An Air‐Stable, Neutral Phenothiazinyl Radical with Substantial Radical Stabilization Energy. Issue 14 (19th February 2020)

• Record Type: Journal Article
• Authors: Sigmund, Lukas M.; Ebner, Fabian; Jöst, Christoph; Spengler, Jonas; Gönnheimer, Nils; Hartmann, Deborah; Greb, Lutz
• Is Part Of: Chemistry. Volume 26:Issue 14(2020)
• Page Start: 3152
• Page End: 3156
• Publication Date: 2020-02-19
• Subjects: aminyl radicals -- phenothiazines -- radical stabilization energy -- radicals -- redox chemistry; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201905238
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: The vital effect of radical states on the pharmacological activity of phenothiazine‐based drugs has long been speculated. Whereas cationic radicals of N‐substituted phenothiazines show high stability, the respective neutral radicals of N‐unsubstituted phenothiazines have never been isolated. Herein, the 1, 9‐diamino‐3, 7‐di‐ tert ‐butyl‐ N 1, N 9 ‐bis(2, 6‐diisopropylphenyl)‐10 H ‐phenothiazin‐10‐yl radical (SQH2 . ) is described as the first air‐stable, neutral phenothiazinyl free radical. The crystalline dark‐blue species is characterized by means of EPR and UV/Vis/near‐IR spectroscopy, as well as cyclic voltammetry, spectro‐electrochemical analysis, single‐crystal XRD, and computational studies. The SQH2 . radical stands out from other aminyl radicals by an impressive radical stabilization energy and its parent amine has one of the weakest N−H bond dissociation energies ever determined. In addition to serving as open‐shell reference in medicinal chemistry, its tridentate binding pocket or hydrogen‐bond‐donor ability might enable manifold uses as a redox‐active ligand or proton‐coupled electron‐transfer reagent. Abstract : Out in the open : An air‐stable phenothiazinyl radical was synthesized and characterized by means of experiments, spectroscopy, and computational investigations. The crystalline dark‐blue compound shows addressable redox activity and represents the first N‐unsubstituted phenothiazine‐based aminyl radical.