Polyoxometalates are extensively researched chemical entities with well-documented applications ranging from photochemical processes to hydrogen evolution reactions. Niobium and tantalum, two metals that naturally co-occur, present separation challenges experimentally. Consequently, the stability of mixed Lindqvist polyoxoniobates and tantalates was investigated. Density functional theory (DFT) and time-dependent DFT simulations are employed to determine the electronic structures of these compounds. It was found that the cohesive energy of tantalum-based species is lower than that of niobium-based species, suggesting reduced stability in the formation of Lindqvist hexatantalate, with energies of -1846 and 0 kJ mol-1, respectively. The spectrum analysis indicates Nb- O being dominant in the charge-transfer process and therefore more suitable for photochemical applications. This study aims to elucidate the electronic structure and spectroscopic characteristics of mixed Lindqvist species, enhancing understanding for future applications.

Kojic acid is a natural product produced by many fungal species and has a wide range of applications. The chelating and antioxidant capacity are associated with their chemical and biological properties. In this study, some molecular modifications were proposed and substituted and hydroxylated phenyl moieties were introduced in the basic structure of kojic acid. The antioxidant capacities were calculated by DFT/B3LYP/6-311++G(2d,2p). Different antioxidant mechanisms were considered such as frontier molecular orbitals (HOMO, LUMO, and GAP), electron (IP, SET, and SPLET), or hydrogen transfers (BDEOH and HAT) on gas phase and PCM methods. The phenyl increases the antioxidant capacity, especially when an electron donating group (EDG) is found at the para position of the phenyl ring when compared to electron withdrawing groups (EWGs), for all studied mechanisms. The chemical stability agrees with spin density contributions for their cationic free radicals and semiquinones. A structural similarity between hydroxylated derivatives of kojic acid and quercetin was observed on gas phase and water. The lower BDEOH values at the phenol positions are more important for the antioxidant capacity than at the enol position. Phenolic semiquinones are more stables than enolic ones. The chemical stability depends on the number of resonance structures and the positions where the unpaired electron can be found with the highest contributions. In conclusion, phenyl substitution is a valuable molecular modification for the increase on antioxidant capacity of kojic acid. Quercetin analogues of kojic acid were proposed as strong antioxidant derivatives.

Quinoline derivatives play a crucial role in antimalarial therapy, and their biological properties are highly dependent of their basicity, particularly at the amine groups. The Amine moieties significantly contribute to the antioxidant capacity of quinoline derivatives through electron transfer mechanisms. A theoretical study was conducted to investigate the structure-nucleophilicity and antioxidant capacity of quinoline derivatives, specifically chloroquine and quinine, through electron transfer using DFT/B3LYP/6-311++G(2d,2p) methods. The HOMO values were utilized to assess nucleophilicity, while the ionization potential was indicative of electron donating capacity. To explore different aspects of the molecules, three approaches were proposed: simplification, fragmentation, and modification on amine moieties. Our findings reveal a synergistic effect between 4-amino-quinoline and tertiary amine in quinoline derivatives, enhancing their overall antioxidant capacity. However, the presence of the chlorine atom decreases its contribution as an electron withdrawing group. Chloroquine exhibits a higher antioxidant capacity when compared to quinine, and their respective electron donation abilities are correlated with their pKa values. The synergistic effect between the 4-amino-quinoline and tertiary amine is particularly evident in chloroquine, surpassing the antioxidant capacity of 6-methoxy-4-methyl-quinoline moiety in quinine.

Kojic acid is a natural product produced by many fungal species and has a wide range of applications. The chelating and antioxidant capacity are associated with their chemical and biological properties. In this study, some molecular modifications were proposed. The phenyl moieties were introduced in the basic structure of kojic acid. Their antioxidant capacities were theoretically evaluated via DFT method by using the functional B3LYP with 6-311++G(2d,2p) basis set. Different antioxidant mechanisms were considered such as frontier molecular orbitals (HOMO, LUMO, and GAP), electron (IP, SET, and SPLET), or hydrogen transfers (BDEOH and HAT). The inclusion of phenyl increases the antioxidant capacity, especially when an electron donating group (EDG) is found at the para position of the phenyl ring when compared to electron withdrawing groups (EWGs), for all studied mechanisms. The chemical stability agrees with spin density contributions for their cationic free radicals and semiquinones. In conclusion, phenyl substitution is an important molecular modification that increases the antioxidant capacity of kojic acid.

