This is an outdated version published on 2023-12-01. Read the most recent version.

Experimental and theoretical studies on (2E,5E)-2,5-bis(2-methoxybenzylidene)cyclopentanone: Structural, electrochemical, spectroscopic features, solid-state interactions, molecular docking and adsorption studies onto 2D carbon nanomaterials


  • Veprim Department of Chemistry, FNSM, University of Prishtina, Kosovo; Institute of Chemistry, FNSM, Ss. Cyril and Methodius in Skopje, N. Macedonia
  • Arianit Department of Chemistry, Faculty of Natural Sciences and Mathematics, University of Tetovo, N. Macedonia
  • Nataša Institute of Chemistry, Faculty of Natural Sciences and Mathematics, Ss. Cyril and Methodius University in Skopje, N. Macedonia
  • Ramiz Department of Chemistry, FMNS, University of Prishtina, Kosovo
  • Avni Department of Chemistry, FMNS, University of Prishtina, Kosovo
  • Jane Bogdanov Institute of Chemistry, Faculty of Natural Sciences and Mathematics, Ss. Cyril & Methodius University in Skopje, N. Macedonia



(2E,5E)-2,5-bis(2-methoxybenzylidene)cyclopentanone, spectroscopic characterization, cyclic voltammetry, DFT, graphene, adsorption, molecular docking, solid-state interactions


A monocarbonyl analog of curcumin, (2E,5E)-2,5-bis(2-methoxybenzylidene)-cyclopentanone (B2MBCP), was prepared and characterized via spectroscopic methods (NMR, UV-Vis, FT-IR, and MS). Furthermore, density functional calculations were implemented to study the molecular structure and spectroscopic features, as well as adsorption properties. In addition, Hirshfeld surface and NBO theoretical analysis were carried out. The reduced density gradient (RDG) analysis via non-covalent interactions (NCI) and interaction region indicator (IRI) indicate the presence of extensive Van der Waals interactions. These interactions are classified in different contributions and energy stabilization from Hirshfeld surface analysis where the dominant type of contacts are H···H contacts. The molecular docking studies of B2MBCP with DNA revealed cooperative interactions that led to intercalation. The results from the cyclic voltammetry (CV) measurements agreed with the calculated energies of the frontier orbitals and the compound structure. Theoretical studies indicated that the relatively flat B2MBCP is adsorbed onto a graphene surface, with a significant adsorption energy of –41.19 kcal/mol. The results of this study provide a better overall picture of the properties of MAC with a cyclopentanone core and can be taken as a useful guide in the search for new biologically active compounds and new possible means of delivery.


(1) Govindarajan, V. S.; Stahl, W. H., Turmeric —Chemistry, Technology, and Quality. Critical Reviews in Food Science & Nutrition 1980, 12 (3), 199–301.

(2) Fuloria, S.; Mehta, J.; Chandel, A.; Sekar, M.; Rani, N. N. I. M.; Begum, M. Y.; Subramaniyan, V.; Chidambaram, K.; Thangavelu, L.; Nordin, R.; Wu, Y. S.; Sathasivam, K. V.; Lum, P. T.; Meenakshi, D. U.; Kumarasamy, V.; Azad, A. K.; Fuloria, N. K., A comprehensive review on the therapeutic potential of Curcuma longa Linn. in relation to its major active constituent curcumin. Front. Pharmacol. 2022, 13, 820806.

(3) Salehi, B.; Stojanović-Radić, Z.; Matejić, J.; Sharifi-Rad, M.; Anil Kumar, N. V.; Martins, N.; Sharifi-Rad, J., The therapeutic potential of curcumin: A review of clinical trials. Eur. J. Med. Chem. 2019, 163, 527–545.

(4) Ammon, H. P.; Wahl, M. A., Pharmacology of Curcuma longa. Planta Med. 1991, 57 (1), 1–7.

(5) Thangapazham, R. L.; Sharma, A.; Maheshwari, R. K., Multiple molecular targets in cancer chemoprevention by curcumin. AAPS J. 2006, 8 (3), E443-9.

(6) Jayaprakasha, G. K.; Jena, B. S.; Negi, P. S.; Sakariah, K. K., Evaluation of antioxidant activities and antimutagenicity of turmeric oil: A byproduct from curcumin production. Z. Naturforsch. C 2002, 57 (9–10), 828–835.

