Search Results (524)

This study investigates anion–anion assemblies involving perhalate anions, XO₄⁻ (X = Cl, Br, I), in crystal structures retrieved from the Cambridge Structural Database to clarify the nature of the intermolecular interactions frequently interpreted as halogen bonds. Molecular electrostatic surface potential analysis demonstrates that isolated XO₄⁻ anions do not exhibit electrophilic σ-holes on the halogen or oxygen atoms along the O–X bond extensions, thereby precluding their role as conventional halogen- or chalcogen-bond donors. Gas-phase calculations further show that direct anion–anion assemblies are intrinsically repulsive and unstable in isolation. However, when dielectric screening is introduced through implicit solvation models, metastable dimeric and oligomeric arrangements consistent with crystallographic motifs become accessible. Complementary QTAIM, IGMH, NBO, and SAPT analyses show that the observed X···O and O···O contacts are weak, environment-assisted anti-electrostatic interactions arising from a combination of dielectric screening, polarization, dispersion, and donor–acceptor contributions. The results demonstrate that the structural organization of perhalate anions in crystalline environments is governed primarily by collective environmental and crystal-packing effects rather than intrinsic attractive interactions between isolated anions. Full article

This study presents a quantum chemical investigation of halogen–π interactions involving halogen molecules (F₂, Cl₂, Br₂, and I₂) and a series of π-systems, including benzene, alkenes, and alkynes. Special emphasis is placed on the role of the position of the unsaturated bond (terminal vs. internal) in determining the strength and nature of these interactions. Geometry optimizations and interaction energies were calculated at the wB97X-D3/def2-TZVPP level of theory, with additional validation against CCSD(T)/CBS data. Energy decomposition analysis using SAPT0 and QTAIM analysis were also performed. The results show a clear increase in interaction strength from F₂ to I₂, with interaction energies ranging from −0.47 to −5.61 kcal/mol. The position of the double or triple bond and the local symmetry of the π-system significantly influence interaction energies, with internal and more substituted alkenes and alkynes forming stronger interactions than terminal analogs. SAPT analysis shows that halogen–π interactions are governed by a balance of electrostatic and dispersion contributions, with electrostatics representing the largest attractive term in most cases, whereas dispersion becomes increasingly important for heavier halogens and more extended π-systems and benzene. QTAIM analysis confirms the noncovalent nature of these interactions, with increasing electron density at bond critical points correlating with stronger binding. Full article

Background/Objectives: The dual inhibition of the COX-2 and 5-LOX pathways, in addition to sEH inhibition, presents a superior approach to managing inflammation while mitigating the cardiovascular adverse effects typically associated with conventional NSAIDs. These multi-target agents are safer and more efficient as they inhibit the synthesis of pro-inflammatory leukotrienes while preserving cardioprotective epoxyeicosatrienoic acids. Methods: This study reports the development of multi-target inhibitors to mitigate inflammatory and cardiovascular conditions. We examined a series of tetrahydroindazole-sulfonamide hybrids (3a–g and 4a–e) against the enzymes COX-1/2, 5-LOX, and sEH. Results: Compound 3b outperformed celecoxib as a multi-target agent, inhibiting COX-2 (IC₅₀ = 0.08 µM, SI = 82), 5-LOX (IC₅₀ = 0.46 µM), and sEH (IC₅₀ = 21.95 nM) in many metrics. In cellular experiments, 3b showed strong cardioprotective and anti-inflammatory effects, significantly reducing TNF-α (65.58%), LDH (76.26%), and CK-MB (76.76%) levels compared to LPS-treated controls. Molecular docking validated these findings, indicating that 3b was comparable to celecoxib at the COX-2 site via a thorough six hydrogen-bond network and achieves considerable sEH affinity through specialized halogen bonding and aromatic stacking. These results indicate that 3b effectively provides dual anti-inflammatory and cardioprotective effects. Conclusions: Our findings suggest that targeting the COX/5-LOX/sEH pathways simultaneously offers a balanced multi-target profile for treating complex inflammatory diseases while minimizing cardiovascular risks. Full article

