Cd(II) Derivatives of Substituted Phenylacetic Acids, Synthesis, Spectroscopic Characterization and Binding Studies with DNA
DOI:
https://doi.org/10.53560/PPASA(62-4)704Keywords:
Mixed Ligands, Spectroscopic Techniques, Auxiliary Ligands, Surface Binding, Multinuclear NMRAbstract
The methoxy substituted phenylacetic acid (MeOPhA) and chloro substituted phenoxyacetic acid (ClPhA) were used to synthesized eight new Cd(II) based complexes. The nitrogen donor 2,2′- bipyridine (MeOPhA2, ClPhA2) and 1,10-phenanthroline (MeOPhA3, ClPhA3) were used as auxiliary ligands for the synthesis of mixed ligand complexes. These complexes were characterized by FT-IR and multinuclear NMR (1H and 13C-NMR) spectroscopic techniques. The FT-IR spectra of the complexes showed characteristic COO- asymmetric and COO- symmetric vibrational bands indicating metal coordination through oxygen. Moreover, their difference, i.e., Δν reveal that the selected ligands are coordinated to the Cd(II) center in a bidentate manner. The 1H-NMR and 13C-NMR data recorded in deuterated solvents also supported successful synthesis in pure forma as well as metal coordination through carboxylate group. The nature of the complex–DNA interaction was examined, and the impact of hetero ligand attachment on binding strength and reactivity was assessed using UV–visible spectroscopy. The obtained data confirmed the effective binding ability through partial intercalation and groove binding through spontaneous process for all the complexes.
References
1. K.J. Franz and N. Metzler-Nolte. Introduction: metals in medicine. Chemical Reviews 119(2): 727-729 (2019).
2. S. Hamaya, K. Oura, A. Morishita, and T. Masaki. Cisplatin in liver cancer therapy. International Journal of Molecular Sciences 24(13): 10858 (2023).
3. A.V. Ciurea, L-A. Glavan, H.P. Costin, R-A. Covache-Busuioc and F.M. Brehar. Celebrating 70 years of DNA discovery: exploring the Blueprint of Life. Journal of Medicine and Life 17(4): 387 (2024).
4. U. Hollstein. Actinomycin. Chemistry and mechanism of action. Chemical Reviews 74(6): 625-652 (1974).
5. M. Kciuk, A. Gielecińska, S. Mujwar, D. Kołat, Ż. Kałuzińska-Kołat, I. Celik, and R. Kontek. Doxorubicin an agent with multiple mechanisms of anticancer activity. Cells 12(4): 659 (2023).
6. A.C. Hangan, L.S. Oprean, L. Dican, L.M. Procopciuc, B. Sevastre, and R.L. Lucaciu. Metal-based drug DNA interactions and analytical determination methods. Molecules 29(18): 4361 (2024).
7. S. Muthaiah, A. Bhatia, and M. Kannan. Stability of Metal Complexes. In: Stability and Applications of Coordination Compounds. A.N. Srivastva (Ed.). London, United Kingdom pp. 23-40 (2020).
8. S. Naz, S. Ullah, U. Iqbal, S. Yousuf, S. Rahim, N. Muhammad, R. Fatima, I.U. Haq, A. Haider, and S. Ali. Homo-and heteroleptic 3-methylbenzoates of zinc (II) ion based on N-donor heterocycles; structure, DNA binding and pharmacological evaluation. Journal of Molecular Liquids 368: 120792 (2022).
9. P.K. Panchal, H.M. Parekh, P.B. Pansuriya, and M.N. Patel. Bactericidal activity of different oxovanadium (IV) complexes with Schiff bases and application of chelation theory. Journal of Enzyme Inhibition and Medicinal Chemistry 21(2): 203-209 (2006).
10. P. Pandey, G. Manibalan, and R. Murugavel. Controlling metal coordination geometry in dinuclear zinc and cadmium hydroxy aryl carboxylates incorporating five-membered aromatic cyclic amine co-ligands. Inorganica Chimica Acta 551: 121461 (2023).
