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ADAM Dissertation May__2016.Pdf © Adam Ahmed Abdallah Sulaiman 2016 ii This dissertation is dedicated to my lovely parents, my wife Lana, my kids (Razzan and Aamin) and to who taught me a letter iii ACKNOWLEDGMENTS My first and foremost thanks to Almighty Allah for giving me strength, power and patience to complete my postgraduate study successfully. My special thanks to King Fahd University of Petroleum and Minerals (KFUPM) for providing me an opportunity to achieve my Ph.D. degree in Chemistry Department. My appreciation connected to the formal Chairman Dr. Abdullah Al-Hamadan for his great efforts that enable me to complete my study. Also, I would like to express my special thanks to current Chairman Dr. Abdulaziz Al-Saadi and Graduate Coordinator Prof. Bassam El-Ali for their supports and facilities provided by Chemistry Department. I would like to connect my gratitude and special thanks to my advisor Prof. Anvar Husein A. Isab for his encouragement, he accepted me when I was in my sixth semester. I want to thank him for his support, guidance and wisdom words without his enthusiasm and dedication this work could not be possible by Allah's willing. I wish to appreciate and acknowledge my committee members Dr. Mohammed Fettouhi, Dr. Hassan Al-Muallem, Prof. Mohammed I. M. Wazeer and Prof. Akhtar Naqvi for their help, advice, guidance and revision of my dissertation. Further, I need to give my thanks to Mr. Mohammed Arab and Mr. Mansour Al-Zaki for their support to use IR, Elemental analyzer, and NMR. Heartfelt thanks to Dr. Musa M. Musa and Dr. Abdel-Nasser Kawde for their help beside a permission to do a part of my work in their labs. Many thanks to Dr. Mohammed Altaf for his help and advice. Thank you kindly, my parents for your sacrifices, my wife Lana, my kids Razzan and Aamin for your prayers, support, and advice. Thanks to Sudanese Students in KFUPM. iv TABLE OF CONTENTS ACKNOWLEDGMENTS .............................................................................................. iv TABLE OF CONTENTS ................................................................................................. v LIST OF TABLES .......................................................................................................... x LIST OF FIGURES ...................................................................................................... xvi LIST OF ABBREVIATIONS ......................................................................................xxvi ABSTRACT .............................................................................................................. xxviii xxxi .................................................................................................................. ملخص الرسالة CHAPTER 1....................................................................................................................1 INTRODUCTION ...........................................................................................................1 1.1. Gold(III) complexes ..................................................................................................1 1.2 Gold(I) complexes ..................................................................................................3 1.3 RESEARCH OBJECTIVES ...................................................................................6 CHAPTER 2....................................................................................................................8 LITERATURE REVIEW ................................................................................................8 2.1. Gold(III) complexes ..............................................................................................8 2.2 Gold(I) Complexes ...............................................................................................17 2.2.1 Complexes formed from (P, S, Se) donor ligands ...........................................17 2.2.2 Complexes fromed from (P, C, N) donor ligands............................................22 CHAPTER 3..................................................................................................................26 SYNTHESIS, ANTI-CANCER EVALAUTION OF NEW MIXED-LIGAND GOLD(I) COMPLEXES WITH DITHIOCARBAMATES AND PHOSPHINES ..........................26 3.1 EXPERIMENTAL SECTION..................................................................................26 v 3.2 Synthesis of binuclear Gold(I) complexes with mixed bis-phosphine and dithiocarbamate ligands ....................................................................................27 3.2.1[Au2((1R,2R)-N,N-Bis[2-(diphenylphosphino)benzyl]cyclohexane-1,2-diamine) Cl2] with dialkyl and diaryldithiocarbamate ligands (1-5) ................................27 3.2.2 [Au2(Bis[(2-diphenylphosphino)ethyl]ammonium chloride)Cl2] with dialkyl and diaryldithiocarbamates (6-9) .....................................................................32 3.2.3 [Au2(Bis[2-(dicyclophosphino)ethyl]amine)Cl2] with dialkyl and diaryldithiocarbamates (10-13) ........................................................................36 3.2.4 [Au2((1S,2S)-N,N-Bis[2-(diphenylphosphino)benzyl]cyclohexane-1,2-diamine) Cl2] with dialkyl and diaryldithiocarbamates (14-17) .......................................39 3.3 Synthesis of gold(I) complexes with mono-phosphine and dithiocarbamate ligand.42 3.3.1 Chlorido(2-(diphenylphosphino)ethylamine )Au(I) with dialkyl and dibenzyl-dithiocarbamates (18-22) ..................................................................42 3.3.2 Chlorido((1R,2R)-2-(diphenylphosphino)-2,3-dihydro-1H-inden-1-amine)Au(I) with dialkyl and dibenzyl-dithiocarbamate complexes (23-26) ........................45 3.3.3 Chlorido(1R,2R)-2-(diphenylphosphino)-1-aminocyclohexane)Au(I) with dialkyl and dibenzyl-dithiocarbamates complexes (27-30) ...............................48 3.3.4 Chlorido(2-(di-i-propylphosphino)ethylamine)Au(I) with dialkyl and dibenzyldithiocarbamates complexes (31-34) ..................................................51 3.3.5 Gold(I) with mixed tri(o-methoxyphenyl)phosphine and triphenylphosphine complexes (35-37)...........................................................................................54 3.4 Single crystal structure determination ...................................................................56 3.5 MTT assay for in vitro cytotoxicity of gold(I) complexes .....................................56 3.6 Results and Discussion .........................................................................................58 3.6.1 Gold(I) complexes with mixed bis-phosphine and dithiocarbamates ligands (2-17) ..............................................................................................................58 vi 3.6.1.1 Spectroscopic analysis ................................................................................58 3.6.2.2 Gold(I) phosphine complexes (35-37) .........................................................73 3.6.3 Single crystal X-ray structure of complex 27 ..................................................74 3.6.4 In vitro cytotoxic activities of gold(I) monophosphine complexes (18-22, 35 and 37)… ................................................................................................................77 CHAPTER 4..................................................................................................................81 SYNTHESIS, CHARACTERIZATION AND IN VITRO CYTOTOXIC EVALUATION OF GOLD(I) CARBENE COMPLEXES WITH SELONE LIGANDS ..........................81 4.1 Introduction ..........................................................................................................81 4.2. Experimental Section ..........................................................................................82 4.2.1 Materials and Instrumentation ........................................................................82 4.2.2 Synthesis of gold(I) carbene complexes with selones (39-50) .........................83 4.3 Results and Discussion .........................................................................................89 4.3.1 Spectroscopic characterizations ......................................................................89 4.3.2 Single crystal X-ray structure determination ..................................................97 4.3.3 In vitro cytotoxic activities of gold(I) complexes (38-50) ............................. 104 CHAPTER 5................................................................................................................ 110 SYNTHESIS AND CHARACTERIZATION OF (TRI-TERT-BUTYLPHOSPHINO)GOLD(I) THIONE COMPLEXES ....................... 110 5.1 Introduction ........................................................................................................... 110 5.2 Experimental Section ......................................................................................... 111 5.2.1 Materials and instrumentation .......................................................................... 111 5.2.2 Synthesis of (tri-tert-butylphosphino)gold(I) thione complexes (52-55) ........... 111 5.3 Results and discussion ........................................................................................... 113 5.3.1 Spectroscopic characterization ......................................................................... 113 vii 5.3.2 Signal crystal X-ray structure determination .................................................... 117 CHAPTER 6...............................................................................................................
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