Biocytin-Based pH-Stimuli Responsive Supramolecular Multivariant Hydrogelator for Potential Applications

Self-assembly is one of the important and fruitful methods to develop various biomaterials, especially hydrogels, from biologically important small molecules. Two such molecules are d-biotin (B-vitamin), which plays several vital roles in biology and is used in the biomedical field, and biocytin, which is used as an intracellular marker and also to identify neurons. Despite the significance of these biomolecules, their usage in the form of hydrogel is very limited. Herein, for the first time, a pH-stimuli responsive supramolecular hydrogel based on biocytin, an amidation product of d-biotin and l-lysine, has been developed to extend the use of d-biotin, biocytin, and l-lysine in the biomedical field. The newly developed hydrogelator such as N_α-(fluorenylmethoxycarbonyl)-d-biocytin) [FmB] exhibited pH-dependent hydrogelation and exhibited a thixotropic and thermally reversible nature at a physiological pH, while it displayed a supergelator nature at an acidic pH. Electron microscopic analysis of FmB hydrogel indicated the formation of a fibrous network structure. Various biophysical measurements including CD, FT-IR, fluorescence, and powder XRD demonstrated that intermolecular interactions such as aromatic and hydrogen bonding stabilize the fibrous structure of FmB. Importantly, the FmB hydrogel was found to be viable for the cells and displayed specific bactericidal activity against Escherichia coli. Since making hydrogels directly with drugs or vitamins rather than inclusion in other hydrogels (matrix) may provide new biomaterials that can act as self-delivery systems, we believe that the newly developed multivariant biocytin-based supramolecular hydrogel can significantly advance the application of biotin and biocytin in various fields.