Estimation of pKa, Analgesic, CNS Depressant Activities of Imidazolinone Derivatives By Correlation With Theoretical Parameters Based on Quantum Chemical Method
JOURNAL OF EDUCATION AND SCIENCE,
2018, Volume 27, Issue 4, Pages 29-45
AbstractRegression analysis is used for the estimation of the pKa values, %analgesic activity (%AA) and % decreasing activity of central nervous system (CNS) depressant property (%DA) of eight substituted imidazolin-5(4H)-ones by using various types of descriptors as parameters. These parameters are based on quantum chemical treatments. They were derived by employing semi-empirical calculations represented by Austin model 1 (AM1). The parameters used for representing the variation observed in the pka values, %AA and %DA are atomic, structural, and molecular properties, including charges on hetro atoms present in the compounds, energies of HOMO (EHOMO) and LUMO (ELUMO)orbitals, hardness of molecules (η) , chemical potential (μ) electrophilicity index (ω), total energy (TE), stretch (Str), bend (Bd), 1,4-Vander Waals interactions (1,4VDW), and Non1,4- Vander Waals interactions (Non 1,4-VDW). The relation of pKa, %AA, and %DA and each of these parameters of the studied compounds is investigated.
Depending on these relations, three sets of parameters were constructed, each of them representing the most sufficiently and reliable set to describe the effect of substituents and structure of imidazolinone under consideration on the studied properties with highly predictive power indicated by high consistency between the calculated and experimental values expressed by correlation coefficient values (R2) close to unity and standard error (SE) less than %5 of the experimental values.
The three sets of parameters were used for the estimation of pKa, %AA and %DA of a number of hypothetical compounds with structures similar to those considered before but with different substituents as a test of the validity of the derived parameters. The calculated values were within acceptable range compared with other values found in the literature.
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