Esteban E. Baquero

Single-Conformation Ultraviolet and Infrared Spectroscopy of Model Synthetic Foldamers : β-Peptides Ac-β3-hPhe-NHMe and Ac-β3-hTyr-NHMe

The conformational preferences and infrared and ultraviolet spectral signatures of two model beta-peptides, Ac-beta3-hPhe-NHMe (1) and Ac-beta3-hTyr-NHMe (2), have been explored under jet-cooled, isolated molecule conditions. The mass-resolved, resonant two-photon ionization spectra of the two molecules were recorded in the region of the S0-S1 origin of the phenyl or phenol ring substituents, respectively. UV-UV hole-burning spectroscopy was used to determine that two conformations of 1 are present, with the transitions due to conformer A, with S0-S1 origin at 34431 cm(-1), being almost 20 times larger than those due to conformer B, with S0-S1 origin at 34404 cm(-1). Only one conformation of 2 was observed. Resonant ion-dip infrared spectroscopy provided single-conformation infrared spectra in the 3300-3700 cm(-1) region. The spectra of conformer A of both molecules have H-bonded and free amide NH stretch infrared transitions at 3400 and 3488 cm(-1), respectively, while conformer B of 1 possesses bands at 3417 and 3454 cm(-1). For comparison with experiment, full optimizations of all low-lying minima of 1 were carried out at the DFT B3LYP/6-31+G* and RIMP2/aug-cc-pVDZ levels of theory, and single point MP2/6-31+G* calculations at the DFT geometries. On the basis of the comparison with previous studies in solution and the calculated results, conformer A of 1 and 2 were assigned to a C6 conformer, while conformer B of 1 was assigned to a unique C8 structure with a weak intramolecular H-bond. The reasons for the preference for C6 over C8 structures and the presence of only two conformations in the jet-cooled spectrum are discussed in light of the predictions from calculations.

Single-conformation ultraviolet and infrared spectroscopy of model synthetic foldamers: β-peptides Ac-β3-hPhe- β3-hAla-NHMe and Ac-β3-hAla-β3- hPhe-NHMe

The conformational preferences and infrared and ultraviolet spectral signatures of two model beta-peptides, Ac-beta3-hPhe-beta3-hAla-NHMe (1) and Ac-beta3-hAla-beta3-hPhe-NHMe (2), have been explored under jet-cooled, isolated-molecule conditions. The mass-resolved, resonant two-photon ionization spectra of the two molecules were recorded in the region of the S0-S1 origin of the phenyl substituents (37,200-37,800 cm(-1)). UV-UV hole-burning spectroscopy was used to determine the ultraviolet spectral signatures of five conformational isomers of both 1 and 2. Transitions due to two conformers (labeled A and B) dominate the R2PI spectra of each molecule, while the other three are minor conformers (C-E) with transitions a factor of 3-5 smaller. Resonant ion-dip infrared spectroscopy was used to obtain single-conformation infrared spectra in the 3300-3700 cm(-1) region. The infrared spectra showed patterns of NH stretch transitions characteristic of the number and type of intramolecular H-bonds present in the beta-peptide backbone. For comparison with experiment, full optimizations of low-lying minima of both molecules were carried out at DFT B3LYP/6-31+G*, followed by single point MP2/6-31+G* and selected MP2/aug-cc-pVDZ calculations at the DFT optimized geometries. Calculated harmonic vibrational frequencies and infrared intensities for the amide NH stretch vibrations were used to determine the beta-peptide backbone structures for nine of the ten observed conformers. Conformers 1B, 1D, and 2A were assigned to double ring structures containing two C6 H-bonded rings (C6a/C6a), conformers 1A and 2B are C10 single H-bonded rings, conformers 1C and 2D are double ring structures composed of two C8 H-bonded rings (C8/C8), and conformers 1E and 2E are double ring/double acceptor structures in which two NH groups H-bond to the same C=O group, thereby weakening both H-bonds. Both 1E and 2E are tentatively assigned to C6/C8 double ring/double acceptor structures, although C8/C12 structures cannot be ruled out unequivocally. Finally, no firm conformational assignment has been made for conformer 2C whose unusual infrared spectrum contains one very strong H-bond with NH stretch frequency at 3309 cm(-1), a second H-bonded NH stretch fundamental of more typical value (3399 cm(-1)), and a third fundamental at 3440 cm(-1), below that typical of a branched-chain free NH. The single conformation spectra provide characteristic wavenumber ranges for the amide NH stretch fundamentals ascribed to C6 (3378-3415 cm(-1)), C8 (3339-3369 cm(-1)), and C10 (3381-3390 cm(-1)) H-bonded rings.

