STRUCTURAL STUDIES OF CYCLOPEPTIDES - SOLID-STATE AND SOLUTION CONFORMATION OF CYCLO(L-HISTIDYL-D-HISTIDYL)

The solid-state and solution conformation of cyclo(l-His-d-His), carried out by X-ray diffraction analysis and n.m.r. spectroscopy, respectively, is reported. The compound crystallizes in the monoclinic system, space group P21/a with a= 7.726, b= 9.877, c= 8.430 Å. β= 106.8 and Z = 2. The cyclic dipeptide retains in the solid-state a crystallographic center of symmetry: each molecule sitting on it presents a very flat chair conformation with alternating positive and negative conformational angles, whose values are in the range 5–6. The imidazole groups of the side chains are planar, making an angle of 78 with the average plane of the 2.5-piperazinedione ring. These aromatic groups are folded back over the 2.5-piperazinedione ring and they “sandwich” it from opposite sides. Packing is obtained through an H-bonding scheme which involves the N-H donors of the peptide groups as well as the N-H groups of the imidazole moieties. In water solution, at pHs equal to 2.55 and 8, the molecule retains on the average an element of symmetry since only one set of signals is observed for the His protons in the n.m.r. spectrum. From coupling constants the predominant conformation was calculated to be all gauche, in excellent agreement with the solid-state results.