Synthesis and evaluation of lipoic acid - donepezil hybrids for Alzheimer's disease using a straightforward strategy.

Alzheimer's disease is associated with a progressive loss of neurons and synaptic connections in the cholinergic system. Oxidative stress contributes to neuronal damages and to the development of amyloid plaques and neurofibrillary tangles. Therefore, antioxidants have been widely studied to mitigate the progression of Alzheimer's disease, and among these, lipoic acid has demonstrated a neuroprotective effect.

A colorimetric assay adapted to fragment screening revealing aurones and chalcones as new arginase inhibitors.

Arginase, a difficult-to-target metalloenzyme, is implicated in a wide range of diseases, including cancer, infectious, and cardiovascular diseases. Despite the medical need, existing inhibitors have limited structural diversity, consisting predominantly of amino acids and their derivatives. The search for innovative arginase inhibitors has now extended to screening approaches.

Adsorption of water in Na-LTA zeolites: an ab initio molecular dynamics investigation.

The very wide range of applications of LTA zeolites, including the storage of tritiated water, implies that a detailed and accurate atomic-scale description of the adsorption processes taking place in their structure is crucial. To unravel with an unprecedented accuracy the mechanisms behind the water filling in NaA, we have conducted a systematic ab initio molecular dynamics investigation. Two LTA structural models, the conventional Z4A and the reduced one ZK4, have been used for static and dynamic ab initio calculations, respectively.

Negative Impact of Citral on Susceptibility of to Antibiotics.

Essential oils (EOs) or their components are widely used by inhalation or nebulization to fight mild respiratory bacterial infections. However, their interaction with antibiotics is poorly known. In this study we evaluated the effects of citral, the main component of lemongrass oil, on susceptibility of to antibiotics.

Fate of cisplatin and its main hydrolysed forms in the presence of thiolates: a comprehensive computational and experimental study.

Interaction of platinum-based drugs with proteins containing sulphur amino acids is usually argued as one of the major reasons for the observed resistance to these drugs, mainly due to the deactivation of the native compounds by very efficient thiolation processes in the organism. In this work, we have investigated the detailed thermodynamics and kinetics of reaction between cisplatin cis-[PtCl2(NH3)2] and its major hydrolysed forms (monohydroxocisplatin cis-[PtCl(OH)(NH3)2] and monoaquacisplatin cis-[PtCl(H2O)(NH3)2]+) with various thiolates (methanethiolate, cysteine and glutathione) and methionine. We have used a demanding quantum chemistry approach at the MP2 and DFT levels of theory to determine the Gibbs free energies and the barrier of reactions of the most possible reaction paths.

Methionine oxidation by hydrogen peroxide in peptides and proteins: A theoretical and Raman spectroscopy study.

The oxidation of proteins results in their deterioration via the oxidation of reactive amino acids. Oxidation of the amino acid, methionine plays an important role during biological conditions of oxidative stress, and equally a role in protein stability. In this study the oxidation of the methionine residue using the tripeptide GlyMetGly with respect to hydrogen peroxide has been studied using both Raman spectroscopy and DFT calculations.

Empirical force field for cisplatin based on quantum dynamics data: case study of new parameterization scheme for coordination compounds.

Parameterization of molecular complexes containing a metallic compound, such as cisplatin, is challenging due to the unconventional coordination nature of the bonds which involve platinum atoms. In this work, we develop a new methodology of parameterization for such compounds based on quantum dynamics (QD) calculations. We show that the coordination bonds and angles are more flexible than in normal covalent compounds.

Theoretical insights into the mechanism of redox switch in heat shock protein Hsp33.

Heat shock protein 33 (Hsp33) is activated in the presence of H2O2 by a very interesting redox switch based on a tetra-coordinated zinc-cysteine complex present in the fully reduced and inactive protein form. The oxidation of this zinc center by H2O2 induces formation of two S-S bridges and the zinc release followed by the protein unfolding. We report here a theoretical study of the step-by-step sequence of the overall process starting with the oxidation of the first cysteine residue and ending with the zinc release.

An experimental and theoretical study of the amino acid side chain Raman bands in proteins.

The Raman spectra of a series of tripeptides with the basic formula GlyAAGly where the central amino acid (AA) was tryptophan, tyrosine, phenylalanine, glycine, methionine, histidine, lysine and leucine were measured in H2O. The theoretical Raman spectra obtained using density functional theory (DFT) calculations at the B3LYP/6-311+G(2df,2pd) level of theory allows a precise attribution of the vibrational bands. The experimental results show that there is a blue shift in the frequencies of several bands of the amino acid side chains in tripeptides compared to free amino acids, especially in the case of AAs containing aromatic rings.

Hemoglobin as a nitrite anhydrase: modeling methemoglobin-mediated N2O3 formation.

Nitrite has recently been recognized as a storage form of NO in blood and as playing a key role in hypoxic vasodilation. The nitrite ion is readily reduced to NO by hemoglobin in red blood cells, which, as it happens, also presents a conundrum. Given NO's enormous affinity for ferrous heme, a key question concerns how it escapes capture by hemoglobin as it diffuses out of the red cells and to the endothelium, where vasodilation takes place.

Cysteine oxidation by the superoxide radical: a theoretical study.

The cysteine residue oxidation by the superoxide radical in the gas phase and in aqueous solution is studied using the integrated molecular orbital+molecular orbital (IMOMO) method combining the quadratic configuration interaction [QCISD(T)] and density functional (DFT) methods. The molecular environment effects are systematically investigated by considering two alternative directions of attack of the superoxide radical on the thiol and two different cysteine residue conformations. It is found that hydrogen bonding and the electrostatic interactions between the superoxide radical and cysteine side chain significantly affect the reaction energy barrier, as compared to that derived for the simple thiol model methanethiol.

Mechanism of thiol oxidation by the superoxide radical.

In spite of the large quantity of experimental work that deals with the oxidation of thiols by superoxide, the mechanism of this reaction is still controversial. The ab initio molecular orbital calculations reported here predict that the main reaction pathway includes the formation of a three-electron-bonded adduct followed by the elimination of the hydroxide anion, giving the sulfinyl radical as the reaction product. The alternative reaction pathway consisting of hydrogen atom transfer from the thiol to the protonated superoxide radical involves a reaction energy barrier that is significantly higher.

Selenocysteine versus cysteine reactivity: a theoretical study of their oxidation by hydrogen peroxide.

The cysteine and selenocysteine oxidation by H2O2 in vacuo and in aqueous solution was studied using the integrated molecular orbital + molecular orbital (IMOMO) method combining the quadratic configuration method QCISD(T) and the spin projection of second-order perturbation theory PMP2. It is shown that including in the model system of cysteine (selenocysteine) residue up to 20 atoms has significant consequences upon the calculated reaction energy barrier. On the other hand, it is demonstrated that free cysteine and selenocysteine have very similar reaction energy barriers, 77-79 kJ mol(-1) in aqueous solution.

Mechanism of cysteine oxidation by a hydroxyl radical: a theoretical study.

Cysteine oxidation by HO(.) was studied at a high level of ab initio theory in both gas phase and aqueous solution. Potential energy surface scans in the gas phase performed for the model system methanethiol+HO(.

A computational study of thiolate and selenolate oxidation by hydrogen peroxide.

Ab initio molecular orbital calculations have been used to study the effects of the molecular environment on the oxidation of thiolate and selenolate by hydrogen peroxide. The reaction was first examined in vacuo at the QCISD(T)/6-311+G(2df,2pd)//MP2/6-311+G(d,p) level of theory. It was found for both thiolate and selenolate that a reactant aggregate is formed, which has a dissociation rate constant comparable to the activation rate constant (about 10(-3) s(-1) for thiolate and 10(-1) s(-1) for selenolate).