Solution Equilibrium Studies on Salicylidene Aminoguanidine Schiff Base Metal Complexes: Impact of the Hybridization with L-Proline on Stability, Redox Activity and Cytotoxicity

Abstract

The proton dissociation processes of two tridentate salicylidene aminoguanidine Schiff bases (SISC, Pro-SISC-Me), the solution stability and electrochemical properties of their Cu(II), Fe(II) and Fe(III) complexes were characterized using pH-potentiometry, cyclic voltammetry and UV-visible, 1H NMR and electron paramagnetic resonance spectroscopic methods. The structure of the proline derivative (Pro-SISC-Me) was determined by X-ray crystallography. The conjugation of L-proline to the simplest salicylidene aminoguanidine Schiff base (SISC) increased the water solubility due to its zwitterionic structure in a wide pH range. The formation of mono complexes with both ligands was found in the case of Cu(II) and Fe(II), while bis complexes were also formed with Fe(III). In the complexes these tridentate ligands coordinate via the phenolato O, azomethine N and the amidine N, except the complex [Fe(III)L2]+ of Pro-SISC-Me in which the (O,N) donor atoms of the proline moiety are coordinated beside the phenolato O, confirmed by single crystal X-ray crystallographic analysis. This binding mode yielded a stronger Fe(III) preference for Pro-SISC-Me over Fe(II) in comparison to SISC. This finding is also reflected in the lower redox potential value of the iron-Pro-SISC-Me complexes. The ligands alone were not cytotoxic against human colon cancer cell lines, while complexation of SISC with Cu(II) resulted in moderate activity, unlike the case of its more hydrophilic counterpart.

The Release of a Highly Cytotoxic Paullone Bearing a TEMPO Free Radical from the HSA Hydrogel: An EPR Spectroscopic Characterization

“…The cell culture plastic was obtained from Sarstedt (Nümbrecht, Germany). The human Colo 205 cells were cultured as described in our previous work using Roswell Park Memorial Institute (RPMI) 1640 medium [66]. HL was dissolved in DMSO using 10 mM concentration, and the DMSO content was always lower than 1% (v/v) in the final samples.…”

Comparative Solution Equilibrium Studies on Anticancer Estradiol-Based Conjugates and Their Copper Complexes

“…The anisotropic g-tensor and A coupling constants obtained from the EPR spectra recorded at 77 K (Figure 9a) are shown in Table S2 together with the EPR parameters of the Cu(II) complexes of DMAP and other ligand-bearing (N,N,O) donor sets. The EPR parameters of the isolated DMA-E2 and PMA-E2 complexes are very similar to those of the [CuL] + complex of DMAP and the complexes of salicylaldehyde (2-(2-hydroxybenzylidene)hydrazinecarboximidamide (SISC) [36], (E)-2-((3-aminopyridin-2-yl)methylene)hydrazinecarboxamide (oxo-triapine) [37], and the L-phenylalanine derivatives of cis/trans-2-aminocyclohexanecarboxylic acid (c/tACHC) [38]. Based on this similarity, the (N,N,O) coordination mode was proposed for the isolated DMA-E2 and PMA-E2 complexes.…”

“…The following supporting information can be downloaded at: https:// www.mdpi.com/article/10.3390/inorganics12020049/s1; Figures S1-S8: 1 H and 13 C NMR spectra of PMAP, DMAP, PMA-E2, and DMA-E2; Figure S9 S1: Electrochemical data for the Cu(II)-DMAP/DMA-E2/PMAP systems; Table S2: Anisotropic EPR parameters of complexes for comparison. References [36][37][38] are cited in the supplementary materials.…”

A Review of the Biological Activity of Amidrazone Derivatives

“…Cu(II) complex 90 showed antiproliferative activity against the Colo-205 adenocarcinoma cell line and low toxicity to MRC-5 human lung fibroblasts [ 86 ]. Another Cu(II) complex, 91 , at concentration 100 µg/mL, showed a similar (almost total) antiproliferative activity to cisplatin against colon CX-1 and colon SW-948 cancer and epidermal A431 cell lines but was about 12-fold less toxic than the reference drug [ 49 ].…”