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A DFT Study on the Radical Structures and HOMO-LUMO Analysis of Azathioprine

Year 2019, , 1165 - 1173, 31.08.2019
https://doi.org/10.18185/erzifbed.468345

Abstract

Azathioprine (Imuran) is used for to treat of numerous debilitating skin diseases. Azathioprine is an
immunosuppressive antimetabolite used to prevent the body from rejecting a transplanted kidney.
By
means of EPR spectroscopy, this compound was studied experimentally before. But experimental searchers were only able to determine g value. For this reason, the EPR parameters (a and g value) have been determined
theoretically in the present study. Furthermore HOMO and LUMO analysis have been carried out by density functional theory (DFT/B3LYP) method with 6-311++G (d,p) as basis set. Since HOMO and LUMO are most
important orbitals in molecules,
these orbitals are very useful to understand some molecular properties such as
the
chemical reactivity, kinetic stability, optical polarizability, chemical hardness and softness and
electronegativity. Moreover, from
the results of the DFT calculations, we obtained as follows: the total energy,
the
total dipole moment of the molecule (µ), absolute hardness ), absolute electron negativity (χ) and reactivity
index (ω).

References

  • Ambroż, H., Kornacka, E., Marciniec, B., Ogrodowczyk, M., & Przybytniak, G. (2000). EPR study of free radicals in some drugs γ-irradiated in the solid state. Radiation Physics and Chemistry, 58(4), 357-366.
  • Chtita, S., Ghamali, M., Larif, M., Adad, A., Hmammouchi, R., Bouachrine, M., & Lakhlifi, T. (2013). Prediction of biological activity of imidazo [1, 2-a] pyrazine derivatives by combining DFT and QSAR results. IJIRSET, 2(12), 7962.
  • Frisch, M. J. T., G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Montgomery, Jr., J. A.; Vreven, T.; Kudin, K. N.; Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.; Scalmani, G.; , Rega, N. P., G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Bakken, V.; Adamo, C.;, Jaramillo, J. G., R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.; Strain, M. C.; , Farkas, O. M., D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.; , & Al-Laham, M. A. P., C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; and Pople, J. A. (2003). Gaussian 03. Wallingford CT: Gaussian, Inc. Retrieved from http://www.gaussian.com/g_misc/g03/citation_g03.htm
  • Irvine. (2008). Spartan 08. CA 92612, USA: Wavefunction Inc.
  • Issaoui, N., Ghalla, H., Bardak, F., Karabacak, M., Dlala, N. A., Flakus, H., & Oujia, B. (2017). Combined experimental and theoretical studies on the molecular structures, spectroscopy, and inhibitor activity of 3-(2-thienyl) acrylic acid through AIM, NBO, FT-IR, FT-Raman, UV and HOMO-LUMO analyses, and molecular docking. Journal of Molecular Structure, 1130, 659-668.
  • Makhyoun, M. A., Massoud, R. A., & Soliman, S. M. (2013). Tautomerism and spectroscopic properties of the immunosuppressant azathioprine. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 114, 394-403.
  • Milosavljević, S., Juranić, I. O., Aljančić, I., Vajs, V., & Todorović, N. (2003). Conformation analysis of three germacranolides by the PM3 semi-empirical method. Journal of the Serbian Chemical Society, 68(4-5), 281-289.
  • Osmanoğlu, Y. E., Sütçü, K., & Başkan, M. H. (2017). EPR investigation of gamma-irradiated l-citrulline, α-methyl-dl-serine, 3-fluoro-dl-valine and N-acetyl-l-cysteine. Journal of Molecular Structure, 1130, 291-295.
  • Patel, A. A., Swerlick, R. A., & McCall, C. O. (2006). Azathioprine in dermatology: the past, the present, and the future. Journal of the American Academy of Dermatology, 55(3), 369-389.
  • Pillai, A. A., & Levitsky, J. (2009). Overview of immunosuppression in liver transplantation. World Journal of Gastroenterology: WJG, 15(34), 4225. Prasath, M., Govindammal, M., & Sathya, B. (2017). Spectroscopic investigations (FT-IR & FT-Raman) and molecular docking analysis of 6-[1-methyl-4-nitro-1H-imidazol-5-yl) sulfonyl]-7H-purine. Journal of Molecular Structure, 1146, 292-300.
  • Rauk, A. (2004). Orbital interaction theory of organic chemistry: John Wiley & Sons.
  • Streitwieser, A. (1961). Molecular orbital theory for organic chemists. New York: John Wiley and Sons, Inc..
  • Swarbrick, J. (2013). Encyclopedia of pharmaceutical technology: CRC Press.
  • W.J. Cook, C. E. B. (1975). J. Pharm. Sci., 64 221–225.

