Search Results (34)

This study focuses on the search for new effective synthetic antimicrobial compounds as a tool against the widespread presence of microorganisms resistant to existing drugs. Five derivatives of [1,3]thiazolo[3,2-b][1,2,4]triazoles were synthesized using an accessible protocol based on electrophilic heterocyclization and were characterized using infrared (FTIR) and nuclear magnetic resonance (NMR) spectroscopies, and their in vitro antimicrobial and antifungal activities were evaluated using the agar plate diffusion method and the microdilution plate procedure. Both antibacterial (Gram-positive and Gram-negative) and antifungal activities were found for the examined samples. The minimum inhibitory concentration (MIC) varied from 0.97 to 250 µg/mL, and the minimum bactericidal concentration (MBC) from 1.95 to 500 µg/mL. Compound 2a showed good antifungal action against Candida albicans and Saccharomyces cerevisiae with minimum fungicidal concentration (MFC) 125 and MIC 31.25 µg/mL. The molecular docking revealed that the 2-heptyl-3-phenyl-6,6-trimethyl-5,6-dihydro-3H-[1,3]thiazolo[3,2-b][1,2,4]triazol-7-ium cation stands out as a highly promising candidate for further investigation due to a wide range of interactions, including conventional hydrogen bonds, π–σ, π–π T-shaped, and hydrophobic alkyl interactions. The synthesis and preliminary evaluation of [1,3]thiazolo[3,2-b][1,2,4]triazoles yielded promising antimicrobial and antifungal candidates. The diverse interaction profile of the 2-heptyl derivative salt allows this compound’s selection for further biological studies. Full article

This study integrates molecular dynamics (MD) simulations and density functional theory (DFT) computations to elucidate the unique adsorption characteristics of phenol and para-chlorophenol onto sepiolite by examining structural deformation, electronic properties, and adsorption energetics. The hydroxyl group (-OH) of phenol mainly determines its adsorption process since it has a quite negative Mulliken charge (−0.428) and significant electrophilic reactivity (fi⁺ = 0.090), therefore enabling strong hydrogen bonding with the silanol (-SiOH) groups of sepiolite. By π-π interactions with the electron-rich siloxane (-Si-O-Si-) surfaces, the aromatic carbons in phenol improve stability. The close molecular structure allows minimum deformation energy (E_def = 94.18 kcal/mol), hence optimizing alignment with the sepiolite surface. The much negative adsorption energy (E_ads = −349.26 kcal/mol) of phenol supports its further thermodynamic stability. Conversely, because of its copious chlorine (-Cl) component, para-chlorophenol runs against steric and electrical obstacles. The virtually neutral Mulliken charge (−0.020) limits electrostatic interactions even if the chlorine atom shows great electrophilicity (fi⁺ = 0.278). Chlorine’s electron-withdrawing action lowers the hydroxyl group’s (fi⁺ = 0.077) reactivity, hence lowering hydrogen bonding. Moreover, para-chlorophenol shows strong deformation energy (E_def = 102.33 kcal/mol), which causes poor alignment and less access to high-affinity sites. With less negative than phenol, the adsorption energy for para-chlorophenol (E_ads = −317.53 kcal/mol) indicates its reduced thermodynamic affinity. Although more evident in para-chlorophenol because of the polarizable chlorine atom, van der Waals interactions do not balance its steric hindrance and reduced electrostatic interactions. With a maximum Qmax = 0.78 mmol/g, isotherm models confirm the remarkable adsorption capability of phenol in contrast to Qmax = 0.66 mmol/g for para-chlorophenol. By hydrogen bonding and π-cation interactions, phenol builds a dense and structured adsorption layer, and para-chlorophenol shows a chaotic organization with reduced site use. Supported by computational approaches and experimental validation, the results provide a comprehensive knowledge of adsorption mechanisms and provide a basis for the design of adsorbents catered for particular organic pollutants. Full article

