl
Pd
N
N
C
C
O
C
O
N
Cl
Pd
Cl
O
Cl
OCH3
OCH3
10
41
4
C6H5COCl
DMF
r.t., 6 h,
NH2
N
N
NH2
N
H2N
Cl
Cl
Pd
O
290292
90
304306
89
O
C
C
N
(Ph3P)2PdCl2
1
N
N
C
O
Cl
Pd
N
C
O
C
O
N
N
C
Cl
Pd
Cl
O
Cl
11
5
N
N
H2N
N
Cl
p-NO2C6H4COCl,
DMSO
r.t, 6 h
NH2
NH2
Pd
O 2N
Cl
O
O
C
C
NO2
NO2
N
(Ph3P)2PdCl2
O 2N
N
1
N
C
O
Cl
Pd
N
N
C
C
O
C
O
N
Cl
Pd
Cl
O
Cl
NO2
NO2
12
N. B: Yield % was calculated on the basis of (Ph3P)2PdCl2..
42
2.2.2 Synthesis of 2,4,6-Tris(di-amido)-1,5-diazine Palladium(II) chloride 13-17
The compounds 13-17 were synthesized by treating pyrimidine (0.2 g) with different
aroylchlorides in the presence of (Ph3P)2PdCl2 in different solvents at room temperature for 6-7
hours as shown in Scheme 2.2 and Table 2.
Cl
Pd
O
NH2
O
R
C R
C
H2 N
N
(Ph3P)2PdCl2
N
Cl
RCOCl
N
NH2
3-7
DMF / DMSO / Neat
r.t, 6-7 h
2
R
C
O
Cl
Pd
Cl
R
N
O
N
N
C
13-17
R
C
O
C
O
N
Cl
Pd
Cl
R
3, 13 R= C6H4CH3(p)
4, 14 R= C6H4Cl(p)
5, 15 R= C6H4OCH3(p)
6, 16 R= C6H5
7, 17 R= C6H4NO2(p)
43
Table 2:
Sl.
No
Substrate
Reagents and
conditions
Products
(13-17)
m. p.
( °C)
Yield
%
324326
90
308310
90
315317
96
1
NH2
H
C
N
Cl
p-CH3C6H4COCl
DMSO
r.t, 6-7 h
Pd
H 3C
O
CH3
O
C
NH2
N
H2N
Cl
CH3
C
N
(Ph3P)2PdCl2
2
H 3C
N
C
O
Cl
Pd
N
N
C
O
C
O
Cl
Pd
N
C
Cl
O
Cl
CH3
CH3
13
NH2
1
C
N
Cl
Pd
Cl
NH2
N
H2N
H
p-ClC6H4COCl,
DMF
r.t., 6-7 h
Cl
O
O
C
C
Cl
Cl
N
(Ph3P)2PdCl2
Cl
N
C
O
Cl
2
Pd
N
N
Cl
C
O
C
O
Pd
N
C
Cl
O
Cl
Cl
Cl
14
NH2
2
C
N
H
Cl
p-CH3OC6H4COCl
DMSO
r.t, 6-7 h
Pd
H3CO
O
N
OCH3
O
C
H2N
Cl
OCH3
C
N
NH2
(Ph3P)2PdCl2
H3CO
N
C
O
Cl
Pd
N
N
C
C
O
C
O
N
Cl
Pd
Cl
O
Cl
2
OCH3
OCH3
15
44
NH2
3
C
N
Cl
Pd
O
NH2
N
H2N
H
C6H5COCl
DMF
r.t., 6-7 h
Cl
280282
90
305307
92
O
C
C
N
(Ph3P)2PdCl2
N
C
O
Cl
Pd
N
C
O
C
O
N
N
C
Cl
Pd
Cl
O
Cl
2
16
NH2
4
C
N
H
Cl
p-NO2C6H4COCl,
DMSO
r.t, 6-7 h
Pd
O 2N
O
H2N
NH2
NO2
O
C
N
Cl
NO2
C
N
(Ph3P)2PdCl2
O 2N
N
C
O
Cl
Pd
N
N
C
C
O
C
O
N
Cl
Pd
Cl
O
Cl
2
NO2
NO2
17
N. B: Yield % was calculated on the basis of (Ph3P)2PdCl2..
45
2.3 Mechanism of the reactions:
46
2.4 Characterization:
2.4.1 Characterization of 2,4,6-Tris(di-4-methylbenzamido)-1,3,5-triazine palladium(II)
chloride 8
The compound was synthesized from 2,4,6-triamino-1,3,5-triazine (melamine) with the reaction of
p-methyl benzoyl chloride by stirring at room temperature for 6-7 hours in the presence of
(Ph3P)2PdCl2 and solvent (DMF).
The structure of the compound was established by various spectral data.
In IR spectrum of the compound the absorption band was found at 3134.1 cm-1 due to the C-H
(aro) stretching absorption, whereas a broad band at 3085.9 cm-1 stretching absorption represents
the (C=H) aliphatic group. Absorption band at 1720.4 cm-1 display keto (C=O) group. Stretching
absorption max 1664.5, 1575.7, 1288.4 and 488.72 cm-1 stretching bands indicated the presence of
C=N, aromatic C=C,C-N and Pd-Cl respectively.
In IH NMR spectrum of compound 8, the chemical shift at H 2.46 (s, 6×3H, Ar-CH3) was found
as a singlet for the hydrogen atoms in six CH3 groups. Chemical shift at H 7.24 (d, 6×2H, Ar-H,
J=8.0 Hz) showed a doublet for aromatic protons of C -3 ́, C-5 ́ carbon of six phenyl rings and H
7.91 (d, 6×2H, Ar-H, J=8.5 Hz) showed another doublet for similar protons of C-2 ́, C-6 ́ carbon of
six phenyl rings.
In the 13C NMR spectral data of compound 8, the chemical shift  21.86 indicated the presence of
six identical carbons in six methyl groups (Ar-CH3).The chemical shift at  130.36 and 129.31 was
found for the two carbons (C-1 ́, C-4 ́) of phenyl rings. The peak at  126.71 represent aromatic
carbons of C-2 ́, C-6 ́ and carbons of C-3 ́, C-5 ́of six phenyl rings respectively. The chemical shift
at  144.75 was obtained for the carbons C-2, C-4 and C-6 of melamine ring. The chemical shift at
 172.64 was obtained for carbonyl carbon (C=O).
Mass spectrometry data indicated the proposed structure of metallodendrimer compound 8,
Positive-molecular ion mass peak (M+) 1363.08 indicated the molecular ion of the compound.
Cl
Pd
H 3C
O
Cl
CH3
O
C
CH3
C
N
H 3C
N
N
C
C
O
Cl
Pd
N
N
C
C
O
N
O
Cl
Pd
Cl
O
Cl
CH3
CH3
8
47
2.4.2 Characterization of 2,4,6-Tris(di-4-chlorobenzamido)-1,3,5-triazine palladium(II)
chloride 9
The compound was synthesized from 2,4,6-triamino-1,3,5-triazine (melamine) with the reaction of
p-chlorobenzoyl chloride by stirring at room temperature for 6-7 hours by using (Ph3P)2PdCl2 in
presence of DMSO.
The structure of the compound was established by various spectral data.
In IR spectrum of the compound , the absorption band was found at 3095.4 cm-1 due to the C-H
(aro) stretching absorption, whereas a broad band at 1683.7 cm-1 represents the keto (C=O) group.
Strong absorption band at 1593.1 cm-1 displays strong C=N stretching absorption. max 1323.1 cm1
stretching bands indicated the presence of C=C in phenyl ring and max 1093.6 cm-1 indicated the
presence of aromatic C-N stretching and strong absorption band in 761.8 and 472.92 cm-1 display
C-Cl and Pd-Cl stretching absorption.
In IH NMR spectrum of compound, chemical shift at H 7.46 (d, 6×2H, Ar-H, J=7.5 Hz) showed a
doublet for aromatic protons of C -3 ́, C-5 ́ of six phenyl rings and H 8.04 (d, 6×2H, Ar-H, J=7.0
Hz) showed another doublet for similar protons of C-2 ́, C-6 ́ carbon of six phenyl rings.
In the 13C NMR spectral data of the compound, the chemical shift at  127.0 and 128.87 was found
for the two tertiary carbons C
-1 ́and C -4 ́ of phenyl rings. The peak at  129.36 and 131.35
represent the aromatic carbons of C -2 ́, C-6 ́and C -3 ́, C-5 ó f six phenyl rings respectively. The
chemical shift at  141.47 was obtained for the carbons C-2, C-4 and C-6 of melamine ring. The
chemical shift at  161.30 was obtained for carbonyl carbon (C=O). Mass spectrometry data
indicated the proposed structures of metallodendrimers compound 9. Positive-molecular ion
mass peak (M+) 1481.58 indicated the molecular ion of the compound.
Cl
Pd
Cl
O
Cl
Cl
O
Cl
C
C
N
Cl
N
N
C
C
O
Cl
Pd
N
N
N
C
C
O
O
Cl
Pd
Cl
O
Cl
Cl
Cl
9
48
2.4.3 Characterization of 2,4,6-Tris(di-4-methoxybenzamido)-1,3,5-triazine palladium(II)
chloride 10
The compound was synthesized from 2,4,6-triamino-1,3,5-triazine (melamine) with the reaction of
p-methoxybenzoyl chloride by stirring at room temperature for 6-7 hours in the presence of
(Ph3P)2PdCl2 and solvent (DMF).
The structure of the compound was established by various spectral data
In IR spectrum of the compound the absorption band was found at 3014.5 cm -1 due to the C-H
(aro) stretching absorption, whereas a broad band at 2984.85 cm-1 stretching absorption represents
the (C=H) aliphatic group. Absorption band at 16083.91 cm-1 display keto (C=O) group.
Stretching absorption max 1304.84, 1288.4 and 1027.13 cm-1 stretching bands indicated the
presence of C=N, aromatic C=C and C-N respectively.
In IH NMR spectrum of compound 10, the chemical shift at H 3.79 ppm (s, 6×3H, Ar-OCH3) was
found as a singlet for the hydrogen atoms in six -OCH3 groups. Chemical shift at H 6.99 ppm (
m, 6×2H, Ph-H) showed a doublet for aromatic protons of C -3 ́, C-5 ́ carbon of six phenyl rings
and H 7.923 ppm ( 6×2H, Ph-H) showed another doublet for similar protons of C-2 ́, C-6 ́ carbon
of six phenyl rings.
In the
13
C NMR spectral data of compound 10, the chemical shift C 55.406 indicated the
presence of six identical carbons in six methyl groups (Ar-OCH3).The chemical shift at ), C
123.037 ppm and C 113.798 ppm was found for the two carbons (C-1 ́, C-4 ́) of phenyl rings. The
peak at C 131.355 ppm represent aromatic carbons of C-2 ́, C-6 ́ and carbons of C -3 ́, C-5 ́of six
phenyl rings respectively. The chemical shift at C 162.86 ppm was obtained for the carbons C-2,
C-4 and C-6 of melamine ring. The chemical shift at C 167.047 ppm was obtained for carbonyl
carbon (C=O).
Cl
Pd
H3CO
O
Cl
OCH3
O
C
OCH3
C
N
H3CO
N
N
C
C
O
Cl
Pd
N
N
O
N
C
C
O
Cl
Pd
Cl
O
Cl
OCH3
OCH3
10
49
2.4.4 Characterization of 2,4,6-Tris(di-4-benzamido)-1,3,5-Triazine palladium(II) chloride 11
Compound 11 was synthesized from 2,4,6-triamino-1,3,5-triazine (malamine) with the reaction of
benzoyl chloride and DMF by stirring at room temperature for 6-7 hours in presence of
(Ph3P)2PdCl2.
The structure of the compound was established by various spectral data.
