The use of chemical diversity, i.e. regioisomeric as well as disulfide and diselenide probes, as mechanistic, thermodynamic, and hydrolytic controls, has thus been a key element in testing and rationalising RX1's selenolthiol-selectivity. More broadly, the rationally-designed panel of selenium-containing motifs we present here complements the all-sulfur series we have reported to allow functional comparison and selectivity screening across a total of >40 biocompatible dichalcogenide redox probes, with a level of intercomparability and rigour that to our knowledge has not yet been attempted. It was our aim to increase the breadth and depth of this body of data, and particularly also to provide explicit mechanistic descriptions (Fig. -S4) of how these small molecule probes have been designed for selectivity despite lacking the protein recognition features upon which genetic approaches can rely. Our hope is that by doing so, this research will both inspire new chemical approaches in the still-untapped field of redox chemical biology, and will also open doors for a range of powerful biological studies: revealing the key cellular redox networks in action, and addressing them through therapeutics targeted by the physiology and the pathology of TrxR1.