title: Reactions of gold(III) complexes with serum albumin.
abstract: The reactions of a few representative gold(III) complexes -[Au(ethylenediamine)2]Cl3, [Au(diethylentriamine)Cl]Cl2, [Au(1,4,8,11-tetraazacyclotetradecane)](ClO4)2Cl, [Au(2,2',2'-terpyridine)Cl]Cl2, [Au(2,2'-bipyridine)(OH)2][PF6] and the organometallic compound [Au(6-(1,1-dimethylbenzyl)-2,2'-bipyridine-H)(OH)][PF6]- with BSA were investigated by the joint use of various spectroscopic methods and separation techniques. Weak metal-protein interactions were revealed for the [Au(ethylenediamine)2]3+ and [Au(1,4,8,11-tetraazacyclotetradecane)]3+ species, whereas progressive reduction of the gold(III) centre was observed in the cases of [Au(2,2'-bipyridine)(OH)2]+ and [Au(2,2',2'-terpyridine)Cl]2+. In contrast, tight metal-protein adducts are formed when BSA is reacted with either [Au(diethylentriamine)Cl]2+ and [Au(6-(1,1-dimethylbenzyl)-2,2'-bipyridine-H)(OH)]+. Notably, binding of the latter complex to serum albumin results in the appearance of characteristic CD bands in the visible spectrum. It is suggested that adduct formation for both of these gold(III) complexes occurs through coordination at the level of surface histidines. Stability of these gold(III) complexes/serum albumin adducts was tested under physiologically relevant conditions and found to be appreciable. Metal binding to the protein is tight; complete detachment of the metal from the protein has been achieved only after the addition of excess potassium cyanide. The implications of the present results for the pharmacological activity of these novel cytotoxic agents are discussed.
authors: Department of Chemistry, University of Florence, Italy Department of Chemistry, University of Sassari, Italy.
authors: Giordana
authors: G
authors: Marcon
authors: Luigi
authors: L
authors: Messori
authors: Pierluigi
authors: P
authors: Orioli
authors: Maria Agostina
authors: MA
authors: Cinellu
authors: Giovanni
authors: G
authors: Minghetti
mesh_terms: D000818:Animals; D002417:Cattle; D002942:Circular Dichroism; D003603:Cytotoxins / Q000737:chemistry / Q000633:toxicity; D006046:Gold / Q000737:chemistry* / Q000633:toxicity; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry* / Q000633:toxicity; D011190:Potassium Cyanide / Q000737:chemistry; D012710:Serum Albumin, Bovine / Q000737:chemistry*; D012996:Solutions / Q000737:chemistry; D014462:Ultrafiltration
chemical_list: D003603:Cytotoxins; D009942:Organometallic Compounds; D012996:Solutions; D012710:Serum Albumin, Bovine; D006046:Gold; D011190:Potassium Cyanide