A NUCLEAR MAGNETIC RESONANCE STUDY OF ANHYDRIDES OF ARGININOSUCCINIC ACID AND RELATED GUANIDINO COMPOUNDS

Argininosuccinic acid forms two cyclic anhydrides. Inconsistencies between the chemical and physical properties of anhydrides I and II and the structures previously considered for these compounds have been clarified by a study of the proton magnetic resonance spectra of argininosuccinic acid, the two anhydrides, and other model compounds (guanidinoacetic acid, guanidinosuccinic acid, their respective anhydrides and creatinine). The resonances of the carbon-bound protons observed in D2O and also in trifluoroacetic acid have been assigned. Changes in the resonance positions of certain protons of the guanidino acids as compared with their respective anhydrides served to indicate the positions involved in cyclization. The results show that anhydride I contains a fivemembered ring structure in which the α-carboxyl group of the succinyl moiety is in anhydride linkage with the terminal nitrogen of the ornithine moiety. Anhydride II also contains a five-membered ring structure, the same carbonyl group being linked to the imino nitrogen of the amidine group. The resonances of the nitrogen-bound protons (in trifluoroacetic acid solution) suggest that in several of the guanidino acids, protonation may occur on the CNC nitrogen as well as on the imino nitrogen. The spectra for the guanidino anhydrides strongly support a five-membered ring structure for guanidinosuccinic anhydride similar to that of anhydride II. In these two structures and in the structures assigned to guanidinoacetic anhydride and to creatinine, the double bond is located in the cyclic configuration, conjugate with the carbonyl oxygen. Anhydride I is exceptional in that the double bond is nonconjugate. In accord with this, anhydride II and the model anhydrides are apparently protonated on the carbonyl oxygen in trifluoroacetic acid while anhydride I is protonated on nitrogen. The physical and chemical properties of these compounds are discussed and shown to be in harmony with these conclusions, particularly with the location of the anhydride linkages, with the protonation in acid solution and with the conjugate or nonconjugate assignments of the double bonds. © 1969, American Chemical Society. All rights reserved.