Identification of a Prenyl Chalcone as a Competitive Lipoxygenase Inhibitor: Screening,Biochemical Evaluation and Molecular Modeling Studies

Cyclooxygenase (COX) and lipoxygenase (LOX) are key targets for the development of new anti-inflammatory agents. LOX, which is involved in the biosynthesis of mediators in inflammation and allergic reactions, was selected for a biochemical screening campaign to identify LOX inhibitors by employing the main natural product library of Brazilian biodiversity. Two prenyl chalcones were identified as potent inhibitors of LOX-1 in the screening. The most active compound, (E)-2-O-farnesyl chalcone, decreased the rate of oxygen consumption to an extent similar to that of the positive control, nordihydroguaiaretic acid. Additionally, studies on the mechanism of the action indicated that (E)-2-O-farnesyl chalcone is a competitive LOX-1 inhibitor. Molecular modeling studies indicated the importance of the prenyl moieties for the binding of the inhibitors to the LOX binding site, which is related to their pharmacological properties.     

A coupled density functional-molecular mechanics Monte Carlo simulation method: The water molecule in liquid water

A theoretical model to investigate chemical processes in solution is described. It is based on the use of a coupled density functional/molecular mechanics Hamiltonian. The most interesting feature of the method is that it allows a detailed study of the solute's electronic distribution and of its fluctuations. We present the results for isothermal-isobaric constant-NPT Monte Carlo simulation of a water molecule in liquid water. The quantum subsystem is described using a double-zeta quality basis set with polarization orbitals and nonlocal exchange-correlation corrections. The classical system is constituted by 128 classical TIP3P or Simple Point Charge (SPC) water molecules. The atom-atom radial distribution functions present a good agreement with the experimental curves. Differences with respect to the classical simulation are discussed. The instantaneous and the averaged polarization of the quantum molecule are also analyzed. © 1996 by John Wiley & Sons, Inc.     

Photoinduced NO release by visible light irradiation from pyrazine-bridged nitrosyl ruthenium complexes

The binuclear complex [RuII(NH3)5(pz)RuII(bpy)2(NO)](PF6)5 was prepared and characterized by elemental analysis, UV-vis, and IR spectroscopy. The complex UV-vis spectrum has presented bands at 242, 286, and 530 nm in acetate buffer solution at pH 4.5. The photochemical study by laser flash-photolysis at 532 nm showed the NO release account from the NO measured by a NO sensor. The quantum yield for NO release (0.025 +/- 0.004 mol einsten-1) was determined with a laser flash-photolysis apparatus (Continuum Q-switched Nd:YAG laser). The major irradiation product of the [RuII(NH3)5(pz)RuII(bpy)2(NO)]5+ complex besides nitric oxide is [RuIII(NH3)5(pz)RuII(bpy)2(H2O)]5+.     

Theoretical analysis of aggregation in block‐copolymer films: The optical signature

We focus this work on the theoretical investigation of the block‐copolymer poly[oxyoctyleneoxy‐(2,6‐dimethoxy‐1,4phenylene‐1,2‐ethinylene‐phenanthrene‐2,4diyl) named as LaPPS19, recently proposed for optoelectronic applications. We used for that a variety of methods, from molecular mechanics to quantum semiempirical techniques (AM1, ZINDO/S‐CIS). Our results show that as expected isolated LaPPS19 chains present relevant electron localization over the phenanthrene group. We found, however, that LaPPS19 could assemble in a π‐stacked form, leading to impressive interchain interaction; the stacking induces electronic delocalization between neighbor chains and introduces new states below the phenanthrene‐related absorption; these results allowed us to associate the red‐shift of the absorption edge, seen in the experimental results, to spontaneous π‐stack aggregation of the chains. © 2009 Wiley Periodicals, Inc. Int J Quantum Chem, 2010     

Protonation of water clusters induced by hydroperoxyl radical surface adsorption

We have investigated the HO(2) adsorption and acid dissociation process on the surface of (H(2)O)(20) and (H(2)O)(21) clusters by using quantum-chemistry calculations. Our results show that the radical forms a stable hydrogen-bond complex on the cluster. The HO(2) acid dissociation is more favorable in the case of the (H(2)O)(21) cluster, for which the inner water molecule plays a crucial role. In fact, acid dissociation of HO(2) is found to occur in two steps. The first step involves H(2) O autoionization in the cluster, and the second one involves the proton transfer from the HO(2) radical to the hydroxide anion. The presence of the HO(2) radicals on the surface of the cluster facilitates water autoionization in the cluster.     

Combined ab initio and classical molecular dynamics simulations of alkyl-lithium aggregates in ethereal solutions

Molecular dynamics simulations of organolithium aggregates in solution are reported for the first time. We use a combined quantum/classical force field (the so-called QM/MM approach) and study ethyl-lithium aggregates in dimethyl ether (DME) solvent. The solutes are described at the Density Functional Theory level while solvent molecules are described using molecular mechanics. NVT Molecular Dynamics simulations at 200 K are carried out in the Born–Oppenheimer approximation. After equilibration, the production phase was run for 80 ps (monomer), 40 ps (dimer) and 26 ps (tetramer). The analysis of the results focuses on Li coordination as a function of aggregate size and we show that the total Li coordination number is always 4. No decoordination has been observed along the simulations. Fluctuations of the structures are predicted to be large in some cases and possible implications on reactivity are discussed.     

Structure of hydrogen tetroxide in gas phase and in aqueous environments: relationship to the hydroperoxyl radical self-reaction

Structural Chemistry - Hydrogen polyoxides are important species in atmospheric chemistry, advanced oxidation processes for wastewater treatment, and biological processes, among other fields....     

Catechins: Therapeutic Perspectives in COVID-19-Associated Acute Kidney Injury

Data obtained from several intensive care units around the world have provided substantial evidence of the strong association between impairment of the renal function and in-hospital deaths of critically ill COVID-19 patients, especially those with comorbidities and requiring renal replacement therapy (RRT). Acute kidney injury (AKI) is a common renal disorder of various etiologies characterized by a sudden and sustained decrease of renal function. Studies have shown that 5–46% of COVID-19 patients develop AKI during hospital stay, and the mortality of those patients may reach up to 100% depending on various factors, such as organ failures and RRT requirement. Catechins are natural products that have multiple pharmacological activities, including anti-coronavirus and reno-protective activities against kidney injury induced by nephrotoxic agents, obstructive nephropathies and AKI accompanying metabolic and cardiovascular disorders. Therefore, in this review, we discuss the anti-SARS-CoV-2 and reno-protective effects of catechins from a mechanistic perspective. We believe that catechins may serve as promising therapeutics in COVID-19-associated AKI due to their well-recognized anti-SARS-CoV-2, and antioxidant and anti-inflammatory properties that mediate their reno-protective activities.