Polar Hydrogen Bond Acceptor Research Articles

Effect of anion α-functionalization on the water affinity of thermo-responsive phosphonium acetate-derived ionic liquids

This study presents a facile method for assessing the effect of anion functional group substitution on the water affinity of phosphonium-acetate ionic liquids. By combining the same cation with three different α-substituted carboxylate anions, the effect of anion functional group substitution on the IL miscibility with water and hygroscopicity was experimentally evaluated and rationalized using COSMO-RS sigma profile analysis. Lower critical solution temperature (LCST) phase separation experiments and water vapor partial pressure measurements revealed that there is a stark α-substitution dependency on the affinity of water for acetate [AcO], pivalate [PivO], and trifluoroacetate [TFA] derived tributyl(octyl)phosphonium [P4448] ILs. It was found that the IL water affinities varied as: [P4448][AcO] > [P4448][PivO] > [P4448][TFA]. With the lowest water partial pressure and no LCST driven phase separation, [P4448][AcO] exhibited a high affinity for water. On the other hand, [P4448][PivO] and [P4448][TFA] exhibited LCST-driven phase separation and room temperature immiscibility, respectively, with higher water partial pressures, as a result of relatively weak water affinities. COSMO-RS sigma profile analysis revealed that the aliphatic carboxylate anions should incorporate apolar interactions commensurate with or greater than the polar hydrogen bond acceptor interactions for phase immiscibility of the corresponding IL with water. It was found that the relative magnitudes of apolar and polar interactions, assessed using the anion sigma profile peak intensity ratio (Ir), are directly correlated with the IL water affinity, and inversely correlated with the solution water activity coefficient. Therefore, it was concluded that Ir forms a quantitative link between the structural changes at the molecular level and the bulk water affinity exhibited by the ionic liquid as a whole.

Prediction of solvatochromic parameters of electronic transition energy for characterizing dipolarity/polarizability and hydrogen bonding donor interactions in binary solvent systems of liquid nonpolar-polar mixtures, CO2-expanded liquids and supercritical carbon dioxide with cosolvent

Solvatochromic parameter of electronic transition energy (ET) provides information on dipolarity/polarizability and hydrogen bonding donor interactions in the solvation shell. In this work, a predictive framework is proposed for estimating ET values of phenol blue indicator in three mixed-solvent systems as (i) liquid nonpolar-polar mixtures, (ii) CO2-expanded liquid solvent and (iii) supercritical carbon dioxide (scCO2)-polar cosolvent mixtures. The equations of the ET framework for binary mixtures of nonpolar solvent with polar hydrogen bond acceptor (HBA) solvent can be directly adopted from the previous framework for Kamlet-Taft dipolarity/polarizability (KT-π*) [Ind. Eng. Chem. Res. 2020, 59, 12319–12330] because of the linearity of the homomorphism line between ET and KT-π* for pure nonpolar solvents and pure polar HBA solvents. However, due to specific hydrogen bonding interactions of the phenol blue with polar hydrogen bond donor (HBD) solvents, the ET framework for binary mixtures of nonpolar solvent with polar HBD solvent was the modification by the addition of HBD contribution factor. The HBD contribution factor can be simply estimated by a deviation of an actual ET value of pure HBD solvents from the homomorphism line. To validate the framework, the ET values of seventeen liquid nonpolar-polar mixtures, (ii) three CO2-expanded solvent mixtures and (iii) five scCO2-polar cosolvent mixtures collected from the literature were used. The framework was found to give a reliable ET value with an overall deviation of 0.26% and was also applicable to ET values of Reichardt, Nile red and HxQMBu2 indicators with an overall deviation of 1.73%, 0.36% and 0.40%, respectively. Only four properties of pure components are required for predictions as: (i) gas-phase dipole moment of polar component, (ii) CO2 density, (iii) ET and KT-π* values and (iv) homomorphism relationship between ET and KT-π* values.

Structural requirements for molecular design of positive allosteric modulators of AMPA receptor

Positive allosteric modulators of AMPA receptor are prospective for the development of safe and efficacious agents for the correction of disruption of the central nervous system functions. Joint application of molecular docking, MFTA and CoMFA QSAR modelling, and pharmacophore analysis affords a consistent picture of structural requirements for molecular design of novel promising bivalent modulators with high activity, including overall twisted-staple shape of a molecule, hydrophobic central core, and polar hydrogen bond acceptor groups in peripheral parts of a molecule.

