Insights on molecular modeling and supramolecular arrangement of bilastine polymorphs.

CONTEXT: The advancement in the development of second-generation drugs in the field of antihistamines represents a significant milestone in the management of allergic diseases, targeting the effects of histamine. The efficacy of bilastine in treating allergic disorders has sparked interest in investigating its polymorphism, a crucial property that impacts quality, safety, and effectiveness as per regulatory guidelines. This study examines the polymorphism of bilastine, focusing on two crystalline forms labeled as Form I and Form II. Utilizing advanced analytical techniques, the research explores the structural characteristics and molecular interactions within these forms. Geometric parameters, such as bond lengths, bond angles, and torsion angles, are examined to comprehend molecular conformations and crystal packing arrangements. Hydrogen bonding, covalent bonds, and van der Waals forces contribute to the unique supramolecular arrangements in these forms. This study provides a significant contribution to understanding bilastine's polymorphism, offering critical insights to researchers and regulatory bodies to ensure the quality, efficacy, and safety of antihistamine products. METHODS: The molecular conformation of two bilastine forms was obtained through DFT with the exchange-correlation functional M06-2X and the 6-311 + + G(d,p) basis set, and the results were compared with the experimental X-ray. The atomic coordinates were obtained directly from the crystalline structures, and charge transfer was also investigated using frontier molecular orbitals (HOMO and LUMO), and MEP map in order to evaluate the energies associated with charge transfers and regions of high electron affinity. The geometric and topological parameters and intermolecular interactions in the crystals were analyzed using Hirshfeld Surface.

TYROBP/DAP12 knockout in Huntington's disease Q175 mice cell-autonomously decreases microglial expression of disease-associated genes and non-cell-autonomously mitigates astrogliosis and motor deterioration.

INTRODUCTION: Huntington's disease (HD) is a fatal neurodegenerative disorder caused by an expansion of the CAG trinucleotide repeat in the Huntingtin gene (HTT). Immune activation is abundant in the striatum of HD patients. Detection of active microglia at presymptomatic stages suggests that microgliosis is a key early driver of neuronal dysfunction and degeneration. Recent studies showed that deletion of Tyrobp, a microglial protein, ameliorates neuronal dysfunction in Alzheimer's disease amyloidopathy and tauopathy mouse models while decreasing components of the complement subnetwork. OBJECTIVE: While TYROBP/DAP12-mediated microglial activation is detrimental for some diseases such as peripheral nerve injury, it is beneficial for other diseases. We sought to determine whether the TYROBP network is implicated in HD and whether Tyrobp deletion impacts HD striatal function and transcriptomics. METHODS: To test the hypothesis that Tyrobp deficiency would be beneficial in an HD model, we placed the Q175 HD mouse model on a Tyrobp-null background. We characterized these mice with a combination of behavioral testing, immunohistochemistry, transcriptomic and proteomic profiling. Further, we evaluated the gene signature in isolated Q175 striatal microglia, with and without Tyrobp. RESULTS: Comprehensive analysis of publicly available human HD transcriptomic data revealed that the TYROBP network is overactivated in the HD putamen. The Q175 mice showed morphologic microglial activation, reduced levels of post-synaptic density-95 protein and motor deficits at 6 and 9 months of age, all of which were ameliorated on the Tyrobp-null background. Gene expression analysis revealed that lack of Tyrobp in the Q175 model does not prevent the decrease in the expression of striatal neuronal genes but reduces pro-inflammatory pathways that are specifically active in HD human brain, including genes identified as detrimental in neurodegenerative diseases, e.g. C1q and members of the Ccr5 signaling pathway. Integration of transcriptomic and proteomic data revealed that astrogliosis and complement system pathway were reduced after Tyrobp deletion, which was further validated by immunofluorescence analysis. CONCLUSIONS: Our data provide molecular and functional support demonstrating that Tyrobp deletion prevents many of the abnormalities in the HD Q175 mouse model, suggesting that the Tyrobp pathway is a potential therapeutic candidate for Huntington's disease.

Structural and Anticancer Studies of Methoxyflavone Derivative from Strychnos pseudoquina A.St.-Hil. (Loganiaceae) from Brazilian Cerrado.