In IR spectrum of compound 11, the absorption band was found at 3072.4 cm-1 due to the C-H
(aro) stretching absorption, whereas a broad band at 1683.7 cm-1 represents the keto (C=O) group.
Strong absorption band at 1675.5 cm-1 displays strong C=N stretching absorption. max 1585.4 cm1
stretching bands indicated the presence of C=C in phenyl ring and max 1294.1 cm-1 indicated the
presence of aromatic C-N stretching.
In IH NMR spectrum of compound 11, Chemical shift at H 7.45 (t, 6×2H, Ar-H, J=7.5 Hz was
found for the two carbons (C-1 ́, C-4 ́) of phenyl rings , 7.62 (t, 6×1H, Ar-H, J=6.5 Hz) showed a
doublet for aromatic protons of C -3 ́, C-5 ́ carbon of six phenyl rings and H 8.15 (d, 6×2H, Ar-H,
J=7.0 Hz) showed another doublet for similar protons of C-2 ́, C-6 ́ carbon of six phenyl rings.
In 13C NMR spectral data of compound 11, the peak at  130.34 was found for two the carbons (C1 ,́ C-4 ́) of phenyl ring chemical shift at  128.60 and  129.46 represent the aromatic carbons of
C-2 ́, C-6 ́ and carbons of C-3 ́, C-5 ́of six phenyl rings respectively. The chemical shift at  133.94
ppm was obtained for the carbons C-2, C-4 and C-6 of malamine ring and at  172.77 was
obtained for carbonyl carbon (C=O).
Cl
Pd
O
Cl
O
C
C
N
N
N
C
O
Cl
Pd
N
C
N
C
O
C
O
N
Cl
Pd
Cl
O
Cl
11
50
2.4.5
Characterization
of
2,4,6-Tris(di-4-nitrobenzamido)-1,3,5-triazine
palladium(II)
chloride 12
The compound 12 was synthesized from 2,4,6-triamino-1,3,5-triazine (malamine) with the
reaction of 4-nitrobenzoylchloride and DMF by stirring at room temperature for 6-7 hours in
presence of (Ph3P)2PdCl2.
The structure of the compound was established by various spectral data.
In IR spectrum of the compound , the absorption band was found at 3080.21 cm-1 due to the C-H
(aro) stretching absorption, whereas a broad band at 1758.10 cm-1 represents the keto (C=O)
group. Strong absorption band at 1592.13 cm-1 displays strong C=N stretching absorption. max
1322.23 cm-1 stretching bands indicated the presence of C=C in phenyl ring and max 1092.67 cm-1
indicated the presence of aromatic C-N stretching.
In IH NMR spectrum of compound, chemical shift at H 8.104 ( 6×2H, Ar-H) showed a doublet for
aromatic protons of C -3 ́, C-5 ́ of six phenyl rings and H 8.297 ppm ( 6×2H, Ph-H) showed
another doublet for similar protons of C-2 ́, C-6 ́ carbon of six phenyl rings.
In the
13
C NMR spectral data of the compound, the chemical shift at C 123.688 ppm and C
136.455 ppm was found for the two tertiary carbons C -1 ́and C-4 ́ of phenyl rings. The peak at C
130.684 ppm represent the aromatic carbons of C -2 ́, C-6 ́ and C-3 ́, C-5 ó f six phenyl rings. The
chemical shift at C 150.012 ppm was obtained for the carbons C-2, C-4 and C-6 of melamine ring.
The chemical shift at C 165.819 ppm was obtained for carbonyl carbon (C=O).
Cl
Pd
O 2N
O
Cl
NO2
O
C
NO2
C
N
O 2N
N
N
C
O
Cl
Pd
N
N
C
C
O
C
O
N
Cl
Pd
Cl
O
Cl
NO2
NO2
12
51
2.4.6
Characterization
of
2,4,6-Tris(di-4-methylbenzamido)-1,5-diazine
Palladium(II)
chloride 13
The compound 13 was synthesized from 2,4,6-triamino-1,5-diazine (pyrimidine) with reaction of
p-methyl benzoyl chloride and DMSO by stirring at room temperature for about 6-7 hours in
presence of (Ph3P)2PdCl2.
The structure of the compound was established by various spectral data.
In IR spectrum of compound 13, the absorption band was found at 3052.29 cm-1 and 2976.31 cm-1
due to the C=H (aro) and C-H (ali) stretching absorption respectively, whereas a broad band at
1710.20 cm-1 represents the keto (C=O) group. Strong absorption band at 1611.69 cm-1 displays
strong C=N stretching absorption. max 1418.69 cm-1 stretching bands indicated the presence of
C=C in phenyl ring, 468.72 and 1360.20 cm-1 indicated the presence of Pd-Cl and aromatic C-N
stretching.
In IH NMR spectrum of compound, chemical shift at H 8.104 ( 6×2H, Ar-H) showed a doublet for
aromatic protons of C -3 ́, C-5 ́ of six phenyl rings and H 8.297 ppm ( 6×2H, Ph-H) showed
another doublet for similar protons of C-2 ́, C-6 ́ carbon of six phenyl rings.
In the
13
C NMR spectral data of compound 13, the chemical shift  21.63 ppm indicated the
presence of carbons in three methyl groups (Ar-CH3). The chemical shift at  131.28 ppm and 
129.71 ppm was found for two tertiary carbons (C-1 ́, C-4 ́) of phenyl rings. The peak at  130.50
ppm represents the aromatic carbons of C -2 ́, C-6 ́ and carbons of C -3 ́, C-5 ó f six phenyl rings
respectively. The chemical shift at  144.63 ppm was obtained for the carbons C-2, C-3, C-4 and
C-6 of pyrimidine ring and  172.33 ppm was obtained for carbonyl carbon (C=O).
Mass spectrometry data indicated the proposed structure of metallodendrimer compound, 13.
Positive-molecular ion mass peak (M+) 1369.44 indicated the molecular ion of the compound.
Cl
Pd
H 3C
O
Cl
CH3
O
C
CH3
C
N
H 3C
N
C
C
O
Cl
Pd
N
N
C
C
O
N
O
Cl
Pd
Cl
O
Cl
CH3
CH3
13
52
2.4.7
Characterization
of
2,4,6-Tris(di-4-chlorobenzamido)-1,5-diazine
palladium(II)
chloride 14
The compound 14 was synthesized from 2,4,6-triamino-1,5-diazine (pyrimidine) with reaction of
p-chlorobenzoyl chloride in presence of solvent DMSO by stirring at room temperature for about
6-7 hours in presence of (Ph3P)2PdCl2.
The structure of the compound was established by various spectral data.
In IR spectrum of compound 14, the absorption band was found at 3094.89(s) cm-1 due to the C=H
(aro) stretching absorption, whereas a broad band at 1620.20 cm-1 represents the keto (C=O)
group. Strong absorption band at 1592.29(s) cm-1 displays strong C=N stretching absorption. max
1424.48(m-w) cm-1 stretching bands indicated the presence of C=C in phenyl ring, max 1092.71(s)
and 460 cm-1 indicated the presence of aromatic C-N and Pd-Cl stretching.
In IH NMR spectrum of compound 14, chemical shift at H 8.01 ppm (d, 6×2H, Ar-H) showed a
doublet for aromatic protons of C -3 ́, C-5 ́ of six phenyl rings and H 7.27 ppm (d, 6×2H, Ar-H)
showed another doublet for similar protons of C -2 ́, C-6 ́ carbon of six phenyl rings. The chemical
shift at H 4.96 ppm (s, 1H, -C-H) was obtained for the proton (-CH) of carbon (C-3) of
pyrimidine ring.
In the 13C NMR spectral data of compound 14, the chemical shift at  129.73 ppm and 130.67 ppm
was found for the two tertiary carbons (C-1 ́and C-4 ́) of phenyl ring. The peak at  132.34 ppm
represents the aromatic carbons of C
-2 ́, C-6 ́ and carbons C -3 ́, C-5 ó f six phenyl rings
respectively. The chemical shift at  140.24 ppm was obtained for the carbons C-2, C-3, C-4 and
C-6 of pyrimidine ring. The chemical shift at  16.71 ppm was obtained for carbonyl carbon
(C=O).
Mass spectrometry data indicated the proposed structure of metallodendrimer compound
14. Positive-molecular ion mass peak (M+) 1479.55 indicated the molecular ion of the compound.
Cl
Pd
Cl
O
Cl
Cl
O
C
Cl
C
N
Cl
N
C
C
O
Cl
Pd
N
N
O
N
C
C
O
Cl
Pd
Cl
O
Cl
Cl
Cl
14
53
2.4.8 Characterization of 2,4,6-Tris(di-4-methoxybenzamido)-1,5-diazine Palladium(II)
Chloride 15
Compound 15 was synthesized from 2,4,6-triamino-1,5-diazine (pyrimidine) with reaction of pmethyl benzoyl chloride and DMSO by stirring at room temperature for 6-7 hours in presence of
(Ph3P)2PdCl2.
The structure of the compound was established by various spectral data.
In IR spectrum of compound 15, the absorption band was found at 3052.29 cm-1 and 2976.31cm-1
due to the C=H (aro) and C-H (ali) stretching absorption respectively, whereas a broad band
at16083.91 cm-1 represents the keto (C=O) group. Strong absorption band at1304.84 cm-1 displays
strong C=N stretching absorption. max 2664.75 cm-1 and 2645.16 cm-1 stretching bands indicated
the presence of C=C in phenyl ring and max 1027.13 cm-1 indicated the presence of aromatic C-N
stretching.
In IH NMR spectrum of compound 15, the chemical shift at H 3.8 ppm (s, 6×3H, Ar-OCH3) was
found as a singlet for the hydrogen atoms in six aromatic methyl (-OCH3) groups. Chemical shift
at H 7.8 ppm( 6×2H, Ph-H) showed a doublet for aromatic protons of C -3 ́, C-5 ́ carbons of six
phenyl rings and H 6‟9 ppm (d, 6×2H, Ar-H) showed another doublet for similar protons of
carbons C -2 ́, C-6 ́ of six phenyl rings. The chemical shift at H 3.3 ppm (s, 1H, -C-H) was
obtained for the proton (-CH) of carbon (C-3) of pyrimidine ring.
In the
13
C NMR spectral data of compound 15, the chemical shift C 55.406 ppm indicated the
presence of carbons in three methyl groups (Ar-OCH3). The chemical shift at C 122.947 ppm and
C 113.732 ppm was found for two tertiary carbons (C-1 ́, C-4 )́ of phenyl rings. The peak at C
131.287 ppm represents the aromatic carbons of C -2 ́, C-6 ́ and carbons of C -3 ́, C-5 ́of six phenyl
rings respectively. The chemical shift at C 162.803 ppm was obtained for the carbons C-2, C-3,
C-4 and C-6 of pyrimidine ring and C 166.957 ppm was obtained for carbonyl carbon (C=O).
Cl
Pd
H3 CO
O
Cl
OCH3
O
C
OCH3
C
N
H3CO
N
C
C
O
Cl
Pd
N
N
O
N
C
C
O
Cl
Pd
Cl
O
Cl
OCH3
OCH3
15
54
2.4.9 Characterization of 2,4,6-Tris(di -benzamido)-1,5-Diazine palladium(II) chloride 16
The compound 16 was synthesized from 2,4,6-triamino-1,5-diazine (pyrimidine) with the reaction
of benzoyl chloride and DMF by stirring at room temperature for 6-7 hours in presence of
(Ph3P)2PdCl2.
The structure of the compound was established by various spectral data.
In IR spectrum of compound 16, the absorption band was found at 3072.4 cm-1 due to the C-H
(aro) stretching absorption, whereas a broad band at 1691.4 cm-1 represents the keto (C=O) group.
