Hydrogen Bond Acceptor Molecules Research Articles

Deep eutectic solvents: Quantum chemical investigation, thermal stability and physicochemical properties

The current quantum-based research focuses on the eutectic mixtures formulated by combining hydrogen bond donors (Urea, Lactic acid, Xylitol, Proline Xylitol) and acceptor (Betaine, Choline chloride, Proline) molecules. The quantum chemical investigation reveals that DESs Choline chloride-Proline and Choline chloride-Xylitol are the best solvents with the lowest energy gap, highest chemical softness, and the least chemical hardness. FTIR spectroscopy spectra provided evidence of the production of new hydrogen bonds between the two DES components, illuminating the mechanisms behind the impact of the components on the physicochemical characteristics of the DESs. The thermal stability, viscosity, electrical conductivity of DESs under the effect of type of HBAs/HBDs was studied. The influence of the water on the electrical conductivity, density and viscosity are discussed. The initiation of decomposition temperatures for DESs was derived from dynamic thermogravimetric analysis (TGA). DESs have the second level of thermal stability, which means they can be used in technological processes with a range of operating temperatures within ∼ 100–150 °C.

Local composition-regular solution theory for analysis of pharmaceutical solubility in mixed-solvents

Local composition regular solution theory (LC-RST) model was developed by introducing non-equal i–j and j–i parameters into regular solution theory (RST) to account for specific molecular interactions. The LC-RST model was applied to the correlation of solubilities of active pharmaceutical ingredients (API) in hydrogen bond donor (HBD) – hydrogen bond acceptor (HBA) mixed-solvent systems. In the assessment of 32 API-mixed-solvent systems that contained 11 different APIs and 1947 data, it was determined that the LC-RST model had a logarithmic average relative deviation (ARDln) in solubility of 0.028, the Wilson model had an ARDln value of 0.24 and the purely predictive RST model had an ARDln value of 1.29. Partial molar excess enthalpies and entropies of the API in the mixed-solvents determined from the LC-RST model allowed estimation of API solubility regions where specific interactions occur between API and HBD-HBA complex molecules. In the correlation scheme, component numbers were designated as API molecule (1) – HBD molecule (2) - HBA molecule (3) and systems were grouped according to HBD molecule interactions with the API (pro-solvent, anti-solvent, synergistic with HBA molecule). Phenomenological parameter sensitivity analysis of the LC-RST model showed that dominant specific interactions tended to be 1–2 or 2–1 molecules for pro-solvent groupings, 2–3 or 2–3 molecules for anti-solvent groupings and all i–j and j-–i molecular pairs for synergistic HBD-HBA molecule groupings. Based on parameters determined from a given API-mixed-solvent system, the LC-RST model allows qualitative prediction of solubilities for other systems. The LC-RST model is simple to apply and it retains inherent predictive characteristics of regular solution theory.

Computational insights into deep eutectic solvent design: Modeling interactions and thermodynamic feasibility using choline chloride & glycerol

To address climate change and environmental concerns, the chemical process industries are increasingly adopting green technology and exploring eco-friendly waste management practices. Deep Eutectic Solvents (DES) have emerged as promising green solvents with diverse applications in the industries in separation processes, catalysis, drug design, and a lot more. However, the ideal way for modeling ionic interactions within the hydrogen-bond acceptor (HBA) during DES synthesis remains uncertain, and theoretical insight on the formation mechanism of energetically stable DESs from choline chloride (CHL) and urea (URE) is yet to be explored. In this study, we investigate different modeling approaches (no bond, generic bond, or single bond) for ionic interactions in hydrogen-bond acceptor (HBA) molecules during DES synthesis and the thermodynamic feasibility of forming an energetically stable DES using choline chloride (CHL) and urea (URE) through theoretical calculations (PM3, HF, and DFT). Our findings indicate that the choice of modeling approach does not significantly affect the outcomes across calculation levels. The H-X DES formation pathway emerges as the most viable route for CHL: GLC DES synthesis, offering strong binding energy and high exothermicity. This pathway provides a robust solution for synthesizing energetically stable DES with potential applications in various industries. Researchers can consider alternative calculation levels when DFT becomes cost-prohibitive to optimize computational costs. Our study contributes valuable insights into DES design and synthesis, promoting environmentally sustainable and cost-effective processes.

