Accepted Manuscript
Cation – π interactions: complexes of Guanidinium and simple aromatic sys‐
tems
Fernando Blanco, Brendan Kelly, Ibon Alkorta, Isabel Rozas, José Elguero
PII:
DOI:
Reference:
S0009-2614(11)00705-6
10.1016/j.cplett.2011.06.012
CPLETT 29351
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Chemical Physics Letters
Received Date:
Accepted Date:
12 May 2011
6 June 2011
Please cite this article as: F. Blanco, B. Kelly, I. Alkorta, I. Rozas, J. Elguero, Cation – π interactions: complexes
of Guanidinium and simple aromatic systems, Chemical Physics Letters (2011), doi: 10.1016/j.cplett.2011.06.012
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Cation– interactions: complexes of Guanidinium and
simple aromatic systems
Fernando Blanco,a Brendan Kelly,b Ibon Alkorta,c Isabel Rozasb,* and José Elgueroc
a
Molecular Design Group, School of Biochemistry and Immunology,
University of Dublin, Trinity College, Dublin 2, Ireland
b
School of Chemistry, University of Dublin, Trinity College, Dublin 2, Ireland
c
Instituto de Química Médica (CSIC), Juan de la Cierva 3, 28006-Madrid, Spain
Abstract
We have theoretically studied, in gas phase and using PCM-water solvation, the complexes
established by the biologically relevant guanidinium cation and simple aromatic systems
(benzene, naphthalene and pyridine). In gas phase only hydrogen bonded complexes were
obtained, whereas using PCM-water different cation– complexes for the three aromatic
systems were found. The interactions established within these complexes have been analyzed
by means of the Atoms in Molecules and Natural Bond Orbital approaches. Finally,
experimental evidence of the cation– interactions created by guanidinium was found in the
crystal structure of N-(5-methylpyridin-2-yl)guanidinium chloride, which was also
theoretically analyzed.
*Corresponding author, Phone: (+353)18963731, Fax: (+353)16712826, email: [email protected].
Introduction
Since the first evidence of a cation– interaction, published by Kerbale in 1981,1 where it was
found that benzene stabilizes K+ ions in the gas phase better than in water, there has been a
vast interest for the experimental and computational study of this type of interaction. MeotNer established that not only metallic cations but also organic ones were good binders in the
gas phase.2 Burley et al. found a significant tendency for cations to be in close proximity to
aromatic rings when analyzing 33 high resolution protein crystals structures;3 and Flocco and
Mowbray realized that the guanidinium group of Arg is arranged just directly over the center
of the rings of aromatic amino acids more often than was expected.4
Around
1986,
when
researching
in
supramolecular
chemistry,
Dougherty
used
adamantylammonium salts to bind some cyclophanes. Unexpectedly, it was the ammonium
moiety and not the aliphatic one what bound into the hydrophobic pocket of the host even in
aqueous solution. Moreover, in several studies that followed this one, phenyl hosts were
found to bind cationic guests more strongly than neutral or electron rich molecules and this
interaction was even stronger and more specific in water, where other strong non-covalent
interactions such as hydrogen bonds (HBs) fail.5 Later on, Dougherty group carried out a
survey of the protein database showing that cation-stabilization is a major aspect of protein
structure and enzyme catalysis; in general Arg is the residue found to bind most often.6,7
In the 90s Janet M. Thornton and co. developed a series of programs (SIRIUS) to analyze the
preferred packing arrangements between protein residues based on crystallographic
information.8 This allowed them to study a number of amino-aromatic interactions finding
that out of 1171 interactions, 123 were ‘above ring’ and from these 76 were stacked.9 As well,
by the analysis of 55 high resolution protein structures, they found that aromatic amino acids
act better in stacking interactions than as HB acceptors.10
The study of cation– interactions in protein stability and DNA or RNA binding proteins has
been the objective of several studies by Gromiha and co. They found that Arg has a higher
preference to form cation–
interactions than Lys and that the roles of these cation–
interactions are different from other non-covalent contacts in the stability of protein
structures.11,12,13
In a very recent and interesting review Diederich and co. summarize results reported since
2003 in arene–arene, perfluoroarene–arene, S···aromatic, cation– , and anion– interactions,
as well as hydrogen bonding to
systems. In the particular case of cation– interactions, it is
emphasized not only the importance of investigations on model systems for the quantification
of the interactions, but also how this particular type of interactions has been used in ligand
design, de novo peptide design, and to control some organic syntheses.14
Some authors have suggested that these contacts come from the cation interacting with the
quadrupole moment of the aromatic monomer. Thus, Cubero et al. performed theoretical
calculations on a series of compounds with a similar aromatic core demonstrating that
polarization is a large contribution to cation– interactions.15 In this sense, Frontera et al., in a
recent review, have deepened in the understanding of the forces involved in these interactions.
They found that some physical properties of the aromatic rings and of the interacting ion are
directly related to the strength of the interaction (i.e. the duality of arenes with very small
quadrupole moment or the anion binding affinity of electronrich molecules with large
polarizability due to very extended -systems) and also they analysed the effect of combining
other weak interactions to the ion– ones.16
Continuing with our interest in the interactions and properties of the guanidinium cation17,18
and considering its special characteristics (quasi-planar structure and positive charge
delocalized over the entire system) we study here the complexes formed by this particular
cation and some simple aromatic rings to understand the established cation– interactions.
Thus, fundamental aromatic systems were chosen: benzene (2), as a 1-ring aromatic system,
naphthalene (3), as a 2-ring aromatic system, and pyridine (4), as one of the simplest nitrogen
containing heteroaromatic systems (Figure 1). We have recently found that the correct
description of the interactions of this group requires the inclusion of solvation effects by
means of PCM calculations with aqueous environment; hence, this type of calculation has
also been included in the present study. Moreover, our synthetic work in aromatic
guanidinium derivatives19 has provided us with the crystal structure of 5-methyl(pyridine-2yl)guanidinium hydrochloride, experimentally confirming the tendency of these groups to
form cation– interactions.
Computational Methods
The systems have been optimized using both the Gaussian0320 and Gaussian0921 packages at
the M05-2X22 computational level with the 6-31+G(d,p)23 and the 6-311+G(d,p)24 basis sets.
The M05-2X functional has been shown to be able to properly describe weak interactions
taking into account dispersion forces where other traditional functionals fail.25 Frequency
calculations have been performed at the lower computational level to confirm that the
resulting optimized structures are energetic minima. Effects of water solvation have been
included by means of the SCFR-PCM approaches implemented in the Gaussian-09 package
including dispersing, repulsing and cavitating energy terms of the solvent in the optimization.
The interaction energy of the complexes in the present article has been calculated as the
difference between the supermolecule’s energy and the sum of energies of the isolated
monomers in their minimum energy configuration. The interaction energy in gas phase has
been corrected from the inherent basis set superposition error (BSSE) using the full
counterpoise method.26
The electron density of the complexes has been analyzed within the Atoms in Molecules
(AIM) theory27 using the AIMPAC,28 MORPHY,29,30 and AIMALL31 programs. The Natural
Bond Orbital (NBO) method32 has been used to analyze the interaction of the occupied and
unoccupied orbitals with the NBO-3 program33 since this kind of interaction is of utmost
importance in the formation of hydrogen bonds and other charge transfer complexes.
Results and Discussion
Structure and Energy
Considering the almost planar structure of guanidinium cation (with a delocalized positive
charge) and the basic features common to all aromatic systems (planar and with a delocalized
-cloud), three different possible initial complexes were considered: (i) stacked systems either
staggered (1:2-SS, 1:3-SS, and 1:4-SS) or eclipsed (1:2-SE, 1:3-SE and 1:4-SE); (ii) T-shape
(1:2-T and 1:3-T); or (iii) perpendicular (1:4-P) configurations (Figure 1).
(a)
(b)
Figure 1. (a) Guanidinium cation and aromatic rings studied in this work and (b) simplified
models of the interactions established.
In the gas phase, no stacked complex was obtained since all of them evolved to complexes
formed by hydrogen bond (HB) interactions in T-shape (1:2-T or 1:3-T) or perpendicular
(1:4-P) dispositions (Figure 2). In the particular case of the guanidinium-naphthalene
complex starting from a stacked disposition, it evolved to a ‘leaning’ T-shape configuration
(1:3-T’) in which two of the N-H bonds of guanidinium were interacting not with the centre
of the aromatic rings as in the T-shape complex, 1:3-T (C2v), but symmetrically with one C
atom of each of the 6-membered rings (Figure 2). This leaning T-shape structure has slightly
better interaction energy (<1 kJ mol–1) than the C2v complex 1:3-T (Table 1).
