Research Article
BibTex RIS Cite

Investigation of Molecular Structures, Basicity Constants and their Interactions with Tumor-Associated Proteins of 2-((phenylimino)methyl)phenol Derivative Schiff Bases by Computational Methods

Year 2025, Volume: 46 Issue: 4, 812 - 824, 30.12.2025

Burcu Çöpcü , Sultan Erkan , Duran Karakaş

https://doi.org/10.17776/csj.1686893

Abstract

HL1–HL5 Schiff bases were designed by attaching methyl, ethyl, isopropyl, and chloro substituents to the imine group of the 2-((phenylimino)methyl)phenol structure. The experimentally determined basicity constant of the Schiff bases were calculated at various computational levels and a comparative analysis was performed. The B3LYP/6-31G(d) level was determined as the optimal level. The geometries of HL1–HL5 Schiff bases were optimized at the B3LYP/6-31G(d) level. IR and NMR spectra were calculated. The ground state molecular structures of Schiff bases were characterized from IR stretching frequencies, 1H-NMR and 13C-NMR chemical shift values obtained from the optimized structures. Some molecular descriptors, basicity constants (pKb), and proton affinities (PA) of the HL1–HL5 Schiff bases were calculated from aqueous-phase and gas-phase optimizations, respectively. It was found that there is an almost linear proportional relationship between the pKb values of Schiff bases and their HOMO energies and proton affinities. Schiff bases were docked to protein chains with PDB codes 3HY3 and 1M17 in cell lines and their docking poses, binding energies (BE), interaction energies (IE) and total interaction energies (TIE) were calculated. To investigate whether there is a relationship between basicity strength and antitumor activity, BE, IE and TIE graphs were drawn against pKb values of Schiff bases. It was found that the antitumor activity of Schiff bases with high pKb values was generally high. However, it was determined that there was no linear relationship between pKb value and antitumor activity.

Keywords

Antitumor activity Basicity constant Proton affinity Schiff base

Supporting Institution

Sivas Cumhuriyet Üniversitesi Bilimsel Araştırma Projeleri

Project Number

F-2022-662

Thanks

Sivas Cumhuriyet Üniversitesi Bilimsel Araştırma projeleri komisyonuna verdikleri destek için teşekkür ederiz.

