Synthesis, spectroscopic characterization, density functional theory analysis, and molecular docking studies of diorganotin (IV) complexes with sterically congestedligands

Abstract

Diorganotin (IV) complexes have attracted considerable attention due to their diverse structural features and promising biological properties. The investigation into diorganotin (IV) compounds as potential antimicrobial agents is an active and captivating area of research, particularly emphasizing the synthesis and characterization of diorganotin (IV) complexes with bioactive and sterically hindered ligands. In this study, novel diorganotin (IV) azomethine chelates were synthesized from sterically hindered 4-(2’-mercapto-phenyl-iminoaryl/alkyl)-2,4-dihydro-5-methyl-2-phenyl-3H-pyrazol-3-ones, characterized, and evaluated for their antimicrobial potential. These complexes were obtained by reacting dimethyltin dichloride with the corresponding disodium salts in benzene and characterized through infrared, 1H, 13C, and 119Sn nuclear magnetic resonance spectroscopy, along with molecular weight determination. Structural optimization and electronic property analyses were performed using density functional theory (DFT) at the B3LYP/LanL2DZ level. Conceptual DFT descriptors indicated subtle variations in reactivity, with Chelate-4 exhibiting the highest softness and the lowest energy gap, suggesting enhanced electron-accepting capability. Molecular docking studies were conducted on the ligand moieties (L-1 to L-4) against proteins from Gram-positive and Gram-negative bacteria using cephalosporin and sulfamethoxazole as reference drugs. Ligand L-4 displayed superior binding affinities across all targets, aligning with its DFT-predicted reactivity. Absorption, distribution, metabolism, and excretion analysis revealed that while L-1 and L-2 showed favorable drug-likeness and oral bioavailability, L-4 demonstrated higher lipophilicity and possible metabolic concerns despite its potent antibacterial potential.

Keywords

Dimethyltin dichloride / Infrared / Nuclear magnetic resonance / Azomethines / ADME / Molecular docking / Density functional theory

Funding

None.

Conflict of interest

The authors declare that they have no competing interests.

References

[1] Hadjikakou SK, Hadjiliadis N. Antiproliferative and anti-tumor activity of organotin compounds. Coord Chem Rev. 2009; 253(1-2):235-49. doi: 10.1016/j.ccr.2008.09.017

[2] Nath M, Sharma CL, Sharma N. Dibutyltin(IV) complexes of schiff bases derived from aminoacids. Synth React Inorg Met Org Chem. 1991; 21(5):807-24. doi: 10.1080/15533179108016844

[3] Bhambhani S, Saxena S, Rai AK. New dibutylgermanium (IV) complexes of sterically demanding 4-(2’-mercapto phenyl iminoalkyl/aroyl)-2, 4-dihydro-5-methyl-2-phenyl- 3h-pyrazol-3-ones: Preparation and structural elucidation. Main Group Met Chem. 1998; 21(12):747-750. doi: 10.1515/MGMC.1998.21.12.747

[4] Nath M, Yadav R, Eng G, Nguyen TT, Kumar A. Characteristic spectral studies, and antimicrobial and anti-inflammatory activities of diorganotin (IV) derivatives of dipeptides. J Organomet Chem. 1999; 577(1):1-8. doi: 10.1016/S0022-328X(98)01017-1

[5] Bhambhani S, Saxena S, Rai AK. Synthetic and structural aspects of certain diorganosilicon (IV) chelates derived from sterically demanding 4-(2’-mercapto phenyl imino alkyl/ aryl)-2,4-dihydro-5-methyl-2-phenyl-2H-pyrazol-3-ones. Phosphorus Sulfur Silicon Relat Elem. 2000; 157(1):29-41. doi: 10.1080/10426500008040510

[6] Sharma J, Singh YP, Rai AK. Synthesis, characterization and structural elucidation of monoorganodi (chloro) Sn(IV) complexes of heterocyclic dithiocarbamates. Main Group Met Chem. 2000; 23(5):317-20. doi: 10.1515/MGMC.2000.23.5.317

[7] Sharma J, Singh Y, Bohra R, Rai AK. Synthesis and spectral studies of diorganotin heterocyclic dithiocarbamate complexes: The crystal structure of (CH3)2Sn[(S2CNCH2CH2CH2CH2CH2]2. Polyhedron. 1996; 15(7):1097-1102. doi: 10.1016/0277-5387(95)00341-X

[8] Singh HL, Singh J. Synthesis, spectroscopic, molecular structure, and antibacterial studies of dibutyltin (IV) Schiff base complexes derived from phenylalanine, isoleucine, and glycine. Bioinorg Chem Appl. 2014; 2014(1): 716578. doi: 10.1155/2014/716578