1:2-T
1:3-T
1:3-T’
1:4-P
Figure 2.- Guanidinium-aromatic system complexes obtained at M05-2X/6-311+G(dp) level
in the gas phase.
In the three T-shape complexes, two N-H groups of guanidinium seem to interact with C=C
double bonds (1:2-T),
-cloud (1:3-T) and aromatic C atoms (1:3T’) of benzene or
naphthalene with interacting distances around 2.4
(see Table 2). In the case of the
perpendicular complex 1:4-P, the guanidinium N-H groups simultaneously interact with the
pyridinic N atom with shorter interaction distances (2.06 , see Table 2).
However, when considering aqueous solvation by means of the PCM approximation, not only
T-shape and perpendicular complexes were obtained, but also several stacked cation–
complexes were optimized. Regarding the hydrogen bonded complexes obtained at PCM
level with benzene and pyridine, their optimized geometries were similar to those obtained in
the gas phase. However, the guanidinium cation in the T-shaped complex with naphthalene,
when in an aqueous environment, turns around the C(+)-N perpendicular axis to the aromatic
ring in such a way that it moves from interacting with the centers of both 6-membered rings to
pointing, each of the interacting NH2 groups, to C-2 and C-5 in a diagonal manner (Figure 3).
Table 1. Absolute (hartree), BSSE (kJ mol-1) and interaction (kJ mol-1) energies of the
Guanidinium:Aromatic complexes studied at M05-2X/6-311+G(d,p) computational level in
the gas phase and PCM (water solvent).
Gas
PCM
ETotal
EI
EI+BSSE
ETotal
EI
1:2-SS
Unstable
–
–
–438.156157
–9.8
1:2-SE
Unstable
–
–
–438.155871
–9.0
1:2-T
–438.096013
–60.2
–57.5
–438.158698
–16.4
1:3-SS
Unstable
–
–
–591.824323
–18.8
1:3-T’
–591.769257
–78.4
–74.7
–
–
1:3-T
–591.768842
–77.3
–73.8
–591.824422
–19.0
1:4-SS
Unstable
–
–
–454.197110
–5.4
1:4-SE
Unstable
–
–
–454.197334
–6.0
1:4-P
–454.149429
–97.1
–94.3
–454.208322
–34.9
Benzene formed two types of stacked complexes with guanidinium in aqueous environment,
one eclipsed (1:2-SE) and one, slightly more stable, staggered (1:2-SS) (Table 1). In both
structures, the central C atom of guanidinium does not lie on top of the centre of the aromatic
ring, as could be expected, but on one of the C atoms in the 1:2-SE complex and on top of a
C-C bond in the staggered complex (Figure 3). The cation– complex with naphthalene (1:3SS) shows the guanidinium cation centered over one of the C atoms of the middle C4a-C8a
bond. Finally, in aqueous solvation, pyridine forms two type of stacked complexes (Figure 3),
one staggered (1:4-SS) where the carbocation C is located on top of the middle of the ring,
and another, with a similar interaction energy (difference of 0.6 kJ mol–1, Table 1), eclipsed
and displaced in such a way that the guanidinium C atom is on top of C3 of the pyridine ring
and two of the guanidinium N atoms are on top of C2 and C4 of the ring, respectively.
1:2-SS
1:2-SE
1:3-SS
1:3-T
1:4-SS
1:4-SE
Figure 3.- Stacked cation– complexes (1:2-SS, 1:2-SE, 1:3-SS, 1:4-SS and 1:4-SE) and Tshape guanidinium-naphthalene complex (1:3-T) obtained at M05-2X/6-311+G(dp) level in
PCM-water. Two views of each complex are presented for the sake of clarity.
