Rate-Tunable, Metal-Mediated Amide Bond Cleavage for the Controlled Release of Pharmaceuticals.

ABSTRACT: That the incorporation of N-methyl amino acids adjacent to a hydrolytic, azamacrocyclic metal complex results in rate-tunable, metal-mediated amide bond cleavage (TMAC) under physiological conditions. Spectroscopic and crystallographic data provide unprecedented mechanistic insight: the Ga³⁺ complex of (7-amido-1,4,7-triazonane-1,4-diyl)diacetic acid polarizes the amide bond proximal to canonical and noncanonical amino acids, forming two coordination isomers with different cleavage rates, N₃O₃ (fast) and N₄O₂ (slow) in aqueous solution. Both were characterized by NMR spectroscopy and identified by single-crystal X-ray diffraction. Subsequent hydrolysis of the amide bond occurs by exogenous nucleophilic attack, as demonstrated by

SUBMITTER: Zhong Z 

PROVIDER: S-EPMC12636028 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature