STRUCTURAL STUDIES OF DITHIOCARBAMATE
METAL COMPLEXES AND DICARBOXLIC ACID
METAL SALTS
BY
JIMMY AHMAD
A thesis submitted in fulfilment of the requirement for the
degree of Master of Science in Biosciences
Kulliyyah of Science
International Islamic University Malaysia
DECEMBER 2016
ABSTRACT
This thesis composed of two chapters of work applying the elements of coordination
chemistry, supramolecular chemistry and crystal engineering. A total of eleven (11) metal
complexes were successfully synthesised and the crystals of each complex were characterised
using Single Crystal X-ray Diffraction (SCXRD) analysis. Crystallographic study is the main
focus of this research principally to highlight the molecular interactions that govern the crystal
formation. The first part of the chapters described a series of transition metal ions; Fe(III),
Co(III), Ni(II), Cu(II), Zn(II) and Cd(II), each coordinated with sodium morpholine-4carbodithioate ligand, Na[S2CNC4H8O]. This series displayed versatile coordination modes;
mononuclear complexes for Fe(III), Co(III), Ni(II) and Cu(II), bimetallic complex for Zn(II)
and polymeric complex for Cd(II). This chapter outlined the structural aspect of
dithiocarbamate complexes and its binding behaviour towards transition metal groups. All
complexes were characterised using SCXRD and spectroscopic techniques including FT-IR
and PXRD. CHN elemental analysis was done to analyse elemental composition of each
complex. TGA was performed to study the thermal stability of each complex.
The second part of the chapters described a metal salt series of 2,6pyridinedicarboxylic acid (H2dipic). In this series, anionic metal complexes were
prepared and stabilised by organic cations to form five (5) metal salts complexes. The
complexes were synthesised using H2dipic as the coordinating ligand (anion) and
amine as the counter ion (cation) with Ni(II), Cu(II) and Cd(II) metal ions to give
complexes of [Ni(dipic)2][enH2], [Cd(dipic)3][enH2]2, [Cu(dipic)2][1mpH2],