The Cerrado biome is the world's largest and most diversified tropical savanna. Despite its diversity, there remains a paucity of scientific discussion and evidence about the medicinal use of Cerrado plants. One of the greatest challenges is the complexity of secondary metabolites, such as flavonoids, present in those plants and their extraction, purification, and characterization, which involves a wide range of approaches, tools, and techniques. Notwithstanding these difficulties, the search for accurately proven medicinal plants against cancer, a leading cause of death worldwide, has contributed to this growing area of research. This study set out to extract, purify, and characterize 3-O-methylquercetin isolated from the plant Strychnos pseudoquina A.St.-Hil. (Loganiaceae) and to test it for antiproliferative activity and selectivity against different tumor and nontumor human cell lines. A combined-method approach was employed using 1H and 13C nuclear magnetic resonance, thermogravimetric analysis, differential scanning calorimetry, single-crystal X-ray diffraction, Hirshfeld surface analysis, and theoretical calculations to extensively characterize this bioflavonoid. 3-O-methylquercetin melts around 275 °C and crystallizes in a nonplanar conformation with an angle of 18.02° between the pyran ring (C) and the phenyl ring (B), unlike quercetin and luteolin, which are planar. Finally, the in vitro cytotoxicity of 3-O-methylquercetin was compared with data from quercetin, luteolin, and cisplatin, showing that structural differences influenced the antiproliferative activity and the selectivity against different tumor cell lines.

The effect of water molecules on paraquat salts: from physicochemical properties to environmental impact in the Brazilian Cerrado.

Introduction: The green revolution model that is followed in the Brazilian Cerrado is dependent on mechanization, chemical fertilization for soil dressing and correction, and the use of herbicides. Paraquat is a methyl viologen herbicide marketed as bipyridylium dichloride salts and used (in low doses) to combat weeds in their post-emergence stage. It is a non-selective pesticide that causes the peroxidation of the lipids that make up the cell membrane, and when it comes into contact with foliage, it results in the death of the plant. Methods: The effect of water molecules co-crystallized in Paraquat salt structures was analyzed in anhydrous, dihydrate, and trihydrate forms to understand those physicochemical properties in its redox activity. The frontier molecular orbitals were also carried out using DFT to obtain the chemical reactivity of the bipyridylium cation. Finally, the supramolecular arrangements were evaluated to analyze the physicochemical stability and acquire insights on superoxide anions. Results and discussion: The electronic structure indicated that the BP cation presents an acidic character due to its low ELUMO value, while the salt has a more basic character due to its high EHOMO value. For this reason, the BP ion is more susceptible to reduction during the weeds' photosynthesis process. During the process of plant photosynthesis, PQ is reduced to form a stable radical cation. In the supramolecular arrangement, the presence of water molecules increases the number of strong H-bonds, while the weak/moderate H-bonds are stabilized. PQ's toxic effects are observed in wildlife, domesticated animals, human populations, and ecosystems. The influence of PQ on the terrestrial environment is limited because of the soil adsorption capacity associated with good agricultural practices. The current use of good agricultural practices in the Cerrado seems not to prevent the environmental impacts of herbicides like PQ because it aims for the expansion and profitability of large-scale farming based on input-intensive practices instead of sustainable agriculture processes.

Photoantimicrobial chitosan-gelatin-pomegranate peel extract films for strawberries preservation: From microbiological analysis to in vivo safety assessment.

This study aimed to investigate the application of biopolymeric materials (chitosan, gelatin, and pomegranate peel extract as photosensitizer) and antimicrobial photodynamic therapy (aPDT) on the physicochemical and microbial safety of strawberries. The photosensitizer potential of the materials was confirmed by a light-dose-dependent photobleaching profile. The application of light (525 nm; 50 J cm-2) decreased by >2 log CFU mL-1 the survival of Staphylococcus aureus on the surface of the photoactive-biopolymeric films. Moreover, the materials did not present in vivo cytotoxicity using Danio rerio (Zebrafish) as well as cytophytotoxic, genotoxic, or mutagenic potentials against Allium cepa plant model, which points out their safety to be used as films without posing a risk to the humans and the environment. The photoactive-polymeric coatings were able to maintain the strawberries weight, and the association with green light was 100 % effective in delaying fungal contamination. These coated-strawberries presented a significant reduction in S. aureus survival after light application (5.47-4.34 log CFU mL-1). The molecular level analysis of the photoactive compound cyanidin-3-glucoside indicates absorption on UV-Vis consistent with aPDT action. Therefore, this study showed that the antimicrobial effects of aPDT combined with photoactive-biopolymeric coatings were enhanced, while the quality of the strawberries was maintained.

