The bioorthogonal nature of the oxime functionality makes it an effective bioconjugation strategy. A variety of novel hybrid materials with a wide range of biomedical applications have been developed taking advantage of the relative ease of oxime bond formation between alkoxyamine- and aldehyde-/ketone-containing molecules. Oxime ligations proceed through pH-dependent imine-based reactions with low reactivity at pH 7.0 in the absence of aniline catalysts. However, the ability of anilines to readily react with endogenous aldehydes and ketones render oxime ligations “biorestricted”. We previously reported the pH-dependent chemoselective oxidation of N-terminal N-phenylglycines to form α-imino amide intermediates in situ, followed by coupling with aminooxy functional groups to give oximes under mild conditions. In this study, we use a small molecule approach to dissect the mechanism of oxime ligation via in situ mild oxidation of N-arylglycines. Density functional theory (DFT) methods were also employed to examine the proposed mechanism on model systems, with primary focus on the energetics of the reaction steps in neutral and acidic conditions.

Mechanistic study of oxime ligation via in situ oxidation of N-phenylglycinyl peptides

2019 Spring National Meeting

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.