RESUMEN

A series of novel organogermanium(IV) catecholates 1-9 of the general formula R'2Ge(Cat), where R' = Ph, Et, have been synthesized. Compounds were characterized by 1H, 13C NMR, IR spectroscopy, and elemental analysis. The molecular structures of 1-3, 6, and 8 in crystal state were established using single-crystal X-ray analysis. The complexes are tetracoordinate germanium(IV) compounds containing a dioxolene ligand in a dianion (catecholato) form. Electrochemical transformations of target germanium(IV) complexes have been studied by cyclic voltammetry. The electro-oxidation mechanism of complexes 1-5, 7, and 10 (the related complex Ph2Ge(3,5-Cat) where 3,5-Cat is 3,5-di-tert-butylcatecholate) involves the consecutive formation of mono- and dicationic derivatives containing the oxidized forms of redox-active ligands. The stability of the generated monocations depends both on the hydrocarbon groups at the germanium atom and on the substituents in the catecholate ring. Compounds 6, 8, and 9 are oxidized irreversibly under the electrochemical conditions with the formation of unstable complexes. The radical scavenging activity and antioxidant properties of new complexes were estimated in the reaction with DPPH radical, ABTS radical cation, and CUPRACTEAC assay. It has been found that compounds 8 and 9 with benzothiazole or phenol fragments are more active in DPPH test. The presence of electron-rich moieties in the catecholate ligand makes complexes 5 and 7-9 more reactive to ABTS radical cation. The value of CUPRACTEAC for organogermanium(IV) catecholates varies from 0.23 to 1.45. The effect of compounds 1-9 in the process of lipid peroxidation of rat liver (Wistar) homogenate was determined in vitro. It was found that most compounds are characterized by pronounced antioxidant activity. A feature of complexes 1, 3, and 5-9 is the intensification of the antioxidant action with the incubation time. In the presence of additives of complexes 3, 5, 6, and 8, an induction period was observed during the process of lipid peroxidation.

Asunto(s)

Antioxidantes , Catecoles , Germanio , Antioxidantes/química , Antioxidantes/farmacología , Antioxidantes/síntesis química , Catecoles/química , Catecoles/farmacología , Animales , Germanio/química , Oxidación-Reducción , Complejos de Coordinación/química , Complejos de Coordinación/farmacología , Complejos de Coordinación/síntesis química , Ratas , Técnicas Electroquímicas , Cristalografía por Rayos X , Estructura Molecular

RESUMEN

A number of novel di- and triorganotin(IV) complexes 1-5 (Ph2SnL1, Ph2SnL2, Et2SnL2, Ph3SnL3, Ph3SnL4) with mono- or dianionic forms of thio-Schiff bases containing antioxidant sterically hindered phenol or catechol fragments were synthesized. Compounds 1-5 were characterized by 1H, 13C NMR, IR spectroscopy, and elemental analysis. The molecular structures of complexes 1 and 2 in the crystal state were established by single-crystal X-ray analysis. The antioxidant activity of new complexes as radical scavengers was estimated in DPPH and ABTS assays. It was found that compounds 4 and 5 with free phenol or catechol fragments are more active in these tests than complexes 1-3 with tridentate O,N,S-coordinated ligands. The effect of compounds 1-5 on the promoted oxidative damage of the DNA by 2,2'-azobis(2-amidinopropane) dihydrochloride and in the process of rat liver (Wistar) homogenate lipid peroxidation in vitro was determined. Complexes 4 and 5 were characterized by more pronounced antioxidant activity in the reaction of lipid peroxidation in vitro than compounds 1-3. The antiproliferative activity of compounds 1-5 was investigated against MCF-7, HTC-116, and A-549 cell lines by an MTT test. The values of IC50 are significantly affected by the presence of free antioxidant fragments and the coordination site for binding.

Asunto(s)

Complejos de Coordinación , Compuestos Orgánicos de Estaño , Ratas , Animales , Antioxidantes/farmacología , Fenol , Bases de Schiff/química , Ratas Wistar , Compuestos Orgánicos de Estaño/química , Fenoles/farmacología , Catecoles/farmacología , Complejos de Coordinación/química , Ligandos

RESUMEN

New complexes of zinc(ii) and copper(ii) with 2-furoic acid (Hfur), acetic acids and N-donor ligands with the compositions [Zn2(fur)4] n (1), [Zn2(fur)4(NH2py)2] (2, NH2py = 3-aminopyridine), [Zn(fur)2(neoc)] (3, neoc = 2,9-dimethyl-1,10-phenantroline), [Zn(OAc)2(neoc)] (4, OAc = acetat-anion), and [Cu(fur)2(neoc)(H2O)] (5) were synthesized. The structures of the compounds were established by single crystal X-ray diffraction analysis. Complexes 1 and 2 are binuclear; whereas 3-5 are mononuclear. The stabilization of supramolecular architectures in crystals for compounds 1-5 occurs due to π-π-bonding between heterocycles and hydrogen interactions that provide good solubility in aqueous solutions. The stability of the complexes upon dissolution in 5% dextrose and 0.9% NaCl was confirmed by UV-vis spectroscopic and NMR (1H) data. The study of in vitro biological activity was carried out against the non-pathogenic strain of Mycolicibacterium smegmatis that is a model for M. tuberculosis. The synergistic effect of ligands is observed for complexes 3-5 and is characterized by an increase in the biological activity values. On passage from Zn2+ to Cu2+ complexes, the biological activity increases and the maximum effect is observed for compound [Cu(fur)2(phen)]. Analysis of the transcriptomic profiles of the M. smegmatis mc 2 155 strain under the pressure of the copper complex [Cu(fur)2(phen)] made it possible to isolate 185 genes, one quarter of which are associated with the compensation of iron deficiency in the bacterial strain. Genes associated with the transport and metabolism of heavy metals, biosynthesis of fatty and amino acids, biodegradation and transport of urea were also isolated.