Molecular basis of two pyrimidine-sulfonylurea herbicides: from supramolecular arrangement to acetolactate synthase inhibition.

CONTEXT: The design and synthesis of safe and highly active sulfonylurea herbicides is still a challenge. Therefore, following some principles of structure-activity relationship (SAR) of sulfonylurea herbicides, this work focuses on evaluating two sulfonylurea derivatives bearing electron-withdrawing substituents, namely, -(CO)OCH3 and -NO2 on the aryl group, on herbicidal activity. To understand the effects caused by the substituent groups, the molecular and electronic structures of the sulfonylureas were evaluated by density functional theory. Likewise, the crystalline supramolecular arrangements of both compounds were analyzed by Hirshfeld surface, QTAIM, and NBO, with the aim of verifying changes in intermolecular interactions caused by substituent groups. Finally, through a toxicophoric analysis, we were able to predict the interacting groups in their biological target, acetolactate synthase, and verify the interactions with the binding site. METHODS: All theoretical calculations were conducted using the highly parameterized empirical exchange-correlation functional M06-2X accompanied by the diffuse and polarized basis set 6-311++G(d,p). The atomic coordinates were obtained directly from the crystalline structures, and from the energies of the frontier molecular orbitals (HOMO and LUMO), chemical descriptors were obtained that indicated the influence of the functional groups in the sulfonylureas on the reactivity of the molecules. The intermolecular interactions in the crystals were analyzed using the Hirshfeld, QTAIM, and NBO surfaces. Toxicophoric modeling was performed by the PharmaGist webserver and molecular docking calculations were performed by the GOLD 2022.1.0 software package so that the ligand was fitted to the binding site in a 10 Å sphere. For this, genetic algorithm parameters were used using the ChemPLP scoring function for docking and ASP for redocking.

Studies on charge transfer of enalapril maleate: from solid-state to molecular dynamics.

INTRODUCTION: Enalapril maleate is an antihypertensive ethyl ester pro-drug with two crystalline forms. A network of hydrogen bonds in both polymorphs plays an important role on solid-state stability, charge transfer process and degradation reactions (when exposed to high humidity, temperature and/or pH changes). COMPUTATIONAL PROCEDURES: Supramolecular arrangement was proposed by Hirshfeld surface using the CrystalExplorer17 software and quantum theory of atoms in molecules. The electronic structure properties were calculated using the functional hybrid M06-2X with 6-311++G** base function employing diffuse and polarization functions to improve the description of hydrogen atoms on intermolecular interactions. Also, the H+ charge transfer between enalapril and maleate molecules was performed using Car-Parrinello molecular dynamics with the Verlet algorithm. In both simulations, the temperature of the ionic system was maintained around 300 K using the Nosé-Hoover thermostat and the electronic system evolved without the use of the thermostat. RESULTS: This work evaluates the effect of maleate on the structural stability of enalapril maleate solid state. The electronic structural analysis points out a partially covalent character for N1-H∙∙∙O7 interaction; and the molecular dynamic showed a decentralized hydrogen on maleate driving a decomposition by charge transfer process while a centered hydrogen driving the stabilization. The charge transfer process and the mobility of the proton (H+) between enalapril and maleate molecules was demonstrated using supramolecular modeling analyses and molecular dynamics calculations.

Structural basis of antibacterial photodynamic action of curcumin against S. aureus.

