Search Results (459)

Access to clean water is a pressing global concern and membrane technologies play a vital role in addressing this challenge. Thin-film composite membranes prepared via interfacial polymerization (IPol) using meta-phenylenediamine (MPD) and trimesoyl chloride (TMC) exhibit excellent separation performance, but face limitations such as fouling and low hydrophilicity. This study investigated the interaction between MPD and sulfonated zinc phthalocyanine, Zn(SO₂⁻)₄Pc, as a potential strategy for enhancing membrane properties. Using Density Functional Theory (DFT) and Time-Dependent DFT (TD-DFT), we analyzed the optimized geometries, electronic structures, UV–Vis absorption spectra, FT-IR vibrational spectra, and molecular electrostatic potentials of MPD, Zn(SO₂⁻)₄Pc, and their complexes. The results show that MPD/Zn(SO₂⁻)₄Pc exhibits reduced HOMO-LUMO energy gaps and enhanced charge delocalization, particularly in aqueous environments, indicating improved stability and reactivity. Spectroscopic features confirmed strong interactions via hydrogen bonding and π–π stacking, suggesting that Zn(SO₂⁻)₄Pc can act as a co-monomer or additive during IPol to improve polyamide membrane functionality. A conformational analysis of MPD/Zn(SO₂⁻)₄Pc was conducted using density functional theory (DFT) to evaluate the impact of dihedral rotation on molecular stability. The 120° conformation was identified as the most stable, due to favorable π–π interactions and intramolecular hydrogen bonding. These findings offer computational evidence for the design of high-performance membranes with enhanced antifouling, selectivity, and structural integrity for sustainable water treatment applications. Full article

Background/Objectives: Understanding the molecular interactions between small bioactive compounds and serum albumins is essential for drug development and pharmacokinetics. Noraucuparin, a biphenyl-type phytoalexin with promising pharmacological properties, has shown a strong binding affinity to bovine serum albumin (BSA), a model protein for drug transport. This study aims to elucidate the structural and energetic characteristics of the noraucuparin–BSA complex under physiological and slightly elevated temperatures. Methods: Microsecond-scale molecular dynamics (MD) simulations and Molecular Mechanics Generalized Born Surface Area (MMGBSA)-binding-free energy calculations were performed to investigate the interaction between noraucuparin and BSA at 298 K and 310 K. Conformational flexibility and per-residue energy decomposition analyses were conducted, along with interaction network mapping to assess ligand-induced rearrangements. Results: Noraucuparin preferentially binds to site II of BSA, near the ibuprofen-binding pocket, with stabilization driven by hydrogen bonding and hydrophobic interactions. Binding at 298 K notably increased the structural mobility of BSA, affecting its global conformational dynamics. Key residues, such as Trp213, Arg217, and Leu237, contributed significantly to complex stability, and the ligand induced localized rearrangements in the protein’s intramolecular interaction network. Conclusions: These findings offer insights into the dynamic behavior of the noraucuparin–BSA complex and enhance the understanding of serum albumin–ligand interactions, with potential implications for drug delivery systems. Full article

The radical-mediated intramolecular translocation of cyano groups has been recognized as a useful tool for the site-selective functionalization of organic molecules. The process is believed to proceed through the addition of an in situ-generated carbon-centered radical to the nitrile triple bond, followed by the β-scission of the resulting cyclic iminyl radical intermediate to relocate the cyano group and produce a more stable carbon radical for further elaboration. Beginning in the early 1960s and continuing for the next forty years, the research in this particular area has seen a surge of growth during the past two decades with advancements in radical chemistry and photocatalysis. The present article attempts to conduct a comprehensive review of existing studies on this topic by covering the literature from 1961 to 2025. The procedures developed for the purpose are grouped and discussed in four sections according to the strategies used to generate the initial carbon radicals, which include (i) hydrogen-atom transfer (HAT), (ii) radical addition to the π system, (iii) halogen-atom transfer (XAT), and (iv) the homolytic fission of a C-C single bond. In each section, a specific emphasis will be placed on reaction conditions, substrate scopes, and mechanisms. Full article