Comparing the interaction energies of the complexes obtained in both gas phase and aqueous
solution, a difference of around 40-60 kJ mol–1 is observed always favoring the interactions in
the gas phase. This could be expected considering the big influence that solvation has on the
interactions established by the guanidinium cation as we have recently proved.34 Additionally,
the fact that the stacked systems (with small EI values ranging from –5.4 to –18.8 kJ mol–1)
were only observed in PCM computations could be explained by the effect that the modeled
water solvation around the cation lowers the HB donor ability of the N-H groups, allowing for
other types of weaker interactions such as the cation– one.
Analysis of the electron density
We have used the topological analysis of the electron density to evaluate the characteristics of
bonds and weak interactions. The graphical analysis of the complexes studied here (see some
examples in Figure 4) indicates the presence of intermolecular bond critical points (BCP) in
both cation– and hydrogen bonded complexes. These BCPs present small values of the
electron density ( ) and positive Laplacian (∇2 ) as presented in Table 2, indicating the closed
shell characteristics of the weak interactions established among the monomers.35,36
Table 2. Interaction distances ( , first atom from guanidinium and second from aromatic
system) and AIM results (electron density and Laplacian of the electron density at the BCPs,
a.u.) of the interactions established within the guanidinium-aromatic complexes.
d(X…Y)
(BCP)
∇2 (BCP)
2(N…C)
3.33
0.0078
0.0225
H …C
2.81
0.0080
0.0241
H …C
2.77
0.0080
0.0242
N …C
3.32
0.0081
0.0240
N …C
3.32
0.0081
0.0245
H …C
2.74
0.0081
0.0242
H …C
2.41
0.0125
0.0386
H …C
2.44
0.0123
0.0364
H …C
2.45
0.0113
0.0366
H …C
2.49
0.0109
0.0332
C …C
3.10
0.0085
0.0298
…
3.32
0.0077
0.0223
Environment
1:2-SS
1:2-SE
1:2-T
PCM
PCM
Gas
PCM
1:3-SS
PCM
N C
2(N…C)
3.42
0.0068
0.0207
1:3-T’
Gas
2(H…C)
2.39
0.0124
0.0396
1:3-T
Gas
2(H…C)
2.60
0.0090
0.0300
4(H…C)
2.64
0.0080
0.0280
H …C
2.42
0.0116
0.0389
H …C
2.51
0.0097
0.0315
N …C
3.35
0.0063
0.0178
…
N N
3.22
0.0078
0.0247
N …C
3.28
0.0071
0.0200
2(N…C)
3.33
0.0074
0.0234
Gas
2(H…N)
2.05
0.0237
0.0746
PCM
2(H…N)
2.08
0.0227
0.0744
PCM
1:4-SS
1:4-SE
1:4-P
PCM
PCM
In those complexes interacting in a T-shape or perpendicular approach (1:2-T; 1:3-T; 1:3-T’;
1:4-P) and optimized both in the gas phase and PCM-water, BCPs were found between two of
the N-H groups of the guanidinium cation (HB donors) and the C atoms connected by the system or, in the case of pyridine, the aromatic N atom (HB acceptors). In the case of the
stacked complexes (1:2-SS; 1:2-SE; 1:3-SS; 1:4-SS; and 1:4-SE), BCPs were found between
some of the N and H atoms of guanidinium and some of the C atoms of benzene, naphthalene
and pyridine as well as with the N atom of pyridine (Figure 4). As well, a number of ring and
cage critical points (RCP and CCP) were found between both molecular planes (i.e.
guanidinium and aromatic systems). This intricate electron density scenario has been
previously described by Cubero et al.37 and Zhikol et al.38 when studying different staked
cation– complexes.
1:2-T (Gas)
1:3-T (PCM)
1:4-P (Gas)
1:2-SE (PCM)
1:3-SS (PCM)
1:4-SS (PCM)
Figure 4. Molecular graph (AIM) of the hydrogen bonded complexes 1:2-T, 1:3-T and 1:4-P
(up) and the cation– complexes 1:2-SS, 1:3-SS and 1:4-SS calculated at the M05-2X/6311+G(d,p) computational level in the gas phase or PCM-water as indicated in each graph.
Red, yellow and green balls indicate bond, ring and cage critical points respectively.
