Interaction of Melanin with Metal Ions Modulates Their Cytotoxic Potential

Melanin is one the most common biological pigments. In humans, specialized cells called melanocytes synthesize the pigment from tyrosine and 3,4-dihydroxyphenylalanine via enzyme-catalyzed reactions and spontaneous processes. The formed melanin granule consists of nanoaggregates of oligomers containing different monomers. Although the main biological function of melanin is protection against damage from solar radiation, melanin may also be involved in protection against oxidative stress. In the latter function, sequestration of redox-active metal ions and scavenging of reactive oxygen species are of importance. The paper reviews basic physicochemical properties of melanin responsible for binding of metal ions and discusses specific conditions that may induce cytotoxicity of metal ions such as iron and copper by facilitating their redox activation and release from melanin. While the value of EPR spectroscopy and other EPR-related techniques for the study of melanin is emphasized, the concomitant use of other physicochemical methods is the most efficient approach.

Antioxidant Synergy of Mitochondrial Phospholipase PNPLA8/iPLA2γ with Fatty Acid–Conducting SLC25 Gene Family Transporters

Patatin-like phospholipase domain-containing protein PNPLA8, also termed Ca2+-independent phospholipase A2γ (iPLA2γ), is addressed to the mitochondrial matrix (or peroxisomes), where it may manifest its unique activity to cleave phospholipid side-chains from both sn-1 and sn-2 positions, consequently releasing either saturated or unsaturated fatty acids (FAs), including oxidized FAs. Moreover, iPLA2γ is directly stimulated by H2O2 and, hence, is activated by redox signaling or oxidative stress. This redox activation permits the antioxidant synergy with mitochondrial uncoupling proteins (UCPs) or other SLC25 mitochondrial carrier family members by FA-mediated protonophoretic activity, termed mild uncoupling, that leads to diminishing of mitochondrial superoxide formation. This mechanism allows for the maintenance of the steady-state redox status of the cell. Besides the antioxidant role, we review the relations of iPLA2γ to lipid peroxidation since iPLA2γ is alternatively activated by cardiolipin hydroperoxides and hypothetically by structural alterations of lipid bilayer due to lipid peroxidation. Other iPLA2γ roles include the remodeling of mitochondrial (or peroxisomal) membranes and the generation of specific lipid second messengers. Thus, for example, during FA β-oxidation in pancreatic β-cells, H2O2-activated iPLA2γ supplies the GPR40 metabotropic FA receptor to amplify FA-stimulated insulin secretion. Cytoprotective roles of iPLA2γ in the heart and brain are also discussed.

Enhancing The Photocatalytic Conversion Of Pt(IV) Substrates By Flavoprotein Engineering

Our recent work demonstrates that certain flavoproteins can catalyze the redox activation of Pt(IV) prodrug complexes under light irradiation. Herein, we used site directed mutagenesis on the mini Singlet Oxygen Generator (mSOG) to modulate the photocatalytic activity of this flavoprotein towards two model Pt(IV) substrates. Among the prepared mutants, Q103V mSOG displayed enhanced catalytic efficiency as a result of its longer triplet excited state lifetime. This study shows, for the first time, that protein engineering can improve the catalytic capacity of a protein towards metal-containing substrate.

Enhancing The Photocatalytic Conversion Of Pt(IV) Substrates By Flavoprotein Engineering

Our recent work demonstrates that certain flavoproteins can catalyze the redox activation of Pt(IV) prodrug complexes under light irradiation. Herein, we used site directed mutagenesis on the mini Singlet Oxygen Generator (mSOG) to modulate the photocatalytic activity of this flavoprotein towards two model Pt(IV) substrates. Among the prepared mutants, Q103V mSOG displayed enhanced catalytic efficiency as a result of its longer triplet excited state lifetime. This study shows, for the first time, that protein engineering can improve the catalytic capacity of a protein towards metal-containing substrate.

Steering the methanol steam reforming reactivity of intermetallic Cu–In compounds by redox activation: stability vs. formation of an intermetallic compound–oxide interface

To compare the properties of intermetallic compounds and intermetallic compound–oxide interfaces, Cu–In was used as a model to correlate stability limits, self-activation and redox activation with the inherent methanol steam reforming performance.

Activation by oxidation and ligand exchange in a molecular manganese vanadium oxide water oxidation catalyst

Combined theoretical and experimental studies shed light on the initial steps of redox-activation of a molecular manganese vanadium oxide water oxidation catalyst.

The Development of New Methods of Disposal of Processing Sulfur Wastes from a Hydro-carbon Feedstock to various Sulfur Derivatives

The tendency to reduce the content of sulfur compounds in particular H2S and low molecular thiols (RSH) in oil products sets the task of their extraction and disposal in order to obtain practically useful sulfur compounds. Hydrogen sulfide and thiols can be extracted from hydrocarbon fractions using N-methylpyrrolidone-as selective solvent. Hydrogen sulfide can be extracted from the residual oil products using a low energy exposure such as ultrasound and a constant magnetic field. The releasing gas is concentrated in N-methylpyrrolidone. Further, hydrogen sulfide and mercaptans can be used in the chemical synthesis of biologically active thioethers containing a catechol fragment. Another way of H2S and RSH utilization is the chemical adsorption of acidic components by modified polynuclear pivalate (acetate) zinc(II) silica gel. As a result of the interaction of complexes with H2S and RSH, it is possible to obtain zinc sulfide or zinc thiolates, which can be used in various fields of industry or agriculture. Hydrogen sulfide and thiols can also be applied in the electrochemical or microvaved assisted organic synthesis. This approach is promising from the standpoint of environmental safety of synthesis and low energy costs of the reactions. The SH-functionalization of hydrocarbons (indan, indene, decalin, tetralin, naphthalene and 1,2-dihydronaphthalene) leads to obtain biologically active compounds. Keywords: hydrogen sulfide, thiols, extraction, N-methylpyrrolidone, ultrasonic and magnetic treatment, microwave, redox activation

Oxidation of Erythrocytes Enhance the Production of Reactive Species in the Presence of Artemisinins

In red blood cells, hemoglobin iron represents the most plausible candidate to catalyze artemisinin activation but the limited reactivity of iron bound to hemoglobin does not play in favor for its direct involvement. Denatured hemoglobin appears a more likely candidate for artemisinin redox activation because it is expected to contain reactive iron and it has been described to release free heme and/or iron in erythrocyte. The aim of our study is to investigate, using three different methods: fluorescence, electron paramagnetic resonance and liquid chromatography coupled to mass spectrometry, how increasing the level of accessible iron into the red blood cells can enhance the reactive oxygen species (ROS) production derived from artemisinin. The over-increase of iron was achieved using phenylhydrazine, a strong oxidant that causes oxidative stress within erythrocytes, resulting in oxidation of oxyhemoglobin and leading to the formation of methemoglobin, which is subsequently converted into irreversible hemichromes (iron (III) compounds). Our findings confirmed, using the iron III chelator, desferrioxamine, the indirect participation of iron (III) compounds in the activation process of artemisinins. Furthermore, in strong reducing conditions, the activation of artemisinin and the consequent production of ROS was enhanced. In conclusion, we demonstrate, through the measurement of intra-erythrocytic superoxide and hydrogen peroxide production using various methods, that artemisinin activation can be drastically enhanced by pre-oxidation of erythrocytes.