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An Air‐Stable, Neutral Phenothiazinyl Radical with Substantial Radical Stabilization Energy
Author(s) -
Sigmund Lukas M.,
Ebner Fabian,
Jöst Christoph,
Spengler Jonas,
Gönnheimer Nils,
Hartmann Deborah,
Greb Lutz
Publication year - 2020
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201905238
Subject(s) - chemistry , radical , phenothiazine , electron paramagnetic resonance , photochemistry , dissociation (chemistry) , cyclic voltammetry , electron transfer , bond dissociation energy , homolysis , reagent , electrochemistry , medicinal chemistry , organic chemistry , electrode , nuclear magnetic resonance , pharmacology , medicine , physics
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 (SQH 2 . ) 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 SQH 2 . 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.