Laser Spectroscopy of Conformationally Constrained α/β-Peptides: Ac-ACPC-Phe-NHMe and Ac-Phe-ACPC-NHMe†

Single-conformation ultraviolet and infrared spectra have been recorded under the isolated molecule conditions of a supersonic expansion for three conformationally constrained alpha/beta-peptides, Ac-L-Phe-ACPC-NHMe (alpha(L)beta(ACPC)), Ac-ACPC-L-Phe-NHMe (beta(ACPC)alpha(L)), and Ac-ACPC-D-Phe-NHMe (beta(ACPC)alpha(D)). These three molecules are close analogues of the hAla-containing alpha/beta-peptide counterparts Ac-L-Phe-beta(3)-hAla-NHMe, Ac-beta(3)-hAla-L-Phe-NHMe, and Ac-beta(3)-hAla-D-Phe-NHMe, which have been studied recently by James et al. (J. Am. Chem. Soc. 2009, 131, 6574). Incorporation of the beta-amino acid trans-2-aminocyclopentanecarboxylic acid (ACPC) constrains the beta-peptide backbone via the cyclopentane ring, producing clear changes in the conformational preferences relative to the unconstrained analogues. The conformational control is manifested most obviously in the complete absence of C6 H-bonded rings, which were dominant in the unconstrained alpha/beta-peptides. The most stable C6 ring structure (C6a) in the absence of the ACPC ring cannot be formed in its presence, while a secondary C6 ring (C6b) has its energy destabilized by approximately 20 kJ/mol. In alpha(L)beta(ACPC), the preference for C5 structures in the N-terminal position, combined with the strong preference for C8 structures in the beta-peptide subunit, leads to the observation of two C5/C8 bifurcated double ring conformers. Both C8/C7 sequential double rings and C11 single rings are observed in beta(ACPC)alpha(L) and beta(ACPC)alpha(D). Here, the ACPC ring selectively stabilizes the C8a ring over other possible C8 structures. Finally, the combined evidence from IR and UV spectra lead to tentative assignments for diastereomeric pairs, exhibiting small but understandable shifts in the IR and UV spectra induced by the change in chirality at the alpha-peptide chiral center.

Entropy-driven population distributions in a prototypical molecule with two flexible side chains: O-(2-acetamidoethyl)-N-acetyltyramine

Resonant two-photon ionization (R2PI), resonant ion-dip infrared (RIDIR), and UV-UV hole-burning spectroscopies have been employed to obtain conformation-specific infrared and ultraviolet spectra under supersonic expansion conditions for O-(2-acetamidoethyl)-N-acetyltyramine (OANAT), a doubly substituted aromatic in which amide-containing alkyl and alkoxy side chains are located in para positions on a phenyl ring. For comparison, three single-chain analogs were also studied: (i) N-phenethyl-acetamide (NPEA), (ii) N-(p-methoxyphenethyl-acetamide) (NMPEA), and (iii) N-(2-phenoxyethyl)-acetamide (NPOEA). Six conformations of OANAT have been resolved, with S(0)-S(1) origins ranging from 34,536 to 35,711 cm(-1), denoted A-F, respectively. RIDIR spectra show that conformers A-C each possess an intense, broadened amide NH stretch fundamental shifted below 3400 cm(-1), indicative of the presence of an interchain H bond, while conformers D-F have both amide NH stretch fundamentals in the 3480-3495 cm(-1) region, consistent with independent-chain structures with two free NH groups. NPEA has a single conformer with S(0)-S(1) origin at 37,618 cm(-1). NMPEA has three conformers, two that dominate the R2P1 spectrum, with origin transitions between 35,580 and 35,632 cm(-1). Four conformations, one dominate and three minor, of NPOEA have been resolved with origins between 35,654 and 36,423 cm(-1). To aid the making of conformational assignments, the geometries of low-lying structures of all four molecules have been optimized and the associated harmonic vibrational frequencies calculated using density functional theory (DFT) and RIMP2 methods. The S(0)-S(1) adiabatic excitation energies have been calculated using the RICC2 method and vertical excitation energies using single-point time-dependent DFT. The sensitivity of the S(0)-S(1) energy separation in OANAT and NPOEA primarily arises from different orientations of the chain attached to the phenoxy group. Using the results of the single-chain analogs, tentative assignments have been made for the observed conformers of OANAT. The RIMP2 calculations predict that interchain H-bonded conformers of OANAT are 25-30 kJ/mol more stable than the extended-chain structures. However, the free energies of the interchain H-bonded and extended structures calculated at the preexpansion temperature (450 K) differ by less than 10 kJ/mol, and the number of extended structures far outweighs the number of H-bonded conformers. This entropy-driven effect explains the presence of the independent-chain conformers in the expansion, and cautions future studies that rely solely on relative energies of conformers in considering possible assignments.

