European Journal of Chemistry

Hydrothermally synthesized (N,O)-linked Cu(II)-based coordination complex as a potential antibacterial agent


Main Article Content

Anmol Chettri
Sudarshan Pradhan
Pritika Gurung
Sriparna Roy
Biswajit Sinha


The N,O-linked Cu(II)-based coordination complex was synthesized hydrothermally and characterized by SC-XRD, FTIR spectroscopy, and FE-SEM. Single crystal X-ray diffraction studies showed that the complex crystallizes in a square pyramidal geometry and belongs to the monoclinic crystal system with the space group P21/n. Crystal data for C14H13CuN3O6: a = 8.7355(11) Å, b = 17.646(2) Å, c = 9.8036(12) Å, β = 98.506(6)°, = 1494.6(3) Å3, Z = 4, μ(MoKα) = 1.500 mm-1, Dcalc = 1.701 g/cm3, 5120 reflections measured (4.616° ≤ 2Θ ≤ 49.982°), 1953 unique (Rint = 0.0316, Rsigma = 0.0718) which were used in all calculations. The final R1 was 0.0380 (I > 2σ(I)) and wR2 was 0.0972 (all data). The experimental antibacterial activity studies performed using the disc diffusion method revealed that the complex is indeed acting as a good antibacterial agent against Staphylococcus aureus and Escherichia coli. A better understanding of the binding mechanisms was uncovered through comparative molecular docking investigations. The docking score for the target S. aureus glyrase complex with DNA (PDB id-2XCS) was found to be -7.1 kcal/mol, while the docking score for dialkylglycine decarboxylase (PDB id-1D7U) was -5.2 kcal/mol. The high docking score of the complex with the target protein allowed the complex to act as a potential antibacterial agent. These results were also supported by other theoretical studies such as DFT calculations and pharmacokinetic studies. The correlation between the HOMO-LUMO energy gap and antibacterial activity was studied computationally. Hirshfeld surface analysis and pharmacokinetic studies were also performed for this crystal for a better understanding of the intermolecular interactions and ADME properties.

icon graph This Abstract was viewed 309 times | icon graph Article PDF downloaded 179 times icon graph Article CIF FILE downloaded 0 times

How to Cite
Chettri, A.; Pradhan, S.; Gurung, P.; Roy, S.; Sinha, B. Hydrothermally Synthesized (N,O)-Linked Cu(II)-Based Coordination Complex As a Potential Antibacterial Agent. Eur. J. Chem. 2023, 14, 429-438.

Article Details

Crossref - Scopus - Google - European PMC

[1]. Aakeröy, C. B.; Champness, N. R.; Janiak, C. Recent advances in crystal engineering. CrystEngComm 2010, 12, 22-43.

[2]. Wong-Foy, A. G.; Matzger, A. J.; Yaghi, O. M. Exceptional H2 saturation uptake in microporous Metal−Organic frameworks. J. Am. Chem. Soc. 2006, 128, 3494-3495.

[3]. Abrahams, B. F.; FitzGerald, N. J.; Robson, R. Cages with tetrahedron-like topology formed from the combination of cyclotricatechylene ligands with metal cations. Angew. Chem. Int. Ed Engl. 2010, 49, 2896-2899.

[4]. Deng, H.; Doonan, C. J.; Furukawa, H.; Ferreira, R. B.; Towne, J.; Knobler, C. B.; Wang, B.; Yaghi, O. M. Multiple functional groups of varying ratios in metal-organic frameworks. Science 2010, 327, 846-850.

[5]. Gándara, F.; Medina, M. E.; Snejko, N.; Gutiérrez-Puebla, E.; Proserpio, D. M.; Angeles Monge, M. Ligand dependent topology changes in six zinc coordination polymers. CrystEngComm 2010, 12, 711-719.

[6]. Niu, M.; Huang, F.; Cui, L.; Huang, P.; Yu, Y.; Wang, Y. Hydrothermal synthesis, structural characteristics, and enhanced photocatalysis of SnO2/α-Fe2O3 semiconductor nanoheterostructures. ACS Nano 2010, 4, 681-688.

[7]. Baibarac, M.; Baltog, I.; Smaranda, I.; Scocioreanu, M.; Lefrant, S. Hybrid organic-inorganic materials based on poly(o-phenylenediamine) and polyoxometallate functionalized carbon nanotubes. J. Mol. Struct. 2011, 985, 211-218.

