As an extension of the above studies on mononuclear phosphinegold(I) thio-lates, complexes with bidentate phosphines were investigated.62 An interesting phenomenon was recognized for Au(I) complexes of bis(diphenylphosphino) ethane (dppe) in that the dinuclear species rearranged in solution to give the unusual bis-chelated, tetrahedrally coordinated Au(I) species, [Au(dppe)2]+ (10),63 65 represented schematically in Figure 26.3. These, too, along with their Cu(I) and Ag(I) analogues, proved to present exciting cytotoxicity profiles. Another important result was the observation that [Au(dppe)2]+ when co-administered with cisplatin was more effective than either species administered individually, indicating some sort of synergic effect.63 A series of bis-chelated phosphine analogues with the general formula [Au(R2PYPR2)]X (where R and Y is alkyl or aryl; X is the counter ion such as halide, etc.) were also screened for anti-tumour potential in a subsequent study.64
From the data obtained in this study it was apparent that the nature of the X counter ion in [Au(R2PYPR2)]X had little influence upon their potency against B16 melanoma.64 The most active complexes had phosphorus-bound phenyl groups, i.e. [Au(dppe)2]+ (10). It was suggested that the reduced potency of complexes with phosphorus-bound ethyl substituents could be correlated to their enhanced reducing ability,64 i.e. ability to be oxidized to phosphineoxides.
Despite the encouraging in vitro and in vivo results, clinical trials for [Au(dppe)2]+ could not proceed as a result of acute toxicity associated with this species in organs such as the heart, liver and lungs.66
Subsequent work in this area, conducted primarily by Berners-Price, McKeage et al. has focussed on moderating the lipophilicity of the tetrahedral phosphine gold(I) complexes so as to enhance their anti-mitochondrial activity,67 as there is increasing evidence to suggest that these complexes target mitochondria in tumour cells.68,69
Figure 26.3 Chemical structure of cationic [Au(dppe)2]+ (10)
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