A revised understanding of the speciation of gold(<scp>iii</scp>) dithiocarbamate complexes in solution

The cytotoxic series of cis-platin mimics "[AuX₂(dtc)]" (X = Cl, Br; dtc = dithiocarbamate) were recently patented as promising anticancer metallotherapeutics. Using a range of dialkyl-, cyclic alkyl- and diaryl-dithiocarbamate ligands, we have discovered that "[AuX₂(dtc)]" actually exist in solution as a mixture containing neutral [AuX₂(dtc)] and cationic [Au(dtc)₂]⁺. For the latter, single crystal X-ray crystallography proved that a variety of halide-containing anions such as [AuX₄]^-, [AuX₂]^- and even X^- balanced the charge. Based on a thorough investigation into the synthesis of these compounds, we discovered that literature syntheses which claim to produce pure material in fact generate mixtures. In some cases the major component of the mixture is actually the <i>cationic</i> [Au(dtc)₂]⁺ rather than the claimed <i>neutral</i> [AuX₂(dtc)]. Refinement of the synthetic conditions led to a mixture where the neutral [AuX₂(dtc)] was the dominant component, from which pure solid [AuX₂(dtc)] could be obtained by fractional crystallisation. However, the isomerisation process immediately restarted upon dissolution of the crystalline material, thus it is not possible to obtain pure [AuX₂(dtc)] in solution. This discovery has important ramifications for any future use of these compounds, especially as therapeutics since the solution-phase speciation means that "pure" [AuX₂(dtc)] cannot exist under biologically relevant conditions. A critical reinterpretation of existing literature data demonstrates that there is already significant uncertainty surrounding which component(s) of this mixture are biologically active.