Synthesis of Monastrol, Kinesin-5 inhibitör and ınvestigation of its charge transfer complexes

Yıl 2016, Cilt: 20 Sayı: 3, 425 - 431, 01.12.2016

Mustafa Arslan , Nurcan Berber

https://doi.org/10.16984/saufenbilder.67697

Öz

Monastrol which is a kinesin-5 inhibitor have been synthesized using 3-hydroxybenzaldehyde, thiourea and ethylasetoasetate in the presence of Alumina Sulphonic Acid (ASA) catalyst in solvent free system. Charge transfer complexes between monastrol as a donor and acceptors such as tetracyanoquinomethane (TCNQ) and 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) have been studied spectrophotometrically in acetonitrile at 21 ^oC. The stoichiometry of the complexes was found to be 1:1 ratio by the Job method between donor and acceptors with the maximum absorption band at a wavelength of 742nm and 546nm respectively. The equilibrium constants were determined by Benesi-Hildebrand and thermodynamic parameters of the complexes by Van’t Hoff equation.

Anahtar Kelimeler

Spectrophotometer, charge transfer complexes, monastrol, TCNQ, DDQ

Kinesin-5 inhibitörü olan Monastrol bileşiğinin sentezi ve yük transferi kompleks etkileşmelerinin incelenmesi

Öz

Kinesin-5 inhibitörü olarak kullanılan Monastrol, çözücüsüz ortamda alümina sülfonik asit (ASA) katalizörü varlığında 3-hidroksibenzaldehit, tiyoüre ve etilasetoasetat kullanılarak sentezlenmiştir. Elektron verici (Donör, D) olarak monastrol, elektron alıcı (Akseptör, A) olarak tetrasiyanoquinometan (TCNQ) kullanılmış ve bunlar ile 2,3-dikloro-5,6-disiyano-p-benzokinon (DDQ) bileşikleri arasındaki yük transfer kompleksleri asetonitril içinde 21 °C'de spektrofotometrik olarak incelenmiştir. Komplekslerin stokiyometrisi, Job yöntemi kullanılarak incelenmiş, elektron verici ve alıcılar arasında TCNQ ile 742 nm ve DDQ ile 546 nm dalga boyunda maksimum absorbsiyon bandında 1:1 oranında olduğu bulunmuştur. Komplekslerin denge sabiti Benesi-Hildebrand ve termodinamik parametreleri Van't Hoff denklemi ile belirlenmiştir.

