Ketoprofen Molekülünün Olası Radikallerine ait Elektron Spin Rezonans Spektrum Simülasyonları

Öz

Bu çalışmada Ketoprofen molekülünün moleküler yapısı Yoğunluk Fonksiyonelleri Teorisi metodu ve Moleküler Mekanik Kuvvet Alanları yöntemi kullanılarak açığa çıkarılmıştır. Öncelikle Ketoprofen molekülünün konformasyonel uzay taraması Moleküler Mekanik Kuvvet Alanları metodu kullanılarak gerçekleştirilmiştir. Ketoprofen molekülünün en kararlı yapısı Yoğunluk Fonksiyonelleri Teorisi metodu yardımıyla bulunmuştur. Ketoprofen molekülünün geometri parametreleri ve Nükleer Manyetik Rezonans parametreleri, Yoğunluk Fonksiyonel Teorisi yöntemi yardımıyla hesaplanmıştır. Olası radikaller, ketoprofen molekülünün en kararlı yapısı kullanılarak modellenmiştir. Bu olası radikallerin Elektron Spin Rezonans parametreleri Yoğunluk Fonksiyonları Teorisi yöntemi ile hesaplanmıştır. Hesaplanan Elektron Spin Rezonans parametreleri JEOL IsoSimu/Fa Versiyon 2.2.0 simülasyon programında kullanılmış ve olası radikallerin teorik Elektron Spin Rezonans spektrumları elde edilmiştir.

Anahtar Kelimeler

• Elektron Spin Rezoanans
• Yoğunluk Fonksiyonelleri Teorisi
• Ketoprofen
• Radikal Simülasyonları

Electron Spin Resonance Spectrum Simulations of Possible Radicals of the Ketoprofen Molecule

Öz

In this study, the molecular structure of Ketoprofen molecule, which is the drug active ingredient , was revealed by using the Density Functional Theory method and the Molecular Mechanical Force Field method. First of all, conformational space scanning in the Ketoprofen molecule was performed by the Molecular Mechanical Force Field method. The most stable structure of the ketoprofen molecule was found with the help of the Density Functional Theory method. The geometry parameters of the ketoprofen molecule and the Nuclear Magnetic Resonance parameters were calculated with the help of the Density Functional Theory method. Possible radicals were modeled using the most stable structure of the ketoprofen molecule. Electron Spin Resonance parameters of these possible radicals were calculated with the Density Functions Theory method. The calculated Electron Spin Resonance parameters were used in the JEOL IsoSimu/Fa Version 2.2.0 simulation program and theoretical Electron Spin Resonance spectra of possible radicals were obtained.

Anahtar Kelimeler

• Electron Spin Resonance,
• Density Functional Theory
• Ketoprofen
• Radical Simulations

Kaynakça

1. El-Kamel AH, Sokar MS, Al Gamal SS, Naggar VF. Preparation and evaluation of ketoprofen floating oral delivery system. International Journal of Pharmaceutics. 2001; 220 (1-2): 13-21.
2. Kokki H, Karvinen M, Jekunen A. Pharmacokinetics of a 24-hour intravenous ketoprofen infusion in children. Acta Anaesthesiologica Scandinavica. 2002; 46(2): 194-98.
3. Vueba ML, Batista de Carvalho LAE, Veiga F, Sousa JJ, Pina ME. Influence of cellulose ether polymers on ketoprofen release from hydrophilic matrix tablets. European Journal of Pharmaceutics and Biopharmaceutics. 2004; 58(1): 51-59.
4. Earley B, Crowe MA. Effects of ketoprofen alone or in combination with local anesthesia during the castration of bull calves on plasma cortisol, immunological, and inflammatory responses. Journal of Animal Science. 2002; 80(4): 1044-52.
5. Chuang YP, Xue J, Du Y, Li M, An HY, Phillips DL. Time-Resolved Resonance Raman and Density Functional Theory Investigation of the Photochemistry of (S)-Ketoprofen. Journal of Physical Chemistry B. 2009; 113(30): 10530-39.
6. Lekun L, Gao H. First principles study on the molecular structure and vibrational spectra of ketoprofen. Spectrochimica Acta PartA. 2012; 97: 329-39.
7. Abdel-Shafi AA. Effect of β-cyclodextrin on the excited state proton transfer in 1-naphthol-2-sulfonate. Spectrochimica Acta PartA. 2001; 57(9): 1819-28.
8. Dodziuk H, Demchuk OM, Schilf W, Dolgonos G. Synthesis and NMR study of a first generation dendrimer having four branches involving four glycine and one carbomoyl-(3,7-dimethoxy-2-naphthalene) groups and attempts to complex it with α-, β-or γ-cyclodextrins. Journal of Molecular Structure. 2004; 693(1-3): 145-51.

