Gas-Phase Amidation of Carboxylic Acids with Woodward's Reagent K Ions.

Zhou Peng, Alice L Pilo, Carl A Luongo, Scott A McLuckey

Journal of the American Society for Mass Spectrometry 2015 Oct

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Gas-phase amidation of carboxylic acids in multiply-charged peptides is demonstrated via ion/ion reactions with Woodward's reagent K (wrk) in both positive and negative mode. Woodward's reagent K, N-ethyl-3-phenylisoxazolium-3'-sulfonate, is a commonly used reagent that activates carboxylates to form amide bonds with amines in solution. Here, we demonstrate that the analogous gas-phase chemistry occurs upon reaction of the wrk ions and doubly protonated (or doubly deprotonated) peptide ions containing the carboxylic acid functionality. The reaction involves the formation of the enol ester intermediate in the electrostatic complex. Upon collisional activation, the ethyl amine on the reagent is transferred to the activated carbonyl carbon on the peptide, resulting in the formation of an ethyl amide (addition of 27 Da to the peptide) with loss of a neutral ketene derivative. Further collision-induced dissociation (CID) of the products and comparison with solution-phase amidation product confirms the structure of the ethyl amide.

Citation

Zhou Peng, Alice L Pilo, Carl A Luongo, Scott A McLuckey. Gas-Phase Amidation of Carboxylic Acids with Woodward's Reagent K Ions. Journal of the American Society for Mass Spectrometry. 2015 Oct;26(10):1686-94