Hydrogen Bond Acceptor Ability Research Articles

Nucleation of Insoluble Drugs in Solvents with Different Hydrogen Bond Donor and Acceptor Abilities─A Case Study of Probenecid

Nucleation of Insoluble Drugs in Solvents with Different Hydrogen Bond Donor and Acceptor Abilities─A Case Study of Probenecid

Polarity of Aqueous Solutions

This short review describes the expansion of the solvatochromic approach utilizing water-soluble solvatochromic dyes to the analysis of solvent features of aqueous media in solutions of various compounds. These solvent features (polarity/dipolarity, hydrogen bond donor ability (HBD acidity), and hydrogen bond acceptor ability (HBA basicity)) vary depending on the nature and concentration of a solute. Furthermore, the solvent features of water (the solvent dipolarity/polarizability and hydrogen bond donor ability) in solutions of various compounds describe multiple physicochemical properties of these solutions (such as the solubility of various compounds in aqueous solutions, salting-out and salting-in constants for polar organic compounds in the presence of different inorganic salts, as well as water activity, osmotic coefficients, surface tension, viscosity, and the relative permittivity of aqueous solutions of different individual compounds) and are likely related to changes in the arrangement of hydrogen bonds of water in these solutions.

Spectroscopic determination of the acidity constants and the effects of pH, temperature and solvents on the tautomerism of 1-substituted phenyl-3,5-diphenylformazans

UV–visible spectra were used to determine the acidity constants and the tautomeric properties of 1-substituted phenyl-3,5-diphenylformazans. The protonation and deprotonation behaviors of the compounds were investigated at different pHs. Protonation was observed for all compounds as two protons were acquired and deprotonation as one proton was lost. The effects of solvents on the tautomerism of 1-substituted phenyl-3,5-diphenylformazans were also investigated in neutral, acidic, and basic solutions at different pH and temperatures. The tautomerism interconversion percentages for the studied formazans were calculated from the absorption spectra obtained for different solvents at various temperatures. It was observed that the chelate form of the studied formazans was the dominant structure. It was concluded that the type of the substituents and hydrogen bonding acceptor ability of the solvents were the significant factors for the interaction in tautomerism.

Recombination of hydrogen bonds clipping interfacial film effectively for dehydrated tight oil

Tight oil is an important unconventional oil resource. However, during the extraction process of tight oil, a large amount of tight oil emulsion is generated, combined with offshore oil releases, have caused serious environmental problems. Owing to the high content of resin molecules, which adsorbed the interfacial water molecules in the form of hydrogen bonds, as well as tightly bound resin molecules via π–π stacking, the interface structure is stable; hence, it is difficult to separate oil and water. In this study, the hydrogen-bond energy of O atoms in common groups and water molecules was analyzed, and the efficient separation of oil and water was realized by the regulation of hydrogen-bond energies of the demulsifier molecules and interfacial water molecules. The O atoms in EO, PO, ester group and hydroxyl group were named as Type 1–6 O atoms. The compatibility of the demulsifier and tight oil was improved by the introduction of an aromatic structure, which combined with the tight oil molecules via π–π stacking. At the same time, by the introduction of Types 1–6 O atoms, the electronegativity (Hydrogen bond acceptor ability) of the demulsifier molecules was optimized to improve the hydrogen-bond energy formed between the demulsifier and water molecules effectively; then, the interfacial resin molecules were replaced to form stronger hydrogen bonds with water molecules, weakening the π-π stacking interaction between resin molecules for clipping the interfacial film; thus, the mass-transfer efficiency of water molecules at the oil–water interfacial is enhanced.