[Ni(dipic)2][1epH2] and [Cd2(dipic)4(opdH)2][opdH]2 respectively. These complexes
are charge-dependent compounds, which were stabilised by protonated amines, viz.,
ethylenediamine (enH2), 1-methylpiperazine (1mpH2), 1-ethylpiperazine (1epH2) and
o-phenylenediamine (opH). This series focuses on the self-assembly of the molecules
and the non-covalent interactions present in the crystal structures, which combined the
principle of crystal engineering and supramolecular chemistry. Henceforth, the selfassembly and molecular recognition process between the ligand, amine and metal ion
(and also solvent) will lead to the deprotonation of the ligand and subsequent
protonation of the organic counter ions in order to achieve stability in the crystal
structure formation. Crystal structures of all the metal salt complexes were determined
using SCXRD. Additional analysis for structural comparison between the bulk
materials and crystal data from SCXRD was done via PXRD.
ii
‫ﺧﻼﺻﺔ اﻟﺒﺤﺚ‬
‫ﯾﺘﻜﻮن ھﺬا اﻟﺒﺤﺚ ﻣﻦ ﻓﺼﻠﯿﻦ ﻣﺘﻌﻠﻘﯿﻦ ﺑﺘﻄﺒﯿﻖ ﻋﻨﺎﺻﺮ اﻟﻜﯿﻤﯿﺎء اﻟﺘﻨﺴﯿﻘﯿﺔ‪ ،‬واﻟﻜﯿﻤﯿﺎء اﻟﻔﻮق ﺟﺰﯾﺌﯿﺔ‪،‬‬
‫واﻟﮭﻨﺪﺳﺔ اﻟﺒﻠﻮرﯾﺔ‪ .‬ﺗﻢ ﺑﻨﺠﺎح اﺳﺘﺤﺪاث اﺣﺪى ﻋﺸﺮة )‪ (11‬ﻣﻌﻘﺪة ﻓﻠﺰﯾﺔ‪ ،‬وﺗﻢ ﺗﺼﻨﯿﻒ ﺑﻠﻮراﺗﮭﺎ‬
‫ﺑﺎﺳﺘﺨﺪام ﺗﺤﻠﯿﻞ ﺣﯿﻮد اﻷﺷﻌﺔ اﻟﺴﯿﻨﯿﺔ ﻟﻠﺒﻠﻮر اﻟﻤﻔﺮد )‪ .(SCXRD‬ﻛﺎن اﻟﺘﺮﻛﯿﺰ اﻷﺳﺎﺳﻲ ﻟﮭﺬا‬
‫اﻟﺒﺤﺚ ھﻲ اﻟﺪراﺳﺔ اﻟﺒﻠﻮرﯾﺔ ﻷﺟﻞ ﺗﺴﻠﯿﻂ اﻟﻀﻮء ﻋﻠﻰ اﻟﺘﻔﺎﻋﻼت اﻟﺠﺰﯾﺌﯿﺔ اﻟﺘﻲ ﺗﺤﺪد ﺗﻜﻮن‬
‫اﻟﺒﻠﻮرات‪ .‬ﯾﺸﺮح اﻟﺠﺰء اﻷول ﻣﻦ اﻟﻔﺼﻮل ﺳﻠﺴﻠﺔ أﯾﻮﻧﺎت اﻟﻔﻠﺰات اﻻﻧﺘﻘﺎﻟﯿﺔ‪ ،‬وھﻲ اﻟﺤﺪﯾﺪ اﻟﺜﻼﺛﻲ‬
‫)‪ ،Fe(III‬واﻟﻜﻮﺑﺎﻟﺖ اﻟﺜﻼﺛﻲ )‪ ،Co(III‬واﻟﻨﯿﻜﻞ اﻟﺜﻨﺎﺋﻲ )‪ ،Ni(II‬واﻟﻨﺤﺎس اﻟﺜﻨﺎﺋﻲ )‪،Cu(II‬‬
‫واﻟﺰﻧﻚ اﻟﺜﻨﺎﺋﻲ )‪ ،Zn(II‬واﻟﻜﺎدﻣﯿﻮم اﻟﺜﻨﺎﺋﻲ )‪ ،Cd(II‬وﻛﻠﮭﺎ ﻛﺎﻧﺖ ﻣﻨﺴﻘﺔ ﻣﻊ راﺑﻄﺔ ﻣﻮرﻓﻮﻟﯿﻦ‪-4-‬‬
‫ﻛﺎرﺑﻮ ﺛﻨﺎﺋﻲ اﻟﺜﯿﻮﯾﺖ اﻟﺼﻮدﯾﻮم ]‪ .Na[S2CNC4H8O‬أظﮭﺮت ھﺬه اﻟﺴﻠﺴﻠﺔ أوﺿﺎع ﺗﻨﺴﯿﻖ‬
‫ﻣﺘﻌﺪدة‪ ،‬وﻣﻌﻘﺪات وﺣﯿﺪة اﻷﻧﻮﯾﺔ ﻟﻠﺤﺪﯾﺪ اﻟﺜﻼﺛﻲ )‪ ،Fe(III‬واﻟﻜﻮﺑﺎﻟﺖ اﻟﺜﻼﺛﻲ )‪ ،Co(III‬واﻟﻨﯿﻜﻞ‬
‫اﻟﺜﻨﺎﺋﻲ )‪ ،Ni(II‬واﻟﻨﺤﺎس اﻟﺜﻨﺎﺋﻲ )‪ ،Cu(II‬وﻣﻌﻘﺪة ﺛﻨﺎﺋﯿﺔ اﻟﻔﻠﺰ ﻟﻠﺰﻧﻚ اﻟﺜﻨﺎﺋﻲ )‪ Zn(II‬وﻣﻌﻘﺪات‬
‫ﺑﻮﻟﻤﺮﯾﺔ ﻟﻠﻜﺎدﻣﯿﻮم اﻟﺜﻨﺎﺋﻲ )‪ .Cd(II‬ﺑﯿّﻦ ھﺬا اﻟﻔﺼﻞ اﻟﺠﺎﻧﺐ اﻟﮭﯿﻜﻠﻲ ﻟﻤﻌﻘﺪات ﺛﻨﺎﺋﻲ اﻟﺜﯿﻮﻛﺎرﺑﺎﻣﺎت‬
