Search Results (301)

In the present work, a novel series of eleven sulfonate derivatives with potent inhibitory activity against butyrylcholinesterase (BChE) is reported. Of these, compounds 2-[(E)-(2-Benzoylhydrazinylidene)methyl]phenyl 5-(dimethylamino)naphthalene-1-sulfonate (5c, IC₅₀ = 1.11 µM) and tert-butyl (2E)-2-[(2-{[5-(dimethylamino)naphthalene-1-sulfonyl]oxy}phenyl)methylidene]hydrazine-1-carboxylate (5b, IC₅₀ = 11.51 µM) exhibit stronger inhibitory activity than rivastigmine, the reference compound, and exhibit high selectivity for BChE over AChE (e.g., selectivity index 57 for 5c). Interestingly, compound 5c also exhibited anti-inflammatory effects, which is important for potential therapeutic applications, especially in Alzheimer’s disease. These new compounds were designed through a structure-based approach using molecular modeling techniques (docking, molecular dynamic (MD) simulations, and QTAIM (quantum theory of atoms in molecules) calculations). The most promising compounds show no detectable toxic effects and satisfy Lipinski’s rule of five, indicating that they represent attractive starting structures for the design of new derivatives acting as specific BChE inhibitors. In addition, our results indicate that relatively simple computational techniques such as docking calculations and toxicity prediction programs can be valuable when properly used in the search of new candidates for this particular target. Docking calculations show that the more active compounds of this series reach the bottom region of the gorge interacting with residues within the active site of BChE. However, our data further suggest that the use of more precise techniques, such as MD simulations and QTAIM analysis, is necessary to obtain detailed insight into ligand–enzyme interactions. Regarding QTAIM calculations, they demonstrate that such computations are very useful to evaluate the molecular interactions of the different molecular complexes. In summary, we report a new series of sulfonate derivatives as promising starting structures for the development of new selective BChE inhibitors. Full article

This study explored the electronic and structural tunability of fullerene (C₆₀) derivatives via functionalization with heteroatoms (O, S, Se) in mono-, di-, and tri-bridged configurations, including covalently modeled dimers. Calculations were performed using density functional theory (DFT) at the B3LYP/6-31G(d,p) level. Electronic descriptors such as total dipole moments (TDMs), HOMO–LUMO energy gaps (ΔE), global reactivity descriptors, total density of states (TDOS), molecular electrostatic potential (MESP) and non-covalent interactions (NCIs) were analyzed to elucidate how functionalization alters reactivity and stability. Key findings indicate that TDM increases and ΔE decreases in all functionalized C₆₀; for example, the TDM increased from 0 Debye for C₆₀ to 2.156 Debye for C₆₀–O–S–Se, and ΔE decreased from 2.762 eV (C₆₀) to 2.532 eV (C₆₀–Se), indicating enhanced reactivity. This aligns with global reactivity descriptors such as reduced ionization energy and hardness. Mapped MESP surfaces showed activation around heteroatom sites. Quantum theory of atoms in molecules (QTAIM) and NCI analyses revealed that while mono-bridged structures retain covalent linkages, dimeric systems such as C₆₀–O–C₆₀ and C₆₀–S–C₆₀ relax into weak, van der Waals-type interactions. OPDOS (overlap population density of states) highlighted antibonding character between the fragments in the conduction region. These results demonstrate that heteroatom functionalization enhances the electronic properties of C₆₀, making it a promising candidate for optoelectronic, organic photovoltaic, and sensor applications. Full article

We report a rare family of pyridine-coordinated iodobismuthate(III) salts supported by alkyltriphenylphosphonium and tetraphenylphosphonium cations. Reactions of BiI₃ with Ph₃PR⁺I⁻ (R = Me, Et, ⁿPr, ⁿBu, Ph) in neat pyridine, followed by crystallization, yield structurally tunable bismuth-halide-pyridine anions dictated by reagent stoichiometry. Combination of BiI₃ and Ph₃PR⁺I⁻ in 2:1 ratio produced [Ph₃PR]₂[BiI₅Py], 1 (R = Me, Et, ⁿPr, Ph), while combination in 1:1 ratio resulted in three compounds: [Ph₃PR][cis-BiI₄Py₂], 2 (R = ⁿPr, Ph), [Ph₃PR][trans-BiI₄Py₂], 3 (R = Me, Et, Ph), and [Ph₃PR]₂[transoid-Bi₂I₈Py₂], 4 (R = Me, Et, ⁿPr, ⁿBu, Ph). In many cases, the compounds were isolated as Py or Et₂O solvates, and in some cases, multiple degrees of solvation or polymorphism were encountered. Hirshfeld analysis of 1–4 showed the major anion–cation/anion/solvent interactions to be H⋯I, H⋯H, and C⋯H. Diffuse reflectance measurements of representative compounds, all of which were yellow-orange to red-orange, revealed bandgaps in the range of 1.9–2.2 eV, where density-of-states KS-DFT calculations attribute the absorption to metal-centered charge transfer within the anionic unit. NLMO and QTAIM analyses further indicate predominantly ionic Bi(III)–I/pyridine bonding with robust inner-sphere coordination that is insensitive to anion speciation. Full article