References

  • [1] Schiff H., Mittheilungen aus dem Universitätslaboratorium in Pisa: eine neue Reihe organischer Basen, Justus Liebigs Annalen der Chemie, 131(1) (1864) 118-119.
  • [2] Chen W., Ou W., Wang L., Hao Y., Cheng J., Li J., Liu Y. N., Synthesis and biological evaluation of hydroxyl-substituted Schiff-bases containing ferrocenyl moieties, Dalton Transactions, 42(44) (2013) 15678-15686.
  • [3] Ali A., Abdullah N., Maah M. J., Synthesis, characterization, and antioxidant studies on 4-phenyl-1,3,5-triazine-2,6diamine Schiff bases and their nickel (II), copper (II) and zinc (II) complexes, (2013).
  • [4] Scheurer A., Maid H., Hampel F., Saalfrank R. W., Toupet L., Mosset P., van Eikema Hommes N. J., Influence of the Conformation of Salen Complexes on the Stereochemistry of the Asymmetric Epoxidation of Olefins, (2005).
  • [5] Dey M., Rao C. P., Saarenketo P. K., Rissanen K., Mono-, di-and tri-nuclear Ni (II) complexes of N-, O-donor ligands: structural diversity and reactivity, Inorganic Chemistry Communications, 5(11) (2002) 924-928.
  • [6] Shokohi-Pour Z., Chiniforoshan H., Sabzalian M. R., Esmaeili S. A., Momtazi-Borojeni A. A., Cobalt (II) complex with novel unsymmetrical tetradentate Schiff base (ON) ligand: in vitro cytotoxicity studies of complex, interaction with DNA/protein, molecular docking studies, and antibacterial activity, Journal of Biomolecular Structure and Dynamics, 36(2) (2018) 532-549.
  • [7] Chohan Z. H., Sumrra S. H., Youssoufi M. H., Hadda T. B., Metal based biologically active compounds: Design, synthesis, and antibacterial/antifungal/cytotoxic properties of triazole-derived Schiff bases and their oxovanadium (IV) complexes, European Journal of Medicinal Chemistry, 45(7) (2010) 2739-2747.
  • [8] Ghorai P., Saha R., Bhuiya S., Das S., Brandão P., Ghosh D., Saha A., Syntheses of Zn (II) and Cu (II) Schiff base complexes using N, O donor Schiff base ligand: crystal structure, DNA binding, DNA cleavage, docking and DFT study, Polyhedron, 141 (2018) 153-163.
  • [9] Kazemi Z., Rudbari H. A., Sahihi M., Mirkhani V., Moghadam M., Tangestaninejad S., Gharaghani S., Synthesis, characterization and biological application of four novel metal-Schiff base complexes derived from allylamine and their interactions with human serum albumin: experimental, molecular docking and ONIOM computational study, Journal of Photochemistry and Photobiology B: Biology, 162 (2016) 448-462.
  • [10] Faraj M.E., Jumaa F.H., Preparation, diagnostics and biological evaluation of new Schiff base and tetrazole derivatives, Materials Today: Proceedings, 49 (2022) 35-3557.
  • [11] Sondhi S.M., Singh N., Kumar A., Lozach O., Meijer L., Novel Hydralazine Schiff Base Derivatives and Their Antimicrobial, Antioxidant and Antiplasmodial Properties, Bioorganic & Medicinal Chemistry, 14 (2006) 3758–3765.
  • [12] Souza A. O. D., Galetti F., Silva C. L., Bicalho B., Parma M. M., Fonseca S. F., De Oliveira M. C., Antimycobacterial and cytotoxicity activity of synthetic and natural compounds, Química Nova, 30(7) (2007) 1563-1566.
  • [13] Guo Z., Xing R., Liu S., Zhong Z., Ji X., Wang L., Li P., Antifungal properties of Schiff bases of chitosan, N-substituted chitosan and quaternized chitosan, Carbohydrate Research, 342(10) (2007) 1329-1332.
  • [14] Kaya S., Erkan S., Karakaş D., Computational investigation of molecular structures, spectroscopic properties and antitumor-antibacterial activities of some Schiff bases, Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 244 (2021) 118829.
  • [15] Rizwan M., Ali S., Shahzadi S., Sharma S. K., Qanungo K., Shahid M., Mahmood S., Synthesis, characterization, HOMO–LUMO study, and antimicrobial activity of organtin (IV) complexes of 4-piperidine carboxamide and its Schiff base, Journal of Coordination Chemistry, 67(2) (2014) 341-351.
  • [16] Parr R. G., Szentpály L. V., Liu S., Electrophilicity index, Journal of the American Chemical Society, 121(9) (1999) 1922-1924.
  • [17] Parr R. G., Donnelly R. A., Levy M., Palke W. E., Electronegativity: the density functional viewpoint, The Journal of Chemical Physics, 68(8) (1978) 3801-3807.
  • [18] Parr R. G., Pearson R. G., Absolute hardness: companion parameter to absolute electronegativity, Journal of the American Chemical Society, 105(26) (1983) 7512-7516.
  • [19] Mishra V. R., Ghanavatkar C. W., Mali S. N., Chaudhari H. K., Sekar N., Schiff base clubbed benzothiazole: synthesis, potent antimicrobial and MCF-7 anticancer activity, DNA cleavage and computational study, Journal of Biomolecular Structure and Dynamics, (2019).
  • [20] Kaya S., Erkan S., Karakaş D., Computational design and characterization of platinum‐II complexes of some Schiff bases and investigation of their anticancer‐antibacterial properties, Applied Organometallic Chemistry, (2022) e6805.
  • [21] Çukurovali A., Yilmaz I., Özmen H., Ahmedzade M., Cobalt (II), copper (II), nickel (II) and zinc (II) complexes of two novel Schiff base ligands and their antimicrobial activity, Transition Metal Chemistry, 27(2) (2002) 171-176.
