Browsing by Subject "photolabile"

The concept of light-activated "caged" metal ions was first introduced for Ca2+. These high affinity coordination complexes are activated by UV light to release calcium ions intracellularly and have found widespread use in understanding the many roles of calcium in biological processes. There is an unmet need for photocaging ligands for biologically relevant transition metal ions. Described here are the first examples of uncaging biologically important d-block metal ions using photoactive ligands.

New nitrogen-donor ligands that contain a photoactive nitrophenyl group within the backbone have been prepared and evaluated for their metal binding affinity. Exposure of buffered aqueous solutions of apo-cage or metal-bound cage to UV light induces cleavage of the ligand backbone reducing the denticity of the ligands. Characterization of several caging compounds reveals that quantum efficiency and metal binding affinity can be tuned by modifications to the parent structure. The change in reactivity of caged vs. uncaged metal for promoting hydroxyl radical formation was demonstrated using the in vitro deoxyribose assay. The function of several of these compounds in vivo pre- and post-photolysis has been validated using MCF-7 cells. This strategy of caging transition metals ions is promising for applications where light can trigger the release of metal ions intracellularly to study metal trafficking and distribution, as well as, selectively impose oxidative stress and/or metal toxicity on malignant cells causing their demise.

The ability to manipulate the coordination chemistry of metal ions has significant ramifications for the study and treatment of metal-related health concerns, including iron overload, UV skin damage, and microbial infection among many other conditions. To address this concern, chelating agents that change their metal binding characteristics in response to external stimuli have been synthesized and characterized by several spectroscopic and chromatographic analytical methods. The primary stimuli of interest for this work are light and hydrogen peroxide.

Herein we report the previously unrecognized photochemistry of aroylhydrazone metal chelator ((E)-N′-[1-(2-hydroxyphenyl)ethyliden]isonicotinoylhydrazide) (HAPI) and its relation to HAPI metal binding properties. Based on promising initial results, a series of HAPI analogues was prepared to probe the structure-function relationships of aroylhydrazone photochemistry. These efforts elucidate the tunable nature of several aroylhydrazone photoswitching properties.

Ongoing efforts in this laboratory seek to develop compounds called prochelators that exhibit a switch from low to high metal binding affinity upon activation by a stimulus of interest. In this context, we present new strategies to install multiple desired functions into a single structure. The prochelator 2-((E)-1-(2-isonicotinoylhydrazono)ethyl)phenyl (E)-3-(2,4-dihydroxyphenyl)acrylate (PC-HAPI) is masked with a photolabile trans-cinnamic acid protecting group that releases umbelliferone, a UV-absorbing, antioxidant coumarin along with a chelating agent upon UV irradiation. In addition to the antioxidant effects of the coumarin, the released chelator (HAPI) inhibits metal-catalyzed production of damaging reactive oxygen species. Finally a peroxide-sensitive prochelator quinolin-8-yl (Z)-3-(4-hydroxy-2-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)oxy)phenyl)acrylate (BCQ) has been prepared using a novel synthetic route for functionalized cis-cinnamate esters. BCQ uses a novel masking strategy to trigger a 90-fold increase in fluorescence emission, along with the release of a desired chelator, in the presence of hydrogen peroxide.