Reactions of N-sulfonylpyrroles yielding metal complexes with potential anti-cancer activity

Abstract

The dissertation describes the synthesis of sulfonylimine ligands from N-sulfonylpyrrole. These ligands form metal complexes with various transition metals and are to be tested for activity against cancer cells. The introductory chapter sets the scene by describing transition metals in existing therapy and current investigations on transition metals in therapy. It also covers current methodology for deprotonation of N-sulfonylpyrrole leading to carbon-carbon bond formation. The second chapter describes the experimental work performed in this project. A synthetic route towards sulfonylimine ligands, 4-methyl-N-[phenyl(1H-pyrrol- 2yl)methylene]benzenesulfonamide 15 and N-[phenyl(1H-pyrrol- 2yl)methylene]benzenesulfonamide 6, is described. The mechanism for the 1,4- migration of the sulfonyl group was investigated in a crossover experiment and was found to occur via an intra molecular shift. The sulfonylimine ligands were complexed with late transition metals from the first row (cobalt(II), nickel(II), copper (I), copper(II) and zinc(II)), second row (palladium(II) and silver(I))and third row (platinum(II)), and were submitted for testing against cancer cells. The first row transition metal complexes did not show activity against HeLa cancer cells, while in the second row, activity was observed for the silver complexes. The third row metal complex also showed anti-cancer activity. Previously reported methodology employing Grignard reagent and catalytic amine base to deprotonate N-sulfonylpyrrole and quenching with electrophiles was extended to indole, imidazole and benzimidazole ring systems. Results obtained were comparable to those reported using lithium bases. Addition of lithium chloride to the Grignard reagent reduces the mole equivalent of the reagent required for deprotonation. A comparison between the arylsulfonyl and dimethylsulfamoyl protecting groups in pyrrole and imidazole showed that arylsulfonyl are better protecting groups for pyrrole, while dimethylsulfamoyl is a better protecting group for imidazole. All synthesized organic structures were characterized by NMR spectral data, mass spectrometry and melting points where applicable. The synthesized metal complexes were characterized by mass spectroscopy, infrared spectroscopy and X-ray crystallography where applicable.