Strong absorption band at1683.7 cm-1 displays strong C=N stretching absorption. max 1585.4 cm1
stretching bands indicated the presence of C=C in phenyl ring and max 1294.1 cm-1 indicated the
presence of aromatic C-N stretching.
In IH NMR spectrum of compound 16, Chemical shift at H 7.45 (t, 6×2H, Ar-H, J=7.5 Hz was
found for the two carbons (C-1 ́, C-4 ́) of phenyl rings , 7.62 (t, 6×1H, Ar-H, J=6.5 Hz) showed a
doublet for aromatic protons of C -3 ́, C-5 ́ carbon of six phenyl rings and H 8.15 (d, 6×2H, Ar-H,
J=7.0 Hz) showed another doublet for similar protons of C-2 ́, C-6 ́ carbon of six phenyl rings.
In 13C NMR spectral data of compound 16, the peak at  130.34 was found for two the carbons (C1 ,́ C-4 ́) of phenyl ring. Chemical shift at  128.60 and  129.46 represent the aromatic carbons of
C-2 ́, C-6 ́ and carbons of C-3 ́, C-5 ́of six phenyl rings respectively. The chemical shift at  133.94
ppm was obtained for the carbons C-2, C-4 and C-6 of ring of pyrimidine ring, chemical shift at 
144.75 ppm was obtained for the carbons C-3 of pyrimidine ring and at  172.77 was obtained for
carbonyl carbon (C=O).
Cl
Pd
O
Cl
O
C
C
N
N
C
O
Cl
Pd
N
N
C
C
O
C
O
N
Cl
Pd
Cl
O
Cl
16
55
2.4.10
Characterization
of
2,4,6-Tris(di-4-nitrobenzamido)-1,5-diazine
palladium(II)
chloride 17
The compound 17 was synthesized from 2,4,6-triamino-1,5-diazine (pyrimidine) with reaction of
4-nitrobenzoylchloride and DMF by stirring at room temperature for 6-7 hours in presence of
(Ph3P)2PdCl2.
The structure of the compound was established by various spectral data.
In IR spectrum of the compound , the absorption band was found at 3080.21 cm-1 due to the C-H
(aro) stretching absorption, whereas a broad band at 1758.10 cm-1 represents the keto (C=O)
group. Strong absorption band at 1592.13 cm-1 displays strong C=N stretching absorption. max
1322.23 cm-1 stretching bands indicated the presence of C=C in phenyl ring and max 1092.67 cm-1
indicated the presence of aromatic C-N stretching.
In IH NMR spectrum of compound, chemical shift at H 8.043 ( 6×2H, Ar-H) showed a doublet for
aromatic protons of C -3 ́, C-5 ́ of six phenyl rings and H 8.221 ppm ( 6×2H, Ph-H) showed
another doublet for similar protons of C -2 ́, C-6 ́ carbon of six phenyl rings and H 7.544 ppm for
1H of pyrimidine ring.
In the
13
C NMR spectral data of the compound, the chemical shift at C 123.614 ppm and C
130.677 ppm was found for the two tertiary carbons C -1 ́and C-4 ́ of phenyl rings. The peak at C
137.040 ppm and C 149.921ppm represent the aromatic carbons of C -2 ́, C-6 ́ and C-3 ́, C-5 ́of six
phenyl rings. The chemical shift at C 149.921 ppm was obtained for the carbons C-2, C-4 and C-6
of pyrimidine ring. The chemical shift at C 161.163 ppm (C-3 of pyrimidine ring) and C 166.20
ppm was obtained for carbonyl carbon (C=O).
Cl
Pd
O 2N
O
Cl
NO2
O
C
NO2
C
N
O 2N
N
C
O
Cl
Pd
N
N
C
C
O
C
O
N
Cl
Pd
Cl
O
Cl
NO2
NO2
17
56
Scanning Electron Microscope (SEM) and Energy Dispersive X-ray (EDX) Spectroscopic
Analysis of the compounds (8, 9, 13 and 14)
2.5 General Discussion:
Scanning electron microscope (SEM) is a type of electron microscope that produces images of a
sample by scanning it with a focused beam of electrons. The electrons interact with atoms in the
sample, producing various signals that can be detected and that contain information about the
sample's surface topography and composition. SEM is known to the best choice because of its
potential in precise analysis of a solid surface. To get more clear insight about the surface
morphology Scanning Electron Microscopic (SEM) analysis was employed. Chemical
composition and morphological structure of a material depends on the synthesis conditions such as
temperature, concentration of reactants and products etc. The SEM images of the compounds were
taken in a Scanning Electron Microscope at an accelerating voltage of 10 KV with magnifications
ranging from 50.00-1.00 µm. The sphericity of the micrographs was found good.
Energy-dispersive X-ray spectroscopy (EDS, EDX, or XEDS), sometimes called energy
dispersive X-ray analysis (EDXA) or energy dispersive X-ray microanalysis (EDXMA), is an
analytical technique used for the elemental analysis or chemical characterization of a sample. It
relies on an interaction of some source of X-ray excitation and a sample. Its characterization
capabilities are due in large part to the fundamental principle that each element has a unique
atomic structure allowing unique set of peaks on its X-ray spectrum. The number and energy of
the X-rays emitted from a specimen can be measured by an energy-dispersive spectrometer. As the
energy of the X-rays is characteristic of the difference in energy between the two shells, and of the
atomic structure of the element from which they were emitted, this allows the elemental
composition of the specimen to be measured. Metal detection or investigation of metallodendrimer
has been performed by employing Energy Dispersive X-ray or EDX method. The EDX spectrum
was taken by selecting a zone or area of a specific particle of the sample. EDX makes use of the
X-ray spectrum emitted by a solid sample bombarded with a focused beam of electrons to obtain a
localized chemical analysis. All elements from atomic number 4 (Be) to 92 (U) can be detected in
principle, though all instruments are equipped for light elements (Z< 10). The details of the SEM
images and EDX spectra of some of the synthesized compounds are shown below-
57
2.5.1a SEM images and EDX spectrum of compound 2,4,6-Tris(di-4-methylbenzamido)1,3,5-triazine palladium(II) chloride 8
The SEM images of the compound 8 were taken in a Scanning Electron Microscope and described
as the following way. 2.5.1 shows the SEM image of different magnification range of compound 8
synthesized as described in chapter-3. This image represented as “blooming flower”
By applying from 10 kv
10.3mmx800 SE(M) to 10 kv
10.3mmx40 k SE(M), the range of
particle size of the compound
were found 50.0 µm to 1.00 µm.
like structure.
58
2.5.1b
EDX
spectrum
of
compound
2,4,6-Tris(di-4-methylbenzamido)-1,3,5-triazine
palladium(II) chloride 8
Project 1
2.5.1b EDX of 2, 4, 6-Tris (di-4-methylbenzamido)-1, 3, 5-triazine palladium chloride, 8
Spectrum
In stats.
C
N
O
Cl
Pd
Sum Spectrum
Yes
61.31
22.73
15.55
0.24
0.17
61.31
0.00
61.31
61.31
22.73
0.00
22.73
22.73
15.55
0.00
15.55
15.55
0.24
0.00
0.24
0.24
0.17
0.00
0.17
0.17
Mean
Std. deviation
Max.
Min.
Processing option: All elements analysed (Normalised)
All results in atomic%
59
Element
App
Intensity
Weight%
Weight%
Atomic%
CK
NK
OK
Cl K
Pd L
Conc.
4.81
0.25
0.68
0.03
0.05
Corrn.
1.7203
0.2077
0.7187
0.8090
0.6701
55.35
23.93
18.69
0.64
1.39
Sigma
4.73
4.04
3.16
0.56
1.38
61.31
22.73
15.55
0.24
0.17
Totals
100.00
Spectrum processing:
Peaks possibly omitted: 0.935, 1.055, 1.744,
2.066keV
Processing option: All elements analyzed
(Normalised)
Number of iterations = 3
Standard:
C
CaCO3 1-Jun-1999 12:00 AM
N
Not defined 1-Jun-1999 12:00 AM
O
SiO2 1-Jun-1999 12:00 AM
Cl
KCl 1-Jun-1999 12:00 AM
From EDX analysis, the presence of metal (Palladium) was well observed and it was 1.39% of
Pd Pd 1-Jun-1999 12:00 AM
weight and 0.17 % of atomic of the compound. From EDX analysis chlorine was found to be
o.64% of weight and 0.24% of atomic of the compound. So it can be said that palladium metal was
present as palladium chloride in our synthesized compound and the reaction was successful for the
preparation of the required metallodendrimer.
2.5.2a SEM images and EDX of compound of 2,4,6-Tris(di-4-chlorobenzamido)-1,3,5-triazine
palladium(II) chloride 9
The SEM images of the compound 9 were taken in a Scanning Electron Microscope and described
as the following way. 2. 5. 2 shows the SEM image of different magnification range of compound
9 synthesized. This image represented as “leafs of tree” like structure.
60
2.5.2a SEM images of compound of 2,4,6-Tris(di-4-chlorobenzamido)-1,3,5-triazine
palladium(II) chloride 9
By applying from 10 kv 10.3 mm x300
SE(M) to 10 kv 10.2mmx1.0 k SE(M), the
range of particle size of the compound
were found 100.0 µm to 50.00 µm.
61
2.5.2b EDX of compound of 2,4,6-Tris(di-4-chlorobenzamido)-1,3,5-triazine palladium
(II) chloride 9
Project Notes:
2.5.2b EDX of 2,4,6-Tris(di-4-chlorobenzamido)-1,3,5 triazine palladium(II) chloride 9
.
.
Element
CK
NK
OK
Cl K
Pd L
App
Conc.
0.63
0.03
0.44
0.07
0.00
Intensity
Corrn.
1.0216
0.2184
0.9428
0.8182
0.6677
Totals
Weight%
47.23
9.03
36.32
6.88
0.54
Weight%
Sigma
11.02
12.18
8.74
3.10
7.90
Atomic%
55.80
9.15
32.22
2.76
0.07
100.00
Spectrum processing:
Peaks possibly omitted: 0.800, 0.936, 2.063, 8.047keV
Processing option: All elements analyzed (Normalised)
Number of iterations = 3
Standard:
C
CaCO3 1-Jun-1999 12:00 AM
N
Not defined 1-Jun-1999 12:00 AM
O
SiO2 1-Jun-1999 12:00 AM
Cl
KCl 1-Jun-1999 12:00 AM
Pd Pd 1-Jun-1999 12:00 AM
62
From EDX analysis, the presence of metal (Palladium) is well observed and it is .54% of weight
and 0.07 % of atomic of the compound. In our synthesized compound 9, there was chlorine atom
but from EDX analysis the amount of chlorine was found to be high as compared to required
amount of the dendrimer and was o.64% of weight and 0.24% of atomic of the compound. So it
can be said that palladium metal was present as palladium chloride in our synthesized compound
and so it can be said that the reaction was successful for the preparation of the required
metallodendrimer.
2.5.3a
SEM
images
of
compound
of
2,4,6-Tris(di-4-methylbenzamido)-1,5-diazine
palladium(II) chloride 13
The SEM images of the compound 13 were taken in a Scanning Electron Microscope and
described as the following way. 2.5.3 shows the SEM image of different magnification range of
compound 13. This image represented as “branches of tree without leafs” like structure. By
applying from 10 kv 10.1mmx400 k SE(M) to 10 kv 10.1 mmx110 k SE(M), the range of particle
size of the compound were found 100 µm to 500 nm.