We report a straightforward and versatile synthetic route to pyridinium-fused 1,3-selenazoles via the electrophilic cyclization of 2-pyridylselenyl chloride with alkynes. The reaction proceeds efficiently under mild conditions with representative terminal and internal alkynes. While the cyclization exhibits high regioselectivity favoring the 3-substituted isomer for most substrates, reactions with 2-pyridyl- and 2-quinolylacetylenes yield regioisomeric mixtures. DFT calculations rationalize this divergence, revealing a competition between kinetic and thermodynamic control; the 3-isomer is kinetically favored, while the 2-isomer is thermodynamically stabilized by an ancillary chalcogen bond between the selenium atom and the pyridine nitrogen of the alkyne substituent. Molecular structures were confirmed by single-crystal X-ray diffraction, and the non-covalent interactions governing supramolecular assembly in the solid state were rigorously analyzed using MEP surfaces, the QTAIM, and NBO analysis. Antifungal evaluation identified several compounds with notable activity against phytopathogenic fungi, highlighting the potential of this novel heterocyclic scaffold in agrochemical applications. Full article

Density functional theory (DFT) was used to investigate how bisubstitution doping in graphene alters its electronic structure and interfacial stability with two model lignocellulosic binders, carboxymethylcellulose (CMC), and a representative aromatic fragment (LCmA). The properties were evaluated at the ωB97X-D/LANL2DZ level for pristine graphene and its bisubstitution-doped variants with nitrogen (graphene-2N) and sulfur (graphene-2S), integrating frontier orbitals, electrostatic potential (ESP) maps, electronic localization functions (ELF/LOL), and QTAIM topology. Doping with 2N markedly reduces the HOMO–LUMO gap from 0.16052 eV (graphene) to 0.10560 eV (−34.2%), while 2S reduces it to 0.14222 eV (−11.4%), evidencing different electronic activation mechanisms. The interaction energies show doping-controlled selectivity: In pristine graphene, adsorption strongly favors LCmA ($\mathsf{\Delta }{E}_{int}$ = −99.3 kcal·mol⁻¹) over CMC (−23.7 kcal·mol⁻¹); in graphene-2N, CMC coupling intensifies (−93.7 kcal·mol⁻¹) while maintaining a high interaction with LCmA (−74.3 kcal·mol⁻¹); and in graphene-2S, CMC remains favorable (−71.9 kcal·mol⁻¹) while LCmA falls to a practically marginal regime (−4.1 kcal·mol⁻¹). QTAIM the presence of confirms closed-layer interactions in all complexes (∇²Pc > 0, H > 0, |V|/G < 1), with |V|/G close to unity for graphene–LCmA (0.994) and less compaction when doped with 2N (0.760 for 2N–LCmA). The bisubstitution modulates the electronic heterogeneity of the basal plane and redefines the binder–surface compatibility, favoring the multipoint anchoring of polar ligands in 2N and penalizing efficient aromatic stacking in 2S. Full article

Phenothiazine is a heteroaromatic molecule capable of various noncovalent interactions, including halogen bonding and π-stacked association. Despite its broad use in functional materials and pharmaceutical ingredients, a systematic comparison of these interaction modes has been lacking. Here, we report a combined experimental and computational study of intermolecular interactions of phenothiazine with a prototypical halogen-bond (HaB) donor (tetrabromomethane), planar π-electron acceptors (tetracyanopyrazine and tetrafluoro-p-benzoquinone), and multifunctional species capable of both interaction types (iodo- and bromo-3,5-dinitrobenzenes). X-ray structural analysis revealed that CBr₄ forms exclusively C–Br···π halogen bonds with the aromatic rings of phenothiazine, whereas all π-acceptors yield alternating donor–acceptor stacks characterized by multiple short contacts indicative of multicenter interactions. Notably, co-crystals of iodo- and bromodinitrobenzenes with phenothiazine display only π-stacked architectures. Density-functional calculations showed that isolated HaB complexes involving N, S, or π sites of phenothiazine possess comparable binding energies (≈−3 kcal mol⁻¹), whereas π-stacked complexes are substantially stronger (≈−9–12 kcal mol⁻¹). QTAIM, NCI, NBO, and energy-decomposition analyses indicated that while amounts of charge transfer in halogen-bonded and π-stacked complexes are comparable, the enhanced stability of the latter originates primarily from a large dispersion contribution. These results rationalize the solid-state preference for π-stacking over halogen bonding in systems where both motifs are accessible and clarify the hierarchy and physical origin of noncovalent interactions involving phenothiazine, providing guidance for the design of supramolecular assemblies and functional materials based on this versatile electron donor. Full article

A comprehensive MD + QC methodology was developed and applied to evaluate various aspects of Arbidol interactions with functional amino acids of surface proteins of influenza virus and SARS-CoV-2. The spatial structure, solvation features, conformational behavior of Arb AA (AA–Trp, Tyr, Phe, and Val) complexes were established, and the statistics of intermolecular interactions in the complex were described. It was found that Arb can participate in strong and long-lived π-π stacking interactions with aromatic amino acids. The binding energy (BE) of Arbidol and amino acids in aqueous solution was estimated using an explicit solvation model, QTAIM analysis and correlation of BE vs. total electron density at the bond critical points of the complex. Theoretical calculations were validated by experimental studies of fluorescence (FL) quenching of aromatic AA by Arbidol. Spectral-fluorescent properties of Arbidol hydrochloride in aqueous solutions were studied, and the luminescence quantum yield for the electronically excited state of Arb was determined. Full article

Eight H-bonded salts of arsenic acid and nitrogen bases (2,4,6-trimethylpyridine, pyridine-2,6-diamine, pyridin-4-ol, 4-methoxypyridine, 4-methoxyaniline, 1,3,5-triazine-2,4,6-triamine, diethylamine and N¹,N¹,N²,N²-tetraethylethane-1,2-diamine) were studied in the solid state by single crystal X-ray diffraction technique and DFT calculations. In all cases quite short (≤2.65 Å) OHO bonds were found in the self-assembled supramolecular ribbons or 2D networks of dihydrogen arsenates, constituting a repertoire of five different H-bonding patterns (motifs). The electron localization function maps revealed the spots of the nucleophilic sites on oxygen atoms that determine the preferable directions for H-bonding of H₂AsO₄⁻ anions observed in the crystal packing. Analysis of the electrostatic potential maps for isolated species has demonstrated that upon H-bonding between H₂AsO₄⁻ anions and protonated nitrogen bases, NH⁺⋯⁻OAsO(OH)₂, the redistribution of electron density within the anion provides otherwise virtually non-existent electrophilic sites on hydrogen atoms, which balances the Coulomb repulsion and allows for the anion⋯anion pairing within the crystal. The topological analysis of the calculated crystalline electron density after relaxation of the hydrogen atoms’ positions was used to classify the OHO bonds as moderately strong ones (with an interaction energy up to 65 kJ/mol) and revealed a high degree of ionicity of molecular moieties within ion pairs (with an absolute charge up to 0.87 e). For the strongest OHO and NHO bonds, the noticeable covalent character was shown by using the crystal orbital Hamiltonian population analysis. Full article

Non-covalent contacts play a significant role in binding between fragments in supramolecular assemblies. Understanding the non-covalent binding capabilities of closo-borate anions and their derivatives is a significant research challenge, due to their ability to interact with biomolecules. The present work was focused on the theoretical study of non-covalent complexes between glycine and closo-borate anions [B_nH_n−1X]^y− (X = H, NH₃, OH, SH, F; n = 10, 12; y = 1, 2). The main binding patterns between glycine and cluster systems were defined, and the effect of the exo-polyhedral substituent on the stability of non-covalent complexes was analysed. Complexes based on ammonium and hydroxy derivatives of closo-borate anions [B_nH_n−1X]^y− (X = NH₃, OH; n = 10, 12; y = 1, 2) were the most stable among all the derivatives considered. The findings of this work can be applied to the design of non-covalent complexes of closo-borate systems with biomolecules. Full article