11. M.K. Abd Elnabi, N.E. Elkaliny, M.M. Elyazied, S.H. Azab, S.A. Elkhalifa, S. Elmasry, M.S. Mouhamed, E.M. Shalamesh, N.A. Alhorieny, and et al. Toxicity of heavy metals and recent advances in their removal: a review. Toxics 11(7): 580 (2023).
12. M.R. Rahimzadeh, M.R. Rahimzadeh, S. Kazemi, and A-A. Moghadamnia. Cadmium toxicity and treatment: an update. Caspian Journal of Internal Medicine 8(3): 135-145 (2017)
13. K.S. Egorova and V.P. Ananikov. Toxicity of metal compounds: knowledge and myths. Organometallics 36(21): 4071-4090 (2017)
14. Z. Zhang, C. Bi, D. Buac, Y. Fan, X. Zhang, J. Zuo, P. Zhang, N. Zhang, L. Dong, and Q.P. Dou. Organic cadmium complexes as proteasome inhibitors and apoptosis inducers in human breast cancer cells. Journal of Inorganic Biochemistry 123: 1-10 (2013).
15. K. Kanude and P. Jain. Biosynthesis of CdS nanoparticles using Murraya Koenigii leaf extract and their biological studies. International Journal of Scientific Research in Multidisciplinary Studies 3(7): 5-10 (2017).
16. H.M. Jirjes, A.A. Irzoqi, L.A. Al-Doori, M.A. Alheety, and P.K. Singh. Nano cadmium (II)-benzyl benzothiazol-2-ylcarbamodithioate complexes: synthesis, characterization, anti-cancer and antibacterial studies. Inorganic Chemistry Communications 135: 109110 (2022).
17. K.N. Aziz, K.M. Ahmed, R.A. Omer, A.F. Qader, and E.I. Abdulkareem. A review of coordination compounds: structure, stability, and biological significance. Reviews in Inorganic Chemistry 45(1): 1-19 (2025).
18. F. Mazhar, S. Naz, S. Muzaffar, R. Fatima, S. Yousuf, S. Ali, A. Haider, and K.S. Munawar. Mixed ligand triorganotin (IV) complexes based on oxygen and nitrogen heterocycles; exploration of the geometry and DNA binding potential. Journal of Molecular Structure 1345:143004 (2025).
19. M-L. Hu, A. Morsali, and L. Aboutorabi. Lead (II) carboxylate supramolecular compounds: coordination modes, structures and nano-structures aspects. Coordination Chemistry Reviews 255(23-24): 2821-2859 (2011).
20. S. Muzaffar, S. Naz, F. Mazhar, Z. Rashid, M. Bibi, S. Yousuf, S. Ali, A. Haider and K.S. Munawar. Heteroleptic Zn (II) complexes; synthesis, spectral characterization, DNA interaction, enzyme inhibition and docking studies. Journal of Molecular Structure 1326: 141078 (2025).
21. D. Rixson, G.G. Sezer, E. Alp, M.F. Mahon, and A.D. Burrows. Synthesis, structures and properties of metal–organic frameworks prepared using a semi-rigid tricarboxylate linker. Crystal Engineering Communication 24(4): 863-876 (2022).
22. J. Rockenberger, L. Tröger, A. Kornowski, T. Vossmeyer, A. Eychmüller, J. Feldhaus, and H. Weller. EXAFS studies on the size dependence of structural and dynamic properties of CdS nanoparticles. The Journal of Physical Chemistry B 101(14): 2691-2701 (1997).
23. K. Shivaji, S. Mani, P. Ponmurugan, C.S. De Castro, M.L. Davies, M.G. Balasubramanian, and S. Pitchaimuthu. Green-synthesis-derived CdS quantum dots using tea leaf extract: antimicrobial, bioimaging, and therapeutic applications in lung cancer cells. ACS Applied Nano Materials 1(4): 1683-1693 (2018).
24. M. Oelschlägel, S.R. Kaschabek, J. Zimmerling, M. Schlömann, and D. Tischler. Co-metabolic formation of substituted phenylacetic acids by styrene-degrading bacteria. Biotechnology Reports 6: 20-26 (2015).
25. M. Mazik and P. Seidel. Synthesis of 2-[(3, 4, 5-Triphenyl) phenyl] acetic acid and derivatives. Molbank 2024(2): M1837 (2024).
