Hayati SARI, Müge GEMİLİ, Duygu ERSEN, Yahya NURAL

Acid Dissociation Constants of 5,5-Diphenylpyrrolidine N- Aroylthioureas and Stability Constants of their Pt(II) and Ni(II) Complexes in Acetonitrile-Water Hydroorganic Solvent

In this study, acid dissociation constants of 5,5-diphenylpyrrolidine N-aroylthiourea derivatives, exhibiting anti(myco)bacterial activity, were determined by potentiometric titration in 30% (v/v) acetonitrile-water hydroorganic solventat 25 ± 0.1 °C, at an ionic background of 0.1 mol / L of NaCl using the HYPERQUAD computer program. Three acid dissociation constants were determined for each compound 1a-e and we suggest that these acid dissociation constants are related to the carboxyl, enol and enthiol groups. Stability constants of their Pt(II) and Ni(II) complexes were also determined by potentiometric titration under the same conditions stated above using the HYPERQUAD computer program. The ligands behave as bidentate and bind to the metal atom via the S and O atoms. In various pH conditions, the different complex forms were formulated as ML2, MHL, MH2L2, MHL2, MH2, MH5L2 and MH-4L between Pt2+/Ni2+ ions and 5,5-diphenylpyrrolidine N-aroylthioureas. Stability constants of the complexes show that the ligands 1a-e form complexes with Pt(II) and Ni(II) metals as 2:1. The stability of the complexes formed by the ligands and platinum were found to follow the order: 3d > 3a > 3e > 3c > 3b. The stability of the complexes formed by the ligands and nickel were found to follow the order: 4d > 4c > 4a > 4b > 4e. As a result, generally the platinum complexes formed with these ligands are more stable than their nickel complexes

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[1] Mazák, K.; Noszál, B. Advances in microspeciation CBÜ Fen Bil. Dergi., Cilt 13, Sayı 1, 2017, 125-138 s CBU J. of Sci., Volume 13, Issue 1, 2017, p 125-138 135 of drugs and biomolecules: Species-specific concentrations, acid-base properties and related parameters. J. Pharm. Biomed. Anal. 2016; 130, 390- 403.
[2] Babic´, S.; Horvat, A.J.M.; Pavlovic´, D.M.; Kasˇtelan-Macan, M. Determination of pKa values of active pharmaceutical ingredients. Trends in Analytical Chemistry. 2007; 26, 1043–1061.
[3] Meloun, M.; Borovská, S.; Vrána, A. The thermodynamic dissociation constants of the anticancer drugs camptothecine, 7-ethyl-10-hydroxycamptothecine, 10- hydroxycamptothecine and 7-ethylcamptothecine by the least-squares nonlinear regression of multiwavelength spectrophotometric pH-titration data. Anal. Chim. Acta. 2007; 584, 419-432.
[4] Roda, G.; Dallanoce, C.; Grazioso, G.; Liberti, V.; De Amici, M. Determination of acid dissociation constants of compounds active at neuronal nicotinic acetylcholine receptors by means of electrophoretic and potentiometric techniques. Anal. Sci. 2010; 26, 51-54.
[5] Aslan, N.; Erden, P.E.; Doğan, A.; Canel, E.; Kılıç, E. Protonation constants of some alanyl dipeptides in mixed aqueous organic solvents. J. Solution Chem. 2016; 45, 299-312.
[6] Dohoda, D.; Tsinman, K.; Tsinman, O.; Wang, H.; Tam, K.Y. Spectrophotometric pKa determination of ionizable pharmaceuticals: Resolution of molecules with weak pH-dependent spectral shift. . Pharmaceut. Biomed. Anal. 2015; 114, 88–96.
[7] Shelley, J.C.; Cholleti, A.; Frye, L.L.; Greenwood, J.R.; Timlin, M.R.; Uchimaya, M. Epik: a software program for pKa prediction and protonation state generation for drug-like molecules. J. Comput. Aided. Mol. Des. 2007; 21, 681–691.
[8] Grover, M.; Singh, B.; Bakshi, M.; Singh, S. Quantitative structure–property relationships in pharmaceutical research–Part 1. Pharma. Sci. Technol. To. 2000; 3, 28-35.
