Relationship between experimental pK_a values in aqueous solution and a gas phase bond length in bicyclo[2.2.2]octane and cubane carboxylic acids

Abstract

Linear correlations were established between the calculated bond lengths and the pK a or σ I values for a series of 4-substituted bicyclo[2.2.2]octane-1-carboxylic acid and 4-cubane-1-carboxylic acid derivatives. The bond lengths have been calculated at a modest computational level, HF/6-31G(d), both in the gas phase and with the continuum solvation model, polarisable continuum model (PCM). In general, the best correlations are obtained when the PCM model is taken into account, especially when neutral and charged molecules are considered together. The best models in each case show square correlation coefficients (R 2 ) larger than 0.9 and indicate that they can be used as predictive tools. These results expand previous results that indicate the possibility of a relationship between gas phase bond length and pK a values in aqueous solution and indicate that such relationships are more general than hitherto expected.

Enhancement of Thermodynamic Gas‐Phase Acidity and Basicity of Water by Means of Secondary Interactions

“…An analysis of the interatomic distances between the hydrogen atom involved in the HB and the oxygen atom of the water molecule in the protonated systems shows a linear relationship with the calculated PA (R 2 =0.96). This relationship is similar to those recently proposed to correlate the pKa with bond distances ,,,,…”

“…This relationship is similar to those recently proposed to correlate the pKa with bond distances. [33,34,35,36,37]…”

Substituent effects in 1-nitro-4-substituted bicyclo[2.2.2]octane derivatives: inductive or field effects?

“…Then, by analysis of a properly chosen set of data, the inductive constants σ I [23] and the resonance constants σ R were obtained [24]. Controversy between the interpretation of substituent effects as inductive or through-space is not yet decisively resolved [12,[25][26][27][28][29][30][31][32]. It is important to mention that interactions like those in 4-substituted bicyclo[2.2.2]octane-1-carboxylic acid derivatives were named recently as inductive/ field interactions.…”

pKa prediction for acidic phosphorus‐containing compounds using multiple linear regression with computational descriptors

“…Based on the respective characteristics of these two techniques, quantum QSPR methods have been developed in recent years, in which the molecular descriptors and detailed information are provided by quantum chemical computations. [16,17] These methods are not restricted by the experimental conditions and do not require the precision in pure first-principles methods.…”

“…The fittings of various descriptors such as empirical atomic charges, electrostatic energies, cavity energies, dispersion energies, repulsion interactions, and bond lengths to pK a have been reported in the literature. [15,17,19] A broad range of substrates have also been investigated, including alcohols, phenols, and carboxylic acids with different pK a ranges. Both single and multiple variable regressions have been reported.…”