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.

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.

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.

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.

Effect of ortho- and para-chlorine substitution on hydroxychlorochalcone.

This work describes a comparative molecular structure of two hydroxychlorochalcones with an emphasis on their planarity. Hirshfeld surface analysis investigates the effect of ortho- and para-chlorine substitution on supramolecular arrangement and physical chemical properties. The molecular conformation of 2'-hydroxy-4',6'-dimethyl-2-chlorochalcone and 2'-hydroxy-4',6'-dimethyl-4-chlorochalcone chalcones was obtained through DFT with the exchange-correlation functional M06-2X and the 6-311++G(2d,2p) basis set, and the results were compared with the experimental X-ray data in order to get insights on the effect of ortho- and para-chlorine substitution. The charge transfer into entire main carbon chain was also investigated using frontier molecular orbitals (HOMO and LUMO), NBO, and MEP map in order to describe the comparative conformational stability due to the resonance effect produced by π electron displacements. Finally, the intermolecular observed interactions were analyzed by QTAIM, with the M06-2X/6-311G++(d,p) theory level.

Synthesis, characterization, and computational study of a new heteroaryl chalcone.

This work presents the synthesis of the chalcone (E)-3-(2,6-difluorophenyl)-1-(furan-2-yl)-prop-2-en-1-one molecule through the equimolar reaction between 1-(furan-2-yl)-ethenone and 2,6-difluorobenzaldehyde. The crystallographic characterization and the extensive theoretical study regarding electronic properties were obtained. The supramolecular arrangement was described by X-ray diffraction and Hirshfeld surfaces. Optimized geometrical structure was obtained by density functional theory, and the electronic study for differences between the solid and gas phases was carried out with M062-X at 6-311++G(2d,2p) basis set. Natural bond orbital, frontier molecular orbitals (HOMO-LUMO), and molecular electrostatic potential map were determined to elucidate the information related to the charge transfer in the molecule. The theoretical and experimental vibrational spectra were plotted, which included the IR intensities, the calculated and experimental vibrational frequencies, and the assigned vibrational modes for the main groups of DTP.