RYOJI KUSAKA, Department of Chemistry, Purdue University, West Lafayette, IN 47907, and Department of Chemistry, Graduate School of Science, Hiroshima University, Higashi-Hiroshima, 739-8526, Japan; DI ZHANG, PATRICK WALSH, JOSEPH GORD AND TIMOTHY S. ZWIER, Department of Chemistry, Purdue University, West Lafayette, IN 47907; BRIAN F. FISHER AND SAMUEL H. GELLMAN, Department of Chemistry, University of Wisconsin, Madison, WI 53706.

Synthetic foldamers composed of heterogeneous backbones offer constructs for building unique secondary structures. alpha/ gamma-peptides juxtapose the alpha-amino acid sub-units typical of proteins with gamma-amino sub-units. Gellman and co-workers have developed efficient syntheses of alpha/ gamma-peptides that incorporate a cyclohexyl ring constraint at the gamma3- gamma4 bond to limit backbone torsional mobility, and found that they form helices held together by C=O( i ) cdot cdot cdotH-N( i +3) H-bonds composing 12-membered rings both in solution and in crystalline form. This talk will present a detailed study of the single-conformation double-resonance UV and IR spectroscopy of Ac-Ala- gammaACHC-NH-benzyl ( alpha gamma) and Ac- gammaACHC-Ala-NH-benzyl ( gamma alpha) capped peptides, in which gammaACHC residues are constrained by a cis cyclohexyl ring at gamma3- gamma4 bond with an ethyl group at gamma2 position. The two alpha gamma and gamma alpha peptides have three amide groups that are the minimum length necessary to form a 12-membered H-bond. Conformational assignments were made using the NH stretch, C=O stretch (amide I), and NH bend (amide II) regions of the IR spectrum with the aid of DFT calculations. The double-resonance UV and IR spectroscopy uncovered the presence of 6 conformers for alpha gamma and 4 conformers for gamma alpha. In the two peptides, three of ten structures incorporate bifurcated double rings made of 12-membered C=O(1) cdot cdot cdotH-N(3) ring, which is the first stage of the 12-helix, and 7- or 9-membered C=O(1) cdot cdot cdotH-N(2) ring via nearest-neighbor interaction. The other seven structures are constructed based on 5-, 7-, and 9-membered nearest-neighbor H-bonds. The similarities and differences between structures observed for the two two alpha gamma and gamma alpha peptides will be discussed.