The biological and medicinal chemistry of bismuth

Abstract

Peter Sadler (right) studied for his first and second degrees at the University of Oxford His doctorate \vas on bioinorganic chemistry under the direction of Professors H. O. A. Hill and R. J. P. Williams. After two years as a Medical Research Council Research Fellow at the llniver.iitv of Camhritlce ami National Institute far Medical Research, he ioine.it the Denartment of Cheinistrv at Birkheck Colleve. University of London, where lie was successively Lecturer, Reader in Biological Inorganic Chemistry, and Professor of Chemistry. On the 1st of October 1996 lie took up the Cnini Brown Chair of Chemistry at the University of Edinburgh. In 1993 he was recipient of the Royal Society of Chemistry Award for Inorganic Biochemistry and he is currently Chairman of the EC COST Action DS [The Chemistry of M'étals in Medicine]. His research interests lie in this area. Hongzhe Sun (left) received his M. Sc in 1990 from The Chinese Academy of Sciences and then he moved to Nanjing University (China) as a research associate and later a lecturer. He received his Ph. D. from the University of London in 1996 under the supervision of Professor Peter Sadler and is currently a Glaxo Wellcome Research Fellow in Professor Sadler's laboratory at the University of Edinburgh. Hongyan Li (center) is doing her Ph. D. work under the supervision of Peter Sadler. Bismuth compounds have been widely used in medicine for more than 200 years, and new bismuth-containing drugs are now being developed. However the biological chemistry of bismuth is poorly understood. We review here methods for the study of bismuth compounds, and use of Bi(III) in antiulcer, antibacterial, anti-HIV and radiotherapeutic agents is described. The chemistry of Bi(III) carboxylates and aminocarboxylates is dominated by intermolecular interactions which lead to polymeric structures. Bi(III) exhibits a highly variable coordination number and coordination geometry, and alkoxide ligands can induce a strong stereochemical "lone-pair effect". Bi(III) can bind to both Zn(II) sites (e.g. metallothionein) and Fe(III) sites (e. g. transferrin) in proteins. Further work is needed to understand the relationship between the structures and dynamics of bismuth compounds and their bioactivity. © VCH Verlagsgesellschaft mbH,.