Predicting biological activity and design of 5-HT antagonists through assessment of ANN-QSAR models in the context of Alzheimer's disease.

Context: Alzheimer's disease (AD) is the leading cause of dementia around the world, totaling about 55 million cases, with an estimated growth to 74.7 million cases in 2030, which makes its treatment widely desired. Several studies and strategies are being developed considering the main theories regarding its origin since it is not yet fully understood.

Antioxidant capacity of simplified oxygen heterocycles and proposed derivatives by theoretical calculations.

Context: Some structural properties can be involved in the antioxidant capacity of several polyphenol derivatives, among them their simplified structures. This study examines the contribution of simplified structure for the antioxidant capacity of some natural and synthetic antioxidants. The resonance structures were related to the π-type electron system of carbon-carbon double bonds between both phenyl rings.

A PLS study on the psychotropic activity for a series of cannabinoid compounds.

Introduction: The use of the Cannabis sativa plant by man has been common for centuries due to its numerous therapeutic properties resulting from the compounds present in it, called cannabinoids. However, the use of these compounds as drugs is still limited due to the psychotropic effects caused by them. The proteins that act as receptors of cannabinoid compounds were identified and characterized, being called CB1 and CB2 receptors.

Towards a relationship between photoluminescence emissions and photocatalytic activity of AgSeO: combining experimental data and theoretical insights.

A systematic theoretical and experimental study was carried out to find a relationship between photoluminescence emissions and photocatalytic activity of AgSeO obtained by different synthesis methods (sonochemistry, ultrasonic probe, coprecipitation and microwave assisted hydrothermal synthesis). Experimental characterization techniques (XRD with Rietveld refinement, Raman, FTIR, UV-vis, XPS and photoluminescence spectroscopy) were used to elucidate its structural order at short, medium, and long ranges. Morphological analysis performed by FE-SEM showed distinct morphologies due to the different methods of synthesis.

Examining the Effect of Charged Lipids on Mitochondrial Outer Membrane Dynamics Using Atomistic Simulations.

The outer mitochondrial membrane (OMM) is involved in multiple cellular functions such as apoptosis, inflammation and signaling via its membrane-associated and -embedded proteins. Despite the central role of the OMM in these vital phenomena, the structure and dynamics of the membrane have regularly been investigated in silico using simple two-component models. Accordingly, the aim was to generate the realistic multi-component model of the OMM and inspect its properties using atomistic molecular dynamics (MD) simulations.

Drug design of new 5-HTR antagonists aided by artificial neural networks.

Alzheimer's Disease (AD) is the most frequent illness and cause of death amongst the age related-neurodegenerative disorders. The Alzheimer's Disease International (ADI) reported in 2019 that over 50 million people were living with dementia in the world and this number could potentially be around 152 million by 2050.5-hydroxtryptamine subtype 6 receptor (5-HTR) has been identified as a potential anti-amnesic drug target and therefore, the administration of 5-HTR antagonists can likely mitigate the memory loss and intellectual deterioration associated with AD.

On polarization functions for Gaussian basis sets.

In this work, we introduce a technique to choose polarization functions directly from the primitive set of Gaussian exponent without the necessity to optimize or even reoptimized them. For this purpose, initially, we employed Gaussian basis sets generated by using the Polynomial Generator Coordinate Hartree-Fock (PGCHF) method, and later we extended our technique to the cc-pVQZ and pc-3 Gaussian basis sets in order to show how our technique works and how good it is. Using the new polarized basis sets, from our technique, total electronic energies, equilibrium geometries, and vibrational frequencies were calculated for a set of molecules containing atoms from H(Z = 1) to Ba(Z = 56).

Experimental and theoretical study on structure-tautomerism among edaravone, isoxazolone, and their heterocycles derivatives as antioxidants.

Edaravone is a heterocyclic pyrazolone compound. It has pronounced effect against free radicals, however renal and hepatic disorders have been reported. Isoxazolones are considered bioisosteric analogues of pyrazolones and may have comparable properties.

Microwave-Driven Hexagonal-to-Monoclinic Transition in BiPO: An In-Depth Experimental Investigation and First-Principles Study.