(7) Sharma, R. A.; Steward, W. P.; Gescher, A. J., Pharmacokinetics and pharmacodynamics of curcumin. Adv. Exp. Med. Biol. 2007, 595, 453–470.

(8) Maheshwari, R. K.; Singh, A. K.; Gaddipati, J.; Srimal, R. C., Multiple biological activities of curcumin: a short review. Life Sci. 2006, 78 (18), 2081–2087.

(9) Nelson, K. M.; Dahlin, J. L.; Bisson, J.; Graham, J.; Pauli, G. F.; Walters, M. A., The essential medicinal chemistry of curcumin. J. Med. Chem. 2017, 60 (5), 1620–1637.

(10) Lin, L.; Shi, Q.; Su, C.-Y.; Shih, C. C.-Y.; Lee, K.-H., Antitumor agents 247. New 4-ethoxycarbonylethyl curcumin analogs as potential antiandrogenic agents. Bioorg. Med. Chem. 2006, 14 (8), 2527–2534.

(11) Dimmock, J. R.; Padmanilayam, M. P.; Zello, G. A.; Nienaber, K. H.; Allen, T. M.; Santos, C. L.; De Clercq, E.; Balzarini, J.; Manavathu, E. K.; Stables, J. P., Cytotoxic analogues of 2,6-bis(arylidene)cyclo¬hexanones. Eur. J. Med. Chem. 2003, 38 (2), 169–177.

(12) Liang, G.; Yang, S. L.; Shao, L. L.; Zhao, C. G.; Xiao, J.; Lv, Y. X.; Yang, J.; Zhao, Y.; Li, X. K., Synthesis, structure, and bioevaluation of 2,5-bis(arylmethenyl) cyclopentanones. Journal of Asian Natural Products Research 2008, 10 (10), 957–965.

(13) Zhao, C.; Liu, Z.; Liang, G., Promising curcumin-based drug design: mono-carbonyl analogues of curcumin (MACs). Curr. Pharm. Des. 2013, 19 (11), 2114–2135.

(14) Shetty, D.; Kim, Y. J.; Shim, H.; Snyder, J. P., Eliminating the heart from the curcumin molecule: monocarbonyl curcumin mimics (MACs). Molecules 2014, 20 (1), 249–292.

(15) Liang, G.; Shao, L.; Wang, Y.; Zhao, C.; Chu, Y.; Xiao, J.; Zhao, Y.; Li, X.; Yang, S., Exploration and synthesis of curcumin analogues with improved structural stability both in vitro and in vivo as cytotoxic agents. Bioorganic and Medicinal Chemistry 2009, 17 (6), 2623–2631.

(16) Hadzi-Petrushev, N.; Bogdanov, J.; Krajoska, J.; Ilievska, J.; Bogdanova-Popov, B.; Gjorgievska, E.; Mitrokhin, V.; Sopi, R.; Gagov, H.; Kamkin, A.; Mladenov, M., Comparative study of the antioxidant properties of monocarbonyl curcumin analogues C66 and B2BrBC in isoproteranol induced cardiac damage. Life Sci. 2018, 197, 10–18.

(17) Stamenkovska, M.; Hadzi-Petrushev, N.; Nikodinovski, A.; Gagov, H.; Atanasova-Panchevska, N.; Mitrokhin, V.; Kamkin, A.; Mladenov, M., application of curcumine and its derivatives in the treatment of cardiovascular diseases: A review. Int. J. Food Prop. 2021, 24 (1), 1510–1528.

(18) Stojchevski, R.; Angelovski, M.; Velichkovikj, S.; Hadzi-Petrushev, N.; Mladenov, M.; Bogdanov, J. B.; Poretsky, L.; Avtanski, D., 557-P: Effect of monocarbonyl curcumin analogues C66 and B2BrBC on pancreatic expression of genes related to insulin signaling pathway and oxidative stress in streptozotocin-induced diabetes, June 3–7 2022.

(19) Todorovska, I.; Dragarska, K.; Bogdanov, J., A combined 2D- and 3D-QSAR study, design and synthesis of some monocarbonyl curcumin analogs as potential inhibitors of MDA-MB-231 breast cancer cells. Chem. Proc. 2022, 12 (1), 5.

