P. Perez et al., A semiquantitative description of electrostatics and polarization substituent effects: Gas-phase acid-base equilibria as test cases, J PHYS CH A, 104(51), 2000, pp. 11993-11998
A semilocal (regional) model to describe the effects of chemical substituti
on on gas-phase acid-base reactivity is developed and tested. A simple rela
tionship connecting regional changes in electron density and global changes
in electronic chemical potential is used to describe inductive (electrosta
tic) substituent effects. Electronic (polarization) substituent effects are
described in terms of regional changes in local softness at the active sit
e, that are responses to changes in electronic chemical potential induced b
y chemical substitution. The model correctly explains the variations of the
gas-phase acidity of alkyl alcohols and some thio derivatives within a loc
al hard and soft acid and bases (HSAB) rule. Increase in local softness is
correlated with a decrease in proton affinity of the conjugated base and th
erefore with an enhancement of the gas-phase acidity. It is shown that this
is basically a HSAB result. The local analysis based on second-order varia
tions in electron density (i.e,, regional changes in the Fukui function) is
consistent with the classical analysis based on first-order variations in
electron population at the active site: a decrease in the electronic chemic
al potential induced by substitution results in a decrease in the electron
population at the site (inductive effect, -I), thereby stabilizing the conj
ugated base and therefore increasing the acidity of the neutral parent mole
cule.