[8]. Ngo, H. T.; Liu, X.; Jolliffe, K. A. Anion recognition and sensing with Zn(ii)-dipicolylamine complexes. Chem. Soc. Rev. 2012, 41, 4928.

[9]. Zeng, Z.; Matuschek, D.; Studer, A.; Schwickert, C.; Pöttgen, R.; Eckert, H. Synthesis and characterization of inorganic-organic hybrid materials based on the intercalation of stable organic radicals into a fluoromica clay. Dalton Trans. 2013, 42, 8585-8596.

[10]. Xu, H.; Chen, R.; Sun, Q.; Lai, W.; Su, Q.; Huang, W.; Liu, X. Recent progress in metal-organic complexes for optoelectronic applications. Chem. Soc. Rev. 2014, 43, 3259-3302.

[11]. Manikandamathavan, V. M.; Weyhermüller, T.; Parameswari, R. P.; Sathishkumar, M.; Subramanian, V.; Nair, B. U. DNA/protein interaction and cytotoxic activity of imidazole terpyridine derived Cu(ii)/Zn(ii) metal complexes. Dalton Trans. 2014, 43, 13018-13031.

[12]. Lemoine, P.; Viossat, B.; Morgant, G.; Greenaway, F. T.; Tomas, A.; Dung, N.-H.; Sorenson, J. R. J. Synthesis, crystal structure, EPR properties, and anti-convulsant activities of binuclear and mononuclear 1,10-phenanthroline and salicylate ternary copper(II) complexes. J. Inorg. Biochem. 2002, 89, 18-28.

[13]. Lavie-Cambot, A.; Cantuel, M.; Leydet, Y.; Jonusauskas, G.; Bassani, D. M.; McClenaghan, N. D. Improving the photophysical properties of copper(I) bis(phenanthroline) complexes. Coord. Chem. Rev. 2008, 252, 2572-2584.

[14]. Devereux, M.; O Shea, D.; Kellett, A.; McCann, M.; Walsh, M.; Egan, D.; Deegan, C.; Kędziora, K.; Rosair, G.; Müller-Bunz, H. Synthesis, X-ray crystal structures and biomimetic and anticancer activities of novel copper(II)benzoate complexes incorporating 2-(4′-thiazolyl)benzimidazole (thiabendazole), 2-(2-pyridyl)benzimidazole and 1,10-phenanthroline as chelating nitrogen donor ligands. J. Inorg. Biochem. 2007, 101, 881-892.

[15]. Ma, C.; Chen, C.; Liu, Q.; Liao, D.; Li, L. The first structurally characterized trinuclear dipicolinato manganese complex and its conversion into a mononuclear species by ligand substitution. Eur. J. Inorg. Chem. 2003, 2003, 1227-1231.

[16]. Ranjbar, M.; Aghabozorg, H.; Moghimi, A. A seven-coordinate pyridine-2,6-dicarboxylate-bridged cadmium(II) complex, at 110 K. Acta Crystallogr. Sect. E Struct. Rep. Online 2002, 58, m304-m306.

[17]. Ma, C.; Fan, C.; Chen, C.; Liu, Q. Aqua(dipicolinato-κ3O2,N,O6)(1,10-phenanthroline-κ2N,N′)manganese(II) monohydrate. Acta Crystallogr. C 2002, 58, m553-m555.

[18]. Koman, M.; Melnı́k, M.; Moncol, J. Crystal and molecular structure of copper(II)(pyridine-2,6-dicarboxylato)(2,6-dimethanolpyridine). Inorg. Chem. Commun. 2000, 3, 262-266.

[19]. Kanai, Y. Simultaneous determination of iron(II) and iron(III) oxides in geological materials by ion chromatography. Analyst 1990, 115, 809-812.

[20]. Hindle, A. A.; Hall, E. A. H. Dipicolinic acid (DPA) assay revisited and appraised for spore detection. Analyst 1999, 124, 1599-1604.

[21]. Anandan, K.; Vittal, R. R. Endophytic Paenibacillus amylolyticus KMCLE06 extracted dipicolinic acid as antibacterial agent derived via dipicolinic acid synthetase gene. Curr. Microbiol. 2019, 76, 178-186.

[22]. Şahin, E.; İde, S.; Kurt, M.; Yurdakul, Ş. Structural investigation of dibromobis(benzimidazole)Zn(II) complex. J. Mol. Struct. 2002, 616, 259-264.