Antimicrobial photodynamic therapy (aPDT) is an alternative tool to commercial antibiotics for the inactivation of pathogenic bacteria (e.g., S. aureus). However, there is still a lack of understanding of the molecular modeling of the photosensitizers and their mechanism of action through oxidative pathways. Herein, a combined experimental and computational evaluation of curcumin as a photosensitizer against S. aureus was performed. The radical forms of keto-enol tautomers and the energies of curcumin's frontier molecular orbitals were evaluated by density functional theory (DFT) to point out the photodynamic action as well as the photobleaching process. Furthermore, the electronic transitions of curcumin keto-enol tautomers were undertaken to predict the transitions as a photosensitizer during the antibacterial photodynamic process. Moreover, molecular docking was used to evaluate the binding affinity with the S. aureus tyrosyl-tRNA synthetase as the proposed a target for curcumin. In this regard, the molecular orbital energies show that the curcumin enol form has a character of 4.5% more basic than the keto form - the enol form is a more promising electron donor than its tautomer. Curcumin is a strong electrophile, with the enol form being 4.6% more electrophilic than its keto form. In addition, the regions susceptible to nucleophilic attack and photobleaching were evaluated by the Fukui function. Regarding the docking analysis, the model suggested that four hydrogen bonds contribute to the binding energy of curcumin's interaction with the ligand binding site of S. aureus tyrosyl-tRNA synthetase. Finally, residues Tyr36, Asp40, and Asp177 contact curcumin and may contribute to orienting the curcumin in the active area. Moreover, curcumin presented a photoinactivation of 4.5 log unit corroborating the necessity of the combined action of curcumin, light, and O2 to promote the photooxidation damage of S. aureus. These computational and experimental data suggest insights regarding the mechanism of action of curcumin as a photosensitizer to inactivate S. aureus bacteria.

(E)-2-Benzylidenecyclanones: Part XVIII Study the Possible Link between Glutathione Reactivity and Cancer Cell Cytotoxic Effects of Some Cyclic Chalcone Analogs A Comparison of the Reactivity of the Open-Chain and the Seven-Membered Homologs.

Non-enzymatic thiol addition into the α,ß-unsaturated carbonyl system is associated with several biological effects. In vivo, the reactions can form small-molecule thiol (e.g., glutathione) or protein thiol adducts. The reaction of two synthetic (4'-methyl- and 4'-methoxy substituted) cyclic chalcone analogs with reduced glutathione (GSH) and N-acetylcysteine (NAC) was studied by (high-pressure liquid chromatography-ultraviolet spectroscopy) HPLC-UV method. The selected compounds displayed in vitro cancer cell cytotoxicity (IC50) of different orders of magnitude. The structure of the formed adducts was confirmed by (high-pressure liquid chromatography-mass spectrometry) HPLC-MS. The incubations were performed under three different pH conditions (pH 3.2/3.7, 6.3/6.8, and 8.0/7.4). The chalcones intrinsically reacted with both thiols under all incubation conditions. The initial rates and compositions of the final mixtures depended on the substitution and the pH. The frontier molecular orbitals and the Fukui function were carried out to investigate the effects on open-chain and seven-membered cyclic analogs. Furthermore, machine learning protocols were used to provide more insights into physicochemical properties and to support the different thiol-reactivity. HPLC analysis indicated diastereoselectivity of the reactions. The observed reactivities do not directly relate to the different in vitro cancer cell cytotoxicity of the compounds.

Kinetics, mechanism, and tautomerism in ametryn acid hydrolysis: From molecular structure to environmental impacts.

The excessive use of pesticides and the demand for environmentally friendly compounds have driven the focus to detailed studies of the environmental destination of these compounds. Degradation by hydrolysis of pesticides, when released into the soil, can result in the formation of metabolites with potentially adverse effects on the environment. Moving in this direction, we investigated the mechanism of acid hydrolysis of the herbicide ametryn (AMT) and predicted the toxicities of metabolites through experimental and theoretical approaches. The formation of ionized hydroxyatrazine (HA) occurs with the release of the SCH3- group and the addition of H3O+ to the triazine ring. The tautomerization reactions privileged the conversion of AMT into HA. Furthermore, the ionized HA is stabilized by an intramolecular reaction that provides the molecule in two tautomeric states. Experimentally, the hydrolysis of AMT was obtained under acidic conditions and at room temperature with HA as the main product. HA was isolated in a solid state through its crystallization as organic counterions. The mechanism of conversion of AMT to HA and the experimental investigation of the reaction kinetics allowed us to determine the dissociation of CH3SH as the rate-controlling step in the degradation process that culminates in a half-life between 7 and 24 months under typical acid soil conditions of the Brazilian Midwest - region with strong agricultural and livestock vocation. The keto and hydroxy metabolites showed substantial thermodynamic stability and a decrease in toxicity compared to AMT. We hope that this comprehensive study will support the understanding of the degradation of s-triazine-based pesticides.