Antibiotic pollution, particularly via tetracycline (TC), poses significant environmental risks due to its recalcitrance and potential to induce antibiotic resistance. This study employed density functional theory (DFT) and transition state theory (TST) to investigate TC degradation by hydroxyl radicals (·OH), focusing on hydrogen atom transfer (HAT) and radical adduct formation (RAF) pathways. Geometry optimizations and vibrational analysis validated stationary points, while intrinsic reaction coordinate (IRC) calculations confirmed transition states. Key findings reveal that RAF pathways exhibit lower activation barriers (1.23–30.33 kJ/mol) and greater exothermicity (−164.42 kJ/mol) compared to HAT pathways (3.51–42.04 kJ/mol, −109.58 kJ/mol), making them kinetically and thermodynamically dominant. Frontier molecular orbital (FMO) analysis links HAT to TC’s HOMO (π-orbital character on aromatic rings) and RAF to its LUMO (electrophilic sites). Rate constants calculated at 298 K (TST with Wigner correction) confirm RAF’s kinetic superiority (up to 7.0 × 10¹¹ s⁻¹), surpassing HAT’s fastest pathway (6.2 × 10¹¹ s⁻¹). These insights advance the understanding of TC degradation mechanisms and help with the design of efficient photocatalytic oxidation processes for antibiotic removal. Full article

The Prostate cancer (PC) is a major problem all over worldwide and this is the second highest cancer-related mortality rate after lung cancer all over worldwide. At least 299,010 likely cases in men were reported in the US in 2024 and about 35,250 deaths are reported. The overexpression of prostate-specific membrane antigen (PSMA) is a key factor in the progression of prostate cancer and contributes to metastasis in lymph nodes, soft tissues and bones metastasis. The numerous studies have reported that, Glu-ureido-based molecules exhibit high binding affinity for PSMA. The earliest imaging agents developed from this structure were labeled with radioactive halogen isotopes and demonstrated nanomolar binding affinity, leading to exceptional imaging properties. Hence the Glu-ureido chemical moiety is a very important template as inhibitor of PSMA. In this study to explore the chemical structural and electronic features of Glu-Ureido structure with the aid of quantum chemistry computer simulations. In this study, first optimized the structure of this chemical structure using the B3LYP 6311-G (++, d, p) basis set. In this study investigated the maximal quantity of electronic charge transfer (N_max), chemical hardness (η), electrostatic potential, chemical potential (µ) and electrophilicity (ω). By the using Natural Bond Orbital (NBO) analysis, the examination shows that the molecule’s chemically active regions π-electron-electron delocalization within the molecule that contribute to its stability. Full article

This work investigated the substitution of the aldehyde with a pyran functional group in D-π-aldehyde dye to improve cell performance. This strategy was suggested by recent work that synthesized D-π-aldehyde dye, which achieved a maximum absorption wavelength that was only slightly off the threshold for an ideal sensitizer. Therefore, DFT and TD-DFT were used to investigate the effect of different pyran substituents to replace the aldehyde group. The pyran groups reduced the dye energy gap better than other known anchoring groups. The proposed dyes showed facile intermolecular charge transfer through the localization of HOMO and LUMO orbitals on the donor and acceptor parts, which promoted orbital overlap with the TiO₂ surface. The studied dyes have HOMO and LOMO energy levels that could regenerate electrons from redox potential electrodes and inject electrons into the TiO₂ conduction band. The lone pairs of oxygen atoms in pyran components act as nucleophile centers, facilitating adsorption on the TiO₂ surface through their electrophile atoms. Pyrans increased the efficacy of dye sensitizers by extending their absorbance range and causing the maximum peak to redshift deeper into the visible region. The effects of the pyran groups on photovoltaic properties such as light harvesting efficiency (LHE), free energy change of electron injection, and dye regeneration were investigated and discussed. The adsorption behaviors of the proposed dyes on the TiO₂ (1 1 0) surface were investigated by means of Monte Carlo simulations. The calculated adsorption energies indicates that pyran fragments, compared to the aldehyde in the main dye, had a greater ability to induce the adsorption onto the TiO₂ substrate. Full article

