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Current Pharmaceutical Analysis

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ISSN (Print): 1573-4129
ISSN (Online): 1875-676X

Research Article

Spectroscopic Determination of Dissociation Constants of Some 4- nitrobenzaldehyde-4-substituted phenyl-1-carbonylhydrazones in Sodium Hydroxide Media

Author(s): Mirjana S. Jankulovska*, Ilinka Spirevska, Vesna Dimova and Milena Jankulovska

Volume 17, Issue 6, 2021

Published on: 01 May, 2020

Page: [812 - 821] Pages: 10

DOI: 10.2174/1573412916999200502025457

Abstract

Purpose: Hydrazones are a class of azomethines with a wide spectrum of pharmacological properties that are influenced by the pH of the media. The purpose of this study was to investigate acidbase properties of five 4-nitrobenzaldehyde-4-substitutedphenyl-1-carbonylhydrazones in sodium hydroxide media (14>pH>7).

Methods: The dissociation process was followed by UV-Vis spectroscopy, in ethanol-water (V/V, 1:1) solutions, at room temperature. Semiempirical methods AM1 and PM3 were applied for determination of the deprotonation enthalpies.

Results: The changes in the UV-Vis spectra, as well as the deprotonation enthalpies, suggested that the dissociation process for four investigated hydrazones with an amide group took place in one step. The exception with two dissociation steps was hydrazone with amide and hydroxyl group. The pH region of dissociation was from pH 10.8 to pH 11.6 for the first step and between pH 11.7 and pH 12.1 for the second step of dissociation. The influence of the ethanol on the UV-Vis spectra was eliminated by the method of Characteristic Vector Analyses (CVA). The stoichiometric dissociation constants were determined numerically (pKHA = n·pH + logI) and graphically (intercept of the dependence of logI on pH) from the absorbance data using experimental and reconstructed UV-Vis spectra, at three different ionic strengths. Thermodynamic dissociation constants were estimated graphically as an intercept of dependence of dissociation constant on the square root of the ionic strength.

Conclusion: The obtained results demonstrated that the influence of the substituents on pKHA values was not significant, except for hydrazone with amide and hydroxyl group. Namely, the dissociation of the amide group of this hydrazone was retarded due to the influence of the phenolic group.

Keywords: Hydrazones, dissociation, dissociation constants, deprotonation enthalpy, UV-Vis spectroscopy, semi-empirical methods.