26. H. Singh, P. Pinacho, D.A. Obenchain, M.M. Quesada-Moreno, and M. Schnell. The many forms of alpha-methoxy phenylacetic acid in the gas phase: flexibility, internal dynamics, and their intramolecular interactions. Physical Chemistry Chemical Physics 24(44): 27312-27320 (2022).
27. G. Smith. Low-dimensional coordination polymeric structures in alkali metal complex salts of the herbicide (2,4-dichlorophenoxy) acetic acid (2,4-D). Crystal Structure Communications 71(2): 140-145 (2015).
28. C. Sen, M. Kumar, Z. ul Nisa, N.A. Ashashi, A. Frontera, S.C. Sahoo and H.N. Sheikh. Coordination polymers of manganese (II), cobalt (II), nickel (II) and cadmium (II) decorated with rigid pyrazine-2,3-dicarboxylic acid linker: synthesis, structural diversity, DFT study and magneto-luminescence properties. Polyhedron 187: 114629 (2020).
29. A. Kumar, A.K. Singh, H. Singh, V. Vijayan, D. Kumar, J. Naik, S. Thareja, J.P. Yadav, P. Pathak, and et al. Nitrogen containing heterocycles as anticancer agents: a medicinal chemistry perspective. Pharmaceuticals 16(2): 299 (2023).
30. E.C. Constable and C.E. Housecroft. The early years of 2,2′-bipyridine A ligand in its own lifetime. Molecules 24(21): 3951 (2019).
31. P.G. Sammes and G. Yahioglu. 1, 10-Phenanthroline: a versatile ligand. Chemical Society Reviews 23(5): 327-334 (1994).
32. S. Naz, M. Sirajuddin, I. Hussain, A. Haider, A. Nadhman, A. Gul, S. Faisal, S. Ullah, S. Yousuf, and S. Ali. 2-Phenylbutyric acid based organotin (IV) carboxylates; synthesis, spectroscopic characterization, antibacterial action against plant pathogens and in vitro hemolysis. Journal of Molecular Structure 1203: 127378 (2020).
33. A. Sarfraz, S. Naz, A. Haider, K.S. Munawar, R. Fatima, S. Yousuf, M.N. Tahir, Y. Wasti, I.U. Haq, and S. Ali. Synthesis, Characterization, and in vitro pharmacological evaluation of Zinc (II) complexes of cycloalkanes and bioactive nitrogen donor heterocycles: Journal of Molecular Liquids 418:126713 (2025).
34. S. Naz, N. Uddin, K. Ullah, A. Haider, A. Gul, S. Faisal, A. Nadhman, M. Bibi, S. Yousuf, and S. Ali. Homo- and heteroleptic Zinc (II) carboxylates: synthesis, structural characterization, and assessment of their biological significance in in vitro models. Inorganica Chimica Acta 511: 119849 (2020).
35. I. Samfira, S. Rodino, P. Petrache, R. Cristina, M. Butu, and M. Butnariu. Characterization and identity confirmation of essential oils by mid infrared absorption spectrophotometry. Digest Journal of Nanomaterials and Biostructures 10(2): 557-566 (2015).
36. K.I. Hadjiivanov, D.A. Panayotov, M.Y. Mihaylov, E.Z. Ivanova, K.K. Chakarova, S.M. Andonova, and N.L. Drenchev. Power of infrared and Raman spectroscopies to characterize metal-organic frameworks and investigate their interaction with guest molecules. Chemical Reviews 121(3): 1286-1424 (2020).
37. P.N. Nelson and R.A. Taylor. Theories and experimental investigations of the structural and thermotropic mesomorphic phase behaviors of metal carboxylates. Applied Petrochemical Research 4(3): 253-285 (2014).
38. G.B. Deacon and R.J. Phillips. Relationships between the carbon-oxygen stretching frequencies of carboxylato complexes and the type of carboxylate coordination. Coordination Chemistry Reviews 33(3): 227-250 (1980).