An Exploration of the Hydrogen Bond Donor Ability of Ammonia.

Ammonia is an important molecule due to its wide use in the fertiliser industry. It is also used in aminolysis reactions. Theoretical studies of the reaction mechanism predict that in reactive complexes and transition states, ammonia acts as a hydrogen bond donor forming N-H⋅⋅⋅O hydrogen bond. Experimental reports of N-H⋅⋅⋅O hydrogen bond, where ammonia acts as a hydrogen bond donor are scarce. Herein, the hydrogen bond donor ability of ammonia is investigated with three chalcogen atoms i. e. O, S, and Se using matrix isolation infrared spectroscopy and electronic structure calculations. In addition, the chalcogen bond acceptor ability of ammonia has also been investigated. The hydrogen bond acceptor molecules used here are O(CH3 )2 , S(CH3 )2 , and Se(CH3 )2 . The formation of the 1 : 1 complex has been monitored in the N-H symmetric and anti-symmetric stretching modes of ammonia. The nature of the complex has been delineated using Atoms in Molecules analysis, Natural Bond Orbital analysis, and Energy Decomposition Analysis. This work presents the first comparison of the hydrogen bond donor ability of ammonia with O, S, and Se.

Quantum chemical investigation of choline chloride-based deep eutectic solvents

The current quantum-based research focuses on the eutectic mixtures formulated by combining hydrogen bond donors (malic acid, tartaric acid, oxalic acid, ethylene glycol, and glycerol) and acceptor (choline chloride) molecules. Choline chloride (ChCl) is used as a hydrogen bond acceptor (HBA) having specified mole ratios with hydrogen bond donors (HBDs) to develop five deep eutectic solvents (DESs). Density functional theory (DFT) is used to examine the molecular dynamics (MD) of DESs to interpret the method's validity and quantum chemical aspects. The resemblance of the experimental Fourier-transform-infrared (FT-IR) vibrational frequencies with the calculated vibrational frequencies validates the Becke, 3-parameter, Lee–Yang–Parr (B3LYP) functional with basis set 6-31G. The frontier molecular orbitals (FMOs) and quantum chemical investigation reveal that among five solvents, DES1 (ChCl: EG) is the best solvent with the lowest energy gap (0.02 eV), highest chemical potential (0.19 eV), chemical softness (42.73 eV), and electrophilicity index (1.55 eV) and with least chemical hardness (0.01 eV) and electronegativity (−0.19 eV). This quantum acumen provides an effective revelation to design the required conductive solvents based on the DFT study. The density of states (DOS) provides insight that how many states were occupied in the unit of energy and can be used to evaluate the electronic structure. DFT-B3LYP/6-31G is used to simulate vibrational and quantum features of the experimentally prepared DESs.

In-depth DFT insights into the crucial role of hydrogen bonding network in CO2 fixation into propylene oxide promoted by Biomass-Derived deep eutectic solvents

The CO2 fixation into epoxide to produce cyclic carbonate is a promising route to realize the large-scale utilization of CO2. In this work, a detailed DFT investigation has been carried out to elucidate the mechanistic details of the CO2 conversion into propylene carbonate (PC) catalyzed by bio-mass derived deep eutectic solvents (bio-DESs), obtained by combining hydrogen bond donor (HBD) and hydrogen bond acceptor (HBA) molecules. Our calculations support the known beneficial effect of hydrogen bonds in activating the epoxide. On the other hand, DFT results also show that hydrogen bonds and transfers do also stabilize the negative charge of determining intermediates, with the consequent undesired effect of reducing the nucleophilicity of the oxygen atom involved in the final ring closure step. Moreover, hydrogen bonds are also established between the HBDs and the PC product, thus hampering its release.Our theoretical results offer an in-depth understanding of the CO2 fixation involving bio-DESs, which can guide towards the development of more efficient bio-catalysts.

Application of deep eutectic solvents in protein extraction and purification.

