188891-22-7Relevant academic research and scientific papers
Model Studies for New o-Nitrobenzyl Photolabile Linkers: Substituent Effects on the Rates of Photochemical Cleavage
Holmes, Christopher P.
, p. 2370 - 2380 (1997)
Both a model phenacyl and o-nitrobenzyl photolabile linker from the literature along with four new o-nitrobenzyl linkers were prepared and the kinetics of their photolytic cleavage examined in solution. The linkers were prepared by amidation of the carboxylic acid anchoring tether with benzylamine, and the cleavable benzylic substituent was chosen to be either acetic acid or acetamide. Irradiation of the linkers in four solvents (methanol, p-dioxane, and aqueous buffer ± dithiothreitol) at 365 nm and analysis via HPLC afforded kinetic rates of cleavage suitable for comparative purposes. The phenacyl linker was found to cleave slowly under aqueous conditions with no detectable cleavage being observed in the organic solvents. Known o-nitrobenzyl linker 4 showed modest rates of cleavage in aqueous and organic solvents. Incorporation of two alkoxy groups in the benzene ring to generate the veratryl-based linker 13a increased the rate of cleavage dramatically, and introduction of an additional benzylic methyl group (13b) increased the rate of cleavage by an additional 5 fold. Increasing the length of the anchoring carboxylic acid tether from acetic to butyric acid (19) improved the cleavage kinetics modestly in organic media and slightly diminished the rates in water. The amide model linker 21 cleaved from 3 to 7 times faster than the corresponding ester linkage 19. An amide-generating linker 26 was prepared, and its performance to generate photolabile solid supports was briefly examined. The stability of the linker and subsequent cleavage upon photolysis from the support of an isotopically enriched 4-thiazolidinone was demonstrated by gel phase 13C NMR.
Photolabile Linkers: Exploiting Labile Bond Chemistry to Control Mode and Rate of Hydrogel Degradation and Protein Release
Dasgupta, Srimoyee,Kloxin, April M.,Kloxin, Christopher J.,Levalley, Paige J.,Neelarapu, Raghupathi,Sutherland, Bryan P.
supporting information, p. 4671 - 4679 (2020/04/10)
Photolabile moieties have been utilized in applications ranging from peptide synthesis and controlled protein activation to tunable and dynamic materials. The photochromic properties of nitrobenzyl (NB) based linkers are readily tuned to respond to cytocompatible light doses and are widely utilized in cell culture and other biological applications. While widely utilized, little is known about how the microenvironment, particularly confined aqueous environments (e.g., hydrogels), affects both the mode and rate of cleavage of NB moieties, leading to unpredictable limitations in control over system properties (e.g., rapid hydrolysis or slow photolysis). To address these challenges, we synthesized and characterized the photolysis and hydrolysis of NB moieties containing different labile bonds (i.e., ester, amide, carbonate, or carbamate) that served as labile crosslinks within step-growth hydrogels. We observed that NB ester bond exhibited significant rates of both photolysis and hydrolysis, whereas, importantly, the NB carbamate bond had superior light responsiveness and resistance to hydrolysis within the hydrogel microenvironment. Exploiting this synergy and orthogonality of photolytic and hydrolytic degradation, we designed concentric cylinder hydrogels loaded with different cargoes (e.g., model protein with different fluorophores) for either combinatorial or sequential release, respectively. Overall, this work provides new facile chemical approaches for tuning the degradability of NB linkers and an innovative strategy for the construction of multimodal degradable hydrogels, which can be utilized to guide the design of not only tunable materials platforms but also controlled synthetic protocols or surface modification strategies.
