A study of solute-solute interactions of amides dissolved in N-methylformamide by enthalpic interaction coefficients

Enthalpies of dilution of formamide, acetamide, propionamide, butyramide and hexanamide, dissolved in N-methylformamide have been measured calorimetrically at 25°C. From the results McMillan-Mayer coefficient related enthalpic pair and triplet interaction coefficients have been calculated. Except for those of formamide, all pair coefficients are negative, whereas the triplet terms are positive. The values in the protic solvent N-methylformamide presented in this paper together with those published before are compared with results for corresponding solutes dissolved in the aprotic solvent N,N-dimethylformamide. A discussion of the dependence of the interaction coefficients on the applied concentration scale is given and conversion factors are presented. The influence of hydrogen bonding, of substituent effects on this hydrogen bonding, and of polarophobic interaction is discussed. The latter is comparable in N,N-dimethyl-and N-methylformamide. The enthalpic pair interaction coefficients have been correlated with the Excess Group Additivity approach.To whom correspondence should be addressed.     

Enthalpic interaction coefficients of amides dissolved in N,N-dimethylformamide

Enthalpies of dilution of propionamide, butyramide, pentanamide, hexanamide, N-pentylacetamide, N,N-dipentylacetamide, N-ethylhexanamide and N,N-diethylhexanamide dissolved in N,N-dimethylformamide as solvent have been measured calorimetrically at 25°C. The results are interpreted in terms of the McMillan-Mayer theory. Enthalpic interaction parameters are obtained for pairs, triplets and some quadruplets of solute molecules. All enthalpic pair interaction coefficients are negative, whereas those for triplets are positive. For unsubstituted amides the change of the enthalpic coefficients with the number of C-atoms differs considerably from that of the substituted compounds. The concept of polarophobic interaction is used for the interpretation of the results in connection with the assumption of formation of solute-solvent associates. For solutes with longer alkyl chains the results cannot be described satisfactorily in terms of the additivity approach of Savage and Wood. Probably the pair interactions of these compounds are not the result of interaction in a random way. Also the linear dependence of the pair interaction coefficients of the larger molecules with the number of C-atoms and the results for the unsubstituted amides support the occurrence of preferential orientations for these compounds.     

Enthalpic interaction coefficients of formamides dissolved in N,N-dimethylformamide

Enthalpies of dilution of formamide, N-methylformamide, N-ethylformamide, N-propylformamide, N-butylformamide, N-pentylformamide, N,N-diethyl-formamide, N,N-dipropylformamide, N,N-dibutylformamide, and N,N-dipentyl-formamide dissolved in N,N-dimethylformamide as solvent have been measured calorimetrically at 25°C. The results are interpreted in terms of the McMillan-Mayer theory. Enthalpic interaction parameters are obtained for pairs, triplets, and in some cases, quadruplets of solute molecules. In general, the enthalpic pair interaction coefficients are negative, whereas the triplet coefficients are positive. The interaction enthalpies are positive only for N-methylformamide and formamide. The magnitudes of the enthalpic pair and triplet interaction coefficients increase with increasing number of C atoms in the N-alkyl groups. The results for the formamides presented in this paper are compared with those for corresponding acetamides published earlier. Although the trends are comparable, distinct differences are observed. The contribution of the -CH₃ group at the CO side of the dialkylacetamides to the enthalpic interaction coefficients appears to be negligible. The same is true for -CH₂ groups at the NH side of a number of amides and related compounds. The enthalpic pair interaction coefficients of the mono-N-alkylsubstituted formamides show a shift of about 100 J-kg-mol^–2 as compared with isomeric N-alkylacetamides. This is discussed in terms of the difference in proton donating and accepting ability of several types of amide molecules. It is concluded that substitution effects should be incorporated in additivity models for these type of systems.     

Correlation of solute-solute interaction enthalpies in dimethylformamide by group additivity

The Savage and Wood group additivity method has been applied to enthalpic pair interaction coefficients of more than 30 solutes dissolved in N,N-dimethylformamide. The results are not satisfactory. Better results are obtained by using a method which accounts for the differences in the numbers of molecular groups between solute and solvent molecules. With this excess group additivity method reasonable correlations are obtained even for solutes as large as dipeptide amides.     

