THE EVALUATION OF PROTONATION ENERGY OF MOLECULES IN TERMS OF QUANTUM THEORETICAL DESCRIPTORS - Theoretical and Computational Research in the 21st Century - page 215

ones because even the largest differences between Gaussian-3 and CBS
methods mentioned earlier were still comparable with the accuracy of the
typical PA measurement.
The PA scale of small aminal cages was investigated by Rivera et al[71]
using the experimental (FT-IR) and theoretical (DFT) methodologies. The
formation constant (K f ) was determined for 1:1 hydrogen-bonded com-
plexes between p-fl uorophenol (PEP) and some aminal cage type (B) in
CCl 4 at 298K using FT-IR spectrometry. Then, the total interaction energy
(E PFF…B ), the energy of protonation (E HB+ ), the HOMO-LUMO gap values
and Fukui index were calculated using the DFT/B3LYP/6-31G(d,p) level
of theory as theoretical scales was observed, evidence for the existence of
a relationship between the total energy of interaction calculated by struc-
tural parameters and proton affi nity in this series.
We may summarize the above survey in the following way. The primary
experimental methods used for measurement of gaseous PA was ion cyclo-
tron resonance (ICR) spectroscopy for measurement of the proton transfer
to another base, or chemical ionization (CI) measurements to “bracket”
the compound between two bases of known PA. These measurements are
experimentally diffi cult to perform and interpret [72]. Their accuracy de-
pends on the presence of chemical equilibrium between the species, a cer-
tainty in the local temperature in the measurement cell, and the assumption
that the rotational and vibrational components of ∆ST are zero or known.
In addition, there may be uncertainty as to the site of protonation on the
molecule. Despite these diffi culties, there exists a scale of relative proton
affi nities, which is well-established and well-accepted [18]. The relative
values of PA's are most often determined by mass spectroscopic measure-
ment of the equilibrium constant for the proton-exchange gas phase reac-
tions [4,18,73-75], and the absolute proton affi nities can be obtained from
ionization thresholds [18]. However, these “acid-base” adducts are not
stable and/or does not exist in all cases. In addition, experimental determi-
nation of the PAs of molecules is not easy [75].
An alternative to the measurement of PAs of small molecules is their
determination through the measure of the probability of a chemical group
to be protonated/unprotonated. The probability of a chemical group to be
protonated/unprotonated is given by the legend pKa which is defi ned by
pKa = -log[A - ][H + ]/[AH]. The pKa of a protonable group strongly de-
pends on its molecular environment. It is possible to measure the pKa
experimentally, but this is generally not an easy task.