Biradical Formation by Deprotonation in Thiazole-Derivatives: The Hidden Nature of Dasatinib

06 November 2019, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

The formation of stable organic biradicals by a deprotonation process is reported for a series of conjugated heterocycles that share a Ph-N(H)-2-thiazole structural motif. We characterise the paramagnetic electronic ground state by means of continuous-wave and pulse EPR. We propose a simple valence bond mechanism for a deprotonation-induced formation of paramagnetic organic molecules, based on the interplay between the electronegativity of heteroatomic groups and the recovery of aromaticity to stabilise the biradical species. The Ph-N(H)-2-thiazole motif is found in a variety of biologically active molecules, exemplified here with the anticancer drug Dasatinib, and our results suggest a radical-based mechanism for the protein kinase inhibition activity of the drug. The existence of this structure-property relationship for an elementary chemical motif suggests that biradical species may be more prevalent than previously thought and have an important role in bioorganic chemistry.

Keywords

biradical
EPR
organic magnetism
Dasatinib
anti-cancer drug
thiazole-derivatives

Supplementary materials

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Biradicals v8 ESI
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