Anahtar Kelimeler

Spektrofotometre, yük transfer kompleksleri, monastrol, TCNQ, DDQ

Kaynakça

• D.S. Bose, M. Sudharshan, S.W. Chavhan, “New protocol for Biginelli reaction-a practical synthesis of Monastrol,” Arkivoc, vol. 3, pp. 228-236, Feb. 2005.
• C.O. Kappe, “Biologically active dihydropyrimidones of the Biginelli-type - a literature survey,” Eur.J.Med.Chem, vol. 35, no. 12, pp. 1043-1052, Dec. 2000.
• R. Zheng, X. Wang, H. Xu, J. Du, “Bronsted Acidic Ionic Liquid: An Efficient and Reusable Catalyst for the Synthesis of 3,4-Dihydropyrimidin-2(1H)-ones,” Synthetic Commun vol. 36, no. 11, pp. 1503-1513, Aug. 2006.
• C.O. Kappe, “100 Years Of The Biginelli Dihydropyrimidine Synthesis,” Tetrahedron, vol. 49, no. 32, pp. 6937-6963, Aug. 1993.
• C.O. Kappe, “Recent advances in the Biginelli dihydropyrimidine synthesis. New tricks from an old dog,” Accounts. Chem. Res. Vol. 33, no. 12, pp. 879-888, Apr. 2000.
• D Russowsky, R.F.S. Canto, S.A.A. Sanches, M.G.M. D’Oca, A. de Fatima, R.A. Pilli, L.K. Kohn, M.A. Antonio, J.E. de Carvalho, “Synthesis and differential antiproliferative activity of Biginelli compounds against cancer cell lines: Monastrol, oxo-monastrol and oxygenated analogues,” Bioorg. Chem. vol. 34, no. 4, pp. 173-182, Aug. 2006.
• E. Klein, S. DeBonis, B. Thiede, D.A. Skofias, F. Kozielski, L. Lebeau, “New chemical tools for investigating human mitotic kinesin Eg5,” Bioorg & Med. Chem. vol. 15, no. 19, pp. 6474-6488, Oct. 2007.
• P. Taboada, M.G. Pichel, S. Barbosa, D. Attwood, V. Mosquera, “Effect of temperature on the volume and compressibilities of some amphiphilic penicillins in aqueous solution” Phys. Chem. Chem.Phys. vol. 5, no. 4, pp. 703-709. Apr. 2003
• D.K. Roy, A. Saha, A.K. Mukherjee, “Spectroscopic and thermodynamic study of charge transfer complexes of cloxacillin sodium in aqueous ethanol medium”, Spectrochim. Acta A. vol. 61, no. 9, pp. 2017-2022, July 2005.
• R.S. Mulliken, W.B. Pearson,”Molecular Complexes,” New York: Wiley Publishers, 1969, pp.16-48.
• R. Foster, ”Charge Transfer Complexes,” London: Academic Press, 1969, pp. 25-50.
• M.M.A. Hamed, M.I. Abdel-Hamid, M.R. Mahmoud, “Molecular complexes of some N-aryldithiocarbamates with pi-electron acceptors,” Monatshefte fur Chemie vol. 129, no. 2, pp. 121-127, Feb. 1998.
• A. Dozal, H. Keyzer, H.K. Kim, W.W. Way, “Charge transfer complexes of K vitamins with several classes of antimicrobials”, Int. J. Antimic. Ag. vol. 14, no. 3, pp. 261-265, Apr. 2000.
• E.H. El-Mossalamy, A.S. Amin, A.A. Khalil, “Charge transfer complexes of some oxazolones with iodine”, Spectrochim. Acta A. vol. 58, no. 1, pp. 67-72, Jan. 2002.
• M. Arslan, H. Duymus, “Spectroscopic studies of charge transfer complexes between colchicine and some pi acceptors”, Spectrochim. Acta A. vol. 67, no. 3-4, pp. 573-577, July. 2007.
• H. Duymus, M. Arslan, M. Kucukislamoglu, M. Zengin, “Charge transfer complex studies between some non-steroidal anti-inflammatory drugs and pi-electron acceptors”, Spectrochim. Acta A. Vol. 65, no. 5, pp. 1120-1124, Dec. 2006.
• H. Demirhan, M. Arslan, M. Zengin, M. Kucukislamoglu, "Investigation of charge transfer complexes formed between mirtazapine and some pi acceptors," J. of Spectroscopy , 1- 7 , 2013. 10.1155/2013/875953
• F.A.N. El-Dien, G.G. Mohamed, E.Y.Z.A. Farag, “Spectrophotometric determination of flucloxacillin and dicloxacillin in pure and dosage forms”, Spectrochim. Acta A. vol. 64, no. 1, pp. 210-215, May. 2006.
• P. Kalimuthu, A. Sivanesan, S.A. John, “Charge-transfer interaction of aromatic thiols with 2,3-dichloro-5,6-dicyano-p-benzoquinone: Spectral and quantum mechanical studies,” J. Phys. Chem. A. vol. 111, no. 48, pp. 12086-12092, Dec. 2007.
• M.S. Refat, H.A.D. Ahmed, L.A. El-Zayat, “Spectroscopic, synthesis and structural studies of piperidine-chloranilic acid and piperidine-picric acid charge transfer complexes,” Can. J. Anal. Sci. Spect. vol. 51, no. 3, pp. 147-163, Sep. 2006.
• M.E. El-Zaria, A.R. Genady, “Spectroscopic studies of charge transfer complexes of meso-tetra-p-tolylporphyrin and its zinc complex with some aromatic nitro acceptors in different organic solvents,” Appl. Organomet. Chem. vol. 21, no. 11, pp. 983-993, Nov. 2007.
• M. Wojdyla, B. Derkowska, Z. Lukasiak, W. Bala, “Absorption and photoreflectance spectroscopy of zinc plithalocyanine (ZnPc) thin films grown by thermal evaporation”, Mater. Lett. vol. 60, no. 29-30, pp. 3441-3446, Dec. 2006.
• E.A. Taha, S.M. Soliman, H.E. Abdellatef, M.M. Ayad, “Colorimetric methods for the determination of some tricyclic antidepressant drugs in their pure and dosage forms,” Microchim. Acta vol. 140, no. 3-4, pp. 175-182, Oct. 2002.
• S. Imre, M.T. Dogaru, C.E. Vari, T. Muntean, L. Kelemen, “Validation of an HPLC method for the determination of ciprofloxacin in human plasma,” J. Pharmaceut. Biomed. vol. 33, no. 1, pp.125-130, Sep. 2003.
• F. Yakuphanoglu, M. Arslan, “Determination of thermo-optic coefficient, refractive index, optical dispersion and group velocity parameters of an organic thin film,” Physica B vol. 393, no. 1-2, pp. 304-309, Apr. 2007.
• M. Arslan, F.B. Atak, F. Yakuphanoglu, “Synthesis and refractive index dispersion properties of the N,N ',N ''-trinaphthylmethyl melamine-DDQ complex thin film”, Opt. Mater. vol. 29, no. 5, pp. 516-520, Jan. 2007.
• F. Yakuphanoglu, M. Arslan, “The fundamental absorption edge and optical constants of some charge transfer compounds,” Opt. Mater. vol. 27, no. 1, pp. 29-37, Oct. 2004.
• S. Besoluk, M. Kucukislamoglu, M. Nebioglu, M. Zengin, M. Arslan, “Solvent-free synthesis of dihydropyrimidinones catalyzed by alumina sulfuric acid at room temperature”, J. Iran. Chem. Soc. vol. 5, no.1, pp. 62-66, Mar. 2008.
• R. Job, Advenced Physicochemical Exp., London: Pitman, 1964, pp 12-26
• H. A. Benesi, J.H. Hildebrand, “A Spectrophotometric Investigation of the Interaction of Iodine with Aromatic Hydrocarbons,” J. Am. Chem. Soc. vol. 71, no. 8, pp. 2703-2707, Aug. 1949.
• A.S. Amin, G.O. El-Sayed, Y.M. Issa, “Utility Of Certain Pi-Acceptors For The Spectrophotometric Determination Of Norfloxacin,” Analyst vol. 120, no. 4, pp. 1189-1193, Apr. 1995.
• A.A.A. Boraei, “Spectroscopic study on charge transfer molecular complexes of pyrazole derivatives with some π-electron acceptors,” Spectrochim. Acta A vol. 58, no. 9, pp. 1895-1901, Jul. 2002.
• E.H. El-mossalamy, “Molecular spectroscopic studies of charge transfer complexes of thiourea derivatives with benzoquinones,” J. Mol. Liq. vol. 123, no. 2-3, pp. 118-123, Jan. 2006.