‫وﺳﻠﻮﻛﮭﺎ اﻟﺮﺑﻄﻲ ﻣﻊ اﻟﻔﻠﺰات اﻻﻧﺘﻘﺎﻟﯿﺔ‪ .‬ﺗﻢ ﺗﺼﻨﯿﻒ ﻛﻞ اﻟﻤﻌﻘﺪات ﺑﺎﺳﺘﺨﺪام ‪ SCXRD‬واﻟﻄﺮق‬
‫اﻟﻄﯿﻔﯿﺔ ﻣﺜﻞ ‪ FT-IR‬و ‪ .PXRD‬ﺗﻢ اﻟﻘﯿﺎم ﺑﺘﺤﻠﯿﻞ ‪ CHN‬اﻟﻌﻨﺼﺮي ﻟﺘﺤﻠﯿﻞ اﻟﻤﺤﺘﻮى اﻟﻌﻨﺼﺮي‬
‫ﻟﻜﻞ ﻣﻌﻘﺪة‪ .‬وﺗﻢ اﻟﻘﯿﺎم ﺑﺎﻟــ ‪ TGA‬ﻟﺪراﺳﺔ اﻻﺳﺘﻘﺮار اﻟﺤﺮاري ﻟﻜﻞ ﻣﻌﻘﺪة‪.‬‬
‫ﺷﺮح اﻟﺠﺰء اﻟﺜﺎﻧﻲ ﻣﻦ اﻟﻔﺼﻮل ﺳﻠﺴﻠﺔ اﻷﻣﻼح اﻟﻔﻠﺰﯾﺔ ﻟﺤﻤﺾ اﻟﺒﯿﺮﯾﺪﯾﻦ اﻟﻜﺎرﺑﻮﻛﺴﯿﻠﯿﻚ ‪2,6-‬‬
‫‪ pyridinedicarboxylic acid‬أو‪ . H2dipic‬ﺗﻢ ﺗﺤﻀﯿﺮ وﺗﺜﺒﯿﺖ اﻟﻤﻌﻘﺪات اﻟﻔﻠﺰﯾﺔ اﻷﻧﯿﻮﻧﯿﺔ ﻓﻲ‬
‫ھﺬه اﻟﺴﻠﺴﻠﺔ ﺑﺎﻟﻜﺎﺗﯿﻮﻧﺎت اﻟﻌﻀﻮﯾﺔ ﻟﺘﻜﻮﯾﻦ ﺧﻤﺴﺔ )‪ (5‬ﻣﻌﻘﺪات ﻟﻸﻣﻼح اﻟﻔﻠﺰﯾﺔ‪ .‬ﺗﻢ اﺳﺘﺤﺪاث‬
‫اﻟﻤﻌﻘﺪات ﺑﺎﺳﺘﺨﺪام ‪ H2dipic‬ﻛﺮﺑﯿﻄﺔ ﻣﻨﺴﻘﺔ )أﻧﯿﻮن(‪ ،‬وﺑﺎﺳﺘﺨﺪام اﻷﻣﯿﻨﺎت ﻛﺄﯾﻮﻧﺎت ﻣﻀﺎدة‬
‫)ﻛﺎﺗﯿﻮن( ﻣﻊ اﻷﯾﻮﻧﺎت اﻟﻔﻠﺰﯾﺔ ﻟﻠﻨﯿﻜﻞ اﻟﺜﻨﺎﺋﻲ )‪ ،Ni(II‬واﻟﻨﺤﺎس اﻟﺜﻨﺎﺋﻲ )‪ ،Cu(II‬واﻟﻜﺎدﻣﯿﻮم‬
‫اﻟﺜﻨﺎﺋﻲ )‪ Cd(II‬ﻹﻋﻄﺎء اﻟﻤﻌﻘﺪات اﻟﺘﺎﻟﯿﺔ‪ ،[Ni(dipic)2][enH2] :‬و ‪،[Cd(dipic)3][enH2]2‬‬
‫]‪[Ni(dipic)2][1epH2‬و‬
‫و‬
‫]‪،[Cu(dipic)2][1mpH2‬‬
‫و‬
‫‪ .[Cd2(dipic)4(opdH)2][opdH]2‬ﺗﻌﺘﺒﺮ ھﺬه اﻟﻤﻌﻘﺪات ﻣﺮﻛﺒﺎت ﻣﻌﺘﻤﺪة ﻋﻠﻰ اﻟﺸﺤﻨﺔ‪ ،‬وﺗﻢ‬
‫ﺗﺜﺒﯿﺘﮭﺎ ﺑﺄﻣﯿﻨﺎت ﻣﻌﻄﯿﺔ ﻟﻠﺒﺮوﺗﻮﻧﺎت‪ ،‬وھﻲ إﯾﺜﯿﻠﯿﻦ ﺛﻨﺎﺋﻲ اﻷﻣﯿﻦ )‪ ،(enH2‬و ‪-1‬ﻣﯿﺜﯿﻞ اﻟﺒﺎﯾﺒﯿﺮازﯾﻦ‬
‫)‪ ،(1mpH2‬و ‪-1‬إﯾﺜﯿﻞ اﻟﺒﯿﺒﯿﺮازﯾﻦ )‪ ،(1epH2‬و ﻋﻀﯿﺪة اﻷورﺛﻮ ﻓﯿﻨﯿﻠﯿﻦ ﺛﻨﺎﺋﻲ اﻷﻣﯿﻦ )‪.(oph‬‬
‫رﻛﺰت ھﺬه اﻟﺴﻠﺴﻠﺔ ﻋﻠﻰ اﻟﺘﺠﻤﯿﻊ اﻟﺬاﺗﻲ ﻟﻠﺠﺰﯾﺌﯿﺎت‪ ،‬واﻟﺘﻔﺎﻋﻼت اﻟﻐﯿﺮ ﺗﺴﺎھﻤﯿﺔ اﻟﻤﻮﺟﻮدة ﻓﻲ‬
‫ﺑﻨﯿﺎت اﻟﺒﻠﻮرات‪ ،‬واﻟﺘﻲ ﺟﻤﻌﺖ ﺑﯿﻦ ﻣﺒﺎديء ھﻨﺪﺳﺔ اﻟﺒﻠﻮرات واﻟﻜﯿﻤﯿﺎء اﻟﻔﻮق ﺟﺰﯾﺌﯿﺔ‪ .‬وﻟﺬﻟﻚ ﻓﺈن‬
‫ﻋﻤﻠﯿﺎت اﻟﺘﺠﻤﯿﻊ اﻟﺬاﺗﻲ واﻟﺘﻌﺮف اﻟﺠﺰﯾﺌﻲ ﺑﯿﻦ اﻟﺮﺑﯿﻄﺔ‪ ،‬و اﻷﻣﯿﻦ‪ ،‬واﻷﯾﻮن اﻟﻔﻠﺰي )وأﯾﻀﺎ‬
‫اﻟﻤﺤﺎﻟﯿﻞ( ﺳﻮف ﺗﻘﻮد إﻟﻰ ﺗﺨﻠﯿﺺ اﻟﺒﺮوﺗﻮﻧﺎت ﻣﻦ اﻟﺮﺑﯿﻄﺔ‪ ،‬وﻣﻦ ﺛﻢ إﻋﻄﺎء اﻟﺒﺮوﺗﻮﻧﺎت ﻟﻸﯾﻮﻧﺎت‬
‫اﻟﻌﻀﻮﯾﺔ اﻟﻤﻀﺎدة ﻟﺘﺤﻘﯿﻖ اﻻﺳﺘﻘﺮار ﻓﻲ ﺗﺸﻜﯿﻞ ﺑﻨﯿﺔ اﻟﺒﻠﻮرة‪ .‬ﺗﻢ ﺗﺤﺪﯾﺪ ﺑﻨﯿﺎت اﻟﺒﻠﻮرات ﻟﻤﻌﻘﺪات‬
‫اﻷﻣﻼح اﻟﻔﻠﺰﯾﺔ ﺑﺎﺳﺘﺨﺪام ‪ .SCXRD‬وﺗﻢ اﻟﻘﯿﺎم ﺑﺎﻟﺘﺤﺎﻟﯿﻞ اﻹﺿﺎﻓﯿﺔ ﻟﻠﻤﻘﺎرﻧﺔ اﻟﮭﯿﻜﻠﯿﺔ ﺑﯿﻦ اﻟﻤﻮاد‬
‫إﺟﻤﺎﻻ وﺑﯿﻦ ﺑﯿﺎﻧﺎت اﻟﺘﺒﻠﻮر ﻣﻦ ‪ SCXRD‬ﺑﺎﺳﺘﺨﺪام ‪.PXRD‬‬
‫‪iii‬‬
APPROVAL PAGE
I certify that I have supervised and read this study and that in my opinion, it conforms
to acceptable standards of scholarly presentation and is fully adequate, in scope and
quality, as a thesis for the degree of Master of Science (Biosciences).
