Acidity constants, prediction

Both AMI and MNDO methods correctly predict the predominance of the oxo-thione form for A-monosubstituted 2-thiouracils in the gas phase (89JCS(P2)1507). The gas phase calculated relative stabilities, proton affinities and aqueous phase calculated acidity constants predicted the higher stability of the oxo-thione form of 6-propyl-2-thiouracil compared to the hydroxy(thiol) tautomer (04JST(679)33). 

Obviously, to model these effects simultaneously becomes a very complex task. Hence, most calculation methods treat the effects which are not directly related to the molecular structure as constant. As an important consequence, prediction models are valid only for the system under investigation. A model for the prediction of the acidity constant pfQ in aqueous solutions cannot be applied to the prediction of pKj values in DMSO solutions. Nevertheless, relationships between different systems might also be quantified. Here, Kamlet s concept of solvatochro-mism, which allows the prediction of solvent-dependent properties with respect to both solute and solvent [1], comes to mind. 

The rate of saponification of ethyl 2-thenoate, in contrast to ethyl 3-thenoate, was found to be considerably slower than predicted from the pKa of the acid, showing that the reactivities of thiophenes do not parallel those of benzene. The first explanation, that this was produced by a steric effect of the ring sulfur similar to the case in or /lo-substituted benzenes and in ethyl 1-naphthoate, could not be upheld when the same effect was found in ethyl 2-furoate. It was later ascribed to a stereospecific acid strengthening factor, involving the proper relation of the carboxylic hydrogen and the heteroatom, as the rate of saponification of 2-thienylacrylic acid was in agreement with that predicted from the acid constants. ... 

A simple case where the general a constants in Table 8.5 do not succeed in correlating acidity constants is when the acid or base function is in direct resonance with the substituent. This may occur in cases such as substituted phenols, anilines, and pyridines. For example, owing to resonance (see Fig. 8.4), a para nitro group decreases the pKa of phenol much more than would be predicted from the o para constant obtained from the dissociation of p-nitrobenzoic acid. In such resonance cases (another example would be the anilines), a special set of o values (denoted as oJpara) has been derived (Table 8.5) to try to account for both inductive and resonance... 

In the absence of special transport mechanisms (which is not proven, see further in the text), the vacuolar accumulation ratios (VAR) could be predicted from a derivation of the Hendelson-Hasselbach equation using the calculated log/) values. Indeed, for a diacidic base, the log D is a function of the acidity constants (pka) and the partition coefficient (log P) ... 

It is important to note that the Pow used is that for pH 7 (Pow)- Consider 2,4-dichlorophenoxyacetic acid the predicted plot gradient would be much higher if Pow was used in equation (6.8) rather than P ow. This implies that the compound ionises from neutral to anion on or near the liquid-liquid interface (within the diffusion layer). Therefore, for ionisable compounds, the rate constants koa and kai, must also include the ionisation process. Because proton transfer is fast it has not been explicitly described here. 

The peptides, which are composed of only a few amino acids, exhibit predictable behavior in CZE in that their mobility (electrophoretic migration) can be predicted on the basis of their size (mass) and their charge characteristics. The charge of such peptides can be predicted from the pKa values of individual amino acids contained in them. For larger peptides and proteins, the calculation of charge based on ionization constant is not trivial and can not be easily calculated based on the pKas of the free amino aids. Besides the mass-to-charge ratio, the other factors that affect mobility are hydrophobic-ity, primary sequence, conformational difference, and the chirality of amino acids. This point has been demonstrated by an investigation on several nonapeptides of identical composition but with different primary sequences ... 

Calculate dissociation constants of carboxylic acids, and predict the relative acidities of substituted carboxylic acids. 

Table 4-1 shows the predicted solvent influence on the acidity constants for various charge types of acid/base pairs. 

On CNDO/2 calculations with pK (as base) = 2.30 for triazole, the basicities of H and AH tautomers are estimated to be equal, and maximum separation of protonated nitrogens i.e. N-1 and N-4 rather than N-1 and N-2) is predicted to afford the most stable cation (68TL3727). Acidity constants of 1,2,4-triazoles correlate with total and rr-electron densities but not with the lone pair character of the pyridine-type N in MO calculations (70JCS(B)i692, 70BCJ3344). 

Kaminski, G.A. Accurate prediction of absolute acidity constants in water with a polarizable force field Substituted phenols, methanol, and imidazole. J. Phys. Chem. B 2005, 109(12), 5884-90. 

