Estrutura e reatividade de complexos organometálicos de Au(III)

Abstract

In the last decade, Au(III) complexes become an important class of compounds with promising anticancer effects. Generally, under physiological conditions the Au(III) complexes are quite reactive due to the high affinity of gold ions toward cellular nucleophiles, and due to the instability through the intracellular redox reactions. Density functional theory (DFT) methods were herein applied to calculate the standard reduction potential of nine Au(III) organometallic complexes of the type [Au3+(R-C^N^C)L]n, using available experimental data as benchmark. Overall, the DFT methods lead to satisfactory results, with absolute error lower than 170 mV. The CAM-B3LYP functional in combination with the SMD solvation model was superior to wB97xD, M11-L and B3LYP results, with absolute error of 81 mV relative to ferrocene/ferrocenium (Fc+/Fc) redox couple. However, in spite of the larger error found for B3LYP results, the qualitative trend was closer to the observed one, which allowed the proposal of a scaling model using the experimental reduction potential as dependent variable and the calculated reaction Gibbs free energy as independent variable. The linear regression was statistically acceptable (R2=0.8) at B3LYP level and lead to an average error of only 35 mV. Besides, the variable-temperature H-atom addition/abstraction (VT-HAA) approach was applied for the redox couples with non-equivalent charges (complexes containing chloride as ligand), leading to a significant improvement in the reduction potential prediction. The mean absolute error was only 87 mV without any scaling procedure, which is much lower than found for standard approach, 144 mV. Moreover, the reactivity of Au(III) complexes was studied including two different pathways to the reduction of the [Au3+(C^N^C)Cl] complex, which involve ligand exchange reactions associated with reduction processes in the presence of bionucleophiles of interest (H2O, CH3SH CH3SeH e meim-4). The DFT results show that the most favorable reaction path passes firstly through chloride-exchange ( =2.59 M-1 s-1 for CH3SeH) and then the Au(III) metabolite is promptly reduced to the corresponding Au(I) analogue with ring-opening (ɛ˚=+0.33 V for CH3SeH derivative).