Hydrogen bonding acids

Where FCl is the solute gas-liquid partition coefficient, r is the tendency of the solvent to interact through k- and n-electron pairs (Lewis basicity), s the contribution from dipole-dipole and dipole-induced dipole interactions (in molecular solvents), a is the hydrogen bond basicity of the solvent, b is its hydrogen bond acidity and I is how well the solvent will separate members of a homologous series, with contributions from solvent cavity formation and dispersion interactions. 

Finally, none of the ionic liquids were found to be hydrogen bond acids [5], although this may well be a consequence of the salts selected, none of which had a cation that would be expected to act as a hydrogen bond donor. Earlier qualitative measurements on ionic liquid stationary phases of mono-, di-, and trialkylammo-nium salts suggest that hydrogen bond donation can be important where a potentially acidic proton is available [7-9]. More recent work, with [BMIM] salts, also indicates that these ionic liquids should be considered to be hydrogen bond donor solvents [10]. However, this has yet to be quantified. 

It can easily be shown that the value of K" is inversely proportional to the value of K and that K is dependent on both the cation and the anion of the ionic liquid. Eience, it is entirely consistent with this model that the difference made by changing the anion should depend on the hydrogen bond acidity of the cation. 

The difference in the hydrogen bond acidities and basicities was far more marked. The a value is largely determined by the availability of hydrogen bond donor sites on the cation. Values range from 0.8-0.9 for the monoalkylammonium salts, and are slightly lower (0.3-0.8) for the imidazolium salts. In the absence of a... 

A crystallographic scale of acidity has been developed. Measuring the mean C—H O distances in crystal structures correlated well with conventional P a(DMSO) values. An ab initio study was able to correlate ring strain in strained hydrocarbons with hydrogen-bond acidity. ... 

The correlation of Snyder s solvent strength e° with molecular dipolarity and polarizability (7t ) and the hydrogen-bond acidity (a) and the hydrogen-bond basicity ((3) solvatochromic parameters for adsorption chromatography can be achieved, although most papers on solvatochromic parameters deal with reversed-phase systems [18]. 

Murray,). S., Politzer, P. Relationships between solute hydrogen-bond acidity/ basicity and the calculated electrostatic potential./. Chem. Res. (S) 1992,... 

Reynolds, D., Abraham, M. H. Rapid method for estimating octanol-water partition coefficient (logPocr) from isocratic RP-HPLC and a hydrogen bond acidity term (Aj.J. Liquid Chromatogr. 

Overall, we have shown that family-independent correlations can be obtained for solute hydrogen bond acidity and basicity, as quantitated by a 1 and log KHB. These are well represented at the HF/6-31G level by an electrostatic potential term alone, V or V, . , respectively (Hagelin et al. 1995). 

Abraham, M. H., R P. Duce, P. L. Grellier, D. V. Prior, J. J. Morris, and P. J. Taylor. 1988. A Thermodynamically Based Scale of Solute Hydrogen-bond Acidity. Tetrahedron Letts. 29, 1587. 

Hagelin, J., T. Brinck, M. Berthelot, J. S. Murray, and P. Politzer. 1995. Family Dependent Relationships Between Computed Molecular Surface Quantities and Solute Hydrogen Bond Acidity/Basicity and Solute-Induced Methanol O-H Infrared Frequency Shifts. Can. J. Chem. 73, 483. 

Polymers can be characterized via the Kamlet-Taft approach which describes the ability of a species to act as a hydrogen bond acid (ai), the ability to act as a hydrogen bond base (Pj), the dipolarity/polarizability (7ti ), and the size of a species. These parameters are obtained by dissolving solvatochromic indicator dyes in the respective polymer and by measuring the shift of their absorbance maxima18. 

Polymer (dry) Hydrogen bond acidity Hydrogen bond basicity Polarizability Et (30)... 

All these reactions are thermodynamically favourable in the direction of proton transfer to hydroxide ion but the rate coefficients are somewhat below the diffusion-limited values. In broad terms, the typical effect of an intramolecular hydrogen bond on the rate coefficient for proton removal is to reduce the rate coefficient by a factor of up to ca 105 below the diffusion limit. Correspondingly the value of the dissociation constant of the acid is usually decreased by a somewhat smaller factor from that of a non-hydrogen-bonded acid. There are exceptions, however. 

