Coarse-Grained Model of Phytic Acid for Predicting the Supramolecular Architecture of Ionically Cross-Linked Chitosan Hydrogels.

Phytic acid is a polyphosphate whose ionized form is used as a cross-linking agent to formulate chitosan-based nanoparticles and hydrogels as carriers with remarkable adhesivity and biocompatibility. To predict the underlying cross-linking pattern responsible for the structural arrangement in the chitosan hydrogels, we put forth coarse-grained parametrization of the phytic acid compatible with the Martini 2.3P force field. The bonded parameters giving the distinctive representation of the phosphate substitutes to the -inositol ring of phytic acid are optimized by a structural comparison to the conformation sampled with the GROMOS 56A force field. The chitosan strand is coarse-grained following a similar approach, and the cross-interaction terms are optimized to reproduce the atomistic features of phytate-mediated cross-linking. The predicted binding motifs of the phytic acid-chitosan complexation enable us to rationalize the structural characteristics of the reticulated chitosan in a semi-dilute solution. The model describes a network topology affected by the phytic acid concentration and a nonmonotonous behavior of the mean pore size caused by a poor predilection for the parallel strand alignment near the charge neutralization of the phytic acid-chitosan complex.