Previously, we have described exponential relationships between the interaction distance and
the electron density or the Laplacian at the BCPs for hydrogen bonded systems.39,40 Thus, we
have searched for such exponential relationships in all the complexes (gas phase or PCMwater) studied here. Even though no correlation was found for the five stacked cation–
complexes (1:2-SS, 1:2-SE, 1:3-SE, 1:4-SS and 1:4-SE) optimized with PCM-water, very
good correlations exist when only the distances and density parameters for the hydrogen
bonded complexes (1:2-T, 1:3-T, 1:3-T’ and 1:4-P) are considered both at the gas and
aqueous phases:
(BCP) = 1.01e–1.82d(XY) (R² = 0.990) and ∇2 (BCP) = 2.76e–1.76d(XY) (R² =
0.98); for XY= HC or HN. Therefore, it seems that this type of relationships which is always
found in hydrogen bonded systems cannot be extended to stacking interactions.
Natural Bond Orbital analysis
The NBO analysis of these complexes was carried out to assess the charge transferred and
orbital interactions established and the results are presented in Table 3. The study of the NBO
charges shows that in those complexes formed by HB interactions there is a charge transfer
from the aromatic systems (e-donors) to the guanidinium cation (e-acceptor) as indicated by
the tabulated positive values. However, in the stacking cation– systems insignificant or no
charge-transfer from the guanidinium towards the aromatic rings is observed.
The NBO second order perturbation energy [E(2), in Table 3 only values > 1.3 kJ mol-1 are
presented] reveals, in the hydrogen bonded complexes studied here, orbital interactions from
the C-C or C-N bonding orbitals of the aromatic molecules to the antibonding orbitals of the
guanidinium N-H groups (BD [C,N]C
BD* NH). In the particular case of pyridine
complex 1:4-P, the most important orbital interaction is established from the pyridine N lone
pair to the antibonding N-H orbital of the guanidinium (LP N
BD* NH). In the stacked
complexes, the most important orbital interactions are established from the C-C bonding
orbitals to an “empty” lone pair of the guanidinium central C atom (BD CC
sometimes to an antibonding N-H orbital (BD CC
the orbitals traditionally taken to define a
LP* C) and
BD* NH). It is interesting to notice how
system (BD CC or BD NC) are involved in the
stacking interactions. In general, the orbital interactions observed in all these complexes
involve a donation from the aromatic system to guanidinium. However, in most of the stacked
cation– complexes the opposite is observed [LP CG or NG
BD* C(N)C, see Table 3 and
Supplementary Information] although with small E(2) values (ranging from 0.4 to 2.9 kJ
mol-1) .
We have found that, in general, the E(2) values follow a similar trend to the absolute EIs in
the complexes calculated using PCM-water. Hence, results obtained for the hydrogen bonded
complexes (largest EI values, Table 1) show larger E(2) energies than the stacked complexes.
The exception is 1:3T with medium EI but low E(2), maybe because the HBs are established
with the
–cloud of naphthalene. This could indicate that orbital interactions play an
important role in the stabilization of the complexes. Even though in previous studies we found
an exponential correlation between E(2) and the
at the BCP,41 no such correlation was found
in the complexes studied here.
Table 3.- Orbital energy [E(2),a kJ mol-1] and charge transfer (e, aromatic
guanidinium,
positive values). Orbital interactions from the guanidinium to the aromatic systems are
indicated in italics.
1:2-SS
1:2-SE
PCM
PCM
Gas
PCM
Charge
0.000
BD CC
LP* CG
11.7
BD CC
BD* NH
2.2
BD CC
BD* NH
1.8
BD* CC
LP NG
1.5
BD* CC
LP NG
1.0
BD CC
LP* CG
12.3
BD CC
BD* NH
1.8
LP CG
1.4
BD CC
BD* NH
17.2
BD CC
BD* NH
10.8
BD CC
BD* NH
12.2
BD CC
BD* NH
4.6
BD CC
BD* NH
3.3
BD* CC
LP NG
1.2
BD* CC
1:2-T
E(2)a
0.001
0.022
0.011
1:3-SS
PCM
BD CC
LP* CG
16.5
-0.001
1:3-T’
Gas
BD CC
BD* NH
9.9
0.018
1:3-T
Gas
PCM
1:4-SS
1:4-SE
PCM
PCM
BD CC
BD* NH
8.9
BD CC
BD* NH
2.0
BD CC
BD* NH
2.5
BD CC
BD* NH
3.3
BD CC
BD* NH
3.3
BD CC
BD* NH
3.0
BD CC
BD* NH
3.0
BD CC
BD* NH
2.9
BD CC
BD* NH
2.9
BD CC
BD* NH
5.9
BD CC
BD* NH
4.6
BD CC
BD* NH
2.7
BD CC
BD* NH
1.7
BD CC
LP* CG
11.7
BD* CC
LP NG
2.2
BD* CC
LP NG
1.3
BD CC
LP* CG
10.1
BD CC
BD* NH
1.4
LP NG
2.9
LP N
BD* NH
33.3
LP N
BD* NH
30.9
BD* CC
1:4-P
Gas
PCM
a
-1
Only values > 1.3 kJ mol
Supplementary Information.
