13C n.m.r. study of conformational equilibria in solutions of methyl N-benzoyl-l-leucyl-l-histidinate monohydrate

¹³C n.m.r. spectra for the title compound are reported in CDCl₃ and also in pure and acidified DMSO solutions. In all cases, cis/trans isomerization about the amide bond occurs. For the cis isomers, severe steric compression shifts the ortho phenyl and leucyl β-CH₂ resonances to higher field. In CDCl₃ solution, two imidazole conformations are present. In one, the imidazole group is freely rotating about the β-CH₂-C(ring) bond, whilst the nitrogen-bound proton participates in a dynamic tautomeric equilibrium, rapid on the n.m.r. time-scale, between the two ring nitrogen atoms. In the other, the imidazole ring is protonated at N1 and held in a relatively rigid conformation by hydrogen-bonding between N3, the water molecule, and the amide carbonyl group oxygen atom. The major imidazole species present in DMSO solution is the N1-protonated tautomer. Small amounts of the N3 tautomer are also present, but in this solvent proton exchange between the two sites is slow on the n.m.r. time-scale. In acidified DMSO, both nitrogen atoms are protonated.