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. Among these strategies, the 5-HT6 receptor antagonism emerges as an auspicious and viable symptomatic treatment approach for AD. The 5-HT6 receptor belongs to the G protein-coupled receptor (GPCR) family and is closely implicated in memory loss processes. As a serotonin receptor, it plays an important role in cognitive function. Consequently, targeting this receptor presents a compelling therapeutic opportunity. By employing antagonists to block its activity, the 5-HT6 receptor's functions can be effectively modulated, leading to potential improvements in cognition and memory. METHODS:Addressing this challenge, our research explored a promising avenue in drug discovery for AD, employing Artificial Neural Networks-Quantitative Structure-Activity Relationship (ANN-QSAR) models. These models have demonstrated great potential in predicting the biological activity of compounds based on their molecular structures. By harnessing the capabilities of machine learning and computational chemistry, we aimed to create a systematic approach for analyzing and forecasting the activity of potential drug candidates, thus streamlining the drug discovery process. We assembled a diverse set of compounds targeting this receptor and utilized density functional theory (DFT) calculations to extract essential molecular descriptors, effectively representing the structural features of the compounds. Subsequently, these molecular descriptors served as input for training the ANN-QSAR models alongside corresponding biological activity data, enabling us to predict the potential efficacy of novel compounds as 5-hydroxytryptamine receptor 6 (5-HT6) antagonists. Through extensive analysis and validation of ANN-QSAR models, we identified eight new promising compounds with therapeutic potential against AD.

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. There is a series of 50 cannabinoid compounds that was studied through quantum and chemometric methods in order to obtain a mathematical model that could relate the structure of these compounds to their psychotropic activity. That model proved to be effective by predicting the psychoactivity of the 50 compounds from the series and elucidating relevant characteristics that imply in psychoactivity. However, most of these 50 compounds do not have experimental data of biological activity with CB1 and CB2 receptors. This study aims to generate QSAR models in order to predict the biological activity of the 50 cannabinoid compounds and then relate the predicted biological activity values to the already known psychoactivity. Another series of cannabinoid compounds was selected to generate and validate QSAR models, aiming to predict the biological activity of the 50 cannabinoid compounds with both CB1 and CB2 receptors. The PLS-CB1 and PLS-CB2 QSAR models were generated and validated in this work, proving to be highly predictive, and the biological activities (pK ) of the 50 cannabinoid compounds were predicted by them. It is important to highlight compounds Ic14, Ic18, and Ic19 (psychotropic inactive) which presented higher predicted pK values than the main cannabinoid compounds (Δ9-THC and Δ8-THC). Also, compound Ic21 stood out as the highest value of the predicted biological activities in the interaction with the CB2 receptor. The generated PLS models and the predicted pKi values of the 50 cannabinoid compounds can provide valuable information in the drug design of new cannabinoid compounds that can interact with CB1 and CB2 receptors in a therapeutic way with no psychotropic effects.

