Industrial Research Fellow, investigating the coordination of technetium and rhenium to peptides and the synthesis of low molecular weight radiopharmaceuticals. His research interests centered on the applications of technetium and rhenium radiopharmaceuticals to oncology and neurology. In 1998, he joined the platinum development team at AnorMed, Inc., as a Senior Developmental Scientist. His current research interests include the design and synthesis of new Pt antitumor agents and the design of efficient processes for large-scale manufacture of Pt compounds. Christen Giandomenico received his Ph.D. degree in Chemistry from Columbia University and has held Post-doctoral positions at the University of Chicago and the Stanford Research Institute. In 1985 he joined Johnson-Matthey where he was a co-inventor of JM216, the first orally active platinum anticancer drug. He is a named inventor on six patents and is the author of 19 scientific articles. In 1996 he helped found AnorMED, a company dedicated to the discovery and development of metal-based therapeutics. He is currently Director of Chemical Development at AnorMED.

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At present, there is no general description of the interactions between nitrogen heterocycles and the active catalyst sites in heterogeneous hydrodenitrogenation (HDN) catalysts that promote hydrogenation and then hydrogenolysis of the C-N bond. We have attempted to model such interactions through studies of the reactions of osmium and ruthenium clusters with common HDN model substrates, including quinoline, pyridine, tetrahydroquinoline (THQ), and piperidine. Os3(CO)12 and Ru3(CO)12 with quinoline Or pyridine lead to complexes of the general formula 3(µ-:µ-Y) (CO) 10 (M = Ru, Os; Y = C9H6N, C9H8N, C5H8N) or 3(µ-:µ-)2(00)8 (M = Ru, Os; Y = C5H4N, C9H6N). The reactions of Os3(CO)12 with aliphatic heterocyclic amines leads to complexes having stoichiometries of 083(µ-:µ-Y)(CO)10 (Y = C5H8N, C9H8N, C9H6N), 83(µ-)2(µ-)(µ-0( 0)8 (Y = C9H8N, Y' = C9HeN), or Os3(M-H:M-Y)2(CO)8 (Y = C9H6N), and when the heterocyclic amine is 1,2,3,4-tetrabydroquinoline (THQ), a small amount of free quinoline is also produced. As a general rule, both aliphatic and aromatic nitrogen heterocycles undergo -metalation during reactions with both homogeneous and heterogeneous metal complexes or particles. In the case of osmium and ruthenium, metalation results in the formation of metalloazocyclobutenes even when the starting heterocycle is saturated. Thus, activation / dehydrogenation of the N-H and -C-H bonds of secondary amines occurs readily in the systems described here. Reaction pathways for the formation of the various products and their relationships to hydrogenation and dehydrogenation catalysis are proposed.

Two unwanted contaminants, 3,4,3',4'-tetrachloroazoxybenzene (TCAOB) and 3,4,3',4'-tetrachloroazobenzene (TCAB), formed in the commercial synthesis of 3,4-dichloroaniline or of herbicides made from 3,4-dichloroaniline, were responsible for three outbreaks of acne among chemical workers. TCAOB and TCAB are approximately isosteric to 2,3,7,8-tetrachlorodibenzo-p-dioxin and 2,3,7,8-tetrachlorodibenzofuran, two well-known contaminants that cause acne. All four of these agents are potent inducers of hepatic aryl hydrocarbon hydroxylase activity and compete for stereospecific binding sites in the hepatic cytosol, which are thought to be the receptor sites for the induction of this enzyme. Among the chlorinated azoxy and azobenzenes, the potency of a congener to induce aryl hydrocarbon hydroxylase activity correlates with its binding affinity for the hepatic cytosol specific binding sites and its capacity to induce acne; this relation between structure and activity parallels that observed for the chlorinated dibenzo-p-dioxins and dibenzofurans.

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