The role of carbon‐donor hydrogen bonds in stabilizing tryptophan conformations

Although most side-chain torsion angles correspond to low-energy rotameric positions, deviations occur with significant frequency. One striking example arises in Trp residues, which have an important role in stabilizing protein structures because of their size and mixed hydrophobic/hydrophilic character. Ten percent of Trp side-chains have unexplained conformations with chi(2) near 0 degrees instead of the expected 90 degrees. The current work is a structural and energetic analysis of these conformations. It is shown that many Trp residues with these orientations are stabilized by three-center carbon-donor hydrogen bonds of the form C-H...X...H-C, where X is a polar hydrogen-bond acceptor in the environment of the side-chain. The bridging hydrogen bonds occur both within the Trp side-chain and between the side-chain and the local protein backbone. Free energy maps of an isolated Trp residue in an explicit water environment show a minimum corresponding to the off-rotamer peak observed in the crystallographic data. Bridging carbon-donor hydrogen bonds are also shown to stabilize on-rotamer Trp conformations, and similar bridging hydrogen bonds also stabilize some off-rotamer Asp conformations. The present results suggest a previously unrecognized role for three-center carbon-donor hydrogen bonds in protein structures and support the view that the off-rotamer Trp side-chain orientations are real rather than artifacts of crystallographic refinements. Certain of the off-rotamer Trp conformations appear to have a functional role.

Nonspecific Solute–Solvent Interactions in Binary Solvent Mixtures Containing an Aprotic Hydrogen-Bond Acceptor and a Hydrogen-Bond Donor: Dipolarity/Polarizability and Refractive Index

This work presents an analysis of the relationships between molecular–microscopic solvent descriptors that consider different type of interactions (π*, π* 2, and E T N scales), for binary mixtures made of a polar hydrogen-bond acceptor solvent and a cosolvent with hydrogen-bond donor capability. The solvent descriptors consider different types of interactions for binary mixtures of a polar hydrogen-bond acceptor solvent and a cosolvent with hydrogen-bond donor capability. The study pays particular attention to the influence of the dipolarity/polarizability solvent property contamination by specific interactions due to the preferential solvation of the reference indicators by the cosolvent. It also gives the refractive indexes of the mixtures and relates these values with π2 * values calculated from β-carotene, thus providing an equation which can be used to estimate an unknown molecular–microscopic binary mixture solvent property from the measurement of the macroscopic property.

Characterization of solvent mixtures: preferential solvation of chemical probes in binary solvent mixtures of polar hydrogen-bond acceptor solvents with polychlorinated co-solvents

The use of chemical probes for the characterization of chemical properties is explored for aprotic binary solvent mixtures. The solvatochromic indicators N,N-diethyl-4-nitroaniline, 4-nitroanisole, 4-nitroaniline and 4-nitrophenol were used to characterize binary solvent mixtures of a polar aprotic hydrogen-bond acceptor solvent (ethyl acetate, acetonitrile and dimethyl sulfoxide) with a polychlorinated hydrogen-bond donor solvent (chloroform or dichloromethane). The solvent parameters π*, α and β of the binary mixtures were calculated from the solvatochromic shifts of the indicators. In each case the degree of convergence for a solvent property values obtained from different probes was analyzed. Data obtained by using the non-polar solvatochromic indicator β-carotene are additionally presented. The behavior of the solvent systems was analyzed according to their deviation from ideality due to preferential solvation of the solutes and the complicated intermolecular interactions of the two components of the solvent mixture. The validity of the concept of an intrinsic absolute property of a solvent mixture and whether such a property can be defined by means of chemical probes is discussed. Theoretical equations (preferential solvation models) were used to compute the solvatochromic data. The results were analyzed and related to the solvent effects on some aromatic nucleophilic substitution reactions, comparing the application of single- and multiparametric treatments of solvent effects. Copyright © 1999 John Wiley & Sons, Ltd.

