Structures and Solvation Energies Effects Versus Temperature. An MP2 Investigations in the Framework of Cluster Model.

Structures, relative stabilities, solvation enthalpies, and free energies of the cluster in gas and in water phases were investigated in this work using Moller-Plesset perturbation theory (MP2) and considering a temperature range of 40-400 K. The 12 HO molecules are distributed between the first, second, and third solvation shells. The calculated distances distances in gas phase are in good agreement with the experimental range which confirms the strong influence of long-distance interactions in cluster stabilization.

Understanding the Photophysical Properties of Pd and Pt Transition-Metal Isocorroles: A Theoretical Investigation.

The main photophysical properties of recently synthesized Pd- and Pt-isocorroles, characterized and proposed as potential photosensitizers in photodynamic therapy, have been investigated and rationalized using density functional theory and its time-dependent formulation. Both the 5 and 10-(2-pyrrolyl)-5,10,15-tris(4-methylphenyl) isomers have been considered. In addition to determining the minimum energy structures of the ground and excited states, we have calculated the excitation energies, spin-orbit coupling constants, nonradiative intersystem crossing rate constants and two photons cross section.

The Effect of Chalcogen-Chalcogen Bond Formation in the New Delhi Metallo-β-Lactamase 1 Enzyme to Counteract Antibiotic Resistance.

New Delhi metallo-β-lactamase 1 (NDM-1) is an enzyme involved in the drug resistance of many bacteria against most of the widely adopted antibiotics, such as penicillins, cephalosporins, and carbapenems. Consequently, inhibiting NDM-1 swiftly has gained significant interest as a strategy to counteract this bacterial defense mechanism, thereby restoring the effectiveness of antibiotics. Among the inhibitors tested against the enzyme, ebselen () showed particularly promising results.

On the dual role of (+)-catechin as primary antioxidant and inhibitor of viral proteases.

Natural antioxidants have become the subject of many investigations due to the role that they play in the reduction of oxidative stress. Their main scavenging mechanisms concern the direct inactivation of free radicals and the coordination of metal ions involved in Fenton-like reactions. Recently, increasing attention has been paid to non-covalent inhibition of enzymes involved in different diseases by the antioxidants.

Gallic acid improves color quality and stability of red wine via physico-chemical interaction and chemical transformation as revealed by thermodynamics, real wine dynamics and benchmark quantum mechanical calculations.

The aim of this study was to explore the copigmentation effect of gallic acid on red wine color and to dissect its mechanism at the molecular level. Three-dimensional studies, e.g.

Intermolecular interactions between malvidin-3-O-glucoside and caffeic acid: Structural and thermodynamic characterization and its effect on real wine color quality.

The copigmentation effect between malvidin-3-O-glucoside and caffeic acid was comprehensive inquiry on the model wine solution, theoretical simulation and real wine. Thermodynamic parameters were determined by UV/Visible spectroscopy and Isothermal titration calorimetry (ITC). Theoretical data were obtained employing a dispersion-corrected density functional approach.

Primary Antioxidant Power and M SARS-CoV-2 Non-Covalent Inhibition Capabilities of Miquelianin.

The antioxidant power of quercetin-3-O-glucuronide (miquelianin) has been studied, at the density functional level of theory, in both lipid-like and aqueous environments. In the aqueous phase, the computed pK equilibria allowed the identification of the neutral and charged species present in solution that can react with the ⋅OOH radical. The Hydrogen Atom Transfer (HAT), Single Electron Transfer (SET) and Radical Adduct Formation (RAF) mechanisms were considered, and the individual, total and fraction corrected rate constants were obtained.

Chalcogen atom effect on the intersystem crossing kinetic constant of oxygen- and sulfur disubstituted heteroporphyrins.

The modulation of the photophysical properties of di-substituted porphyrin rings upon the oxygen and sulfur-for-nitrogen replacement has been investigated at density functional theory (DFT) and its time-dependent formulation (TDDFT). The considered properties range from structural behaviors and excitation energies to spin-orbit coupling (SOC) and nonradiative intersystem kinetic constants. Results show that the SOC strongly increase upon chalcogen substitution and, accordingly, the computed nonradiative kinetic constant also indicate an efficient singlet-triplet intersystem crossing in the sulfur containing macrocycle.

On the antibacterial photodynamic inactivation mechanism of Emodin and Dermocybin natural photosensitizers: A theoretical investigation.

A DFT and TDDFT study has been carried out on monomeric anthraquinones Emodin and Dermocybin (Em, Derm) recently proposed as natural antibacterial photosensitizers able to act also against gram-negative microbes. The computational study has been performed considering the relative amount of neutral and ionic forms of each compound in water, with the variation of pH. The occurrence of both Type I and Type II photoreactions has been explored computing the absorption properties of each species, the spin-orbit coupling constants (SOC), the vertical ionization potentials and the vertical electron affinities.