Graphical Abstract
[1]
Rollas, S.; Küçükgüzel, S.G. Biological activities of hydrazone derivatives. Molecules, 2007, 12(8), 1910-1939.
[http://dx.doi.org/10.3390/12081910] [PMID: 17960096]
[2]
Uppal, G.; Bala, S.; Kamboj, S.; Saini, M. Therapeutic review exploring antimicrobial potential of hydrazones as promising lead. Pharma Chem., 2011, 3, 250-268.
[3]
Narang, R.; Narasimhan, B.; Sharma, S. A review on biological activities and chemical synthesis of hydrazide derivatives. Curr. Med. Chem., 2012, 19(4), 569-612.
[http://dx.doi.org/10.2174/092986712798918789] [PMID: 22204327]
[4]
Verma, G.; Marella, A.; Shaquiquzzaman, M.; Akhtar, M.; Ali, M.R.; Alam, M.M. A review exploring biological activities of hydrazones. J. Pharm. Bioallied Sci., 2014, 6(2), 69-80.
[http://dx.doi.org/10.4103/0975-7406.129170] [PMID: 24741273]
[5]
Salgin-Gökşen, U.; Gökhan-Kelekçi, N.; Göktaş, O.; Köysal, Y.; Kiliç, E.; Işik, S.; Aktay, G.; Özalp, M. 1-Acylthiosemicarbazides, 1,2,4-triazole-5(4H)-thiones, 1,3,4-thiadiazoles and hydrazones containing 5-methyl-2-benzoxazolinones: synthesis, analgesic-anti-inflammatory and antimicrobial activities. Bioorg. Med. Chem., 2007, 15(17), 5738-5751.
[http://dx.doi.org/10.1016/j.bmc.2007.06.006] [PMID: 17587585]
[6]
Coa, J.C.; Cardona-Galeano, W.; Restrepo, A. Fe3+ chelating quinoline-hydrazone hybrids with proven cytotoxicity, leishmanicidal, and trypanocidal activities. Phys. Chem. Chem. Phys., 2018, 20(31), 20382-20390.
[http://dx.doi.org/10.1039/C8CP04174A] [PMID: 30043008]
[7]
Sedaghat, T.; Yousefi, M.; Bruno, G.; Rudbari, H.A.; Motamedi, H.; Nobakht, V. Synthesis, spectral characterization, crystal structure and antibacterial studies of diorganotin(IV) complexes with isonicotinoyl hydrazone derivatives. Polyhedron, 2014, 79, 88-96.
[http://dx.doi.org/10.1016/j.poly.2014.04.061]
[8]
Banerjee, S.; Mondal, S.; Chakraborty, W.; Sen, S.; Gachhui, R.; Butcher, R.J. Syntheses, X-ray crystal structures, DNA binding, oxidative cleavage and antimicrobial studies of two Cu (II) hydrazone complees. Polyhedron, 2009, 28, 2785-2793.
[http://dx.doi.org/10.1016/j.poly.2009.05.071]
[9]
Shakdofa, M.M.E.; Shtaiwia, M.H.; Morsya, N.; Abdel-rasseld, T.M.A. Metal complexes of hydrazones and their biological, analytical and catalytic applications: A review. Main Group Chem., 2014, 13, 187-218.
[http://dx.doi.org/10.3233/MGC-140133]
[10]
Liu, M.; Wang, Y.; Wangyang, W.Z.; Liu, F.; Cui, Y.L.; Duan, Y.S.; Wang, M.; Liu, S.Z.; Rui, C.H. Design, synthesis, and insecticidal activities of phthalamides containing a hydrazone substructure. J. Agric. Food Chem., 2010, 58(11), 6858-6863.
[http://dx.doi.org/10.1021/jf1000919] [PMID: 20450195]
[11]
Nataliya, P.; Belskaya, A.; Dehaen, W.; Bakuleva, V.A. Synthesis and properties of hydrazones bearing amide, thioamide and amidine functions. ARKIVOC, 2010, (i), 275-332.
[12]
Mao, J.; Wang, Y.; Wan, B.; Kozikowski, A.P.; Franzblau, S.G. Design, synthesis, and pharmacological evaluation of mefloquine-based ligands as novel antituberculosis agents. ChemMedChem, 2007, 2(11), 1624-1630.
[http://dx.doi.org/10.1002/cmdc.200700112] [PMID: 17680579]
[13]
Mohan, M.; Gupta, M.P.; Chandra, L.; Jha, N.K. Synthesis, characterization and antitumour properties of some metal(II) complexes of 2-pyridinecarboxaldehyde 2′-pyridylhydrazone and related compounds. Inorg. Chim. Acta, 1988, 151, 61-68.
[http://dx.doi.org/10.1016/S0020-1693(00)83485-4]
[14]
Aggarwal, N.; Kumar, R.; Srivastva, C.; Dureja, P.; Khurana, J.M. Synthesis of nalidixic acid based hydrazones as novel pesticides. J. Agric. Food Chem., 2010, 58(5), 3056-3061.
[http://dx.doi.org/10.1021/jf904144e] [PMID: 20131903]
[15]
Wu, J.; Song, B.A.; Hu, D.Y.; Yue, M.; Yang, S. Design, synthesis and insecticidal activities of novel pyrazole amides containing hydrazone substructures. Pest Manag. Sci., 2012, 68(5), 801-810.
[http://dx.doi.org/10.1002/ps.2329] [PMID: 22190278]
[16]