For a reaction occurring by the mechanism in Scheme 4, a first-order dependence of the rate on base concentration [B] would be observed. For Scheme 3, with the base present in excess, the rate expression (53) is obtained and the observed first-order rate coefficient (/cob ) for ionisation of the hydrogen-bonded acid is given by (54). Equation (54) reduces to (55) if the condition k t k2 [B] applies and (56) is obtained if k 2 < k2 [B]. For all... 

It is of interest to consider the form of the Bronsted plot or Eigen plot to be expected for reaction of a series of related intramolecularly hydrogen-bonded acids with hydroxide ion by the mechanisms in Schemes 5 and 6. The effect of a substituent on the value of the dissociation constant of an intramolecularly hydrogen-bonded acid (8 log K) will be two-fold. The stability of the undissociated acid will be modified because of a substituent effect on the... 

Fig. 14 Predicted variation in forward (/cB) and reverse (kM+) rate coefficients for proton transfer from an intramolecularly hydrogen-bonded acid (HA-) to bases (B) (solid line) and comparison with normal proton-transfer behaviour (dashed line)...

The first experimental data for a reaction involving proton transfer from a hydrogen-bonded acid to a series of bases which were chosen to give ApK-values each side of ApK=0 are given in Fig. 15 (Hibbert and Awwal, 1976, 1978 Hibbert, 1981). The results were obtained for proton transfer from 4-(3-nitrophenylazo)salicylate ion to a series of tertiary aliphatic amines in aqueous solution, as in (64) with R = 3-nitrophenylazo. Kinetic measurements were made using the temperature-jump technique with spectrophoto-metric detection to follow reactions with half-lives down to 5 x 10"6s. The reciprocal relaxation time (t ), which is the time constant of the exponential... 

In the two examples of buffer catalysis of proton transfer from an intramolecularly hydrogen-bonded acid which have been discussed, it seems reasonably certain that the mechanism in Scheme 7 applies. The reactions are of the first order with respect to the catalyst B and it therefore follows that proton removal from the non-hydrogen-bonded species is rate-limiting k j > 2[B]- If this step consists of diffusion-controlled proton removal from a low concentration intermediate, the value k2 lx 109dm3 moP s-1 will apply for proton transfer to an amine. In the case of proton removal by hydroxide ion from 4-(3-nitrophenylazo)salicylate ion, the reaction was found to be of the first order in hydroxide ion up to the highest concentrations which could be studied (0.003 mol dm-3) with a rate... 

The conclusions reached about proton transfer from phenylazoresorcinol monoanions are quite different from the behaviour which has been described for other hydrogen-bonded acids. For phenylazoresorcinol monoanions, it appears that direct attack by base on the hydrogen-bonded proton is an important process and can compete with two-step proton removal. For two-step proton transfer through an open form of the phenylazoresorcinol monoanion it is found that the rate of proton transfer from the open form is... 

In an excellent paper, Zhao et al. [29] assembled a carefully reviewed literature set of human absorption data on 241 drugs. They showed that a linear regression model built with 5 Abraham descriptors could fit percent human absorption data reasonably well (r2 = 0.83, RMSE = 14%). The descriptors are excess molar refraction (E), polarizability (S), hydrogen bond acidity (A), hydrogen bond basicity (B), and McGowan volume (V), all related to lipophilicity, hydrophilicity, and size. In a follow-on paper, data on rat absorption for 151 drugs was collected from the literature and modeled using the Abraham descriptors [30]. A model with only descriptors A and B had r2 = 0.66, RMSE = 15%. 

The parameters a and p indicate the capacity of a solvent to donate or accept a hydrogen bond from a solute, i.e., the solvent s hydrogen bond acidity or basicity. % is intended to reflect van der Waals-type solute-solvent interactions (dipolar, dispersion, exchange-repulsion, etc.). Equation (43) was subsequently expanded to include a term representing the need to create a cavity for the solute (and thus to interrupt solvent-solvent interactions).188 For this purpose was used the Hildebrand solubility parameter, 5, which is defined as the square root of the solvent s energy of vaporization per unit volume.189 Thus Eq. (43) becomes,190... 

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