Investigating the Cytotoxicity of Ru(II) Polypyridyl Complexes by Changing the Electronic Structure of Salicylaldehyde Ligands

  • Inorg Chem. 2024 Jan 15;63(2):1083-1101. doi: 10.1021/acs.inorgchem.3c03414.
Maryam Taghizadeh Shool  1 ,  Hadi Amiri Rudbari  1 ,  José V Cuevas-Vicario  2 ,  Andrea Rodríguez-Rubio  2 ,  Claudio Stagno  3 ,  Nunzio Iraci  3 ,  Thomas Efferth  4 ,  Ejlal A Omer  4 ,  Tanja Schirmeister  5 ,  Olivier Blacque  6 ,  Nakisa Moini  7 ,  Esmail Sheibani  1 ,  Nicola Micale  3
Affiliations
  • 1. Department of Chemistry, University of Isfahan, 81746-73441 Isfahan, Iran.
  • 2. Departamento de Química, Facultad de Ciencias, Universidad de Burgos, Plaza Misael Bañuelos s/n, 09001 Burgos, Spain.
  • 3. Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres 31, I-98166 Messina, Italy.
  • 4. Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany.
  • 5. Department of Medicinal Chemistry, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany.
  • 6. Department of Chemistry, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
  • 7. Department of Chemistry, Faculty Chemistry, Alzahra University, Vanak, P.O. Box 1993891176, 1993891176 Tehran, Iran.
PMID: 38156413 DOI: 10.1021/acs.inorgchem.3c03414
Abstract

A novel class of Ru(II)-based polypyridyl complexes with an auxiliary salicylaldehyde ligand [Ru(phen)2(X-Sal)]BF4 {X: H (1), 5-Cl (2), 5-Br (3), 3,5-Cl2 (4), 3,5-Br2 (5), 3-Br,5-Cl (6), 3,5-I2 (7), 5-NO2 (8), 5-Me (9), 4-Me (10), 4-OMe (11), and 4-DEA (12), has been synthesized and characterized by elemental analysis, FT-IR, and 1H/13C NMR spectroscopy. The molecular structure of 4, 6, 9, 10, and 11 was determined by single-crystal X-ray diffraction analysis which revealed structural similarities. DFT and TD-DFT calculations showed that they also possess similar electronic structures. Absorption/emission spectra were recorded for 2, 3, 10, and 11. All Ru-complexes, unlike the pure ligands and the complex lacking the salicylaldehyde component, displayed outstanding antiproliferative activity in the screening test (10 μM) against CCRF-CEM leukemia cells underlining the crucial role of the presence of the auxiliary ligand for the biological activity. The two most active derivatives, namely 7 and 10, were selected for continuous assays showing IC50 values in the submicromolar and micromolar range against drug-sensitive CCRF-CEM and multidrug-resistant CEM/ADR5000 leukemia cells, respectively. These two compounds were investigated in silico for their potential binding to duplex DNA well-matched and mismatched base pairs, since they showed remarkable selectivity indexes (2.2 and 19.5 respectively) on PBMC cells.

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