[9] Şanli, S.; Altun, Y.; Şanli, N.; Alsancak, G.; Beltran, J.L. Solvent effects on pKa values of some substituted sulfonamides in acetonitrile-water binary mixtures by the UV-spectroscopy method. J. Chem. Eng. Data. 2009; 54, 3014-3021.
[10] Öğretir, C.; Yarlıgan, S.; Demirayak, Ş.; Arslan, T. A theoretical approach to acidity-basicity behaviour of some biologically active 6-phenyl-4,5-dihydro-3(2H)- pyridazinone derivatives. J. Mol. Struc-Theochem. 2003; 666-667, 609-615.
[11] Narin, I.; Sarioglan, S.; Anilanmert, B.; Sari, H. pKa Determinations for montelukast sodium and levodropropizine. J. Solution Chem. 2010; 39, 1582-1588.
[12] Sanli, S.; Altun, Y.; Guven, G. Solvent effects on pKa values of some anticancer agents in acetonitrilewater binary mixtures. J. Chem. Eng. Data. 2014; 59, 4015-4020.
[13] Wiczling, P.; Struck-Lewicka, W.; Siluk, D.; Markuszewski, M.J.; Kaliszan, R. The simultaneous determination of hydrophobicity and dissociation constant by liquid chromatography–mass spectrometry. J. Pharmaceut. Biomed. Anal. 2014; 94, 180-187.
[14] Demiralay, E.Ç.; Üstün, Z.; Daldal, Y.D. Estimation of thermodynamic acidity constants of some penicillinase-resistant penicillins. J. Pharmaceut. Biomed. Anal. 2014; 91, 7-11.
[15] Cabot, J.M.; Fuguet, E.; Rosés, M. Internal standard capillary electrophoresis as a highthroughput method for pKa determination in drug discovery and development. ACS Comb. Sci. 2014; 16, 518-525.
[16] Rodríguez-Barrientos, D.; Rojas-Hernández, A.; Gutiérrez, A.; Moya-Hernández, R.; Gómez-Balderas, R.; Ramírez-Silva, M.T. Determination of pKa values of tenoxicam from 1H NMR chemical shifts and of oxicams from electrophoretic mobilities (CZE) with the aid of programs SQUAD and HYPNMR. Talanta. 2009; 80, 754-762.
[17] Kadhum, A.A.A. Determination and studying the factors affecting the stability constant values of some azo dyes. Journal of Al-Qadisiyah for Pure Science, 2008; 13, 1-14.
[18] Rosotti, F.J.C.; Rosotti, H. The determination of stability constants and other equilibrium constants in solution. McGraw-Hill, New York, 1961.
[19] El-Sherif, A.A.; Shehata, M.R.; Shoukry, M.M.; Mahmoud, N. Potentiometric study of speciation and thermodynamics of complex formation equilibria of diorganotin (IV) dichloride with 1-(2- aminoethyl)piperazine. J. Solution Chem. 2016; 45, 410-430. CBÜ Fen Bil. Dergi., Cilt 13, Sayı 1, 2017, 125-138 s CBU J. of Sci., Volume 13, Issue 1, 2017, p 125-138 136
[20] Baile, M.B.; Kolhe, N.S.; Deotarse, P.P.; Jain, A.S.; Kulkarni, A.A. Metal ion complex-potential anticancer drug. International Journal of Pharma Research Review. 2015; 4, 59-66.
[21] Allardyce, C.S.; Dorcier, A.; Scolaro, C.; Dyson, P.J. Development of organometallic (organo-transition metal) pharmaceuticals. Appl. Organometal. Chem. 2005; 19, 1-10.
[22] Shobana, S.; Subramaniam, P.; Dharmaraja, J.; Arvindnarayan, S. Stability and structural studies on Ni (II)–5-fluorouracil mixed ligand complex systems. J. Solution Chem. 2016; 45, 334-358.
[23] Fazary, A.E.; Al-Shihri, A.S.; Saleh, K.A.; Alfaifi, M.Y.; Alshehri, M.A.; Elbehairi, S.E.I. Di-and tri-valent metal ions interactions with four biodegradable hydroxamate and cataecholate siderophores: New insights into their complexation equilibria. J. Solution Chem. 2016; 45, 732-749.