BD NC
BD* NH
4.8
BD NC
BD* NH
4.7
LP N
BD* NH
27.4
LP N
BD* NH
27.4
BD NC
BD* NH
3.6
BD NC
BD* NH
3.4
0.012
0.007
-0.002
-0.002
0.045
0.035
are presented. The whole set of values is gathered in the
N-(Pyridin-2-yl)guanidinium salts: an experimental case of cation– interactions
Recent research in our group has demonstrated the conformational preference of different
N-(pyridin-2-yl)guanidinium cations due to a stabilizing intramolecular HB (IMHB, Figure
5a).17 During the course of that study, it was possible to resolve the crystal structure of the 5methyl derivative (5) by X-ray spectroscopy (Figure 5a,b) revealing a stacked cation–
interaction between the pyridine ring of one monomer and the guanidinium group of another,
piling up to four units alternating the aromatic and cationic moieties to optimize the contacts.
In this tetramer, the relative position of the pyridinic N atom alternates every two pairs, being
on the same side in the upper dimer and on opposite sides in the lower one (Figure 5b).
Thus, we have carried out the theoretical study [M05-2X/6-311+G(d,p)] of the cation–
interactions in the two possible dimers of N-(pyridin-2-yl)guanidinium found in the crystal
optimizing the structures not only in the gas phase, but also in water and DMSO using the
PCM approach. As in our theoretical study with simple aromatic systems, no stacked cation–
system was obtained in the gas phase; however, these stacking systems were found when
PCM-solvation in water (Figure 5c) or in DMSO was considered. The most stable dimer was
that with the pyridinic N atoms in opposite sides (Figure 5c, right), by 1.9 kJ mol-1 in both
solvents. The interaction energies obtained for both dimers showed that they were more stable
in water than in DMSO by 1.8 kJ mol-1.
The AIM analysis of these dimers showed the corresponding BCPs between C or N atoms of
the pyridin-2-yl ring and N atoms of the guanidinium moiety as well as a number of ring and
cage critical points in between the planes of the monomers (Figure 5d), in agreement with our
results for the guanidinium complexes with benzene, naphthalene and pyridine.
(a)
-1
(b)
-1
EI= -22.4 kJ mol
EI= -24.3 kJ mol
(c)
(d)
Figure 5. X-ray crystal structure of N-(5-methylpyridin-2-yl)guanidinium chloride (5): (a)
isolated monomer, (b) tetramer as in the crystal unit cell, (c) optimized structures and (d) AIM
critical points of the two dimers present in the crystal tetramer studied at M05-2X/6311+G(d,p) level (PCM-water).
Conclusions
We have theoretically studied the complexes formed between guanidinium and simple
aromatic systems such as benzene, naphthalene and pyridine in the gas phase and using PCM
water solvation. In the gas phase only hydrogen bonded complexes were obtained for the
three aromatic systems, whereas using PCM-water different cation–
complexes were
optimized.
The interaction energies in gas phase were corrected of the BSSE and the values obtained
were much larger than those resulting from the PCM-water calculations. The cation seems to
modify its interactions (HBs or stacking) depending on the surrounding solvation that
competes with the other monomer in the formation of the complexes. Additionally, the
interaction energies of those complexes formed by HBs are larger (more stabilizing) than for
the cation– systems.
The analysis of the electron density showed the expected BCPs for the hydrogen bonded
complexes (both at gas phase and PCM) and BCPs associated to the cation–
dimers.