丝氨酸在蔗糖水溶液中的稀释焓

利用LKB 2277生物活性检测仪分别测定了298.15 K时丝氨酸在不同组成的蔗糖水溶液中的稀释焓, 利用McMillan-Mayer理论,计算了丝氨酸在不同组成的蔗糖水溶液中的焓对相互作用系数,并与其在葡萄糖水溶液中的焓对相互作用系数h2进行了比较.结果表明,丝氨酸在蔗糖和葡萄糖水溶液中的焓对相互作用系数h2都是负值,并且随着糖浓度的增加,h2系数的绝对值逐渐减少.根据溶质-溶质相互作用和溶质-溶剂相互作用对结果进行了解释.     

丙氨酸在蔗糖-水混合溶剂中的焓对相互作用

利用LKB2277生物活性检测仪测定了298.15 K时丙氨酸分别在不同组成的蔗糖- 水混合溶剂中的稀释焓,利用McMillan-Mayer理论,计算了丙氨酸在不同组成的蔗 糖-水混合溶剂中的焓对相互作用系数h_2,并与其在葡萄糖-水混合溶剂中的焓对 相互作用系数h_2进行了比较。结果表明,丙氨酸的h_2分别在葡萄糖和蔗糖的摩尔 分数为0.1009和0.05843处出现极大值,极值点位置的不同与糖分子所含羟基数目 的多少有关,根据溶质-溶质相互作用和溶质-溶剂相互作用对结果进行了解释。     

Interactions between terminally substituted amino acids in an aqueous and a non-aqueous environment. Enthalpic interaction coefficients in water and in N,N-dimethylformamide at 25°C

Enthalpies of dilution of the N-acetyl amides of glycine, L-alanine, L-valine, L-leucine, and L-phenylalanine, dissolved in N,N-dimethylformamide (DMF) as a solvent have been measured at 25°C. The results obtained have been analyzed to give the enthalpic interaction (or virial) coefficients of the solutes and these are compared with information previously obtained in aqueous systems. There are marked differences in the interaction properties in the two solvents and, while the additivity approach of Savage and Wood is applicable to the solutes in water it is not suitable for representing the interactions in DMF. A correlation is presented between the enthalpic second virial coefficients in DMF and the propensity of side-chains to be in proximity in globular proteins.     

Enthalpies of Dilution of D-p-Hydroxyphenylglycine in Buffer Solutions at Different pH

The effect of pH on the dilution enthalpies of D-p-hydroxyphenylglycine in phosphate buffer solutions has been investigated by isothermal titration microcalorimetry at 298.15 K. The corresponding homogeneous enthalpic interaction coefficients have been calculated according to the excess enthalpy concept. The results show that the enthalpies of dilution of D-p-hydroxyphenylglycine in phosphate buffer solutions at different pH are all positive. The overall trend is that enthalpies of dilution become more positive with an increase of pH, but there is a minimum of the enthalpy of dilution at pH = 7.0. The enthalpic pair interaction coefficients, h ₂, all have negative values. The results are interpreted from the point of view of solute-solute and solute-solvent interactions involved in the solvent effects.     

甲酰胺在乙二醇-水混合溶剂中的稀释焓

酰胺是肽的基本结构单元, 而且在蛋白质的二级结构中与酰胺联系的氢键对蛋白质的稳定起着十分重要的作用. 作为蛋白质模型化合物热力学性质研究的一部分, 报道了甲酰胺在乙二醇水溶液中的稀释焓.      

Enthalpic homogeneous pair interaction coefficients of L-alpha-amino acids as a hydrophobicity parameter of amino acid side chains

Enthalpies of dilution of aqueous solutions of L-alpha-cysteine, L-alpha-histidine, L-alpha-asparagine, L-alpha-glutamine, L-alpha-arginine, L-alpha-tryptophan, and L-alpha-glutamic acid in water at a temperature of 298.15 K have been measured. The values of dilution enthaply were used to determine enthalpic homogeneous pair interaction coefficients which characterize the interactions between zwitterions of the examined L-alpha-amino acids in water. Approachable literature data of hydrophobic scales have been analyzed to obtain average values. The obtained values of enthalpic pair interaction coefficients have been put together with an average hydrophobic scale.     

