Study of chemical reactivity and molecular interactions of the hydrochlorothiazide-4-aminobenzoic acid cocrystal using spectroscopic and quantum chemical approaches.

In this study, the molecular, electronic, and chemical properties of the drug hydrochlorothiazide (HCTZ) are determined after cocrystallization with 4-aminobenzoic acid (4-ABA). Analysis has been performed to understand how those variations lead to alteration of physical properties and chemical reactivity in the cocrystal HCTZ-4ABA. IR and Raman characterizations were performed along with quantum chemical calculations. A theoretical investigation of hydrogen bonding interactions in HCTZ-4ABA has been conducted using two functionals: B3LYP and wB97X-D. The results obtained by B3LYP and wB97X-D are compared which leads to the conclusion that B3LYP is the best applied function (density functional theory) to obtain suitable results for spectroscopy. The chemical reactivity descriptors are used to understand various aspects of pharmaceutical properties. Natural bond orbital (NBO) analysis and quantum theory of atoms (QTAIM) are used to analyze nature and strength of hydrogen bonding in HCTZ-4ABA. QTAIM analyzed moderate role of hydrogen bonding interactions in HCTZ-4ABA. The calculated HOMO-LUMO energy gap shows that HCTZ-4ABA is chemically more active than HCTZ drug. These chemical parameters suggest that HCTZ-4ABA is chemically more reactive and softer than HCTZ. The results of this study suggest that cocrystals can be a good alternative for enhancing physicochemical properties of a drug without altering its therapeutic properties.

In the process of polysaccharide gel formation: A review of the role of competitive relationship between water and alcohol molecules.

Polysaccharides have emerged as versatile materials capable of forming gels through diverse induction methods, with alcohol-induced polysaccharide gels demonstrating significant potential across food, medicinal, and other domains. The existing research mainly focused on the phenomena and mechanisms of alcohol-induced gel formation in specific polysaccharides. Therefore, this review provides a comprehensive overview of the intricate mechanisms underpinning alcohol-triggered gelation of different polysaccharides and surveys their prominent application potentials through rheological, mechanical, and other characterizations. The mechanism underlying the enhancement of polysaccharide network structures by alcohol is elucidated, where alcohol displaces water to establish hydrogen bonding and hydrophobic interactions with polysaccharide chains. Specifically, alcohols change the arrangement of water molecules, and the partial hydration shell surrounding polysaccharide molecules is disrupted, exposing polysaccharides' hydrophobic groups and enhancing hydrophobic interactions. Moreover, the pivotal influences of alcohol concentration and addition method on polysaccharide gelation kinetics are scrutinized, revealing nuanced dependencies such as the different gel-promoting capabilities of polyols versus monohydric alcohols and the critical threshold concentrations dictating gel formation. Notably, immersion of polysaccharide gels in alcohol augments gel strength, while direct alcohol addition to polysaccharide solutions precipitates gel formation. Future investigations are urged to unravel the intricate nexus between the mechanisms underpinning alcohol-induced polysaccharide gelation and their practical utility, thereby paving the path for tailored manipulation of environmental conditions to engineer bespoke alcohol-induced polysaccharide gels.

Bis(amino acidato)copper(II) compounds in blood plasma: a review of computed structural properties and amino acid affinities for Cu2+ informing further pharmacological research.

Neutral bis(amino acidato)copper(II) [Cu(aa)2] coordination compounds are the physiological species of copper(II) amino acid compounds in blood plasma taking the form of bis(l-histidinato)copper(II) and mixed ternary copper(II)-l-histidine complexes, preferably with l-glutamine, l-threonine, l-asparagine, and l-cysteine. These amino acids have three functional groups that can bind metal ions: the common α-amino and carboxylate groups and a side-chain polar group. In Cu(aa)2, two coordinating groups per amino acid bind to copper(II) in-plane, while the third group can bind apically, which yields many possibilities for axial and planar bonds, that is, for bidentate and tridentate binding. So far, the experimental studies of physiological Cu(aa)2 compounds in solutions have not specified their complete geometries. This paper provides a brief review of my group's research on structural properties of physiological Cu(aa)2 calculated using the density functional theory (DFT) to locate low-energy conformers that can coexist in aqueous solutions. These DFT investigations have revealed high conformational flexibility of ternary Cu(aa)2 compounds for tridentate or bidentate chelation, which may explain copper(II) exchange reactions in the plasma and inform the development of small multifunctional copper(II)-binding drugs with several possible copper(II)-binding groups. Furthermore, our prediction of metal ion affinities for Cu2+ binding with amino-acid ligands in low-energy conformers with different coordination modes of five physiological Cu(aa)2 in aqueous solution supports the findings of their abundance in human plasma obtained with chemical speciation modelling.