Present theoretical and experimental work provides an in-depth understanding of the morphological, structural, electronic, and optical properties of hexagonal and monoclinic polymorphs of bismuth phosphate (BiPO). Herein, we demonstrate how microwave irradiation induces the transformation of a hexagonal phase to a monoclinic phase in a short period of time and, thus, the photocatalytic performance of BiPO. To complement and rationalize the experimental results, first-principles calculations have been performed within the framework of density functional theory.

Advances and Perspectives in Applying Deep Learning for Drug Design and Discovery.

Discovering (or planning) a new drug candidate involves many parameters, which makes this process slow, costly, and leading to failures at the end in some cases. In the last decades, we have witnessed a revolution in the computational area (hardware, software, large-scale computing, etc.), as well as an explosion in data generation (big data), which raises the need for more sophisticated algorithms to analyze this myriad of data.

A Proposal for the Mechanism of the CH + CO Reaction.

Few experimental studies on the CH + CO global reaction propose H, CO, and HCO as major products. However, the reaction mechanisms behind this process have not yet been elucidated. Moreover, some intriguing kinetic particularities were noticed in these previous investigations.

New consensus multivariate models based on PLS and ANN studies of sigma-1 receptor antagonists.

The treatment of neuropathic pain is very complex and there are few drugs approved for this purpose. Among the studied compounds in the literature, sigma-1 receptor antagonists have shown to be promising. In order to develop QSAR studies applied to the compounds of 1-arylpyrazole derivatives, multivariate analyses have been performed in this work using partial least square (PLS) and artificial neural network (ANN) methods.

Relativistic Prolapse-Free Gaussian Basis Sets of Quadruple-ζ Quality: (aug-)RPF-4Z. III. The f-Block Elements.

The f-block elements are addressed in this third part of a series of prolapse-free basis sets of quadruple-ζ quality (RPF-4Z). Relativistic adapted Gaussian basis sets (RAGBSs) are used as primitive sets of functions while correlating/polarization (C/P) functions are chosen by analyzing energy lowerings upon basis set increments in Dirac-Coulomb multireference configuration interaction calculations with single and double excitations of the valence spinors. These function exponents are obtained by applying the RAGBS parameters in a polynomial expression.

Accurate Gaussian basis sets for atomic and molecular calculations obtained from the generator coordinate method with polynomial discretization.

Accurate Gaussian basis sets for atoms from H to Ba were obtained by means of the generator coordinate Hartree-Fock (GCHF) method based on a polynomial expansion to discretize the Griffin-Wheeler-Hartree-Fock equations (GWHF). The discretization of the GWHF equations in this procedure is based on a mesh of points not equally distributed in contrast with the original GCHF method. The results of atomic Hartree-Fock energies demonstrate the capability of these polynomial expansions in designing compact and accurate basis sets to be used in molecular calculations and the maximum error found when compared to numerical values is only 0.

Understanding the cytotoxicity or cytoprotective effects of biological and synthetic quinone derivatives by redox mechanism.

Quinones represent an important class of biological compounds, but are also involved with toxicological intermediates and among their hazardous effects include cytotoxicity, immunotoxicity, and carcinogenesis. The structure-toxicity relationship for quinone derivatives has been used to cytotoxicity or cytoprotective effects by redox mechanism is determined using quantum chemical calculations through the density functional theory (DFT). According to our DFT study, the electron acceptance is related with LUMO, electron affinity, and stabilization energy values.

Relativistic Prolapse-Free Gaussian Basis Set of Quadruple-ζ Quality: (aug-)RPF-4Z. I. The s- and p-Block Elements.

This study reports a new relativistic prolapse-free Gaussian basis set series of quadruple-ζ quality, RPF-4Z, and an augmented version that includes extra diffuse functions, aug-RPF-4Z, for all the s- and p-block elements. The relativistic adapted Gaussian basis sets (RAGBSs), which are free of variational prolapse, were used as the starting primitive sets. Exponents of correlating/polarization functions were taken from a polynomial version of the generator coordinate Dirac-Fock (p-GCDF) method, in which the previously optimized RAGBS parameters are applied.