Moreover, NBO analysis of the orbital interactions showed, for the HB dimers, transfer from
the bonding C-C bond of benzene or naphthalene and the lone pair of the pyridinic N to the
antibonding N-H bonds of guanidinium. For the cation– complexes, C-C bonding orbitals
interact to an “empty” lone pair of the guanidinium central C atom and sometimes to an
antibonding N-H orbital.
Finally, experimental evidence of the cation– interactions established by the guanidinium
cation was found in the crystal structure of N-(5-methylpyridin-2-yl)guanidinium chloride.
This compound was also theoretically studied and the results were in agreement with those
obtained with the guanidinium:[benzene, naphthalene, pyridine] systems. Considering the
interesting results obtained studies with other aromatic systems of biological relevance are
being performed.
Acknowledgments
This work was supported by the Ministerio de Ciencia e Innovación (Project No. CTQ200913129-C02-02) and the HEA-PRTLI-5 (BK). Thanks are given to the CTI (CSIC, Spain) and
to the IITAC cluster (TCHPC-TCD, Ireland) for allocation of computer time.
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H
H
(a
)
N
H
N
H
N
H
H
guanidinium (1)
N
benzene (2)
naphthalene (3)
pyridine (4)
(b
)
Figure 1. (a) Guanidinium cation and aromatic rings studied in this work and (b)
simplified models of the interactions established.
1:2-T
1:3-T
1:3-T’
1:4-P
Figure 2.- Guanidinium-aromatic system complexes obtained at M05-2X/6-311+G(dp)
level in the gas phase.
1:2-SS
1:2-SE
1:3-SS
1:3-T
1:4-SS
1:4-SE
Figure 3.- Stacked cation– complexes (1:2-SS, 1:2-SE, 1:3-SS, 1:4-SS and 1:4-SE) and
T-shape guanidinium-naphthalene complex (1:3-T) obtained at M05-2X/6-311+G(dp)
level in PCM-water. Two views of each complex are presented for the sake of clarity.
1:2-T (Gas)
1:3-T (PCM)
1:4-P (Gas)
1:2-SE (PCM)
1:3-SS (PCM)
1:4-SS (PCM)
Figure 4. Molecular graph (AIM) of the hydrogen bonded complexes 1:2-T, 1:3-T and
1:4-P (up) and the cation– complexes 1:2-SS, 1:3-SS and 1:4-SS calculated at the M052X/6-311+G(d,p) computational level in the gas phase or PCM-water as indicated in each
graph. Red, yellow and green balls indicate bond, ring and cage critical points
respectively.
(a)
-1
(b)
-1
EI= -22.4 kJ mol
EI= -24.3 kJ mol
(c)
(d)
Figure 5. X-ray crystal structure of N-(5-methylpyridin-2-yl)guanidinium chloride (5):
(a) isolated monomer, (b) tetramer as in the crystal unit cell, (c) optimized structures and
(d) AIM critical points of the two dimers present in the crystal tetramer studied at M052X/6-311+G(d,p) level (PCM-water).
Table 1. Absolute (hartree), BSSE (kJ mol-1) and interaction (kJ mol-1) energies of the
Guanidinium:Aromatic complexes studied at M05-2X/6-311+G(d,p) computational level
in the gas phase and PCM (water solvent).
Gas
PCM
ETotal
EI
EI+BSSE
ETotal
EI
1:2-SS
Unstable
–
–
–438.156157
–9.8
1:2-SE
Unstable
–
–
–438.155871
–9.0
1:2-T
–438.096013
–60.2
–57.5
–438.158698
–16.4
1:3-SS
Unstable
–
–
–591.824323
–18.8
1:3-T’
–591.769257
–78.4
–74.7
–
–
1:3-T
–591.768842
–77.3
–73.8
–591.824422
–19.0
1:4-SS
Unstable
–
–
–454.197110
–5.4
1:4-SE
Unstable
–
–
–454.197334
–6.0
–454.149429
–97.1
–94.3
–454.208322
–34.9
1:4-P
Table 2. Interaction distances ( , first atom from guanidinium and second from aromatic
system) and AIM results (electron density and Laplacian of the electron density at the
BCPs, a.u.) of the interactions established within the guanidinium-aromatic complexes.
