Supramolecular nucleoside-based gel: molecular dynamics simulation and characterization of its nanoarchitecture and self-assembly mechanism

Amongst the diversity of existing supramolecular hydrogels, nucleic acid-based hydrogels are of particular interest for potential drug delivery and tissue engineering applications because of their inherent biocompatibility. Hydrogel performance is directly related to nanostructure and the self-assembly mechanism of the material, an aspect that is not well understood for nucleic acid-based hydrogels in general and has not yet been explored for cytosine based hydrogels in particular. Herein, we use a broad range of experimental characterization techniques along with molecular dynamics simulations to demonstrate the complementarity and applicability of both approaches for nucleic acid-based gelators in general and propose the self-assembly mechanism for a novel supramolecular gelator, N⁴-octanoyl-2'-deoxycytidine. The experimental data and the MD simulations are in complete agreement with each other and demonstrate the formation of a hydrophobic core within the fibrillar structures of these mainly water-containing materials. The characterization of the distinct duality of environments in this cytidine based gel will form the basis for further encapsulation of both small hydrophobic drugs and biopharmaceuticals (proteins and nucleic acids) for drug delivery and tissue engineering applications.