63
2.5.3a SEM images of compound of 2,4,6-Tris(di-4-methylbenzamido)-1,5-diazine
palladium(II) chloride 13
64
2.5.3b EDX of compound of 2,4,6-Tris(di-4-methylbenzamido)-1,5-diazine palladium(II)
chloride 13
Spectrum processing:
Peaks possibly omitted: 0.800, 0.935, 2.065, 8.04keV
Processing option: All elements analyzed (Normalised)
Number of iterations = 2
Standard:
C
CaCO3 1-Jun-1999 12:00 AM
N
Not defined 1-Jun-1999 12:00 AM
O
SiO2 1-Jun-1999 12:00 AM
Cl
KCl 1-Jun-1999 12:00 AM
Pd Pd 1-Jun-1999 12:00 AM
Element
CK
NK
OK
Cl K
Pd L
Totals
App
Conc.
0.82
0.09
0.55
0.01
0.04
Intensity
Corrn.
1.5609
0.2966
0.8784
0.8218
0.6804
Weight%
34.51
20.88
39.70
0.82
4.10
Weight%
Sigma
8.04
7.48
7.09
2.26
6.12
Atomic%
41.60
21.58
35.93
0.33
0.56
100.00
65
From EDX analysis, the presence of metal (Palladium) is well observed and it was 4.10% of
weight and 0.056 % of atomic of the compound. From EDX analysis chlorine was found to be
0.82% of weight and 0.33% of atomic of the compound. So it can be said that palladium metal was
present as palladium chloride in our synthesized compound and the reaction was successful for the
preparation of the required metallodendrimer.
2.5.4a SEM images and EDX of compound 2,4,6-Tris(di-4-chlorobenzamido)-1,5-diazine
palladium chloride(II) 14
The SEM images of the compound 14 were taken in a Scanning Electron Microscope and
described as the following way. 2.5.4a shows the SEM image of different magnification range of
compound 14. This image represented as like structure “rectangular fiber.” Each chain stacked
with neighboring chain by π-π stacking interaction and formed fibrical morphology. The fibers are
stabilized by π-stacking of the aromatic core of the ligands. By applying from 10 kv 10.1mmx500
k SE(M) to 10 kv 10.1mmx7.0 k SE(M), the range of particle size of the compound were found
100 µm to 5 µm.
66
2.5.4a SEM images of 2,4,6-Tris(di-4-chlorobenzamido)-1,5-diazine palladium(II)
chloride 14
67
2.5.4b EDX of compound 2,4,6-Tris(di-4-chlorobenzamido)-1,5-diazine palladium(II)
chloride 14
Project Notes:
Spectrum processing:
Peaks possibly omitted: 0.799, 0.935, 2.067, 8.045, 8.925keV
Processing option: All elements analyzed (Normalised)
Number of iterations = 3
Standard:
C
CaCO3 1-Jun-1999 12:00 AM
N
Not defined 1-Jun-1999 12:00 AM
O
SiO2 1-Jun-1999 12:00 AM
Cl KCl 1-Jun-1999 12:00 AM
Element
App
Intensity
Weight%
Pd Pd 1-Jun-1999
12:00 AM
Conc.
Corrn.
CK
NK
OK
Cl K
Pd L
0.64
0.04
0.97
1.10
0.01
0.3804
0.1760
0.8691
0.8571
0.6576
38.85
5.10
25.99
29.81
0.25
Weight%
Sigma
6.33
3.42
3.08
3.31
1.90
Atomic%
53.32
6.00
26.78
13.86
0.04
From EDX analysis, the presence of metal (Palladium) is well observed and it is 0.25% of weight
and 0.04 % of atomic of the compound. From EDX analysis the amount of chlorine was found to
be high as compared to required amount of the dendrimer and was 29.81% of weight and 13.06%
of atomic of the compound. So it can be said that palladium metal was present as palladium
chloride in our synthesized compound and the reaction was successful for the preparation of the
required metallodendrimer.
68
Experimental Data
3. General discussion
Unless otherwise noted, all reagents were reagent grade and were used without purification.
Dehydrated DMF, DMSO were used as reaction solvent. These solvents were purchased from
Aldrich and used as received. De-ionized water was used in the experiment where required.
The melting point of the synthesized compounds were determined by open capillary tubes by a
melting point apparatus (Model BUCHI, B-540). The IR specrtra were taken on a Shimadzu FTIR
8400S Fourier Transform. Infrared Spectrophotometer (400-4000 cm-1) with KBr pellets. 1H-NMR
and
13
C-NMR spectra were recorded at 300 MHz and 75 MHz, respectively, on a JEOL AL
300/BZ instrument. Chemical shifts were given relative to TMS. Mass spectra (MS) were
measured by using AXIMA-CFR, Shimadzu/Kratos TOF Mass spectrometer. Analytical thin layer
chromatography (TLC) were Merck aluminium oxide 60 F254 neutral or silica gel 60 F254 coated
on 25 TCC aluminium sheets (20 × 20 cm). Flash column chromatographic. All reagents were
purchased from Sigma Aldrich and were directly used without further purification.
3.1 Synthesis of 2,4,6-Tris(di-4-methylbenzamido)-1,3,5-triazine palladium(II) chloride 8
The mixture of 0.2 g (0.00158 mol) melamine, 3 mL p-methylbenzoylchloride and 8 mol% of bistriphenyl phosphine Palladium (II) chloride was added in 5 mL of DMF and the reaction mixture
was stirred at room temperature for around 5-6 hours in a 250 mL round bottom flask. The
progress of the reaction was monitored. At the starting of the reaction, the mixture was turned into
a clear solution and gradually it turned into white solid. After 6 hours the reaction was stopped by
adding distilled water. After a while it was filtered under suction on a Buchner funnel and washed
with sufficient distilled water, washed with sodium bicarbonate to remove completely any
remaining acid. Finally the product was crystallized by using ethyl acetate and the required
compound was obtained which was white crystalline solid.
69
Cl
Pd
H3C
Cl
O
O
C
C
CH3
CH3
N
H3C
N
COCl
NH2
C
O
(Ph3P)2PdCl2,
Cl
N
N
r.t , 6-7 h
H2N
NH2
N
N
Pd
N
N
C
O
C
O
N
C
Cl
Pd
Cl
O
Cl
DMF
CH3
CH3
CH3
MF: C51N6H42O6 Pd3Cl6
MW: 1366.8938
Physical analysis: white crystalline solid, m. p: 328-330 ̊ C, odorless and 90 % of yield.
Analytical analysis:
IR (KBr): max (cm-1) 3010.43 (C-H aro.), 1760.21 (C=O), 1612.52 (C=N), 1416.23 (C=C
aro.), 1288.46 (C-N), 1332.46 (CH3), 488.72 (Pd-Cl) cm-1.
1
H NMR (300 MHz, CD3OD): H 2.39 ppm (s, 6×3H, Ar-CH3), H 7.28 ppm (6×2H, Ph-H) and
H 7.923 ppm (6×2H, Ph-H).
13
C NMR (75 MHz, CD3OD ): C 21.634 (6C of 6CH3), C 129.07 ppm (C-1 of benzene ring)
C 130.506 ppm (C-2, C-6, C-3, C-5 of benzene ring), C 131.28 ppm (C-4 of benzene ring), C
144.37 ppm (C-2, C-4, C-6 of melamine ring) and C 170.02 ppm (C=O).
3.2 Synthesis of 2,4,6-Tris(di-4-chlorobenzamido)-1,3,5-triazine palladium(II) chloride 9
The mixture of 0.2 g (0.00158 mol) melamine, 3 mL p-chlorobenzoylchloride and 8 mol% of
bis-triphenyl phosphine Palladium (II) chloride was added in 5 mL of DMSO in a round bottle
flask and the reaction was carried out by a similar procedure described by compound 8.
Cl
Pd
COCl
NH2
Cl
O
Cl
O
Cl
(Ph3P)2PdCl2,
C
N
N
Cl
C
N
6 hrs, DMSO
H2N
N
Cl
NH2
N
r.t.
Cl
N
C
O
Cl
Pd
N
N
C
C
O
C
O
N
Cl
Pd
Cl
O
Cl
Cl
1
Cl
9
70
MF: C45N6H24O6Pd3Cl12
MW: 1489.4047
Physical analysis: White crystalline solid, m. p: 310-312 ̊ C, odorless and 90 % of yield.
Analytical analysis:
IR (KBr): max (cm-1) 3080.21 (C-H aro.), 1758.1 (C=O), 1592.13 (C=N aro.), 1322.23 (C=C
aro.), 1092.67 (C-N aro.), 472.92 (472.92) cm-1.
1
H NMR (300. MHz, CD3OD): H 7.27 ppm (6×2H, Ph-H) and H 7.92 ppm (6×2H, Ph-H).
13
C NMR (75 MHz, CD3OD): C 129.73 ppm (C-1 of benzene ring), C 132.34 ppm (C-2, C-6,
C-3, C-5 of benzene ring), C 130.67 ppm (C-4 of benzene ring), C 140.24 ppm (C-2, C-4, C-6
of melamine ring) and C 168.71 ppm (C=O).
3.3 Synthesis of 2,4,6-Tris(4-methoxybenzamido)-1,3,5-triazine palladium(II) chloride 10
The mixture of 0.2 g (0.00158 mol) melamine, 3 mL p-methoxybenzoylchloride and 8 mol% of
bis-triphenyl phosphine Palladium (II) chloride was added in 5 mL of DMSO in a 250 ml round
bottle flask. The reaction was carried out by a similar procedure described by compound 8.
Cl
Pd
H3CO
O
Cl
OCH3
O
C
OCH3
C
N
COCl
NH2
H3CO
N
(Ph3P)2PdCl2,
C
N
N
O
r.t , 5-6 h
H2N
NH2
N
Cl
Pd
DMSO
CH3O
N
N
N
C
O
C
O
N
Cl
Pd
Cl
O
Cl
OCH3
1
C
OCH3
10
71
MF: C51N6H42O12Pd3Cl6
MW: 1462.8902
Physical analysis: White crystalline solid, m. p: 320-322 ̊ C, odorless and 95 % of yield.
Analytical analysis:
IR (KBr): max (cm-1) 3014.5, 2984.85, 2844.13, 2664.75, 2645.16, 16083.91, 1304.84,
1027.13 and 844.85 cm-1
1
H NMR (300 MHz, CD3OSCD3): H 3.79 ppm (s, 6×3H, Ar-OCH3), H 6.99 ppm (m, 6×2H,
Ph-H) and H 7.923 ppm (6×2H, Ph-H).
13
C NMR (75 MHz, CD3OD ): C 55.406 (6C of 6OCH3), C 113.798 ppm (C-4 of benzene
ring) C 131.355 ppm (C-2, C-6, C-3, C-5 of benzene ring), C 123.037 ppm (C-1 of benzene
ring), C 162.86 ppm (C-2, C-4, C-6 of melamine ring) and C 167.047 ppm (C=O).
3.4 Synthesis of 2,4,6-Tris(di-benzamido)-1,3,5-triazine palladium(II) chloride 11
The mixture of 0.2 g (0.00158 mol) melamine, 3.5 ml benzoylchloride and 8 mol% of bistriphenyl phosphine palladium (II) chloride was added in 6 mL DMF in a 250 ml round bottle
flask and the reaction was carried out by a similar procedure described by compound 8
COCl
NH2
Cl
Pd
(Ph3P)2PdCl2,
O
N
N
Cl
O
C
C
N
r.t , 6-7 h
H2N
NH2
N
N
DMSO
N
C
C
O
Cl
Pd
N
N
C
C
O
N
O
Cl
Pd
Cl
O
Cl
1
11
72
MF: C45N6H30O6Pd3Cl6
MW: 1282.7343
Physical analysis: White crystalline solid, m. p: 290-292oC, odorless and 90% of yield.
Analytical analysis:
IR (KBr): max (cm-1) 3072.4, 1691.5, 1683.7, 1585.4 and 1294.1 cm-1.
