molecules Review Recent Advances in Chemical Biology Using Benzophenones and Diazirines as Radical Precursors 1,2, , 1,2, Muhammad Murtaza Hassan * y and Olasunkanmi O. Olaoye y 1 Department of Chemical and Physical Sciences, University of Toronto Mississauga, 3359 Mississauga Road North, Mississauga, ON L5L 1C6, Canada;
[email protected] 2 Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, ON M5S 3H6, Canada * Correspondence:
[email protected]; Tel.: +1-905-569-4588 These authors contributed equally to this work. y Academic Editor: Edward Lee-Ruff Received: 18 April 2020; Accepted: 9 May 2020; Published: 13 May 2020 Abstract: The use of light-activated chemical probes to study biological interactions was first discovered in the 1960s, and has since found many applications in studying diseases and gaining deeper insight into various cellular mechanisms involving protein–protein, protein–nucleic acid, protein–ligand (drug, probe), and protein–co-factor interactions, among others. This technique, often referred to as photoaffinity labelling, uses radical precursors that react almost instantaneously to yield spatial and temporal information about the nature of the interaction and the interacting partner(s). This review focuses on the recent advances in chemical biology in the use of benzophenones and diazirines, two of the most commonly known light-activatable radical precursors, with a focus on the last three years, and is intended to provide a solid understanding of their chemical and biological principles and their applications. Keywords: photoaffinity labelling; benzophenone; diazirine; radical precursors; interactome; SABRE; hyperpolarizing agents; crosslinking; photochemistry 1. Introduction The use of radicals or photoactivatable radical precursors has become ubiquitous in the fields of medicinal chemistry and chemical biology in the past three decades.