[23]. Dong, G.-Y.; Fan, L.-H.; Yang, L.-X.; Khan, I. U. Aqua(1H-benzimidazole-κN3)(pyridine-2,6-dicarboxylato-κ3O2,N,O6)copper(II) 0.75-hydrate. Acta Crystallogr. Sect. E Struct. Rep. Online 2010, 66, m532-m532.

[24]. Feng, S.; Xu, R. New materials in hydrothermal synthesis. Acc. Chem. Res. 2001, 34, 239-247.

[25]. Klančnik, A.; Piskernik, S.; Jeršek, B.; Možina, S. S. Evaluation of diffusion and dilution methods to determine the antibacterial activity of plant extracts. J. Microbiol. Methods 2010, 81, 121-126.

[26]. Spackman, M. A.; Jayatilaka, D. Hirshfeld surface analysis. CrystEngComm 2009, 11, 19-32.

[27]. Paul Gleeson, M.; Hersey, A.; Hannongbua, S. In-silico ADME models: A general assessment of their utility in drug discovery applications. Curr. Top. Med. Chem. 2011, 11, 358-381.

[28]. Sheldrick, G. M. (1997). SHELX-97. University of Göttingen, Germany.

[29]. Altomare, A.; Burla, M. C.; Camalli, M.; Cascarano, G. L.; Giacovazzo, C.; Guagliardi, A.; Moliterni, A. G. G.; Polidori, G.; Spagna, R. SIR97: a new tool for crystal structure determination and refinement. J. Appl. Crystallogr. 1999, 32, 115-119.

[30]. Lala, M.; Modak, D.; Paul, S.; Sarkar, I.; Dutta, A.; Kumar, A.; Bhattacharjee, S.; Sen, A. Potent bioactive methanolic extract of wild orange (Citrus macroptera Mont.) shows antioxidative, anti-inflammatory, and antimicrobial properties in in vitro, in vivo, and in silico studies. Bull. Natl. Res. Cent. 2020, 44, 81.

[31]. Boyanova, L.; Gergova, G.; Nikolov, R.; Derejian, S.; Lazarova, E.; Katsarov, N.; Mitov, I.; Krastev, Z. Activity of Bulgarian propolis against 94 Helicobacter pylori strains in vitro by agar-well diffusion, agar dilution and disc diffusion methods. J. Med. Microbiol. 2005, 54, 481-483.

[32]. Mini Shobi, T.; Gowdu Viswanathan, M. B. Antibacterial activity of di-butyl phthalate isolated from Begonia malabarica. J. Appl. Biotechnol. Bioeng. 2018, 5 (2), 101-104.

[33]. Jiang, Q. Natural forms of vitamin E: metabolism, antioxidant, and anti-inflammatory activities and their role in disease prevention and therapy. Free Radic. Biol. Med. 2014, 72, 76-90.

[34]. Panda, S.; Jafri, M.; Kar, A.; Meheta, B. K. Thyroid inhibitory, antiperoxidative and hypoglycemic effects of stigmasterol isolated from Butea monosperma. Fitoterapia 2009, 80, 123-126.

[35]. Pisano; Kumar; Medda; Gatto; Pal; Fais; Era; Cosentino; Uriarte; Santana; Pintus; Matos Antibacterial activity and molecular docking studies of a selected series of hydroxy-3-arylcoumarins. Molecules 2019, 24, 2815.

[36]. Trott, O.; Olson, A. J. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem. 2009, 31, 455-461.

[37]. Kouranov, A. The RCSB PDB information portal for structural genomics. Nucleic Acids Res. 2006, 34, D302-D305.

[38]. Bax, B. D.; Chan, P. F.; Eggleston, D. S.; Fosberry, A.; Gentry, D. R.; Gorrec, F.; Giordano, I.; Hann, M. M.; Hennessy, A.; Hibbs, M.; Huang, J.; Jones, E.; Jones, J.; Brown, K. K.; Lewis, C. J.; May, E. W.; Singh, O.; Spitzfaden, C.; Shen, C.; Shillings, A.; Theobald, A. F.; Wohlkonig, A.; Pearson, N. D.; Gwynn, M. N. The 2.1A crystal structure of S. aureus Gyrase complex with GSK299423 and DNA 2010. (accessed April 9, 2023).

