Single-conformation and diastereomer specific ultraviolet and infrared spectroscopy of model synthetic foldamers: alpha/beta-peptides.
Resonant two-photon ionization (R2PI), UV hole-burning (UVHB), and resonant ion-dip infrared (RIDIR) spectroscopies have been used to record single-conformation infrared and ultraviolet spectra of three model synthetic foldamers with heterogeneous backbones, alpha/beta-peptides Ac-beta(3)-hAla-L-Phe-NHMe (betaalphaL), Ac-beta(3)-hAla-D-Phe-NHMe (betaalphaD), and Ac-L-Phe-beta(3)-hAla-NHMe (alphabetaL), isolated and cooled in a supersonic expansion. BetaalphaL and betaalphaD are diastereomers, differing only in the configuration of the alpha-amino acid residue; betaalphaL and alphabetaL contain the same residues, but differ in residue order. In all three alpha/beta-peptides the beta(3)-residue has S absolute configuration. UVHB spectroscopy is used to determine that there are six conformers of each molecule and to locate and characterize their S(0)-S(1) transitions in the origin region. RIDIR spectra in the amide NH stretch region reflect the number and strength of intramolecular H-bonds present. Comparison of the RIDIR spectra with scaled, harmonic vibrational frequencies and infrared intensities leads to definite assignments for the conformational families involved. C8/C7(eq) double-ring structures are responsible for three conformers of betaalphaL and four of betaalphaD, including those with the most intense transitions in the R2PI spectra. This preference for C8/C7(eq) double rings appears to be dictated by the C7(eq) ring of the alpha-peptide subunit. Three of the conformers of betaalphaL and betaalphaD form diastereomeric pairs (A/A', C/C', and G/G') that have nearly identical S(0)-S(1) origin positions in the UV and belong to the same conformational family, indicating no significant change associated with the change in chirality of the alpha-peptide subunit. However, betaalphaL favors formation of a C6/C5 conformer over C11, while the reverse preference holds in betaalphaD. Calculations indicate that the selective stabilization of the lowest-energy C11(g(+)) structure in betaalphaD occurs because this structure minimizes steric effects between the beta(2) methylene group and C=O(1). In the alpha/beta-peptide alphabetaL, two conformers dominate the spectrum, one assigned to a C5/C8 bifurcated double-ring, and the other to a C5/C6 double-ring structure. This preference for C5 rings in the alpha/beta-peptide occurs because the C5 ring is further stabilized by an amide NH...pi interaction involving an NH group on the adjacent amide, as it is in the alpha-peptides. Comparison of the NH stretch spectra of C8/C7(eq) structures in betaalphaL with their C7(eq)/C8 counterparts in alphabetaL shows that the central amide NH stretch is shifted to lower frequency by some 50-70 cm(-1) due to cooperative effects associated with the central amide accepting and donating a H-bond to neighboring amide groups. This swaps the ordering of the C8 and C7 NH stretch fundamentals in the two molecules.
Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, Indiana 47907-2084, USA.
William H
WH
James
Esteban E
EE
Baquero
V Alvin
VA
Shubert
Soo Hyuk
SH
Choi
Samuel H
SH
Gellman
Timothy S
TS
Zwier
D008962:Models, Theoretical; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D013055:Spectrophotometry, Infrared / Q000379:methods*; D013056:Spectrophotometry, Ultraviolet / Q000379:methods*; D013237:Stereoisomerism
D010455:Peptides