Benzophenone was encapsulated in molecular crystals of fully fluorinated coordination complexes, [ML₂] [1, M = Cu²⁺ and Pd²⁺, L = bis(pentafluorobenzoyl)-methanido⁻], forming a unique chiral co-crystal with a ratio of [ML₂]:benzophenone = 2:3, while no encapsulation was observed in the corresponding non-fluorinated complexes [M(dbm)₂] (dbm = dibenzoylmethanido⁻). Notable π-hole···π and metal(M)···π interactions were detected between the complex and the adapted orientation of benzophenone in the co-crystals. Analyses from crystal structures and thermogravimetric (TG) results indicated that the encapsulation and thermal stability of benzophenone in these molecular crystals correlate well with the electrophilic characteristics shown by the electrostatic potential (ESP) at the metal centers, which is enhanced by fluorination: Cu²⁺ > Pd²⁺ >> Pt²⁺. The recognition of benzophenone is driven by π-holes created by the electron-withdrawing nature of fluorine atoms and the electron-deficient metal ion enhanced by the aromatic fluorine, demonstrating that the effect of electrostatic molecular recognition is as significant as oxygen coordination, as shown in comparative studies with 1,1-diphenylethylene. Full article

This study reveals a new non-covalent interaction called a π-hole halogen bond, which is directional and potentially non-linear compared to its sister analog (σ-hole halogen bond). A π-hole is shown here to be observed on the surface of halogen in halogenated molecules, which can be tempered to display the aptness to form a π-hole halogen bond with a series of electron density-rich sites (Lewis bases) hosted individually by 32 other partner molecules. The [MP2/aug-cc-pVTZ] level characteristics of the π-hole halogen bonds in 33 binary complexes obtained from the charge density approaches (quantum theory of intramolecular atoms, molecular electrostatic surface potential, independent gradient model (IGM-δg^inter)), intermolecular geometries and energies, and second-order hyperconjugative charge transfer analyses are discussed, which are similar to other non-covalent interactions. That a π-hole can be observed on halogen in halogenated molecules is substantiated by experimentally reported crystals documented in the Cambridge Crystal Structure Database. The importance of the π-hole halogen bond in the design and growth of chemical systems in synthetic chemistry, crystallography, and crystal engineering is yet to be fully explicated. Full article

Solvation properties are key for understanding the interactions between solvents and solutes, making them critical for optimizing chemical synthesis and biochemical applications. Designable solvents for targeted optimization of these end-uses could, therefore, play a big role in the future of the relevant industries. The tailorable nature of protic ionic liquids (PILs) as designable solvents makes them ideal candidates. By alteration of their constituent structural groups, their solvation properties can be tuned as required. The solvation properties are determined by the polar and non-polar interactions of the PIL, but they remain relatively unknown for PILs as compared to aprotic ILs and their characterization is non-trivial. Here, we use solvatochromic dyes as probe molecules to investigate the solvation properties of nine previously uncharacterized alkyl- and dialkylammonium PILs. These properties include the Kamlet–Aboud–Taft (KAT) parameters: π* (dipolarity/polarizability), α (H-bond acidity) and β (H-bond basicity), along with the E_T(30) scale (electrophilicity/polarizability). We then used molecular dynamics simulations to calculate the radial distribution functions (RDF) of 21 PILs, which were correlated to their solvation properties and liquid nanostructure. It was identified that the hydroxyl groups on the PIL cation increase α, π* and E_T(30), and correspondingly increase the cation–anion distance in their RDF plots. The hydroxyl group, therefore, reduces the strength of the ionic interaction but increases the polarizability of the ions. An increase in the alkyl chain length on the cation led to a decrease in the distances between cations, while also increasing the β value. The effect of the anion on the PIL solvation properties was found to be variable, with the nitrate anion greatly increasing π*, α and anion–anion distances. The research presented herein advances the understanding of PIL structure–property relationships while also showcasing the complimentary use of molecular dynamics simulations and solvatochromic analysis together. Full article

Thiadiazole (THD) derivatives are famous for their exceptional chemical properties and versatile biological activities. In this work, we report computational investigations of the structure, reactivity, and binding affinity of three 1,3,4-THD derivatives (THDs) toward the SARS-CoV-2 main protease (Mpro). Hirshfeld surface (HS) analyses are carried out in conjunction with topological calculations in the context of the quantum theory of atoms in molecules (QTAIM) and reduced density gradient (RDG) to unravel the nature and magnitude of noncovalent interactions that contribute to maintaining these THDs. The three approaches consistently indicate that the titled THDs are mainly stabilized by weak intramolecular H…H, C-H…π, C-H…N, and N-H..H interactions in their monomeric forms, while their dimers also exhibit intermolecular π…π stacking and T-shaped contacts. In addition, Hirshfeld atomic charges, frontier molecular orbitals (FMOs), Fukui functions, and molecular electrostatic potential (MEP) reveal that the pyrrolic H atom (ring F) and the imidazole N atom (ring E) are the preferred binding sites for nucleophilic and electrophilic attacks, respectively. Finally, docking and molecular dynamics simulations demonstrate the remarkable binding profile of THDs toward the Mpro, which can be related to potential inhibitory activity. Full article

This study presents a comprehensive exploration of the structure–reactivity relationship of (E)-3-bromo-4-((4-((1-(4-chlorophenyl)ethylidene)amino)-5-phenyl-4H-1,2,4-triazol-3-yl)thio)-5-((2-isopropylcyclohexyl)oxy)furan-2(5H)-one. The study embarked on an in-depth investigation into the solid-state crystal structure of this organic compound, employing computational Density Functional Theory (DFT) and related methodologies, which have not extensively been used in the examination of such compounds. A single-crystal X-ray diffraction (SCXRD) analysis was initially performed, supplemented by a Hirshfeld surfaces analysis. This latter approach was instrumental in visualizing and quantifying intermolecular interactions within the crystal structures, offering a detailed representation of the molecule’s shape and properties within its crystalline environment. The concept of energy framework calculations was utilized to understand the varied types of energies contributing to the supramolecular architecture of the molecules within the crystal. The Conceptual DFT (CDFT) was applied to predict global reactivity descriptors and local nucleophilic/electrophilic Parr functions, providing a deeper understanding of the compound’s chemical reactivity properties. The aromatic character and π–π stacking ability were also evaluated with the help of LOLIPOP and ring aromaticity measures. This comprehensive approach not only provides a detailed description of the structure and properties of the investigated compound but also offers valuable insights into the design and development of new materials involving 1,2,4-triazole systems. Full article

A new class of spirocyclic imines (SCIs) has been theoretically investigated by applying a variety of quantum chemical methods and basis sets. The uniqueness of these compounds is depicted by various peculiarities, e.g., the incidence of planar six-membered rings each with two imine groups (two π bonds) and the incorporation of the isosteres carbon, silicon, or germanium spiro centers. Additional peculiarities of these novel SCIs are mirrored by their three-dimensionality, the simultaneous occurrence of nucleophilic and electrophilic centers, and the cross-hyperconjugative (spiro-conjugation) interactions, which provoke charge mobility along the spirocyclic scaffold. Substitution of SCIs with strong electron-withdrawing substituents, like the cyano group or fluorine, enhances their docking capability and impacts their reactivity and charge mobility. To gain thorough knowledge about the molecular properties of these SCIs, their structures have been optimized and various quantum chemical concepts and models were applied, e.g., full NBO analysis and the frontier molecular orbitals (FMOs) theory (HOMO-LUMO energy gap) and the chemical reactivity descriptors derived from them. For the assessment of the charge density distribution along the SCI framework, additional complementary quantum chemical methods were used, e.g., molecular electrostatic potential (MESP) and Bader’s QTAIM. Additionally, using the aromaticity index NICS (nuclear independent chemical shift) and other criteria, it could be shown that the investigated cross-hyperconjugated sila and germa SCIs are spiro-aromatics of the Heilbronner Craig-type Möbius aromaticity. Full article

