Density Functional Theory Studies of Some Barbiturates on Lipophilicity

Year 2021, Volume: 11 Issue: 2, 487 - 502, 31.12.2021

Sümeyya Serin , Ali Bayri

https://doi.org/10.37094/adyujsci.970824

Abstract

This paper deals with the evaluation of lipophilicity expressed by logPow parameter of ten barbiturate derivatives generally used as sedative-hypnotics based on Density Functional Theory (DFT) calculations. All geometry optimizations and frequency calculations have been carried out by using DFT/B3LYP/ 6-311++G (d,p) basis set in gas phase and also in water and n-octanol phases. Gibbs free energies of solvation for studied barbiturates were calculated to predict logPow. The correlation between the calculated logPow values and available data in literature has been examined. Root mean square error (RMSE), mean square error (MSE), mean absolute deviation (MAD) and mean absolute percentage error (MAPE) statistics were utilized in measuring predictive accuracy (forecast performance) of DFT method used in this study. Accordingly, the reasonable results have been obtained in estimating the partition coefficient of the mentioned ten barbiturate derivatives by DFT/B3LYP/6-311++G (d,p) method. The lipophilicity tendency of the studied barbiturates was interpreted with the help of the calculated quantum chemical descriptors such as HOMO energy (EHOMO), LUMO energy (ELUMO), molecular volume (Vm), electrophilicity index (ω). ELUMO, Vm, and ω descriptors gave reasonable results rather than EHOMO. Also, the 3D molecular lipophilicity potential (MLP) maps that display the accumulative lipophilic contributions of each atom in studied barbiturates were visualized.

Keywords

DFT, Barbiturate, Solvation free energy, Error analysis

Bazı Barbitüratların Lipofilikliği Üzerine Yoğunluk Fonksiyonel Teori Çalışmaları

Abstract

Bu makale, Yoğunluk Fonksiyonel Teori (YFT) hesaplamalarına dayalı olarak, genellikle sedatif-hipnotik olarak kullanılan on barbitürat türevinin logPow parametresi ile ifade edilen lipofilikliğinin değerlendirilmesini ele almaktadır. Tüm geometri optimizasyonları ve frekans hesaplamaları, gaz fazında ve ayrıca su ve n-oktanol fazlarında DFT/B3LYP/6-311++G (d,p) temel seti kullanılarak yapılmıştır. LogPow değerlerini tahmin etmek için, çalışılan barbitüratların Gibbs serbest solvasyon enerjileri hesaplanmıştır. Hesaplanan logPow değerleri ile literatürdeki mevcut veriler arasındaki korelasyon incelenmiştir. Bu çalışmada kullanılan YFT yönteminin tahmin doğruluğunun (tahmin performansı) ölçülmesinde ortalama karekök hata (RMSE), ortalama kare hata (MSE), ortalama mutlak sapma (MAD) ve ortalama mutlak yüzde hata (MAPE) istatistiklerinden yararlanılmıştır. Buna göre, bahsedilen on barbitürat türevinin dağılım katsayısının DFT/B3LYP/6-311++G (d,p) yöntemi ile tahmin edilmesinde makul sonuçlar elde edilmiştir. İncelenen barbitüratların lipofilisite eğilimi, HOMO enerjisi (EHOMO), LUMO enerjisi (ELUMO), moleküler hacim (Vm), elektrofilik indeks (ω) gibi hesaplanan kuantum kimyasal tanımlayıcılar yardımıyla yorumlanmıştır. ELUMO, Vm ve ω tanımlayıcıları EHOMO değerine kıyasla daha makul sonuçlar vermiştir. Ayrıca, çalışılan barbitüratlarda her bir atomun birikimli lipofilik katkılarını gösteren 3 boyutlu moleküler lipofiliklik potansiyeli (MLP) haritaları görselleştirilmiştir.

Keywords

YFT; Barbiturat; Solvasyon serbest enerjisi; Hata analizi.

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