Structure and redox stability of [Au(III)(X^N^X)PR3] complexes (X = C or N) in aqueous solution: The role of phosphine auxiliary ligand

The choice of the auxiliary ligand in Au(III) complexes is of paramount importance in tuning their reactivity and biological activity. Tertiary phosphines are one of the most used auxiliary ligands in gold compounds, due to their stereo-electronic properties that confer stability and lipophilicity to these metallodrugs. The redox stability of [Au(III)(C^N^C)PR3]+ (A) (C^N^C = 2,6-diphenylpyridine) and [Au(III)(N^N^N)PR3]3+ (N^N^N = 2,2′:6′,2″-terpyridine) (B) complexes (where R is the phosphine substituent groups with different steric and electronic properties) was herein investigated for a set of 41 phosphines, using the predicted standard reduction potential (εo) for Au(III)/Au(I) electrochemical system as reference. For the complexes A, εo spread over 829 mV and all values were negative, whereas for the complexes B εo were positive and covered a narrower range of 507 mV. The phosphines with high buried volume (%Vbur ≥ 32%) decrease the complex stability despite being strong σ-donors. Both steric and electronic properties were used as molecular descriptors to build quantitative structure-property relationships (QSPR), which showed that the %Vbur plays the major role on the redox stability of the studied Au(III) complexes. For complexes B where the phosphine affects both Au(III) and Au(I) forms, the steric impact is more pronounced on the Au(I) reduced species. The electron-donating ability of phosphines is also important and plays a greater role on the redox stability of complexes B than complexes A. These outcomes are certainly useful to predict the redox stability of Au(III) complexes which, in turn, should affect their chemical reactivity against biological targets. Standard reduction potential of the [Au(III)(X^N^X)PR3] complexes (X = C or N) is quantitatively represented by steric and electronic descriptors. The ligands C^N^C = 2,6-diphenylpyridine and N^N^N = 2,2′:6′,2″-terpyridine. The phosphines are represented as PR3 with R being substituent groups with different steric and electronic properties. [Display omitted] •Standard reduction potential for gold(III) complexes is calculated in aqueous solution.•Predictive relationships are proposed including steric and electronic parameters.•Steric effects play a primary role on the redox stability of the gold(III) complexes.•Redox stability can be modulated by controlling the phosphine auxiliary ligand volume.