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Bazı Barbitüratların Lipofilikliği Üzerine Yoğunluk Fonksiyonel Teori Çalışmaları

Year 2021, Volume 11, Issue 2, 487 - 502, 31.12.2021
https://doi.org/10.37094/adyujsci.970824

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.

References

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  • [51] Gaillard, P., Carrupt, P.A., Testa, B., Boudon, A., Molecular lipophilicity potential, a tool in 3D QSAR: method and applications, Journal of Computer-Aided Molecular Design, 8, 83−96, 1994.
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Density Functional Theory Studies of Some Barbiturates on Lipophilicity

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

References

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  • [2] Adams, R.D., Victor, M., Ropper, A.H., Epilepsy and other seizure disorder. Adams RD (Ed). Principles of Neurology. Seventh ed., New York; McGraw-Hill 331-365, 2001.
  • [3] Brodie, M.J., Kwan, P., The star systems: overview and use in determining antiepileptic drug choice, CNS Drugs, 15(1), 1–12, 2001.
  • [4] Sander, J.W., The use of antiepileptic drugs-principles and practice, Epilepsia, 45, 28-34, 2004.
  • [5] Yamatogi, Y., Principles of antiepileptic drug treatment of epilepsy. Psychiatry and Clinical Neurosciences, 58(3), 3-6, 2004.
  • [6] Brenner, G.M., Stevens, C.W., Pharmacology (4th ed.). Philadelphia, PA: Elsevier/Saunders, 204p, 2013.
  • [7] Engel, J., Epilepsy: A comprehensive textbook (2nd ed.). Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins., 1431p, 2008.
  • [8] Cuenca-Benito, M., Sagrado, S., Villanueva-Camanas, R.M., Medina- Hernandez, M. J., Quantitative retention-structure and retention-activity relationships of barbiturates by micellar liquid chromatography, Journal of Chromatography A, 814, 121-132, 1998.
  • [9] Henry, D., Block, J.H., Andersen, J.L., and Carlson, G.R., Use of high-pressure liquid chromatography for quantitative structure-activity relationship studies of sulfonamides and barbiturates. Journal of Medicinal Chemistry, 19(5), 619-626, 1976.
  • [10] Hansch, C., Andersen, S.M., Structure-activity relationship in barbiturates and its similarity to that in other narcotics, Journal of Medicinal Chemistry, 10(5), 745-753, 1967.
  • [11] Mayer, J.M., van de Waterbeemd, H., Development of quantitative structure-pharmacokinetic relationships. Environmental Health Perspectives, 61, 295-306, 1985.
  • [12] Gupta, S.P., QSAR studies on drug acting at the central nervous system, Chemical Reviews, 89, 1765-1800, 1989.
  • [13] Carter, M.D., Stephenson, V.C., Weaver, D.F., Are anticonvulsants ‘two thirds’ of local anesthetics? A quantum pharmacology study, Journal of Molecular Structure: THEOCHEM), 638, 57-62, 2003.
  • [14] Tasso, S.M., Bruno-Blanch, L.E., Moon, S.C., Estiu, G.L., Pharmacophore searching and QSAR analysis in the design of anticonvulsant drugs. Journal of Molecular Structure: THEOCHEM), 504, 229-240, 2000.
  • [15] Serdaroğlu, G., Ortiz, J.V., Ab initio calculations on some antiepileptic drugs such as phenytoin, phenobarbital, ethosuximide and carbamazepine, Structural Chemistry, 28, 957-964, 2017.
  • [16] Fong, C.W., Statins in terapy: understanding their hydrophilicity, lipohilicity, binding to 3-hydroxy-3-methylglutaryl-CoA reductase, ability to cross the blood brain barrier and metabolic stability based on electrostatic molecular orbital studies. European Journal of Medicinal Chemistry, 85, 661-674, 2014.
  • [17] Hansch, C., Björkroth, J. P., and Leo, A., Hydrophobicity and central nervous system agents: on the principle of minimal hydrophobicity in drug design. Journal of Pharmaceutical Sciences, 76(9), 663-687, 1987.
  • [18] Michalik, M., Lukes, V., The validation of quantum chemical lipophilicity prediction of alcohols, Acta Chimica Slovaca, 9(2), 89-94, 2016.
  • [19] Iwase, K., Komatsu, K., Hirono, S., Nakagawa, S., Moriguchi, I., Estimation of hydrophobicity based on the solvent- accessible surface area of molecules. Chemical and Pharmaceutical Bulletin, 33(5), 2114-2121, 1985.
  • [20] Du, Q., Arteca, G.A., Mezey, P.G., Heuristic lipophilicity potential for computer-aided rational drug design, Journal of Computer-Aided Molecular Design, 11, 503-515, 1997.
  • [21] Hansch, C. and Dunn, W.J., Linear relationships between lipophilic character and biological activity of drugs, Journal of Pharmaceutical Sciences, 61(1), 1-19, 1972.
  • [22] Hansch, C., Fujita, T., p-σ-π Analysis. A method for the correlation of biological activity and chemical structure, Journal of the American Chemical Society, 85, 1616-1626, 1964.
  • [23] Fujita, T., Hansch, C., Iwasa, J., The correlation of biological activity of plant growth regulators and chloromycetin derivatives with hammett constants and partition coefficient, Journal of the American Chemical Society, 85, 2817-2824, 1963.
  • [24] Pinal, R., Yalkowsky, S. H., Solubility and partitioning VII: solubility of barbiturates in water, Journal of Pharmaceutical Sciences, 76(1), 75-85, 1987.
