Studies on the stability and stabilization of trans-cyclooctenes through radical inhibition and silver (I) metal complexation. Issue 32 (9th August 2019)

• Record Type: Journal Article
• Authors: Fang, Yinzhi; Judkins, Joshua C.; Boyd, Samantha J.; am Ende, Christopher W.; Rohlfing, Katarina; Huang, Zhen; Xie, Yixin; Johnson, Douglas S.; Fox, Joseph M.
• Is Part Of: Tetrahedron. Volume 75:Issue 32(2019)
• Page Start: 4307
• Page End: 4317
• Publication Date: 2019-08-09
• Subjects: Bioorthogonal chemistry -- Trans-cyclooctene -- Stability -- Radical inhibitor -- Silver complexation -- Cellular labeling; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tet.2019.05.038
• Languages: English
• ISSNs: 0040-4020

Abstract

Abstract: Conformationally strained trans- cyclooctenes (TCOs) engage in bioorthogonal reactions with tetrazines with second order rate constants that can exceed 10 6 M −1 s −1 . The goal of this study was to provide insight into the stability of TCO reagents and to develop methods for stabilizing TCO reagents for long-term storage. The radical inhibitor Trolox suppresses TCO isomerization under high thiol concentrations and TCO shelf-life can be greatly extended by protecting them as stable Ag(I) metal complexes. 1 H NMR studies show that Ag-complexation is thermodynamically favorable but the kinetics of dissociation are very rapid, and TCOAgNO3 complexes are immediately dissociated upon addition of NaCl which is present in high concentration in cell media. The AgNO3 complex of a highly reactive s-TCO-TAMRA conjugate was shown to label a protein-tetrazine conjugate in live cells with faster kinetics and similar labeling yield relative to a 'traditional' TCO-TAMRA conjugate. Graphical abstract: Image 1