Manallack, D.T. The pK(a) distribution of drugs: application to drug discovery. Perspect. Medicin. Chem., 2007, 1, 25-38.
[http://dx.doi.org/10.1177/1177391X0700100003] [PMID: 19812734]
[17]
Grujić, M.; Popović, M.; Popović, G.; Nikolic, K.; Agbaba, D. Protolytic equilibria of sartans in micellar solutions of differently charged surfactans. J. Pharm. Sci., 2016, 105(8), 2444-2452.
[http://dx.doi.org/10.1016/j.xphs.2016.06.007] [PMID: 27422089]
[18]
Babić, S.; Horvat, A.J.M.; Mutavdžić-Pavlovic, D.M.; Kastelan-Macan, M. Determination of pKa values of active pharmaceutical ingredients. Trends Analyt. Chem., 2007, 26(11), 1043-1061.
[http://dx.doi.org/10.1016/j.trac.2007.09.004]
[19]
Reijenga, J.; van Hoof, A.; van Loon, A.; Teunissen, B. Development of methods for the determination of pKa values., Anal. Chem. Insights, 2013, 8 ACI-S12304..
[20]
Beltran, J.L.; Sanli, N.; Fonrodona, G.; Barron, D.; Özkan, G.; Barbosa, J. Spectrophotometric, potentiometric and chromatographic pKa values of polyphenolic acids in water and acetonitrile–water media. Anal. Chim. Acta, 2003, 484(2), 253-264.
[http://dx.doi.org/10.1016/S0003-2670(03)00334-9]
[21]
Hossain, M.; Obi, C.; Shrestha, A.; Khan, M. UV-metric, pHmetric and RP-HPLC methods to evaluate the multiple pka values of a polyprotic basic novel antimalarial drug lead, cyclen bisquinoline. Modern chemistry & Applications, 2014, 2(4), 1-7..
[22]
Pathare, B.; Tambe, V.; Patil, V. A review on various analytical methods used in determination of dissociation constant. Int. J. Pharm. Pharm. Sci., 2014, 6(8), 26-34.
[23]
Polat, M.B.; Doğan, A.; Başci, N.E. Spectrophotometry, potentiometry and HPLC in determination of acidity constant for cabergoline and tadalafil. J. Res. Pharm., 2019, 23(2), 177-186.
[http://dx.doi.org/10.12991/jrp.2019.123]
[24]
Vildal, S.L.; Vargas, H.C. Spectrophotometric Determination of the pKa, isosbestic point and equation of absorbance vs. pH for a universal pH indicator. Am. J. Anal. Chem., 2014, 5, 1290-1301.
[http://dx.doi.org/10.4236/ajac.2014.517135]
[25]
Meloun, M.; Pilařová, L.; Pfeiferová, A.; Pekárek, T. Method of UV-metric and pH-metric determination of dissociation constants of ionizable drugs: valsartan. J. Solution Chem., 2019, 48(8-9), 1266-1286.
[http://dx.doi.org/10.1007/s10953-019-00913-y]
[26]
Cabot, J.M.; Fuguet, E.; Ràfols, C.; Rosés, M. Fast high-throughput method for the determination of acidity constants by capillary electrophoresis II. Acidic internal standards. J. Chromatogr. A, 2010, 1217(52), 8340-8345.
[http://dx.doi.org/10.1016/j.chroma.2010.10.060] [PMID: 21087770]
[27]
Pérez-Urquiza, M.; Beltrán, J.L. Determination of the dissociation constants of sulfonated azo dyes by capillary zone electrophoresis and spectrophotometry methods. J. Chromatogr. A, 2001, 917(1-2), 331-336.
[http://dx.doi.org/10.1016/S0021-9673(01)00707-5] [PMID: 11403485]
[28]
Pathare, B.; Tambe, V.; Dhole, S.; Patil, V. An update on various analytical techniques based on UV Spectroscopy used in determination of dissociation constant. Int. J. Pharm., 2014, 4(1), 278-285.
[PMID: 25448588]
[29]
Carlos, H.; Martínez, R.; Dardonville, C. Rapid determination of ionization constants (pKa) by UV spectroscopy using 96-Well microtiter plates. Med. Chem. Lett, 2013, 4, 142-145.
[http://dx.doi.org/10.1021/ml300326v]
[30]
Berkhout, J.H.; Ram, A.H. Recent advancements in spectrophotometric pKa determinations: A review. Indian J. Pharm. Educ., 2019, 53(4), S475-S480.
[http://dx.doi.org/10.5530/ijper.53.4s.141]
[31]
Sıdır, Y.G.; Sıdır, I.; Berber, H. Spectroscopic determination of acid dissociation constants of N-substituted-6-acylbenzothiazolone derivatives. J. Phys. Chem. A, 2011, 115(20), 5112-5117.
[http://dx.doi.org/10.1021/jp2018549] [PMID: 21534535]
[32]
Aksu Ateş, N.; Berber, H.; Yaman, M. Synthesis, characterization and spectroscopic studies on tautomerism and acidity constants of certain 4-(phenyldiazenyl) benzene-1,3-diol derivatives, J. Sci. and Tech. B – Theo. Sci., 2016, 4(1), 11-28.
[33]