Enthalpic Interaction Coefficients of Formamide in Aqueous Methanol and Ethanol Solutions at 298.15 K

The dilution enthalpies of formamide in aqueous methanol and ethanol solutions have been determined using a CSC-4400 isothermal calorimeter at 298.15 K. The homogeneous solution enthalpic interaction coefficients have been calculated over a range of alcohol concentrations according to the excess enthalpy concept. The results show that the enthalpic pair interaction coefficients h ₂ of formamide are negative in aqueous alcohol solutions and pass through a minimum in mixed solvents, whereas the h ₂ coefficients of formamide in aqueous ethanol solutions are more negative than those in aqueous methanol solutions. The results are discussed in terms of solute-solute and solute-solvent interactions.     

Enthalpies of Dilution of Colchicine in Aqueous NaCl Solutions

The concentration effect on the dilution enthalpies (Δ_dil H _m) of colchicine (COL) in aqueous NaCl solutions has been investigated by isothermal titration microcalorimetry at 298.15 K. The corresponding homogeneous enthalpic interaction coefficients have been calculated according to the excess enthalpy concept. The results show that the dilution enthalpies of COL in aqueous NaCl solutions at different mass fractions are positive. The overall trend is that enthalpies of dilution become more positive with the increase of the salt mass fraction. The values of enthalpic pair-wise interaction coefficients, h ₂, have been obtained by fitting the data of the enthalpies of dilution with a viral expansion. The results can be interpreted from the view of solute-solute and solute-solvent interactions involved in the solvent effects.     

Solute-solute-solvent interactions in dilute aqueous solutions. Microcalorimetric study of isomeric butanediols

The heats of dilution of butane-1,2-diol, butane-1,3-diol, and butane-1,4-diol and of their mixtures were determined at 25°C. The virial enthalpic coefficients of the excess enthalpies of the binary and ternary solutions were evaluated and compared with the literature data for isomeric mono- and polyols. The enthalpic pair interaction coefficients of isomeric diols are positive. The highest value is observed for butane-1,2-diol thus supporting the importance of steric and nearest neighbors effects in the hydration properties of isomeric compounds. Mixed enthalpic coefficients were also determined and discussed.     

Enthalpies of interaction of glycine with some amides in aqueous solutions at 298.15 K

The dissolution enthalpies of glycine in aqueous solutions of acetamide, N-methylacetamide, N,N-dimethylacetamide, N-ethylformamide, N,N-diethylformamide and N,N-diethylacetamide were measured at 298.15 K. The enthalpic pair interaction coefficients of glycine zwitterion-amide molecules were determined by using standard solution enthalpies of glycine in water and aqueous solutions of amides. The additivity of groups concept of Savage and Wood was used to estimate the contribution of each of the functional groups of the studied amides.     

Enthalpies of solution of glycine in aqueous solutions of 1,2-diols and glycerol at 25°C

Dissolution enthalpies of glycine in mixtures of water with 1,2-ethanediol, 1,2-propanediol, 1,2-butanediol, 1,2-pentanediol, 1,3-propanediol and glycerol have been measured at 25°C. The enthalpic pair interaction coefficients of the glycine zwitterion with the polyalcohol molecule have been determined by using the standard solution enthalpies of glycine in water and in aqueous solutions of the polyalcohols. The values of the resultant enthalpic interaction coefficients are interpreted assuming a criterion in the form of the effect of hydrophobic alkyl radicals on the interactions between the hydroxyl groups of polyalcohols and the zwitterion of glycine.     