(20) Lozanovski, Z.; Petreska-Stanoeva, J.; Bogdanov, J., Development of a spectrophotometric method for assessment of the relative reactivity of monocarbonyl analogs of curcumin with 2-(dimethylamino)ethanethiol. Maced. J. Chem. Chem. Eng. 2023, 42 (1), 13–24.

(21) Zamrus, S. N. H.; Akhtar, M. N.; Yeap, S. K.; Quah, C. K.; Loh, W. S.; Alitheen, N. B.; Zareen, S.; Tajuddin, S. N.; Hussin, Y.; Shah, S. A. A., Design, synthesis and cytotoxic effects of curcuminoids on HeLa, K562, MCF-7 and MDA-MB-231 cancer cell lines. Chem. Cent. J. 2018, 12 (1), 31.

(22) Zoete, V.; Rougée, M.; Dinkova-Kostova, A. T.; Talalay, P.; Bensasson, R. V., Redox ranking of inducers of a cancer-protective enzyme via the energy of their highest occupied molecular orbital. Free Radic. Biol. Med. 2004, 36 (11), 1418–1423.

(23) Vatsadze, S. Z.; Gavrilova, G. V.; Zyuz’kevich, F. S.; Nuriev, V. N.; Krut’ko, D. P.; Moiseeva, A. A.; Shumyantsev, A. V.; Vedernikov, A. I.; Churakov, A. V.; Kuz’mina, L. G.; Howard, J. A. K.; Gromov, S. P., Synthesis, structure, electrochemistry, and photophysics of 2,5-dibenzylidenecyclopentanones containing in benzene rings substituents different in polarity. Russ. Chem. Bull. 2016, 65 (7), 1761–1772.

(24) De Assis, L. K.; Damasceno, B. S.; Carvalho, M. N.; Oliveira, E. H. C.; Ghislandi, M. G., Adsorption capacity comparison between graphene oxide and graphene nanoplatelets for the removal of coloured textile dyes from wastewater. Environ. Technol. 2020, 41 (18), 2360–2371.

(25) Kini, S. G.; Choudhary, S.; Mubeen, M., Synthesis, docking study and anticancer activity of coumarin substituted derivatives of benzothiazole. 2012, 2 (1), 51–60.

(26) Sastry, S. S. M.; Panjikar, S.; Raman, R. K. S. Graphene and Graphene Oxide as a Support for Biomolecules in the Development of Biosensors. Nanotechnology, Science and Applications 2021, 14 (October), 197–220.

(27) Huber, I.; Rozmer, Z.; Gyöngyi, Z.; Budán, F.; Horváth, P.; Kiss, E.; Perjési, P., structure activity relationship analysis of antiproliferative cyclic C5-curcuminoids without DNA binding: design, synthesis, lipophilicity and biological activity. J. Mol. Struct. 2020, 1206, 127661.

(28) Zhao, C.-G.; Yang, J.; Huang, Y.; Liang, G.; Li, X.-K., Crystal structure of ortho-(2E,5E)-2,5-bis(2-methoxybenzylidene) cyclopentanone, C21H20O3. Kristallogr. - New Cryst. Struct. 2009, 224 (2), 337–338.

(29) Weber, W. M.; Hunsaker, L. A.; Abcouwer, S. F.; Deck, L. M.; Vander Jagt, D. L., Anti-oxidant activities of curcumin and related enones. Bioorg. Med. Chem. 2005, 13 (11), 3811–3820.

(30) Tirado-Rives, J.; Jorgensen, W. L., Performance of B3LYP density functional methods for a large set of organic molecules. J. Chem. Theory Comput. 2008, 4 (2), 297–306.

(31) Zheng, D.; Zhang, M.; Zhao, G., Combined TDDFT and AIM insights into photoinduced excited state intramolecular proton transfer (ESIPT) mechanism in hydroxyl-and amino-anthraquinone solution. Scientific Reports 2017, 7 (1), 1–10.

(32) Li, Y.; Chu, T.-S. DFT/TDDFT Study on the sensing mechanism of a fluorescent probe for hydrogen sulfide: excited state intramolecular proton transfer coupled twisted intramolecular charge transfer. J. Phys. Chem. A 2017, 121 (28), 5245–5256.