……………………………………..
Fiona How
Supervisor
……………………………………..
Siti Nadiah Abdul Halim
Co-Supervisor
I certify that I have read this study and that in my opinion it conforms to acceptable
standards of scholarly presentation and is fully adequate, in scope and quality, as a
thesis for the degree of Master of Science (Biosciences).
……………………………………..
Jamaluddin Mohd Daud
Internal Examiner
……………………………………..
Lo Kong Mun
External Examiner
This thesis was submitted to the Department of Biotechnology and is accepted as a
fulfilment of the requirement for the degree of Master of Science (Biosciences).
……………………………………..
Suhaila Mohd Omar
Head, Department of Biotechnology
This thesis was submitted to the Kulliyyah of Science and is accepted as a fulfilment
of the requirement for the degree of Master of Science (Biosciences).
……………………………………..
Kamaruzzaman Yunus
Dean, Kulliyyah of Science
iv
DECLARATION
I hereby declare that this dissertation is the result of my own investigations, except where
otherwise stated. I also declare that it has not been previously or concurrently submitted as a
whole for any other degrees at IIUM or other institutions.
Jimmy Ahmad
Signature...........................................................
Date.........................................
v
COPYRIGHT PAGE
INTERNATIONAL ISLAMIC UNIVERSITY MALAYSIA
DECLARATION OF COPYRIGHT AND AFFIRMATION OF
FAIR USE OF UNPUBLISHED RESEARCH
STRUCTURAL STUDIES OF DITHIOCARBAMATE METAL
COMPLEXES AND DICARBOXYLIC ACID METAL SALTS
I declare that the copyright holders of this thesis is
Jimmy Ahmad
Copyright © 2016 Jimmy Ahmad. All rights reserved.
No part of this unpublished research may be reproduced, stored in a retrieval
system, or transmitted, in any form or by any means, electronic, mechanical,
photocopying, recording or otherwise without prior written permission of the
copyright holder except as provided below
1.
Any material contained in or derived from this unpublished research
may be used by others in their writing with due acknowledgement.
2.
IIUM or its library will have the right to make and transmit copies
(print or electronic) for institutional and academic purposes.
3.
The IIUM library will have the right to make, store in a retrieved
system and supply copies of this unpublished research if requested by
other universities and research libraries.
By signing this form, I acknowledged that I have read and understand the IIUM Intellectual
Property Right and Commercialization policy.
Affirmed by Jimmy Ahmad
……..……………………..
………………………..
Signature
Date
vi
ACKNOWLEDGEMENTS
You can spend minutes, hours, days, weeks, or even months over-analysing a
situation; trying to put the pieces together, justifying what could've, would've
happened... or you can just leave the pieces on the floor and move on. This is the
beginning of real me. It’s lonely. To be more powerful than any man you know, to be
special and to pretend you’re a fool.
For 3 years, I have dedicated my time, passion, fortune and sweat hoping to find the
tranquillity and serenity of joyful life but it rarely ended in amity. Life isn’t always
going to be perfect or go our way, but the recurring acknowledgement of what is
working in our lives can help us not only to survive but surmount our difficulties.
Be careful of who you trust, the devil was once an angel. Along the way, I have met
friends and foes. People that constantly smiling with evil delight. Truthfully, we don’t
meet people by accident, they are meant to cross our path for a reason.
They say, imagine with all your mind, believe with all your heart, achieve with all
your might. Sometimes you’ve got to do what you think is right, and damn the
consequences. To me, to exist is a wonder, to grow is a necessity, to learn is a
challenge, to understand is a blessing, to teach is a privilege, to love is a miracle and
to die is an adventure.
Thank you to the amazing people who’ve helped me throughout this journey. You
gave me your time, the most thoughtful gift of all.
To these people, THANK YOU!
