Object's details: Synthesis and Physico-Chemical Properties in Aqueous Medium of All Possible Isomeric Bromo Analogues of Benzo-1H-Triazole, Potential Inhibitors of Protein Kinases.

Provider:Repozytorium Instytutu Biochemii i Biofizyki Polskiej Akademii Nauk

Description

Title:
Synthesis and Physico-Chemical Properties in Aqueous Medium of All Possible Isomeric Bromo Analogues of Benzo-1H-Triazole, Potential Inhibitors of Protein Kinases.
Creator:
Wąsik, Romualda;
Wińska, Patrycja;
Poznański, Jarosław;
Shugar, David
Description:
In ongoing studies on the role of the individual bromine atoms of 4,5,6,7-tetrabromobenzotriazole (TBBt) in its relatively selective inhibition of protein kinase CK2α, we have prepared all the possible two mono-, four di-, and two tri- bromobenzotriazoles, and determined their physico-chemical properties in aqueous medium. They exhibited a general trend of a decrease in solubility with an increase in the number of bromines on the benzene ring, significantly modulated by the pattern of substitution. For a given number of attached bromines, this was directly related to the electronic effects resulting from different sites of substitution, leading to marked variations of pKa values for dissociation of the triazole proton. Experimental data (pKa, solubility) and ab initio calculations demonstrated that hydration of halogenated benzotriazoles is driven by a subtle balance of hydrophobic and polar interactions. The combination of QM-derived free energies for solvation and proton dissociations was found to be a reasonably good predictor of inhibitory activity of halogenated benzotriazoles vs CK2α. Since the pattern of halogenation of the benzene ring of benzotriazole has also been shown to be one of the determinants of inhibitory potency vs some viruses and viral enzymes, the present comprehensive description of their physico-chemical properties should prove helpful in efforts to elucidate reaction mechanisms, including possible halogen bonding, and the search for more selective and potent inhibitors.
Object availability:
free access
Date:
2012.05.25
Type:
Article;
PeerReviewed
Language:
English
Format:
application/pdf
Publisher:
ACS
Relation: http://eprints.ibb.waw.pl/628 ;http://pubs.acs.org/journal/jpcbfk ;
10.1021/jp301561x
Subject:
QD Chemistry
Identifier: http://eprints.ibb.waw.pl/628/1/2012_JPChB.pdf ;
Wąsik, Romualda and Wińska, Patrycja and Poznański, Jarosław and Shugar, David (2012) Synthesis and Physico-Chemical Properties in Aqueous Medium of All Possible Isomeric Bromo Analogues of Benzo-1H-Triazole, Potential Inhibitors of Protein Kinases. The journal of physical chemistry. B, 116 (24). pp. 7259-7268. ISSN 1520-5207
Data provider:
Repozytorium Instytutu Biochemii i Biofizyki Polskiej Akademii Nauk

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Object's details: Synthesis and Physico-Chemical Properties in Aqueous Medium of All Possible Isomeric Bromo Analogues of Benzo-1H-Triazole, Potential Inhibitors of Protein Kinases.

Description

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