Quantum Chemical Analysis of Structural and Conformational Properties of Methisazone and Prototropic Tautomerism of Isatin

Мова статті: 
Англійська
Автор(и) статті: 
Ol’ha I. Bolsunova, Ol’ha O. Brovarets’, Dmytro M. Hovorun, Leonid A. Zaika, Anatoliy I. Potopalsky
Вихідні данні статті: 
International Review of Biophysical Chemistry. – 2011. - Vol. 2, n. 5, pp. 159-164
Назва журналу: 
International Review of Biophysical Chemistry
Рік публікації: 
2011
Volume: 
2
Issue: 
5
Ключові слова: 
Antiviral, Antitumor and Antifungal Drugs, Isatin, Izatizon, Methisazone, Thiosemicarbazone, Quantum Chemical Investigation
Ключове слово: 
antiviral
Ключове слово: 
antitumor and antifungal drugs
Ключове слово: 
isatin
Ключове слово: 
izatizon
Ключове слово: 
methisazone
Ключове слово: 
thiosemicarbazone
Ключове слово: 
quantum chemical investigation
The conformational diversity of methisazone and prototropic molecular tautomerism of isatin were investigated by means of ab initio calculations at the MP2/6-311++G(2df,pd)//DFT B3LYP/6-311++G(d,p) level of theory. A comprehensive conformational, energetical and polar analysis of the methisazone (1-methyl-1H-indole-2,3-dione 3-thiosemicarbazone), a thiosemicarbazone, was provided. We established that flexibility of the thiosemicarbazone group causes conformational diversity of methisazone molecule. Structural, energetical and electron-topological characteristics of specific intramolecular contacts in methisazone conformers were analyzed. In general, two types of H-bonds (NH…O, CH…N), one type of dihydrogen bond (CH…HN) and three types of van der Waals contacts (N…N, N…O, C…O) were detected by performing electron density topological analysis for all 11 conformers of methisazone. A wide range of biological activity of izatizon based on conformational capacity of methisazone molecule, the main constituent part of this drug, was shortly discussed. Five molecular prototropic tautomers of isatin (1H-indole-2,3-dione) – one diketo and four enol tautomeric forms - were indicated. All five isomers have relative Gibbs free energies within a wide range of ~40 kcal∙mol−1 at physiological temperature. The possible biochemical role of tautomeric forms of isatin was briefly discussed.
Назва підрозділу: 
ІВТ
Кафедра молекулярної біології, біотехнології та біофізики
ІНСТИТУТ ВИСОКИХ ТЕХНОЛОГІЙ Матеріали дозволено використовувати на умовах GNU FDL без незмінюваних секцій та Creative Commons Attribution/Share-Alike
Дизайн: Інститут високих технологій
Ivan Ivanov