Exploring solvation behaviour of biocompatible ionic liquid 2-hydroxyethylammonium formate + polyethylene glycols mixtures: Role of oxyethylene and hydroxyl units of PEGs

The favourable modification of the physicochemical properties of the ionic liquid with green co-solvent and their molecular level characterization with spectroscopic techniques is the area of current research. Further, the co-solvent modified ionic liquid mixtures furnishes interesting properties which render the utility of these solvents in several important applications. In the current work, the effects of addition of two polyethylene glycols (PEGs) with average molecular weights of 200, and 600 on solvent properties of IL 2-hydroxyethyl ammonium formate (HEF) has been explored with the help of solvatochromic absorbance probes. The physicochemical characteristics of the ionic liquid mixtures are altered in an unexpectedly positive way when PEGs are added to IL HEF. The absorbance behaviour of the solvatochromic probes Reichardt dye 33 shows interestingly positive non-ideal behaviour, which may be attributed to the high dipolarity/polarizability (π*) and hydrogen bond donor ability (HBD) (α) of the HEF + PEG mixtures. Further, the Kamlet-Taft parameters, including hydrogen bond acceptor ability (HBA) (β), and hydrogen bond donor ability (HBD) (α), and dipolarity/polarizability (π*) of the HEF + PEG binary mixtures display nonideality, which may be because of the strong Hydrogen bond networking of HEF-PEG molecules along with solute-HEF/PEG interaction present in the mixtures. Moreover, the preferential solvation approach has been invoked to explore the solute–solvent/solvent–solvent interactions present in the HEF + PEGs binary mixtures. The Redlich–Kister (CNIBS/R–K) theoretical model predicts the experimental results obtained by solvatochromic probe studies in satisfactory manner. The results of the DFT and FTIR study also predict the possibility of the H-bonding interactions in HEF + PEGs mixtures.

Spectroscopic study of solvent effects on the electronic absorption spectra of morpholine and its complexes

The electronic absorption spectra of morpholine and its five morpholine complexes have been studied in different solvents of various polarities. The regression and correlation coefficients have been calculated with the SPSS program. Solvation energy relationships were deduced from spectral shifts and correlated with solvent parameters α (solvent hydrogen bond donor acidity), β (solvent hydrogen bond acceptor basicity), and π* (dipolarity/polarizability). The percentage contributions of the calculated solvatochromic parameters show that classic solvation effects play a major role in explaining the spectral shifts in all investigated complexes. The blue shift of [Fe(MOR)3Cl3]·4H2O, [Ni(MOR)4Cl2]·4H2O, and [Cu(MOR)4Cl2]·6H2O complexes is due to the formation of hydrogen bonds, which suggests the stabilization of the ground electronic state compared with the excited state. [CuNi(MOR)2Cl4]·4H2O and [CuZn(MOR)3Cl4]·2H2O are mixed metal complexes that suffer a red shift due to the solute-solvent interactions, which causes stabilization of the excited solute state with increasing solvent polarity. The bands are affected by specific solute-solvent interactions including hydrogen bond donor ability (acidity) and hydrogen bond acceptor ability (basicity) and nonspecific solute-solvent interactions including electromagnetic interaction between the dipole moments of solute and polar solvents.

Hydrogen bond properties of Se in [ROH-Se(CH3)2] complexes (R = H, CH3, C2H5): matrix-isolation infrared spectroscopy and theoretical calculations.

Se is now considered as a potential centre for hydrogen bond interactions. The hydrogen bond acceptor ability of Se has been investigated in [ROH-Se(CH3)2] complexes (R = H, CH3, and C2H5) using matrix-isolation infrared spectroscopy and electronic structure calculations. The first impression of the IR spectra of the hydrogen bond complexes of [ROH-Se(CH3)2] in N2 and Ar matrices is presented here. Moreover, no spectroscopic data are available for the [HOH-Se(CH3)2] complex. Vibrational spectra in the OH stretching region indicate the formation of the [ROH-Se(CH3)2] complex under the matrix-isolation conditions. Comparison of the experimental spectra with the simulated vibrational frequencies at different levels of theory confirms the formation of the 1 : 1 cluster of [ROH-Se(CH3)2] stabilised by O-H⋯Se hydrogen bond interactions. Multiple conformers of the [CH3OH-Se(CH3)2] complex having marginally different stabilisation energies have been predicted from electronic structure calculations and signatures of the same have been observed under the cold conditions of matrix isolation. Conformer specific assignment of the 1 : 1 cluster of [C2H5OH-Se(CH3)2] (anti and gauche forms) has been carried out in both the matrices. Concentration dependent experiments indicate the formation of higher order clusters and/or mixed clusters along with the formation of a 1 : 1 cluster for CH3OH and C2H5OH. The nature of the selenium centred hydrogen bond has been delineated using AIM, NBO and energy decomposition analysis. A comparison of similar complexes of H2O, CH3OH, and C2H5OH with O, S and Se indicates that Se is not far away in hydrogen bond acceptor ability compared to O and S.