Single Conformation Spectroscopy of a Flexible Bichromophore : 3-(4-Hydroxyphenyl)-N-benzylpropionamide

Resonant two-photon ionization (R2PI), UV hole-burning (UVHB), and resonant ion-dip infrared (RIDIR) spectroscopy have been used to study the single-conformation infrared and ultraviolet spectroscopy of 3-(4-hydroxyphenyl)-N-benzylpropionamide (HNBPA, HOC6H5CH2CH2(CO)NHCH2C6H5) cooled in a supersonic expansion. UVHB determines the presence of three conformers, two of which dominate the spectrum. RIDIR spectra in the OH stretch (3600-3700 cm(-1)), amide NH stretch (3450-3500 cm(-1)), and CO stretch (1700-1750 cm(-1)) regions reveal the presence of small shifts in these fundamentals that are characteristic of the folding of the flexible chain and the ring-ring and ring-chain interactions. On the basis of a comparison of the experimental frequency shifts with calculations, the two major experimentally observed conformers are assigned to two folded structures in which the two aromatic rings are (nominally) face-to-face and perpendicular to one another. The perpendicular structure has a transition assignable to the S0-S2 origin, while the face-to-face structure does not, consistent with a faster nonradiative process in the latter case. The calculated structures and vibrational frequencies are quite sensitive to the level of theory due to the flexibility of the interconnecting chain and the importance of dispersive interactions between the two aromatic rings.

Direct measurement of the energy thresholds to conformational isomerization. II. 3-indole-propionic acid and its water-containing complex.

The methods of stimulated emission pumping-hole-filling spectroscopy (SEP-HFS) and population transfer spectroscopy (SEP-PTS) were used to place direct experimental bounds on the energetic barriers to conformational isomerization in 3-indole-propionic acid (IPA) and its water-containing complex. By contrast with tryptamine (Paper I), IPA has only two conformations with significant population in them. The structures of the two conformers are known from previous work [P. M. Felker, J. Phys. Chem. 96, 7844 (1992)]. The energy thresholds for A-->B and B-->A isomerizations are placed at 854 and 754 cm(-1), respectively. Lower bounds on the isomerization barrier in the two directions are determined from the last transition not observed in the SEP-PT spectra. These are placed at 800 and 644 cm(-1) for A-->B and B-->A, respectively. The combined results place bounds on the relative energies of the A and B minima, with E(B)-E(A)=46-210 cm(-1). Like the IPA monomer, the IPA-H2O complex forms two conformational isomers. Both these isomers incorporate the water molecule as a bridge between the carbonyl and OH groups of the carboxylic acid. Previous rotational coherence measurements (L. L. Connell, Ph.D. thesis, UCLA, 1991) have determined that these complexes retain the same IPA conformational structure as the monomers. SEP-PTS and SEP-HFS were carried out on the IPA-H2O complexes. It was demonstrated that it is possible to use SEP to drive conformational isomerization between the two conformational isomers of IPA-H2O. Bounds on the energy barriers to conformational isomerization are not effected greatly by the presence of the water molecule, with Ebarrier(A-->B)=771-830 cm(-1) and Ebarrier(B-->A)=583-750 cm(-1). This is a simple consequence of the fact that the barrier is an intramolecular barrier, and the water molecule is held fixed in the COOH pocket, where it interacts with the ring only peripherally during the isomerization process. Finally, changes in the SEP-PT spectral intensity in transitions near the top of the barrier to isomerization as a function of the position of SEP excitation relative to the pulsed valve exit provide some insight to the competition between vibrational relaxation and isomerization in a molecule the size of IPA.