(33) Berisha, A., Interactions between the aryldiazonium cations and graphene oxide: A DFT study. J. Chem. Chem. Eng. 2019, 2019.

(34) Berisha, A.; Combellas, C.; Kanoufi, F.; Médard, J.; Decorse, P.; Mangeney, C.; Kherbouche, I.; Seydou, M.; Maurel, F.; Pinson, J., Alkyl-modified gold surfaces: characterization of the Au-C bond. Langmuir 2018, 34 (38), 11264–11271.

(35) Lu, T.; Chen, F. Multiwfn: A., Multifunctional wavefunction analyzer. J. Comput. Chem. 2012, 33 (5), 580–592.

(36) Yamada, Y.; Gohda, S.; Abe, K.; Togo, T.; Shimano, N.; Sasaki, T.; Tanaka, H.; Ono, H.; Ohba, T.; Kubo, S.; Ohkubo, T.; Sato, S., Carbon materials with controlled edge structures. Carbon N. Y. 2017, 122, 694–701.

(37) Humphrey, W.; Dalke, A.; Schulten, K., VMD: Visual molecular dynamics. J. Mol. Graph. 1996, 14 (1), 33–38, 27–28.

(38) Hourahine, B.; Aradi, B.; Blum, V.; Bonafé, F.; Buccheri, A.; Camacho, C.; Cevallos, C.; Deshaye, M. Y.; Dumitrică, T.; Dominguez, A.; Ehlert, S.; Elstner, M.; Van der Heide, T.; Hermann, J.; Irle, S.; Kranz, J. J.; Köhler, C.; Kowalczyk, T.; Kubař, T.; Lee, I. S.; Lutsker, V.; Maurer, R. J.; Min, S. K.; Mitchell, I.; Negre, C.; Niehaus, T. A.; Niklasson, A. M. N.; Page, A. J.; Pecchia, A.; Penazzi, G.; Persson, M. P.; Řezáč, J.; Sánchez, C. G.; Sternberg, M.; Stöhr, M.; Stuckenberg, F.; Tkatchenko, A.; Yu, V. W.-Z.; Frauenheim, T., DFTB+, a software package for efficient approximate density functional theory based atomistic simulations. J. Chem. Phys. 2020, 152 (12), 124101.

(39) Hamed, R.; Jodeh, S.; Hanbali, G.; Safi, Z.; Berisha, A.; Xhaxhiu, K.; Dagdag, O., Eco-friendly synthesis and characterization of double-crossed link 3d graphene oxide functionalized with chitosan for adsorption of sulfamethazine from aqueous solution: Experimental and DFT цalculations. Front. Environ. Sci. Eng. China 2022, 10.

(40) Sundaraganesan, N.; Joshua, B. D.; Radjakoumar, T., Molecular structure and vibrational spectra of 2-chlorobenzoic acid by density functional theory and ab-initio Hartree-Fock цalculations. Indian J. Pure Appl. Phys. 2009.

(41) Saleem, H.; Krishnan, A. R.; Erdogdu, Y.; Subash-chandrabose, S.; Thanikachalam, V.; Manikandan, G., Density Functional theory studies on 2,5-bis(4-hydroxy-3-methoxybenzylidene)cyclopentanone. J. Mol. Struct. 2011, 999 (1), 2–9.

(42) Sajan, D.; Udaya Lakshmi, K.; Erdogdu, Y.; Hubert Joe, I., Molecular structure and vibrational spectra of 2,6-bis(benzylidene)cyclohexanone: A density functional theoretical study. Spectrochim. Acta A Mol. Biomol. Spectrosc. 2011, 78 (1), 113–121.

(43) George, J.; Thomas, A. K.; Sajan, D.; Sathiyamoorthi, S.; Srinivasan, P.; Joy, N.; Philip, R., Experimental and DFT/TD-DFT approach on photo-physical and NLO properties of 2, 6-bis (4-chlorobenzylidene) cyclohexan-one. Opt. Mater. 2020, 100, 109620.

(44) Organic Electrochemistry, Hammerich, O., Lund, H., Eds.; 4th edition revised and expanded; Marcel Dekker, Inc.: New York, NY, 2000.

