Synthesis of Chemical Models of Hydrolase Enzymes for Intramolecular Catalysis.

• Main Author: Ndi, Cornelius Ndi
• Format: Others
• Published: Digital Commons @ East Tennessee State University 2011
• Subjects: Intramolecular; Nucleophilic; General acid/base; Hydrolase; Chemistry; Organic Chemistry; Physical Sciences and Mathematics
• Online Access: https://dc.etsu.edu/etd/1356; https://dc.etsu.edu/cgi/viewcontent.cgi?article=2547&context=etd

Most nuclease enzymes can hydrolyze phosphoester bonds (in DNA and RNA) by using metal ions cofactors that coordinate and activate water molecules in the enzymes' active sites. However, there are some hydrolase enzymes (including nucleases) that can function without the aid of metal ions. 2,6-Di(1H-imidazol-2-yl)phenol, a model compound for hydrolase enzyme, was synthesized by the reaction between ethylenediamine and dimethyl-3-carboxysalicylate, initially resulting in the formation of diimidazoline. The diimidazoline was subsequently aromatized to the diimidazole by dehydrogenation over palladium. The overall reaction yield was low; therefore, other dehydrogenation transformation reactions were tried but all failed to improve the yield. Converting this diimidazolphenol into diimidazolphenyl monophoshpate derivative was attempted but failed to give desired products. Synthesis of 2,2'-anthracene-1,8-diylbis-1H-imidazole, another model compound for hydrolase enzymes, was attempted using dimethyl-1,8-anthracenedicarboxylate, but synthesis was unsuccessful due to solubility problem.