Understanding the molecular determinants of antioxidant activity in natural phenolic compounds is essential for explaining their biological performance and designing new radical scavengers. In this work, the radical-scavenging mechanisms of three major ginger phenolics—6-gingerol (GIN), 6-shogaol (SHO), and 6-paradol (PAR)—were systematically investigated using density functional theory (DFT) thermochemistry at the M06-2X/6-31+G(d,p) level in the gas phase, benzene, and water. Three canonical pathways—hydrogen atom transfer (HAT), single-electron transfer followed by proton transfer (SET–PT), and sequential proton loss–electron transfer (SPLET)—were evaluated through full optimization and frequency calculations at 298.15 K, combined with the SMD solvation model. Frontier molecular orbital (FMO), molecular electrostatic potential (MEP), and quantum theory of atoms in molecules (QTAIM) analyses were employed to correlate electronic structure with reactivity. The results reveal a distinct solvent-dependent mechanistic crossover. In the gas phase and benzene, the low dielectric constant suppresses charge separation, making HAT the thermodynamically dominant pathway. In water, strong stabilization of ionic species lowers both the ionization and deprotonation barriers, allowing SPLET and SET–PT to become competitive or even preferred. Across all media, the phenolic O–H group is the principal reactive site, while the aliphatic O–H of GIN remains inactive. SHO exhibits the most versatile redox profile, combining a highly conjugated α,β-unsaturated chain with favorable charge delocalization; PAR is somewhat less redox-active, while GIN shows intermediate performance governed by intramolecular hydrogen bonding. The assembled thermodynamics for HOO• scavenging confirm that all three phenolics are thermodynamically competent antioxidants (ΔG° ≈ −4 kcal mol⁻¹ in water), with comparable driving forces; electronic descriptors indicate SHO is the most redox-flexible, GIN(phenolic) is moderately and PAR is somewhat less charge-transfer-prone, while GIN(aliphatic) remains inactive. These findings provide a comprehensive structure-to-mechanism correlation for ginger phenolics and establish a predictive framework for solvent-controlled antioxidant behavior in phenolic systems. Full article

For a family of 24-atom triazine macrocycles, a single intramolecular hydrogen bond (IMHB) network leads to a conserved, hinge-like motif in solution. Modifications to the backbone of these macrocycles preserve this motif. Modifications to peripheral sites lead to conformational isomers due to hindered bond rotation while conserving the hinge motif. Here, a competitive IMHB network is introduced by the addition of a hydrogen bond donor on the periphery. Cyclization remains quantitative, but multiple conformers result. Three conformers are derived from the hinge motif. Three others are attributed to a new motif that utilizes the new IMHB network. Crystallographic analysis confirms this hypothesis and establishes that this new motif differs significantly from the original with respect to overall shape and disposition of groups. Variable temperature ¹H NMR spectroscopy is used to partially assign the spectra because conformers adopting the hinge motif undergo dynamic motion on the NMR timescale, while the new motif appears static. QTAIM analysis corroborates the hydrogen bond designations in the new conformer and categorizes these interactions as moderate and strong. Full article

Chemical bonds among carbon atoms are central to chemistry. A general working principle regarding these interactions is that these contacts become stronger as the carbon atoms become closer to each other. Nevertheless, there are long, yet strong single C–C bonds that challenge this interpretation. Herein, we perform a quantitative thorough decomposition of the electronic energy of hexaphenylethane and several derivatives of this molecule with increasingly bulkier substituents. For this purpose, we exploit state-of-the-art methods of wave function analysis for the examination of the chemical bonding scenario in the examined systems, namely, the quantum theory of atoms in molecules (QTAIM) and the interacting quantum atoms (IQA) electronic energy partition. Our results reveal the predominance of collective non-covalent interactions over the central, covalent one in the chemical bonding of the examined molecules, in particular for those that have been synthesized in the laboratory. The QTAIM and IQA methods also showed that, besides London dispersion, electron sharing comprises an important contribution to the abovementioned collective interactions. Overall, our results give valuable insights about the importance of collective interactions in the investigated systems and they aid in the understanding of the nature of long, yet stable single C–C bonds. Full article