Deep eutectic solvents (DESs) are a mixture of hydrogen bond donor (HBD) and hydrogen bond acceptor (HBA) molecules that can consist, respectively, of natural plant metabolites such as sugars, carboxylic acids, amino acids, and ionic molecules, which are for the vast majority ammonium salts. Media such as DESs are modular tools of sustainability that can be pointed toward the extraction of bioactive molecules due to their excellent physicochemical properties, their relatively low price, and accessibility. The present review focuses on the application of DESs for protein extraction and purification. The in-depth effects and principles that apply to DES-mediated extraction using various renewable biomasses will be discussed as well. One of the most important observations being made is that DESs have a clear ability to maintain the biological and/or functional activity of the extracted proteins, as well as increase their stability compared to traditional solvents. They demonstrate true potential for a reproducible but more importantly, scalable protein extraction and purification compared to traditional methods while enabling waste valorization in some particular cases.

Anion recognition by urea metal-organic frameworks: remarkable sensitivity for arsenate and fluoride ions.

Functionalized metal-organic frameworks (F-MOFs) are known as a promising chemical sensors since they have specific merits like fixed functionalized ligands projecting into the pores which can be utilized to enhance sensitivity and selectivity. Due to the important role of anions in biological process and environmental systems, there is an increasing interest in synthesis and design of new receptors for anions. Urea groups can operate as a hydrogen bond donating site with hydrogen bond acceptor molecules. Strong and directional hydrogen-bonding between the positive urea groups and anions could reduce vibrational quenching and enhance the fluorescence intensity. In this study, two luminescent porous urea decorated MOFs have been successfully assembled and structurally characterized. Luminescence studies of these MOFs toward anions revealed that these F-MOFs exhibit high sensitivity and selectivity toward H2AsO4- and F- anions as two major ground water pollutants. Moreover, the proposed materials have been applied for the removal of arsenate and nitrate in contaminant well water samples. Graphical abstract.

Two-dimensional infrared spectroscopic study of cytochrome c peroxidase activity in deep eutectic solvent.

Deep eutectic solvents (DESs) prepared by mixing hydrogen-bond donor and acceptor molecules have been found to be of use in several applications. Recently, it was shown that DESs can enhance the peroxidation activity of cytochrome c. Here, to elucidate the effects of DESs on the peroxidase activity of cytochrome c, we carried out linear and nonlinear infrared spectroscopic studies of the CO stretch mode of carbon monoxide cytochrome c (COCytc) in ethylammonium chloride (EAC)/urea DES. The FTIR spectrum of COCytc shows a significant spectral shift upon addition of the DES. The broadening and red-shifting of the CO band are observed in both urea and DES solutions, which are induced by the change of the distal ligands around the heme. Although the FTIR study is sensitive to structural changes in the active site, it does not provide quantitative information about structural dynamics related to the catalytic activity itself. Thus, we carried out two-dimensional IR spectroscopy of the CO mode, which suggests that there is a different conformer that could be related to the enhanced catalytic activity in DES. In particular, the spectral diffusion dynamics of that conformer exhibits quite different behavior. The experimental results lead us to propose a hypothesis that the DES increases the population of the conformer with distal ligand lysines close to the reaction center through the combining effect of urea and EAC, which results in the enhancement of the peroxidase activity of cytochrome c. We anticipate that the present experimental work stimulates future investigations of the effects of DES on biocatalysis.

Role of the hydrogen bond donor component for a proper development of novel hydrophobic deep eutectic solvents

The environmental impact of chemical applications can be reduced by using novel solvents with green properties. In this field, Deep Eutectic Solvents (DESs) are promising liquids thanks to their low toxicity, high eco-compatibility and high easiness and “greenness” of preparation. DESs are mixtures of a hydrogen bond donor molecule (HBD) and a hydrogen bond acceptor molecule (HBA) at the proper molar ratio. In this paper, we present the preparation of novel hydrophobic deep eutectic solvents and the studies of their properties: density, eutectic profiles, ranges of water separation, contamination of the separated phases, extraction capabilities of phenol model polluting molecules, capabilities of extraction at acidic and basic conditions. Interesting results emerged about the role of the components of the DESs because of the use of a properly-chosen set of liquids. Their capabilities were dependent on the nature of the HBD molecule, and in particular on its hydrophobicity. Even the DESs with highly water-soluble HBA showed to be easily separable from water and really efficacious as extracting agents when prepared with hydrophobic HBDs. The results of the extractions of pollutants in acid and basic conditions showed the capability of water separation and extraction efficiency of these mixtures even with water at pH = 2 and pH = 9; therefore, the phenols could interact with these liquids without involvement of any acid/base-type of interactions.

