Search Results (171)

Understanding the intrinsic Li–H₂ interaction, decoupled from substrate effects, is essential to rationalize the performance of lithium-decorated hydrogen storage materials. To address the current lack of a clean theoretical baseline, we characterized the sequential H₂ adsorption on the gas-phase Li₆ superatomic cluster using high-level density functional theory (DFT), complemented by Energy Decomposition Analysis (EDA), QTAIM, and NICS(0) calculations. Li₆ acts as a structurally rigid platform (RMSD < 0.032 Å) where ligand-induced polarization progressively strengthens its σ-aromaticity (NICS(0) from −2.917 to −13.98 ppm) and increases the HOMO–LUMO gap up to 5.05 eV. EDA identifies the binding as field-activated physisorption, electrostatically dominated (65–67%) and mechanistically distinct from Kubas coordination, as confirmed by QTAIM closed-shell interaction parameters. Negative cooperativity governs an effective loading capacity of n = 2 molecules under cryogenic conditions (T_eq = 143.76 and 114.64 K), while an entropic bottleneck renders higher loading non-spontaneous at all temperatures. These results establish Li₆(H₂)_n as a foundational gas-phase reference, providing a systematic, contamination-free descriptor set for the intrinsic Li–H₂ interaction. This framework is essential for isolating the electronic role of the lithium superatom and unambiguously identifying substrate-induced modulations in supported hydrogen storage materials. Full article

Zinc and iron are essential micronutrients in crop nutrition, and polymer-based nanogels have emerged as promising carriers to modulate their availability in sustainable agricultural systems. Here, a polymeric model receptor was designed to investigate how the nature and position of electron-donating (–NH₂) and electron-withdrawing (–NO₂) substituents control the recognition of Zn²⁺ and Fe²⁺ cations. Using a combination of density functional theory calculations, energy decomposition analysis with natural orbitals for chemical valence (EDA–NOCV), electrostatic potential (ESP) mapping, and quantum theory of atoms in molecules (QTAIM) method, the receptor–cation interactions are dissected into electrostatic, Pauli repulsion, orbital, and dispersion contributions. The results show that complex stability is governed mainly by orbital and electrostatic terms, with Fe²⁺ forming the most stable complex (−393.57 kcal mol⁻¹) with regard to a Zn²⁺ similar complex (−288.80 kcal mol⁻¹). Zn²⁺ complexes exhibit a broad tunability with substituent pattern. Electron-donating groups systematically strengthen both electrostatic and orbital components, whereas nitro substituents display a pronounced positional effect, ranging from strong destabilization to significant stabilization of Zn²⁺ binding. These findings establish molecular-level guidelines for engineering polymeric nanogels with tunable affinity and selectivity toward micronutrient cations in agricultural applications. Full article

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

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

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

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

Carbon dioxide is naturally present in the Earth’s atmosphere and plays a role in regulating and balancing the planet’s temperature. However, due to various human activities, the amount of carbon dioxide is increasing beyond safe limits, disrupting the Earth’s natural temperature regulation system. Today, CO₂ is the most prevalent greenhouse gas; as its concentration rises, significant climate change occurs. Therefore, there is a need to utilize anthropogenically released carbon dioxide in valuable fuels, such as formic acid (HCOOH). Single-atom catalysts are widely used, where a single metal atom is anchored on a surface to catalyze chemical reactions. In this study, we investigated the potential of Cu@Phosphorene as a single-atom catalyst (SAC) for CO₂ reduction using quantum chemical calculations. All computations for Cu@Phosphorene were performed using density functional theory (DFT). Mechanistic studies were conducted for both bimolecular and termolecular pathways. The bimolecular mechanism involves one CO₂ and one H₂ molecule adsorbing on the surface, while the termolecular mechanism involves two CO₂ molecules adsorbing first, followed by H₂. Results indicate that the termolecular mechanism is preferred for formic acid formation due to its lower activation energy. Further analysis included charge transfer assessment via NBO, and interactions between the substrate, phosphorene, and the Cu atom were confirmed using quantum theory of atoms in molecules (QTAIM) and non-covalent interactions (NCI) analysis. Ab initio molecular dynamics (AIMD) calculations examined the temperature stability of the catalytic complex. Overall, Cu@Phosphorene appears to be an effective catalyst for converting CO₂ to formic acid and remains stable at higher temperatures, supporting efforts to mitigate climate change. Full article

Background/Objectives: Understanding the stabilization mechanisms of amino acid conformations in different solvent environments is crucial for elucidating biomolecular interactions and crystallization processes. This study presents a comprehensive computational investigation of glycine, the simplest amino acid, in both its canonical and zwitterionic forms when interacting with dimethyl sulfoxide (DMSO) molecules. Methods: Using density functional theory (DFT) calculations at the B3LYP/6-311++G(d,p) level with empirical dispersion corrections, we examined the conformational landscape of glycine–DMSO clusters with one and two DMSO molecules, as well as implicit solvent calculations, and compared them with analogous water clusters. Results: Our results demonstrate that while a single water molecule is insufficient to stabilize the zwitterionic form of glycine, one DMSO molecule successfully stabilizes this form through specific interactions between the S=O and the methyl groups of DMSO and the NH₃⁺ and the oxoanion group of zwitterionic glycine, respectively. Topological analysis of the electron density using QTAIM and NCI methods reveals the nature of these interactions. When comparing the relative stability between canonical and zwitterionic forms, we found that two DMSO molecules significantly reduce the energy gap to approximately 12 kJ mol⁻¹, suggesting that increasing DMSO coordination could potentially invert this stability. Implicit solvent calculations indicate that in pure DMSO medium, the zwitterionic form becomes more stable below 150 K, while remaining less stable at room temperature, contrasting with aqueous environments where the zwitterionic form predominates. Conclusions: These findings provide valuable insights into DMSO’s unique role in biomolecular stabilization and have implications for protein crystallization protocols where DMSO is commonly used as a co-solvent. Full article