The adsorption of the drug gemcitabine on nucleobases was investigated using a dispersion-corrected density functional theory (DFT) study. The planar structure of complexes is more stable than those with stacked and buckle-angled configurations. The complexes were found to possess at least two intermolecular hydrogen bonds. The binding energy and interaction energy are both negative, with the highest values observed for the gemcitabine–guanine and the lowest in the gemcitabine–thymine complex. The complex formation was found to be an enthalpy-driven process. Pyrimidine nucleobases have a lower enthalpy of formation than purine nucleobases. The computed HOMA and NICS values on the gemcitabine–nucleobase complexes show a substantial increase compared to the pristine nucleobases. An MESP analysis of the complexes shows a directional interaction and electron density shift between the gemcitabine and the nucleobases. A QTAIM analysis indicates that the intermolecular hydrogen bonds have a partial covalent character. The computed bond energy demonstrates that intermolecular NH⋅⋅⋅N bonds are more potent than other bonds. An energy decomposition analysis using the DLPNO−CCSD(T) method indicates that the complexes exhibit a substantial electrostatic attraction, and dispersion contributes the least towards the system stability. The intermolecular bonds are stronger than the intramolecular bonds in the drug–nucleobase complexes. The strength of intramolecular bonds is determined by the deformation of the gemcitabine ring during the complex formation. Full article

Sotolon is a chiral furanone derivative featuring three distinct oxygen atoms at carbonyl, hydroxyl, and cyclic ether groups that can serve as hydrogen-bond acceptor sites, making it an ideal model system for probing water’s preferential interactions with competing functional groups. In this study, the rotational spectrum of sotolon and its microsolvated complexes, representing the early stages of hydration, was investigated using chirped-pulse Fourier transform microwave (CP-FTMW) spectroscopy. The conformational landscape of sotolon is dominated by a single conformer stabilized by an intramolecular O–H···O=C hydrogen bond. During hydration, water molecules disrupt this interaction by forming closed hydrogen-bonded cycles, resulting in mono- and dihydrated complexes. High-level theoretical calculations underscore the central role of electrostatic interactions in stabilizing these hydrated structures. Furthermore, A/E splittings observed in the rotational spectrum, arising from the internal rotation of one of sotolon’s methyl groups, provide insight into how hydration modulates the methyl internal rotation barrier. Full article

1,2,4-Cyclohexatrienes are strained, reactive intermediates often formed by the tetradehydro-Diels–Alder (TDDA) reaction of a conjugated enyne bearing a tethered alkyne as the enynophile. The ene component is commonly the π-bond of an aromatic group. In this focused study, we investigated the reactivity of a symmetrical substrate in which the pair of terminal ene moieties were simple 2-propenyl groups. The intermediate 1,2,4-cyclohexatriene, now bearing a 5-isopropenyl group, underwent competitive aromatization (the most usual outcome of the strain-relieving event of the cyclohexatriene), along with an intramolecular [1,5]-hydrogen atom migration, ultimately producing a non-benzenoid, pyrrole derivative. This represents a previously unknown process for a 1,2,4-cyclohexatriene derivative. Mechanistic aspects of the competitive processes were revealed by experiments performed in the presence of various protic additives (MeOD and BHT). Full article

This study investigates the influence of weak hydrogen bonds on the conformational properties and spectral characteristics of cannabidiol (CBD). Using a combination of FTIR and NMR spectroscopy, we analyze the effects of intramolecular hydrogen bonding, particularly the O-H∙∙∙π interactions, on the molecular behavior of CBD in chloroform solution. FTIR spectra reveal distinct ν_s(O-H) stretching bands at 3603 cm⁻¹ and 3425 cm⁻¹, corresponding to free and hydrogen-bonded -OH groups, respectively, with experimental results aligning closely with computational data for CBD conformers. Notably, conformer 1a predominates in solution, with weaker hydrogen bonding observed for the -OH(B) group compared to -OH(A). Additionally, the formation of -OH∙∙∙π hydrogen bonds affects key vibrational bands in the 1700–1300 cm⁻¹ region. NMR analysis shows significant shifts in proton and carbon signals, emphasizing the influence of hydrogen bonding on CBD’s electronic environment. The observed changes in coupling constants, although subtle, further highlight the impact of these interactions on spin–spin coupling. Overall, these findings provide deeper insights into the structural and electronic factors governing CBD’s behavior in solution, offering a basis for future studies on hydrogen bonding in biomolecules and their pharmacological implications. Full article