  • [25] Nadendla, R.R., Principles of organic medicinal chemistry. New Age International (P) Ltd., New Delhi, Publishers, chapter 3, 16-17p, 2005.
  • [26] Sekulić, T.D., Smoliński, A., Mandić, A., Lazić, A., Chromatographic and in silico assessment of logP measures for new spirohydantoin derivatives with anticancer activity, Journal of Chemometrics, 32, 1-13, 2018.
  • [27] Frisch, M.J., Trucks, G.W., Schlegel, H. B., Scuseria, G. E., Robb, M. A. et al. Gaussian 09, Revision D.01, Gaussian, Inc., Wallingford, CT 2009.
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  • [29] Becke, A.D., A new mixing of Hartree–Fock and local density functional theories, The Journal of Chemical Physics, 98, 1372–1377, 1993.
  • [30] Lee, C., Yang, W., Parr, R.G., Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density, Physical Review B, 37, 785–789, 1988.
  • [31] Tomasi, J., Mennucci, B., Cance`s, E., The IEF version of the PCM solvation method: an overview of a new method addressed to study molecular solutes at the QM ab initio level, Journal of Molecular Structure (Theochem), 464, 211–226, 1999.
  • [32] Mennucci, B., Cance`s, E., and Tomasi, J., Evaluation of solvent effects in isotropic and anisotropic dielectrics and in ionic solutions with a unified integral equation method: Theoretical bases, computational implementation, and numerical applications, The Journal of Physical Chemistry B, 101, 10506-10517, 1997.
  • [33] Cance`s, E., Mennucci, B., Tomasi, J., A new integral equation formalism for the polarizable continuum model: Theoretical background and applications to isotropic and anisotropic dielectrics, The Journal of Physical Chemistry, 107, 3032-3041, 1997.
  • [34] Foresman, J.B., Keith, T.A., Wiberg, K.B., Snoonian, J., Frisch, M.J., Solvent effects. 5. Influence of cavity shape, truncation of electrostatics, and electron correlation on ab initio reaction field calculations, The Journal of Physical Chemistry, 100, 16098–16104, 1996.
  • [35] Koopmans, T. Über die zuordnung von wellenfunktionen und eigenwertenzu den einzelnen elektronen eines atoms, Physica., 1, 104-113, 1934.
  • [36] Fukui, K., The Role of Frontier Orbitals in chemical reactions, Science, 218: 747–754, 1982.
  • [37] Janak, J.F., Proof that ∂E/∂ni=εin density-functional theory, Physical Review B, 18 (12), 7165-7168, 1978.
  • [38] Parr, R.G., and Pearson, R.G., Absolute hardness: companion parameter to absolute electronegativity, Journal of the American Chemical Society, 105, 7512-7516, 1983.
  • [39] Pearson, R.G., Absolute electronegativity and hardness correlated with the molecular orbital theory, Proceedings of the National Academy of Sciences, USA.83, 8440-8441, 1986.
  • [40] Parr, R.G., Szentpaly, L.V., Liu, S., Electrophilicity Index, Journal of the American Chemical Society, 121, 1922-1924, 1999.
  • [41] Perdew, J.P., Levy, M., Physical Content of the Exact Kohn-Sham Orbital Energies: Band Gaps and Derivative Discontinuities, Physical Review Letters, 51 (20), 1884-1887, 1983.
  • [42] Perdew, J.P., Parr, R.G., Levy, M., Balduz, J.L., Density-Functional Theory for Fractional Particle Number: Derivative Discontinuities of the Energy, Physical Review Letters, 49 (23), 1691- 1694, 1982.
  • [43] Foresman, J.B., Frisch, Æ. Exploring chemistry with electronic structure methods, third edition, Gaussian, Inc. Wallingford, CT USA, 2015.
  • [44] Garrido, N.M., Queimada, A. J., Jorge, M., Macedo, E. A., and Economou, I. G., 1-Octanol/water partition coefficients of n-alkanes from molecular simulations of absolute solvation free energies, Journal of Chemical Theory and Computation, 5, 2436-2446, 2009.
  • [45] Pernot, P., Civalleri, B., Presti, D., Savin, A., Prediction uncertainty of density functional approximations for properties of crystals with cubic symmetry, The Journal of Physical Chemistry A, 119, 5288−5304, 2015.
  • [46] Lewis, D.F.V., The calculation of molar polarizabilities by the CNDO/2 method: correlation with the hydrophobic parameter, logP, Journal of Computational Chemistry, 10, 145-151, 1989.
  • [47] Gao, S., Cao, C., A new approach on estimation of solubility and n-octanol/ water partition coefficient for organohalogen compounds, International Journal of Molecular Sciences, 9, 962-977, 2008.
  • [48] Zhou, W., Zhai, Z., Wang, Z., Wang, L., Estimation of n-octanol/water partition coefficients (Kow) of all PCB congeners by density functional theory, Journal of Molecular Structure: THEOCHEM, 755, 137–145, 2005.
  • [49] Padmanabhan, J., Parthasarathi, R., Subramanian, V., Chattaraj, P. K., QSPR models for polychlorinated biphenyls:n-octanol/water partition coefficient, Bioorganic & Medicinal Chemistry, 14, 1021–1028, 2006.
  • [50] http://www.molinspiration.com
  • [51] Gaillard, P., Carrupt, P.A., Testa, B., Boudon, A., Molecular lipophilicity potential, a tool in 3D QSAR: method and applications, Journal of Computer-Aided Molecular Design, 8, 83−96, 1994.
  • [52] Pajouhesh, H., Lenz, G.R., Medicinal chemical properties of successful central nervous system drugs, NeuroRx, 2, 541–553, 2005.