Molecular Pedal Motion Influences Thermal Expansion Properties within Isostructural Hydrogen-Bonded Co-crystals

The influence of molecular pedal motion on the thermal expansion properties of three isostructural hydrogen-bonded co-crystals based upon resorcinol is reported. The resulting co-crystals all exhibit discrete four-component assemblies held together by O–H···N hydrogen bonds and comprise resorcinol (res) with a series of isosteric bipyridines, namely, 4,4′-azopyridine (4,4′-AP), trans-1,2-bis(4-pyridyl)ethylene (4,4′-BPE), and 1,2-bis(4-pyridyl)acetylene (4,4′-BPA). The ability to change the core of the hydrogen bond acceptor molecules from an azo (N═N) to an ethylene (C═C) and finally an acetylene (C≡C) group affords co-crystals that differ in their tendency to undergo dynamic pedal motion in the organic solid state. All three co-crystals, 2(res)•2(4,4′-AP), 2(res)•2(4,4′-BPE), and 2(res)•2(4,4′-BPA), exhibit thermal expansions that correlate with the strength of the noncovalent interactions, as well as the propensity of the core to undergo pedal motion.

Effects of Alkyl Groups on Excess-Electron Binding to Small-Sized Secondary Amide Clusters: A Combined Experimental and Computational Study.

Excess-electron binding to dimers and trimers of secondary amide molecules was studied by a combination of photoelectron spectroscopy and theoretical calculations. Vertical detachment energies (VDEs) of the cluster anions were measured in the range of a few hundred millielectronvolts. We found a tendency for VDE to decline with extension of alkyl side chains. It was fairly reproduced by results of quantum chemical calculations based on density functional theory. For the optimized structures of the cluster anions, the excess electron is located diffusively around the dangling NH group of the hydrogen-bond acceptor molecule. Dipole moment values calculated for the vertically detached neutrals are consistent with the motif of dipole-bound anions. Alkyl groups are likely to inhibit a close interaction between the excess electron and amide groups. It appears to be incompatible with a previously reported trend that the yield of the trimer anions is enhanced with extension of the side chains.

Adsorption, Dissociation, and Dehydrogenation of Water Monomer and Water Dimer on the Smallest 3D Aluminum Particle. The O-H Dissociation Barrier Disappears for the Dimer.

We present a detailed mechanistic study on the interaction and reaction of water monomer and water dimer with the smallest 3D aluminum particle (Al6) by employing density functional and explicitly correlated coupled cluster CCSD(T)-F12 theories. Water adsorption, dissociation, and dehydrogenation are considered. For the monomer reaction, where core-valence correlation and an extrapolation to the complete basis set limit is allowed for, our coupled cluster calculations predict the O-H dissociation barrier of about 2 kcal/mol. For the dimer reaction, two distinct reaction paths are identified, initiated by forming separate dimer complexes wherein (H2O)2 adsorbs mainly via the oxygen atom of the donor H2O molecule. The key O-H dissociation transition states of the dimer reaction involve a concerted migration of two H atoms resulting in the dissociation of the donor molecule and formation of the OH-water complex adsorbed on the metal cluster's surface. The most remarkable feature of both dimer reaction energy profiles is the lack of the overall energy barrier for the (rate-determining) O-H dissociation. The hydrogen bond acceptor molecule is suggested to have an extra catalytic effect on the O-H dissociation barrier of the hydrogen bond donor molecule by removing this barrier. A similar effect on the dehydrogenation step is indicated.