Ahmad Abidin, Farizah Othman,
Julie Ellyzer Ahmad, Dr Siti Nadiah Abdul Halim,
Dr Fiona How, Dr Nazzatush Shimar Jamaludin, Nor Izzati Nazri,
Siti Artikah Mahmud Safbri, Amalina Mohamed Sooudin,
Wannur Sofiasalamah Khairiah Ab Rahman,
Alexandra Elbakyan, Larry Page,
Sergey Brin, Jimmy Wales,
Larry Sanger,
and
Izyan Hazwani Baharuddin
“Nothing in life is to be feared; it is only to be understood”
-Marie Curie-
vii
TABLE OF CONTENTS
Abstract .................................................................................................................... ii
Approval page .......................................................................................................... iv
Declaration ............................................................................................................... v
Copyright Page......................................................................................................... vi
Acknowledgements .................................................................................................. vii
List of Tables ........................................................................................................... x
List of Figures .......................................................................................................... xi
List of Symbols ........................................................................................................ xiii
List of Abbreviations ............................................................................................... xiv
CHAPTER ONE .................................................................................................... 1
1.1 Literature Review ................................................................................... 1
1.2 Research Objectives................................................................................ 6
1.3 Experimental ........................................................................................... 7
1.3.1 Materials and Instrumentations ..................................................... 7
1.3.2 Synthesis of sodium morpholine-4-carbodithioate ....................... 8
1.3.3 Synthesis of Dithiocarbamate Metal Complexes .......................... 9
1.3.4 Anti-bacterial Activity Assay........................................................ 11
1.4 Results and Discussion ........................................................................... 12
1.4.1 Synthesis and Spectroscopic Studies ............................................ 12
1.4.2 Single Crystal X-Ray Crystallography Studies ............................. 13
1.4.3 X-Ray Powder Diffraction Studies ............................................... 31
1.4.4 Thermal Analysis of the Complexes ............................................. 33
1.4.5 Bacterial Inhibitory Screening ...................................................... 36
1.5 Conclusion .............................................................................................. 37
CHAPTER TWO ................................................................................................... 38
2.1 Introduction and Literature Review ........................................................ 38
2.2 Research Objectives................................................................................ 45
2.3 Experimental ........................................................................................... 46
2.3.1 Materials and Instrumentations ..................................................... 46
2.3.2 Synthesis of Dicarboxylic Acid Metal Salts ................................. 47
2.4 Results and Discussion ........................................................................... 53
2.4.1 Synthesis and General Characterisation ........................................ 53
2.4.2 X-ray Crystallography Studies ...................................................... 55
2.4.2.1 Crystal Structure of 1a ...................................................... 55
2.4.2.2 Crystal Structure of 4a ...................................................... 59
2.4.2.3 Crystal Structure of 2b ...................................................... 61
2.4.2.4 Crystal Structure of 1c ...................................................... 64
2.4.2.5 Crystal Structure of 4d ...................................................... 66
2.4.3 Powder X-ray Diffraction ............................................................. 80
viii
2.5 Conclusion .............................................................................................. 82
REFERENCES ...................................................................................................... 83
APPENDIX ............................................................................................................ 90
TGA Thermogram for Complex 1 ................................................................ 91
TGA Thermogram for Complex 2 ................................................................ 92
TGA Thermogram for Complex 3 ................................................................ 93
TGA Thermogram for Complex 4 ................................................................ 94
TGA Thermogram for Complex 5 ................................................................ 95
TGA Thermogram for Complex 6 ................................................................ 96
ix
LIST OF TABLES
Table No.
Page No.
1.1
Physical and spectroscopic data for Na[S2CNC4H8O] and its
metal complexes
13
1.2
Crystal Data and Structure Refinement Parameter for Complex
1–6
24
1.3
Selected Bond Lengths for Complex 1–6
25
1.4
Selected Bond Angles for Complex 1–6
26
1.5
TGA temperature range and decomposition steps for all
complexes
32
2.1
Selected bond lengths
67
2.2
Selected bond angles
69
2.3
Hydrogen bond geometry of 1a, 4a, 2b, 1c and 4d
71
2.4
Crystal Data and Structure Refinement Parameter for 1a, 4a, 2b,
1c and 4d
73
x
LIST OF FIGURES
Figure No.
Page No.
1.1
Blomstrand–Jørgensen’s chain theory proposition of (a)
CoCl3·6NH3 and (b) CoCl3·4NH3; both with three available
chlorides
2
1.2
Three classes of dithiocarbamate
4
1.3
Schematic representation for the synthesis of Na[S2CNC4H8O]
8
1.4
The molecular structure of complex 1 showing atom-labelling
scheme
14
1.5
Crystal packing view along the a*-axis
15
1.6
The molecular structure of complex 2 showing atom-labelling
scheme
16
1.7
Crystal packing view along the a-axis
17
1.8
The molecular structure of complexes 3 (a) and 4 (b) showing
atom-labelling scheme
18
1.9
Crystal packing of complexes 3 and 4 showing undulating layers
along the b-axis
19
1.10
The molecular structure of complex 5 showing atom-labelling
scheme
20
1.11
Crystal packing diagram for complex 5 showing a discreet eightmembered ring
21
1.12
The molecular structure of complex 6 showing atom-labelling
scheme
22
1.13
Crystal packing diagram for complex 6
23
1.14
Comparison between observed and simulated PXRD graphs
appear to be superimposed on each other
30
1.15
TGA thermogram for complexes 1(red), 2(blue), 3(green),
4(black), 5(pink) and 6(yellow)
Inhibitory activity against bacterial strains measured by zone on
inhibition (mm) by ligand and its metal complexes; 1a-6a with
streptomycin as the standard drug
33
Schematic representation of the relationship between (a) noncovalent, (b) covalent and (c) coordination crystal engineering
38
1.16
2.1
xi
34
2.2
Dipicolinic acid
42
2.3
Expected structure for the formation of metal salts
51
2.4
Asymmetric unit of 1a with schematic numbering
53
2.5
Each hydrogen from the protonated amines forms a hydrogen
bonds with three different anion moieties
55
2.6
π-π stacking exist on each pyridine with their respective adjacent
pyridine rings moieties
55
2.7
The crystal packing of 1a as view along the a-axis. The dipic
complex forms an undulating layers along the c-axis maintained
by the pi-pi interactions and hydrogen bonds
56
2.8
Balls and sticks model of 4a with schematic numbering and its
respective symmetry labels (i = -x,+y,1/2-z)
57
2.9
Crystal packing of 4a as view from b-axis. The packing
networks form a linear layers along the a-axis maintained by
hydrogen bonds from en and water molecules thus create a 3dimensional networks
58
2.10
Asymmetric unit of 2b with schematic labelling
59
2.11
The crystal lattice is dominated by hydrogen bonds from N–
H···O and O–H···O from protonated amines and waters
molecules
60
2.12
π-π stacking exist on each pyridine with their respective adjacent
pyridine rings moieties
61
2.13
In the crystal packing, as the result from the π-π stacking and
intermolecular hydrogen bonds, the anions and cations form
distinct layers of anions and cations thus created a 3-dimensional
networks
61
2.14
Balls and sticks model of 1c with schematic labelling
62
2.15
Packing diagram of complex 1c shows a distinct layers consist
of anion and cation stacking on each other. Water molecules are
eliminated for clarity
63
2.16
Complete fragment of crystal 4d. Labelling are omitted for
clarity.