[24] Fazary, A.E.; Alshihri, A.S.; Alfaifi, M.Y.; Saleh, K.A.; Elbehairi, S.E.I.; Fawy, K.F.; Abd-Rabboh, H.S.M. Gibbs energies of protonation and complexation of platinum and vanadate metal ions with naringenin and phenolic acids: Theoretical calculations associated with experimental values. J. Chem. Thermodynamics. 2016; 100, 7-21.
[25] Polat, F.; Atabey, H.; Sari, H.; Cukurovali, A. Potentiometric study of equilibrium constants of a novel triazine–thione derivative and its stability constants with Hg2+, Cu2+, Ni2+, Pb2+, and Zn2+ metal ions in ethanol and water mixed. Turk. J. Chem. 2013; 37, 439-448.
[26] Jelić, R.; Marković, S.; Petrović, B. Equilibrium studies on complex formation reactions of dichlorido [(R,R)-trans-1, 2-diaminocyclohexane] platinum (II) complex with ligands of biological significance. Monatsh. Chem. 2011; 142, 985-992.
[27] Ferraro, A.; Fabbricino, M.; van Hullebusch, E.D.; Esposito, G.; Pirozzi, F. Effect of soil/contamination characteristics and process operational conditions on aminopolycarboxylates enhanced soil washing for heavy metals removal: a review. Rev. Environ. Sci. Biotechnol. 2016; 15, 111-145.
[28]Saeed, A.; Flörke, U.; Erben, M.F. A review on the chemistry, coordination, structure and biological properties of 1-(acyl/aroyl)-3-(substituted) thioureas. J. Sulfur. Chem. 2014; 35, 318-355.
[29] Saeed, A.; Zaib, S.; Pervez, A.; Mumtaz, A.; Shahid, M.; Iqbal, J. Synthesis, molecular docking studies, and in vitro screening of sulfanilamidethiourea hybrids as antimicrobial and urease inhibitors. Med. Chem. Res. 2013; 22, 3653-3662.
[30] Döndaş, H.A.; Nural, Y.; Duran, N.; Kilner, C. Synthesis, crystal structure and antifungal / antibacterial activity of some novel highly functionalized benzoylaminocarbothioyl pyrrolidines. Turk. J. Chem. 2006; 30, 573-583.
[31] Plutín, A.M.; Alvarez, A.; Mocelo, R.; Ramos, R.; Castellano, E.E.; da Silva, M.M.; Colina-Vegas, L.; Pavan, F.R.; Batista, A.A. Anti-Mycobacterium tuberculosis activity of platinum (II)/N,Ndisubstituted-N′-acyl thiourea complexes. Inorg. Chem. Commun. 2016; 63, 74-80.
[32] Saeed, S.; Rashid, N.; Jones, P.G.; Ali, M.; Hussain, R. Synthesis, characterization and biological evaluation of some thiourea derivatives bearing benzothiazole moiety as potential antimicrobial and anticancer agents. Eur. J. Med. Chem. 2010; 45, 1323- 1331.
[33] Saeed, A.; Al-Rashida, M.; Hamayoun, M.; Mumtaz, A.; Iqbal, J. Carbonic anhydrase inhibition by 1-aroyl-3-(4-aminosulfonylphenyl)thioureas. J. Enzyme Inhib. Med. Chem. 2014; 29, 901-905.
[34] Rauf, M.K.; Yaseen, S.; Badshah, A.; Zaib, S.; Arshad, R.; Ud-Din, I.; Tahir, M.N.; Iqbal, J. Synthesis, characterization and urease inhibition, in vitro anticancer and antileishmanial studies of Ni (II) complexes with N,N,N′-trisubstituted thioureas. J. Biol. Inorg. Chem. 2015; 20, 541-554.
[35] Xie, J.; Cheng, Z.; Yang, W.; Liu, H.; Zhou, W.; Li, M.; Xu, Y. Crystal structures and antimicrobial and cytotoxic activities of zinc (II), nickel (II) and copper (II) complexes of N-(piperidylthiocarbonyl)benzamide. Appl. Organomet. Chem. 2015; 29, 157-164.
[36] Nural, Y.; Kilincarslan, R.; Dondas, H.A.; Cetinkaya, B.; Serin, M.S.; Grigg, R.; Ince, T.; Kilner, C. Synthesis of Ni (II), Pd (II) and Cu (II) metal complexes of novel highly functionalized aroylaminocarbo-N-thioyl pyrrolidines and their activity against fungi and yeast. Polyhedron. 2009; 28, 2847-2854.
