Carbonyl-17O n.m.r. of amino acid and peptide carboxamide and methyl ester derivatives.

Specific carbonyl enrichment with 17O of amino acid OMe esters by up to 10(3) times over natural abundance was affected by treating [17O]-alpha-COOH amino acids with SOCl2 in MeOH. Carbonyl-[17O]-Gly-NH2, Gly-NHCH3 and Gly-N(CH3)2 were obtained from [17O]-Gly-OMe by (methyl)aminolysis with NH3, CH3NH2 and (CH3)2NH gases respectively. Peptide [17O]-carboxamides were prepared by (methyl)aminolysis of Z-Pro-Leu-[17O]-Gly-OMe followed by catalytic hydrogenation to remove the Z group. 17O chemical shifts of amino acid and peptide carboxamides in H2O, MeOH, CH3CN and DMSO were 260-324 p.p.m. downfield relative to H2O, depending on alpha-NH2 ionization, substitution on both amino groups and solvent H bonding, primarily to amide oxygen. Introduction of an amide-N methyl group usually caused upfield shifts (approx. -10 p.p.m.), attributed to elimination of one NH bond, while a second N methylation had the opposite effect. Amino acid and peptide OMe ester carbonyl-[17O] resonances appeared 326-359 p.p.m. downfield relative to H2O reflecting on side chain interactions, state of alpha-NH2 ionization and H-bonding with the solvent. Effective rotational correlation times for glycine and peptide carboxamide-[17O], calculated from T2 relaxation data, were of similar magnitude to values derived from solution properties and depended on the molecular weight and solvent viscosity.