3.1.1. Solubility of chitosan
A highly deacetylated polymer has been used to
explore methods of characterization [99]. The
solution properties of a chitosan depend not only
on its average DA but also on the distribution of the
acetyl groups along the main chain in addition of
the molecular weight [57,60,100]. The deacetylation,
usually done in the solid state, gives an irregular
structure due the semicrystalline character of the
initial polymer. Examination of the role of the
protonation of chitosan in the presence of acetic
acid [101] and hydrochloric acid on solubility[102]
showed that the degree of ionization depends on the
pH and the pK of the acid. Solubilization of
chitosan with a low DA occurs for an average
degree of ionization a of chitosan around 0.5; in
HCl, a ¼ 0:5 corresponds to a pH of 4.5–5.
Solubility also depends on the ionic concentration,
and a salting-out effect was observed in excess of
HCl (1 M HCl), making it possible to prepare the
chlorhydrate form of chitosan. When the chlorhydrate
and acetate forms of chitosan are isolated,
they are directly soluble in water giving an acidic
solution with pK0 ¼ 670.1 [102], in agreement with
previous data [103] and corresponding to the
extrapolation of pK for a degree of protonation
a ¼ 0. Thus, chitosan is soluble at pH below 6.
The solubility of chitosan is usually tested in
acetic acid by dissolving it in 1% or 0.1 M acetic
acid. We demonstrated that the amount of acid
needed depends on the quantity of chitosan to be
dissolved [101]. The concentration of protons
needed is at least equal to the concentration of
NH2 units involved.
In fact, the solubility is a very difficult parameter
to control: it is related to the DA, the ionic
concentration, the pH, the nature of the acid used
for protonation, and the distribution of acetyl
groups along the chain, as well as the conditions
of isolation and drying of the polysaccharide. It is
important also to consider the intra-chain H bonds
involving the hydroxyl groups as shown below. The
role of the microstructure of the polymer is clearly
shown when a fully deacetylated chitin is reacetylated
in solution; the critical value of chitosan DA
to achieve insolubility in acidic media is then greater
than 60%. In addition, solubility at neutral pH has
also been claimed for chitosan with DA around
50% [60].
Recently, a water-soluble form of chitosan at
neutral pH was obtained in the presence of glycerol
2-phosphate [104–107]. Stable solutions were obtained
at pH 7–7.1 and room temperature, but a gel
formed on heating to about 40 1C. The sol–gel
transition was partially reversible and the gelation
temperature depended slightly upon experimental
conditions (Figs. 8 and 9).