Heteroaromatic salvinorin A analogue (P-3 l) elicits antinociceptive and anxiolytic-like effects.

Previous studies have attributed the prominent analgesic, hallucinogenic, sedative, and anxiolytic properties of Salvia divinorum to Salvinorin A. However, the overall pharmacological profile of this isolate limits its clinical applications. To address these limitations, our study evaluates the C(22)-fused-heteroaromatic analogue of salvinorin A [2-O-salvinorin B benzofuran-2-carboxylate] (P-3l) in mice nociception and anxiety models while assessing possible mechanism of action. In comparison with the control group, orally administered P-3l (1, 3, 10, and 30 mg/kg) attenuates acetic acid-induced abdominal writhing, formalin-induced hind paw licking, the thermal reaction to the hotplate, and/or aversive response in the elevated plus-maze, open field, and light-dark box; and potentiates the effect of morphine and diazepam at sub-effective doses (1.25 and 0.25 mg/kg, respectively) without eliciting significant alterations in relative organ weight, or haematological or biochemical parameters. The in vivo blockade of P-3 l effects by naloxone (non-selective opioid receptor antagonist), naloxonazine (antagonist of specific subtypes mu1 of µ-OR), and nor-binaltorphimine (selective ĸ-OR antagonist) supports initial results from binding assays and the interpretations made possible from computational modeling of the interactions of P-3 l with the opioid receptor subtypes. In addition to the opioidergic mechanism, the blockade of the P-3 l effect by flumazenil suggests benzodiazepine binding site involvement in its biological activities. These results support P-3 l potentially possessing clinical utility and substantiate the need for additional pharmacological characterization.

Microglial INPP5D limits plaque formation and glial reactivity in the PSAPP mouse model of Alzheimer's disease.

INTRODUCTION: The inositol polyphosphate-5-phosphatase D (INPP5D) gene encodes a dual-specificity phosphatase that can dephosphorylate both phospholipids and phosphoproteins. Single nucleotide polymorphisms in INPP5D impact risk for developing late onset sporadic Alzheimer's disease (LOAD). METHODS: To assess the consequences of inducible Inpp5d knockdown in microglia of APPKM670/671NL /PSEN1Δexon9 (PSAPP) mice, we injected 3-month-old Inpp5dfl/fl /Cx3cr1CreER/+ and PSAPP/Inpp5dfl/fl /Cx3cr1CreER/+ mice with either tamoxifen (TAM) or corn oil (CO) to induce recombination. RESULTS: At age 6 months, we found that the percent area of 6E10+ deposits and plaque-associated microglia in Inpp5d knockdown mice were increased compared to controls. Spatial transcriptomics identified a plaque-specific expression profile that was extensively altered by Inpp5d knockdown. DISCUSSION: These results demonstrate that conditional Inpp5d downregulation in the PSAPP mouse increases plaque burden and recruitment of microglia to plaques. Spatial transcriptomics highlighted an extended gene expression signature associated with plaques and identified CST7 (cystatin F) as a novel marker of plaques. HIGHLIGHTS: Inpp5d knockdown increases plaque burden and plaque-associated microglia number. Spatial transcriptomics identifies an expanded plaque-specific gene expression profile. Plaque-induced gene expression is altered by Inpp5d knockdown in microglia. Our plaque-associated gene signature overlaps with human Alzheimer's disease gene networks.

Self-Disinfecting Urethral Catheter to Overcome Urinary Infections: From Antimicrobial Photodynamic Action to Antibacterial Biochemical Entities.

Medical-device-related infections are considered a worldwide public health problem. In particular, urinary catheters are responsible for 75% of cases of hospital urinary infections (a mortality rate of 2.3%) and present a high cost for public and private health systems. Some actions have been performed and described aiming to avoid it, including clinical guidelines for catheterization procedure, antibiotic prophylaxis, and use of antimicrobial coated-urinary catheters. In this review paper, we present and discuss the functionalization of urinary catheters surfaces with antimicrobial entities (e.g., photosensitizers, antibiotics, polymers, silver salts, oxides, bacteriophage, and enzymes) highlighting the immobilization of photosensitizing molecules for antimicrobial photodynamic applications. Moreover, the characterization techniques and (photo)antimicrobial effects of the coated-urinary catheters are described and discussed. We highlight the most significant examples in the last decade (2011-2021) concerning the antimicrobial coated-urinary catheter and their potential use, limitations, and future perspectives.

