Molecular Modeling Insights on the Pharmaceuticals and Hypotheses of Alzheimer's Disease.

Alzheimer's disease (AD) stands as the predominant contributor to dementia cases. The ongoing developments in our understanding of its pathogenesis have sparked the interest of researchers, driving them to explore innovative treatment approaches. Existing therapies incorporating cholinesterase inhibitors and/or NMDA antagonists have shown limited improvement in alleviating symptoms.

Chemiluminescence of a Firefly Luciferin Analogue Reveals that Formation of the Key Intermediate Responsible for Excited State Generation Occurs on a Fully Concerted Step.

The chemiluminescence (CL) reaction of eight different 2-(4-hydroxyphenyl)-4,5-dihydrothiazole-4-carboxylate esters with an organic superbase and oxygen was investigated through a kinetic and computational study. These esters are all analogues to the luciferin substrate involved in efficient firefly bioluminescence. The kinetic data obtained from CL emission and light absorption assays were used in the context of linear free energy relationships (LFER); we obtained the Hammett reaction constant ρ = +1.

Synergistic Interaction of Hyperbranched Polyglycerols and Cetyltrimethylammonium Bromide for Oil/Water Interfacial Tension Reduction: A Molecular Dynamics Study.

Applying surfactants to reduce the interfacial tension (IFT) on water/oil interfaces is a proven technique. The search for new surfactants and delivery strategies is an ongoing research area with applications in many fields such as drug delivery through nanoemulsions and enhanced oil recovery. Experimentally, the combination of hyperbranched polyglycerol (HPG) with cetyltrimethylammonium bromide (CTAB) substantially reduced the observed IFT of oil/water interface, 0.

Diving into the optoelectronic properties of Cu(II) and Zn(II) curcumin complexes: a DFT and wavefunction benchmark.

Context: Curcumin is a popular food additive around the world whose medicinal properties have been known since ancient times. The literature has recently highlighted several biological properties, but besides the health-related usages, its natural yellowish color may also be helpful for light-harvesting applications. This research aims to close a knowledge gap regarding the photophysical description of curcumin and its metallic complexes.

Benchmarking DFT functionals for photophysics of pyranoflavylium cations.

An intense absorption, phosphorescence, a long triplet excited state lifetime and singlet oxygen generation capabilities are characteristics of pyranoflavylium cations, analogues to pyranoanthocyanidins originated in the maturation process of red wine. Such properties make these compounds potential photosensitizers to be applied in photodynamic therapy. In this context, the photophysical processes underlying that treatment critically depend on the electronic structure of the pyranoflavylium molecules.

Mechanisms for the Deactivation of the Electronic Excited States of α-(2-Hydroxyphenyl)--phenylnitrone: From Intramolecular Proton and Charge Transfer to Structure Twisting and Aggregation.

The search for new prominent chemosensors is significantly related to the rationalization of possible multiple pathways of excited-state deactivation. We have prepared and studied compound α-(2-hydroxyphenyl)--phenylnitrone (Nit-OH), observing that Nit-OH is stable in acetonitrile solution under UV-vis light. The experimentally observed 540 nm fluorescence for Nit-OH was shown to be related to excitation at 360 nm from the highest occupied molecular orbital to the lowest unoccupied molecular orbital (HOMO-LUMO transition).

Photochemical and photophysical properties of tetracarboxylic acid phthalocyanines from glycolic and lactic acids in homogeneous and micro heterogeneous media.

Glycolic acid and lactic acid substituted zinc phthalocyanines were studied concerning their photophysical and photochemical properties in eight organic solvents (homogeneous medium) and in aqueous media with the presence of CTAB and PVP 360 surfactants. Solvent effects were investigated according to several physical solvent parameters, including studies that used more than one parameter at a time, such as the E(30) scale and the Lippet-Mataga equation. Computational studies were realized and was found in good agreement with experimental data indicating J-type dimers' formation through hydrogen bonds, which may not affect the spectroscopic properties.

Metal-Cocatalyst Interaction Governs the Catalytic Activity of M-Porphyrazines for Chemical Fixation of CO.

Chemical fixation of CO to produce cyclic carbonates can be a green and atomic efficient process. In this work, a series of porphyrazines (Pzs) containing electron-withdrawing groups and central M ions (where M = Mg, Zn, Cu, and Co) were synthesized and investigated as catalysts for the cycloaddition of CO to epoxides. Then, the efficiency of the Pzs was tested by varying cocatalyst type and concentration, epoxide, temperature, and pressure.