[9] Zhang Q, Zhang M, Wang H, et al. A series of two-photon absorption organotin (IV) cyano carboxylate derivatives for targeting nuclear and visualization of anticancer activities. J Inorg Biochem. 2019; 192:1-6. doi: 10.1016/j.jinorgbio.2018.12.009

[10] Adeyemi JO, Onwudiwe DC. Organotin (IV) dithiocarbamate complexes: Chemistry and biological activity. Molecules. 2018; 23(10):2571. doi: 10.3390/molecules23102571

[11] Singh HL, Dhingra N, Bhanuka S. Synthesis, spectral, antibacterial and QSAR studies of tin and silicon complexes with Schiff base of amino acids. J Mol Struct. 2023;1287:135670. doi: 10.1016/j.molstruc.2023.135670

[12] Shah FA, Sirajuddin M, Ali S, Abbas SM, Tahir MN, Rizzoli C. Synthesis, spectroscopic characterization, X-ray structure and biological screenings of organotin (IV) 3-[(3, 5-dichlorophenylamido)] propanoates. Inorg Chim Acta. 2013; 400:159-168. doi: 10.1016/j.ica.2013.12.022

[13] Liu J, Lin Y, Liu M, et al. Synthesis, structural characterization and cytotoxic activity of triorganotin 5-(salicylideneamino) salicylates. Appl Organomet Chem. 2019; 33(3):e4715. doi: 10.1002/aoc.4715

[14] Latha A, Elangovan N, Manoj KP, et al. Synthesis, single crystal (XRD), spectral characterization, computational (DFT), quantum chemical modelling and anticancer activity of di (p-bromobenzyl)(dibromo)(1, 10-phenanthroline) tin(IV) complex. J Indian Chem Soc. 2022; 99(10):100714. doi: 10.1016/j.jics.2022.100714

[15] Bhaskar C, Elangovan N, Sowrirajan S, et al. Synthesis, XRD, Hirshfeld surface analysis, DFT studies, cytotoxicity and anticancer activity of di(m-chlorobenzyl)(dichloro) (4,7-diphenyl-1,10-phenanthroline) tin(IV) complex. J Mol Struct. 2022;1267:133542. doi: 10.1016/j.molstruc.2022.133542

[16] Sharma A, Dhingra N, Singh HL, Khaturia S, Bhardawaj U. New complexes of organotin(IV) and organosilicon(IV) with 2-{(3,4-dimethoxybenzylidene) amino}-benzenethiol: Synthesis, spectral, theoretical, antibacterial, docking studies. J Mol Struct. 2022;1261:132812. doi: 10.1016/j.molstruc.2022.132812

[17] Pooyan M, Shariatinia Z, Mohammadpanah F, et al.. In vitro cytotoxicity evaluation of organotin(IV) complexes derived from bisphosphoramide ligand: DNA binding and molecular docking studies. J Mol Liq. 2023;391:123442. doi: 10.1016/j.molliq.2023.123442

[18] Mansour MS, Ibrahium AT, El-Sherif AA, Mahmoud WH. Organotin(IV) complexes: Synthesis, characterization, DFT, and molecular docking studies unveiling their potential biomedical uses. Appl Organomet Chem. 2024; 38(11):e7656. doi: 10.1002/aoc.7656

[19] Meng XY, Zhang HX, Mezei M, Cui M. Molecular docking: A powerful approach for structure-based drug discovery. Curr Comput Aided Drug Des. 2011; 7(2):146-157. doi: 10.2174/157340911795677602

[20] Palafox MA, Tardajos G, Guerrero-Martínez A, et al. FT-IR, FT-Raman spectra, density functional computations of the vibrational spectra and molecular geometry of biomolecule 5-aminouracil. Chem Phys. 2007; 340(1-3):17-31. doi: 10.1016/j.chemphys.2006.11.020

[21] Khan MA, Kesharwani MK, Bandyopadhyay T, Ganguly B. Remarkable effect of hydroxylamine anion towards the solvolysis of sarin: A DFT study. J Mol Struct Theochem. 2010; 944(1-3):132-136. doi: 10.1016/j.theochem.2009.10.003

[22] Vogel AI. A Textbook of Quantitative Inorganic Analysis. 3rd ed. London, UK: The English Language Book Society and Longman; 1961.

[23] Frisch MJ, Trucks GW, Schlegel HB, et al. Gaussian 03, Revision 03. Wallingford CT: Gaussian, Inc.; 2004.

