Insight into chemically reactive metabolites of aliphatic amine pollutants: A de novo prediction strategy and case study of sertraline.

The uncommon metabolic pathways of organic pollutants are easily overlooked, potentially leading to idiosyncratic toxicity. Prediction of their biotransformation associated with the toxic effects is the very purpose that this work focuses, to develop a de novo method to mechanistically predict the reactive toxicity pathways of uncommon metabolites from start aliphatic amine molecules, which employed sertraline triggered by CYP450 enzymes as a model system, as there are growing concerns about the effects on human health posed by antidepressants in the aquatic environment. This de novo prediction strategy combines computational and experimental methods, involving DFT calculations upon sequential growth, in vitro and in vivo assays, dissecting chemically reactive mechanism relevant to toxicity, and rationalizing the fundamental factors.

Copper(II)-Assisted Degradation of Pheophytin by Reactive Oxygen Species.

The central ion Mg is responsible for the differences between chlorophyll a and its free base in their reactivity toward metal ions and thus their resistance to oxidation. We present here the results of spectroscopic (electronic absorption and emission, circular dichroism, and electron paramagnetic resonance), spectroelectrochemical, and computational (based on density functional theory) investigations into the mechanism of pheophytin, a degradation that occurs in the presence of Cu ions and O. The processes leading to the formation of the linear form of tetrapyrrole are very complex and involve the weakening of the methine bridge due to an electron withdrawal by Cu(II) and the activation of O, which provides protection to the free ends of the opening macrocycle.

A Personal Account on Inorganic Reaction Mechanisms.

The presented Review is focused on the latest research in the field of inorganic chemistry performed by the van Eldik group and his collaborators. The first part of the manuscript concentrates on the interaction of nitric oxide and its derivatives with biologically important compounds. We summarized mechanistic information on the interaction between model porphyrin systems (microperoxidase) and NO as well as the recent studies on the formation of nitrosylcobalamin (CblNO).

Hydroxychloroquine-Loaded Chitosan Nanoparticles Induce Anticancer Activity in A549 Lung Cancer Cells: Design, BSA Binding, Molecular Docking, Mechanistic, and Biological Evaluation.

The current study describes the encapsulation of hydroxychloroquine, widely used in traditional medicine due to its diverse pharmacological and medicinal uses, in chitosan nanoparticles (CNPs). This work aims to combine the HCQ drug with CS NPs to generate a novel nanocomposite with improved characteristics and bioavailability. HCQ@CS NPs are roughly shaped like roadways and have a smooth surface with an average size of 159.

Microstructure, Physical and Biological Properties, and BSA Binding Investigation of Electrospun Nanofibers Made of Poly(AA-co-ACMO) Copolymer and Polyurethane.

In this study, poly(AA-co-ACMO) and polyurethane-based nanofibers were prepared in a ratio of 1:1 (NF11) and 2:1 (NF21) as antimicrobial carriers for chronic wound management. Different techniques were used to characterize the nanofibers, and poly(AA-co-ACMO) was mostly found on the surface of PU. With an increase in poly(AA-co-ACMO) dose from 0 (PU) and 1:1 (NF11) to 2:1 (NF21) in the casting solution, the contact angle (CA) was reduced from 137 and 95 to 24, respectively, and hydrophilicity was significantly increased.

DNA Binding and Cleavage, Stopped-Flow Kinetic, Mechanistic, and Molecular Docking Studies of Cationic Ruthenium(II) Nitrosyl Complexes Containing "NS" Core.

This work aimed to evaluate in vitro DNA binding mechanistically of cationic nitrosyl ruthenium complex [RuNOTSP] and its ligand (TSPH) in detail, correlate the findings with cleavage activity, and draw conclusions about the impact of the metal center. Theoretical studies were performed for [RuNOTSP], TSPH, and its anion TSP using DFT/B3LYP theory to calculate optimized energy, binding energy, and chemical reactivity. Since nearly all medications function by attaching to a particular protein or DNA, the in vitro calf thymus DNA (ctDNA) binding studies of [RuNOTSP] and TSPH with ctDNA were examined mechanistically using a variety of biophysical techniques.

Reactivity of non-organometallic ruthenium(II) polypyridyl complexes and their application as catalysts for hydride transfer reactions.