[37] Maurya, M.R.; Uprety, B.; Avecilla, F.; Tariq, S.; Azam, A. Palladium (II) complexes of OS donor N-(diCBÜ Fen Bil. Dergi., Cilt 13, Sayı 1, 2017, 125-138 s CBU J. of Sci., Volume 13, Issue 1, 2017, p 125-138 137 (butyl/phenyl) carbamothioyl) benzamide and their antiamoebic activity. Eur. J. Med. Chem. 2015; 98, 54- 60.
[38] Nkabyo, H.A.; Hannekom, D.; McKenzie, J.; Koch, K.R. Light-induced cis/trans isomerization of cis-[Pd (L-S, O)2] and cis-[Pt (L-S,O)2] complexes of chelating N,N-dialkyl-N′-acylthioureas: Key to the formation and isolation of trans isomers. J. Coord. Chem. 2014; 67, 4039-4060.
[39] San Tan, S.; Al-Abbasi, A.A.; Tahir, M.I.; Kassim, M.B. Synthesis, structure and spectroscopic properties of cobalt (III) complexes with 1-benzoyl-(3,3- disubstituted) thiourea. Polyhedron. 2014; 68, 287-294.
[40] Yang, W.; Liu, H.; Li, M.; Wang, F.; Zhou, W.; Fan, J. Synthesis, structures and antibacterial activities of benzoylthiourea derivatives and their complexes with cobalt. J. Inorg. Biochem. 2012; 116, 97-105.
[41] Lain, S.; Hollick, J.J.; Campbell, J.; Staples, O.D.; Higgins, M.; Aoubala, M.; McCarthy, A.; Appleyard, V.; Murray, K.E.; Baker, L.; Thompson, A.; Mathers, J.; Holland, S.J.; Stark, M.J.; Pass, G.; Woods, J.; Lane, D.P.; Westwood, N.J. Discovery, in vivo activity, and mechanism of action of a small-molecule p53 activator. Cancer Cell. 2008; 13, 454-463.
[42] Abdelaziz, M.A.; El-Sehrawi, H.M.; Mohareb, R.M. Synthesis, cytotoxicity and toxicity of thieno [2,3- d] pyrimidine derivatives derived from 2-amino-3- cyano-4,5,6,7-tetrahydrobenzo [b] thiophene. Med. Chem. Res. 2015; 24, 3932-3948.
[43] Stasevych, M.; Zvarych, V.; Lunin, V.; Halenova, T.; Savchuk, O.; Dudchak, O.; Vovk, M.; Novikov, V. Novel anthraquinone-based derivatives as potent inhibitors for receptor tyrosine kinases. Indian J. Pharm. Sci. 2015; 77, 634-637.
[44] Nural, Y.; Döndaş, H.A.; Grigg, R.; Şahin, E. Polysubstituted fused ring bicyclic thiohydantoins from aminocarbo-N-thioylpyrrolidines derived from azomethine ylide 1,3-dipolar cycloadditions. Heterocycles, 2011; 83, 2091-2114.
[45] Ettinger, U.; Kumari, V.; Zachariah, E.; Galea, A.; Crawford, T.J.; Corr, P.J.; Taylor, D.; Das, M.; Sharma, T. Effects of procyclidine on eye movements in schizophrenia. Neuropsychopharmacol. 2003; 28, 2199-2208.
[46] Fujiki, A.; Tsuneda, T.; Sugao, M.; Mizumaki, K.; Inoue, H. Usefulness and safety of bepridil in converting persistent atrial fibrillation to sinus rhythm. Am. J. Cardiol. 2003; 92, 472-475.
[47] Elboray, E.E.; Grigg, R.; Fishwick, C.W.G.; Kilner, C.; Sarker, M.A.B.; Aly, M.F.; H. Abbas-Temirek, H. X Y–ZH compounds as potential 1, 3-dipoles. Part 65: Atom economic cascade synthesis of highly functionalized pyrimidinylpyrrolidines. Tetrahedron. 2011; 67, 5700-5710.