Allen, R.I.; Box, K.J.; Comer, J.E.A.; Peake, C.; Tam, K.Y. Multiwavelength spectrophotometric determination of acid dissociation constants of ionizable drugs. J. Pharm. Biomed. Anal., 1998, 17(4-5), 699-712.
[http://dx.doi.org/10.1016/S0731-7085(98)00010-7] [PMID: 9682153]
[34]
Pandey, M.M.; Jaipal, A.; Kumar, A.; Malik, R.; Charde, S.Y. Determination of pK(a) of felodipine using UV-Visible spectroscopy. Spectrochim. Acta A Mol. Biomol. Spectrosc., 2013, 115, 887-890.
[http://dx.doi.org/10.1016/j.saa.2013.07.001] [PMID: 23906645]
[35]
Dubey, S.; Singhvi, G.; Tyagi, A.; Agarwal, H.; Krishna, K. Spectrophotometric determination of pKa and Log P of Risperidone. J. Appl. Pharm. Sci., 2017, 7(11), 155-118.
[36]
Elsherif, K.; Shuwat, H.; Najar, A. Spectral Study of 1,4-bis(3-(2-pyridyl) pyrazol-1- ylmethyl)benzene (PPB): UV-VIS absorption spectra investigation in single and binary solvents and spectrophotometric determination of the dissociation constant (pKb). Eurasian J. Anal. Chem, 2017, 12(1), 67-82.
[http://dx.doi.org/10.12973/ejac.2017.00145a]
[37]
Zalewski, R.I.; Géribaldi, S. Adaptation of characteristic vector analysis to pKBH+ calculations of very weak basesfrom incomplete ultraviolet spectral data. J. Chem. Soc. Perkin Trans, 1988, 2, 113-115.
[http://dx.doi.org/10.1039/P29880000113]
[38]
Garcia, B.; Casado, R.M.; Castillo, J.; Ibeas, S.; Domingo, I.; Leal, J.M. Acidity constants of benzamide and some ortho-substituted derivatives. J. Phys. Org. Chem., 1993, 6, 101-106.
[http://dx.doi.org/10.1002/poc.610060206]
[39]
Stepanchikova, A.V.; Lagunin, A.A.; Filimonov, D.A.; Poroikov, V.V. Prediction of biological activity spectra for substances: evaluation on the diverse sets of drug-like structures. Curr. Med. Chem., 2003, 10(3), 225-233.
[http://dx.doi.org/10.2174/0929867033368510] [PMID: 12570709]
[40]
Dewar, M.J.S.; Dieter, K.M. Evaluation of AM1 Calculated Proton Affinities and Deprotonation Enthalpies. J. Am. Chem. Soc., 1986, 108, 8075-8086.
[http://dx.doi.org/10.1021/ja00285a033]
[41]
Steawart, J.J.P. Optimization of Parameters for Semi-Empirical Methods I-Method. J. Comput. Chem., 1989, 10, 209-216.
[http://dx.doi.org/10.1002/jcc.540100208]
[42]
Jankulovska, M.; Čolančeska-Rağenovic, K.; Dimova, V.; Spirevska, I.; Makreski, P. Synthesis and characterization of new p-substituted aromatic hydrazones., Org. Chem., An Ind. J., 2012, 8, 326-334..
[43]
Rajput, A.P.; Rajput, S.S.; Patil, Z.B. Synthesis of benzaldehyde substituted phenyl carbonyl hydrazones and their formylation using Vilsmeier-Haack reaction. Int. J. Pharm. Tech. Res., 2009, 1(4), 1605-1611.
[44]
Kristallovich, E.L.; Eshimbetov, A.G.; Chuvylkin, V.D.; Belenkii, L.I.; Shakhidoyatov, Kh.M. Nature of π-electronic transitions in UV spectra of deoxyvasicionone and its derivatives. Chem. Nat. Compd., 2003, 39(5), 495-500.
[http://dx.doi.org/10.1023/B:CONC.0000011127.28348.ca]
[45]
Brahmankar, D.M.; Jaiswal, S.B. Biopharmaceutics & pharmacokinetics; 2nd Ed.; Vallabh prakashan: Delhi. , 2009.
[46]
Davis, C.T.; Geissman, T.A. Basic dissociation constants of some substituted flavones. J. Am. Chem. Soc., 1954, 76, 3507-3511.
[http://dx.doi.org/10.1021/ja01642a045]
[47]
Doğan Daldal, Y.; Çubuk Demiralay, E.; Ozkanb, S.A. Effect of organic solvent composition on dissociation constants of some reversible acetylcholinesterase inhibitors. J. Braz. Chem. Soc., 2016, 27(3), 493-499.
[48]
Zalewski, R.I.; Géribaldi, S. Adaptation of characteristic vector analysis to pKBH+ calculations of very weak bases from incomplete ultraviolet spectral data. J. Chem. Soc. Perkin Trans, 1988, 2, 113-115.
[http://dx.doi.org/10.1039/P29880000113]
[49]
King, E.J. Acid-Base Equilibria; Pergamon Press: Oxford, 1965.
[50]
Jankulovska, M.; Spirevska, I.; Cholancheska Ragjenovikj, K. Determination of the dissociation constants of some p-substituted aromatic hydrazones. Contributions, Sec. Math. Tech. Sci. MANU, 2011, XXXII(1-2), 23-43.

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