182122-16-3Relevant academic research and scientific papers
Enzymatic- and light-degradable hybrid nanogels: Crosslinking of polyacrylamide with acrylate-functionalized Dextrans containing photocleavable linkers
Klinger, Daniel,Landfester, Katharina
, p. 1062 - 1075 (2012/06/01)
Enzymatically cleavable and light-degradable hybrid nanogels were prepared by free radical inverse miniemulsion copolymerization of acrylamide (AAm) with a newly synthesized functional dextran crosslinker containing acrylate moieties attached to the backbone via a photolabile linker, that is, dextran-photolabile linker-acrylate (Dex-PL-A). The Dex-PL-A/AAm feed ratio was systematically varied to investigate the influence of the particle composition on the gel properties. The resulting hydrogel nanoparticles were examined with regard to their degradation behavior upon the appliance of the two orthogonal stimuli by turbidity measurements in combination with dynamic light scattering. Although continuous photolytic cleavage of the photolabile linkers between polyacrylamide chains and dextran molecules was found to proceed fast and quantitatively yielding completely disintegrated networks, stepwise irradiation resulted in partial degradation of crosslinking points. Thus, nanogels of a desired specific degree of swelling (DGS) can be obtained by adjusting the irradiation time accordingly. Partial enzymatic cleavage of the dextran backbones of the Dex-PL-A crosslinking molecules resulted in an increase in the DGS of the nanogels up to a constant value. Subsequent irradiation of those swollen hydrogel particles was used to fully degrade the network structure in a second step. Hence, a two-step degradation profile was realized by the combination of the two orthogonal stimuli.
Dual stimuli-responsive poly(2-hydroxyethyl methacrylate-co-methacrylic acid) microgels based on photo-cleavable cross-linkers: PH-dependent swelling and light-induced degradation
Klinger, Daniel,Landfester, Katharina
, p. 9758 - 9772 (2012/04/04)
Dual stimuli-responsive p(HEMA-co-MAA) microgels were prepared in a facile way by inverse miniemulsion copolymerization of 2-hydroxyethyl methacrylate (HEMA) with methacrylic acid (MAA) and two kinds of newly synthesized photodegradable cross-linkers. The pH-dependent swelling behavior induced by the protonation/deprotonation of the methacrylic acid groups in the network-forming polymer was investigated by means of the particle volume change as determined by DLS measurements. Photolytic degradation experiments were conducted by irradiation with UV light which led to particle disintegration caused by cleavage of the photolabile cross-linking points. The degradation behavior of the microgels was investigated with respect to degradation rates and changes in the degree of swelling. Those parameters were found to depend on the pH value of the solvent, the light intensities, and the irradiation wavelengths applied. For similar conditions, the degradation profile was demonstrated to strongly depend not only on the molecular structure of the cross-linking molecule but also on the molecular weight of the network-forming copolymers. The particular combination of the stimuli described is designed as a new strategy to two different swelling/degradation profiles. This dual stimuli-responsiveness was shown to enable the efficient loading and subsequent release of myoglobin as a model protein. Here a slow diffusion controlled release (induced by changes of the pH) was combined with a fast degradation controlled (induced by irradiation) on-demand release. This novel two-step release profile is proposed to bear great potential for delivery applications.
Model Studies for New o-Nitrobenzyl Photolabile Linkers: Substituent Effects on the Rates of Photochemical Cleavage
Holmes, Christopher P.
, p. 2370 - 2380 (2007/10/03)
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.
Facile synthesis of a o-nitrobenzyl photolabile linker for combinatorial chemistry
Teague, Simon J.
, p. 5751 - 5754 (2007/10/03)
Two facile syntheses are described of the o-nitrobenzyl alcohol photolabile linker (5). This compound is a valuable intermediate in the preparation of combinatorial libraries, where it allows release from the solid support to give libraries of acids.
