Three enantiomeric pairs consisting of copper(II) complexes with tridentate Schiff bases have been synthesized for employing in biological assessments: 1∞[Cu₂(R/S-salmet)₂(H₂O)] (1-R/S·H2O), 1∞[Cu(R/S-3-HOMe-5-Me-salmet)] (2-R/S), and 1∞[Cu(R/S-3-MeO-salmet)] (3-R/S) (where R/S-salmetH₂, R/S-3-HOMe-5-Me-salmetH₂, and R/S-3-MeO-salmetH₂ result from the condensation of R/S-methionine with salicylaldehyde, 2-hydroxy-3-(hydroxymethyl)-5-methylbenzaldehyde, and 3-methoxy-salicylaldehyde, respectively, in a 1 : 1 molar ratio). The crystal structures of 1-R·H2O and 2-R/S are reported. Moreover, the 1-R/S·H2O enantiomers have been subjected to a single-crystal-to-single-crystal (SC-SC) transformation by heating at 160 °C to afford their dehydrated forms, 1∞[Cu₂(R/S-salmet)₂] (1-R/S), whose structures have also been crystallographically determined. The coordination polyhedra of the metal centers, the binding modes of the ligands, and the 1-D double chain assemblies generated by the chiral mononuclear units are comparatively described. The diffuse reflectance UV-Vis and circular dichroism (CD) spectra of compounds 1-R/S·H2O, 1-R/S, and 2-R/S are analysed with respect to their structural peculiarities and compared to those of 3-R/S. The UV-Vis and CD spectra of solutions of 1-R/S, 2-R/S, and 3-R/S point to the collapse of the double chains via dissolution. Biological tests performed on the model eukaryote Saccharomyces cerevisiae indicated low toxicity for 1-R/S, 2-R/S, and 3-R, and moderate toxicity for 3-S. The S-type complexes were accumulated by cells in higher quantity compared to their R-type counterparts due to selective transport via the high-affinity S-methionine transporter, Mup1. A chemogenomic analysis of 3-S toxicity performed on a collection of yeast knockout mutants revealed that most of the deleted genes identified in the screen were involved in the cell response to oxidative stress, calcium-mediated response, or metal homeostasis. Altogether, it was concluded that 3-S accumulation may perturb the redox state of the cell, also interfering with the calcium-mediated response to oxidative stress or metal-related oxidative stress.

• PMID: 36250294
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Journal Article

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Maxim C, Ene CD, Nicolau I, Ruta LL, Farcasanu IC

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