1
H NMR (300 MHz, CDCl3): H 7.45 (t, 6×2H, Ar-H, J=7.5 Hz), 7.62 (t, 6×1H, Ar-H, J=6.5
Hz), H 8.15 (d, 6×2H, Ar-H, J=7.0 Hz).
13
C NMR (75 MHz, CDCl3): C 128.60, 129.46, 130.34, 133.94, 144.75 and 172.77 ppm.
3. 5 Synthesis of 2,4,6-Tris(di-4-nitrobenzamido)-1,3,5-triazine palladium(II) chloride 12
The mixture of 0.2 g (0.00158 mol) melamine, 1.8 g p-nitrobenzoylchloride and 8 mol% of bistriphenyl phosphine Palladium (II) chloride was added in 5 mL of DMF in a 250 ml round
bottle flask and the reaction was carried out by a similar procedure described by compound 8
Cl
Pd
COCl
NH2
O2N
O
(Ph3P)2PdCl2,
NO2
O
NO
C
N
N
Cl
2
C
N
6 hrs, DMSO
H 2N
NH2
N
r.t.
O2N
N
N
NO2
C
O
Cl
Pd
N
N
C
C
O
C
O
N
Cl
Pd
Cl
O
Cl
NO2
1
NO2
12
73
MF: C45N12H24O18Pd3Cl6
MW: 1552.7196
Physical analysis: White crystalline solid, m. p: 304-306 ̊ C, odorless and 89% of yield.
Analytical analysis:
IR (KBr): max (cm-1) 3080.21 (C-H aro.), 1758.1 (C=O), 1592.13 (C=N aro.), 1322.23 (C=C
aro.), 1092.67 (C-N aro.) cm-1.
1
H NMR (300 MHz, CD3OD): H 8.104 ppm (6×2H, Ph-H) and H 8.297 ppm (6×2H, Ph-H).
13
C NMR (75 MHz, CD3OD): C 123.688 ppm (C-1 of benzene ring), C 130.684 ppm (C-2, C-
6, C-3, C-5 of benzene ring), C 136.455 ppm (C-4 of benzene ring), C 150.012 ppm (C-2, C-4,
C-6 of melamine ring) and C 165.819 ppm (C=O).
3.6 Synthesis of 2,4,6-Tris(di-4-methylbenzamido)-1,5-diazine Palladium(II) chloride 13
The mixture of 0.1 g (0.00159 mol) Triaminopyrimidine, 3 mL p-toluoylchloride and 8 mol%
in presence of (Ph3P)2PdCl2 in 8 mL of DMSO in a 250 ml round bottle flask and the reaction
was carried out by a similar procedure described by compound 8
Cl
Pd
COCl
NH2
H3C
O
(Ph3P)2PdCl2
N
O
C
NH2
3
C
N
5-6 h, DMSO
H2N
CH3
CH
CH
N
Cl
r.t
CH3
H3C
N
C
C
O
Cl
Pd
N
N
N
C
C
O
O
Cl
Pd
Cl
O
Cl
CH3
2
CH3
13
74
MF: C52N5H43O6Pd3Cl6
MW: 1365.9057
Physical analysis: White crystalline solid, m. p. 324-326 C, odorless and 90 % yield.
Analytical analysis:
IR (KBr): max (cm-1) 3052.29 (C=H aro.), 2976.31 (C-H ali.), 1710.20 (C=O), 1611.69
(C=N), 1418.69 (C=C), 1360.20 (C-N aro.), 468.72 (Pd-Cl) cm-1.
1
H NMR (300 MHz, CD3OD): H 2.3 ppm (s, 6×3H, Ar-CH3), H 7.23 ppm (d, 6×2H, Ar-H,),
H 7.80 ppm (d, 6×2H, Ar.-H ) and H 4.96 ppm (s, 1H, C-H) ppm.
13
C NMR (75 MHz, CD3OD): C 21.63 ppm (C of CH3), 129.28 ppm (C4 of benzene ring),
130.50 ppm (C2, C6, C3, C5 of benzene ring), 131.28 ppm (C1 of benzene ring), 144.63 ppm
(C2, C3, C4, C6 of pyrimidine ring) and 172.33 (C=O) ppm.
3.7 Synthesis of 2,4,6-Tris(di-4-chlorobenzamido)-1,5-diazine Palladium(II) chloride 14
The mixture of 0.2 g (0.00159 mol) 2, 4, 6 triaminopyrimidine, 3mL p-chlorobenzoylchloride
and 8 mol% of bis-triphenyl phosphine Palladium (II) chloride (Ph3P)2PdCl2 was added in 10
mL DMF in a 250 ml round bottle flask and the reaction was carried out by a similar procedure
described by compound 8
Cl
Pd
Cl
O
COCl
NH2
Cl
C
N
CH
N
6 hrs, DMF
H2N
Cl
O
C
(Ph3P)2PdCl2
Cl
N
NH2
Cl
N
r.t.
C
O
Cl
Cl
Pd
N
N
C
C
O
C
O
N
Cl
Pd
Cl
O
Cl
Cl
2
Cl
14
75
MF: C46N5H25O6Pd3Cl12
MW: 1488.4166
Physical analysis: White crystalline solid, m. p: 308-310 C, odorless and 90 % of yield.
Analytical analysis:
IR (KBr): max (cm-1) 3094.89 (C=H aro.), 1680.20 (C=O), 1592.29 (C=N), 1424.489 (C=C
aro.), 1092.71 (C-N), 460 (Pd-Cl).
1
H NMR (300 MHz, CD3OD): H 4.96 ppm (s, 1H, -C-H), H 8.01 ppm (d, 6×2H, Ar-H,)
And H 7.27 ppm (d, 6×2H, Ar-H).
13
C NMR (75 MHz, CD3OD): C 129.73 ppm (C-1 of benzene ring), 130.67 ppm (C-4 of
benzene ring), 132.34 ppm (C-2, C-6, C-3, C-5 of benzene ring), 140.24 ppm (C-2, C-3, C-4
and C-6 of pyrimidine ring), and 168.71 (C=O) ppm.
3.8 Synthesis of 2,4,6-Tris(4-methoxybenzamido)-1,5-Diazine palladium(II) chloride
15
The mixture of 0.2 g (0.00159 mol) 2, 4, 6 triaminopyrimidine, 3mL p-chlorobenzoylchloride
and 8 mol% of bis-triphenyl phosphine Palladium (II) chloride (Ph3P)2PdCl2 was added in 10
mL DMF in a 250 ml round bottle flask and the reaction was carried out by a similar procedure
described
by
compound
Cl
Pd
H3CO
O
Cl
OCH3
O
OCH
C
3
C
N
H3CO
COCl
NH2
N
(Ph3P)2PdCl2,
r.t , 5-6 h
H2 N
N
NH2
DMSO
OCH3
C
C
O
N
Cl
Pd
N
N
C
C
O
Cl
Pd
Cl
O
Cl
8
OCH3
2
O
N
OCH3
15
76
MF: C52N5H43O12Pd3Cl6
MW: 1461.9012
Physical analysis: White crystalline solid, m. p: 315-317 oC, odorless and 96% of yield.
IR (KBr): max (cm-1) 3014.5, 2984.85, 2844.13, 2664.75, 2645.16, 16083.91, 1304.84,
1027.13 844.85 cm-1
1
H NMR (300 MHz, CD3OSCD3): H 3.8 ppm (s, 6×3H, Ar-OCH3), H 6.9 ppm (6×2H, Ph-H),
H 7.8 ppm (6×2H, Ph-H) and H 3.3 ppm (1H of pyrimidine ring).
13
C NMR (75 MHz, CD3OD ): C 55.406 (6C of 6OCH3), C 113.732 ppm (C-4 of benzene
ring) C 131.287 ppm (C-2, C-6, C-3, C-5 of benzene ring), C 122.947 ppm (C-1 of benzene
ring), C 162.803 ppm (C-2, C-3, C-4, C-6 of pyrimidine ring) and C 166.957 ppm (C=O).
3.9 Synthesis of 2,4,6-Tris(di-benzamido)-1,5-Diazine palladium palladium(II) chloride
16
The mixture of 0.2 g (0.00159 mol) melamine, 3.2 ml benzoylchloride and 8 mol% of bistriphenyl phosphine palladium (II) chloride was added in 10 mL DMF in a 250 ml round bottle
flask and the reaction was carried out by a similar procedure described by compound 8
Cl
Pd
O
O
C
N
(Ph3P)2PdCl2,
N
N
NH2
5-6 h
C
C
DMF, r.t
H2 N
C
N
COCl
NH2
Cl
O
Cl
Pd
N
N
N
C
C
O
O
Cl
Pd
Cl
O
Cl
2
16
77
MF: C45N6H30O6Pd3Cl6
MW: 1281.7462
Physical analysis: White crystalline solid, m. p: 280-282oC, odorless and 90 % of yield.
Analytical analysis:
IR (KBr): max (cm-1) 3072.4, 1691.5, 1683.7, 1585.4 and 1294.1 cm-1.
1
H NMR (300 MHz, CDCl3): H 7.45 (t, 6×2H, Ar-H, J=7.5 Hz), 7.62 (t, 6×1H, Ar-H, J=6.5
Hz), H 8.15 (d, 6×2H, Ar-H, J=7.0 Hz).
13
C NMR (75 MHz, CDCl3): C 128.60, 129.46, 130.34, 133.94, 144.75 and 172.77 ppm. 3.10
Synthesis of 2,4,6-Tris(di-4-nitrobenzamido)-1,5-Diazine palladium(II) chloride
17
The mixture of 0.2 g (0.00159 mol) melamine, 1.8 g p-nitrobenzoylchloride and 8 mol% of bistriphenyl phosphine Palladium (II) chloride was added in 5 mL of DMSO in a 250 ml round
bottle flask and the reaction was carried out by a similar procedure described by compound 8
Cl
Pd
O2N
O
COCl
NH2
Cl
NO2
O
C
NO2
C
N
(Ph3P)2PdCl2,
N
O2N
N
6 hrs, DMSO
H 2N
N
NH2
C
C
r.t.
O
N
N
NO2
Cl
Pd
O
N
C
C
O
Cl
Pd
Cl
O
Cl
NO2
2
NO2
17
78
MF: C46N11H25O18Pd3Cl6
MW: 1551.7316
Physical analysis: White crystalline solid, m. p: 305-307 ̊ C, odorless and 92 % of yield.
Analytical analysis:
IR (KBr): max (cm-1) 3080.21 (C-H aro.), 1758.1 (C=O), 1592.13 (C=N aro.), 1322.23 (C=C
aro.), 1092.67 (C-N aro.) cm-1.
1
H NMR (300 MHz, CD3OD): H 8.043 ppm (6×2H, Ph-H), H 8.221 ppm (6×2H, Ph-H). H
7.544 ppm 1H of pyrimidine ring.
13
C NMR (75 MHz, CD3OD): C 123.614 ppm (C-4 of benzene ring), C 137.040 ppm (C-3, C-
5 of benzene ring), C 149.921 ppm C-2, C-6 of benzene ring, C 130.677 ppm (C-1 of benzene
ring), C 161.163 ppm (C-3 of pyrimidine ring) and C 166.208 ppm (C=O).