64
2.17
Crystal packing of 4d along the b-axis
65
2.18
π-π interactions between the pyridine rings and odp
66
2.19
Comparison between observed (red) and simulated (blue) PXRD
graphs appear to be superimposed on each other
75
xii
LIST OF SYMBOLS
°C
Degree Celsius
T
Temperature
λmax
Lambda Max
g
Gram
K
Kelvin
ml
Millilitre
μl
Microlitre
CFU/mL
Colony-Forming Units per Millilitre
cm-1
Reciprocal Centimetre (or Wavenumber)
Å
Angstrom
xiii
LIST OF ABBREVIATIONS
H2dipic
dipicolinic acid/2,6-pyridinedicarboxylic acid
dipic
deprotonated dipicolinic acid/2,6-pyridinedicarboxylic acid
mol
mole
mmol
millimole
Na[S2CNC4H8O]
sodium morpholine-4-carbodithioate
CS2
carbon disulphide
NaOH
sodium hydroxide
FeCl3·6H2O
iron(III) chloride hexahydrate
Co(C2H3O2)2·4H2O
cobalt(II) acetate tetrahydrate
NiCl2·6H2O
nickel(II) chloride hexahydrate
CuCl2·H2O
copper(II) chloride hydrate
Zn(C2H3O2)2·2H2O
zinc(II) acetate dihydrate
Cd(C2H3O2)2
cadmium(II) acetate anhydrous
DMSO
dimethyl sulfoxide
MHA
Mueller-Hinton agar
en
ethylenediamine
xiv
1mp
1-methylpiperazine
1ep
1-ethylpiperazine
opd
o-phenylenediamine
xv
CHAPTER ONE
SYNTHESIS, CHARACTERISATION, STRUCTURAL STUDIES
AND SELECTED BACTERIAL INHIBITORY ACTIVITIES OF
MORPHOLINE-4-CARBODITHIOIC ACID COORDINATION
COMPLEXES
1.1 LITERATURE REVIEW
Coordination chemistry is the study of compounds in which a small number of molecules or
ions; called ligands surround the central metal atom or ion. This branched field of chemistry
was propounded by 1913 Nobel Prize winner Alfred Werner, a Swiss chemist who studied the
linkage of atoms in molecules of different compounds of cobalt(III) chloride and ammonia –
([Co(NH3)n]Cln), (Constable & Housecroft, 2013).
The earlier theory in coordination chemistry was preceded with the introduction of the
famous chain theory proposed by Swedish chemist, Christian Wilhelm Blomstrand
(Blomstrand & Berzelius, 1869) and its extension and modification by Sophus Mads
Jørgensen (Constable & Housecroft, 2013; Kauffman, 1975). The chain theory got its name
from the proposition that metal amine complexes contain chains of NH3 molecules. The idea
was that the nitrogen atoms could form chains similar much like carbon and that chloride ions
attached directly to cobalt were bonded more strongly than those bonded to nitrogen (see
Figure 1.1). Blomstrand–Jørgensen’s theory remain unchallenged until 1891 when Alfred
Werner published his famous paper “Beiträge zur Theorie der Affinität und Valenz.”
(Kauffman, 1966). Werner suggested that all six ammonia molecules coordinate to cobalt
atom in an octahedral fashion and are allowed for looser bonding of some chlorides where
CoCl3·6NH3 is actually [Co(NH3)6]Cl3 and CoCl3·4NH3 is actually [CoCl2(NH3)4]Cl.
1
(a)
NH3
Cl
NH3
Co
NH3
NH3
NH3
NH3
Cl
NH3
NH3
NH3
Cl
Cl
(b)
Cl
NH3
Co
Cl
Figure 1.1 Blomstrand–Jørgensen’s chain theory proposition of (a) CoCl3·6NH3 and
(b) CoCl3·4NH3; both with three available chlorides.
Nevertheless, Werner played such a central and almost monopolistic role in
coordination chemistry that his name is no stranger in the coordination chemistry field. These
days, coordination compounds particularly metal–amines are still colloquially called Werner
complexes. The coordination theory not only provided a logical explanation for known
"molecular compounds", but also predicted series of unknown compounds whose eventual
discovery lent further weight to Werner's controversial ideas. He showed how ammonia could
be replaced by water or other groups and he demonstrated the existence of transition series
between amines, double salts and hydrates. Werner recognised and named many types of
inorganic isomerism such as coordination isomerism, polymerisation isomerism, ionisation
isomerism, hydrate isomerism, salt isomerism, coordination position isomerism and valence
isomerism. He also postulated explanations for polynuclear complexes, hydrated metal ions,
hydrolysis and acids and bases (Kauffman, 1994).
In the coordination chemistry realms, the atom within a ligand that is bonded to the
central metal ion is called the donor atom. The number of bond from a ligand to the central
metal atoms varies depending on the donor atoms in the molecular structure of the ligand.