The Co(II) complex [CoCl₂(AImd)₂] (AImd = 1-allylimidazole) was reinvestigated using a combination of experimental and theoretical methods. The previously reported crystal structure was redetermined and Hirshfeld surface analysis and enrichment ratios were added showing that intermolecular H⋯Cl and π⋯π interactions are the primary forces in the crystal structure, while H⋯H interactions dominate the surface of the molecule, making it rather hydrophobic in keeping with a low solubility in water. A Quantum Theory of Atoms in Molecules (QTAIM)/Non-Covalent Interactions (NCI)-Reduced Density Gradient (RDG) analysis on a dimeric model showed that the energies V(r) of the classical H⋯Cl hydrogen bonds range from −3.64 kcal/mol to −0.75 kcal/mol and were augmented by hydrophobic H⋯C interactions of >1 kcal/mol. T-dependent magnetization measurements reveal paramagnetic behavior with an effective magnetic moment of µ_eff = 4.66(2) µ_B. UV-vis absorption spectra in solution showed intense absorptions peaking at 240 nm, corresponding to intraligand π→π* transitions within the 1-allylimidazole moiety and a structured absorption around 600 nm, which is attributed to the spin-allowed d→d transitions of the high-spin Co(II) d⁷ ion in a distorted tetrahedral geometry. Both assignments were confirmed through TD-DFT calculations on the electronic transitions and agree with the DFT-calculated compositions of the frontier molecular orbitals. Molecular docking to hypoxia-inducible factor-1 alpha (HIF-1α) gave a docking score of −5.48 kcal/mol and showed hydrophobic⋯hydrophobic π-stacking interactions with the Ile233, Leu243, Val338, and Leu262 residues. A higher docking score of −6.11 kcal/mol and predominant hydrophobic⋯hydrophobic interactions with Trp296, His279, and Ile281 were found for HIF-1 inhibiting factor (FIH-1). Full article

Organophosphate pesticides are among the most persistent and toxic contaminants in aquatic environments, requiring effective strategies for detection and remediation. In this work, density functional theory (DFT) calculations were employed to investigate the adsorption of nine representative organophosphates (glyphosate, malathion, diazinon, azinphos-methyl, fenitrothion, parathion-methyl, disulfoton, tokuthion, and ethoprophos) on mercaptobenzothiazole disulfide (MBTS) and MBTS-functionalized graphene (G–MBTS). All simulations were performed in aqueous solution using the SMD solvation model with dispersion corrections and counterpoise correction for basis set superposition error. MBTS alone displayed a range of affinities, suggesting potential selectivity across the organophosphates, with adsorption energies ranging from 0.27 to 1.05 eV, malathion being the strongest binder and glyphosate the weakest. Anchoring of MBTS to graphene was found to be highly favorable (1.26 eV), but the key advantage is producing stable adsorption platforms that promote planar orientations and $\pi$–$\pi$/dispersive interactions. But the key advantage is not stronger binding but the tuning of interfacial electronic properties: all G–MBTS–OP complexes show uniform, narrow HOMO-LUMO gaps (∼0.79 eV) and systematically larger charge redistribution. These features are expected to enhance electrochemical readout even when adsorption strength was comparable or slightly lower (0.47–0.88 eV) relative to MBTS alone. A Quantum Theory of Atoms in Molecules (QTAIM) analysis of the G–MBTS–malathion complex revealed a dual stabilization mechanism: multiple weak C–H⋯$\pi$ interactions with graphene combined with stronger S⋯O and hydrogen-bonding interactions with MBTS. These results advance the molecular-level understanding of pesticide–surface interactions and highlight MBTS-functionalized graphene as a promising platform for the selective detection of organophosphates in water. Full article

Highly Hazardous Pesticides (HHPs) pose severe risks to human health and the environment, making it essential to understand their molecular stability and degradation pathways. In this study, the Quantum Theory of Atoms in Molecules (QTAIM) was applied to four representative organophosphate pesticides, allowing the identification of electronically weak bonds as intrinsic sites of lability. These findings are consistent with reported hydrolytic, oxidative, enzymatic, and microbial degradation routes. Importantly, QTAIM descriptors proved largely insensitive to solvation, confirming their intrinsic character within the molecular electronic structure. To complement QTAIM, conceptual DFT (Density Functional Theory) reactivity indices were analyzed, revealing that solvent effects induce more noticeable variations in global and local descriptors than in topological parameters. In addition, a Topological Analysis of the Fukui Function (TAFF) was performed, which mapped nucleophilic, electrophilic, and radical susceptibilities directly onto QTAIM basins. The TAFF analysis confirmed that bonds identified as weak by QTAIM (notably P–O, P–S, and P–N linkages) also coincide with the most reactive sites, thereby reinforcing their mechanistic role in degradation pathways. This integrated framework highlights the robustness of QTAIM, the sensitivity of global and local reactivity descriptors to solvation revealed by conceptual DFT, and the complementary insights provided by TAFF, contributing to risk assessment, remediation strategies, and the rational design of safer pesticides. Full article