title: Computational design of S-nitrosothiol "click" reactions.
abstract: To address a long-standing problem of finding efficient reactions for chemical labeling of protein-based S-nitrosothiols (RSNOs), we computationally explored hitherto unknown (3+2) cycloaddition RSNO reactions with alkynes and alkenes. Nonactivated RSNO cycloaddition reactions have high activation enthalpy (>20 kcal/mol at the CBS-QB3 level) and compete with alternative S-N bond insertion pathway. However, the (3+2) cycloaddition reaction barriers can be dramatically lowered by coordination of a Lewis acid to the N atom of the -SNO group. To exploit this effect, we propose to use reagents with Lewis acid and a strain-activated carbon-carbon multiple bond linked by a rigid scaffold, which can react with RSNOs with small activation enthalpies (∼5 kcal/mol) and high reaction exothermicities (∼40 kcal/mol). The proposed efficient RSNO cycloaddition reactions can be used for future development of practical RSNO labeling reactions.
authors.affiliation: Department of Chemistry, Marquette University, Milwaukee, Wisconsin 53201, USA.
authors.forename: Marat R
authors.initials: MR
authors.lastname: Talipov
authors.forename: Dmitry G
authors.initials: DG
authors.lastname: Khomyakov
authors.forename: Ming
authors.initials: M
authors.lastname: Xian
authors.forename: Qadir K
authors.initials: QK
authors.lastname: Timerghazin
mesh_terms: D057930:Click Chemistry; D003500:Cyclization; D011789:Quantum Theory; D026403:S-Nitrosothiols / Q000138:chemical synthesis* / Q000737:chemistry*
chemical_list: D026403:S-Nitrosothiols