ORGN 180 |
| A variety of molecular machines have undergone impressive development into working linear actuators, rotors, materials capable of information storage, and stimuli-responsive valves. We envision this last class of molecular valves to be of interest for the targeted delivery of therapeutic agents - a phenomenon that would both maximize a drug's beneficial effect while hopefully minimizing adverse side-effects. To address this issue, supramolecular and molecular valves have been developed based on nanoporous silica that respond to stimuli such as UV light, redox processes and changes in pH. Though these valves have been successfully tested in solution, we saw the benefit of developing valves that respond to specific enzyme targets, with the possibility of linking release to the presence of enzymes that are specific and/or overexpressed by various diseases. Herein, we report a valve that undergoes specific cleavage and subsequent release of guest dye molecules in the presence of a model enzyme (Box). Briefly, the surface of the mesoporous MCM-41 silica nanoparticle is functionalized with a short, azide-terminated, ethylene glycol thread, which is able to be included into the cavity of α-cyclodextrin. An acetylene-terminated, adamantyl stopper is then attached, using the co-catalyzed Azide-Alkyne cycloaddition. The adamantyl group is connected to the thread via an ester linkage, which is cleaved by Porcine Liver Esterase (PLE). To achieve release, these ‘active' particles are then exposed to PLE while monitoring Rhodamine B release using luminescence spectroscopy. Current work focuses on developing and testing nanovalves that are responsive to other relevant enzymes and proteases as well as being able to exclusively target diseased cells by exploiting their rapidly emerging characteristics.
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Total Synthesis, Materials, Devices and Switches, Molecular Recognition and Self-Assembly, Biologically-Related Molecules and Processes
8:00 PM-10:00 PM, Sunday, August 19, 2007 BCEC -- Exhibit Hall - B2, Poster
Sci-Mix
Division of Organic Chemistry |