The CH3PH2 and CH3PH isomers: isomerization, hydrogen release, thermodynamic, and spectroscopy properties.

In this study was performed a quantum chemical investigation of the methylphosphine molecule and its radical, which may show potential implications in interstellar processes, and may be crucial atmospheric tracer gasses in the atmosphere of Giant planets. The analyses were performed with the density functional theory and coupled cluster methods. The anharmonic vibrational modes were predicted for all the isomers.

Quantum chemical DFT study of the interaction between molecular oxygen and FeN₄ complexes, and effect of the macrocyclic ligand.

Density functional theory (DFT) was used to examine the interaction between molecular oxygen (O₂) and macrocyclic iron complexes of the type FeN₄ during the formation of FeN₄--O₂ adducts. In order to understand how this interaction is affected by different macrocyclic ligands, O₂ was bonded to iron-tetraaza[14]annulene (FeTAA), iron-tetramethyl-tetraaza[14]annulene (FeTMTAA), iron-hexamethyl-tetraaza[14]annulene (FeHMTAA), iron dibenzotetraaza[14]annulene (FeDBTAA), and two iron-tetramethyl-dibenzotetraaza[14]annulene complexes (FeTMDBTAA1, FeTMDBTAA2). The ground state for FeN₄-O₂ adducts was the open-shell singlet.

Pattern recognition techniques applied to the study of leishmanial glyceraldehyde-3-phosphate dehydrogenase inhibition.

Chemometric pattern recognition techniques were employed in order to obtain Structure-Activity Relationship (SAR) models relating the structures of a series of adenosine compounds to the affinity for glyceraldehyde 3-phosphate dehydrogenase of Leishmania mexicana (LmGAPDH). A training set of 49 compounds was used to build the models and the best ones were obtained with one geometrical and four electronic descriptors. Classification models were externally validated by predictions for a test set of 14 compounds not used in the model building process.

Molecular properties of the PCO radical: heat of formation and the isomerization pathways.

The potential energy surface of [P,C,O] system in the ground state was investigated by quantum chemical methods. Four different isomers were characterized at the B3LYP/aug-cc-pVTZ: COP (i1), cPCO (i2), PCO (i3), and CPO (i4). The linear species i3 is the global minimum in the ground state surface, while i4 is a bent structure, and i2 is a cyclic isomer.

Molecular features related to HIV integrase inhibition obtained from structure- and ligand-based approaches.

Among several biological targets to treat AIDS, HIV integrase is a promising enzyme that can be employed to develop new anti-HIV agents. The aim of this work is to propose a mechanistic interpretation of HIV-1 integrase inhibition and to rationalize the molecular features related to the binding affinity of studied ligands. A set of 79 HIV-1 integrase inhibitors and its relationship with biological activity are investigated employing 2D and 3D QSAR models, docking analysis and DFT studies.

Understanding the molecular aspects of tetrahydrocannabinol and cannabidiol as antioxidants.

An antioxidant mechanism of tetrahydrocannabinol (THC) and cannabidiol (CBD) were compared with a simplified model of α-tocopherol, butylhydroxytoluene and hydroxytoluene in order to understand the antioxidant nature of THC and CBD molecules using DFT. The following electronic properties were evaluated: frontier orbitals nature, ionization potential, O-H bond dissociation energy (BDEOH), stabilization energy, and spin density distribution. An important factor that shows an influence in the antioxidant property of THC is the electron abstraction at the phenol position.

Non-peptidic cruzain inhibitors with trypanocidal activity discovered by virtual screening and in vitro assay.

A multi-step cascade strategy using integrated ligand- and target-based virtual screening methods was developed to select a small number of compounds from the ZINC database to be evaluated for trypanocidal activity. Winnowing the database to 23 selected compounds, 12 non-covalent binding cruzain inhibitors with affinity values (K i) in the low micromolar range (3-60 µM) acting through a competitive inhibition mechanism were identified. This mechanism has been confirmed by determining the binding mode of the cruzain inhibitor Nequimed176 through X-ray crystallographic studies.