As a devastating disease worldwide, rice bacterial leaf blight—caused by Xanthomonas oryzae pv. oryzae (Xoo)—leads to substantial reductions in grain yield. The increasing resistance to conventional bactericides necessitates the development of novel and sustainable control agents. This study evaluated 58 novel alkyl sulfonamide compounds against Xoo. In the turbidimetric assay at 100 mg/L, several compounds showed potent antibacterial activity. Among them, SYAUP-116 and SYAUP-212 exhibited in vitro inhibition comparable to that of streptomycin sulfate at the same concentration. Furthermore, in EC₅₀ determination assays, both compounds yielded lower EC₅₀ values than zinc thiazole. Among the 58 compounds tested, SYAUP-491 exhibited an in vitro EC₅₀ of 6.96 mg/L and achieved 74.1% in vivo therapeutic efficacy at 200 mg/L, representing the most promising lead for further characterization. Molecular docking, based on prior proteomic data, indicates potential stable binding to ribosomal proteins (50S L33/L34 and 30S S5), with the strongest interaction observed for L33 (binding free energy: −5.73 kcal/mol). This suggests a putative mechanism involving ribosome targeting and protein synthesis inhibition, which may be facilitated by hydrophobic interactions and halogen bonds derived from its trifluoromethyl and sulfonamide groups. SYAUP-491 demonstrates significant potential as a novel bactericide for rice bacterial leaf blight, warranting further research on structure-activity optimization, target validation, and field performance. Full article

Cobalt oxide (Co₃O₄), a transition metal oxide with a cubic spinel structure, shows high potential in peroxymonosulfate (PMS) activation, while its catalytic efficiency is often limited by sluggish interfacial charge transfer. In this study, a chlorine-doped Co₃O₄ (Cl-Co₃O₄) was synthesized via a hydrothermal method for the degradation of bisphenol A (BPA) through PMS activation. Systematic characterizations and electrochemical tests demonstrated that chlorine doping could effectively modulate the surface electronic structure of the catalyst, significantly reducing the interfacial charge transfer resistance. Degradation performance evaluations revealed that, compared to pristine Co₃O₄, Cl-Co₃O₄ exhibited a significantly enhanced BPA degradation, achieving near-complete removal of BPA within 15 min under neutral to weakly alkaline conditions. The optimal operational parameters were determined as catalyst dosage of 0.20 g/L, PMS concentration of 0.10 mM and initial pH of 7.0–9.0, with the pseudo-first-order rate constant reaching 0.37 min⁻¹. High-concentration NO₃⁻ showed weak inhibition, while Cl⁻ showed moderate inhibition; 50 mM HCO₃⁻ drastically reduced the rate constant to 0.05 min⁻¹ and almost completely suppressed the reaction. Sulfate (SO₄•⁻) and superoxide (O₂•⁻) radicals were the primary reactive species in this system, explicitly excluding the role of the non-radical electron transfer pathway. Furthermore, three plausible BPA degradation pathways involving C-C bond cleavage, hydroxylation and C-O bond breakage were proposed with 19 intermediates identified. Ecotoxicological assessments based on ECOSAR verified that both acute and chronic toxicity of the intermediates to fish, daphnid and green algae decreased gradually, and the final small-molecule products exhibited significantly lower toxicity than the parent BPA. This study provides a novel strategy for enhancing the PMS activation performance of cobalt-based catalysts by modulating their electronic structures via halogen doping. Full article

Intermolecular interactions play an important role in the formation and stability of co-crystals. In this study, the interaction behaviour of theophylline in co-crystal structures was systematically analysed using data from the Cambridge Structural Database. A total of fifty-three theophylline co-crystal structures were investigated and classified according to their intermolecular interaction motifs. A structured interaction scheme was developed to describe the accessible interaction sites of theophylline, including classical and non-classical hydrogen bonds, as well as halogen bonds and π∙∙∙π interactions. The study revealed theophylline’s high versatility in forming intermolecular interactions, resulting in twenty interaction patterns. Three dominant motifs were identified as occurring most frequently. The results indicate that steric effects influence the accessibility of specific interaction sites, particularly limiting interactions at the carbonyl group located between the two methyl groups. Hirshfeld surface analysis revealed that O∙∙∙H and H∙∙∙H interactions contribute most significantly to the intermolecular interactions in the analysed structures. Full article