79
IR spectra of 2,4,6-Tris(di-4-methylbenzamido)-1,3,5-triazine palladium(II) chloride 8
45
Cl
Cl
CH3
Pd
%T
H 3C
40
O
O
C
C
CH3
N
H3C
N
35
N
C
C
O
Cl
Cl
30
N
Pd
N
O
Cl
Pd
N
C
C
O
Cl
O
25
H3C
CH3
20
468.72
15
1
3600
3200
607.60
542.02
840.99
2400
2000
1800
1600
1400
755.16
1418.69
961.55
2800
1286.56
4000
MSI-07
1680.05
-0
1612.54
2976.26
5
2667.64
3072.71
10
1200
1000
800
600
400
1/cm
H NMR spectra of 2,4,6-Tris(di-4-methylbenzamido)-1,3,5-triazine palladium(II)
chloride 8
Cl
Cl
CH3
Pd
O
H 3C
O
C
CH3
C
N
H3C
N
N
C
O
Cl
Cl
N
Pd
N
C
O
C
O
C
Cl
Pd
N
Cl
O
CH3
H3C
80
13
C NMR spectra of 2,4,6-Tris(di-4-methylbenzamido)-1,3,5-triazine palladium(II)
chloride 8
Cl
Cl
CH3
Pd
O
H 3C
O
C
CH3
C
N
H3C
N
N
C
Cl
Cl
O
N
Pd
C
N
C
O
C
O
Cl
Pd
N
Cl
O
CH3
H3C
Mass spectra of 2,4,6-Tris(di-4-methylbenzamido)-1,3,5-triazine palladium(II) chloride 8
81
IR spectra of 2,4,6-Tris(di-4-chlorobenzamido)-1,3,5-triazine palladium(II) chloride 9
67.5
%T
60
52.5
45
853.53
1322.25
1592.29
1681.98
1425.44
2360.95
15
7.5
4000
MSI-18
1
928.76
1176.62
2675.36
2982.05
22.5
546.84
30
472.58
682.82
37.5
3600
3200
2800
2400
2000
1800
1600
1400
1200
1000
800
600
400
1/cm
H NMR spectra of 2,4,6-Tris(di-4-chlorobenzamido)-1,3,5-triazine palladium(II) chloride
9
82
13
C NMR spectra of 2,4,6-Tris(di-4-methylbenzamido)-1,3,5-triazine palladium(II)
chloride 9
Mass spectra of 2,4,6-Tris(di-4-chlorobenzamido)-1,3,5-triazine palladium(II) chloride 9
83
IR spectra of 2,4,6-Tris(di-4-methoxybenzamido)-1,3,5-triazine palladium(II) chloride 10
Cl
30
O
H3CO
C
%T
H3CO
5
25
O
Cl
Cl
20
Pd
C
O
Cl
Pd
2
O
C
N
/
1
4
C
3
6/
4
5
/
OCH3
/
OCH3
N3
N
6
N
/
/
N
1
2
C
O
C
O
N
Pd
Cl
Cl
OCH3
OCH3
15
10
547.80
504.40
697.29
615.31
773.48
853.53
844.85
926.83
1027.13
1180.47
1167.94
1130.32
1106.21
1324.18
1304.89
1299.10
1263.42
1517.06
1427.37
1414.83
1602.90
1577.82
1687.77
1683.91
2664.75
0
2543.23
3052.45
2983.98
2940.58
2844.13
2827.74
5
-5
-10
4000
MSI-42
1
3600
3200
2800
2400
2000
1800
1600
1400
1200
1000
800
600
400
1/cm
H NMR spectra of 2,4,6-Tris(di-4-methoxybenzamido)-1,3,5-triazine palladium(II)
chloride 10
Cl
O
H3CO
C
H3CO
5
O
Cl
Cl
Pd
C
O
Cl
Pd
C
N
C
2
/
1
4
/
/
3
6/
4
5
/
OCH3
/
OCH3
N3
N
6
N
O
N
1
2
C
O
C
O
N
Pd
Cl
Cl
OCH3
OCH3
84
13
C NMR spectra of 2,4,6-Tris(di-4-methoxybenzamido)-1,3,5-triazine palladium(II)
chloride 10
Cl
O
H3CO
C
H3CO
5
O
Cl
Cl
Pd
C
O
6
N
C
Cl
Pd
O
C
N
4
2
/
/
/
3 /
4 OCH3
1 /
6
5
/
OCH3
N3
N
N 2N
1
C O
Pd
Cl
C O Cl
OCH3
OCH3
85
IR spectra of 2,4,6-Tris(di-4-benzamido)-1,3,5-triazine palladium(II) chloride 11
Cl
O
Cl
Pd
C
O
C
N
N
N
C
C
O
Cl
Pd
N
C
N
O
Cl
Pd
N
C
O
Cl
O
Cl
1
H NMR spectra of 2,4,6-Tris(di-benzamido)-1,3,5-triazine palladium(II) chloride 11
Cl
O
Cl
Pd
C
O
C
N
N
N
C
C
O
Cl
Pd
N
C
N
O
Cl
Pd
N
C
O
Cl
O
Cl
86
13
C NMR spectra of 2,4,6-Tris(di-benzamido)-1,3,5-triazine palladium(II) chloride 11
Cl
Cl
Pd
O
O
C
C
N
N
N
C
C
O
Cl
Pd
N
N
O
Cl
Pd
N
C
C
O
Cl
O
Cl
IR spectra of 2,4,6-Tris(di-4-nitrobenzamido)-1,3,5-triazine palladium(II) chloride 12
Cl
Cl
O
O 2N
C
O2 N
5
O
Cl
Pd
Cl
C
O
6
N
C
Pd
C
N
2
O
/
1
4
/
/
3 /
4 NO2
6/
5
/
NO2
N3
N
C O
1
Cl
Pd
N 2 N
C O
Cl
NO2O2N
87
1
H NMR spectra of 2,4,6-Tris(di-4-nitrobenzamido)-1,3,5-triazine palladium(II) chloride 12
Cl
Cl
Pd
O
O 2N
C
5
Pd
1
/
/
3
6/
4
5
/
NO2
/
NO2
N3
N
N
C
O
C
O
1
Cl
Pd
2 N
N
C
O
Cl
/
4
6
C
O
Cl
C
N
O2 N
2
O
Cl
NO2O2N
13
C NMR spectra of 2,4,6-Tris(di-4-nitrobenzamido)-1,3,5-triazine palladium(II) chloride
12
Cl
Cl
O
O2N
C
O 2N
5
O
Cl
Pd
Cl
C
O
6
N
C
Pd
C
N
2
O
/
1
4
/
/
3 /
4 NO2
6/
5
/
NO2
N3
N
C O
1
Cl
Pd
N 2 N
C O
Cl
NO2O2N
88
IR spectra of 2,4,6-Tris(di-4-methylbenzamido)-1,5-Diazine palladium(II) chloride 13
45
Cl
%T
O
H3C
C
40
H3C
Cl
Pd
N
O
CH3
CH3
C
N
35
O
Cl
Cl
30
Pd
C
O
N
N
C
O
C
O
N
C
Pd
Cl
Cl
CH3
CH3
25
20
15
3600
3200
2800
2400
2000
1800
1600
468.72
607.60
541.05
840.99
960.58
755.16
1184.33
1418.69
1400
1285.60
4000
MSI-21
1681.02
1677.16
-0
1611.58
1126.47
2361.91
5
2652.21
3050.52
2976.26
10
1200
1000
800
600
400
1/cm
1
H NMR spectra of 2,4,6-Tris(di-4-methylbenzamido)-1,5-Diazine palladium(II) chloride
13
C
l
C
l
H
C
3
/
P
d2
OO
/
3
/
4C
H
3
/
H
C
3
/
CC
5
/
N1
6
5
C
H
3
4
N 3
C
OC
l
6
C
2
ON NN
P
d
1
C
O
C
l
C
l
P
dC
O
C
l
C
H
3
C
H
3
89
13
C NMR spectra of 2,4,6-Tris(di-4-methylbenzamido)-1,3,5-Diazine palladium(II)
chloride 13
l
C
l C
H
C
3
H
C
3
/
/
P
d2 3
/
4C
H
OO
3
/
H
/
CC
5 C
3
/
N 16
5
4
N
3
C
OC
l
C6
2
ON NN
P
d
1
C
O
C
l
C
l
P
dC
O
C
l
C
H
3
C
H
3
Mass spectra of 2,4,6-Tris(di-4-methylbenzamido)-1,5-Diazine palladium(II) chloride 13
90
IR spectrum of the compound 2,4,6-Tris(di-4-chlorobenzamido)-1,5-diazine palladium(II)
chloride 14
52.
Cl
Cl
%
5
4
T
O
Cl
C
Cl
5
5
37.
O
Cl
Pd
C
O
Cl
Pd
3
6/
4
5
/
Cl
/
Cl
3
N
C
N
1
Cl
5
1
4
6
N
C
/
C
N
/
/
2
O
2
O
Cl
Pd
N
C
O
Cl
Cl
3
0
22.
5
1
5
7.
5
400
360
320
280
240
200
180
160
140
120
100
80
60
0
0
0
0
0
0
0
0
0
0
0
0
0
1/c
40
0
m
1
H NMR spectrum of the compound 2,4,6-Tris(di-4-chlorobenzamido)-1,5-diazine
palladium(II) chloride 14
Cl
Cl
O
Cl
C
Cl
5
O
Cl
Pd
Cl
C
O
Pd
C
1
4
3 /
4 Cl
6/
5
/
Cl
3
N
C O
6
N
/
C
N
/
/
2
O
N
1
Cl
Cl
Pd
2 N
C O
Cl
Cl
91
13
C
NMR
spectrum of the compound 2,4,6-Tris(di-4-chlorobenzamido)-1,5-diazine
palladium(II) chloride 14
Cl
Cl
O
Cl
C
Cl
5
O
Cl
Pd
Cl
C
O
Pd
C
3
6/
4
5
/
Cl
/
Cl
3
N
N
1
Cl
Mass
1
4
6
N
/
C
N
/
/
2
O
2
C
O
C
O
Cl
Pd
N
Cl
Cl
spectrum of the compound 2,4,6-tris
(di-4-chlorobenzamido)-1,5-diazine
palladium(II) chloride 14
92
IR spectra of 2,4,6-Tris(di-4-methoxybenzamido)-1,5-Diazine palladium(II) chloride 15
Fourth Deriv ativ e
Cl
Cl
35
Pd
O
H3CO
%T
C
30
5
25
/
/
3
4
5
6/
/
OCH3
/
OCH3
3
N
2
N
1
C
O
Cl
/
1
4
N
6
C
O
Pd
Cl
C
N
H3CO
2
O
C
O
C
O
N
Pd
Cl
Cl
OCH3
20
1776.50
OCH3
1923.09
2036.90
15
697.29
773.48
927.79
844.85
1027.13
1167.94
1304.89
1299.10
1261.49
1516.10
1603.86
1683.91
0
1427.37
2545.16
2984.94
2844.13
5
2664.75
2361.91
10
-5
-10
4000
MSI-41
1
3600
3200
2800
2400
2000
1800
1600
1400
1200
1000
800
600
400
1/cm
H NMR spectra of 2,4,6-Tris(di-4-methoxybenzamido)-1,5-Diazine palladium(II)
chloride 15
Cl
O
H3CO
C
H3CO
5
O
Cl
Cl
Pd
C
O
Cl
Pd
C
N
C
/
1
4
/
/
3
6/
4
5
/
OCH3
/
OCH3
3
N
6
N
2
O
N
1
2
C O
N
C O
Pd
Cl
Cl
OCH3
OCH3
93
13
C NMR spectra of 2,4,6-Tris(di-4-methoxybenzamido)-1,5-Diazine palladium(II)
chloride 15
Cl
Cl
Pd
O
H3CO
C
5
O
Pd
Cl
/
1
4
/
/
3
6/
4
5
/
OCH3
/
OCH3
3
N
6
C
N
N
1
C
O
Cl
C
N
H3CO
2
O
2
C O
N
C O
Pd
Cl
Cl
OCH3
OCH3
1
H NMR spectra of 2,4,6-Tris(di-4-nitrobenzamido)-1,5-Diazine palladium(II) chloride 17
Cl
Cl
O
O2N
C
O 2N
5
O
Cl
Pd
Cl
C
O
Pd
/
C
N
1
4
/
/
3
6/
4
5
/
NO2
/
NO2
3
N
6
N
C
2
O
N
1
C
O
C
O
Cl
Pd
2 N
Cl
NO2O2N
94
13
C NMR spectra of 2,4,6-Tris(di-4-nitrobenzamido)-1,5-Diazine palladium(II) chloride
17
Cl
Cl
O
O2N
C
O 2N
5
O
Cl
Pd
Cl
C
O
Pd
C
/
C
N
1
4
/
/
3
6/
4
5
/
NO2
/
NO2
3
N
6
N
2
O
N
1
C
O
C
O
Cl
Pd
2 N
Cl
NO2O2N
95
Conclusion:
The following points can be concluded from the research work A facile method for the synthesis of some highly functionalized dendrimer compounds from the
reaction of commercially available 2,4,6–triamino–1,3,5–triazine (melamine) and 2,4,6-triamino1,5-diazine (pyrimidine) with different aroylchlorides has been developed.