Influence mechanism of different organic solvents on API solvation behaviors: Molecular dynamics simulations

Solubilities of active pharmaceutical ingredients (APIs) in different solvents are important fundamental properties and are of particular interest in purification (e.g. crystallization) of APIs in industry. Therefore, the objective of this work is to investigate the solvation mechanisms of the poorly soluble API ibuprofen in various organic solvents, by using molecular dynamics (MD) simulations. It was found that the solvation performance of ibuprofen in protic solvents mainly depend on van der Waals interaction, while that in aprotic solvents mainly depend on the ability of forming hydrogen bond (H-bond) of the solvents. Wherein, the strength of H-bond between ibuprofen and protic solvents mainly depends on the hydrogen bond donor (HBD) of the solvent, while hydrogen bond acceptor (HBA) ability of solvents directly determines the strength of H-bond between ibuprofen and aprotic solvents. This difference nature in solvation mechanism was due to the structural properties of protic solvents and aprotic solvents. Among them, protic solvents containing hydroxyl group have strong HBD and HBA characteristics, whereas aprotic solvents only show the characteristics of HBA, because it does not contain active hydrogen protons. In general, the MD simulation results revealed that the better solvation performance of ibuprofen in organic solvents corresponds to the higher polarizability of protic solvents or the stronger HBA ability of aprotic solvents. This work is expected to provide theoretical guidance for choosing appropriate solvents during API preparation and development.

Polarity effects on the optical responses of some biologically active molecules with different substituents

Environment polarity characteristics of biomolecules as an important factor can enhance their optical behaviors. Hence, knowledge of environment polarity effects can give valuable information about the function of molecules in different phenomena. In this work, linear, first, and second-order hyperpolarizability of (E)-2-benzylidene-2,3-dihydro-5,6-dimethoxyinden-1-one as pharmacologically important compounds were studied in different environments. The analysis was done by using environment multi-parameter polarity parameters. According to the results, environment polarity has different effects on the linear and nonlinear optical properties of samples. A quantitative study indicated that general solvent effects play important roles in molecular linear behaviors. Furthermore, environments with strong hydrogen bond acceptor ability increase molecular nonlinearity. On the other hand, environment polarity indicated the same effects on the molecular first and second-order nonlinearity. In this case, the studies on the molecular first-order nonlinearity in different solvents can give valuable information about environment effects on the molecular higher-order nonlinearity.

Cooperative catalysis: Condensation-aromatization for synthesis of 2-(4-nitrophenyl)-1H-benzimidazole by silica immobilized Brønsted-Lewis acidic ionic liquid (Si-BLAIL)

Herein, pleasing the advantageous of both Brønsted and Lewis acidic site of Si-BLAIL the condensation-aromatization reaction has been carried out. The striking distinctiveness of work is optimum reaction condition, easy work-up, high yield, catalyst recyclability, non-inertness of reaction flask, simple catalyst loading method. The decreases in the amount of catalyst and reaction time shows good to high (71%–93%) yield suggests about the involvement of some interesting mechanism such as cooperative catalysis. The mechanism has been hypothesizes as, the Si-BLAIL increase the efficiency of condensation reaction possibly by providing the proton in 2-position of cationic imidazolium ring of BLAIL through the hydrogen bond interaction with carbonyl group and nucleophilic activation during aromatization by hydrogen bond acceptor ability of Lewis adduct anion of BLAIL. The catalyst Si-BLAIL shows massive affirm for industrial applications. The Si-BLAIL has identified as the best acid catalyst for 2-(4-nitrophenyl) benzimidazole synthesis with additional benefits of cooperative catalysis.