[48] Dondas, H.A.; Fishwick, C.W.G.; Gai, X.; Grigg, R.; Kilner, C.; Dumrongchai, N.; Kongkathip, B.; Kongkathip, N.; Polysuk, C.; Sridharan, V. Stereoselective palladium-catalyzed four-component cascade synthesis of pyrrolidinyl-, pyrazolidinyl-, and isoxazolidinyl isoquinolines. Angew. Chem. Int. Edit. 2005; 44, 7570-7574.
[49] Dondas, H.A.; Fishwick, C.W.; Grigg, R.; Kilner, C. 1,3-Dipolar cycloaddition of stabilised and nonstabilised azomethine ylides derived from uracil polyoxin C (UPoC): Access to nikkomycin analogues. Tetrahedron. 2004; 60, 3473-3485.
[50] Dondas, H.A.; Grigg, R.; Thornton-Pett, M. Spiro (pyrrolidinyl-2,3′-benzodiazepines) related to MK-329. Tetrahedron. 1996; 52, 13455-13466.
[51] Cayuelas, A.; Ortiz, R.; Nájera, C.; Sansano, J.M.; Larrañaga, O.; de Cózar, A.; Cossío, F.P. Enantioselective synthesis of polysubstituted spironitroprolinates mediated by a (R,R)-me-DuPhos AgFcatalyzed 1,3-dipolar cycloaddition. Org. Lett. 2016; 18, 2926-2929.
[52] Costa, P.R.R.; Sansano, J.M.; Cossío, U.; Barcellos, J.C.F.; Dias, A.G.; Nájera, C.; Arrieta, A.; de Cozar, A.; Cossio, F.P. Synthesis of chromen [4,3-b] pyrrolidines by intramolecular 1, 3-dipolar cycloadditions of azomethine ylides: An experimental and computational assessment of the origin of stereocontrol. Eur. J. Org. Chem.2015; 2015, 4689-4698.
[53] Nejera, C.; Sansano, J.M. Asymmetric 1,3-dipolar cycloadditons of stabilized azomethine ylides with nitroalkenes. Curr. Top. Med. Chem. 2014; 14, 1271- 1282.
[54] D. Ersen, MSc Thesis, Mersin University, Mersin, 2016.
[55] Jeffery, G.H.; Bassett, J.; Mendham, J.; Denney, R.C. Vogel’s Textbook of Quantitative Chemical CBÜ Fen Bil. Dergi., Cilt 13, Sayı 1, 2017, 125-138 s CBU J. of Sci., Volume 13, Issue 1, 2017, p 125-138 138 Analysis, 5th Edn. Longman, London, 1989.
[56] Pettit, L.D. Academic Software, Sourby Farm, Timble, Otley, LS21 2PW, UK, 1992.
[57] Barbosa, J.; Sanz-Nebot, V. Assignment of reference pH-values to primary standard buffer solutions for standardization of potentiometric sensors in acetonitrile-water mixtures. Fresen. J. Anal. Chem. 1995; 353, 148-155.
[58] Gans, P.; Sabatini, A.; Vacca, A. Investigation of equilibria in solution. Determination of equilibrium constants with the HYPERQUAD suite of programs. Talanta. 1996; 43, 1739-1753.
[59] Nural, Y.; Döndaş, H.A.; Sarı, H.; Atabey, H.; Belveren, S.; Gemili, M. Determination of acid dissociation constants (pKa) of bicyclic thiohydantoinpyrrolidine compounds in 20% ethanol-water hydroorganic solvent. Int. J. Anal. Chem. 2014; 2014, Article ID 634194, 6 pages.
[60] Clayden, J.; Greeves, N.; Warren, S.; Wothers, P. Organic chemistry, Oxford University Press, UK, 2007.
[61] Binzet, G.; Zeybek, B.; Kılıç, E.; Külcü, N.; Arslan, H. Determination of the ionization constants of some benzoyl thiourea derivatives in dioxane-water mixture. Journal of Chemistry. 2013; 2013, Article ID 201238, 7 pages.
[62] Atabey, H.; Sari, H.; Al-Obaidi, F.N. Protonation equilibria of Carminic acid and stability constants of its complexes with some divalent metal ions in aqueous solution. J. Solution Chem. 2012; 41, 793-803.

Celal Bayar Üniversitesi Fen Bilimleri Dergisi-Cover

ISSN: 1305-130X
Başlangıç: 2005
Yayıncı: Manisa Celal Bayar Üniversitesi Fen Bilimleri Enstitüsü

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