Reactions of cis -[RuCl 2 (P-P)(bipy)] precursors with the SpymMe 2 ligand (4,6-dimethyl-2pyrimidinethiol) yielded complexes of the [Ru(SpymMe 2 )(P-P)(bipy)]PF 6 type, where P-P = 1,2bis(diphenylphosphino)ethane (dppe - for complex 1 ), 1,3-bis(diphenylphosphino)propane (dppp - for complex 2 ) and 1,1'-bis(diphenylphosphino)ferrocene (dppf - for complex 3 ) and bipy = 2,2'-bipyridine. The new compounds were obtained by displacing the chlorido ligands from the precursors and coordination of one monoanionic 4,6-dimethyl-2-pyrimidinethiol ligand. All complexes were characterized by spectroscopic, electrochemical and elemental analysis techniques, as well as single-crystal X-ray diffraction, where the structures of complexes 1, 2 and 3 showed that the SpymMe 2 ligand coordinates to the ruthenium(II) center as bidentated, yielding complexes with the sulfur atom trans positioned to the nitrogen atom from the bipy ligand. A theoretical study of the structures of the complexes was performed using the DFT/B3LYP method. Distances and angles of optimized structures agree with X-ray experimental data. Furthermore, the calculated IR and UV-Vis spectra are compatible with experimental data. Charge decomposition analysis (CDA) and NBO (natural bond orbitals) charges showed that there was an overall charge transfer from bipy and P-P ligands to the ruthenium centers. Higher electrochemical stability and 1 H and 31 P{ 1 H} NMR shifts of 1, 2 and 3 compared with precursors could be explained by the lower values of calculated molecular orbital energies, NBO charge on atoms and CDA data. Finally, the structure of the isomers of complexes 1, 2 and 3, considering the sulfur atom trans positioned to the phosphorus atom, were optimized, showing that they are slightly less stable, presenting total energy higher, 10.4, 31.5 and 60.5 kJ/mol than 1, 2 and 3 , where nitrogen is trans to the phosphorus atom. (c) 2023 Elsevier B.V. All rights reserved.

The present work deals with studies of the obtaining structures Monoclinic Scheelita (MS) and Tetragonal Zir-conia (TZ) of BiVO4 through an experimental procedure. First, the characterization of the samples evaluates their structural and electronic properties. Then, from the analysis of X-ray diffraction (XRD) for pH 1, occurs the formation of the TZ phase, which with higher processing times, occurs the transformation to the MS phase, different from the pH 5 at which the MS phase was formed, with higher processing times, occurs a formation of a second phase (TZ). The temperature, pressure, and pH values of the hydrothermal treatment contribute to the organization of the crystalline system. For the solar photocatalysis and microbial tests, the MS phase presented the best results because it has a higher absorption in the visible phase, defined morphologies, and low bandgap values.

Electronic structure properties of 13-atom icosahedral alkali metal clusters (X13, X = Li, Na, K, Rb, and Cs) were investigated with the Diffusion Monte Carlo (DMC) and Density Functional Theory (DFT) methods. The overall results of vertical ionization energies, vertical electron affinities and dissociation energies are in good agreement with theoretical/experimental values found in the literature for these clusters. However, the DFT approach investigated, B3LYP, provides larger discrepancies than DMC for dissociation energies. In this case, empirical dispersion corrections seem important to improve the binding energy data from DFT. We also considered heteronuclear alkali metal clusters such as YX12, where the Y atom was placed at the center and also at the face of the initial icosahedral structure of X13. To our knowledge, the results for such heteronuclear clusters are being reported for the first time, providing an important initial step for understanding these systems. This work demonstrates that face-type YX12 clusters are usually more strongly bonded than the respective center-type structures, except for LiNa12, CsRb12, and KCs12 (according to DMC results). In addition, the trends evidenced in binding energies are analysed in details.

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. Trans-resveratrol, phenyl-benzofuran, phenyl-indenone, and benzylidene-benzofuranone are the best basic antioxidant templates among the simplified derivatives studied here. Additionally, the stilbene moiety was found on the molecules with the best antioxidant capacity. Furthermore, our investigation suggests that these compounds can be used as antioxidant scaffold for designing and developing of new promising derivatives. To investigate the structure–antioxidant capacity for sixteen simplified natural and proposed derivatives we have employed density functional theory and used Gaussian 09. Our DFT calculations were performed using the B3LYP functional and the 6-31+G(d,p) basis set. All electron transfer mechanisms were investigated by using values of HOMO, ionization potential, energy affinity, stabilization energies, and spin density distributions.

