Phosphine-mediated Reduction of a Selenocysteine Selenenyl Iodide to a Selenocysteine Selenol

Abstract

Trivalent phosphorus compounds are widely used for the reduction of biologically relevant sulfur- and selenium-containing species due to its strong redox potential, broad pH stability, and ability to minimize unwanted side reactions or competitive interactions with other thiol- or selenol-containing compounds. Selenocysteine selenenyl iodides (Sec–SeIs) have attracted increasing attention as key intermediates in the enzymatic functions of iodothyronine deiodinases. Investigating whether Sec–SeIs can serve as substrates for reduction by trivalent phosphorus compounds could provide valuable insights into the existence and behavior of Sec–SeI in proteins. However, to date, there have been no studies examining the reactivity between trivalent phosphorus compounds and selenenyl iodides. In this study, phosphine-mediated reduction of a selenocysteine selenenyl iodide to a selenocysteine selenol was developed using isolable model compounds stabilized by nanosized molecular cradle. The present study demonstrates that phosphines serve as excellent non-thiol reducing agents for selenenyl iodides, particularly in terms of their high reduction efficiency and lack of interfering thiol or selenol groups.