(45) Fomina, M. V.; Vatsadze, S. Z.; Freidzon, A. Y.; Kuz’mina, L. G.; Moiseeva, A. A.; Starostin, R. O.; Nuriev, V. N.; Gromov, S. P., Structure–property relationships of dibenzylidenecyclohexanones. ACS Omega 2022, 7 (12), 10087–10099.

(46) Abdolhosseinzadeh, S.; Asgharzadeh, H.; Seop Kim, H., Fast and fully-scalable synthesis of reduced graphene oxide. Sci. Rep. 2015, 5, 10160.

(47) Thakur, K.; Kandasubramanian, B., Graphene and graphene oxide-based composites for removal of organic pollutants: A review. J. Chem. Eng. Data 2019, 64 (3), 833–867.

(48) Zhu, X.; Tsang, D. C. W.; Chen, F.; Li, S.; Yang, X., Ciprofloxacin adsorption on graphene and granular activated carbon: kinetics, isotherms, and effects of solution chemistry. Environ. Technol. 2015, 36 (24), 3094–3102.

(49) Mehmeti, V.; Halili, J.; Berisha, A., Which is better for lindane pesticide adsorption, graphene or graphene oxide? An experimental and DFT study. J. Mol. Liq. 2022, 347, 118345.

(50) Aradi, B.; Hourahine, B.; Frauenheim, T., DFTB+, a sparse matrix-based implementation of the DFTB method. J. Phys. Chem. A 2007, 111 (26), 5678–5684.

(51) Hourahine, B.; Sanna, S.; Aradi, B.; Köhler, C.; Niehaus, T.; Frauenheim, T., Self-interaction and strong correlation in DFTB. J. Phys. Chem. A 2007, 111 (26), 5671–5677.

(52) Berisha, A., First principles details into the grafting of aryl radicals onto the free-standing and borophene/Ag(1 1 1) surfaces. Chemical Physics 2021, 544 (January), 111124.

(53) Mehmeti, V.; Sadiku, M., A comprehensive DFT investigation of the adsorption of polycyclic aromatic hydrocarbons onto graphene. Computation 2022, 10 (5), 68.

(54) Fujimoto, H.; Fukui, K., Molecular orbital theory of chemical reactions. Advances in Quantum Chemistry 1972, 6 (C), 177–201.

(55) Woodward, R. B.; Hoffmann, R., The Conservation of orbital symmetry. Angew. Chem. Int. Ed Engl. 1969, 8 (11), 781–853.

(56) Pandya, S. B.; Patel, U. H.; Chaudhary, K. P.; Socha, B. N.; Patel, N. J.; Bhatt, B. S., DNA interaction, cytotoxicity and molecular structure of cobalt complex of 4-amino-n-(6-chloropyridazin-3-yl)benzene sulfonamide in the presence of secondary ligand pyridine. Applied Organometallic Chemistry 2019, 33 (12), 1–14.

(57) Manne, R.; Åberg, T., Koopmans’ theorem for inner-shell ionization. Chem. Phys. Lett. 1970, 7 (2), 282–284.

(58) Dubey, R. P.; Patel, U. H.; Tailor, S. M., DFT studies, hirshfeld surface analysis and crystal structure of novel silver complex of sulfapyridine with secondary ligand pyridine. Mol. Cryst. Liq. Cryst. 2017, 656 (1), 139–152.

(59) McKinnon, J. J.; Jayatilaka, D.; Spackman, M. A., Towards quantitative analysis of intermolecular interactions with Hirshfeld surfaces. Chem. Commun. 2007, No. 37, 3814–3816.

(60) Spackman, M. A.; Jayatilaka, D., Hirshfeld surface analysis. CrystEngComm 2009, 11 (1), 19–32.

(61) Wood, P. A.; McKinnon, J. J.; Parsons, S.; Pidcock, E.; Spackman, M. A., Analysis of the compression of molecular crystal structures using Hirshfeld surfaces. CrystEngComm 2008, 10 (4), 368–376.