On the Role of Temperature in the Depolymerization of PET by FAST-PETase: An Atomistic Point of View on Possible Active Site Pre-Organization and Substrate-Destabilization Effects.

Enzyme FAST-PETase, recently obtained by a machine learning approach, can depolymerize poly(ethylene terephthalate) (PET), a synthetic resin employed in plastics and in clothing fibers. Therefore it represents a promising solution for the recycling of PET-based materials. In this study, a model of PET was adopted to describe the substrate, and all-atoms classical molecular dynamics (MD) simulations on apo- and substrate-bound FAST-PETase were carried out at 30 and 50 °C to provide atomistic details on the binding step of the catalytic cycle.

Sulphur- and Selenium-for-Oxygen Replacement as a Strategy to Obtain Dual Type I/Type II Photosensitizers for Photodynamic Therapy.

The effect on the photophysical properties of sulfur- and selenium-for-oxygen replacement in the skeleton of the oxo-4-dimethylaminonaphthalimide molecule (DMNP) has been explored at the density functional (DFT) level of theory. Structural parameters, excitation energies, singlet-triplet energy gaps (ΔE), and spin-orbit coupling constants (SOC) have been computed. The determined SOCs indicate an enhanced probability of intersystem crossing (ISC) in both the thio- and seleno-derivatives (SDMNP and SeDMNP, respectively) and, consequently, an enhancement of the singlet oxygen quantum yields.

Computational investigation on the antioxidant activities and on the M SARS-CoV-2 non-covalent inhibition of isorhamnetin.

In the present work, we report a computational study on some important chemical properties of the flavonoid isorhamnetin, used in traditional medicine in many countries. In the course of the study we determined the acid-base equilibria in aqueous solution, the possible reaction pathways with the •OOH radical and the corresponding kinetic constants, the complexing capacity of copper ions, and the reduction of these complexes by reducing agents such as superoxide and ascorbic anion by using density functional level of theory Density Functional Theory. Finally, the non-covalent inhibition ability of the SARS-CoV-2 main protease enzyme by isorhamnetin was examined by molecular dynamics (MD) and docking investigation.

On the origin of photodynamic activity of hypericin and its iodine-containing derivatives.

The main photophysical properties, useful for establishing whether hypericin in anionic form and some of its derivatives containing heavy atoms such as iodine, can be proposed for their use in photodynamic therapy, were determined using density functional based computations. The results showed that in the anionic form and in the iodinated derivatives, the absorption wavelength undergoes a bathochromic shift, the singlet-triplet energy gap assumes values ​that allow to excite the oxygen molecule from its ground to the excited singlet state, and that the spin-orbit couplings between singlet and triplet states significantly increase.

Chalcogen Effects in the Photophysical Properties of Dimethylamino-1,8-naphthalimide Dyes Revealed by DFT Investigation.

Thionation of carbonyl groups of known dyes is a rapidly emerging strategy to propose an advance toward heavy-atom-free photosensitizers to be used in photodynamic therapy (PDT). The sulfur-for-oxygen replacement has recently proved to enhance the singlet oxygen quantum yield of some existing fluorophores and to shift the absorption band at longer wavelengths. Drawing inspiration from this challenging evidence, the effect of both sulfur- and selenium-for-oxygen replacement in the skeleton of the oxo-4-dimethylamino-1,8-naphthalimide molecule (DMN) has been analyzed by means of a DFT study.

Inhibition of the carnitine acylcarnitine carrier by carbon monoxide reveals a novel mechanism of action with non-metal-containing proteins.

Both toxic and physiological effects of CO are mostly caused by well described interactions with heme-groups of proteins. Interactions of CO with non-heme proteins have also been unveiled. Besides interaction of CO with mitochondrial heme containing respiratory complexes, a BK channel and the phosphate carrier which do not contain metal cofactors, have been identified as CO targets.

Antioxidant and copper-chelating power of new molecules suggested as multiple target agents against Alzheimer's disease. A theoretical comparative study.

In this study, the scavenging activity against OOH radicals and the copper-chelating ability of two new synthesized molecules (named and ) that can act as multiple target agents against Alzheimer's disease have been investigated at the density functional theory level. The p and molar fractions at physiological pH have been predicted. The main antioxidant reaction mechanisms in lipid-like and water environments have been considered and the relative rate constants determined.

On the Scavenging Ability of Scutellarein against the OOH Radical in Water and Lipid-like Environments: A Theoretical Study.

The antioxidant capability of scutellarein, a flavonoid extracted from different plants of the Scutellaria family, was computationally predicted by considering its reaction with the OOH radical in both lipid-like and water environments. The pKa and equilibrium behavior in the aqueous phase were also calculated. Different reaction mechanisms involving the most populated species were considered.

Activation by Glutathione in Hypoxic Environment of an Azo-based Rhodamine Activatable Photosensitizer. A Computational Elucidation.