2-Bromo-acetamide.

The title compound, C2H4BrNO, crystallizes in the monoclinic space group P21/c with one mol-ecule in the asymmetric unit. The almost planar mol-ecules are organized via N-H⋯O hydrogen bonds into a ladder-type network, which can be characterized by the graph sets R 2 2(8) and R 2 4(8). In addition, the mol-ecules are connected by C-H⋯O and C-H⋯Br contacts.

Crystal structure and Hirshfeld surface analysis of (E)-N-(2-styrylphen-yl)benzene-sulfonamide.

The crystal structure of the title compound C20H17NO2S features hydrogen-bonding and C-H⋯π inter-actions. Hirshfeld surface analysis revealed that H⋯H, C⋯H/H⋯C and O⋯H/H⋯O inter-actions make a major contribution to the crystal packing. Docking studies were carried out to determine the binding affinity and inter-action profile of the title compound with EGFR kinase, a member of the ErbB family of receptor tyrosine kinases, which is crucial for processes such as cell proliferation and differentiation. The title compound shows a strong binding affinity with EGFR kinase, with the most favourable conformation having a binding energy of -8.27 kcal mol-1 and a predicted IC50 of 870.34 nM, indicating its potential as a promising candidate for targeted lung cancer therapy.

Synthesis, crystal structure and Hirshfeld surface analysis of sulfamethoxazolium methyl-sulfate monohydrate.

The mol-ecular salt sulfamethoxazolium {or 4-[(5-methyl-1,2-oxazol-3-yl)sulf-amo-yl]anilinium methyl sulfate monohydrate}, C10H12N3O3S+·CH3O4S-·H2O, was prepared by the reaction of sulfamethoxazole and H2SO4 in methanol and crystallized from methanol-ether-water. Protonation takes place at the nitro-gen atom of the primary amino group. In the crystal, N-H⋯O hydrogen bonds (water and methyl-sulfate anion) and inter-molecular N-H⋯N inter-actions involving the sulfonamide and isoxazole nitro-gen atoms, link the components into a tri-dimensional network, additional cohesion being provided by face-to-face π-π inter-actions between the phenyl rings of adjacent mol-ecules. A Hirshfeld surface analysis was used to verify the contributions of the different inter-molecular inter-actions, showing that the three most important contributions for the crystal packing are from H⋯O (54.1%), H⋯H (29.2%) and H⋯N (5.0%) inter-actions.

Side-chain-induced changes in aminated chitosan: Insights from molecular dynamics simulations.

Chitosan is a functional polymer with diverse applications in biomedicine, agriculture, water treatment, and beyond. Via derivatization of pristine chitosan, its functionality can be tailored to desired applications, e.g. immobilization of biomolecules. Here, we performed molecular dynamics simulations of three aminated chitosan polymers, where one, two, and three long-distanced side chains have been incorporated. These polymers have been previously synthesized and their properties were investigated experimentally, however, the observed dependencies could not be fully explained on the molecular level. Here, we develop a computational protocol for the simulation of functionalized chitosan polymers and perform advanced analysis of their conformational states, intramolecular interactions, and water binding. We demonstrate that intra- and intermolecular forces, especially hydrogen bonds induced by polymer side chain modifications, modulate dihedral angle conformational states of the polymer backbone and interactions with water. We explain the role of the chemical composition of the functionalized chitosans in their tendency to collapse and reveal the key role of the protonation of the amino group near the polymer backbone on the reduction of polymer collapse. We demonstrate that specific binding of water molecules, especially the intermediate water, is more pronounced in the polymer exhibiting such an amino group.