(62) Mohamooda Sumaya, U.; KarunaKaran, J.; Biruntha, K.; MohanaKrishnan, A. K.; Usha, G., Crystal structure and Hirshfeld surface analysis and energy frameworks of 1-(2,4-dimethylphenyl)-4-(4-methoxyphenyl)naphthalene. Acta Crystallographica Section E: Crystallographic Communications 2018, 74 (15), 939–943.

(63) Koenderink, J. J.; Van Doorn, A. J., Surface shape and urvature scales. Image Vis. Comput. 1992, 10 (8), 557–564.

(64) Tan, S. L.; Jotani, M. M.; Tiekink, E. R. T., Utilizing Hirshfeld surface calculations, non-covalent interaction (NCI) Plots and the calculation of interaction energies in the analysis of molecular packing. Acta Crystallographica Section E: Crystallographic Communications 2019, 75, 308–318.

(65) Mackenzie, C. F.; Spackman, P. R.; Jayatilaka, D.; Spackman, M. A., CrystalExplorer model energies and energy frameworks: extension to metal coordination compounds, organic salts, solvates and open-shell systems. IUCrJ 2017, 4, 575–587.

(66) Patel, M. K.; Patel, U. H.; Gandhi, S. A.; Barot, V. M.; Jayswal, J., Solvent effect on neutral Co (II) complexes of paeonol derivative–qualitative and quantitative studies from energy frame work and Hirshfeld surface analysis. J. Mol. Struct. 2019, 1196, 119–131.

(67) Chandraleka, S.; Ramya, K.; Chandramohan, G.; Dhanasekaran, D.; Priyadharshini, A.; Panneerselvam, A., Antimicrobial mechanism of copper (II) 1,10-phenanthroline and 2,2’-bipyridyl complex on bacterial and fungal pathogens. Journal of Saudi Chemical Society 2014, 18 (6), 953–962.

(68) Bhola, Y. O.; Socha, B. N.; Pandya, S. B.; Dubey, R. P.; Patel, M. K., Molecular structure, DFT studies, Hirshfeld surface analysis, energy frameworks, and molecular docking studies of novel (E)-1-(4-chlorophenyl)-5-methyl-N′-((3-methyl-5-phenoxy-1-phenyl-1H-pyrazol-4-Yl) methylene)-1H-1, 2, 3-triazole-4-carbohydrazide. Mol. Cryst. Liq. Cryst. 2019, 692 (1), 83–93.

(69) Göktürk, T.; Sakallı Çetin, E.; Hökelek, T.; Pekel, H.; Şensoy, Ö.; Aksu, E. N.; Güp, R., Synthesis, structural investigations, DNA/BSA interactions, molecular docking studies, and anticancer activity of a new 1,4-disubstituted 1,2,3-triazole derivative. ACS Omega 2023, 8 (35), 31839–31856.

(70) Li, L.; Wu, C.; Wang, Z.; Zhao, L.; Li, Z.; Sun, C.; Sun, T., Density functional theory (DFT) and natural bond orbital (NBO) study of vibrational spectra and intramolecular hydrogen bond interaction of l-ornithine-l-aspartate. Spectrochimica Acta - Part A: Molecular and Biomolecular Spectroscopy 2015, 136 (PB), 338–346.

(71) Lu, T.; Chen, Q., Interaction region indicator: A simple real space function clearly revealing both chemical bonds and weak interactions. Chem. Methods 2021, 1 (5), 231–239.

(72) Thaçi, V.; Hoti, R.; Berisha, A.; Bogdanov, J., Corrosion study of copper in aqueous sulfuric acid solution in the presence of (2E,5E)-2,5-dibenzylidenecyclopentanone and (2E,5E)-Bis[(4-dimethylamino)benzylidene]cyclo-pentanone: Experimental and Theoretical Study. Open Chem. 2020, 18 (1), 1412–1420.





How to Cite

Thaçi, V., Reka, A. A., Ristovska, N., Hoti, R., Berisha, A., & Bogdanov, J. (2023). Experimental and theoretical studies on (2E,5E)-2,5-bis(2-methoxybenzylidene)cyclopentanone: Structural, electrochemical, spectroscopic features, solid-state interactions, molecular docking and adsorption studies onto 2D carbon nanomaterials. Macedonian Journal of Chemistry and Chemical Engineering, 42(2).



Organic Chemistry

Most read articles by the same author(s)