2
Therefore, these ligands can be classified as monodentate, bidentate, tridentate or polydentate
ligands.
Ligands can also be classified as either soft or hard bases. This is related to a concept
known as hard and soft (Lewis) acids and bases (HSAB) concept (also known as the Pearson
acid base concept). HSAB is widely used in chemistry for explaining the stability of
compounds, reaction mechanisms and pathways (Tiekink, Vittal, & Zaworotko, 2010). It
assigns the terms 'hard' bases for ligands which contain small, relatively non-polarisable donor
atoms (such as N, O, and F), and soft bases for ligands which contain larger, relatively
polarisable donor atoms (such as P, S, and Cl). Therefore, the hard bases will bind to hard
acids and soft bases will prefer to the soft acids (Pearson, 1963). This is because the
interaction between hard acids and hard bases and vice versa is primarily electrostatic in
nature, the stability of complexes involving hard acids and hard bases increases as the positive
charge on the metal ion increases and as its radius decreases (Pearson, 1987).
From the scientific literatures, there are more than thousands of reported ligands. This
includes O donors such as carboxylic and oxalate moieties (Evers, Hancock, Martell, &
Motekaitis, 1989), N donors such as piperazine and pyridine moieties (Griesser & Sigel,
1970), and S donors such as dithiocarbazate moieties and dithiocarbamate functional groups
(Tarafder, Asmadi, Talib, Ali, & Crouse, 2001).
Dithiocarbamate is an organic functional group with a general formula R1NCS2− and
is generally prepared from an exothermic reaction between CS2 and amine with the presence
of a base to yield alkaline or ammonium metal salts. There has been a long span of interests in
the coordination compounds of unsaturated sulphur donor chelating ligands, dithiocarbamates,
and their related molecules from chemists, physicist, and biologist and theoretician alike due
to their fascinating chemical properties and possible wide application (Dimitri Coucouvanis,
1970; Plyusnin, Grivin, & Larionov, 1997). Since 1969, there were increase of development
and interest in the study of dithiocarbamate and its complexes that may be apparent due to the
3
progress in the development and advancement of X-ray crystallographic and computational
facilities (Dimitrl Coucouvanis, 1979).
In general, three classes of dithiocarbamate group are present and this classification is
dependent upon the type of amines used in the reaction (see Figure 2.1). These classes are
known as N-monoalkyldithiocarbamate, N-dialkyldithiocarbamate, and/or N-heterocyclicdithiocarbamate which are synthesise from primary, secondary and heterocyclic amines
respectively (Cvek & Dvorak, 2007). Structure reports from N-dialkyldithiocarbamate class
compounds are largely prominent due to the stability of secondary amines compared to
primary amines when forming a complex (Halls, 1969).
S
R
'
HN
R
S
N
S
(a) monoalkyldithiocarbamate
S
O
R
S
(b) dialkyldithiocarbamate
N
S
(c) heterocyclic dithiocarbamate
Figure 1.2 Three classes of dithiocarbamate
Dithiocarbamates are a class of well-known metal-coordinating agents (McCleverty
& Meyer, 2004). Previous research on dithiocarbamates had focus on the ligand design with
different substituents. This includes the combination of the dithiocarbamates with transition
and non-transition metals (Hogarth, 2005) This functional group has the capability to stabilise
a wide range of oxidation states especially with low oxidation states and thus, combination of
dithiocarbamates with a metal ion will yield a stable metal dithiocarbamate complex.
Therefore, many researches had highlighted the synthesis of metal dithiocarbamate
complexes, their chemical and spectroscopic characterisation which were discussed
thoroughly and published in numbers of papers. For example, morpholine-4-carbodithioate
has been studied and reported for about four decades and the earlier study was about the
4
interest in low spin and high spin cross-over phenomenon in an iron complex (Butcher &
Sinn, 1976; Healy & Sinn, 1975).
Dithiocarbamates reported complexes complement the theory of unoccupied d orbitals
to give square planar, tetrahedral, and octahedral or other geometries. These metal complexes
usually are showing homonuclear or dimeric structures. Homonuclear complexes may consist
of one metal centre with various numbers of ligands while dimeric may compose of two metal
centres with one or more bridging ligands. There are times where a polymeric structure was
also obtained using the dithiocarbamates functional groups. This kind of structure had
triggered interest of many chemists to create an infinite array of metal centres extending into
1, 2 or 3 dimensions.
Coordination compounds are distinct chemical species–their properties and behaviour
are different from the metal atom/ion and ligands from which they are composed.
Dithiocarbamates and their complexes have also been broadly investigated for their medical
preliminary treatment. For instance, morpholine dithiocarbamate derivatives have a
favourable anti-bacterial activity. Dithiocarbamates, in particular, have the ability to modulate
key proteins involved in biological processes including apoptosis, oxidative stress
transcription and degradation, which has generated interest in these compounds, not only as
anticancer agents but for treatment of an assortment of other conditions including cocaine
addiction, inflammation, and viral infections.
With a wide range of applications of dithiocarbamates, a growing interest for their
general transition metal chemistry and the characteristic and properties of the complexes have
been developed. A small modification to the ligands can also lead to a significant change in
the structure–behaviour of the complexes formed. Example of such modification is the use of
functionalised
dithiocarbamates
via
strong
sulphur–metal
interactions
to
stabilise
nanoparticles. Moreover, dithiocarbamates have wide range of application in material and
separation sciences, i.e. use to separate different metal ions by high-performance liquid
5
chromatography (HPLC) and capillary gas chromatography (GC). In industrial manufacturing,
they find use as rubber vulcanisation accelerator, as chemotherapeutic agents, pesticides, and
fungicides.
