Reactions of gold(III) complexes with serum albumin

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
CDbands 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 themetal 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.