Copper is an important micronutrient, and it is present in some protein structures, as well as participate in several important biological processes. Due to its importance, some ligands are used and studied like carriers of copper in the biological systems. This work has investigated the affinity of CuII by three ligands of biological interest: N, N, N, N’-tetrakis (2-pyridilmethyl) ethylenediamine (TPEN), triethylenetetramine (TRIEN), and diethyldithiocarbamate (Et2DTC), used for this purpose. The studies were performed by evaluating the CuII d-d band when complexed with these three ligands. The CuII d-d band in aqueous solution appears around 800 nm; when in the presence of TRIEN, this band displaces to 576 nm. TRIEN ligand is substituted by TPEN ligand (d-d band at 689 nm), and finally, in the presence of the Et2DTC ligand, the d-d band displaces to 665 nm. Theoretical calculations were used to obtain the binding energy and the values obtained were −481.85 kcal mol−1 for the CuII-TPEN, −417.80 kcal mol−1 for CuII-TRIEN and −726.72 kcal mol−1 for CuII-Et2DTC. Electrochemical studies showed an oxidation peak at 0.008 V to CuII-TRIEN complex, −0.135 V to CuII-TPEN and 0.150 V to CuII-Et2DTC. These results showed that CuII has a higher affinity by the Et2DTC ligand compared to the other ligands studied.

Oxidative stress is the result of an imbalance between oxidant and antioxidant species, with predominance of oxidative species with harmful action of reactive oxygen species (ROS) and reactive nitrogen species (RNS) on cells. Changes in the levels of nitric oxide (NO•) can be the cause and/ or a result of various pathophysiological processes. The main objective of this review is to address the relationship between oxidative stress and atherosclerosis in order to better understand the main features of this disease.

O dano ao DNA induzido por S(IV) na presença de alguns complexos de Cu(II) em soluções saturadas com ar foi investigado. A adição de S(IV) a uma solução saturada com ar contendo CuII GGA (GGA = glicilglicil-L-alanina), CuII G3 (G3 = triglicina) ou CuII G4 (G4 = tetraglicina) e traços de Ni(II) origina a formação rápida do respectivo complexo de Cu(III), com o simultâneo consumo de oxigênio e a oxidação de S(IV). SO3•- e HO• foram detectados por experimentos de EPR-spin trapping. As quebras das fitas de DNA foram atribuídas aos radicais de óxido de enxofre formados. Na redução de Cu(II)/BCA (BCA = 4,4' dicarboxi-2-2'-biquinolina) por S(IV), com a formação do complexo CuI BCA, há a possível formação de um radical centrado em carbono do BCA ou um radical peróxido (ROO•), capazes de oxidar as bases de DNA. A intensidade do dano ao DNA na presença desses complexos de Cu(II) e S(IV) (10-300 µmol L-1) seguiu a ordem: CuII BCA ∼ CuII G4 ∼ Cu(II) (adicionado como Cu(NO3)2) > CuII G3 ∼ CuII GGA. Especialmente para o CuII BCA, o dano ocorreu mesmo em concentrações baixas de S(IV) (0,1 µmol L-1). Para os complexos de Cu(II) com glicilglicilhistidina, glicilhistidilglicina, glicilhistidillisina e glicilgliciltirosilarginina a formação de Cu(III) e o dano do DNA não foram observados.

The DNA damage induced by S(IV) in the presence of some Cu(II) complexes in air saturated solution was investigated. The addition of S(IV) to an air saturated solution containing CuII GGA (GGA = glycylglycyl-L-alanine), CuII G3 (G3 = triglycine) or CuII G4 (G4 = tetraglycine) and Ni(II) traces, causes rapid formation of the respective Cu(III) complex, with simultaneous O2 uptake and S(IV) oxidation. SO3•- and HO• were detected by EPR-spin trapping experiments. The DNA strand breaks were attributed to the oxysulfur radicals formed. In the reduction of Cu(II)/BCA (BCA = 4,4' dicarboxy-2-2'-biquinoline) by S(IV), with CuI BCA complex formation, there is the possible formation of carbon centered radical of BCA or peroxyl radical (ROO•) capable of oxidizing DNA bases. The intensity of DNA damage in the presence of these Cu(II) complexes and S(IV) (10-300 µmol L-1) followed the order: CuII BCA ∼ CuII G4 ∼ Cu(II) (added as Cu(NO3)2) > CuII G3 ∼ CuII GGA. Specifically for CuII BCA the damage occurred even at lower S(IV) concentration (0.1 µmol L-1). For the Cu(II) complexes with glycylglycylhistidine, glycylhistidylglycine, glycylhistidyllysine and glycylglycyltyrosylarginine the Cu(III) formation and the DNA damage was not observed.

Oxindóis são compostos endógenos encontrados em fluidos e tecidos de mamíferos. Particularmente, isatina (1H-indol-2,3-diona) e seus derivados vêm mostrando uma grande variedade de efeitos no meio biológico, incluindo a inibição de monoamina oxidase, atividade bactericida, fungicida, antiviral e antiproliferativa. Pesquisas mais recentes descrevem estes compostos como inibidores de quinases, uma classe de proteínas envolvidas em várias etapas do ciclo celular. Nesta revisão, complexos de cobre(II) com ligantes derivados de oxindóis são discutidos como potenciais agentes antitumorais, em comparação com outros complexos, com base na proposição de se aliar as propriedades redox e coordenativas do metal à capacidade de afetar os processos de angiogenese e apoptose já demonstrada por esse tipo de ligante.

Oxindoles are endogenous compounds found in mammalian body fluids and tissues. Particularly, isatin (1H-indole-2,3-dione) and its derivatives have shown a variety of biological effects, including inhibition of monoamine oxidase, antibacterial, antifungal, antiviral and antiproliferative activities. Recent reports have described these compounds as efficient inhibitors of kinases, a class of proteins involved in many steps of the cellular cycle. Here, some copper(II) complexes with oxindole-derived ligands are discussed as potential antitumoral agents, in comparison to other complexes, based on the proposal of a synergistic effect on adding the metal coordinating and redox properties to the already demonstrated capability of these ligands to influence the angiogenesis and apoptosis processes.