Environment
d(X…Y)
(BCP)
∇2 (BCP)
1:2-SS
1:2-SE
1:2-T
PCM
PCM
Gas
PCM
1:3-SS
PCM
2(N…C)
3.33
0.0078
0.0225
…
H C
2.81
0.0080
0.0241
…
H C
2.77
0.0080
0.0242
…
N C
3.32
0.0081
0.0240
…
N C
3.32
0.0081
0.0245
…
H C
2.74
0.0081
0.0242
…
H C
2.41
0.0125
0.0386
…
H C
2.44
0.0123
0.0364
…
H C
2.45
0.0113
0.0366
…
H C
2.49
0.0109
0.0332
…
C C
3.10
0.0085
0.0298
…
3.32
0.0077
0.0223
2(N C)
3.42
0.0068
0.0207
2(H…C)
N C
…
1:3-T’
1:3-T
Gas
Gas
PCM
1:4-SS
1:4-SE
PCM
PCM
2.39
0.0124
0.0396
…
2.60
0.0090
0.0300
…
4(H C)
2.64
0.0080
0.0280
…
H C
2.42
0.0116
0.0389
…
H C
2.51
0.0097
0.0315
N…C
3.35
0.0063
0.0178
…
N N
3.22
0.0078
0.0247
…
2(H C)
N C
3.28
0.0071
0.0200
…
3.33
0.0074
0.0234
…
2.05
0.0237
0.0746
…
2.08
0.0227
0.0744
2(N C)
1:4-P
Gas
PCM
2(H N)
2(H N)
Table 3.- Orbital energy [E(2),a kJ mol-1] and charge transfer (e, aromatic
guanidinium, positive values). Orbital interactions from the guanidinium to the aromatic
systems are indicated in italics.
E(2)a
Charge
1:2-SS
1:2-SE
PCM
PCM
BD CC
LP* CG
11.7
BD CC
BD* NH
2.2
BD CC
BD* NH
1.8
BD* CC
LP NG
1.5
BD* CC
LP NG
1.0
BD CC
LP* CG
12.3
BD CC
BD* NH
1.8
LP CG
1.4
BD CC
BD* NH
17.2
BD CC
BD* NH
10.8
BD CC
BD* NH
12.2
BD CC
BD* NH
4.6
BD CC
BD* NH
3.3
BD* CC
LP NG
1.2
BD* CC
1:2-T
Gas
PCM
0.000
0.001
0.022
0.011
1:3-SS
PCM
BD CC
LP* CG
16.5
-0.001
1:3-T’
Gas
BD CC
BD* NH
9.9
0.018
BD CC
BD* NH
8.9
BD CC
BD* NH
2.0
BD CC
BD* NH
2.5
BD CC
BD* NH
3.3
BD CC
BD* NH
3.3
BD CC
BD* NH
3.0
BD CC
BD* NH
3.0
BD CC
BD* NH
2.9
BD CC
BD* NH
2.9
BD CC
BD* NH
5.9
BD CC
BD* NH
4.6
BD CC
BD* NH
2.7
BD CC
BD* NH
1.7
1:3-T
Gas
PCM
0.012
0.007
1:4-SS
1:4-SE
PCM
PCM
BD CC
LP* CG
11.7
BD* CC
LP NG
2.2
BD* CC
LP NG
1.3
BD CC
LP* CG
10.1
BD CC
BD* NH
1.4
LP NG
2.9
LP N
BD* NH
33.3
LP N
BD* NH
30.9
BD* CC
1:4-P
Gas
PCM
BD NC
BD* NH
4.8
BD NC
BD* NH
4.7
LP N
BD* NH
27.4
LP N
BD* NH
27.4
BD NC
BD* NH
-0.002
-0.002
0.045
0.035
3.6
BD NC BD* NH
3.4
Only values > 1.3 kJ mol are presented. The whole set of values is gathered in the
Supplementary Information.
a
-1
Graphical abstract
Highlights
•
•
•
•
•
Pi-cation interactions
Guanidinium cation
Aromatic systems
Truhlar DFT functional
N-(5-methylpyridin-2-yl)guanidinium chloride crystal structure