 The synthesis of metallodendrimer compounds was also carried out by using synthesized
dendrimer in the presence of (Ph3P)2PdCl2 in DMF under room temperature.
 The surface morphology and particle size of the compounds were studied by Scanning Electron
Microscope (SEM) and all the synthesized compounds were found to excellent morphology and
the particle size range from 100 µm to 500 nm. The structure were found like blooming flower
(compound 8), leafs of tree (compound 9), branches of tree without leaf (compound 13),
rectangular fiber (compound 14).
 The presence of the elements of the synthesized compounds were detected by EDX.
 The polar aprotic solvents (DMF, DMSO) were found to the good solvent for this method.
 These synthesized compounds would be important ligands and the metallodendrimers would be
potent catalyst which is under study.
 The most important features of these methods were that, the readily available inexpensive
materials were used under relatively mild conditions and got relatively higher yield.
Therefore, this methodology could be utilized to synthesize the biologically important
metallodendrimers mild conditions.
96
References:
1. a) G. R. Newkome, Z. Q. Yao, G. R. Baker, V. K. Gupta, J. Org. Chem. 1985, 20, 2003.
b) D. A, Tomalia, H. Baker, J. R. Dewald, M. Hall, G. Kallos, S. Martin, J. Roeck, J.
Ryder,
P.
Smith,
J.
Polym.
1985,
17, 117.
c)
D.
A. Tomalia, A. Naylor,
W. A. Goddard, Angew. Chem. Int. Ed. 1990, 29, 138. d) T. Nagasaki, O. Kimura, M.
Ukon, S. Arimori, I. Hamachi, S, Shinkai, J. Chem. Perkin Trans. 1994, 75, 1002. e) J.P.
Majoral, A. M Caminade, Chem. Rev. 1999, 99, 845. f) M. Fischer, F. Vogtle, Angew.
Chem. Int. Ed. 1999, 38, 884. g) P. G. de Germes, H. J. Hervet, Phys. Lett. 1983, 44, 351.
h)
A. M.
Naylor,
W.
A.
Goddard
III,
G.
E.
Kiefer, D. A.
Tomalia,
J. Am. Chem. Soc. 1989, 111, 2339. i) S. Pricl, M. Fermeglia, M. Ferronne, A. Asquini,
Carbon 2003, 41, 2269. j) J. M. J. Frchet, D. A. Tomalia, Dendrimers and Other Dendritic
Polymers. John Wiley & Sons, Inc., New York, 2001.
2. J. M. J. Frechet, Science 1994, 263, 1710.
3.
C. J. Hawker, In Advances in Polymer Science, J. G. Hilbom
Ed.; Springer-Verlag:
Berlin, Heidelberg, 1999, 147, 113.
4. Y. H. Kim, O. W. Webster, J. Am. Chem. Soc. 1990, 112, 4592.
5. T. M. Miller, T. X. Neenan, R. Zayas, H. E. Blair, J. Am. Chem. Soc. 1992, 114, 1018.
6. C. J. Hawker, F. Chu, Macromolecules, 1993, 29, 4370.
7. A. Hult, M. Johansson, E. Malmstrom, In Advances in Polymer Science; J. Roovers, Ed.;
Springer-Verlag; Berlin, Heidelberg, 1999, 1431.
8. a) E. M. M. de Brabander-van den Berg, E. W. Meijer, Angew. Chem. Int. Ed. 1993, 32,
1308. b) J. F. G. A. Jansen, E. M. M. de Brabander-van den Berg, E. W. Meijer, Science
1994, 266, 1226. c) J. F. G. A. Jansen, E. W. Meijer, J. Am. Chem. Soc. 1995, 117, 4417.
9. Jansen, J. F. G. A and Meijer, E. W., “The dendritic box: Shape selective liberation of
encapsulated Guests”. J. Am. Chem. Soc., vol. 117, pp. 4417-4418, 1995.
10. Wooly, K. L., Hawker, C. J. and Frechet, M. J., “Unsymmetrical three-dimensional
macromolecules: Preparation and characterization of strongly dipolar dendritic
macromolecules”, J. Am. Chem. Soc., vol. 115, pp.11496-11505, 1993.
11. Percec, V., Johansen, G., Unger, G. and Zhou, J., “Fluorophobic effect induces the
selfassembly of semifluorinated tapered monodendrons containing crown ethers into
97
supramolecular columnar dendrimers which exhibit a homeotrobic hexagonal columnar
liquid crystalline phase”, J. Am. Chem. Soc., vol. 118, pp. 9855-9866, 1996.
12. Gu, H. E., Li, G. U. O. and Li Fang, M. A., “Synthesis of Novel Dendrimers Containing
amino Acids and Peptides”, Chin. Chem. Lett. vol. 17, 3, pp. 289-292, 2006.
13. Peterson, J., Ebber, A., Allikmaa, V. and Lopp, M., “Synthesis of CZE analysis of
PAMAM dendrimers with an ethylenediamine core”, Proc. Estonian Acad. Sci. Chem.,
vol. 50, 3, pp. 156-166, 2001.
14. Franc, G. and Kakkar, A. K., “Diels–Alder “Click” Chemistry in Designing Dendritic
Macromolecules”, Eur. J. Chem. doi: 10.1002/chem.200900252, 2009.
15. Killops, K. L., Campos, L. M. and Hawker, C. J., “Robust, Efficient, and Orthogonal
Synthesis of Dendrimers via Thiol-ene “Click” Chemistry”, J. Am. Chem. Soc., vol. 130,
15, pp. 5062–5064, 2008.
16. Antoni, P., Nystrom, D., Hawker, C. J. and Malkoch, M., “A chemoselective approach
for the accelerated synthesis of well-defined dendritic architectures”, Chem. Comm., vol.
22, pp. 2249-2251, 2007.
18. Carlmark, A., Hawker, C. J., Hult, A. and Malcoch, M., “New methodologies in the
construction of dendritic materials”, Chem. Soc. Rev., vol. 38, pp. 352 – 362, 2009.
19. Franc, G. and Kakkar, A., “Dendrimer Design Using Cu(I)-Catalyzed Alkyne-Azide
Click Chemistry”, Chem. Comm., vol. 42, pp. 5267 – 5276, 2008.
20. Kostas, I. D., Andreadaki, F, J., Medlycot, E. A.; Hannan, G. S. and Monflier, E.,
“Synthesis of a halo-methylphenylene periphery-functionalized triazine – based dendritic
molecule with a 3, 3΄-dimethyl biphenyl linker using tris (halo-methylphenylene)
triazines as building block”, Tetrahedron Lett., vol. 50, pp. 1851-1854, 2009.
21. Tomalia, D.A., Baker, H., Dewald, J., Hall, M., Kallos, G and Martin, S., A newclass of
polymers: starburst-dendritic, j. macromolecules. Polym. 1985, 17, 117-32.
22. Newcome, G.R., Moorefield, C. N and Vogtle, F., 1996. Dendritic Molecule Concept,
synthesis perspective, VCH publisher.
23. Newkome, G. R.; He, E.; Moorefield, C. N. “Supramolecules with novel properities:
metallodendrimers”, Chem. Rev.; 1999, 99, 1689.
98
24. Vögtle, F.; Plevoets, M.; Nieger, M.; Azzellini, G. C.; Credi, A.; de Cola,L.; de Marchis,
V.; Venturi, M.; Balzani, V.; “Dendrimers IV: Metal Coordination, Selfassembly,
Catalysis”, J. Am. Chem. Soc.; 1999, 121, 6290.
25. Astruc, D.; Chardac, F.; “Dendritic Nanomaterials for Environmental Remediation”,
Chem. Rev.; 2001, 101, 2991.
26. Valerio, C.; Alonso, E.; Ruiz, J.; Blais, J. C.; Astruc, D.; “Frontiers in Transition MetalContaining Polymers”, Angew. Chem. Int. Ed.; 1999, 38, 1747.
27. Albert, M.; van Koten, G. “Intelligent Macromolecules for Smart Devices: From
Materials Synthesis to device applications”, Adv. Mater.; 1999, 11, 171.
28. Balzani, V.; Campagna, S.; Denti, G.; Juris, A.; Serroni, S.; Venturi, M.; “Design,
Synthesis and Characterization of new Supramoleculer Achitectures”, Acc. Chem. Res.;
1999, 31, 26.
29. Oosterom, G. E.; Reek, J. N. H.; Kamer, J. N. H.; van Leeuwen, P. W. N. M.;
“Transition Metal Catalysis Using Functionalized Dendrimers”, Angew. Chem. Int. Ed.;
2001, 40, 1828.
30. S. Hecht, J. M. J. Fréchet, "Dendritic Encapsulation of Function: Applying Nature's Site
Isolation Principle from Biomimetics to Materials Science", Angew. Chem. Int. Ed.;
2001, 40 (1), 74–91.
31. Frechet, Jean M.; Donald A. Tomalia, “Dendrimers and Other Dendritic Polymers”.
New York, NY: John Wiley & Sons, ISBN 978-0-471-63850-6, (March 2002).
32. Fischer, M.; Vogtle, F.; "Dendrimers: From Design to Application-A Progress Report",
Angew. Chem. Int. Ed.; 1999, 38 (7), 884.
33. (a) Bansal, K. K.; Kakde, D.; Gupta, U.; Jain, N. K. “Development and Characterization
of Triazine Based Dendrimers for Delivery of Antitumor Agent", J. Nanosci.
Nanotechnol.; 2010, 10, 8395-8404. b) Chan-Thaw, C. E.;Villa, A.; Katekomol, P.; Su,
D.; Thomas, A.; Prati, L. "Covalent Ttriazine Framework as Catalytic Support for
Liquid Phase Reaction", Nano Lett.; 2010, 10, 537-541.
34. G. R. Newkome, C. N. Moorefield, F. Vogtle, Dendrimers and Dendrons: Concepts.
Syntheses. Applications. 1®* edn; Wiley-VCH: Weinheim, 2001.
35. T. Zincke, Chem. Ber. 1869, 2, 739.
36. C. Fridel, J. M. Crafts, Bull Soc. Chem. 1885, 47, 448.
99
37. C. K. Ingold, L. C. Nickolls, J. Chem. Soc. 1922, 121, 1638.
38. a) P. J. Flory, J. Am. Chem. Soc. 1952, 74, 2718. b) P. J. Flory, Principles of Polymer
Chemistry: Cornell Uniyersity Press: Ithaca, NewYork, 1953.
39. Buhleier, E.; Wehner, W.; Vögtle, F. Synthesis 1978, 2, 155–158.
40. Tomalia, D. A.; Fréchet, J. M. J. J. Polym. Sci. Part A: Polym. Chem. 2002, 40, 2719–
2728.
41. Maciejewski, M. J. Macromol. Sci. A Chem. 1982, 17, 689–703.
42. de Gennes, P. G.; Hervet, H. J. Physique-Lett. 1983, 44, 351–360.
