Backbone fragmentations of [M–H] – anions from peptides. Reinvestigation of the mechanism of the beta prime cleavage

RATIONALE An experimental study has shown that the structure of a β ' ion proposed earlier is incorrect. Backbone cleavage β' anions have structures R(NH – ) from systems [[RNHCH(X)CONHCH(Y)CO 2 H (or C‐terminal CONH 2 ) – H] – (where R is the rest of the peptide molecule and X and Y represent the α side chains of the individual amino acid residues). METHODS Ab initio calculations were carried out at the CAM‐B3LYP/6‐311++g(d,p) level of theory. CONCLUSIONS The calculations suggest that RNH – ions are formed by S N i cyclisation processes involving either (i) the C‐terminal CO 2 – or C‐terminal [CONH] – as appropriate, or (ii) an enolate ion [‐NHC – (Y)‐] cyclising at the backbone CH of the ‐CH(X)‐ group. Concomitant C–N bond cleavage then liberates an RNH – ion, processes which can occur along the peptide backbone. Copyright © 2012 John Wiley & Sons, Ltd.