Development of a correlation equation between the diesterification of maleic anhydride and the acidic ionic liquids nature

The sustainable synthesis of dimethyl maleate via diesterification through the utilization of ionic liquid (IL) is of great importance. However, the relationship between the ILs nature and the reactivity of diesterification is still unclear. Herein, a series of ILs with different structures were selected for the comprehensive investigation of diesterification. The acidity (H0) and Kamlet-Taft solvent parameters (hydrogen bond donor ability (α), hydrogen bond acceptor ability (β), and polarizability (π∗)) of ILs were measured by UV–Visible spectroscopy, and the effects of them on the diesterification of maleic anhydride were also studied in detail. The results indicated that not only H0 of the IL-based catalysis system, but also its α, β, and π∗ influenced the reaction activity of diesterification. Furthermore, a quantifiable correlation was fitted between the natural logarithm of the rate constant and multiple parameters of ILs, indicating that the diesterification rate had a positive correlation with the H0, α, and π∗, and inverse correlation with the β of the IL. A plausible synergetic reaction mechanism for the excellent performance of [(HSO3)PMim][HSO4] has been proposed. Overall, this work thoroughly explored the relationship between the nature of ILs on diesterification in-depth, which will reveal the nature of diesterification in detail.

Room-Temperature Spin Crossover in a Solution of Iron(II) Complexes with N,N'-Disubstituted Bis(pyrazol-3-yl)pyridines.

Here, we report a combined study of the effects of two chemical modifications to an N,N′-disubstituted bis(pyrazol-3-yl)pyridine (3-bpp) and of different solvents on the spin-crossover (SCO) behavior in otherwise high-spin iron(II) complexes by solution NMR spectroscopy. The observed stabilization of the low-spin state by electron-withdrawing substituents in the two positions of the ligand that induce opposite electronic effects in SCO–active iron(II) complexes of isomeric bis(pyrazol-1-yl)pyridines (1-bpp) was previously hidden by NH functionalities in 3-bpp precluding the molecular design of SCO compounds with this family of ligands. With the recent SCO-assisting substituent design, the uncovered trends converged toward the first iron(II) complex of N,N′-disubstituted 3-bpp to undergo an almost complete SCO centered at room temperature in a less polar solvent of a high hydrogen-bond acceptor ability.

Supramolecular Perspective of Coordination Effects on Fluorine Interactions

Coordination effects have been considered through the most common interactions in the crystal structures of fluoro compounds (C–H/F and F/F interactions). The supramolecular profile of these effects is based on quantum-chemical calculations for the assessment of the interaction strength and electrostatic potential maps, which provide a qualitative insight into the examined effect. Coordination of aliphatic fluorides leads to an increase of the negative potential of the F atoms, and, hence, an increase in the hydrogen-bonding acceptor ability (strengthening of C–H/F interactions) and a weakening of the F/F interactions, due to an increase in repulsive interactions between the F atoms. There is no significant change in the potential of the F atoms due to coordination of C6-aromatic fluorides, as in the case of aliphatic ones. This results in slight changes in the strengths of the C–H/F and F/F interactions (coupled with parallel interaction at large offsets, PILO), in a noticeable enhancement of stacking interactions, as well as in a significant enhancement of interactions involving the π-system (F/π and C–H/π interactions). It has also been shown that a decrease in the charge of the metal ions leads to a decrease in the negative potential of the F atom and also that the nature of the metal ion has a significant influence on the value of the potential of the F atoms.

Electronic Effects in the Structure of 1-Ethyl-3-Methylimidazolium Ionic Liquids

In this study, ten 1-ethyl-3-methylimidazolium ionic liquids are analyzed by X-ray photoelectron spectroscopy. A reliable charge correction method is established based upon the binding energy difference between cationic N 1s and C2 1s. It is found that the Caliphatic 1s component is applicable for charge correction only if the Kamlet-Taft hydrogen bond acceptor ability value is larger than 0.77. The electronic environment of nitrogen and sulfur atoms is demonstrated in detail. The impact of the substituent on the binding energy of P 2p and B 1s is discussed.