Enthalpy-entropy contributions to the potential of mean force of nanoscopic hydrophobic solutes

Entropic and enthalpic contributions to the hydrophobic interaction between nanoscopic hydrophobic solutes, modeled as graphene plates in water, have been calculated using molecular dynamics simulations in the isothermal-isobaric (NPT) ensemble with free energy perturbation methodology. We find the stabilizing contribution to the free energy of association (contact pair formation) to be the favorable entropic part, the enthalpic contribution being highly unfavorable. The desolvation barrier is dominated by the unfavorable enthalpic contribution, despite a fairly large favorable entropic compensation. The enthalpic contributions, incorporating the Lennard-Jones solute-solvent terms, largely determine the stability of the solvent separated configuration. We decompose the enthalpy into a direct solute-solute term, the solute-solvent interactions, and the remainder that contains pressure-volume work as well as contributions due to solvent reorganization. The enthalpic contribution due to changes in water-water interactions arising from solvent reorganization around the solute molecules is shown to have major contribution in the solvent induced enthalpy change.     

Solvation of amides of carboxylic acids in aqueous solutions of ethylene glycol

Enthalpies of solution of amides of formic, acetic, and propionic acids with different degrees of N-substitution in aqueous solutions of ethylene glycol were measured at 298.15 K. The concentration of ethylene glycol did not exceed 4 mol kg^–1. The reasons for increasing endothermic values of the enthalpies characterizing the amide transfer from water to a mixed aqueous-organic solvent on going from primary to tertiary amides and from formamides to the corresponding acetamides are discussed. The enthalpic coefficients of pair interactions between amides and ethylene glycol in water were calculated. The endothermicity of the interaction of the alkyl groups of the amide molecules with ethylene glycol results in positive values of the coefficients. The coefficient values increase with the enhancement of the hydrophobic properties of hydrophilic non-electrolytes (urea, formamide, ethylene glycol) due to an increase in the contribution of the hydrophobic component and a decrease in the contribution from the interaction of the polar groups of amides to the total interaction.     

Contribution of charged groups to the enthalpic stabilization of the folded states of globular proteins

In this paper we use the results from all-atom molecular dynamics (MD) simulations of proteins and peptides to assess the individual contribution of charged atomic groups to the enthalpic stability of the native state of globular proteins and investigate how the distribution of charged atomic groups in terms of solvent accessibility relates to protein enthalpic stability. The contributions of charged groups is calculated using a comparison of nonbonded interaction energy terms from equilibrium simulations of charged amino acid dipeptides in water (the "unfolded state") and charged amino acids in globular proteins (the "folded state"). Contrary to expectation, the analysis shows that many buried, charged atomic groups contribute favorably to protein enthalpic stability. The strongest enthalpic contributions favoring the folded state come from the carboxylate (COO(-)) groups of either Glu or Asp. The contributions from Arg guanidinium groups are generally somewhat stabilizing, while N(+)(3) groups from Lys contribute little toward stabilizing the folded state. The average enthalpic gain due to the transfer of a methyl group in an apolar amino acid from solution to the protein interior is described for comparison. Notably, charged groups that are less exposed to solvent contribute more favorably to protein native-state enthalpic stability than charged groups that are solvent exposed. While solvent reorganization/release has favorable contributions to folding for all charged atomic groups, the variation in folded state stability among proteins comes mainly from the change in the nonbonded interaction energy of charged groups between the unfolded and folded states. A key outcome is that the calculated enthalpic stabilization is found to be inversely proportional to the excess charge density on the surface, in support of an hypothesis proposed previously.     

N,N-二甲基甲酰胺在不同浓度氯化钠水溶液中的稀释过程热力学

应用等温流动微量热法测定了298.15 K时N,N-二甲基甲酰胺(DMF)在纯水及不同浓度氯化钠水溶液中的稀释焓, 根据McMillan-Mayer理论计算得到各级同系焓相互作用系数. 结果表明, DMF在纯水及氯化钠水溶液中的焓对相互作用系数h2均为正值, 并且随着氯化钠浓度的增加, h2的值逐渐增大. 根据溶质-溶质相互作用和溶质-溶剂相互作用对结果进行了解释.     

Enthalpies of dilution and homotactic enthalpic interaction coefficients of THF and 1,4-dioxane at 298.15 k

Enthalpies of dilution at 298.15 K of aqueous solutions of THF and 1,4-dioxane have been determined using flow microcalorimetry. The results obtained were used to determine the homotactic enthalpic interaction coefficients that characterize pair interactions of THF and 1,4-dioxane in aqueous solution. These are briefly discussed from the point of view of intermolecular interaction between the hydrated solute species.