Structural Snapshots, Trajectory and Thermodynamics of the Reversible µ-1,2-Peroxo/µ-1,1-Hydroperoxo Dicopper(II) Interconversion.

Hydrogen bonds involving the oxygen atoms of intermediates that result from copper-mediated O2 activation play a key role for controlling the reactivity of Cux/O2 active sites in metalloenzymes and synthetic model complexes. However, structural insight into H-bonding in such transient species as well as thermodynamic information about proton transfer to or from the O2-derived ligands is scarce. Here we present a detailed study of the reversible interconversion of a µ1,2-peroxodicopper(II) complex ([1]+) and its µ1,1-hydroperoxo congener ([2]+) via (de)protonation, including the isolation and structural characterization of several H-bond donor (HBD) adducts of [1]+ and the determination of binding constants. For one of these adducts a temperature-dependent µ1,2-peroxo/µ1,1-hydroperoxo equilibrium associated with reversible H+-translocation is observed, its thermodynamics investigated experimentally and computationally, and effects of H-bonding on spectroscopic parameters of the CuII2(µ1,2-O2) species are revealed. DFT calculations allowed to fully map and correlate the trajectories of H+-transfer and µ1,2-peroxo→µ1,1-peroxo rearrangement. These findings enhance our understanding of two key intermediates in bioinspired Cu2/O2 chemistry.

Partitioning / self-assembly of artificial water channels - toward controlled permselectivity through bilayer membrane.

Artificial water channels (AWCs) have been extensively explored to mimic natural proteins, which enables to effectively transport water while blocking ions. As one of the first AWCs, self-assembled I-quartets (HCx) have showcased high water-permselectivity that can be enhanced by improving their distribution and stability within membrane. The use of long alkyl chains (n>8) is constrained by their low solubility and aggregation. Herein, we considered cycloalkyl moieties, explored for the increase of the solubility favoring enhanced partition and/ for their self-assembly behaviors resulting the formation of effective stable water-channels with increased water permeability in bilayer membranes. This class of cycloalkyl-ureido-ethyl-imidazole amphiphilic (CxUH) channel could serve as a new reference for the effective design of self-assembled artificial water channels, it may give rise to the applications in desalination or in water treatment.

The Hydrogen Bonding in the Hard Domains of the Siloxane Polyurea Copolymer Elastomers.

For probing the structure-property relationships of the polyurea elastomers, we synthesize the siloxane polyurea copolymer elastomer by using two aminopropyl-terminated polysiloxane monomers with low and high number-average molecular weight (Mn), i.e., L-30D and H-130D. To study the influence of the copolymer structures on the film properties, these films are analyzed to obtain the tensile performance, UV-vis spectra, cross-sectional topographies, and glass transition temperature (Tg). The two synthetic thermoplastic elastomer films are characterized by transparency, ductility, and the Tg of the hard domains, depending on the reacting compositions. Furthermore, the film elasticity behavior is studied by the strain recovery and cyclic tensile test, and then, the linear fitting of the tensile data is used to describe the film elasticity based on the Mooney-Rivlin model. Moreover, the temperature-dependent infrared (IR) spectra during heating and cooling are conducted to study the strength and recovery rate of the hydrogen bonding, respectively, and their influence on the film performance is further analyzed; the calculated Mn of the hard segment chains is correlated to the macroscopic recovery rate of the hydrogen bonding. These results can add deep insight to the structure-property relationships of the siloxane polyurea copolymer.

Research on the Thermal Aging Mechanism of Polyvinyl Alcohol Hydrogel.

Polyvinyl alcohol (PVA) hydrogels find applications in various fields, including machinery and tissue engineering, owing to their exceptional mechanical properties. However, the mechanical properties of PVA hydrogels are subject to alteration due to environmental factors such as temperature, affecting their prolonged utilization. To enhance their lifespan, it is crucial to investigate their aging mechanisms. Using physically cross-linked PVA hydrogels, this study involved high-temperature accelerated aging tests at 60 °C for 80 d and their performance was analyzed through macroscopic mechanics, microscopic morphology, and microanalysis tests. The findings revealed three aging stages, namely, a reduction in free water, a reduction in bound water, and the depletion of bound water, corresponding to volume shrinkage, decreased elongation, and a "tough-brittle" transition. The microscopic aging mechanism was influenced by intermolecular chain spacing, intermolecular hydrogen bonds, and the plasticizing effect of water. In particular, the loss of bound water predominantly affected the lifespan of PVA hydrogel structural components. These findings provide a reference for assessing and improving the lifespan of PVA hydrogels.