Therefore it would be much desired to derive the concentrations and acidity constants of particular types of surface sites from some first principles, rather than to fit them as adjustable parameters. This would produce generic charging curves for certain material (rather than for specific sample). Unfortunately verification of such a model is rather difficult in view of contradictory surface charging curves reported in the literature for different samples of the same material (cf Figs. 3,43-3.73). The surface charging depends on many variables, e.g, the PZC is temperature dependent, and the absolute value of ag depends on the nature of the counterions (K versus Na, etc.). Consideration of all these variables would be very tedious, and such effects are mostly ignored in the attempts to predict the surface charging behavior of materials. 

Hemmateenejad, B., Safarpour, M.A. andTaghavi, F. (2003) Application of ab initio theory for the prediction of acidity constants of some 1-hydroxy-9,10-anthraquinone derivatives using genetic neural network./. Mol Struct. (Theochem), 635, 183-190. 

The response surface constructed from this model is shown as a surface plot in Figure 7.6. The resolution response surface was generated by multiplying the peak pair resolutions calculated from the amino acid mobilities predicted by the ANN. For this calculation, it was assumed that the peak widths were constant for each experiment. Therefore, the peak pair resolution calculation was reduced to the difference between the mobility of each of the adjacent peaks. The product resolution was chosen as it gives a simple measure of the overall resolution of the separation, with the largest value representing the greatest spread of the peaks. 

The wavenumbers of the 0 0 transitions for the acid, AH, and the base, A, estimated from the intersection points of the corresponding absorption and fluorescence spectra, are Vo o(AH) = 2.95 pm 1 and Vo o(A ) = 2.65 pm By inserting these data into Equation 5.10 we obtain pA a = 3.2 for the acidity constant of 10 in the excited singlet state. Thus the acidity of 10 is predicted to increase by over six orders of magnitude upon excitation to the lowest singlet state. The prediction was tested by a fluorescence titration The relative fluorescence intensity at the emission... 

The pK of phenalene ionizing to its anion 4 (Case Study 4.1) is about 20. The first absorption band of phenalene lies at vq o 2.9 pm Predict the acidity constant of phenalene in the lowest excited singlet state. [p fa = — 1]... 

The adsorption of silicic acid on a-FeOOH tends to release protons (a) and causes a decrease in surface charge (b). The extent of adsorption as a function of pH can be predicted by an equilibrium model that considers the equilibrium constants given in Equations 22 and 23 and the acidity constant of H SiO and =FeOH, (IS). 

Seiler P, Simultaneous determination of partition coefficient and acidity constant of a substance, Eur. J. Med. Chem., 9, 663-665 (1974). Cited in Lombardo F, Obach RS, Shalaeva MY and Gao F, Prediction of human volume of distribution values for neutral and basic drugs. 2. Extended data set and leave-class-out statistics, /. Med. Chem., 47, 1242-1250 (2004) (ref. 279). NB Titrations were performed by autotitrator in the presence of hi purity dodecane, to allow simultaneous measurement of the log P value. The pH meter was calibrated against three standard solutions. 

The use of LFERs constitutes one of the most powerful means for the elucidation of reaction mechanisms. LFERs also provide us a means to predict reaction rates or bioactivity from more easily measured equilibrium constants such as octanol-water partition coefficients (Ko, ), ionization constants (KJ, or acidity constants (Khb)-Brezonik (1990) has summarized the major classes of LFERs applicable to reactions in aquatic ecosystems (Table 1.2). These empirical correlations pertain to a variety... 

J.A. Keith and E.A. Carter, Quantum chemical benchmarking, validation, and prediction of acidity constants for substituted pyridinium ions and pyr-idinyl radicals, J. Chem. Theory Comput. 8 (2012), pp. 3187-3206. 

A. Habibi-Yangjeh, M. Danandeh-Jenagharad, and M. Nooshyar, Prediction acidity constant of various benzoic acids and phenols in water using linear and nonlinear QSPR models. Bull. Korean Chem. Soc. 26 (2005), pp. 2007-2016. 

A. Habibi-Yangjeh and M. Danandeh-Jenagharad, Prediction of acidity constant for substituted acetic acids in water using artificial neural networks, Indian J. Chem., Sect. B Org. Chem. Inch Med. Chem. 46 (2007), pp. 478 87. 

A. Habibi-Yangjeh, E. Pourbasheer, and M. Danandeh-Jenagharad, Application of principal component-genetic algorithm-artificial neural network for prediction acidity constant of various nitrogen-containing compounds in water, Monatsh. Chem. 140 (2009), pp. 15-27. 

---