Recently, we investigated the substitution behavior of a series of ruthenium(II) complexes of the general formula [Ru(terpy)(NN)Cl]Cl, where terpy = 2,2':6',2″-terpyridine, NN = bidentate ligand, in aqueous solutions. We have shown that the most and least reactive complexes of the series are [Ru(terpy)(en)Cl]Cl (en = ethylenediamine) and [Ru(terpy)(phen)Cl]Cl (phen = 1, 10-phenantroline), respectively, as a result of different electronic effects provided by the bidentate spectator chelates. Polypyridyl amine Ru(II) complex, [Ru(terpy)(en)Cl]Cl and [Ru(terpy)(ampy)Cl]Cl (where ampy = 2-(aminomethyl)pyridine), in which the terpy chelate labilizes the metal center, are able to catalyze the conversion of NAD to 1,4-NADH using sodium formate as a source of hydride.

Equilibrium Studies on Pd(II)-Amine Complexes with Bio-Relevant Ligands in Reference to Their Antitumor Activity.

This review article presents an overview of the equilibrium studies on Pd-amine complexes with bio-relevant ligands in reference to their antitumor activity. Pd(II) complexes with amines of different functional groups, were synthesized and characterized in many studies. The complex formation equilibria of Pd(amine) complexes with amino acids, peptides, dicarboxylic acids and DNA constituents, were extensively investigated.

Synthesis, Biophysical Interaction of DNA/BSA, Equilibrium and Stopped-Flow Kinetic Studies, and Biological Evaluation of bis(2-Picolyl)amine-Based Nickel(II) Complex.

Reaction of bis(2-picolyl)amine () with Ni(II) salt yielded [(BPA)NiCl(HO)] (). The Ni(II) in bound to a ligand, two chloride, and one aqua ligands. Because most medications inhibit biological processes by binding to a specific protein, the stopped-flow technique was used to investigate DNA/protein binding in-vitro, and a mechanism was proposed.

Molecular Parameters Promoting High Relaxivity in Cluster-Nanocarrier Magnetic Resonance Imaging Contrast Agents.

We have investigated the mechanism of relaxivity for two magnetic resonance imaging contrast agents that both employ a cluster-nanocarrier design. The first system termed MnFe-coPS comprises the cluster MnFeO(L)(HO) or MnFe () (L = carboxylate) co-polymerized with polystyrene to form ∼75 nm nanobeads. The second system termed MnBpy-PAm used the cluster Mn(OCCH)(Bpy) or MnBpy () where Bpy = 2,2'-bipyridine, entrapped in ∼180 nm polyacrylamide nanobeads.

Electronic effects on the mechanism of the NAD coenzyme reduction catalysed by a non-organometallic ruthenium(ii) polypyridyl amine complex in the presence of formate.

In the present study, electronic effects on the mechanism of the NAD coenzyme reduction in the presence of formate, catalysed by a non-organometallic ruthenium(ii) polypyridyl amine complex, were investigated. The [Ru(terpy)(ampy)Cl]Cl (terpy = 2,2':6',2''-terpyridine, ampy = 2-(aminomethyl)pyridine) complex was employed as the catalyst. The reactions were studied in a water/ethanol mixture as a function of formate, catalyst, and NAD concentrations at 37 °C.

BSA Interaction, Molecular Docking, and Antibacterial Activity of Zinc(II) Complexes Containing the Sterically Demanding Biomimetic NS Ligand: The Effect of Structure Flexibility.

Two zinc(II) complexes, DBZ and DBZH4, that have (ZnN3S2) cores and differ in the bridging mode of the ligating backbone, effectively bind to BSA. The binding affinity varies as DBZ > DBZH4 and depends on the ligand structure. At low concentrations, both complexes exhibit dynamic quenching, whereas at higher concentrations they exhibit mixed (static and dynamic) quenching.

Investigation of water substitution at Ru complexes by conceptual density function theory approach.

In this paper, we investigated water exchange reactions and substitution of aqua Ru complexes of general formula [Ru(terpy)(N^N)(H O)] (where N^N = ethylenediamine (en), 1,2-(aminomethyl)pyridine (ampy) and 2,2'-bipyridine (bipy)) by ammonia and thioformaldehyde. These reactions were studied in detail by applying conceptual density functional theory. This approach enabled us to gain further insight into the underlying reaction mechanism at the microscopic level (involving only direct participants of the reaction, without the influence of the solvent) and to put the concept of reaction mechanism on a quantitative basis.

Ru(edta) complexes as molecular redox catalysts in chemical and electrochemical reduction of dioxygen and hydrogen peroxide: inner-sphere outer-sphere mechanism.