AgNP Composite Silicone-Based Polymer Self-Healing Antifouling Coatings.

Biofouling poses a significant challenge to the marine industry, and silicone anti-biofouling coatings have garnered extensive attention owing to their environmental friendliness and low surface energy. However, their widespread application is hindered by their low substrate adhesion and weak static antifouling capabilities. In this study, a novel silicone polymer polydimethylsiloxane (PDMS)-based poly(urea-thiourea-imine) (PDMS-PUTI) was synthesized via stepwise reactions of aminopropyl-terminated polydimethylsiloxane (APT-PDMS) with isophorone diisocyanate (IPDI), isophthalaldehyde (IPAL), and carbon disulfide (CS2). Subsequently, a nanocomposite coating (AgNPs-x/PDMS-PUTI) was prepared by adding silver nanoparticles (AgNPs) to the polymer PDMS-PUTI. The dynamic multiple hydrogen bonds formed between urea and thiourea linkages, along with dynamic imine bonds in the polymer network, endowed the coating with outstanding self-healing properties, enabling complete scratch healing within 10 min at room temperature. Moreover, uniformly dispersed AgNPs not only reduced the surface energy of the coating but also significantly enhanced its antifouling performance. The antibacterial efficiency against common marine bacteria Pseudomonas aeruginosa (P.sp) and Staphylococcus aureus (S.sp) was reduced by 97.08% and 96.71%, respectively, whilst the diatom settlement density on the coating surface was as low as approximately 59 ± 3 diatom cells/mm2. This study presents a novel approach to developing high-performance silicone antifouling coatings.

Molecular Design Engineering Regulates the Ground-State Passivation Ability of Benzophenone Derivatives in Perovskite Solar Cells.

Intramolecular hydrogen bonding (H-bonding) involved in the excited-state proton transfer (ESPT) process results in benzophenone derivatives (BPDs) with an excellent ability to passivate defects. However, the BPDs are in a continuing dynamic transition process between the ground state and the excited state under light radiation conditions. The ground-state BPDs may lose their ability to passivate defects, resulting in an increased defect density of the perovskite. Therefore, enhancing the passivation ability of the ground-state BPDs can help to achieve the full passivation ability of their ground state to excited state. Herein, we have researched the various BPDs by density functional theory and found that intramolecular H-bonding can weaken the passivation ability of ground-state BPDs, but intramolecular H-bonding is indispensable in the ESPT process. To address the issue, we investigated the influence of electron-donor properties and dipole moments of hydroxyl (-OH), methoxy (-OCH3), and n-octyloxy (-OC8H17) groups in BPD molecules on their coordination capacity through molecular design engineering. Ultimately, 2-hydroxy-4-n-octyloxy-benzophenone (UV5) with strong electron-donor n-octyloxy (-OC8H17) and elongated carbon-chain structure was selected as an additive, which enhances the passivate defect capability in both the ground and excited states. As a result, the UV5-based champion device achieved a power conversion efficiency (PCE) of 24.46% and remained at 75% of the initial PCE with exposure to UV light. This work focuses on the defect passivation capability of ground-state BPDs for the first time and opens a new concept for applying BPDs in PSCs.

Facile Molecular-Level Refinements for Carbon Quantum Dots via Hydrogen-Bonding-Assisted Selective Isolation.

A novel method for synthesizing and refining high-purity carbon quantum dots (CQDs) using citric acid and diethylenetriamine as precursors is presented, achieved through molecular-level control by exploiting the differences in hydrogen-bonding strength. This process involves precipitation using melamine, extraction into ethanol, and encapsulation with (3-aminopropyl)triethoxysilane (APTES). The resulting APTES-encapsulated CQDs exhibited an enhanced color purity, higher photoluminescence quantum yield, and improved fluorescence stability over a broad pH range. Utilizing these well-defined high-purity CQDs with uniform surface states, it has been revealed that ferric ions are photochemically sensed through the inner filter effect (IFE) mechanism, while mercury ions are detected through the photoinduced electron transfer (PET) mechanism. The versatility of CQDs, coupled with our advanced refinement technology, is expected to contribute significantly to the development of advanced research applications, particularly in displays and sensors.

