The first solid-state route to luminescent Au(I)-glutathionate and its pH-controlled transformation into ultrasmall oligomeric Au(SG) nanoclusters for application in cancer radiotheraphy.

There is still a need for synthetic approaches that are much faster, easier to scale up, more robust and efficient for generating gold(I)-thiolates that can be easily converted into gold-thiolate nanoclusters. Mechanochemical methods can offer significantly reduced reaction times, increased yields and straightforward recovery of the product, compared to the solution-based reactions. For the first time, a new simple, rapid and efficient mechanochemical redox method in a ball-mill was developed to produce the highly luminescent, pH-responsive Au(I)-glutathionate, [Au(SG)]. The efficient productivity of the mechanochemical redox reaction afforded orange luminescent [Au(SG)] in isolable amounts (mg scale), usually not achieved by more conventional methods in solution. Then, ultrasmall oligomeric Au(SG) nanoclusters were prepared by pH-triggered dissociation of [Au(SG)]. The pH-stimulated dissociation of the Au(I)-glutathionate complex provides a time-efficient synthesis of oligomeric Au(SG) nanoclusters, it avoids high-temperature heating or the addition of harmful reducing agent (e.g., carbon monoxide). Therefore, we present herein a new and eco-friendly methodology to access oligomeric glutathione-based gold nanoclusters, already finding applications in biomedical field as efficient radiosensitizers in cancer radiotherapy.