Solvent effects on aromatic nucleophilic substitution reactions. Part 7. Determination of the empirical polarity parameterET(30) for dipolar hydrogen bond acceptor-co-solvent (chloroform or dichloromethane) mixtures. Kinetics of the reactions of halonitrobenzenes with aliphatic amines

Empirical solvent polarity parameters ET(30) were determined by UV/VIS spectroscopy, using Dimroth–Reichardt's betaine dye, as a function of composition, for several binary solvent mixtures [i.e. polar hydrogen bond acceptor (PHBA) solvents+chloroform or dichloromethane]. Each solvent system was analyzed according to its deviations from additivity due to preferential solvation of the chemical probe and also from complicated intermolecular interactions of the mixed solvents. The ET(30) parameter of many of these mixtures has presented synergism. The synergetic effects were more significant for those binary solvent systems in which chloroform is the co-solvent. These results were related to the solvent effects on some aromatic nucleophilic substitution reactions. The kinetics of the reactions between 1-halo-2,4-dinitrobenzenes and primary or secondary aliphatic amines were studied in three solvent systems (PHBA+chloroform) where the synergism for the ET(30) polarity parameter is the rule. In all the aminodehalogenation reactions discussed the formation of the intermediate is the rate-determining step. The kinetic data show a tendency to decrease with decrease in the overall solvation capability of the binary mixture. In general, the reaction rates presented a gradual decrease in the PHBA solvent-rich zone and a large decrease at high co-solvent concentrations. The ET(30) values corresponding to binary dipolar hydrogen bond acceptor–hydrogen bond donor mixtures may be not generally valid for interpreting solvation effects on the reactions under consideration. © 1997 John Wiley & Sons, Ltd.

Solvent effects on aromatic nucleophilic substitution reactions. Part 7. Determination of the empirical polarity parameter ET(30) for dipolar hydrogen bond acceptor–co‐solvent (chloroform or dichloromethane) mixtures. Kinetics of the reactions of halonitrobenzenes with aliphatic amines

Empirical solvent polarity parameters ET(30) were determined by UV/VIS spectroscopy, using Dimroth–Reichardt's betaine dye, as a function of composition, for several binary solvent mixtures [i.e. polar hydrogen bond acceptor (PHBA) solvents+chloroform or dichloromethane]. Each solvent system was analyzed according to its deviations from additivity due to preferential solvation of the chemical probe and also from complicated intermolecular interactions of the mixed solvents. The ET(30) parameter of many of these mixtures has presented synergism. The synergetic effects were more significant for those binary solvent systems in which chloroform is the co-solvent. These results were related to the solvent effects on some aromatic nucleophilic substitution reactions. The kinetics of the reactions between 1-halo-2,4-dinitrobenzenes and primary or secondary aliphatic amines were studied in three solvent systems (PHBA+chloroform) where the synergism for the ET(30) polarity parameter is the rule. In all the aminodehalogenation reactions discussed the formation of the intermediate is the rate-determining step. The kinetic data show a tendency to decrease with decrease in the overall solvation capability of the binary mixture. In general, the reaction rates presented a gradual decrease in the PHBA solvent-rich zone and a large decrease at high co-solvent concentrations. The ET(30) values corresponding to binary dipolar hydrogen bond acceptor–hydrogen bond donor mixtures may be not generally valid for interpreting solvation effects on the reactions under consideration. © 1997 John Wiley & Sons, Ltd.

Nitrogen hyperfine splitting of nitroxide solutions: Differently structured and charged nitroxides as probes of environmental properties

AbstractThe dependence of the nitrogen isotropic coupling constants, aN, on the structure and charge of the radicals, temperature and solvent polarity was analysed for solutions containing the following nitroxides: 4‐hydroxy‐2,2,6,6‐tetramethylpiperidine‐1‐oxyl (Tempol); 4‐trimethylammonium‐2,2,6,6‐tetramethylpiperidine‐1‐oxyl, iodide salt (TempTMA+); 2,2,5,5‐tetramethylpyrrolin‐1‐oxyl‐3‐carboxamide (Tempyo); and 2,2,5,5‐tetramethylpyrrolin‐1‐oxyl‐3‐carboxylate, sodium salt (Tempyca−). Polar hydrogen bond acceptor solvents and hydroxylic solvents were used. In each solvent used, Tempol and Tempyca− showed aN values which were higher, respectively, than those of TempTMA+ and Tempyo due to inductive, structural and charge effects. Such effects were analysed on the basis of the proton and 13C coupling constants. Non‐hydroxylic solvents gave temperature coefficients for aN that were almost independent of solvent polarity. Lower daN/dT values were found for charged radicals. A gradual decrease of temperature coefficients with decreasing hydrogen bond donor (HBD) properties were related to free volume changes of radical molecules. The analysis of the aN dependence on polarity parameters gave the best fitting using a simplified form of the Wertheim reaction field. Tempyca− was greatly affected by changes in polarity. A parameter to account for HBD abilities was also analysed.