In-vitro and in-vivo monitoring of gold(III) ions from intermediate metabolite of sodium aurothiomalate through water-soluble ruthenium (II) complex-based luminescent probe

Abstract

Real-time monitoring of drug metabolism in vivo is of great significance to drug development and toxicology research. The purpose of this study is to establish a rapid and visual in vivo detection method for the detection of an intermediate metabolite of the gold (I) drug. Gold (I) drugs such as sodium aurothiomalate (AuTM) have anti-inflammatory effects in the treatment of rheumatoid arthritis. Gold(III) ions (Au³⁺) are the intermediate metabolite of gold medicine, and they are also the leading factor of side effects in the treatment of patients. However, the rapid reduction of Au³⁺ to Au⁺ by thiol proteins in organisms limits the in-depth study of metabolism of gold drugs in vivo. Here we describe a luminescence Au³⁺ probe (RA) based on ruthenium (II) complex for detecting Au³⁺ in vitro and in vivo. RA with large Stokes shift, good water solubility and biocompatibility was successfully applied to detect Au³⁺ in living cells and vivo by luminescence imaging, and to trap the fluctuation of Au³⁺ level produced by gold (I) medicine. More importantly, the luminescent probe was used to the detection of the intermediate metabolites of gold (I) drugs for the first time. Overall, this work offers a new detection tool/method for a deeper study of gold (I) drugs metabolite.

Keywords: Au(3+); Gold (I) drug; Large Stokes shift; Luminescence imaging; Ruthenium (II) complex; Water-solubility.