Tuğba AYCAN, Filiz ÖZTÜRK, Nilgün ÖZDEMİR, Hümeyra PAŞAOĞLU

Siprofloksasinin Monohidröz Dihidrojen Fosfat Tuzunun Yapısal, Spektral, Biyolojik aktivitesinin araştırılması: Hesaplamalı ve Moleküler Yerleştirme Çalışması

Bu çalışma, Siprofloksasinin Monohidöz Dihidrojen Fosfat Tuzunun (MDPSC) sentezini, spektroskopik ve biyolojik aktivitesini açıklar. Birim hücrenin asimetrik kısmı bir siprofloksasin katyonu, bir dihidrojen fosfat anyonu ve bir su molekülü içerir. Karakterizasyon için kullanılan teknikler, tek kristalli X-ışını kırınımı ve spektroskopik yöntem (IR, UV) ve termal analizdir. Moleküler yapı teorik olarak taban durumu için DFT/B3LYP/6-31G(d, p) yöntemleri kullanılarak optimize edildi ve deneysel değerlerle karşılaştırıldı. Ölçekli teorik titreşim frekansları deneysel değerlerle karşılaştırıldı. Deneysel olarak elde edilen UV-Vis sonuçları, HOMO ve LUMO enerjileri ve MEP gibi hesaplanan elektronik özelliklerle karşılaştırıldı. Titreşim frekansları, bileşiğin ve siprofloksasinin fonksiyonel gruplarıyla ilgili karakteristik bantların karşılaştırılmasıyla çalışılmıştır. TGA ile termal özellikler incelenmiştir. Kompleksin Staphylococcus aerous, Escherichia coli, Candida Albicans, Bacillus Subtilis, Pseudomonas aeruginosa ve Aspergillus Flavus'a karşı yapılan biyolojik çalışma, MIC değerleri 512 µg mL-1 ila 1 µg mL-1 arasında değişen çok güçlü bir antibakteriyel aktivite göstermiştir. Optimize edilmiş kompleks, 5J9B, 5BMM, 5HTG, 1ZUV, 4F0V ve 4YNU’ya yerleştirilmiştir.

Anahtar Kelimeler:

Siprofloksasin, X ışını kırınımı, Spektral analiz, Antimikrobiyal aktivite, Moleküler Modelleme

Investigation of Structural, Spectral, Biological Activity of Monohydrous Dihydrogen Phosphate Salt of Ciprofloxacin: Computational and Molecular Docking Study

The present study describes the synthesis, spectroscopic and biological activity of Monohydrous Dihydrogen Phosphate Salt of Ciprofloxacin (MDPSC). The asymmetrical part of the unit cell contains one ciprofloxacin cation, one dihydrogen phosphate anion and one water molecule. The techniques used for the characterization are single crystal X-ray diffraction and spectroscopic method (IR, UV) and thermal analysis. The molecular structure was theoretically optimized using DFT/B3LYP/6-31G(d,p) methods for ground state, and compared with experimental values. Scaled theoretical vibrational frequencies are compared with experimental values. The UV-Vis results that experimentally obtained are compared with the calculated electronic properties such as HOMO and LUMO energies and the MEP are also investigated. The vibrational frequences has been studied by comparing the characteristic bands related to the functional groups of the compound and the ciprofloxacin. Thermal properties have been investigated with TGA. Biological study of the complex against Staphylococcus aerous, Escherichia coli, Candida Albicans, Bacillus Subtilis, Pseudomonas aeruginosa and Aspergillus Flavus showed very strong antibacterial activity with MIC values ranging from 512 µg mL-1 to 1 µg mL-1. The optimized complex is docked to the 5J9B, 5BMM, 5HTG, 1ZUV, 4F0V and 4YNU.

Keywords:

Ciprofloxacin, X-ray diffraction, Spectral analysis, Antimicrobial activity, Molecular Modelling,