Details

Primary Language English
Subjects Chemistry, Multidisciplinary
Journal Section Physics
Authors

Sümeyya SERİN (Primary Author)
İNÖNÜ ÜNİVERSİTESİ
0000-0002-4637-1734
Türkiye


Ali BAYRİ
INONU UNIVERSITY
0000-0002-8197-1604
Türkiye

Publication Date December 31, 2021
Application Date July 13, 2021
Acceptance Date December 10, 2021
Published in Issue Year 2021, Volume 11, Issue 2

Cite

Bibtex @research article { adyujsci970824, journal = {Adıyaman University Journal of Science}, issn = {2147-1630}, eissn = {2146-586X}, address = {}, publisher = {Adıyaman University}, year = {2021}, volume = {11}, number = {2}, pages = {487 - 502}, doi = {10.37094/adyujsci.970824}, title = {Density Functional Theory Studies of Some Barbiturates on Lipophilicity}, key = {cite}, author = {Serin, Sümeyya and Bayri, Ali} }
APA Serin, S. & Bayri, A. (2021). Density Functional Theory Studies of Some Barbiturates on Lipophilicity . Adıyaman University Journal of Science , 11 (2) , 487-502 . DOI: 10.37094/adyujsci.970824
MLA Serin, S. , Bayri, A. "Density Functional Theory Studies of Some Barbiturates on Lipophilicity" . Adıyaman University Journal of Science 11 (2021 ): 487-502 <https://dergipark.org.tr/en/pub/adyujsci/issue/67254/970824>
Chicago Serin, S. , Bayri, A. "Density Functional Theory Studies of Some Barbiturates on Lipophilicity". Adıyaman University Journal of Science 11 (2021 ): 487-502
RIS TY - JOUR T1 - Density Functional Theory Studies of Some Barbiturates on Lipophilicity AU - Sümeyya Serin , Ali Bayri Y1 - 2021 PY - 2021 N1 - doi: 10.37094/adyujsci.970824 DO - 10.37094/adyujsci.970824 T2 - Adıyaman University Journal of Science JF - Journal JO - JOR SP - 487 EP - 502 VL - 11 IS - 2 SN - 2147-1630-2146-586X M3 - doi: 10.37094/adyujsci.970824 UR - https://doi.org/10.37094/adyujsci.970824 Y2 - 2021 ER -
EndNote %0 Adıyaman University Journal of Science Density Functional Theory Studies of Some Barbiturates on Lipophilicity %A Sümeyya Serin , Ali Bayri %T Density Functional Theory Studies of Some Barbiturates on Lipophilicity %D 2021 %J Adıyaman University Journal of Science %P 2147-1630-2146-586X %V 11 %N 2 %R doi: 10.37094/adyujsci.970824 %U 10.37094/adyujsci.970824
ISNAD Serin, Sümeyya , Bayri, Ali . "Density Functional Theory Studies of Some Barbiturates on Lipophilicity". Adıyaman University Journal of Science 11 / 2 (December 2021): 487-502 . https://doi.org/10.37094/adyujsci.970824
AMA Serin S. , Bayri A. Density Functional Theory Studies of Some Barbiturates on Lipophilicity. ADYU J SCI. 2021; 11(2): 487-502.
Vancouver Serin S. , Bayri A. Density Functional Theory Studies of Some Barbiturates on Lipophilicity. Adıyaman University Journal of Science. 2021; 11(2): 487-502.
IEEE S. Serin and A. Bayri , "Density Functional Theory Studies of Some Barbiturates on Lipophilicity", Adıyaman University Journal of Science, vol. 11, no. 2, pp. 487-502, Dec. 2021, doi:10.37094/adyujsci.970824

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