The reduction of molecular oxygen (O) and hydrogen peroxide (HO) by [Ru(edta)(pz)] (edta = ethylenediaminetetraacetate; pz = pyrazine) has been studied spectrophotometrically and kinetically in aqueous solution. Exposure of the aqua-analogue [Ru(edta)(HO)] to O and HO resulted in the formation of [Ru(edta)(HO)] species, with subsequent formation of the corresponding Ru[double bond, length as m-dash]O complex. A working mechanism for the O and HO reduction reactions mediated by the Ru(edta) complexes is proposed.

Inhaled silica nanoparticles exacerbate atherosclerosis through skewing macrophage polarization towards M1 phenotype.

Background And Aims: Exposure to environmental nanoparticles is related to the adverse impact on health, including cardiovascular system. Various forms of nanoparticles have been reported to interact with endothelium and induce inflammation. However, the potential role of nanoparticles in the pathogenesis of atherosclerosis and their mechanisms of action are still unclear.

Metabolic Response of RAW 264.7 Macrophages to Exposure to Crude Particulate Matter and a Reduced Content of Organic Matter.

Exposure to air pollution from various airborne particulate matter (PM) is regarded as a potential health risk. Airborne PM penetrates the lungs, where it is taken up by macrophages, what results in macrophage activation and can potentially lead to negative consequences for the organism. In the present study, we assessed the effects of direct exposure of RAW 264.

Reaction mechanisms relevant to the formation and utilization of [Ru(edta)(NO)] complexes in aqueous media.

The advancement of Ru(edta) complexes (edta = ethylenediamineteraacetate) mediated reactions, including NO generation and its utilization, has not been systematically reviewed to date. This review aims to report the research progress that has been made in exploring the application of Ru(edta) complexes in trapping and generation of NO. Furthermore, utilization of the potential of Ru(edta) complexes to mimic NO synthase and nitrite reductase activity, including thermodynamics and kinetics of NO binding to Ru(edta) complexes, their NO scavenging (in vitro), and antitumor activity will be discussed.

Experimental and Computational Insight into the Mechanism of NO Binding to Ferric Microperoxidase. The Likely Role of Tautomerization to Account for the pH Dependence.

According to the current paradigm, the metal-hydroxo bond in a six-coordinate porphyrin complex is believed to be significantly less reactive in ligand substitution than the analogous metal-aqua bond, due to a much higher strength of the former bond. Here, we report kinetic studies for nitric oxide (NO) binding to a heme-protein model, acetylated microperoxidase-11 (AcMP-11), that challenge this paradigm. In the studied pH range 7.

High-Pressure Mechanistic Insight into Bioinorganic NO Chemistry.

Pressure is one of the most important parameters controlling the kinetics of chemical reactions. The ability to combine high-pressure techniques with time-resolved spectroscopy has provided a powerful tool in the study of reaction mechanisms. This review is focused on the supporting role of high-pressure kinetic and spectroscopic methods in the exploration of nitric oxide bioinorganic chemistry.

Ligand-Tuning of the Stability of Pd(II) Conjugates with Cyanocobalamin.

Besides the well-known functions performed by vitamin B (CblCN) in biochemical processes of the human body, an increasing interest has been raised by the possibility of its use as a transmembrane drug carrier, capable, among others, of enhancing the accumulation of inorganic cytostatics in cancer cells. The present study was aimed at determining the possibility of the formation of CblCN conjugates with Pd(II) complexes. A key aspect was their stability, which we attempted to tune by appropriate choice of ligands.

Mechanistic Studies on the Reaction between Aquacobalamin and the HNO Donor Piloty's Acid over a Wide pH Range in Aqueous Solution.

Detailed kinetic and mechanistic studies have been carried out on the reaction between aquacobalamin/hydroxocobalamin (CblOH/CblOH) and nitroxyl (HNO) generated by Piloty's acid (PA, -hydroxybenzenesulfonamide) over a wide pH range (3.5-13). The resulting data showed that in a basic solution HNO can react with hydroxocobalamin to form nitrosylcobalamin despite the inert nature of CblOH.

Chlorophyll a π-Cation Radical as Redox Mediator in Superoxide Dismutase (SOD) Mimetics.

The extensive speciation of copper(II) chloride in organic solvents varies with concentration, temperature, pressure and oxygen content, providing the ability to switch between different chlorophyll transmetalation pathways. We found that one of them is exceptionally suitable for the formation and stabilisation of the chlorophyll π-cation radical. This is due to unique redox cycling, which is coupled to the generation and transformation of various reactive oxygen species.