Site selectivity presents a unique challenge when trying to carry out chemical reactions such as functionalization or labeling of molecules in complex systems. Naturally occurring enzymes exhibit exceptional site selective properties, thus, we propose the use of synthetically synthesized molecules that mimic the behavior of naturally occurring enzymes. These synthetic DNA conjugated small molecule catalysts, or Dcats, consist of a DNA aptamer with a molecular recognition domain, linked to a catalyst such as palladium or imidazole. The sequence of the molecular recognition domain, type of catalyst, and location of the linker between the two can be manipulated to be best fitted for the desired reaction. DNA-imidazole conjugates have been shown to increase the rate of ester hydrolysis by upwards of 100 fold. Current work aims to replicate ester hydrolysis reactions such as these, using a palladium catalyst in place of imidazole. Total synthesis of a novel small molecule containing cholic acid, an allyl carbamate, and UV active umbelliferone will allow for a reaction with a DNA-palladium pair whose success can be tracked by quantifying levels of fluorescence produced by the liberation of umbelliferone from the molecule. Using a simpler version of this molecule that was previously synthesized by the lab, trials were done using different sources of palladium catalyst and different ligands. Results show that a Palladium (II) Acetate palladium source, and Triphenylphosphine PPh3 ligand with a ratio of 4:1 respectively yield the most successful reaction. Further work will include testing this molecule, as well as the newer one in the process of being synthesized, in the presence of DNA in addition to the palladium catalyst. Dcats have the potential to be of great use not only in the field of synthetic chemistry, but also in pharmacology and medicine for applications such as targeted drug delivery.

Synthesis of DNA-conjucated small molecule catalysts for improved site selectivity

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