The work here reflects synthesis, DFT studies, Hirshfeld charge analysis and crystal data exploration of pharmacologically important (R)-2-(2-(1,3-dioxoisoindolin-2-yl)propanamido)benzoic acid methyl ester (5) to understand its properties for further chemical transformations. The methyl anthranilate (2) was produced by the esterification of anthranilic acid in an acidic medium. The phthaloyl-protected alanine (4) was rendered by the fusion of alanine with phthalic anhydride at 150 °C, followed by coupling with (2) furnished isoindole (5). The characterization of products was performed using IR, UV-Vis, NMR and MS. Single-crystal XRD also verified the structure of (5) in which N-H⋯O bonding stabilizes the molecular configuration of (5), resulting in the formation of S(6) hydrogen-bonded loop. The molecules of isoindole (5) are connected in the form of dimers, and the π⋯π stacking interaction between aromatic rings further stabilizes the crystal packing. DFT studies suggest that HOMO is over the substituted aromatic ring, the LUMO is present mainly over the indole side, and nucleophilic and electrophilic corners point out the reactivity of the product (5). In vitro and in silico analysis of (5) shows its potential as an antibacterial agent targeting DNA gyrase and Dihydroorotase from E. coli and tyrosyl-tRNA synthetase and DNA gyrase from Staphylococcus aureus. Full article

The aim of this essay is to disclose the similarity of a great variety of reactions that proceed between nucleophiles and π-electrophiles—both aromatic and aliphatic. These reactions proceed via initial reversible addition, followed by a variety of transformations that are common for the adducts of both aliphatic and aromatic electrophiles. We hope that understanding of this analogy should help to expand the scope of the known reactions and inspire the search for new reactions that were overlooked. Full article

In recent years, fluorescent compounds that emit efficiently in the solid state have become particularly interesting, especially those that are easily prepared and inexpensive. Hence, exploring the photophysical properties of stilbene derivatives, supported by a detailed analysis of molecular packing obtained from single-crystal X-ray diffraction data, is a relevant area of research. A complete understanding of the interactions to determine the molecular packing in the crystal lattice and their effect on the material’s physicochemical properties is essential to tune various properties effectively. In the present study, we examined a series of methoxy-trans-stilbene analogs with substitution pattern-dependent fluorescence lifetimes between 0.82 and 3.46 ns and a moderate-to-high fluorescence quantum yield of 0.07–0.69. The relationships between the solid-state fluorescence properties and the structure of studied compounds based on X-ray analysis were investigated. As a result, the QSPR model was developed using PLSR (Partial Least Squares Regression). Decomposition of the Hirshfeld surfaces (calculated based on the arrangement of molecules in the crystal lattice) revealed the various types of weak intermolecular interactions that occurred in the crystal lattice. The obtained data, in combination with global reactivity descriptors calculated using HOMO and LUMO energy values, were used as explanatory variables. The developed model was characterized by good validation metrics (RMSE_CAL = 0.017, RMSE_CV = 0.029, R²_CAL = 0.989, and R²_CV = 0.968) and indicated that the solid-state fluorescence quantum yield of methoxy-trans-stilbene derivatives was mainly dependent on weak intermolecular C…C contacts corresponding to π-π stacking and C…O/O…C interactions. To a lesser extent and inversely proportional, the fluorescence quantum yield was affected by the interactions of the type O…H/H…O and H…H and the electrophilicity of the molecule. Full article

Catalyst-free multicomponent reactions of mixed alkylzinc reagents with Michael acceptors and aldehydes, ketones or activated imines are described. Primary, secondary and tertiary alkylzinc reagents, pre-generated in acetonitrile from the corresponding iodoalkanes, were used in the process, leading to the very efficient formation of a variety of β-hydroxycarbonyl compounds. The imines showed more contrasting results, due to the direct addition of the organozinc compound to the C=N bond. Mechanistic assays involving TEMPO account for a polar instead of a radical character of the reaction. Full article