Abstract
The novel macrocyclic ligands (N4MacL1-N4MacL3) and their Ru(II) complexes were synthesized by using 4-fulorobenzene-1,2-diamine, dicarboxylic acids (malonic acid, succinic acid, glutaric acid), and a 1:1 molar ratio of ligand to metal was used to create their metal complexes with the transition metals Ru (II). These metal complexes were identified using a variety of advanced methods, including, FTIR,1H-NMR, mass spectrophotometry, UV–Visible, PXRD, TGA and density functional theory (DFT) analysis. Kinetic and thermodynamic parameters were computed using the Coats-Redfern equations. Calculations based on molecular modelling (DFT) support the complexes' structural geometry. Synthesized macrocyclic compounds were tested for antimicrobial activity against bacterial strains B. subtilis, S. aureus, E. coli and K. pneumonia and fungal strains A. flavious and fusarium. When the ligands and their Ru(II) complexes were tested for their in vitro antimicrobial properties against some bacterial, fungal strains B. subtilis, S. aureus, E. coli, K. pneumonia and A. flavius, fusarium, respectively results revealed that the Ru(II) macrocyclic complexes were more effective against bacterial and fungal strains than tetraaza macrocyclic ligands (N4MacL1-N4MacL3). The antioxidant capacity of ligands and Ru(II) complexes were also assessed using the DPPH free radical test, with an IC50 range of 10.01–28.45 M. B. subtilis (PDB ID;5H67), S. aureus (PDB ID;3TY7), E. coli (PDB ID;3T88), K. pneumonia (PDB ID;6WII), and F. oxysporum (PDB ID;8EBB) proteins, were all subjected to docking studies using the AutoDock vina programme. Using the SRB test, the anticancer activity was assessed against four distinct cell lines HeLa, MCF-7, A549 and IMR-32. Comparing the ligands and complexes to the reference medication cis-platin revealed that it had far stronger cytotoxic effects. The research presented here proposes using these ligands in the creation of novel anticancer medications.
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References
H. Hrichi, N.A. Elkanzi, A.M. Ali, A. Abdou, Res. Chem. Intermed. 49(5), 2257–2276 (2023)
A.A.S. Al-Hamdani, W. Al-Zoubi, Spectrochim. Acta. Part A: Mole. Biomol. Spect. 75, 137 (2015)
M.A. Arafath, F. Adam, M.B.K. Ahamed, M.R. Karim, M.N. Uddin, B.M. Yamin, A. Abdou, J. Mol. Struct. 1278, 134887 (2023)
K. Babic-Samardžija, N. Hackerman, S.P. Sovilj, V.M. Jovanovic, J. Solid State Electrochem. 12, 155–163 (2008)
W. Sibert, A.H. Cory, J.G. Cory, J. Chem. Soc. Chem. Commun. 2, 154–155 (2002)
S.J. Paisey, P.J. Sadler, Chem. Commun. 3, 306–307 (2004)
X. Liang, J.A. Parkinson, M. Weishaulp, R.O. Gould, S.J. Paisey, H. Park, T.M. Hunter, C.A. Blindauer, S. Parsons, P.J. Sadler, J. Am. Chem. Soc. 124, 9105–9112 (2002)
C. Maxim, M. Badea, A.M. Rostas, M.C. Chifiriuc, G.G. Pircalabioru, S. Avram, R. Olar, Appl. Organomet. Chem. 36(1), e6471 (2022)
R.I. Maurer, P.J. Blower, J.R. Dilworth, C.A. Reynolds, Y. Zheng, G.E.D. Mullen, J. Med. Chem. 45, 1420–1431 (2002)
M.B. Ferrari, F. Bisceglie, G. Pelosi, M. Sassi, P. Tarasconi, M. Cornia, S. Capacchi, R. Albertini, S. Pinelli, J. Inorg. Biochem. 90, 113–126 (2002)
B.W. Harper, A.M. Krause-Heuer, M. P. Grant, M. Manohar, K.B. Garbutcheon Singh, J.R. Aldrich Wright, Chem. Eur. J, 16, 7064–7077 (2010)
N.J. Wheate, S. Walker, G.E. Craig, R. Oun, Dalton Trans 39, 8113–8127 (2010)
