Solvent-dependent conformations of a cyclic tetrapeptide

The conformations of cyclo(-γ-Abu-L-Pro-)2 in several solvents have been characterized by means of 1H and 13C NMR, CD and IR spectra. CD results indicate that the change in polarity of the solvent induces an inversion of the conformation, revealed by the disappearance of the positive peak near 210 nm and then by the gradual appearance of a negative trough near 210 nm having opposite chirality. The data of NMR spectroscopy in CDCl3, CD2Cl2, CD3OH, (CD3)2SO and D2O indicate that cyclo(-γ-Abu-L-Pro-)2 has a C2 symmetric conformation consisting of the cis–trans–cis–trans peptide bond backbone (with two cis γ-Abu-L-Pro bonds) in all solvents, and that the change of polarity of solvent induces the inversion of cis and trans conformations around the Pro αC–CO single bond. (The trans and cis regions describe the rotational states of the Pro αC–CO single bond in which the Pro αC–H is trans and cis to the direction of the Pro carbonyl oxygen atom, respectively). The cis–trans–cis–trans conformation containing the two cis Pro αC–CO bonds in CDCl3 and CD2Cl2 is stabilized by the presence of seven-membered rings consisting of intramolecular hydrogen bonds between γNH and αCO in the γ-Abu residue.