Background: Neglected diseases caused by protozoan parasites remain a major public health burden, particularly in low- and middle-income countries. Among the chemical motifs explored in antiparasitic drug discovery, guanidine-containing compounds have attracted considerable attention due to their strong cationic character, high capacity for hydrogen bonding, and versatility in interacting with biological targets. Methodology: This review summarizes advances reported in the last decade regarding guanidine derivatives with activity against pathogens associated with Chagas disease, human African trypanosomiasis, Leishmaniasis, tuberculosis, toxoplasmosis, dengue and schistosomiasis. Results: Evidence gathered from synthetic, natural, and drug-repurposing studies indicates that the guanidine, guanidine-containing and guanidine-related compounds contribute to modulating biological activity by changing electrostatic interactions, hydrogen-bonding networks, and physicochemical properties, with enzymes, nucleic acids, and membrane-associated targets essential for parasite survival. Across the analyzed studies, several emerging structure–activity relationship trends were identified, including the contribution of polycationic or dicationic architectures, the influence of halogenated or lipophilic substituents, and the dependence of biological activity on the complete molecular framework, including heterocyclic systems, macrocycles, peptide conjugates, hybrid scaffolds, and repurposed drugs. In addition to direct antiparasitic effects, certain guanidine-containing and guanidine-related compounds demonstrate immunomodulatory or host-protective properties, expanding the therapeutic relevance of this class. Despite promising in vitro results, protonation trapping, efflux pump susceptibility, and pharmacokinetic limitations such as poor oral absorption, high polarity, plasma protein binding and limited membrane permeability remain significant challenges for clinical translation. Nonetheless, the integration of medicinal chemistry, computational modeling, and biological screening continues to accelerate the identification of optimized scaffolds. Conclusions: Overall, guanidine-based compounds constitute a promising scaffold for the development of new therapeutic strategies targeting neglected parasitic diseases, and further structural optimization may enable the emergence of candidates with improved efficacy, selectivity, and drug-like properties. Full article

The increasing demand for better dental aesthetics has driven the development of tooth-whitening techniques that are effective while reducing invasiveness. Hydrogen peroxide (HP) and carbamide peroxide (CP) continue to be the most common active ingredients in bleaching products. Various types of light and laser activation have been introduced to speed up the bleaching process and decrease clinical application time. However, published results regarding their effectiveness and biological safety are inconsistent and sometimes contradictory. Aim: The objective of this study was to identify irradiation conditions that optimise the whitening performance of peroxide-based bleaching agents while ensuring safety for dental hard tissues and ocular structures. This objective was achieved through a systematic synthesis and meta-analyses of both experimental and clinical evidence on bleaching techniques, light or laser activation, and related treatment outcomes. Additionally, the study aimed to provide an integrated overview of currently used irradiation technologies, bleaching agents, treatment protocols, and relevant safety considerations. Methods: A multi-stage analytical approach was employed. Evidence was collected from systematic reviews, randomised and non-randomised clinical trials, and laboratory-based in vitro investigations. The studies assessed differences in bleaching agents (HP and CP), their concentrations, and application protocols, as well as various activation systems, including halogen lamps, conventional LEDs, violet LEDs, metal–halide lamps, and laser wavelengths such as visible blue (~440 nm), red or near-infrared (~1.7 µm), and other spectral ranges. Extracted outcome measures included tooth colour improvement (ΔSGU, ΔE), incidence of tooth sensitivity, changes in enamel surface morphology, temperature increases in the pulp chamber, and the bond strength of restorative or orthodontic materials. When methodological compatibility permitted, quantitative synthesis and meta-analysis were conducted to estimate the effects of activation modalities and irradiation parameters. Results: Analysis of data from 28 systematic reviews and numerous clinical and laboratory studies showed that the degree of colour improvement did not consistently rely on peroxide concentration or on whether bleaching was performed in-office or through home-based protocols. In most studies, adding light activation did not produce a clearly superior whitening effect compared to chemically driven bleaching alone. However, certain laser-assisted methods—especially those using blue diode lasers around 440 nm or near-infrared diode lasers near 1.7 µm—were linked with faster whitening responses and, in several in vitro experiments, fewer enamel surface irregularities. Increases in pulp temperature remained below the generally accepted safety threshold of 5.5 °C in the reported experimental conditions. While laser activation reduced treatment time, some studies observed a temporary decrease in the bond strength of orthodontic brackets following bleaching. Photobiomodulation techniques seem promising for reducing post-treatment sensitivity, although more robust clinical evidence is still needed. Conclusions: Targeted activation with diode lasers, especially within the blue and near-infrared spectral ranges, may speed up the whitening process and potentially minimise structural changes to enamel when irradiation parameters are carefully managed. Despite these positive findings, current clinical evidence remains limited. Well-designed randomised controlled trials with standardised treatment protocols are essential to determine the best wavelengths, energy delivery settings, and safety limits for laser-assisted dental bleaching. Full article