Hydrogen bonding in 2,2,2-trifluoroethanol.

CONTEXT: 2,2,2-Trifluoroethanol (TFE) is known as a membrane mimetic solvent. The IR spectrum, 1H NMR spectrum, 13C NMR spin‒lattice relaxation times (T1), and nuclear Overhauser effect (NOE) data are consistent with extensive hydrogen bonding in TFE, but do not lead to structural features of the hydrogen bonding. Hence, DFT computations were carried out. The results predict the existence of a set of H-bonded dimers and trimers. The bond lengths and dihedral angles in these complexes are obtained, together with their dissociation energies. Computations were also performed for the geometry of the two conformers of the isolated monomer. The structure of one of the dimers consists of a 7-member cyclic fragment with a free CF3CH2 side chain. One set of the trimer structures involves the OH of a third monomer H-bonding to one of the F atoms in the CF3 group of the side chain of this dimer, thereby creating three trimer isomers. A fourth trimer cluster is formed from three monomers in which three OH∙∙∙O bonds create a cyclic fragment with three CF3CH2 side chains. The high dissociation energy (with respect to three monomers) indicates the high stability of the trimer complexes. The structural features of the trimer complexes resemble the structure of a conventional liquid crystal molecule and are postulated to resemble the latter in properties and function in solution, but at a much shorter timescale because of the noncovalent bonding. This hydrogen bonding phenomenon of TFE may be related to its function as a membrane memetic solvent. METHODS: Initially, IR and NMR spectroscopic methods were used. Standard procedures were followed. For the computations, a hybrid DFT method with empirical dispersion, ωB97X-D, was used. The basis set, 6-311++G**, is of triple-ζ quality, in which polarization functions and diffuse functions were added for all atoms.

Intermolecular interactions in water and ethanol solution of ethyl acetate: Raman, DFT, MEP, FMO, AIM, NCI-RDG, ELF, and LOL analyses.

CONTEXT: The intermolecular interactions of ethyl acetate (EtOAc)-water (H2O)/ethanol (EtOH) mixtures were investigated using a combination of Raman spectroscopy and quantum chemical calculations. The computational approach was used to analyze the structure of hydrogen-bonded complexes of ethyl acetate with water/ethanol molecules, based on density functional theory (DFT). The calculated frequencies closely matched the experimental Raman values, with differences being under 4%. Experimental data show that when the concentrations of ethyl acetate in the ethyl acetate/water/ethanol solutions were reduced, almost all Raman spectral bands are blue-shifted. The AIM analysis reveals that all the given complexes possess a positive energy density, indicating that the molecules interact electrostatically. The energy and bond length indicate that the methyl group forms relatively weak hydrogen bonds. Analysis indicates that EtOAc forms weak H-bonding C = O∙∙∙H and C-H∙∙∙O, which are recognized as van der Waals interactions. As the amount of ethyl acetate decreases in the complex, the interaction forces also decrease. This could also explain why the bands are blue-shifted. It was discovered that the title complexes' hydrogen bond energy decreased exponentially as bond length increased. METHODS: The geometries of the molecular complexes were optimized using the Gaussian 09W program and the B3LYP/6-311 + + G(d,p) set of functions. The potential energy distribution (PED) analysis was performed using VEDA 4.0 software. Raman spectra were drawn using the Origin 8.5 software. The Multiwfn 3.8 software was used to calculate topological parameters of electron density in molecular systems. GaussView 6.0 and Visual Molecular Dynamics (VMD) 1.9.3 tools were used to visualize all computational results.

Revisiting a natural wine salt: calcium (2R,3R)-tartrate tetrahydrate.

