Release of Calcium through Photoinduced Electron Transfer to Produce Biologically Relevant Hydrogels

Calcium is not only a biologically relevant second messenger but also an ionic trigger that produces rheological changes to certain sensitive biopolymers such as alginate. Alginate, an anionic polysaccharide that has been used for drug encapsulation, forms hydrogels when in the presence of calcium.  The release of calcium with light has several distinct advantages including that light can be directed with high spatial precision rapidly and has wavelength specificity.  Previous methods for uncaging calcium include the photochemical scission of a nitrophenyl derivatized calcium chelators such as EGTA or the reduction of affinity of calcium binding moieties, which can produce harsh conditions for cells.  In our study we affect release of calcium through an electron abstraction mechanism using riboflavin and EDTA. Excited state riboflavin and its derivatives abstract an electron from EDTA causing its degradation and subsequent calcium release.  We used HPLC, MS, and  UV-Vis to track the progress of the reaction. Both steady state and dynamic rheology measurements were taken measure the degree of gelation in the samples. Our calcium photorelease process can produce hydrogels through a spatially precise and biocompatible manner.