Can one use the electronic absorption spectra of metalloporphyrins to benchmark electronic structure methods? A case study on the cobalt porphyrin.

In this article, we describe calculations on the absorption spectrum of cobalt(ii) porphyrin, using density functional (DFT) and multireference n-electron valence perturbation (NEVPT) theories. With these calculations, we describe the lowest-energy states of doublet and quartet spin multiplicities, the excited states that originate the Q and B bands of porphyrins, some higher-energy π-π* excitations and charge-transfer states, HOMO-LUMO gaps, and ionisation potentials. Results undoubtedly show that the position of B band is essentially independent on the DFT functional, while the Q band is better described by pure functionals, and these bands do not depend on the initial state of the transition (whether doublet or quartet) as well.

Competition Between Phenothiazines and BH3 Peptide for the Binding Site of the Antiapoptotic BCL-2 Protein.

The study of proteins and mechanisms involved in the apoptosis and new knowledge about cancer's biology are essential for planning new drugs. Tumor cells develop several strategies to gain proliferative advantages, including molecular alterations to evade from apoptosis. Failures in apoptosis could contribute to cancer pathogenesis, since these defects can cause the accumulation of dividing cells and do not remove genetic variants that have malignant potential.

Photobleaching Efficiency Parallels the Enhancement of Membrane Damage for Porphyrazine Photosensitizers.

Photostability is considered a key asset for photosensitizers (PS) used in medical applications as well as for those used in energy conversion devices. In light-mediated medical treatments, which are based on PS-induced harm to diseased tissues, the photoinduced cycle of singlet oxygen generation has always been considered to correlate with PS efficiency. However, recent evidence points to the fundamental role of contact-dependent reactions, which usually cause PS photobleaching.

Density Functional Theory Applied to Excited State Intramolecular Proton Transfer in Imidazole-, Oxazole-, and Thiazole-Based Systems.

Excited state intramolecular proton transfer (ESIPT) is a photoinduced process strongly associated to hydrogen bonding within a molecular framework. In this manuscript, we computed potential energy data using Time Dependent Density Functional Theory (TDDFT) for triphenyl-substituted heterocycles, which evidenced an energetically favorable proton transfer on the excited state (i.e.

Insights into molecular mechanisms of drug metabolism dysfunction of human CYP2C9*30.

Cytochrome P450 2C9 (CYP2C9) metabolizes about 15% of clinically administrated drugs. The allelic variant CYP2C9*30 (A477T) is associated to diminished response to the antihypertensive effects of the prodrug losartan and affected metabolism of other drugs. Here, we investigated molecular mechanisms involved in the functional consequences of this amino-acid substitution.

Evaluation of degradation mechanism of chlorhexidine by means of Density Functional Theory calculations.

Chlorhexidine (CHD), a germicidal drug, has degradation products that can be hemotoxic and carcinogenic. However, there is no consensus in literature about the degradation pathway. In order to shed light on that mechanism, we have employed Density Functional Theory to study reactants, in different protonation states, products and intermediates involved in the different pathways.

Mechanistic model for the firefly luciferin regeneration in biomimetic conditions: a model for the in vivo process?

The emission of light by fireflies involves the enzymatic oxidation of firefly luciferin and ends up in the formation of 2-cyano-6-hydroxybenzothiazole, and this is recycled back to luciferin by condensation with cysteine. In this work, we suggest a mechanism for this transformation that operates under mild conditions that are similar to in vivo environments (i.e.

Quantum-chemistry descriptors for photosensitizers based on macrocycles.

Phthalocyanines, porphyrins, and chlorins have been widely studied as photosensitizers. Both experimental and computational strategies are employed in order to propose new and more active molecules derived from those macrocycles. In this context, there are two main strategies used: (i) the addition of different substituents and (ii) the complexation of the macrocycle with different metallic ions.

Morphological dependence of silver electrodeposits investigated by changing the ionic liquid solvent and the deposition parameters.

The low toxicity and environmentally compatible ionic liquids (ILs) are alternatives to the toxic and harmful cyanide-based baths used in industrial silver electrodeposition. Here, we report the successful galvanostatic electrodeposition of silver films using the air and water stable ILs 1-ethyl-3-methylimidazolium trifluoromethylsulfonate ([EMIM]TfO) and 1-H-3-methylimidazolium hydrogen sulphate ([HMIM(+)][HSO4(-)]) as solvents and AgTfO as the source of silver. The electrochemical deposition parameters were thoughtfully studied by cyclic voltammetry before deposition.

