Quantum Mechanical Prediction of Dissociation Constants for Thiazol-2-imine Derivatives.
J Chem Inf Model
; 63(10): 2992-3004, 2023 05 22.
Article
em En
| MEDLINE
| ID: mdl-37126823
ABSTRACT
As weak acids or bases, in solution, drug molecules are in either their ionized or nonionized states. A high degree of ionization is essential for good water solubility of a drug molecule and is required for drug-receptor interactions, whereas the nonionized form improves a drug's lipophilicity, allowing the ligand to cross the cell membrane. The penetration of a drug ligand through cell membranes is mainly governed by the pKa of the drug molecule and the membrane environment. In this study, with the aim of predicting the acetonitrile pKa's (pKa(MeCN)) of eight drug-like thiazol-2-imine derivatives, we propose a very accurate and computationally affordable protocol by using several quantum mechanical approaches. Benchmark studies were conducted on a set of training molecules, which were selected from the literature with known pKa(water) and pKa(MeCN). Highly well-correlated pKa values were obtained when the calculations were performed with the isodesmic method at the M062X/6-31G** level of theory in conjunction with SMD solvation model for nitrogen-containing heterocycles. Finally, experimentally unknown pKa(MeCN) values of eight thiazol-2-imine structures, which were previously synthesized by some of us, are proposed.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Água
/
Iminas
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article