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Sayin, K., Karakaş, D., Kariper, S.E., and Sayin, T.A. (2018). Computational study of some fluoroquinolones: Structural, spectral and docking investigations. Journal of Molecular Structure. 1156, p. 172-181.
Lou, B., Boström, D., and Velaga, S.P. (2007). Monohydrous dihydrogen phosphate salts of norfloxacin and ciprofloxacin. Acta Crystallographica Section C: Crystal Structure Communications. 63(12), p. o731-o733.
Blokhina, S., Sharapova, A., Ol’khovich, M., and Perlovich, G. (2017). Sublimation thermodynamics of four fluoroquinolone antimicrobial compounds. Journal of Chemical Thermodynamics. 105, p. 37-43.
Sheldrick, G.M. (2008). A short history of SHELX. Acta crystallographica. Section A, Foundations and Advances. 64(1), p. 112-122.
Farrugia, L.J. (2012). WinGX and ORTEP for Windows: an update. Journal of Applied Crystallography. 45(4), p. 849-854.
Macrae, C.F., Edgington, P.R., McCabe, P., Pidcock, E., Shields, G.P., Taylor, R., Towler, M., and Streek, J.V.D. (2006). Mercury: visualization and analysis of crystal structures. Journal of Applied Crystallography. 39(3), p. 453-457.
Institute, C.a.L.S., Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; approved standard. 2006: Wayne, PA: CLSI.
Institute, C.a.L.S., Reference method for broth dilution antifungal susceptibility testing of yeasts; approved standard. 2002: Wayne, PA: CLSI.
Frisch, M., Trucks, G., Schlegel, H.B., Scuseria, G., Robb, M., Cheeseman, J., Scalmani, G., Barone, V., Mennucci, B., and Petersson, G. (2009). Gaussian 09, revision a. 02, gaussian. Inc., Wallingford, CT. 200.
Polishchuk, A.V., Karaseva, E.T., Emelina, T.B., Cramariuc, O., and Karasev, V.E. (2011). Polymorphism and intramolecular proton transfer in fluoroquinolone compounds. Journal of Fluorescence. 21(6), p. 2117-22.
Krygowski, T.M. (1993). Crystallographic studies of inter-and intramolecular interactions reflected in aromatic character of. pi.-electron systems. Journal of Chemical Information and Computer Sciences. 33(1), p. 70-78.
Gece, G. (2008). The use of quantum chemical methods in corrosion inhibitor studies. Corrosion Science. 50(11), p. 2981-2992.
Sahoo, S., Chakraborti, C.K., and Behera, P.K. (2012). Spectroscopic investigations of a ciprofloxacin/hpmc mucoadhesive suspension. International Journal of Applied Pharmaceutics. 4(3), p. 1-8.
Sadeek, S.A. (2005). Synthesis, thermogravimetric analysis, infrared, electronic and mass spectra of Mn (II), Co (II) and Fe (III) norfloxacin complexes. Journal of Molecular Structure. 753(1-3), p. 1-12.
Sadeek, S.A., Refat, M.S., and Hashem, H.A. (2006). Complexation and thermogravimetric investigation on tin (II) and tin (IV) with norfloxacin as antibacterial agent. Journal of Coordination Chemistry. 59(7), p. 759-775.
Zordok, W.A. (2014). Interaction of vanadium (IV) solvates (L) with second-generation fluoroquinolone antibacterial drug ciprofloxacin: Spectroscopic, structure, thermal analyses, kinetics and biological evaluation (L= An, DMF, Py and Et3N). Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy. 129, p. 519-536.
Acar, B., Yilmaz, I., Çalışkan, N., and Cukurovali, A. (2017). Experimental and theoretical studies of the molecular structure of 7-Methyl-3-[(3-methyl-3-mesityl-cyclobutyl]-5-phenyl-5H-thiazolo[3,2-α]pyrimidine-6-carboxylic acid ethyl ester. Journal of Molecular Structure. 1139, p. 130-136.
O'Boyle, N.M., Tenderholt, A.L., and Langner, K.M. (2008). cclib: a library for package-independent computational chemistry algorithms. Journal of Computational Chemistry. 29(5), p. 839-45.
Neugebauer, U., Szeghalmi, A., Schmitt, M., Kiefer, W., Popp, J., and Holzgrabe, U. (2005). Vibrational spectroscopic characterization of fluoroquinolones. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy. 61(7), p. 1505-17.
Lambert, P. (2002). Mechanisms of antibiotic resistance in Pseudomonas aeruginosa. Journal of the royal society of medicine. 95(Suppl 41), p. 22.
Rapa, R.A., Islam, A., Monahan, L.G., Mutreja, A., Thomson, N., Charles, I.G., Stokes, H.W., and Labbate, M. (2015). A genomic island integrated into recA of V ibrio cholerae contains a divergent recA and provides multi‐pathway protection from DNA damage. Environmental microbiology. 17(4), p. 1090-1102.
Tan, Z., Tan, F., Zhao, L., and Li, J. (2012). The synthesis, characterization and application of ciprofloxacin complexes and its coordination with copper, manganese and zirconium ions. Journal of Crystallization Process and Technology. 2(02), p. 55.