Pnictogen-Assisted Self-Assembly as a Means to Study Mediated Thiol/Disulfide Exchange in Supramolecular Dynamic Covalent Assemblies.

Thiol-disulfide interchange has been a large field of study for both biochemists and physical organic chemists alike due to its prevalence within biological systems and fundamentally interesting dynamic nature. More recently, efforts have been made to harness the power of this reversible reaction to make self-assembling systems of macrocyclic molecules. However, less effort has focused on the fundamental work of isolating these assemblies and studying the factors that control the assembly and sorting of these emerging cyclic systems. A more complete fundamental understanding of factors controlling such self-assembly could also improve understanding of the complex systems biology of thiol exchange while also aiding in the design of dynamic thiol assembly to enable applications ranging from drug delivery and biosensing to new materials synthesis. We have shown previously that pnictogen-assisted self-assembly enables formation of discrete disulfide macrocycles and cages without competition from polymer formation for a wide variety of alkyl thiols. In this study, we report the expansion of pnictogen-assisted self-assembly methods to form disulfide bearing macrocycles from aryl thiol containing ligands, allowing access to previously unreported molecules. These studies complement classical physical organic and chemical biology studies on the rates and products of aryl thiol oxidation to disulfides, and we show that this self-assembly method revises some prevailing wisdom from these key classical studies by providing new product distributions and new isolable products in cyclic disulfide formation.