Molecular Dynamics Simulation of the Arginine-Assisted
Solubilization of Caffeic Acid: Intervention in the Interaction
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Abstract
We
have previously demonstrated that arginine increases the solubility
of aromatic compounds that have poor water solubility, an effect referred
to as the “arginine-assisted solubilization system (AASS)”.
In the current study, we utilized a molecular dynamics simulation
to examine the solubilization effects of arginine on caffeic acid,
which has a tendency to aggregate in aqueous solution. Caffeic acid
has a hydrophobic moiety containing a π-conjugated system that
includes an aromatic ring and a hydrophilic moiety with hydroxyl groups
and a carboxyl group. While its solubility increases at higher pH
values due to the acquisition of a negative charge, the solubility
was greatly enhanced by the addition of 1 M arginine hydrochloride
at any pH. The results of the simulation indicated that the caffeic
acid aggregates were dissociated by the arginine hydrochloride, which
is consistent with the experimental data. The binding free energy
calculation for two caffeic acid molecules in an aqueous 1 M arginine
hydrochloride solution indicated that arginine stabilized the dissociated
state due to the interaction between its guanidinium group and the
π-conjugated system of the caffeic acid. The binding free energy
of two caffeic acid molecules in the arginine hydrochloride solution
exhibited a local minimum at approximately 8 Å, at which the
arginine intervened between the caffeic acid molecules, causing a
stabilization of the dissociated state of caffeic acid. Such stabilization
by arginine likely led to the caffeic acid solubilization, as observed
in both the experiment and the MD simulation. The results reported
in this paper suggest that AASS can be attributed to the stabilization
resulting from the intervention of arginine in the interaction between
the aromatic compounds