2. Academic Validation
  3. Investigating the Cytotoxicity of Ru(II) Polypyridyl Complexes by Changing the Electronic Structure of Salicylaldehyde Ligands

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

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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