  • [22] Raman N., Kulandaisamy A., Shunmugasundaram A., Jeyasubramanian K., Synthesis, spectral, redox and antimicrobial activities of Schiff base complexes derived from 1-phenyl-2, 3-dimethyl-4-aminopyrazol-5-one and acetoacetanilide, Transition Metal Chemistry, 26(1) (2001) 131-135.
  • [23] El-Sherif A. A., Aljahdali M. S., Protonation, complex-formation equilibria, and metal–ligand interaction of salicylaldehyde Schiff bases, Journal of Coordination Chemistry, 66(19) (2013) 3423-3468.
  • [24] Dennington R., Keith T., Millam J., GaussView Version 5, Semichem Inc. Shawnee Mission KS, (2009).
  • [25] Frisch M. J., Trucks G.W., Schlegel H.B., Scuseria G.E., Robb M.A., Cheeseman J.R., Nakatsuji H., Gaussian09 Revision D. 01, Gaussian Inc. Wallingford CT, (2009).
  • [26] Güveli Ş., Özdemir N., Bal-Demirci T., Ülküseven B., Dinçer M., Andaç Ö., Quantum-chemical, spectroscopic and X-ray diffraction studies on nickel complex of 2-hydroxyacetophenone thiosemicarbazone with triphenylphospine, Polyhedron, 29(12) (2010) 2393-2403.
  • [27] Becke A. D., Density-functional exchange-energy approximation with correct asymptotic behavior, Physical Review A, 38(6) (1988) 3098.
  • [28] Rassolov V. A., Ratner M. A., Pople J. A., Redfern P. C., Curtiss L. A., 6‐31G* basis set for third‐row atoms, Journal of Computational Chemistry, 22(9) (2001) 976-984.
  • [29] Cossi M., Barone V., Analytical second derivatives of the free energy in solution by polarizable continuum models, The Journal of Chemical Physics, 109(15) (1998) 6246-6254.
  • [30] Saeidian H., Ramezannejad M., Taheri S., Mirjafary Z., Toward tailoring of robust organobases based on extended π-systems: A density functional theory study of the carbonyl basicity, Computational and Theoretical Chemistry, 1174 (2020) 112700.
  • [31] Gupta M., da Silva E. F., Svendsen H. F., Computational study of thermodynamics of polyamines with regard to CO2 capture, Energy Procedia, 23 (2012) 140-150.
  • [32] Mavrovouniotis M. L., Estimation of standard Gibbs energy changes of biotransformations, Journal of Biological Chemistry, 266(22) (1991) 14440-14445.
  • [33] Muraleedharan K., The pKa values of amine-based solvents for CO2 capture and its temperature dependence—An analysis by density functional theory, International Journal of Greenhouse Gas Control, 58 (2017) 62-70.
  • [34] Hadjeb R., Barkat D., Determination of acid dissociation constants of some substituted salicylideneanilines by spectroscopy. Application of the Hammett relation, Arabian Journal of Chemistry, 10 (2017) S3646-S3651.
  • [35] Ali O. A., Abdel-Rahman L. H., Ramadan R. M., Ruthenium carbonyl derivatives of N-salicylidene-2-hydroxyaniline, Journal of Coordination Chemistry, 60(21) (2007) 2335-2342.
  • [36] Foresman J.B., Frisch A., Exploring chemistry with electronic structure methods: a guide to using Gaussian, (1996).
  • [37] Ariyaeifar M., Rudbari H. A., Sahihi M., Kazemi Z., Kajani A. A., Zali-Boeini H., Gharaghani S., Chiral halogenated Schiff base compounds: green synthesis, anticancer activity and DNA-binding study, Journal of Molecular Structure, 1161 (2018) 497-511.
  • [38] Köse M., Purtas S., Güngör S. A., Ceyhan G., Akgün E., McKee V., A novel Schiff base: Synthesis, structural characterisation and comparative sensor studies for metal ion detections, Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 136 (2015) 1388-1394.
  • [39] Liao G., Chen X., Qiao Y., Liu K., Wang N., Chen P., Yin X., Highly Electron-Deficient Dicyanomethylene-Functionalized Triarylboranes with Low-Lying LUMO and Strong Lewis Acidity, Organic Letters, 23(15) (2021) 5836-5841.
  • [40] Wu D., Li Y., Song G., Cheng C., Zhang R., Joachimiak A., Liu Z. J., Structural basis for the inhibition of human 5, 10-methenyltetrahydrofolate synthetase by N10-substituted folate analogues, Cancer Research, 69(18) (2009) 7294-7301.
  • [41] Stamos J., Sliwkowski M. X., Eigenbrot C., Structure of the epidermal growth factor receptor kinase domain alone and in complex with a 4-anilinoquinazoline inhibitor, Journal of Biological Chemistry, 277(48) (46265-46272).
  • [42] Bikadi Z., Hazai E., Application of the PM6 semi-empirical method to modeling proteins enhances docking accuracy of AutoDock, Journal of Cheminformatics, 1(1) (2009) 1-16.
There are 42 citations in total.

Details

Primary Language English
Subjects Bioinorganic Chemistry
Journal Section Research Article
Authors

Burcu Çöpcü 0000-0001-9372-1867

Sultan Erkan 0000-0001-6744-929X

Duran Karakaş 0000-0002-6770-3726

Project Number F-2022-662
Submission Date April 30, 2025
Acceptance Date November 9, 2025
Publication Date December 30, 2025
Published in Issue Year 2025 Volume: 46 Issue: 4

Cite

APA Çöpcü, B., Erkan, S., & Karakaş, D. (2025). Investigation of Molecular Structures, Basicity Constants and their Interactions with Tumor-Associated Proteins of 2-((phenylimino)methyl)phenol Derivative Schiff Bases by Computational Methods. Cumhuriyet Science Journal, 46(4), 812-824. https://doi.org/10.17776/csj.1686893

Editor