43. Tomalia, D. A.; Baker, H.; Dewald, J.; Hall, M.; Kallos, G.; Martin, S.; Roeck, J.;
Ryder, J.; Smith, P. Polym. J. 1985, 17, 117–132.
44. Newkome, G. R.; Yao, Z.-q.; Baker, G. R.; Gupta, V. K. J. Org. Chem. 1985, 50, 20032004.
45. Hawker, C. J.; Fréchet, J. M. J. J. Am. Chem. Soc. 1990, 112, 7638–7647.
46. Miller, T. M.; Neenan, T. X. Chem. Mater. 1990, 2, 346–349.
47. Gunatillake, P. A.; Odian, G.; Tomalia, D. A. Macromolecules 1988, 21, 1556–1562.
48. Kim, Y. H.; Webster, O. W. J. Am. Chem. Soc. 1990, 112, 4592–4593.
49. Hawker, C. J.; Lee, R.; Fréchet, J. M. J. J. Am. Chem. Soc. 1991, 113, 4583–4588.
50. Gauthier, M.; Möller, M. Macromolecules 1991, 24, 4548–4553.
51. Tomalia, D. A.; Hall, B. M.; Hedstrand, D. M. Macromolecules 1987, 20, 1164–1167.
52. Naylor, A. M.; Goddard III, W. A.; Kiefer, G. E.; Tomalia, D. A. J. Am. Chem. Soc.
1989, 111, 2339–2341.
53. Buhleier, E.; Wehner, W.; Vögtle, F. Synthesis 1978, 2, 155–158.
54. Wörner, C.; Mülhaupt, R. Angew. Chem. Int. Ed. Engl. 1993, 32, 1306–1308.
55. De Brabander-van den Berg, E. M. M.; Meijer, E. W. Angew. Chem. Int. Ed. Engl.
1993, 32, 1308–1311.
56. Tomalia, D. A.; Baker, H.; Dewald, J.; Hall, M.; Kallos, G.; Martin, S.; Roeck, J.;
Ryder, J.; Smith, P. Polym. J. 1985, 17, 117–132.
57. Naylor, A. M.; Goddard III, W. A.; Kiefer, G. E.; Tomalia, D. A. J. Am. Chem. Soc.
1989, 111, 2339–2341.
58. Hawker, C. J.; Fréchet, J. M. J. J. Am. Chem. Soc. 1990, 112, 7638–7647.
100
59. Newkome, G. R.; Yao, Z.-q.; Baker, G. R.; Gupta, V. K. J. Org. Chem. 1985, 50, 2003–
2004.
60. Inoue, K. Prog. Polym. Sci. 2000, 25, 453–571.
61. Zhao, M.; Sun, L.; Crooks, R. M. J. Am. Chem. Soc. 1998, 120, 4877–4878.
62. Balogh, L.; Tomalia, D. A. J. Am. Chem. Soc. 1998, 120, 7355–7356.
63. Gröhn, F.; Bauer, B. J.; Akpalu, Y. A.; Jackson, C. L.; Amis, E. J. Macromolecules
2000, 33, 6042–6050.
64. Scott, R. W. J.; Ye, H.; Henriquez, R. R.; Crooks, R. M. Chem. Mater. 2003, 15, 3873–
3878.
65. Gu, Y.; Xie, H.; Gao, J.; Liu, D.; Williams, C. T.; Murphy, C. J.; Ploehn, H. J. Langmuir
2005, 21, 3122–3131.
66. Peng, Z.; Zhang, J.; Sun, X.; Yang, J.; Diao, J. Colloid Polym. Sci. 2009, 287, 609–614.
67. Atwater, J. E.; Akse, J. R.; Holtsnider, J. T. Materials Letters 2008, 62, 3131–3134.
68. Scott, R. W. J.; Wilson, O. M.; Oh, S.-K.; Kenik, E. A.; Crooks, R. M. J. Am. Chem.
Soc..
2004, 125, 15583–15591
69. Gu, Y.; Wu, G.; Hu, X. F.; Chen, D. A.; Hansen, T.; zur Loye, H.-C.; Ploehn, H. J. J.
Power Sources 2010, 195, 425–434.
70. Newkome, G. R.; He, E.; Moorefield, C. N. Chem. Rev. 1999, 99, 1689–1746.
71. Cuadrado, I.; Morán, M.; Casado, C. M.; Alonso, B.; Losada, J. Coord. Chem.Rev.
1999, 193–195, 395–445.
72. Berger, A.; Gebbink, R. J. M. K.; van Koten, G. Top. Organomet. Chem. 2006, 20, 1–38.
73. (a) King, A. S. H.; Twyman, L. J. J. Chem. Soc., Perkin Trans. 2002, 1, 2209–2218.
(b) van Heerbeek, R.; Kamer, P. C. J.; van Leeuwen, P. W. N. M.; Reek, J. N. Chem.
Rev. 2002, 102, 3717–3756. (c) Ribaudo, F.; van Leeuwen, P. W. N. M.; Reek, J. N. H.
Top. Organomet. Chem. 2006, 20, 39–59.
74. Knapen, J. W. J.; van der Made, A. W.; de Wilde, J. C.; van Leeuwen, P. W. N. M.;
Wijkens, P.; Grove, D. M.; van Koten, G. Nature 1994, 372, 659–663.
75. Reetz, M. T.; Lohmer, G.; Schwickardi, R. Angew. Chem. Int. Ed. Engl. 1997, 36, 1526–
1529.
101
76. Bourque, S. C.; Maltais, F.; Xiao, W.-J.; Tardif, O.; Alper, H.; Arya, P.; Manzer, L. E. J.
Am. Chem. Soc. 1999, 121, 3035–3038.
77. Oosterom, G. E.; van Haaren, R. J.; Reek, J. N. H.; Kamer, P. C. J.; van Leeuwen,
P. W. N. M. Chem. Commun. 1999, 12, 1119–1120.
78. Albrecht, M.; Hovestad, N. J.; Boersma, J.; van Koten, G. Chem. Eur. J. 2001, 7, 12891294.
79. Fischer, M.; Vögtle, F. Angew. Chem. Int. Ed. 1999, 38, 884–905.
80. Navarro, G.; de ILarduya, C. T. Nanomedicine: Nanotechnology, Biology, and Medicine
2009, 5, 287–297.
81. Bielinska, A.; Kukowska-Latallo, J. F.; Johnson, J.; Tomalia, D. A.; Baker Jr., J. R.
Nucleic Acids Research 1996, 24, 2176–2182.
82. Jansen, J. F. G. A.; Meijer, E. W. J. Am. Chem. Soc. 1995, 117, 4417–4418.
83. (a) Malik, N.; Evagorou, E. G.; Duncan, R. Anticancer Drugs 1999, 10, 767–776
(b) Howell, B. A.; Fan, D. Proc. R. Soc. A 2010, 466, 1515–1526.
84. Cheng, Y.; Li, M.; Xu, T. Eur. J. of Med. Chem. 2008, 43, 1791–1795.
85. Shaunak, S.; Thomas, S.; Gianasi, E.; Godwin, A.; Jones, E.; Teo, I.; Mireskandari,
K.; Luthert, P.; Duncan, R.; Patterson, S.; Khaw, P.; Brocchini, S. Nature
Nanobiotechnology 2004, 22, 977–984.
86. (a) Devadoss, C.; Bharathi, P.; Moore, J. S. J. Am. Chem. Soc. 1996, 118, 9635–9644.
(b) Adronov, A.; Fréchet, J. M. J. Chem. Commun. 2000, 18, 1701–1710.
(c) Nantalaksakul, A.; Reddy, D. R.; Bardeen, C. J.; Thayumanavan, S. Photosynthesis
Research 2006, 87, 133–150.
(d) Lo, S. C.; Burn, P. L. Chem. Rev. 2007, 107, 1097–1116.
87. Tomalia, D. A.; Baker, H.; Dewald, J.; Hall, M.; Kallos, G.; Martin, S.; Roeck, J.; Ryder,
J.; Smith, P. Polym. J. 1985, 17, 117–132.
88. Tomalia, D. A.; Hall, B. M.; Hedstrand, D. M. Macromolecules 1987, 20, 1164–1167.
89. Zhao, M.; Sun, L.; Crooks, R. M. J. Am. Chem. Soc. 1998, 120, 4877–4878.
90. Balogh, L.; Tomalia, D. A. J. Am. Chem. Soc. 1998, 120, 7355–7356.
91. Ottaviani, M. F.; Bossmann, S.; Turro, N. J.; Tomalia, D. A. J. Am. Chem. Soc 1994,
116, 661–671.
92. Abe, H.; Tesche, C. B.; Schulze, W. Chem. Phys. 1982, 68, 137–141.
102
93. Gröhn, F.; Bauer, B. J.; Akpalu, Y. A.; Jackson, C. L.; Amis, E. J. Macromolecules
2000, 33, 6042–6050.
94. Scott, R. W. J.; Ye, H.; Henriquez, R. R.; Crooks, R. M. Chem. Mater. 2003, 15, 3873–
3878.
95. Gu, Y.; Xie, H.; Gao, J.; Liu, D.; Williams, C. T.; Murphy, C. J.; Ploehn, H. J. Langmuir
2005, 21, 3122–3131.
96. Peng, Z.; Zhang, J.; Sun, X.; Yang, J.; Diao, J. Colloid Polym. Sci. 2009, 287, 609–614.
97. Atwater, J. E.; Akse, J. R.; Holtsnider, J. T. Materials Letters 2008, 62, 3131–3134.
98. Scott, R. W. J.; Wilson, O. M.; Oh, S.-K.; Kenik, E. A.; Crooks, R. M. J. Am.
Chem.
Soc. 2004, 125, 15583–15591.
99. Gu, Y.; Wu, G.; Hu, X. F.; Chen, D. A.; Hansen, T.; zur Loye, H.-C.; Ploehn, H. J.
J. Power Sources 2010, 195, 425–434.
100. Hedden, R. C.; Bauer, B. J. Macromolecules 2003, 36, 1829–1835.
101. Hedden, R. C.; Bauer, B. J.; Smith, P. A.; Gröhn, F.; Amis, E. Polymer 2002, 43, 5473–
5481.
102. C. Gorman, Advanced Materials, 1998, 10 (4), 295–295.
103. I. Cuadrado, M. S. Morán, C. M. Casado, B. Alonso, J. Losada, Coordination
Chemistry Reviews, 1999, 193-195, 395–445.
104. F. Stoddart, T. Welton, Polyhedron, 1999, 18 (27), 3575. 105.
Venturi, M., Serroni, S., Juris, A., Campagna, S., Balzani, V., Top. Curr. Chem. 1998
, 197, 193.
107. Denti, G., Serroni, S., Juris, A., Ciano, M., Balzani, V. in A. F. Williams, C. Floriani, A
. Merbach (Eds.), Perspectives in Coordination Chemistry, VCH, Basel 1992, p. 153.
108. Serroni, S., Juris, A., Venturi, M., Campagna, S., Resino, I. R., Denti, G., Credi, A.
; Balzani, V., J. Mater. Chem. 1997, 7, 1227.
109. Campagna, S., Denti, G., De Rosa G., Sabatino, G., Ciano, M., Balzani, V., Inor
g. Chem. 1989, 28, 2565.
110. Campagna, S., Denti, G., Sabatino, L., Serroni, S., Ciano, M., Balzani, V., Gazz. Chim
. Ital. 1989, 119, 415.
111. Campagna, S., Denti, G., Sabatino, L., Serroni, S., Ciano, M., Balzani, V., J. Chem. Soc
. Chem. Commun. 1989, 1500.
112. Serroni, S., Juris, A., Campagna, S., Venturi, M., Denti, G., Balzani, V., J. Am. Chem
. Soc. 1994, 116, 9086.
103