English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

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

Heras, C., Reta, D., Valero, R., Albareda Piquer, G., Chilton, N., Fielding, A., et al. (2019). Biradical Formation by Deprotonation in Thiazole-Derivatives: The Hidden Nature of Dasatinib. doi:10.26434/chemrxiv.10101419.v1.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/21.11116/0000-0005-4652-0 Version Permalink: http://hdl.handle.net/21.11116/0000-0005-4653-F
Genre: Paper

Files

show Files
hide Files
:
Biradical_Formation_by_Deprotonation_in_Thiazole-Derivatives__The_Hidden_Nature_of_Dasatinib_v1.pdf (Preprint), 5MB
Name:
Biradical_Formation_by_Deprotonation_in_Thiazole-Derivatives__The_Hidden_Nature_of_Dasatinib_v1.pdf
Description:
Downloaded from chemrxiv.org: 2019-11-27
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
2019
Copyright Info:
© the Author(s)

Locators

show
hide
Description:
-

Creators

show
hide
 Creators:
Heras, C.1, Author
Reta, D.2, Author
Valero, R.3, 4, Author
Albareda Piquer, G.4, 5, 6, Author              
Chilton, N.2, Author
Fielding, A.5, 6, Author
de Moreira, I. P. R.3, 4, Author
Bofill, J. M.1, 4, Author
Calahorra, F. L.1, Author
Affiliations:
1Departament de Química Inorgànica i Orgànica, Sec. de Química Orgànica, Universitat de Barcelona, ou_persistent22              
2School of Chemistry, The University of Manchester, ou_persistent22              
3Departament de Ciència dels Materials i Química Física, Sec. de Química Física, Universitat de Barcelona, ou_persistent22              
4Institut de Química Teòrica i Computacional (IQTCUB), Universitat de Barcelona, ou_persistent22              
5Theory Group, Theory Department, Max Planck Institute for the Structure and Dynamics of Matter, Max Planck Society, ou_2266715              
6Center for Free-Electron Laser Science, ou_persistent22              

Content

show
hide
Free keywords: -
 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.

Details

show
hide
Language(s): eng - English
 Dates: 2019-11-06
 Publication Status: Published online
 Pages: 57
 Publishing info: -
 Table of Contents: -
 Rev. Type: No review
 Identifiers: DOI: 10.26434/chemrxiv.10101419.v1
 Degree: -

Event

show

Legal Case

show

Project information

show

Source

show