[24] Hampele IC, D’Arcy A, Dale GE, et al. Structure and function of the dihydropteroate synthase from Staphylococcus aureus. J Mol Biol. 1997; 268(1):21-30. doi: 10.1006/jmbi.1997.0944

[25] Dennis ML, Lee MD, Harjani JR, et al. 8-mercaptoguanine derivatives as inhibitors of dihydropteroate synthase. Chem Eur J. 2018; 24(8):1922-1930. doi: 10.1002/chem.201704730

[26] Alexander JA, Chatterjee SS, Hamilton SM, Eltis LD, Chambers HF, Strynadka NC. Structural and kinetic analyses of penicillin-binding protein 4 (PBP4) -mediated antibiotic resistance in Staphylococcus aureus. J Biol Chem. 2018; 293(51):19854-19865. doi: 10.1074/jbc.RA118.004952

[27] Caveney NA, Caballero G, Voedts H, et al. Structural insight into YcbB-mediated beta-lactam resistance in Escherichia coli. Nat Commun. 2019; 10(1):1849. doi: 10.1038/s41467-019-09507-0

[28] Saqallah FG, Hamed WM, Talib WH, Dianita R, Wahab HA. Antimicrobial activity and molecular docking screening of bioactive components of Antirrhinum majus (snapdragon) aerial parts. Heliyon. 2022; 8(8):e10391. doi: 10.1016/j.heliyon.2022.e10391

[29] Cochrane SA, Lohans CT. Breaking down the cell wall: Strategies for antibiotic discovery targeting bacterial transpeptidases. Eur J Med Chem. 2020;194:112262. doi: 10.1016/j.ejmech.2020.112262

[30] Lima LM, Da Silva BN, Barbosa G, Barreiro EJ. β-lactam antibiotics: An overview from a medicinal chemistry perspective. Eur J Med Chem. 2020;208:112829. doi: 10.1016/j.ejmech.2020.112829

[31] Griffith EC, Wallace MJ, Wu Y, et al. The structural and functional basis for recurring sulfa drug resistance mutations in Staphylococcus aureus dihydropteroate synthase. Front Microbiol. 2018;9:1369. doi: 10.3389/fmicb.2018.01369

[32] Capasso C, Supuran CT. Dihydropteroate synthase (sulfonamides) and dihydrofolate reductase inhibitors. In: Bacterial Resistance to Antibiotics-From Molecules to Man. New Jersey: John Wiley and Sons; 2019. p. 163-172. doi: 10.1002/978111959352

[33] Silverstein RM, Webster FX, Kiemle DJ. Spectrometric Identification of Organic Compounds. 7th ed. Wiley: New York; 2005. p. 233.

[34] Gielen M. An overview of forty years organotin chemistry developed at the Free Universities of Brussels ULB and VUB. J Braz Chem Soc. 2003;14:870-877. doi: 10.1590/S0103-50532003000500021

[35] Lyčka A, Holeček J, Sebald A, Tkáč I. Multinuclear NMR study of some diorgano (chloro) tin (IV) oxinates and thiooxinates. J Organomet Chem. 1991; 409(3):331-9. doi: 10.1016/0022-328X(91)80019-G

[36] Koopmans T. Ordering of wave functions and Eigenenergies to the individual electrons of an atom. Physica. 1933;1: 104-113.

[37] Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev. 1997; 23(1-3): 3-25. doi: 10.1016/S0169-409X(96)00423-1

[38] Abd-Aziz NA, Awang N, Chan KM, Kamaludin NF, Mohamad AN. Organotin (IV) dithiocarbamate compounds as anticancer agents: A review of syntheses and cytotoxicity studies. Molecules. 2023; 28(15):5841. doi: 10.3390/molecules28155841

[39] Devi J, Taxak B, Kumar B, Rani S. Synthesis, characterization and bioactivity of diorganotin (IV) Schiff base complexes as potential antimalarial and antioxidant agents: Insights through cytotoxicity and molecular docking studies. Dalton Trans. 2025; 54(18):7167-7178. doi: 10.1039/D5DT00274E

[40] Caruso F, Di-Nicola C, Hanna JV, et al. Novel bis (β-diketonato) diorganotin (IV) derivatives containing bulky 4-acyl-5-pyrazolonato ligands: Influence of the steric hindrance of the acyl moiety on the solid-state structures of tin complexes and their behaviour in solution. Inorg Chim Acta. 2011; 367(1):73-84. doi: 10.1016/j.ica.2010.12.008