Insights into chalcone analogues with potential as antioxidant additives in diesel-biodiesel blends.

Biodiesel production is one of the promising strategies to reduce diesel consumption and an important contribution to climate change. However, biodiesel stability remains a challenging problem in biofuel use in the global energy matrix. In this context, organic additives have been investigated to minimize these problems and reduce harmful emissions to comply with fuel requirement standards. In this study, we discuss a comprehensive structural description, a behavior of B15 [85% volume of diesel and 15% volume of biodiesel (B100)] stability in the presence of antioxidants (chalcone analogues), and a theoretical calculation to pave the way for clarifying and expanding the potential of title compounds as an antioxidant additive for diesel-biodiesel blends. Finally, a systematic description of the oxidation stability was undertaken using a specialized machine learning computational pySIRC platform.

New Insights on Glutathione's Supramolecular Arrangement and Its In Silico Analysis as an Angiotensin-Converting Enzyme Inhibitor.

Angiotensin-converting enzyme (ACE) inhibitors are one of the most active classes for cardiovascular diseases and hypertension treatment. In this regard, developing active and non-toxic ACE inhibitors is still a continuous challenge. Furthermore, the literature survey shows that oxidative stress plays a significant role in the development of hypertension. Herein, glutathione's molecular structure and supramolecular arrangements are evaluated as a potential ACE inhibitor. The tripeptide molecular modeling by density functional theory, the electronic structure by the frontier molecular orbitals, and the molecular electrostatic potential map to understand the biochemical processes inside the cell were analyzed. The supramolecular arrangements were studied by Hirshfeld surfaces, quantum theory of atoms in molecules, and natural bond orbital analyses. They showed distinct patterns of intermolecular interactions in each polymorph, as well as distinct stabilizations of these. Additionally, the molecular docking study presented the interactions between the active site residues of the ACE and glutathione via seven hydrogen bonds. The pharmacophore design indicated that the hydrogen bond acceptors are necessary for the interaction of this ligand with the binding site. The results provide useful information for the development of GSH analogs with higher ACE inhibitor activity.

Postnatal Conditional Deletion of Bcl11b in Striatal Projection Neurons Mimics the Transcriptional Signature of Huntington's Disease.

The dysregulation of striatal gene expression and function is linked to multiple diseases, including Huntington's disease (HD), Parkinson's disease, X-linked dystonia-parkinsonism (XDP), addiction, autism, and schizophrenia. Striatal medium spiny neurons (MSNs) make up 90% of the neurons in the striatum and are critical to motor control. The transcription factor, Bcl11b (also known as Ctip2), is required for striatal development, but the function of Bcl11b in adult MSNs in vivo has not been investigated. We conditionally deleted Bcl11b specifically in postnatal MSNs and performed a transcriptomic and behavioral analysis on these mice. Multiple enrichment analyses showed that the D9-Cre-Bcl11btm1.1Leid transcriptional profile was similar to the HD gene expression in mouse and human data sets. A Gene Ontology enrichment analysis linked D9-Cre-Bcl11btm1.1Leid to calcium, synapse organization, specifically including the dopaminergic synapse, protein dephosphorylation, and HDAC-signaling, commonly dysregulated pathways in HD. D9-Cre-Bcl11btm1.1Leid mice had decreased DARPP-32/Ppp1r1b in MSNs and behavioral deficits, demonstrating the dysregulation of a subtype of the dopamine D2 receptor expressing MSNs. Finally, in human HD isogenic MSNs, the mislocalization of BCL11B into nuclear aggregates points to a mechanism for BCL11B loss of function in HD. Our results suggest that BCL11B is important for the function and maintenance of mature MSNs and Bcl11b loss of function drives, in part, the transcriptomic and functional changes in HD.

Theoretical analysis of the effects of counterions on the supramolecular arrangement of sulfamethoxazole.