Experimental determination of the LLE data of systems consisting of {hexane + benzene + deep eutectic solvent} and prediction using the Conductor-like Screening Model for Real Solvents

Recently, deep eutectic solvents (DESs) have proven to be excellent extracting agents in the separation of aromatic components from their mixtures with aliphatic compounds. The tunable properties of the DESs allow to tailor-make optimal solvents for this application. In this work type III DESs, based on chloride quaternary ammonium salts (tetramethylammonium chloride, tetraethylammonium chloride, tetrabutylammonium and tetrahexylammonium chloride) as hydrogen bond acceptor molecules and polyols (ethylene glycol and glycerol) as hydrogen bond donor molecules were used. The liquid-liquid equilibrium (LLE) data of the system {hexane+benzene+DES} was measured at room temperature and atmospheric pressure. The solute distribution ratio and the selectivities were calculated and compared. The highest solute distribution ratios were obtained for salts with long alkyl chain length as hydrogen bond acceptor molecules and for ethylene glycol as hydrogen bond donor molecules.COSMO-RS was used for the prediction of the LLE data of the studied systems. It was found that both the LLE data and the solute distribution ratio of the ternary systems containing DESs can be qualitatively well predicted using this model. Moreover, the LLE data was quantitatively predicted within a root mean square error of 10wt% without the need of any experimental data. This implies that COSMO-RS is an effective screening tool for the optimization of the separation process of aromatic components from {aliphatic+aromatic} mixtures using DESs as extracting agents.

Design and Synthesis of Ternary Cocrystals Using Carboxyphenols and Two Complementary Acceptor Compounds

A strategy combining a ditopic hydrogen-bond donor with two different hydrogen-bond acceptor molecules is proposed for the assembly of simple trimeric building blocks used in the construction of ternary cocrystals. The crystallization of each of three different low symmetry carboxyphenols (3-hydroxybenzoic acid, 6-hydroxy-2-naphthoic acid, and ferulic acid) with acridine and 2-amino-4,6-dimethylpyrimidine yielded ternary cocrystals where the three components are joined by phenol-pyridine and carboxylic acid-amidine synthons. The use of pKa values, beta values, and synthon histories in the selection of the acceptor compounds is discussed. Significant challenges to the growth of the desired ternary products from solution were presented by competing crystalline phases, including the individual components, a variety of binary phases, salts, and hydrates. Molecular electrostatic potentials were used to analyze the donating and accepting abilities of the competing synthons.

Study of the submicron heterogeneity of aqueous solutions of hydrogen-bond acceptor molecules by laser diagnostics methods

Three independent experimental laser techniques (dynamic light scattering, nanoparticle tracking analysis, and laser phase microscopy) have been used to find and quantitatively characterize a lowconcentration domain of existence for the droplet-stratified phase in an aqueous solution of tetrahydrofurane (THF) molecules acting as hydrogen bond acceptors. The concentration and temperature dependences of the light scattering intensity and droplet sizes in the solution have been measured. It is shown that the nanodroplets found have a higher light refractive index than that of water and that they are highly enriched with THF molecules. An estimation of the volume number density of 300-nm droplets, based on the data obtained, yields a value on the order of 108 cm-3. The droplet lifetime is limited by the effect of the buoyancy force and amounts to several days. A crossover is found in the temperature dependence of scattering intensity in the droplet phase, which indicates possible interaction of two order parameters: the THF concentration and the number of hydrogen bonds of THF and H2O molecules. A model stochastic theory is proposed to describe the stratification of solutions with cross hydrogen bonds, which predicts stratification in the low-concentration range adjacent to the spinodal decay region.

Molecular origin of the difference in the HOH bend of the IR spectra between liquid water and ice

The intensity of the HOH bend in the infrared (IR) spectrum of ice is significantly smaller than the corresponding one in liquid water. This difference in the IR intensities of the HOH bend in the two systems is investigated using Molecular Dynamics (MD) simulations with the flexible, polarizable, ab initio based TTM3-F model for water, a potential that correctly reproduces the experimentally observed increase of the HOH angle in liquid water and ice from the water monomer value. We have identified two factors that are responsible for the difference in the intensity of the HOH bend in liquid water and ice: (i) the decrease of the intensity of the HOH bend in ice caused by the strong anti-correlation between the permanent dipole moment of a molecule and the induced dipole moment of neighboring hydrogen bond acceptor molecules, and (ii) the weakening of this anti-correlation by the disordered hydrogen bond network in liquid water. The presence of the anti-correlation in ice is further confirmed by ab initio electronic structure calculations of water pentamer clusters extracted from the trajectories of the MD simulations with the TTM3-F potential for ice and liquid water.