In the present paper, density functional theory (DFT) has been applied to the study of the activation mechanism of a new selenium azo-rhodamine (azoSeRho) in presence of the tripeptide thiol, glutathione (GSH), as potent activatable photosensitizer to be employed in photodynamic therapy. The introduction of the azo group into the conjugated system of the seleno-rhodamine dye and its reaction with GSH allow the selective formation of the active photosensitizer, SeRho. Furthermore, DFT calculations have allowed to shed light on the activation mechanism of the azoSeRho photosensitizer when molecular oxygen is present and hydrogen peroxide is formed.

Antioxidants into Nopal (), Important Inhibitors of Free Radicals' Formation.

Nopal () belonging to the Cactacea family has many nutritional benefits attributed to a wide variety of phenolic and flavonoid compounds. Coumaric acid (COA), ferulic acid (FLA), protocatechuic acid (PRA), and gallic acid (GAA) are the phenolic acids (PhAs) present in nopal. In this study, the role of these PhAs in copper-induced oxidative stress was investigated using the density functional theory (DFT).

Computational Study Reveals the Role of Water Molecules in the Inhibition Mechanism of LAT1 by 1,2,3-Dithiazoles.

The L-type amino acid transporter LAT1, involved in many biological processes including the overexpression of some tumors, is considered a potential pharmacological target. The 1,2,3-Dithiazole scaffold was predicted to inhibit LAT1 by the formation of an intermolecular disulfide bond with the thiolate group of cysteine(s). As a result of the identification of these irreversible covalent inhibitors, we decided to deeply investigate the recognition stage and the covalent interaction, characterizing the chemical structures of the selected ligands.

The Contribution of Density Functional Theory to the Atomistic Knowledge of Electrochromic Processes.

In this review, we provide a brief overview of the contribution that computational studies can offer to the elucidation of the electronic mechanisms responsible for the electrochromism phenomenon, through the use of the density functional theory (DFT) and its time-dependent formulation (TDDFT). Although computational studies on electrochromic systems are not as numerous as those for other physico-chemical processes, we will show their reliability and ability to predict structures, excitation energies, and redox potentials. The results confirm that these methods not only help in the interpretation of experimental data but can also be used for the rational design of molecules with interesting electrochromic properties to be initiated for synthesis and experimental characterization.

The Se-S Bond Formation in the Covalent Inhibition Mechanism of SARS-CoV-2 Main Protease by Ebselen-like Inhibitors: A Computational Study.

The inhibition mechanism of the main protease (M) of SARS-CoV-2 by ebselen (EBS) and its analog with a hydroxyl group at position 2 of the benzisoselenazol-3(2H)-one ring (EBS-OH) was studied by using a density functional level of theory. Preliminary molecular dynamics simulations on the apo form of M were performed taking into account both the hydrogen donor and acceptor natures of the Nδ and Nε of His41, a member of the catalytic dyad. The potential energy surfaces for the formation of the Se-S covalent bond mediated by EBS and EBS-OH on M are discussed in detail.

A Boron-Containing Compound Acting on Multiple Targets Against Alzheimer's Disease. Insights from Ab Initio and Molecular Dynamics Simulations.

Given the multifactorial nature and pathogenesis of Alzheimer's disease, therapeutic strategies are addressed to combine the benefits of every single-target drug into a sole molecule. Quantum mechanics and molecular dynamics (MD) methods were employed here to investigate the multitarget action of a boron-containing compound against Alzheimer's disease. The antioxidant activity as a radical scavenger and metal chelator was explored by means of density functional theory.

Photophysical properties of heavy atom containing tetrasulfonyl phthalocyanines as possible photosensitizers in photodynamic therapy.

The excitation energies, singlet-triplet energy gap and spin-orbit coupling constants for Zn-, GaCl-, Pd-, and Pt- tetrasulfonyl phthalocyanines complexes (ZnPc, GaClPc, PdPc, and PtPc) have been computed by using the density functional theory and employing the M06 exchange-correlation functional. Results show that these systems possess interesting photophysical properties, which make them possible photosensitizers to be proposed in photodynamic therapy (PDT). Absorption energies of all the complexes examined have been found falling inside the so-called therapeutic window (550-800 nm).

Anticancer Activity, DNA Binding, and Photodynamic Properties of a N∧C∧N-Coordinated Pt(II) Complex.

In the effort to discover new targets and improve the therapeutic efficacy of metal-containing anticancer compounds, transition metal complexes that can elicit cytotoxicity when irradiated with light of a proper wavelength and, then, candidates as potential photosensitizers for photodynamic therapy are actively being investigated. In this work, the cytotoxicity in the dark and the photophysical properties of the complex Pt(N∧C∧N)Cl, where the N∧C∧N ligand is 2,6-dipyrido-4-methyl-benzene chloride, are investigated in detail by means of a series of theoretical levels, that is density functional theory and its time-dependent extension together with molecular dynamics (MD) simulations. In the dark, cytotoxicity has been explored by simulating the steps of the mechanism of action of classical Pt(II) complexes.