L. Breydo, V.N. Uversky, Metallomics 3, 1163–1180 (2011)
N.P.E. Barry, P.J. Sadler, Chem. Commun. 49, 5106–5131 (2013)
M. Claudel, J.V. Schwarte, K.M. Fromm, Chemistry 2, 849–899 (2020)
A.C. Munteanu, A. Notaro, M. Jakubaszek, J. Cowell, M. Tharaud, B. Goud, V. Uivarosi, G. Gasser, Inorg. Chem. 59, 4424–4434 (2020)
J.M. Rademaker-Lakhai, D. van den Bongard, D. Pluim, J.H. Beijnen, J.H.M. Schellens, Clin. Cancer Res. 10, 3717–3727 (2004)
S. Leijen, S.A. Burgers, P. Baas, D. Pluim, M. Tibben, E. Van Werkhoven, E. Alessio, G. Sava, J.H. Beijnen, J.H.M. Schellens, Invest. New Drugs 33, 201–214 (2015)
C.G. Hartinger, M.A. Jakupec, S. Zorbas-Seifried, M. Groessl, A. Egger, W. Berger, H. Zorbas, P.J. Dyson, B.K. Keppler, Chem. Biodivers. 5, 2140–2155 (2008)
F. Lentz, A. Drescher, A. Lindauer, M. Henke, R.A. Hilger, C.G. Hartinger, M.E. Scheulen, C. Dittrich, B.K. Keppler, U. Jaehde, Anticancer. Drugs 20, 97–103 (2009)
R. Trondl, P. Heffeter, C.R. Kowol, M.A. Jakupec, W. Berger, B.K. Keppler, Chem. Sci. 5, 2925–2932 (2014)
S. Monro, K.L. Colón, H. Yin, J. Roque, P. Konda, S. Gujar, R.P. Thummel, L. Lilge, C.G. Cameron, S.A. McFarland, Chem. Rev. 119, 797–828 (2019)
F. Li, G. Collins, F.R. Keene, Chem. Soc. Rev. 44, 2529–2542 (2015)
H.M. Southam, J.A. Butler, J.A. Chapman, R.K. Poole, Adv. Microb. Physiol. 71, 1–96 (2017)
G. Amariei, V. Kokol, K. Boltes, P. Letón, R. Rosal, RSC Adv. 8, 28013–28023 (2018)
Subhash, A. Chaudhary, Jyoti, M. Kumar, & R. Solanki, J. Iran Chem. Soc., 20, 2339–2362, (2023)
S. Rani, S. Kumar, S. Chandra, Chemistry 40(10), 940–946 (2010)
A.D. Becke, J. Chem. Phys. 98, 5648 (1993)
P. Sharma, A. Gupta, K. Rao, F.J. Owens, R. Sharma, R. Ahuja, J.O. Guillen, B. Johansson, G. Gehring, Nat. Mater. 2, 673 (2003)
T. Yousef, G.A. El-Reash, O. El-Gammal, R. Bedier, J. Mol. Struct. 1029, 149 (2012)
T. Govindasami, A. Pandey, N. Palanivelu, A. Pandey, Int. J. Org. Chem. 1, 71 (2011)
W.H. El-Shwiniy, W.S. Shehab, W.A. Zordok, J. Mol. Struct. 1199, 126993 (2020)
M.S. Blois, Nature 181, 1199 (1958)
V. Vichai, K. Kirtikara, Nat. Protoc. 1, 1112 (2006)
A. Subhash, Chaudhary, Mamta and Jyoti. Chem. Pap. 77, 5059–5078 (2023)
S.S. Kandil, G.B. El-Hefnawy, E.A. Baker, Thermochim. Acta 414, 105 (2004)
A. Braca, N. De Tommasi, L. Di Bari, C. Pizza, M. Politi, I. Morelli, J. Nat. Prod. 64, 892–895 (2001)
G.A. Giffin, A. Moretti, S. Jeong, S. Passerini, J. Phys. Chem. C 118, 9966 (2014)
L. Kathawate, P.V. Joshi, T.K. Dash, S. Pal, M. Nikalje, T. Weyhermüller, S. Salunke-Gawali, S. J. Mol. Struct. 1075, 397–405 (2014)
A.A. Osowole, A.C. Ekennia, O.O. Olubiyi, M. Olagunju, Res. Chem. Intermed. 43, 2555 (2016)
N. Feizi, R.V. Pinjari, S. Gejji, F. Sayyed, R. Gonnade, S.Y. Rane, J. Mol. Struct. 966, 144 (2010)
S. Jyothi, K. Sreedhar, D. Nagavaju, S.J. Swamy, Can Chem Trans. 3, 368 (2015)
M. Tyagi, S. Chandra, Open. J. Inorg. Chem. 2, 41 (2012)
H.N. Prasad, H.M. Manukumar, C.S. Karthik, L. Mallesha, P. Mallu, Bioorg. Med. Chem. 27(5), 841–850 (2019)
A.B.P. Lever, Inorganic Electronic Spectroscopy, 2nd edn. (Elsevier, New York, 1984)
M.G. Bhowon, H.L.K. Wah, R. Narain, Polyhedron 18, 341 (1999)
A. Hudak, A. Kosturiak, J. Therm. Anal. Calori. 58, 579 (1999)
S. Materazzi, G.D. Ascenzo, S. Aquili, K.M. Kadish, J.L. Bear, Thermochim. Acta 397, 129 (2003)