39. V.P. Singh, S. Singh, D.P. Singh, K. Tiwari, and M. Mishra. Synthesis, spectroscopic (electronic, IR, NMR and ESR) and theoretical studies of transition metal complexes with some unsymmetrical Schiff bases. Journal of Molecular Structure 1058: 71-78 (2014).
40. K. Ullah, S. Ali, A. Haider, S. Naz, S. Yousuf, K.S. Munawar, M.S. Jan, R. Zafar, and R. Kumar. Investigation of pivalic acid-derived organotin (IV) carboxylates: Synthesis, structural insights, interaction with biomolecules, and computational studies. Journal of Molecular Structure 1322: 140444 (2025).
41. J. Strukl and J. Walter. Infrared and Raman spectra of heterocyelic compounds IV: The infrared studies and normal vibrations of some 1: 1 transition metal complexes of 2, 2'-bipyridine. Spectrochimica Acta Part A: Molecular Spectroscopy 27(2): 223-238 (1971).
42. L. Qadeer, S. Ali, A. Haider, N. Uddin, K.S. Munawar, M. Ashfaq, M.N. Tahir, and M.U. Rehman. Synthesis, spectral elucidation and DNA binding studies of cadmium (II) carboxylates with nitrogen donor heteroligands. Inorganic Chemistry Communications 168: 112894 (2024).
43. M. Shiotsuka, Y. Ueno, D. Asano, T. Matsuoka, and K. Sako. Synthesis and photophysical characterization of ruthenium (II) and platinum (II) complexes with bis-pyridylethynyl-phenanthroline ligands as a metalloligand. Transition Metal Chemistry 40(6): 673-679 (2015).
44. L. Pazderski, T. Pawlak, J. Sitkowski, L. Kozerski, and E. Szłyk. 1H NMR assignment corrections and 1H, 13C, 15N NMR coordination shifts structural correlations in Fe (II), Ru (II) and Os (II) cationic complexes with 2,2′‐bipyridine and 1,10‐phenanthroline. Magnetic Resonance in Chemistry 48(6): 450-457 (2010).
45. P. Jolly and R. Mynott. The application of 13C-NMR spectroscopy to organo-transition metal complexes. Advances in Organometallic Chemistry 19: 257-304 (1981).
46. M. Tahir, M. Sirajuddin, M. Zubair, A. Haider, A. Nadman, S. Ali, F. Perveen, H.B. Tanveer, and M.N. Tahir. Designing, spectroscopic and structural characterization and evaluation of biological potential as well as molecular docking studies of Zn (II)-based metallo-pharmaceuticals. Journal of the Iranian Chemical Society 18(7): 1689-1702 (2021).
47. S. Hemalatha, J. Dharmaraja, S. Shobana, P. Subbaraj, T. Esakkidurai, and N. Raman. Chemical and pharmacological aspects of novel hetero MLB complexes derived from NO2 type Schiff base and N2 type 1,10-phenanthroline ligands. Journal of Saudi Chemical Society 24(1): 61-80 (2020).
48. A. Altaf, U. Hashmat, M. Yousaf, B. Lal, S. Ullah, A. Holder, and A. Badshah. Synthesis and characterization of azo-guanidine based alcoholic media naked eye DNA sensor. Royal Society Open Science 3: 160351 (2016).
49. S. Ullah, M. Sirajuddin, Z. Ullah, A. Mushtaq, S. Naz, M. Zubair, A. Haider, S. Ali, M. Kubicki, T.A. Wani, S. Zargar, and M.U. Rehman. Synthesis, Structural Elucidation and Pharmacological Applications of Cu(II) Heteroleptic Carboxylates. Pharmaceuticals 16(5): 693 (2023).
50. J.M. Kelly, A.B. Tossi, D.J. McConnell, and C. OhUigin. A study of the interactions of some polypyridylruthenium (II) complexes with DNA using fluorescence spectroscopy, topoisomerisation and thermal denaturation. Nucleic Acids Research 13(17): 6017-6034 (1985).
51. A. Tarushi, G. Psomas, C.P. Raptopoulou, and D.P. Kessissoglou. Zinc complexes of the antibacterial drug oxolinic acid: structure and DNA-binding properties. Journal of Inorganic Biochemistry 103(6): 898-905 (2009).
