Insights into the mechanism and catalysis of oxime coupling chemistry at physiological pH

Shujiang Wang, Deepanjali Gurav, Oommen Podiyan Oommen, Oommen P Varghese

    Research output: Contribution to journalArticleScientificpeer-review

    13 Citations (Scopus)

    Abstract

    The dynamic covalent-coupling reaction involving α-effect nucleophiles has revolutionized bioconjugation approaches, due to its ease and high efficiency. Key to its success is the discovery of aniline as a nucleophilic catalyst, which made this reaction feasible under physiological conditions. Aniline however, is not so effective for keto substrates. Here, we investigate the mechanism of aniline activation in the oxime reaction with aldehyde and keto substrates. We also present carboxylates as activating agents that can promote the oxime reaction with both aldehyde and keto substrates at physiological pH. This rate enhancement circumvents the influence of α-effect by forming H-bonds with the rate-limiting intermediate, which drives the reaction to completion. The combination of aniline and carboxylates had a synergistic effect, resulting in a ∼14-31-fold increase in reaction rate at pD 7.4 with keto substrates. The biocompatibility and efficiency of carboxylate as an activating agent is demonstrated by performing cell-surface oxime labeling at physiological pH using acetate, which showed promising results that were comparable with aniline.

    Original languageEnglish
    Pages (from-to)5980-5
    Number of pages6
    JournalChemistry: A European Journal
    Volume21
    Issue number15
    DOIs
    Publication statusPublished - 7 Apr 2015
    Publication typeA1 Journal article-refereed

    Keywords

    • Aldehydes
    • Aniline Compounds
    • Carboxylic Acids
    • Catalysis
    • Hydrazones
    • Hydrogen-Ion Concentration
    • Ketones
    • Oximes
    • Journal Article
    • Research Support, Non-U.S. Gov't

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