O.A. El-Gammal, G.A. El-Reash, R.A. Bedier, Appl. Organomet. Chem. 33(10), e5141 (2019)
W. Coats, J.P. Redfern, Nature 201, 68 (1964)
Subhash, Jyoti & A. Chaudhary, Res Chem Intermed. 8(49), (2023)
T. Hatakeyama, F. Quinn, Thermal Analysis: Fundamentals and Applications to Polymer Science (John Wiley, Chichester, 1994)
J.W. Moore, R.G. Pearson, A.A. Frost, Kinetics and Mechanism (Wiley, New york, 1961)
L.H. Abdel-Rahman, R.M. El-Khatib, L.A.E. Nassr, A.M. AbuDief, J. Mol. Struct. 1040, 9–18 (2013)
V. Pushpanathan, S.S.J. Dhas, D.S. Kumar, Bull. Mater. Sci. 44, 1–12 (2021)
Y. A. Alghuwainem, H. M. Abd El-Lateef, M. M. Khalaf, A. A. Abdelhamid, A. Alfarsi, M. Gouda, & A. Abdou, J. Mol. Liq., 369, 120936, (2023)
M. Kumar, P.J. Darolia, S. Chauhan, M. Sindhu, K.K. Verma, S. Garg, ChemistrySelect 6(23), 5778–5790 (2021)
D.A. Filimonov, A.A. Lagunin, T.A. Gloriozova, A.V. Rudik, D.S. Druzhilovskii, P.V. Pogodin, V.V. Poroikov, Chem. Heterocycl. Compd. 50(3), 444–457 (2014)
M. A. I. Al-Gaber, H. M. Abd El-Lateef, M. M. Khalaf, S. Shaaban, M. Shawky, G. G. Mohamed, & A. M. Abu-Dief, Materials, 16(3), 897, (2023)
M.S. Hossain, K.A. Khushy, M.A. Latif, M.F. Hossen, M.A. Asraf, M. Kudrat-E-Zahan, A. Abdou, Russ. J. Gen. Chem. 92(12), 2723–2733 (2022)
M.A. Latif, T. Ahmed, M.S. Hossain, B.M. Chaki, A. Abdou, M. Kudrat-E-Zahan, Russ. J. Gen. Chem. 93(2), 389–397 (2023)
J. Haribabu, G.R. Subhashree, S. Saranya, K. Gomathi, R. Karvembu, D. Gayathri, J. Mol. Struct. 1094, 281 (2015)
H.N. Prasad, A.P. Ananda, T.N. Lohith, P. Prabhuprasad, H.S. Jayanth, N.B. Krishnamurthy, P. Mallu, J. Mol. Struct. 1247, 131333 (2022)
Subhash, A. Chaudhary, Jyoti, M. Kumar, N. Kumar, & N. K. Agarwal, J. Chem. Sci., 134(4), 113, (2022)
H.N. Prasad, A.P. Ananda, S. Sumathi, K. Swathi, K.J. Rakesh, H.S. Jayanth, P. Mallu, J. Mol. Struct. 1268, 133683 (2022)
Acknowledgements
The author (Subhash) is highly thankful to the University Grants Commission, New Delhi, India for financial assistance in the form of a Junior Research Fellowship (NTA Ref. No. 92, CSIR-UGC NET DECEMBER, 2018). The authors gratefully acknowledge DST-FIST programme 2017 (final proposal no. SR/FST/CS-I/2017/12(C) dated 10.5.2018, Department of Chemistry, Kurukshetra University, Kurukshetra) for providing financial support in form of NMR spectral studies. I am also thankful to Dr. Manish Kumar, Maharshi Dayanand University, Rohtak for his goodwill and expert guidance.
Funding
The author (Subhash) is highly thankful to the University Grants Commission, New Delhi, India for financial assistance in the form of a Junior Research Fellowship (NTA Ref. No. 92, CSIR-UGC NET DECEMBER, 2018).
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The idea was suggested by S and AC. The experimental section was performed by J and AP. Interpretation of data, preparing of the manuscript and its editing were performed by S. All authors reviewed the manuscript.
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Subhash, Jyoti, Phor, A. et al. Synthesis, Structural Elucidation, Cytotoxic, Antimicrobial, Antioxidant, Density Functional Theory and Molecular Docking Studies of Mononuclear Ru(II) Complexes of N4O4-Bearing Macrocyclic Ligands. J Inorg Organomet Polym 34, 827–847 (2024). https://doi.org/10.1007/s10904-023-02862-y
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DOI: https://doi.org/10.1007/s10904-023-02862-y