Environmental fires pose a serious threat to energy security, ecosystems and public safety, whilst traditional halogenated flame retardants suffer from limitations such as high environmental residue risks and insufficient flame-retardant efficacy. In this study, sodium alginate (SA) was utilised as the matrix, with the incorporation of ammonium polyphosphate (APP) and phytic acid (PA), in conjunction with SiO₂-APTES surface modification, to prepare nitrogen–phosphorus synergistic bio-based flame-retardant gels. The present study systematically investigated the influence of the N/P molar ratio on the gelation kinetics, rheological behaviour, microstructure and flame-retardant performance of the gel. The study revealed a nitrogen–phosphorus coupled gas–solid two-phase synergistic flame-retardant mechanism. The results indicate that at an N/P ratio of 1/4, the gel forms a stable dual-network structure comprising ionic cross-links and Si–O–P covalent bonds. In the gas phase, the thermal decomposition of APP releases inert NH₃, which dilutes oxygen and quenches gas-phase radicals (·OH, ·H). In the condensed phase, the phosphate groups of PA-catalysed SA form Si–O–P covalent bonds with SiO₂ under the mediation of APTES, creating a dense, insulating char layer. In comparison with the control group (N/P = 0/0), the optimal gel sample (N/P = 1/4) demonstrated a 33% increase in shear stress, a 10% reduction in the peak heat release rate (HRR), a 75% decrease in total smoke production (TSP), and a 150% increase in char layer thickness after combustion, while maintaining adequate mechanical strength, thermal stability, and environmental friendliness. This work provides novel insights and strategies for the development of green, highly efficient flame-retardant materials for environmental fire prevention and control. Full article

In this study, the applicability of achiral column chromatography—including both medium-pressure liquid chromatography (MPLC) and classical gravity-driven techniques—was evaluated as a laboratory method for enantiomeric enrichment of scalemic (non-racemic) samples of axially chiral compounds. As model substrates, 3-(ortho-substituted-phenyl)quinazolin-4-one derivatives were employed. The results confirmed that self-disproportionation of enantiomers (SDE), occurring during column chromatography (SDEvCC), enabled the efficient isolation of enantiomerically pure fractions, with MPLC demonstrating particularly high effectiveness. Additionally, the parameters governing gravity-driven column chromatography were systematically optimized, with particular attention to variables such as eluent type and concentration, stationary phase composition, sample preparation protocol, and solvent purity. Furthermore, leveraging known crystallographic data and quantum chemical calculations based on Density Functional Theory (DFT), a molecular association mechanism was proposed to elucidate the physicochemical basis of the SDE phenomenon. Full article

A series of Group 10 metal dithiocarbonate complexes [M(S₂COⁱPr)₂] (M = Ni 1, Pd 2, Pt 3) was prepared following procedures from the literature and cocrystallized with the ditopic σ/π-hole donor 1,4-diiodotetrafluorobenzene. Single-crystal X-ray diffraction revealed a consistent I···S halogen bonding motif alongside a remarkable diversity in metal-involving interactions across the Ni–Pd–Pt triad. While nickel(II) exhibits strong electrophilic M···S semicoordination, the palladium(II) center displays ambiphilic behavior, and platinum(II) acts exclusively as a nucleophile via π-hole···M bonding. Comprehensive density functional theory studies, including molecular electrostatic potential (MEP) mapping, quantum theory of atoms in molecules/noncovalent interaction plot analyses, and energy decomposition analysis, were used to quantify this competitive balance. The results demonstrate that the increasing nucleophilicity from Ni to Pt, supported by shifting MEP minima and stronger π-hole stabilization energies, dictates the preference for nucleophilic over electrophilic metal-centered contact. Full article

