Pseudotetrahedral Zn(II)-(R or S)-dihalogen-salicylaldiminato complexes with Λ- or Δ-chirality induction at-metal.

Reactions of enantiopure (S or R)-N-1-(phenyl)ethyl-2,4-X1,X2-salicylaldimine (S-H or R-H; X1, X2 = dihalogen) with Zn(II)-nitrate give bis[(S or R)-N-1-(phenyl)ethyl-2,4-X1,X2-salicylaldiminato-κ2N,O]-zinc(II), (Δ-ZnS or Λ-ZnR) with Δ/Λ-chirality induction at-metal in the C2-symmetric molecules. EI-mass spectra show parent ion peaks. X-ray structures indicate that two phenolate-oxygen and two imine-nitrogen atoms from two molecules of the Schiff bases coordinate to the Zn(II) ion in a pseudotetrahedral geometry. Structural analyses give evidence that the S- or R-ligand chirality gives only one diastereomer Δ-ZnS or Λ-ZnR in an enantiopure crystal. Gas-phase optimized structures suggest that the Δ-ZnS or Λ-ZnR diastereomers are slightly more stable than Λ-ZnS or Δ-ZnR by 1-2 kcal mol-1. The intramolecular interactions were analyzed with the Independent Gradient Model (IGM) using the program Multiwfn on the optimized structures and also indicate the diastereomeric preference of Δ-ZnS1 over Λ-ZnS1 (or Λ-ZnR1 over Δ-ZnR1). Variable time and temperature 1H NMR spectra support the presence of only one diastereomer Λ-ZnR or Δ-ZnS in the bulk samples, backed by the simulated spectra which exhibit no diastereomerization in solution. In contrast, the reported Zn(II)-(R or S)-salicylaldiminato/naphthaldiminato complexes show a diastereomeric mixture of both Δ- and Λ-forms and a Δ â‡„ Λ equilibrium in solution. Electronic circular dichroism (ECD) spectra in solution display expected mirror-image relationships for the (S or R)-Schiff base ligands and the (S or R)-ligated complexes. Combined analyses of experimental and simulated ECD spectra further support the notion of diastereomeric excess of Δ-ZnS or Λ-ZnR in solution. The overall results thus suggest the preservation of chirality at-zinc induced by S- or R-ligands in a solid or solution. Supramolecular packing analyses explore different kinds of intermolecular interactions with the strongest one for X⋯O. Only the halogen atom in the para position is involved in these interactions with Br⋯O > Cl⋯O. Hirshfeld surface analyses also support these interactions between two molecules at a distance shorter than the sum of the vdW radii. Comparison of the experimental and simulated PXRD patterns from the single-crystal X-ray structures shows a good matching and confirms the phase purity of the bulk samples.

Platinum(II) and Copper(II) complexes of asymmetric halogen-substituted [NN'O] ligands: Synthesis, characterization, structural investigations and antiproliferative activity.

In order to better understand the effect of structure, halogen substitution, metal ions and ligand flexibility on antiproliferative activity, eight Cu(II) complexes and eight Pt(II) complexes were obtained of 2,4-X1,X2-6-((pyridine-2-ylmethylamino)methyl)phenol and 2,4-X1,X2-6-((pyridine-2-ylmethylamino)ethyl)phenol (where X is Cl, Br, or I) ligands. The compounds were characterized with various techniques, such as FT-IR, NMR, elemental analysis and single-crystal X-ray diffraction (SCXRD). The X-ray structures showed that ligand acts as a bidentate and tridentate donor in Cu(II) and Pt(II) complexes, respectively. This difference in structures is due to the use or non-use of base in the preparation of complexes. Also, complexation of Cl2-H2L1 with CuCl2·2H2O gives two different types of structures: polymer (Cl2-H2L1-Cupolymer) and dimer (Cl2-H2L1-Cudimer), according to the crystal color. In addition, 1H NMR spectrum for platinum complexes display two set of signals that can be attributed to the presence of two isomers in solution. All complexes induced moderate to high reduction in A2780 and HCT116 cancer cell viability. However, only complexes bearing iodo- substituted in ligands exhibited significantly low cytotoxicity in normal fibroblasts when compared with cancer cell lines. The antiproliferative effect exhibited by I2-H2L2-Cu complex in A2780 cell line was due to induction of cell death mechanisms, namely by apoptosis and autophagy. I2-H2L2-Cu complex does not cause DNA cleavage but a slight delay in cell cycle was observed for the first 24 h of exposition. High cytotoxicity was related with the induction of intracellular ROS. This increase in intracellular ROS was not accompanied by destabilization of the mitochondrial membrane which is an indication that ROS are being triggered externally by I2-H2L2-Cu complex and in agreement with an extrinsic apoptosis activation. I2-H2L2-Cu complex has a pro-angiogenic effect, increasing the vascularization of the CAM in chicken embryos. This is also a very important characteristic in cancer treatment since the increased vascularization in tumors might facilitate the delivery of therapeutic drugs. Taken together, these results support the potential therapeutic of the I2-H2L2-Cu complex.

Cytotoxic oxidovanadium(IV) complexes of tridentate halogen-substituted Schiff bases: First dinuclear V(IV) complexes with O → VIV = O → VIV = O core.

The reaction of potentially N,N,O-tridentate Schiff base ligands, Cl-LH, Br-LH, BrCl-LH and H-LH, with [VIVO(acac)2] in 2:1 ratio in methanol gave the corresponding mononuclear and dinuclear oxidovanadium(IV) complexes, VO(Cl-L)2 (1), VO(Br-L)2 (2), [(BrCl-L)2(H2O)V(µ-O)VO(BrCl-L)2] (3) and [(H-L)2(H2O)V(µ -O)VO(H-L)2] (4), in good yields. The ligands and complexes were fully characterized by elemental analysis and FT-IR spectroscopy. The ligands were also characterized by 1H NMR spectroscopy. The oxidation state of V(IV)O with d1 configuration in all synthesized complexes was confirmed by EPR. Moreover, the structures of 2 and 3 were determined by X-ray diffraction (XRD) analysis which revealed them as mono- and dinuclear vanadium(IV) complexes, respectively, with the ligands coordinated as bidentate chelates. The structure of 3 represents the first example of dinuclear V(IV) complex with O â†’ VIV = O â†’ VIV = O core (Cambridge Structural Database (CSD)​, version 5.42, update of May 2021). The cytotoxicity of ligands and complexes was evaluated towards ovarian (A2780), breast (MCF7) and prostate (PC3) cancer cells at 48 h. While ligands showed modest IC50 values (>42 µM), all complexes turned out to be effective in the range 3.9-17.2 µM. In particular, A2780 and MCF7 cell lines were the most sensitive to the newly synthesized V(IV)O complexes.