Klormetiyazol’ün Partisyon Katsayısının Tahmin Edilmesi İçin Hesaplamalı Yöntemlerin Kıyaslama Çalışması

Year 2022, Volume: 9 Issue: 2, 567 - 575, 31.05.2022

Sümeyya Serin , Ali Bayri

https://doi.org/10.31202/ecjse.978741

Abstract

Bu çalışma, kuantum kimyasal hesaplama teknikleri kullanılarak Klormetiazol molekülünün lipofiliklik tahmini, HOMO-LUMO analizi ve elektrostatik yüzey özelliklerinin değerlendirmelerini içermektedir. Tüm geometrik optimizasyonlar, enerji ve frekans hesaplamaları, Hartree-Fock (HF) yöntemi ve iki farklı Yoğunluk Fonksiyonel Teori (YFT) fonksiyoneli B3LYP ve B3PW91 seçilerek altı farklı temel set ile gerçekleştirilmiştir. Çözücü etkisini araştırmak ve ayrıca bölme katsayılarını tahmin etmeye yardımcı olan Gibbs solvasyon serbest enerjilerini elde etmek için tüm hesaplamalar su ve n-oktanol fazları için SMD solvasyon modeli kullanılarak tekrarlanmıştır. Sonuç olarak, uygulanan teorik yöntemler arasında deneysel logP değeri ile en iyi uyum HF/6-31G(d,p) yöntemi ile elde edilmiştir. Ayrıca hesaplamalı yöntemlerin tahmin performansının HF> B3LYP> B3PW91 sırasıyla azaldığı sonucuna varılmıştır.

Keywords

Klormetiyazol, DFT, HOMO-LUMO, Lipofiliklik

Benchmark Study of Computational Methods for Predicting Partition Coefficient of Chlormethiazole

Abstract

The present study contains the evaluations of lipophilicity estimation, HOMO-LUMO analysis, and electrostatic surface properties of Chlormethiazole molecule by using quantum chemical calculation techniques. All geometrical optimizations, energy and frequency calculations were carried out with six different basis sets by choosing the Hartree-Fock (HF) method and two different Density Functional Theory (DFT) functionals B3LYP and B3PW91. All calculations were repeated for the water and n-octanol phases by using SMD solvation model in order to investigate the solvent effect and also to obtain the Gibbs free energies of solvation that help to estimate partition coefficients. As a result, among the applied theoretical methods, the best agreement with the experimental logP value was obtained with the HF/6-31G(d,p) method. Also, it is concluded that the forecast performance of the computational methods decreases in the following order: HF> B3LYP> B3PW91.

Keywords

Chlormethiazole, DFT, HOMO-LUMO, Lipophilicity

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