Cytotoxicity of phenothiazine derivatives associated with mitochondrial dysfunction: a structure-activity investigation.

Phenothiazine derivatives are neuroleptic drugs used in the treatment of schizophrenia and anxiety. Several side effects are described for these drugs, including hepatotoxicity, which may be related to their cytotoxic activity. Working with isolated rat liver mitochondria, we previously showed that phenothiazine derivatives induced the mitochondrial permeability transition associated with cytochrome c release.

Diclofenac on boron-doped diamond electrode: from electroanalytical determination to prediction of the electrooxidation mechanism with HPLC-ESI/HRMS and computational simulations.

Using square-wave voltammetry coupled to the boron-doped diamond electrode (BDDE), it was possible to develop an analytical methodology for identification and quantification of diclofenac (DCL) in tablets and synthetic urine. The electroanalytical procedure was validated, with results being statistically equal to those obtained by chromatographic standard method, showing linear range of 4.94 × 10(-7) to 4.

Riboflavin-photosensitized oxidation is enhanced by conjugation in unsaturated lipids.

Methyl esters of polyunsaturated fatty acids were found to quench triplet-excited riboflavin ((3)Rib) in efficient bimolecular reactions with rate constants, as determined by laser flash photolysis, linearly depending upon the number of bis-allylic methylene (from 1 to 5). Deactivation of (3)Rib is predicted by combining the experimental second-order rate constants k2 determined for acetonitrile/water (8:2, v/v) at 25 °C with density functional theory (DFT) calculations of bond dissociation energy to have an upper limiting value of 1.22 × 10(7) L mol(-1) s(-1) for hydrogen abstraction from bis-allylic methylene groups in unsaturated lipid by (3)Rib.

Copper(II) complexation to 1-octarepeat peptide from a prion protein: insights from theoretical and experimental UV-visible studies.

The octarepeat domain in cellular prion protein (PrP(C)) has attracted much attention over the last 10 years because of its importance in the complexation of copper with PrP(C). The aim of this research was to study the UV-vis spectra of a peptide similar to the 1-repeat of the octarepeat region in PrP(C) using experimental and theoretical approaches and to gain insight into the complexation of the PrP(C) octarepeat domain with copper(II) ions in solution. We found that the copper atom was responsible for the peptide conformation, which allows for charge transfers between its two terminal residues.

The interaction of an azo compound with a surfactant and ion pair adsorption to solid phases.

The adsorption of SPADNS (trisodium salt of 2-(p-sulfophenylazo)-1,8-dihydroxynaphthalene-3,6-disulfonic acid) onto resins XAD 2, XAD 7 and silica gel was studied in the presence and in the absence of the cationic surfactant CTAB (cetyl trimethylammonium bromide). At a ratio of 2.5 CTAB to 1 SPADNS, the surfactant caused a marked increase in SPADNS adsorption.

Reactivity of beer bitter acids toward the 1-hydroxyethyl radical as probed by spin-trapping electron paramagnetic resonance (EPR) and electrospray ionization-tandem mass spectrometry (ESI-MS/MS).

The iso-α-acids or isohumulones are the major contributors to the bitter taste of beer, and it is well-recognized that they are degraded during beer aging. In particular, the trans-isohumulones seem to be less stable than the cis-isohumulones. The major radical identified in beer is the 1-hydroxyethyl radical; however, the reactivity between this radical and the isohumulones has not been reported until now.

Role of physicochemical properties in the activation of peroxisome proliferator-activated receptor δ.

Current researches on treatments for metabolic diseases involve a class of biological receptors called peroxisome proliferator-activated receptors (PPARs), which control the metabolism of carbohydrates and lipids. A subclass of these receptors, PPARδ, regulates several metabolic processes, and the substances that activate them are being studied as new drug candidates for the treatment of diabetes mellitus and metabolic syndrome. In this study, several PPARδ agonists with experimental biological activity were selected for a structural and chemical study.

Light-induced oxidation of unsaturated lipids as sensitized by flavins.

Triplet-excited riboflavin ((3)RF*) was found by laser flash photolysis to be quenched by polyunsaturated fatty acid methyl esters in tert-butanol/water (7:3, v/v) in a second-order reaction with k approximately 3.0 x 10(5) L mol(-1) s(-1) at 25 degrees C for methyl linoleate and 3.1 x 10(6) L mol(-1) s(-1), with DeltaH(double dagger) = 22.