Differentiation and quantitation of isomeric dipeptides by low-energy dissociation of copper(II)-bound complexes

Application of the kinetic method based on the dissociation of transition m etal centered cluster ions is extended from chiral analysis (Tao, W. A.; Zh ang, D.; Nikolaev, E. N.; Cooks, R. G. J. Am. Chem. Soc. 2000, 122, 10598) to quantitative analysis of isomeric mixtures, including those with Leu/Ile substitutions. Copper(II)-bound complexes of pairs of peptide isomers are generated by electrospray ionization mass spectrometry and the trimeric com plex [Cu-II(ref)(2)(A) - H](+) (analyte A, a mixture of isomeric peptides; reference compound ref, usually a peptide) is caused to undergo collisional dissociation. Competitive loss of the neutral reference compound or the ne utral analyte yields two ionic products and the ratio of rates of the two c ompetitive dissociations, viz. the product ion branching ratio R is shown t o depend strongly on the regiochemistry of the analyte in the precursor [Cu -II(A)(ref)(2) - H](+) complex ion. Calibration curves are constructed by r elating the branching ratio measured by the kinetic method, to the isomeric composition of the mixture to allow rapid quantitative isomer analysis. (J Am Soc Mass Spectrom 2001, 12, 490-496) (C) 2001 American Society for Mass Spectrometry.