Reactions of N-sulfonylpyrroles yielding metal complexes with potential anti-cancer activity
Date
2009-03-05T08:15:45Z
Authors
Nxumalo, Winston
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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.