A systematic theoretical and experimental study was carried out to find a relationship between photoluminescence emissions and photocatalytic activity of Ag2SeO4 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. Based on density functional theory (DFT) calculations, it was possible to study in detail the Ag2SeO4 surface properties, including its surface energy, geometry, and electronic structure for the (100), (010), (001), (101), (011), (110), (111), (021), (012) and (121) surfaces. The equilibrium morphology of Ag2SeO4 was predicted as a truncated octahedron with exposed (111), (001), (010) and (011) surfaces. Photoluminescence emissions showed a band covering the visible spectrum, and the Ag2SeO4 obtained by the coprecipitation method presented the most intense band with a maximum in the red region. Photocatalytic results confirmed that Ag2SeO4 synthesized by the sonochemistry method is the best photocatalyst for rhodamine B degradation under UV light irradiation.

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. All major lipid components, phosphatidylinositol (PI), phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylserine (PS), were included in the probed OMM models. Because increased levels of anionic PS lipids have potential effects on schizophrenia and, more specifically, on monoamine oxidase B enzyme activity, the effect of varying the PS concentration was explored. The MD simulations indicate that the complex membrane lipid composition (MLC) behavior is notably different from the two-component PC-PE model. The MLC changes caused relatively minor effects on the membrane structural properties such as membrane thickness or area per lipid; however, notable effects could be seen with the dynamical parameters at the water-membrane interface. Increase of PS levels appears to slow down lateral diffusion of all lipids and, in general, the presence of anionic lipids reduced hydration and slowed down the PE headgroup rotation. In addition, sodium ions could neutralize the membrane surface, when PI was the main anionic component; however, a similar effect was not seen for high PS levels. Based on these results, it is advisable for future studies on the OMM and its protein or ligand partners, especially when wanting to replicate the correct properties on the water-membrane interface, to use models that are sufficiently complex, containing anionic lipid types, PI in particular.

THEORETICAL AND EXPERIMENTAL STUDY OF STRUCTURE AND REACTIVITY RELATED TO METABOLISM AND TOXICITY OF PARACETAMOL. An experimental and theoretical approach on oxidative metabolism of paracetamol was applied for the pharmaceutical chemistry learning. Classical reactions, functional group identification, structural parameter, and chemical reactivity using frontier orbitals and Fukui index were used explaining the main products between N-acetyl-p-benzosemiquinone (NAPQI) and thiolic compounds. The chemoprotection mechanisms by N-acetyl-cysteine on high dosage of paracetamol are consistent with theoretical and experimental results. The methods also described the relationship between the chemical reactivity of quinone-imine system and the induced-toxicity of paracetamol by Michael reaction. These results can be applied in experimental pharmaceutical chemistry teaching.

•Structural, electronic properties and relative stability of PH3F isomers.•Isotropic hyperfine coupling constants, NBO and QTAIM analysis.•Vibrational frequencies and electric dipole moment calculations.•Isomerization, H-elimination and 1,2-hydrogen shift mechanisms.•Thermochemical calculations: H-abstraction vs H-elimination.

The polynomial Generator Coordinate Hartree-Fock Gaussian basis sets, pGCHF, for the atoms Na, Mg, Al, Si, P, S, and Cl were generated using the generator coordinate method based on polynomial integral expansion to discretise the Griffin-Wheeler-Hartree-Fock equations. The pGCHF basis sets were contracted with the CONTRACT program based on the Davidson contraction model through which a set of 9s8p functions for the atoms Na through Cl were obtained. Polarisation exponents generated using the POLARIZATION program were added to the contracted pGCHF Gaussian basis sets. Molecular calculations at the DFT level of theory showed that the pGCHF basis sets can be used to calculate the atomisation energy with accuracy comparable to the well-established pcseg-3, def2-QZVP, and Sapporo-QZP basis sets; also, the complete basis set (CBS) limit estimate was obtained with the pcseg-3/pcseg-4 basis sets.

