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Title of Thesis

Solution-Phase Synthesis of a Combinatorial N,N'-Disubstituted Thioyrea Library: Complexation, Characterization and Biological studiest

Author(s)

Muhammad Khawar Rauf

Institute/University/Department Details
Department of Chemistry / Quaid-i-Azam University, Islamabad
Session
2010
Subject
Inorganic / Analytical Chemistry
Number of Pages
231
Keywords (Extracted from title, table of contents and abstract of thesis)
Biological, Fungicidal, Chemotherapeutic, Drugs, Combinatorial, Disubstituted, Solution, Studiest, Chemical, Complexes, Aromatic, Synthesis, Characterization

Abstract
A chemical library of N, N'-Disubstituted thioureas have been derived from substituted aromatic carboxylic acids and two types of combinatorial strategies have been employed for the construction of chemical library. For high throughput screening of components of the chemical library, solution-phase pool syntheses have been exercised, where each pool consists of four components. All the members of chemical library have also been synthesized by using a parallel mode of solution-phase combinatorial synthesis for the purpose of lead screening/identification, testing, characterization and for assembling of Cu(I)Cu(II) & Pd(II) metal complexes. Copper(I) (1A-19A, 1B-19B, 1C-19C& 1F) and palladium(II) [(1E-14E)] complexes of N, N'-disubstituted thioureas have only been synthesized with some selected thioureas from sub-library-1 and Cu(II) complexes (1D-6D) with isoureas (1-6), prepared from the thioureas derived from benzoic acid.All the thioureas (1a-40a, 1b-40b, 1c-40c, 1d-40d, 1e-40e, 1f-40f & 1g-40g) and complexes have been characterized by elemental analyses, FT-IR, 1H & 13C NMR spectroscopy, mass spectrometry and single crystal XRD. The stability of the Cu(I) complexes in the test medium has
been confirmed by cyclic voltammetric studies. The products of pool syntheses (pools 1-40) have been characterized by mass spectrometry and GC-MS (gas chromatograph coupled with mas spectrometer) techniques. In all the Cu(I) and Pd(II) complexes, neutral N, N′-disubstituted thiourea ligands have been coordinated to the metal atom through the sulphur atom in a terminal mode except (1F), where the deprotonation of NH group of the thiourea ligand has facilitated the bonding of copper atom through N and S. The isoureas (1-6) show bidentate behavior in Cu(II) complexes having square planar geometry (1D-6D).
The thioureas have also been examined for their fungicidal properties and these show significant activity against various fungi strains and low phytotoxicity for the representative monocot plant species. The complexes have been screened for their in vitro cytotoxicity in human cell lines carcinomas A498 (renal), EVSA-T (breast), H226 (lung), IGROV (ovarian), M19 (melanoma-skin), MCF-7 (breast) and WIDR (colon). They show a moderate cytotoxicity against these seven human cancer cell lines in comparison to that of the less active standard chemotherapeutic drugs. Biological screening of the synthesized thioureas and their metal complexes for various targets is in progress.

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S. No. Chapter Title of the Chapters Page Size (KB)
1 0 CONTENTS

 

 
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2

1

INTRODUCTION

1.1 Combinatorial Chemistry
1.2 Historical Perspective
1.3 Types of Combinatorial Libraries
1.4 Types of Combinatorial Synthesis
1.5 Aroyl Substituted Thioureas

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3 2 EXPERIMENTAL AND CHARACTERIZATION

2.1 Chemicals
2.2 Instrumentation
2.3 Parallel Synthesis of Aroyl Thioureas Chemical Library
2.4 Pool Synthesis of Aroyl thioureas Chemical Library
2.5 Synthesis of Metal-Organic Complexes

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4 3 BIOLOGICAL STUDIES

3.1 Biological Screening of N, N'-Disubstituted Thioureas
3.2 Biological Evaluation of Copper(I) and Palladium(II) Complexes
3.3 Conclusions

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5 4 RESULTS AND DISCUSSION

4.1 Infra-Red Spectroscopy
4.2 Multi-nuclear ( 1H, 13C) NMR Spectroscopy
4.3 Single Crystal X-ray Crystallography
4.4 Crystal Structure of Bis[1-benzoyl-3-phenyl thiourea- κ 1 S] palladium(II) chloride (1E)
4.5 Cyclic Voltammetry

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6 5 APPENDIX

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