Amphiphilic phenylalanine derivatives that temporally generate reactive oxygen species from water in the presence of Au(iii) ions

Abstract

Amphiphilic derivatives of phenylalanine (ADFs) have strong self-assembling propensities and yield low molecular weight hydrogels on multiple occassions. The interaction of ADFs with metal ions can result in the morphological changes in the self-assemblies. Herein, we report the interesting consequences of the interaction between four N-protected ADFs with Au(III) ions. In the case of ADF 1, the original nanofibrillar morphology of the self-assemblies spontaneously transformed into uniform nanoglobules of ∼80 nm in diameter upon addition of Au(III) ions. A subsequent reduction of the Au(III) ions to Au(0) nanoparticles (AuNPs) and the surface decoration of the nanoglobules with AuNPs were observed in the course of the next six to eight hours. Simultaneously, multiple reactive oxygen species (ROS) such as hydrogen peroxide (H₂O₂), hydroxyl radicals (˙OH), singlet oxygen and superoxide ions were also found to be present in the reaction medium. These ROS originate from water used as the reaction medium. The ROS production and the reduction of Au(III) were inhibited upon deaeration of the reaction medium and the use of heavy water (D₂O) or organic solvents as the reaction medium, while an increase in the pH of the aqueous medium intensified both these processes. We exploited the temporal ROS generation using the mixture of 1 and Au(III) ions towards anticancer therapy by enhancing the intracellular ROS levels. It is expected that this effort can be expanded into a viable anticancer therapy in the near future by modulating the amount and the rate of ROS-generation through judicious choice of the peptidic ligands and metal ions.