[39]. Malashkevich, V. N.; Strop, P.; Keller, J. W.; Jansonius, J. N.; Toney, M. D. Crystal structures of dialkylglycine decarboxylase inhibitor complexes 1 1Edited by R. Huber. J. Mol. Biol. 1999, 294, 193-200.

[40]. Marini, A.; Hogan, C.; Grüning, M.; Varsano, D. yambo: An ab initio tool for excited state calculations. Comput. Phys. Commun. 2009, 180, 1392-1403.

[41]. Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Montgomery, J. A.; Vreven, T.; Kudin, K. N.; Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.; Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.; Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A. Gaussian 16, Inc., Wallingford CT, 2016.

[42]. Ullah, H.; Shah, A.-U.-H. A.; Bilal, S.; Ayub, K. Doping and dedoping processes of polypyrrole: DFT study with hybrid functionals. J. Phys. Chem. C Nanomater. Interfaces 2014, 118, 17819-17830.

[43]. Frisch, M. J.; Pople, J. A.; Binkley, J. S. Self-consistent molecular orbital methods 25. Supplementary functions for Gaussian basis sets. J. Chem. Phys. 1984, 80, 3265-3269.

[44]. Chiodo, S.; Russo, N.; Sicilia, E. LANL2DZ basis sets recontracted in the framework of density functional theory. J. Chem. Phys. 2006, 125, 104107.

[45]. Aydin, M.; Akins, D. L. DFT studies on solvent dependence of electronic absorption spectra of free-base and protonated porphyrin. Comput. Theor. Chem. 2018, 1132, 12-22.

[46]. Hari, S. In silico molecular docking and ADME/T analysis of plant compounds against IL17A and IL18 targets in gouty arthritis. J. Appl. Pharm. Sci. 2019, 9, 18-26.

[47]. Abdulrahman, H. L.; Uzairu, A.; Uba, S. Computational pharmacokinetic analysis on some newly designed 2-anilinopyrimidine derivative compounds as anti-triple-negative breast cancer drug compounds. Bull. Natl. Res. Cent. 2020, 44, 63.

[48]. Boussery, K.; Belpaire, F. M.; Van de Voorde, J. Physiological aspects determining the pharmacokinetic properties of drugs. In The Practice of Medicinal Chemistry; Elsevier, 2008; pp. 635-654.

[49]. Ntie-Kang, F.; Lifongo, L. L.; Mbah, J. A.; Owono Owono, L. C.; Megnassan, E.; Mbaze, L. M.; Judson, P. N.; Sippl, W.; Efange, S. M. N. In silico drug metabolism and pharmacokinetic profiles of natural products from medicinal plants in the Congo basin. In Silico Pharmacol. 2013, 1, 1.

[50]. Kamath, A.; Brahman, D.; Pilet, G.; Sinha, B.; Tamang, A. [Bis(picolinate-κN:O)Copper(II)] di(benzene1,3,5- tricarboxylic acid): Hydrothermal synthesis, structural characterization, magnetic properties and DFT study. J. Mol. Struct. 2018, 1165, 228-235.

[51]. Silverstein, R. M.; Webster, F. X.; Kiemle, D. J.; Bryce, D. L. Spectrometric identification of organic compounds; 8th ed.; John Wiley & Sons: Chichester, England, 2014.

[52]. Kamath, A.; Pilet, G.; Tamang, A.; Sinha, B. [Diaquo(3,5-dinitrobenzoato-κ1O1)(1,10-phenanthroline-κ2N1:N10)copper(II)] 3,5-dinitrobenzoate: Hydrothermal synthesis, crystal structure and magnetic properties. J. Mol. Struct. 2020, 1199, 126933.

[53]. Frost, R. L.; Locos, O. B.; Ruan, H.; Kloprogge, J. T. Near-infrared and mid-infrared spectroscopic study of sepiolites and palygorskites. Vib. Spectrosc. 2001, 27, 1-13.

[54]. Adams, D. M. Metal-Ligand and Related Vibrations: A Critical Survey of the Infrared and Raman Spectra of Metallic and Organometallic Compounds; St Martin's Press: New York, NY, 1968.

[55]. Bellamy, L. The infra-red spectra of complex molecules; 1975th ed.; Springer: Dordrecht, Netherlands, 1975.