Active pharmaceutical ingredients are formulated as the salt form, aiming to modulate their physicochemical properties. In this regard, the optimization and choice of the salt former have a strong influence on toxicity, therapeutic efficiency, and bioavailability. Sulfamethoxazole (SMZ) salts with Na+, Cl-, and Br- counterions influence in the supramolecular arrangement as well as in their thermodynamic and kinetic parameters. Herein, we analyzed the interactions of the Na+, Cl-, and Br- counterions on the supramolecular arrangement of the sulfamethoxazole salts by Hirshfeld surfaces, fingerprint plots, and theoretical methods-quantum theory of atoms in molecules and natural bond orbitals. Moreover, we evaluated their electronic structure by density functional theory using calculation of the frontier molecular orbitals. Molecular electrostatic potential maps were also obtained to predict the interactions of the counterions along crystalline arrangements. We observed that the structures of [SMZ]+ and [SMZ]- ions differ slightly from the SMZ. The chemical reactivity indices show that the SMZ is kinetically more stable than its respective ions, while its anion is more polarizable, and its cation has a higher global electrophilicity index. The molecular electrostatic potential maps show high charge density in the sulfonyl group (nucleophilic region) and the heterocyclic amino group (electrophilic region). Although the molecular skeleton is identical among the three SMZ species and the presence of different counterions in the formation of the crystalline structure of the salts results in supramolecular arrangements with different patterns of intermolecular interactions, despite being very similar in terms of intensities.

A new quinolinone-chalcone hybrid with potential antibacterial and herbicidal properties using in silico approaches.

Quinolinone-chalcones are hybrid compounds consisting of chalcone and quinolone moieties with biological activity related to their hybrid structure. This work seeks to describe the structural and theoretical parameters related to the physicochemical properties and biological activity of a new quinolinone-chalcone. The synthesis, structural characterization by X-ray diffraction, molecular topology by Hirshfeld surfaces and QTAIM, molecular electronic calculations, and pharmacophore analysis were described. The weak interactions C-H…O, C-H…π, and C-H…Br were responsible for crystal growth and stabilized the crystalline state. The DFT analysis shows that the sulfonamide group region is susceptible to observed interactions, and the frontier molecular orbitals indicate high kinetic stability. Also, pharmacophore analysis revealed potential antibacterial and herbicidal activity; by docking within the active site of TtgR, a transcription regulator for the efflux pump TtgABC from the highly resistant Pseudomonas putida (P. putida) strain DOT-TIE, we showed that the activation of TtgR relies upon the binding of aromatic-harboring compounds, which plays a crucial role in bacterial evasion. In this context, a new quinolinone-chalcone has a higher binding affinity than tetracycline, which suggests it might be a better effector for TtgR.

Remarkable Nonlinear Properties of a Novel Quinolidone Derivative: Joint Synthesis and Molecular Modeling.

A novel 4(1H) quinolinone derivative (QBCP) was synthesized and characterized with single crystal X-ray diffraction. Hirshfeld surfaces (HS) analyses were employed as a complementary tool to evaluate the crystal intermolecular interactions. The molecular global reactivity parameters of QBCP were studied using HOMO and LUMO energies. In addition, the molecular electrostatic potential (MEP) and the UV-Vis absorption and emission spectra were obtained and analyzed. The supermolecule (SM) approach was employed to build a bulk with 474,552 atoms to simulate the crystalline environment polarization effect on the asymmetric unit of the compound. The nonlinear optical properties were investigated using the density functional method (DFT/CAM-B3LYP) with the Pople's 6-311++G(d,p) basis set. The quantum DFT results of the linear polarizability, the average second-order hyperpolarizability and the third-order nonlinear susceptibility values were computed and analyzed. The results showed that the organic compound (QBCP) has great potential for application as a third-order nonlinear optical material.

Cyclohexanone-Based Chalcones as Alternatives for Fuel Additives.

The use of small molecules, such as chalcones and their derivatives, for more efficient fuels is in increasing demand due to environmental factors. Here, three crystal structures (BH I, II, and III) of cyclohexanone-based chalcones were synthesized and described by single-crystal X-ray diffraction and Hirshfeld surface analysis. The supramolecular modeling analysis on the hyperconjugative interaction energies and QTAIM analysis at the ωB97XD/6-311++G(d,p) level of theory were carried out to analyze the intermolecular interactions in the solid-state. The structure-property relationship, frontier molecular orbital, molecular electrostatic potential, and the experimental calorific value analysis show that the three compounds are a good alternative to be used as an additive for some fuels. Our findings represent a further step forward in the development of cheaper and more efficient fuel additives and pose an opportunity for further investigation on similar analogues.