Tuning Zr(IV)-assisted peptide hydrolysis at near-neutral pH

The present study has compared the effects of a total of 17 ligands on Zr(IV)-assisted hydrolysis of the dipeptide Gly–Gly (60 °C, pH 6.8–7.4, t = 4 h and t = 10 h). The macrocyclic azacrown ether ligands 1,4,10,13-tetraoxa-7,16-diazacyclooctadecane and 1,4,10-trioxa-7,13-diazacyclopentadecane produced the overall highest amounts of hydrolysis, followed by the open-chain ligand 2-(2-aminoethoxy)-ethanol. While it was not necessary to have a ring structure to enhance Zr(IV) reactivity, the structural feature “ROCH2CH2OCH2CH2NR” appeared to contribute to increased levels of peptide cleavage.