The pyridine carboxylic acids picolinic acid (2-pyridine carboxylic
acid CAS 98-98-6), nicotinic acid (3-pyridine carboxylic acid
CAS 59-67-6) and isonicotinic acid (4-pyridine carboxylic acid
CAS 55-22-1) are important chemicals used as food additives and
in the drug industry. They exist in solution potentially as four species;
a protonated cationic species, a deprotonated anionic species,
a zwitterion and the neutral species [1–5]. García et al. [3] have
shown that in water near pH values from about 2.8 to 3.6 the dominant
species in the case of picolinic acid is the zwitterion (98%)
with the remainder being the cationic species. The concentration
of the neutral form was very low. Similar results were found for
nicotinic acid and isonicotinic acid. In a very detailed investigation
on nicotinic acid, Nagy and Takács-Novák [4] found that the ratio of
zwitterion to neutral form lies between 23.4 and 31.7, so that the
neutral form in water exists to about 4%. They show also that in the
pure organic solvents methanol and tetrahydrofuran the zwitterion
exists to only about 3%, the major species being the neutral
form (97%). Other workers have also found that the zwitterion is
the predominant form in water near the isoelectric point [5] but
that in a solvent such as 50 w/w% ethanol, the zwitterion to neutral
ratio is near to zero [1,2]. It is thus reasonably clear that for the
pyridine carboxylic acids near the isoelectric point in water, the
zwitterion is the dominant form and that in pure organic solvents
the acids exist almost entirely as the neutral form.