The crystal structure of the salt calcium (2R,3R)-tartrate tetrahydrate {systematic name: poly[[diaqua[µ4-(2R,3R)-2,3-dihydroxybutanedioato]calcium(II)] dihydrate]}, {[Ca(C4H8O8)(H2O)2]·2H2O}n, is reported. The absolute configuration of the crystal was established unambiguously using anomalous dispersion effects in the diffraction patterns. High-quality data also allowed the location and free refinement of all the H atoms, and therefore to a careful analysis of the hydrogen-bond interactions.

Crystallization and intermolecular hydrogen bonding in carbamazepine-polyvinyl pyrrolidone solid dispersions: An experiment and molecular simulation study on drug content variation.

The choice of drug content is a critical factor as far as the solid dispersion is concerned. This investigation aims to build the relationship between the drug content, intermolecular hydrogen bonding and the crystalline of the carbamazepine-polyvinyl pyrrolidone solid dispersion. In this work, the microstructural changes of solid dispersions were investigated using experimental characterization combined with molecular simulation. Experimental investigations demonstrated that increasing the drug content enhances the intermolecular hydrogen bonding between drugs, resulting in the crystalline phase of the drug emerged in the solid dispersion. This negatively affects the solubility and stability of solid dispersions. Molecular simulations were then used to analyze the changes of intermolecular hydrogen bonding at different drug content in the system. It revealed a tenfold increase in drug-drug hydrogen bonding concentration as drug content elevated from 10% to 50%, while the drug-excipient hydrogen bonding concentration decreased by 45%. The correlation analysis proves the significant relationships among the drug content, intermolecular hydrogen bonding, and crystallinity of solid dispersion. Using polynomial fitting analysis, the quantitative relationships between the drug content and crystalline properties were investigated. This study will offer valuable insights into the impact of drug content on the performance of solid dispersion.

Unraveling how hydrogen-bonding networks affect the capture of amphetamine-type stimulants by polymerized deep eutectic solvent modified magnetic biochar: Coupling quantum chemical calculations with experiment.

The abuse of amphetamine-type stimulants (ATSs) has caused irreversible harm to public safety and ecosystems. A novel polymerized deep eutectic solvent modified magnetic pomelo peel biochar (PMBC) was prepared, and the differences in adsorption of four abused amphetamine-type stimulants (ATSs: AMP, MAMP, MDA and MDMA) were due to varying hydrogen bonds quantities and strengths. PMBC showed excellent chemical reactivity to MDMA, with a maximum adsorption capacity of 926.13 µg g-1, which was 3.25, 2.52 and 1.15 times higher than that of AMP, MAMP and MDA, respectively. Modern spectral analysis showed that there were a series of active centers (-COOH, -NH2 and -OH) on the PMBC, which could form hydrogen bond networks with the nitrogen and oxygen functional groups of ATSs. In various chemical environments: pH level (4-11), inorganic ion and organic matter (humic acid), PMBC maintained high activity towards four ATSs. Additionally, the quantum chemical calculations revealed that the methylenedioxy bridge of ATSs can increase the active sites, and the -NH- and -NH2 groups had different hydrogen bond formation capabilities, which together resulted in the adsorption order of PMBC on the four ATSs: MDMA > MDA > MAMP > AMP. Moreover, the hydrogen-bonding binding energies of several common hydrogen-bonding types were compared, including O-H····O, N-H····O/O-H····N and N-H···N. This study laid an empirical and theoretical foundation for the efficient capture of ATSs in water and contributed to the innovative design of materials.

Effect of Solvent on the Optical Rotation of Azatryptophan Derivatives.

Chirally pure enantiomers of differently protected 7-azatryptophan derivatives (R-3c, S-3c, R-3i, S-3i, R-3m, S-3m, R-3aa, and S-3aa) were synthesized, which showed solvent-dependent optical rotation. The obtained results not only exhibited changes in the values but also showed the variation in sign (- or +) with the different solvents studied. The change in optical rotation value was essentially attributed to the electron-donating property, which can be correlated to the donor number of the solvents. There are two types of hydrogen bonds, intramolecular (i.e., form within the structure) and intermolecular (i.e., form with external groups such as solvents). These hydrogen bonds are responsible for the value and sign variations, and 1H NMR experiments were used to further characterize them. The NMR data suggested that hydrogen bond formation is occurring between the Fmoc NH group vicinal to the chiral center and donor group of the corresponding solvent.