Our work in this particular field concentrated on the design and syntheses of morpholine-4carbodithioate complexes which offered new information on fundamental questions
concerning the properties of these systems. Herein, we reported X-ray crystallographic and
structural studies of transition metal morpholine-4-carbodithioate complexes along with
selected bacterial inhibitory activities.
1.2 RESEARCH OBJECTIVES
The study aimed to achieve the following objectives:
1. To design, synthesise and characterise morpholine-4-carbodithioate and its
metal complexes.
2. To study the structural and molecular interactions in the crystal structure
of morpholine-4-carbodithioate metal complexes.
3. To study the thermal properties and selected bacterial sensitivity of
morpholine-4-carbodithioate complexes metal complexes.
6
1.3 EXPERIMENTAL
1.3.1 Materials and Instrumentations
All chemicals and solvents were purchased from commercial sources and used without further
purification.
Melting points were determined on a Krüss KSP1N melting point apparatus.
Elemental analyses for carbon, hydrogen and nitrogen were analysed using PerkinElmer®
2400 Series Elemental Analyser. FT-IR spectra were recorded on a GladiATR with diamond
crystal plate and far-IR optics with the frequency range of 4000-400 cm-1. Thermogravimetric
curves were obtained using TA instrument Q500 at heating rate of 10°/min and a range of 35
°C to 900 °C.
X-ray data for complexes 1 and 2 were collected at 100(2) K on Oxford Supernova
Dual Wavelength diffractometer (λMo
Kα
= 0.71073 Å). High quality crystals were chosen
carefully under a polarising microscope and mounted on a glass fibre. Absorption correction
was performed by multi-scan method using CrysAlis PRO, with empirical absorption
correction using spherical harmonics, implemented in SCALE3 ABSPACK scaling algorithm
(Oxford Diffraction, 2013).
X-ray data for complexes 3–6 were collected at 296(2) K on a Bruker AXS SMART
APEX II diffractometer with a CCD area detector (λMo
Kα
= 0.71073 Å, monochromator =
graphite). High quality crystals were chosen under a polarising microscope and mounted on a
glass fibre. Data processing and absorption correction were accomplished using APEXII
software package (Bruker, 2005).
The structures were solved by charge flipping method using Superflip solution
programme (Palatinus & Chapuis, 2007). Hydrogen atoms were placed in geometrically
7
calculated position and included in the refinement process using riding model with Uiso =
1.2Ueq C(H, H) groups.
All of the data, 1–6 were refined with full matrix least-squares refinement against |F2|
using ShelXL refinement programme (Sheldrick, 2008) and the final refinement include the
atomic position for all the atoms, anisotropic thermal parameters for all the non-hydrogen
atoms, and isotropic thermal parameters for all the hydrogen atoms. The programmes Olex2
(Dolomanov, Bourhis, Gildea, Howard, & Puschmann, 2009), PLATON (Spek, 2009) and
Mercury (Macrae et al., 2008) were used throughout the study.
X-ray powder diffraction was carried out using Siemens D5000, with Cu-Kα radiation
(λ= 0.15418 nm) in the range of 2 theta= 10° to 40° with a step of 0.07° per second.
1.3.2 Synthesis of sodium morpholine-4-carbodithioate, Na[S2CNC4H8O]
Na[S2CNC4H8O] was obtained according to the method by (Marcotrigiano, Pellagani, Preti, &
Tosi, 1975).
O
O
+
Add NaOH
S
C
S
N
S
T< 2 °C
N
H
-
S
Na
Figure 1.3 Schematic representation for the synthesis of Na[S2CNC4H8O].
8
+
Na[S2CNC4H8O] was prepared by titrating CS2 (0.05 mol, 3.00 mL) into morpholine (0.05
mol, 8.6 mL) under a vigorous stirring in chloroform in a controlled temperature, T ≤ 2 °C.
Aqueous solution of 40% (w/v) NaOH (0.05 mol, 5.00 mL) then was added into the mixture
and stirred for approximately three hours at room temperature. The white precipitate was then
isolated upon filtration and wash repeatedly with acetone.
1.3.3 Synthesis of Dithiocarbamate Metal Complexes
Synthesis of Fe[S2CNC4H8O]3 – (1)
Complex 1 has been prepared by titrating methanolic solution of Na[S2CNC4H8O] (7.5 mmol,
1.3892 g) with FeCl3·6H2O (2.5 mmol, 0.6758 g) in 3:1 ligand-to-metal stoichiometric ratios.
Black precipitate immediately formed during the titration process and the mixture was stirred
for approximately three hours. The precipitate was isolated upon filtration and wash
repeatedly with acetone. Black crystals were obtained roughly after 5 days upon
recrystallization in acetone using slow evaporation technique under controlled temperature, T
≤ 0.
Synthesis of Co[S2CNC4H8O]3 – (2)
Complex 2 has been prepared by titrating methanolic solution of Na[S2CNC4H8O] (7.5 mmol,
1.3892 g) with Co(C2H3O2)2·4H2O (2.5 mmol, 0.6227 g) in 3:1 ligand-to-metal stoichiometric
ratios. Dark green precipitate immediately formed during the titration process and the mixture
was stirred for approximately three hours. The precipitate was isolated upon filtration and
wash repeatedly with acetone. Dark green crystals were obtained after a week recrystallization
in acetone using slow evaporation technique under controlled temperature, T ≤ 0.
Synthesis of Ni[S2CNC4H8O]2 – (3)
9