Receptors capable of binding both positive and negative ions are an important domain of supramolecular chemistry with valuable application potential. A Complete thermodynamic description of the equilibria related to ion pair recognition is beneficial in developing the optimized receptor systems, although it represents a difficult task that is rarely resolved due to various coupled processes. Here, we present a comprehensive study of ion pair (NaCl, NaHSO₄, and NaH₂PO₄) binding by a ureido–amide calix[4]arene host in acetonitrile using a series of experimental techniques and molecular dynamics simulations. We devoted particular attention to characterizing the side processes (ion association and salt precipitation) and included them in the models describing ion pair complex formation. For this purpose, a multimethod approach (potentiometry, conductometry, ITC, flame AES) was employed, generating reliable data which provided insight into the thermodynamic effect of each included equilibrium. Positive cooperativity was observed in the context of NaCl and NaHSO₄ binding by the studied calixarene. Computational results related to the NaCl complex in acetonitrile revealed that favorable Coulombic interactions, changes in affinity for solvent molecule inclusion, and intramolecular hydrogen bonding contributed to cation-induced cooperativity. Full article

n-Octanol and related ether alcohols are studied via molecular dynamics (MD) simulations using the two classical all-atom force fields OPLS-AA and CHARMM. The ether alcohols studied possess one ether functionality separated by varying n carbon atoms from the hydroxy group to elucidate how the positioning of the ether functionality affects intra- and intermolecular hydrogen bonding and, in turn, the physical properties of the studied alcohols. Important general trends observed from simulations with both force fields include the following: Intramolecular hydrogen bonding is majorly present in 3-butoxypropanol and 4-propoxybutanol (n = 3 and 4) while being only marginally present for 5-ethoxypentanol and 6-methoxyhexanol (n = 5 and 6) and absent in 1-hexyloxymethanol and 2-pentyloxyethanol (n = 1 and 2). The intramolecular hydrogen bonds formed by 3-butoxypropanol and 4-propoxybutanol are among the most stable ones of all present hydrogen bonds. Intermolecular hydrogen bonding is stronger between hydroxy groups (OH-OH) than between hydroxy and ether groups (OH-OE). An increased temperature causes a reduction in intermolecular OH-OH and OH-OE hydrogen bonding but a slight increase in intramolecular hydrogen bonding. A reduction in end-to-end distances at a higher temperature is also observed for all studied alcohols, which is likely a reflection of increased dihedral bond rotations. Hydrogen bonding extends mostly between just two molecules while hydrogen bonding networks are rare but do exist, involving, in some instances, up to 30 hydrogen bonds. Regardless of force field and temperature, the obtained radial distribution functions (RDFs) mostly show the same features at same distances that only vary in their intensity. 1-hexyloxymethanol forms a very specific and stable intermolecular double OH-OE hydrogen-bonded dimer. Similar double-hydrogen-bonded dimers can be found for the ether alcohols but are only significantly present for 2-pentyloxyethanol. Overall, the main difference between OPLS-AA and CHARMM is their quantitative prediction of the present hydrogen bonding speciation largely due to the stiffer dihedral potentials in OPLS-AA compared to the CHARMM force field. The simulations indicate that (a) the variations in densities are correlated to the reduced packing efficiency caused by intramolecular hydrogen bonding, (b) self-diffusion correlates with the stability of the intermolecular hydrogen bonds, and (c) the presence of hydrogen-bonded networks, although small in numbers, affect the viscosity. Full article

