Design and development of novel bismuth(III) complexes as antibiotics against helicobacter pylori and anti-leishmanial drugs
Creators: name: Peiris, Roshani
Publisher: name: Monash University
Year: 2017
Subjects: Uncategorized

description: This thesis has explored the synthesis and characterisation of novel homo- and hetero-leptic mono-nuclear bismuth(III) complexes and bismuth(III) oxo(hydroxo) clusters derived from five different classes of ligands namely, thiocarboxylic acids (Chapter 2), sulfamates (Chapter 3), β-thioxoketones (Chapter 4), N, N-bis-sulfamides (Chapter 5.1) and DNA bases (Chapter 5.2). The medicinal relevance of the synthesised bismuth(III) complexes as antibiotics for Helicobacter pylori (H. pylori) and the anti-Leishmanial activity of both the free acids and the bismuth(III) complexes against Leishmania major (L. major) promastigotes were assessed (Chapter 6). The synthesis and the characterisation of four new thiocarboxylic acids and eleven different mono-, bis- and tris-substituted bismuth(III) thiocarboxylates was investigated in Chapter 2. The solid state structures of the bismuth(III) complexes, [Bi{SC(=O)C6H5}3] B-1, [PhBi{SC(=O)C6H5}2] B-2, [PhBi{SC(=O)C6H5}2]2 B-2-dimer and [PhBi{S(C=O)C6H4Br}2] B-9 were obtained. Next, the coordination chemistry of bismuth(III) sulfamate complexes was investigated. A variety of sulfamates such as saccharin, thiosaccharin, acetosulfame and cyclamic acid were applied and resulted in the formation of fourteen new homo- and hetero-leptic bismuth(III) complexes including, [Ph2Bi(sac)] (sac-H=saccharin) B-14, [Ph2Bi(tsac)] (tsac-H=thiosaccharin) B-17, [Bi(cyc-H)3] (cyc-H2=cyclamic acid) B-20 and [Ph2Bi(ace)] (ace-H=acetosulfame) B-24. The solid state structures of the bismuth(III) complexes, B-14 and B-17 were determined and discussed. Four new polynuclear bismuth(III) oxo(hydroxo) clusters of the sulfamates including, the largest homo-metallic bismuth(III) oxo-cluster, [Bi50O64(ace)22(H2O)10] B-29 were synthesised and the solid state structures of the clusters [Bi6O4(OH)4(NH2SO3)6] B-28 and [Bi4O2(ace)8(H2O)4]] B-31 were revealed by X-ray crystallography. Synthesis and characterisation of nine different β-thioxoketones and their tris-substituted bismuth(III) derivatives was investigated in Chapter 4. Highlights include, [Bi{C6H5C(=O)CHC(=S)C6H4CF3}3] B-33, [Bi{C5H4NC(=O)CHC(=S)C6H5}3] B-36 and [Bi{C6H5C(=O)CHC(=S)C10H7}3] B-39. The solid state structure of B-36 was determined by X-ray crystallography. Two classes of ligands namely, N, N-bis-sulfamides and DNA bases were selected to explore the chemistry of compounds containing Bi-N bonds. The N, N-bis-sulfamides were synthesised prior to the synthesis of their bismuth(III) complexes. Five new bismuth(III) complexes of N, N-bis-sulfamides including, [Bi2{(C6H5CH(CH3)N)2SO2}3] B-41 and [Bi2{(OCH3C6H4CH2N)2SO2}3] B-44 were synthesised and characterised. The DNA bases, guanine and thymine produced the expected tris-substituted products, while adenine and cytosine gave the tetra-nuclear oxo(hydroxy) species [Bi4O2(adenine)8.12H2O] B-46 and [Bi4(OH)4(cytosine)8.THF] B-49. Chapter 6 explores the potential of bismuth(III) compounds as antibiotics against H. pylori and anti-Leishmanial drugs. The activity of the synthesised bismuth(III) complexes of thiocarboxylates, sulfamates and thioxoketones were assessed for their activity against three strains of H. pylori; 251, 26695 and B128. The results were compared with the standard bismuth drugs. Most of the complexes showed to be highly active comparative to the commercial drugs, showing minimum inhibitory concentrations (MICs) of 6.25-3.125 µg/mL. The activity of the synthesised bismuth(III) complexes of thiocarboxylates, sulfamates, thioxoketones and their corresponding free acids were tested against L. major promastigotes and the results were compared with the activity of commercially available anti-Leishmanial drug Amphotericin B. Many of the free acids and the bismuth(III) complexes showed good anti-Leishmanial activity.