To investigate the potential of halogen-containing building blocks in the development of artificial carbohydrate receptors, the 1,3,5-trisubstituted 2,4,6-triethylbenzene scaffold with halogenated subunits and classical hydrogen bonding sites was used as a model system. In the first studies, the influence of the presence of halogens on the binding properties of compounds bearing benzamidomethyl units was investigated, whereby the type of halogen and its ring position were varied. The question was whether the presence of halogens could lead to an increase in binding effectivity and whether this increase can be attributed to the formation of halogen bonds (especially for X = Br and I in ortho position) with the sugar substrate or to other effects. The binding studies revealed some interesting relationships between structure and binding affinity for the tested compounds 1–9. For those bearing the halogen substituent in the ortho position to the amide functionality, the binding affinity increases in the expected order 4 (o-F) < 3 (o-Cl) < 2 (o-Br) < 1 (o-I). In the presence of small amounts of water in CDCl₃, an increase in binding strength was observed in comparison to experiments conducted in dry CDCl₃. The present studies aim to provide impulses for the use of halogenated building blocks in the design of artificial carbohydrate receptors. Optimizing the type of halogenated units and the receptor architecture should result in more effective carbohydrate receptors capable of functioning effectively in aqueous media through a combination of different noncovalent interactions. Full article

The molecular electrostatic surface potential (MESP) has become a key theoretical tool for probing reactivity in chemical systems. It reveals electrophilic and nucleophilic regions on molecular surfaces, underpinning the understanding of noncovalent interactions such as hydrogen, triel, tetrel, pnictogen, chalcogen, halogen, matere, and aerogen bonding, among many others. These interactions, driven by Coulombic attraction, govern aggregation in molecular and supramolecular systems across solid, liquid, and gas phases. MESP applications span crystal engineering, polymers, biology, catalysis, photovoltaics, and drug discovery. While limitations exist—such as the arbitrariness in defining isodensity surfaces—its impact on advancing both theoretical and applied chemical research is substantial. This review outlines the conceptual foundations of MESP and highlights its broad relevance across the chemical sciences. Full article

One-dimensional hybrid organic–inorganic semiconductors enable band-edge engineering through reduced dimensionality and interfacial orbital hybridization. Nevertheless, the electronic physics of Cu/Ag-based systems has received limited attention. Here, we perform high-throughput first-principles calculations on 90 Cu/Ag halide HOISs derived from experimentally reported parent structures to elucidate bonding-dependent electronic behavior. We uncover a clear transition from electronically isolated inorganic chains in ionic hybrids to strongly hybridized band edges in covalent and mixed-bonding hybrid frameworks, where ligand p orbitals cooperatively couple with Cu-derived states and halogen p orbitals. This hybridization produces p-orbital-dominated band edges, enhanced dispersion, and light-hole effective masses along the 1D chains. Guided by this bonding-driven mechanism, we further identify four Cu-based compounds, which are helpful for tuning light-harvesting properties in low-dimensional hybrid semiconductors. Full article

Highly polar M-mol-X (M = alkali metal, mol = molecule, X = halogen) insertion complexes have been predicted to offer potential practical applications, including molecular interactions with light, ion-pair induced isomerization, etc. In the present work, the insertion complexes of the seven-membered, fused bicyclic norcaradiene and its monocyclic isomer trapped in Li-I, Na-I, and K-I counterion pairs were investigated using ab initio methods. The structures, stability, polarities, and simulated infrared spectra are analyzed and the effects of the insertion on the norcaradiene to cycloheptatriene isomerization process are examined. Furthermore, an uncommon bond between iodine and a fully substituted carbon atom is reported upon and hypothesized to be catalyzed by the presence of the cation in the insertion complexes. Full article