Microbial transglutaminase (mTG) is most frequently utilized in order to increase the gelling properties of soybean protein isolate (SPI), but there are still some limitations of mTG-based hydrogel fabrication technology. Therefore, we aimed to develop a dual modification technique based on enzyme plus organic acid treatment to fabricate SPI hydrogels with high gel strength and stability. Our results showed that mTG plus glucose-δ-lactone (GDL), lactobionic acid (LBA) or maltobionic acid (MBA) treatment could significantly improve the gel strength, textural properties, and water-holding capacity of SPI hydrogels. Also, the addition of these organic acids remarkably reduced the surface hydrophobicity (H₀) and intrinsic fluorescence as well as increased the storage modulus (G′), loss modulus (G″) values, average particle size, and the absolute value of zeta potential of samples. GDL, LBA, or MBA greatly increased the β-sheet level and decreased the α-helix level in hydrogels, as well as dissociated 11S subunits of SPI into 7S subunits. Notably, covalent interactions, hydrogen bonding, and hydrophobic interactions of three organic acids with SPI, as well as the effects of organic acids on the interactions among the intramolecular and intermolecular forces of SPI molecules, contributed to their promoting effects on the formation of hydrogels. The LF-NMR and SEM analyses confirmed the effects of GDL, LBA, and MBA on converting the free water into immobilized and bound water as well as forming a dense stacked aggregate structure. Therefore, GDL, LBA, and MBA are promising agents to be combined with mTG in the fabrication of SPI hydrogels with high gel strength and stability. Full article

Flavone derivatives have emerged as promising antiviral agents, with baicalein demonstrating the potent inhibition of the SARS-CoV-2 main protease (Mpro). In this study, the unique electronic and structural properties of 3-hydroxyflavone (3-HF) were investigated using the density functional theory (B3PW91/cc-pVTZ), providing insights into its potential as a bioactive scaffold. Among mono-hydroxyflavone (n-HF) isomers, 3-HF exhibits an extensive intramolecular hydrogen-bonding network linking the phenyl B-ring to the A- and γ-pyrone C-rings, enabled by the distinctive C3-OH substitution. Despite a slight non-planarity (dihedral angle: 15.4°), this hydrogen-bonding network enhances rigidity and influences the electronic environment. A ¹³C-NMR chemical shift analysis revealed pronounced quantum mechanical effects of the C3-OH group, diverging from the trends observed in other flavones. A natural bond orbital (NBO) analysis highlighted an unusual charge distribution, with predominantly positive charges on the γ-pyrone C-ring carbons, in contrast to the typical negative charges in flavones. These effects impact C1s orbital energies, suggesting that the electronic structure plays a more significant role in ¹³C-NMR shifts than simple ring assignments. Given the established antiviral activity of hydroxylated flavones, the distinct electronic properties of 3-HF may enhance its interaction with SARS-CoV-2 Mpro, making it a potential candidate for further investigation. This study underscores the importance of quantum mechanical methods in elucidating the structure–activity relationships of flavones and highlights 3-HF as a promising scaffold for future antiviral drug development. Full article

In this study, complexes of pregelatinized Chinese yam starch with ferulic acid (PCYS+FA) were prepared using a boiling water bath, with varying levels of Chinese yam starch (CYS) and ferulic acid (FA). The investigation focused on the effects of FA addition (3%, 9%, and 15%) on the physicochemical properties and structure of PCYS+FA complexes. The solubility, swelling, and water-holding capacity of PCYS+FA were compared with those of CYS, with the solubility and swelling showing a gradual enhancement with increasing FA content. The incorporation of FA reduced the thermal stability of CYS, decreasing the initial degradation temperature from 245.94 °C (CYS) to 228.17 °C (PCYS+15%FA). Infrared spectroscopy revealed that CYS and FA were bound through non-covalent intramolecular hydrogen bonding. Furthermore, X-ray diffractograms showed that FA and CYS formed a V-type complex, in which the crystallinity of PCYS reached a minimum of 3.72%, and the degree of molecular ordering was reduced. Scanning electron microscopy analysis demonstrated that FA adhered to the surface of starch granules, resulting in the formation of pores that facilitated the entry of FA molecules into the internal crystal region of starch, allowing them to interact with starch molecules. Full article