Azatioprin Molekülünün Muhtemel Radikallerinin Yapısının Hesaplamalı Yöntemlerle İncelenmesi ve Homo-Lumo Analizi

Year 2019, , 1165 - 1173, 31.08.2019
https://doi.org/10.18185/erzifbed.468345

Abstract

Azatioprin (Imuran) çok sayıda güçten şüren cilt hastalığını tedavi etmek için kullanır. Azatioprin cudun nakledilen breği reddetmesini önlemek için kullanılan bağışıklık bastırıcı bir anti-metabolittir. Bu bileşik,
daha
önce EPR spektroskopisi ile deneysel olarak incelenmiştir. Ama deneysel olarak sadece g değerini
belirleyebilmişlerdir. Bu nedenle, çalışmamızda EPR parametreleri (a ve g değerleri) teorik olarak hesaplanmıştır. Ayrıca HOMO ve LUMO analizi DFT/B3LYP metot ve 6-311++G (d,p) baz seti ile yapılmışr.
HOMO
ve LUMO, moleküllerdeki en önemli orbitaller olduğundan, bu orbitaller kimyasal tepkime, kinetik stabilite,
optik polarizasyon,
kimyasal sertlik ve yumuşakk ve elektronegatiflik gibi bazı moleler özellikleri anlamak için çok faydalıdır. Ayrıca, DFT hesaplamalarının sonuçlarından toplam enerji, molekülün toplam
dipol momenti (µ), mutlak sertlik (η),
mutlak elektron negatifliği (χ) ve reaktiflik indeksi (ω) elde edilmiştir.

References

  • Ambroż, H., Kornacka, E., Marciniec, B., Ogrodowczyk, M., & Przybytniak, G. (2000). EPR study of free radicals in some drugs γ-irradiated in the solid state. Radiation Physics and Chemistry, 58(4), 357-366.
  • Chtita, S., Ghamali, M., Larif, M., Adad, A., Hmammouchi, R., Bouachrine, M., & Lakhlifi, T. (2013). Prediction of biological activity of imidazo [1, 2-a] pyrazine derivatives by combining DFT and QSAR results. IJIRSET, 2(12), 7962.
  • Frisch, M. J. T., G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Montgomery, Jr., J. A.; Vreven, T.; Kudin, K. N.; Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.; Scalmani, G.; , Rega, N. P., G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Bakken, V.; Adamo, C.;, Jaramillo, J. G., R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.; Strain, M. C.; , Farkas, O. M., D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.; , & Al-Laham, M. A. P., C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; and Pople, J. A. (2003). Gaussian 03. Wallingford CT: Gaussian, Inc. Retrieved from http://www.gaussian.com/g_misc/g03/citation_g03.htm
  • Irvine. (2008). Spartan 08. CA 92612, USA: Wavefunction Inc.
  • Issaoui, N., Ghalla, H., Bardak, F., Karabacak, M., Dlala, N. A., Flakus, H., & Oujia, B. (2017). Combined experimental and theoretical studies on the molecular structures, spectroscopy, and inhibitor activity of 3-(2-thienyl) acrylic acid through AIM, NBO, FT-IR, FT-Raman, UV and HOMO-LUMO analyses, and molecular docking. Journal of Molecular Structure, 1130, 659-668.
  • Makhyoun, M. A., Massoud, R. A., & Soliman, S. M. (2013). Tautomerism and spectroscopic properties of the immunosuppressant azathioprine. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 114, 394-403.
  • Milosavljević, S., Juranić, I. O., Aljančić, I., Vajs, V., & Todorović, N. (2003). Conformation analysis of three germacranolides by the PM3 semi-empirical method. Journal of the Serbian Chemical Society, 68(4-5), 281-289.
  • Osmanoğlu, Y. E., Sütçü, K., & Başkan, M. H. (2017). EPR investigation of gamma-irradiated l-citrulline, α-methyl-dl-serine, 3-fluoro-dl-valine and N-acetyl-l-cysteine. Journal of Molecular Structure, 1130, 291-295.
  • Patel, A. A., Swerlick, R. A., & McCall, C. O. (2006). Azathioprine in dermatology: the past, the present, and the future. Journal of the American Academy of Dermatology, 55(3), 369-389.
  • Pillai, A. A., & Levitsky, J. (2009). Overview of immunosuppression in liver transplantation. World Journal of Gastroenterology: WJG, 15(34), 4225. Prasath, M., Govindammal, M., & Sathya, B. (2017). Spectroscopic investigations (FT-IR & FT-Raman) and molecular docking analysis of 6-[1-methyl-4-nitro-1H-imidazol-5-yl) sulfonyl]-7H-purine. Journal of Molecular Structure, 1146, 292-300.
  • Rauk, A. (2004). Orbital interaction theory of organic chemistry: John Wiley & Sons.
  • Streitwieser, A. (1961). Molecular orbital theory for organic chemists. New York: John Wiley and Sons, Inc..
  • Swarbrick, J. (2013). Encyclopedia of pharmaceutical technology: CRC Press.
  • W.J. Cook, C. E. B. (1975). J. Pharm. Sci., 64 221–225.
There are 14 citations in total.

Details

Primary Language English
Subjects Engineering
Journal Section Makaleler
Authors

Ebru Karakaş Sarıkaya

Ömer Dereli

Publication Date August 31, 2019
Published in Issue Year 2019

Cite

APA Karakaş Sarıkaya, E., & Dereli, Ö. (2019). A DFT Study on the Radical Structures and HOMO-LUMO Analysis of Azathioprine. Erzincan University Journal of Science and Technology, 12(2), 1165-1173. https://doi.org/10.18185/erzifbed.468345