Hydrogen bonding of ethanol in supercritical mixtures with CO2 by 1H NMR spectroscopy and molecular simulation

Abstract High pressure 1 H NMR spectroscopic studies of mixtures of CO 2 and ethanol (EtOH) were conducted at a wide range of temperatures (293.15, 308.15, 323.15, and 338.15 K), pressures (5–25.5 MPa) and concentrations ( x EtOH = 0.0017–1.0 mol/mol). The relative chemical shift of the protons in the hydroxyl group was used to describe the degree of hydrogen bonding in ethanol. The dependence of the results on pressure is only weak. The quantification of hydrogen bonding was based on the assumption that the observed shift results from a superposition of the shifts of ethanol molecules differing in the way they are hydrogen bonded. Three different types were distinguished: monomer, donor and acceptor. The monomer shift was found from an extrapolation of the NMR data. Molecular dynamics simulations based on force fields from the literature were carried out for the same mixtures at the same conditions and were used to determine the distribution of differently hydrogen bonded ethanol species. Geometric cluster criteria from the literature were used for identifying the hydrogen bonding and the different types of ethanol species. Using the species distribution from the molecular simulations together with the NMR spectroscopic data, the two state independent numbers for the shifts of the hydrogen bond donor and hydrogen bond acceptor molecules were found. Even though only these two parameters are fitted the large set of experimental data is very well described. This confirms our earlier observations on the CO 2 –methanol system that molecular models of the simple Lennard–Jones plus point charge type as they are used here can describe both thermodynamic properties and the structural effects of hydrogen bonding in solutions.

A new insight on hydrogen bond donor property of bridged B–H–B protons in the interaction of diborane with some hydrogen bond acceptor molecules

Ab initio calculations at the MP2/6-311++G(d,p) computational level were used to analyze the interactions between a molecule of B2H6 with some small molecules which often have both hydrogen bond acceptor (HBA) and hydrogen bond donor (HBD) abilities. Interaction of B2H6 with amine derivatives (NH3, NH2Me, NHMe2, NMe3) as well as H2O, MeOH, OMe2, and CH3CN occurs through its bridged protons (Hb) to form a Hb···X (X = N or O) hydrogen bond complex. On the other hand, interaction of B2H6 with HCN could be as Ht···H dihydrogen bond or Hb···N hydrogen bonding. Topological analyses of the electron density of optimized structures have been carried out using the atoms in molecules (AIMs) methodology. AIM calculations are indicating the HBD characteristic of Hb of B2H6 in its hydrogen bond interaction with X atom of HBA molecules. Stability of the predicted clusters depends on the kind of HBA molecule. In addition, our calculations have been used to determine the Drago–Wayland coefficients of diborane and stabilization energy of adducts formed by the association of the diborane and HBAs.

Effect of Substituents on Hydrogen Bond Strength in Hydrogen-Bonded <em>N</em>-methylacetamide and Uracil Complexes

Theoretical calculations on a series of N-H…O=C hydrogen-bonded complexes containing 1-methyluracil and N-methylacetamide were carried out using B3LYP and MP2 methods. Substituent effects in the hydrogen bond acceptor molecule (1-methyluracil) on the hydrogen bond strength and hydrogen bond cooperativity were explored. The calculation results show that electron donating groups shorten the H…O distance and strengthen the N-H…O=C hydrogen bond, whereas electron withdrawing groups lengthen the H…O distance and weaken the N-H…O=C hydrogen bond. Natural bond orbital (NBO) analysis further indicates that electron donating groups result in a larger positive charge on the H atom and a larger negative charge on the O atom in the N-H…O=C bond, and result in increased charge transfer between the proton donor and acceptor molecules. Electron withdrawing groups show the opposite results. NBO analysis also indicates that electron donating groups result in larger second-order interaction energies between the oxygen lone pair and the N - H antibonding orbital when compared to the 1-methyluracil-containing complex (R=H), while electron withdrawing groups result in smaller second-order interaction energies.