Phospholipase Cζ (PLCζ), a sperm-specific enzyme, plays a critical role in mammalian fertilization. Mutations in PLCζ have been linked to male infertility, as they impair its ability to trigger calcium (Ca²⁺) oscillations necessary for egg activation and embryo development. During fertilization, PLCζ is introduced into the egg, where it hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP₂) into inositol 1,4,5-trisphosphate and diacylglycerol, leading to Ca²⁺ release from the endoplasmic reticulum. Human infertility-associated mutations include H233L, H398P, and R553P, which disrupt PLCζ function. To elucidate the molecular consequences of the mutations, we employed full-atom molecular dynamics simulations to analyze structural perturbations and their impact on PIP₂ and Ca²⁺ binding. Our results reveal that H233L and H398P mutations significantly reduce interactions with PIP₂, disrupting hydrogen bonding and salt bridge formation, leading to misalignment of the substrate. Additionally, these mutations destabilize Ca²⁺ binding by altering its positioning within the active site. In contrast, the R553P mutation primarily affects intramolecular stability and enzyme dynamics without impairing substrate or ion binding. Free energy calculations indicate an increased affinity for PIP₂ in H233L and H398P mutants, leading to an aberrant substrate positioning and compromised hydrolysis. These structural insights help explain the egg activation failure and infertility of patients carrying these mutations. Full article

The kynurenine pathway is a significant metabolic route involved in the catabolism of tryptophan, producing various bioactive metabolites with crucial roles as antioxidants in immune regulation and neurobiology. This study investigates the acid-base properties of picolinic acid, kynurenic acid, kynurenine, and 3-hydroxykynurenine, utilizing computational simulations and experimental techniques, including potentiometric and nuclear magnetic resonance titrations. The results reveal distinct pK_a values, with kynurenic acid exhibiting a single dissociation step around 2.4, while kynurenine displays three dissociation steps governed by interactions between its functional groups. Additionally, 3-hydroxykynurenine shows overlapping dissociations in two separate pH regions, suggesting nuanced behavior influenced by its molecular structure. The analysis of intramolecular hydrogen bonding in protonation microspecies across varying pH highlights the relevance of the charge state and hydrogen transfer potential of these metabolites in the context of their radical scavenging ability. At physiological pH, most kynurenine and 3-hydroxykynurenine entities exist in zwitterionic form, with hydrogen bonding stabilizing the aromatic amino group, which may significantly influence their interactions with proteins and reactive oxygen species. This study provides critical insights into the acid-base equilibria of kynurenine pathway metabolites. Full article

Bacterial outer membrane vesicles (OMVs) are nanoscale extracellular structures produced by Gram-negative bacteria that are critical for microbial biology and host-pathogen interactions and have great potential in biotechnological applications. Despite the availability of fluorescent dyes for OMV studies, many are repurposed from eukaryotic extracellular vesicle research and are not explicitly optimized for OMVs, leading to challenges in achieving consistent labeling, minimizing background noise, and preserving vesicle integrity during analyses. This study evaluates B2, a benzimidazole-derived fluorophore, for OMV labeling in advanced techniques like flow cytometry and confocal microscopy. OMVs were isolated from Escherichia coli strains BL21 and O157, and their integrity was confirmed using transmission electron microscopy (TEM). B2 staining protocols were optimized for OMVs, and fluorescence analyses revealed specific interactions with the vesicle membranes, reducing aggregation and enhancing signal uniformity. Flow cytometry indicated near-complete labeling efficiency (98–100%) with minimal background interference. Confocal microscopy further validated B2’s effectiveness, showing evident OMV internalization into epithelial HT-29 cells and compatibility with other fluorophores. Density functional theory (DFT) calculations, including Fukui function analysis, identified key electrophilic and nucleophilic regions in B2 that facilitate specific hydrogen bonding and polar interactions with membrane components. Non-covalent interaction (NCI) analysis revealed pronounced intramolecular hydrogen bonding along with discrete regions of weak van der Waals interactions. Molecular dynamics simulations suggest that B2 exhibits an affinity for both the hydrophobic core of the lipid bilayer and the core oligosaccharide region of the LPS layer, which collectively ensures sustained retention of the dye. The findings presented in this study position B2 as a valuable fluorophore for OMV research. Full article