Highly efficient separation of 5-hydroxymethylfurfural from imidazolium-based ionic liquids

The hydrogen bond acceptor ability of solvents, the interactions between the anion and cation of ILs, and the hydrogen bonding interaction of the anion with 5-HMF play important roles in the separation of 5-HMF from ILs.

Flavonoid Glycosides with a Triazole Moiety for Marine Antifouling Applications: Synthesis and Biological Activity Evaluation.

Over the last decades, antifouling coatings containing biocidal compounds as active ingredients were used to prevent biofouling, and eco-friendly alternatives are needed. Previous research from our group showed that polymethoxylated chalcones and glycosylated flavones obtained by synthesis displayed antifouling activity with low toxicity. In this work, ten new polymethoxylated flavones and chalcones were synthesized for the first time, including eight with a triazole moiety. Eight known flavones and chalcones were also synthesized and tested in order to construct a quantitative structure-activity relationship (QSAR) model for these compounds. Three different antifouling profiles were found: three compounds (1b, 11a and 11b) exhibited anti-settlement activity against a macrofouling species (Mytilus galloprovincialis), two compounds (6a and 6b) exhibited inhibitory activity against the biofilm-forming marine bacteria Roseobacter litoralis and one compound (7b) exhibited activity against both mussel larvae and microalgae Navicula sp. Hydrogen bonding acceptor ability of the molecule was the most significant descriptor contributing positively to the mussel larvae anti-settlement activity and, in fact, the triazolyl glycosylated chalcone 7b was the most potent compound against this species. The most promising compounds were not toxic to Artemia salina, highlighting the importance of pursuing the development of new synthetic antifouling agents as an ecofriendly and sustainable alternative for the marine industry.

Revealing the role of anisotropic solvent interaction in crystal habit formation of nifedipine

The modification of the crystal habits by the solvent selection approach has been widely applied. However, the underlying regulation mechanism by solvents, specifically solute recognition and assembly process at crystal-solution interface is not yet well-understood. Herein, the effects of solvents on crystal habit and interface assembly of nifedipine (NFD) were investigated by growth experiments in five selected organic solvents of distinct hydrogen bond affinity properties. It was found that the crystal habits of NFD can be tuned by the hydrogen bond acceptor (HBA) ability of solvents, which elevates the aspect ratio of the crystals. The X-ray diffraction (XRD) and differential scanning calorimeter (DSC) further confirmed that no polymorphs were involved and related with the morphology changes. The face indexing calculated by single crystal XRD of experimental morphologies, Hirshfeld surface analysis, and the surface chemistry of the different crystal facets revealed a directionality of solvent interactions with crystal faces, induced by the solute-solvent hydrogen bonding interactions. Further, the strength of the solute-solvent interactions quantified by the adsorption energy calculations and the RDF analyses correlates well with the HBA ability of the solvents and the experimental morphology. In all, it was unveiled that the directionality of solute-solvent hydrogen bonding interactions interrupts anisotropically the recognition and assembly of solutes at the crystal-solution interface, resulting in the modification of the crystal morphology.

Structure activity relationships (SAR) study to design and synthesize new tubulin inhibitors with enhanced anti-tubulin activity: In silico and in vitro analysis