9. Beraldo H, Nacif WF, West DX. Spectral studies of semicarbazones derived from 3- and 4-formylpyridine and 3- and 4-acetylpyridine: crystal and molecular structure of 3-formylpyridine semicarbazone. Spectrochimica Acta PartA. 2001; 57(9): 1847-54.
10. Osmialowski O, Kolehmainen E, Gawinecki R. GIAO/DFT calculated chemical shifts of tautomeric species. 2-Phenacylpyridines and (Z)-2-(2-hydroxy-2-phenylvinyl)pyridines. Magnetic Resonance in Chemistry. 2001; 39(6): 334-40.
11. Meng Z, Carper WR. GIAO NMR calculations for atrazine and atrazine dimers: comparison of theoretical and experimental 1H and 13C chemical shifts. Journal of Molecular Structure Theochem. 2002; 588(1-3): 45-53.
12. Laihia K, Kolehmainen E, Kauppinen R, Lorenc J, Puszko A. Multinuclear 1H, 13C and 15N NMR study of some substituted 2-amino-4-nitropyridines and their N-oxides. Spectrochimica Acta PartA. 2002; 58(7): 1425-35.
13. Depature L, Surpateanu G. Carbanion substituent effects on 1-disubstituted 4-(4′-pyridyl)pyridinium methylide structures using 13C NMR spectroscopy and DFT method. Spectrochimica Acta PartA. 2003; 59(13): 3029-39.
14. Dega-Szafran Z, Katrusiak A, Szafran M. X-ray, NMR and DFT studies of the complex of 1,4-dimethylpiperazine mono-betaine with p-hydroxybenzoic acid. Journal of Molecular Structure. 2006; 785(1-3):160-66.
15. Basly JP, Longy I, Bernard, M. ESR identification of radiosterilized pharmaceuticals: latamoxef and ceftriaxone. International Journal of Pharmaceutics.1997; 58(8):241-45.
16. Basly JP, Basly I, Bernard M. Electron spin resonance detection of radiosterilization of pharmaceuticals: application to four nitrofurans. Analyst.1998; 123(8):1753-56.
17. Ece E, Tasdemir HU, Biyik R, Ozmen A, Sayin U. Paramagnetic characterization and dosimetric properties of Airfix drug and its ingredients (Montelukast sodium, Sorbitol): An EPR and DFT study. Radiation Physics and Chemistry. 2022; 1995: 110082.
18. Ece E, Ozmen A, Biyik R, Sayin U. Gamma irradiation effect on some asthma drugs: EPR detection of radiosterilization. Radiation Protection Dosimetry. 2023; 199(14): 1600-1604.
19. Koksal F, Koseoglu R. EPR of gamma irradiation induced radicals in NaHCO3, CsHCO3 and Na2CO3. Radiation Physics and Chemistry. 2000; 57(1): 59-61.
20. Damian G. EPR investigation of γ-irradiated anti-emetic drugs. Talanta. 2003; 60(5): 923-27.
21. Yordanov ND, Mladenova, R. EPR study of free radicals in bread. Spectro- Chim Acta PartA. 2004; 60(6): 1395-1400.
22. Ciofini I, Adamo C, Barone VJ. Complete structural and magnetic characterization of biological radicals in solution by an integrated quantum mechanical approach: Glycyl radical as a case study. Journal of Chemical Physics. 2004; 121(14): 6710-18.
23. Harriman J E. Theoretical Foundation of Electron Spin Resonance. New York: Academic Press; 1978.
24. Tasdemir HU, Türkkan E, Sayin U, Ozmen A. EPR study of gamma-irradiated 2-Bromo-4′- methoxyacetophenone single crystals. Radiation Effect and Defect in Solids. 2016; 171(3-4): 214-22.
25. Tasdemir HU, Sayin U, Turkkan E, Ozmen A. EPR investigation of gamma irradiated single crystal guaifenesin: A combined experimental and computational study. Radiation Physics and Chemistry. 2016; 121: 61-68.
26. Shao Y, Molnar L, Jung Y, Kussmann J, Ochsenfeld C, Brown S, et al. Spartan’08, Wavefunction, Inc. Irvine, CA. Physical Chemistry Chemical Physics.2006;8:3172-91.
27. Becke AD. Density Functional thermochemistry. III. The role of exact exchange. Journal of Chemical Physics. 1993; 98(7): 5648-52.
28. Lee C, Yang W, Parr RG. Development of the Colle- Salvetti correlation- energy formula into a functional of the electron density. Physical Review B.1988; 37: 785-89.
29. Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, et al.Gaussian 03, Revision E.01, Gaussian, Inc., Pittsburgh, PA. 2003.
30. Guo H, Cai C, Gong H, Chen X. Multi-spectroscopic method study the interaction of anti-inflammatory drug ketoprofen and calf thymus DNA and its analytical application. Spectrochimica Acta Part A. 2011; 79(1): 92-96.
31. Katusin-Razem B, Hamitouchei K, Maltar-Strmecki N, Kos K, Pucic I, Britvic-Budicin S, et al. Radiation sterilization of ketoprofen. Radiation Physics and Chemistry 2005; 73(2): 111-16.
32. Nakajima A, Tahara M, Yoshimura Y, Nakazawa H. Determination of free radicals generated from light exposed ketoprofen. Journal of Photochemistry and Photobiology A:Chemistry. 2005;174(2): 87-89.
33. Mattar SM, Stephens AD. Magnetic Inequivalency, Electron Paramagnetic Resonance, Electronic Structure, Optimal Geometry, and Electronic Spectra of the 4,5-Bis(trifluoromethyl)-1,3,2-dithiazol-2-yl, Radical. Journal of Physical Chemistry A. 2000; 104(16): 3718-32.
34. Ban F, Gauld JW, Wetmore SD, Boyd RJ. In EPR of Free Rad. in Sol. Trends in Methods and App. The Netherlands: Kluwer Academic Pub. Chapter 6; 2003.
35. Neese F. Prediction of electron paramagnetic resonance g-values by coupled perturbed Hartree–Fock and Kohn–Sham theory. Journal Chemical Physics. 2001;115(24):11080-96.
36. Chipman DM. Quantum Mechanical Electronic Structure Calculations with Chemical Accuracy. Netherlands: Kluwer Academic Press; 1995. p. 109-138.