[56]. Nakamoto, K.; Fujita, J.; Tanaka, S.; Kobayashi, M. Infrared spectra of metallic complexes. IV. Comparison of the infrared spectra of unidentate and bidentate metallic complexes. J. Am. Chem. Soc. 1957, 79, 4904-4908.

[57]. McKinnon, J. J.; Jayatilaka, D.; Spackman, M. A. Towards quantitative analysis of intermolecular interactions with Hirshfeld surfaces. Chem. Commun. (Camb.) 2007, 3814-3816.

[58]. Kamath, A.; Brahman, D.; Chhetri, S.; McArdle, P.; Sinha, B. [Diaquobis(p-hydroxybenzoato-κ1O1)(1-methylimidazole- κ1N1)copper(II)]: Synthesis, crystal structure, catalytic activity and DFT study. J. Mol. Struct. 2022, 1247, 131323.

[59]. SenthilKannan, K.; Sivaramakrishnan, V.; Kalaipoonguzhali, V.; Chinnadurai, M.; Kannan, S. Electronic transport, HOMO-LUMO and computational studies of CuS monowire for nano device fabrication by DFT approach. Mater. Today 2020, 33, 2746-2749.

[60]. Gould, T.; Hashimi, Z.; Kronik, L.; Dale, S. G. Single excitation energies obtained from the ensemble "HOMO-LUMO gap": Exact results and approximations. J. Phys. Chem. Lett. 2022, 13, 2452-2458.

[61]. Sutradhar, T.; Misra, A. Role of electron-donating and electron-withdrawing groups in tuning the optoelectronic properties of difluoroboron-napthyridine analogues. J. Phys. Chem. A 2018, 122, 4111-4120.

[62]. Suresh, C. H.; Remya, G. S.; Anjalikrishna, P. K. Molecular electrostatic potential analysis: A powerful tool to interpret and predict chemical reactivity. Wiley Interdiscip. Rev. Comput. Mol. Sci. 2022, 12, e1601.

[63]. Sun, W.; Ma, Z.; Dang, D.; Zhu, W.; Andersson, M. R.; Zhang, F.; Wang, E. An alternating D-A1-D-A2 copolymer containing two electron-deficient moieties for efficient polymer solar cells. J. Mater. Chem. A Mater. Energy Sustain. 2013, 1, 11141-11144.

[64]. Chattaraj, P. K.; Roy, D. R. Update 1 of: Electrophilicity index. Chem. Rev. 2007, 107, PR46-PR74.

[65]. Yourdkhani, S.; Korona, T.; Hadipour, N. L. Structure and energetics of complexes of B12N12 with hydrogen halides-SAPT(DFT) and MP2 study. J. Phys. Chem. A 2015, 119, 6446-6467.

[66]. He, Q.; Li, Q.; Khene, S.; Ren, X.; López-Suárez, F. E.; Lozano-Castelló, D.; Bueno-López, A.; Wu, G. High-loading cobalt oxide coupled with nitrogen-doped graphene for oxygen reduction in anion-exchange-membrane alkaline fuel cells. J. Phys. Chem. C Nanomater. Interfaces 2013, 117, 8697-8707.

[67]. Würthner, F.; Schmidt, R. Electronic and crystal engineering of acenes for solution-processible self-assembling org"anic semiconductors. Chemphyschem 2006, 7, 793-797.

[68]. Kenouche, S.; Sandoval-Yañez, C.; Martínez-Araya, J. I. The antioxidant capacity of myricetin. A molecular electrostatic potential analysis based on DFT calculations. Chem. Phys. Lett. 2022, 801, 139708.

Most read articles by the same author(s)

Most read articles by the same author(s)


Dimensions - Altmetric - scite_ - PlumX

Downloads and views


Download data is not yet available.


Metrics Loading ...
License Terms

License Terms


Copyright © 2024 by Authors. This work is published and licensed by Atlanta Publishing House LLC, Atlanta, GA, USA. The full terms of this license are available at and incorporate the Creative Commons Attribution-Non Commercial (CC BY NC) (International, v4.0) License ( By accessing the work, you hereby accept the Terms. This is an open access article distributed under the terms and conditions of the CC BY NC License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited without any further permission from Atlanta Publishing House LLC (European Journal of Chemistry). No use, distribution, or reproduction is permitted which does not comply with these terms. Permissions for commercial use of this work beyond the scope of the License ( are administered by Atlanta Publishing House LLC (European Journal of Chemistry).