The molecular mechanism of cytoprotective effect on human erythrocytes of aminophenol and salicylates associated derivatives was related to their antioxidant capacity. The oxidative hemolysis induced by water-soluble free-radical initiator 2,2’-azobis-(2-amidine-propane)-dihydrochloride (AAPH) was inhibited by drug candidates named benzaminophen (BZL), salicytamide or 5-acetamide-salicylic acid (ASL), and salibenzamide or 5-benzamide-salicylic acid (BSL) when compared to their parents salicylic acid (SAC) and acetaminophen (ACP). Trolox (TLX) was the most powerful compound and used as positive control. BZL showed a potent effect followed by ACP > BSL > ASL. SAC did not show protective effect in any evaluated concentrations. These results are in accordance with the molecular mechanism by using theoretical calculation of single electron transfers (SET), hydrogen atom transfers (HAT), and sequential proton loss electron transfer (SPLET) by means of DFT/B3LYP/6-31++G(d,p) level of theory. [1,5] Hydrogen shift between carboxyl and phenol moieties and electronic properties related to pKa and other physicalchemical properties can be involved. The molecular association approach provides protective compounds more effective than SAC.

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-HT6R) has been identified as a potential anti-amnesic drug target and therefore, the administration of 5-HT6R antagonists can likely mitigate the memory loss and intellectual deterioration associated with AD. Herein, computational tools were applied to design new 5-HT6 antagonists and their biological activity values were predicted by our QSAR model obtained from Artificial Neural Networks (ANN). The proposed compounds here from the QSAR-ANN model presented significant biological activity values and some of them have achieved pKi above 9.00. Furthermore, our results suggest that the presence of halogen atoms (especially bromine) linked to the aromatic ring at para-position (HYD) contribute considerably to the increase of the biological activity values while bulky groups in the PI position do not culminate with the increase antagonist activity of compounds here analyzed. Finally, the ADME/Tox profile as well as the synthetic accessibility of new proposed compounds qualify them to go on further with experimental procedures and thenceforward their antagonist effects can be confirmed.

Schizophrenia is a psychiatric disorder that affects 20 million people worldwide and the mortality rate is two or three times higher than the average overall population mainly due to high frequency of suicide and other associated comorbidities. The therapeutic approaches used for its treatment, besides do not combat this illness, trigger several side effects, being imperative the development of new medical countermeasures. In the search for new agents, we constructed a statistical model (model A) with a series of aripiprazole-derived using the partial least squares technique, and posteriorly we applied several validation tests to guarantee consistency of model A and its forecasting ability. In addition, molecular docking simulations were employed to extract important information on structural elements involved in the molecular recognition process from receptor-ligand complex. We designed new compounds whose biological activity values were predicted by our model. Among new designed molecules, we highlight compounds 2, 5, 9, and 11 with predicted pK(i) values over 8.5. We underline that the presence of ester moieties attached to the aromatic ring from region A is well tolerated in this position and contributes to increase the pK(i) values; otherwise it is essential that there are no bulky groups in region C. Finally, ADME/Tox properties evaluated via in silico approach for the proposed compounds shed light on their drug-likeness characteristics, indicating that they could be a reliable starting point as potent candidates to further experimental exploration (chemical synthesis, in vitro and in vivo analyses).

Neuropathic pain is a cureless syndrome and affects considerably the life quality of people stricken by it. Drugs currently used for its treatment do not significantly reduce the symptoms and/or have many side effects. In the search for other therapeutic approaches, the sigma-1 receptor has been pointed out as a promising drug target for the treatment of neuropathic pain. As part of our effort to help the development of new therapeutic agents against neuropathic pain, we have applied techniques of quantitative structure-activity relationships (QSAR) to a series of compounds having the pyrimidine as scaffold using Partial Least Squares (PLS) and Artificial Neural Networks (ANN) to design new sigma-1R antagonists. Next, we have calculated a plethora of descriptors, which were selected from correlation matrix and genetic algorithm (AG). The selected descriptors were used to construct PLS and ANN models and, from them, various results were used to design new antagonists. At last, the designed compounds were subjected to the our QSAR models to predict their biological activity values. The new compounds exhibited significant biological affinity values, and among them we can highlight the compounds L2, L4, L14, L17, and L18 with excellent predicted pKi values confirmed by both PLS and ANN models. Therefore, the predictive ability of the PLS and ANN models here presented and their robustness allowed to extract important information that can be used in the design of new compounds as well as to predict their biological activity values.