Tubulysin family of natural products is a class of highly cytotoxic tetrapeptides that induce apoptosis by arresting the mitosis of a cell. In this article, we have analysed 49 reported tubulysin derivatives with known IC50 values to develop two and three-dimensional quantitative structure-activity relationships (2D and 3D QSAR) to explore the critical structural framework required for anti-tubulin activity. In the 2D technique, hologram QSAR (HQSAR models were generated by examining different combinations of the field parameters, number of components, and fragment sizes. Reliability of the best HQSAR model was validated by obtaining optimum values for statistical parameters such as cross-validated (q2 = 0.92) and correlation (r2 = 0.93) coefficients. Further, 3D-QSAR models were generated via CoMFA and CoMSIA methods. In CoMFA, using the Gast-Huck charge assigning method, the best correlation values for q2 and r2coefficients were found to be 0.59 and 0.93, respectively. Whereas in CoMSIA, by considering field contribution parameters such as steric, electrostatic, hydrophobic interactions, and hydrogen bond acceptor ability, a fine model was generated with best cross-validated (q2 = 0.58) and correlation (r2 = 0.94) coefficients values. Tubulysin M is one of the most potent anticancer agents known with an excellent IC50 of 0.02 nM to kill cancer cells. In the present study, tubulysin M co-crystallised with tubulin protein (PDB ID: 4ZOL) was used for molecular docking studies to analyze the drug-protein interactions. The results of QSAR and molecular docking studies were compiled and through in silico studies, structure activity relationships (SAR) were established. The in silico SAR results were utilized to design novel third generation tubulysin derivatives, which are easy to synthesize when compared to complex natural tubulysin derivatives. One of the third generation derivatives, Tub_01, was chemically synthesized and found to have an excellent anticancer activity against cervical cancer cell line (HeLa) with IC50 of 9.4 nM and 88.6 nM for different incubation time.

Chromogenic properties of 2-(2-carbomethoxy-3,4-dichloro-6-hydroxyphenyl)benzoxazole and its Zn(II) and Cd(II) complexes

The chromogenic properties of 2-(2-carbomethoxy-3,4-dichloro-6-hydroxyphenyl)benzoxazole (1) were studied. Solvatochromism of 1 was observed at keto-enol equilibrium due to the ground state intramolecular proton transfer (GSIPT). It was found that solvents with a good hydrogen bond acceptor (β) ability were able to stabilise the keto form of 1. The excited-state intra molecular proton transfer (ESIPT) in molecules of 1 resulted in intense fluorescence with an anomalous Stokes shift of up to 8493 cm−1 and quantum yields of 0.08–0.19. The keto-form of 1 exhibits negative T-type photochromism with a thermally reversible photoconversion to the enol form. The complexes of ligand 1 with Zn(II) and Cd(II) were synthesised. According to X-ray structural analysis, the zinc complex is the neutral complex, which is formed by two oxazole-N and two phenol O donors of ligand 1 which crystallise in a centrosymmetric group with the zinc ion located on the inversion centres. The synthesised complexes possess effective blue fluorescence and resistance to photodegradation.

D‐π‐A Molecular Probe to Unveil the Role of Solute‐Solvent Hydrogen Bonding in Solvatochromism, Location Specific Preferential Solvation and Synergistic Effect in Binary Mixtures

AbstractAn azo dye 4‐(p‐Nitrophenylazo) phenol (NPAP) characterized with a donor‐π‐acceptor (D‐π‐A) framework has been used as a molecular probe to study solvatochromic behavior in neat and binary solvent mixtures comprised of chloroform (a hydrogen bond donor; HBD solvent) and a hydrogen bond acceptor (HBA) solvent. The specificity of the probe lies in its inherent characteristics of having a HBD group and a HBA group at two different ends of the conjugated π‐network. UV‐Vis spectroscopic technique is used for the purpose. The probe demonstrates a very expressive reversal in solvatochromic behavior, with the solvatochromic switch at ET(30) of ∼45 kcal mol−1. Multiparametric treatment of the solvatochromic data using SEV technique displays excellent sensitivity of the probe towards HBA basicity, dipolarity and polarizability of the medium with a smaller but significant contribution from HBD acidity and hydrophobicity/apolarity. The event of preferential solvation in the chloroform‐HBA mixture is explained on the basis of specific solute‐solvent interaction through HBD and HBA ability of the solvent components. HBA solvents preferentially solvate the phenolic site while HBD solvents preferentially solvate the nitrobenzene group through complementary hydrogen bonding, which results in an increase in local concentration at specific sites resulting in synergistic preferential solvation. The proposition of site selective PS through molecular recognition is also supported by theoretical studies.