Vibrational Energy Transport in Peptide Helices after Excitation of C−D Modes in Leu-<i>d</i>₁₀

Vibrational energy transport in a short 310-helical peptide is studied by time-resolved femtosecond infrared spectroscopy. The C−D vibrations of decadeuterated leucine incorporated in the helical chain are excited, and the subsequent flow of vibrational energy through the helix is monitored by employing CO probes at various distances from the heat source as local thermometers. The C−D modes are not resonant to the CO modes, neither directly nor through any Fermi resonance, thereby suppressing resonant energy transfer directly along the CO oscillators of the peptide backbone. In contrast to our previous work (J. Phys. Chem. B 2008, 112, 9091), we no longer find any substantial difference in the vibrational energy transport efficiency after high- or low-energy excitation. That is, the heat diffusion constant of (2.0 ± 0.5) Å2 ps−1 is the same as that after depositing vibrational energy through the ultrafast internal conversion of a covalently bound chromophore

Reactive Intermediates in Peptide Synthesis: First Crystal Structures and <i>ab Initio</i> Calculations of 2-Alkoxy-5(4<i>H</i>)-oxazolones from Urethane-Protected Amino Acids

The structures of the 2-alkoxy-5(4H)-oxazolones derived from 2,2,6,6-tetramethyl-4-[(benzyloxycarbonyl)amino]-1-oxypiperidine-4-carboxylic acid and 2,2,6,6-tetramethyl-4-[(9‘-fluorenylmethoxycarbonyl)amino]-1-oxypiperidine-4-carboxylic acid have been solved by single-crystal X-ray diffraction. The overall geometry of their oxazolone ring compares well with that of 2-alkyl-5(4H)-oxazolones. However, the bond distance from C2 to the exocyclic O(2) atom is shorter than expected for a (sp2)C−O single bond, thus suggesting a significant involvement of a O(2) lone pair in the electron delocalization of the CN π-system. These two structures represent the first examples of 2-alkoxy-5(4H)-oxazolones in the crystal state. Ab initio molecular orbital calculations have been performed on (4S)-2-methoxy-4-methyl-5(4H)-oxazolone and (4S)-2,4-dimethyl-5(4H)-oxazolone [as simple models for 2-alkoxy- and 2-alkyl-5(4H)-oxazolones, respectively, derived from the chiral protein amino acid l-Ala] both in the neutral and deprotonated state. The calculated geometries of the 2-alkoxy- and 2-alkyl-5(4H)-oxazolone systems at the MP2/6-31+G(d,p) level agree well with those experimentally determined in the crystal state. The calculated energetics of deprotonation show only modest differences between the two systems. Conversely, a theoretical investigation of the reaction of model oxazolones with ammonia as a nucleophile indicates that for 2-alkoxy-5(4H)-oxazolones the activation energy of the rate-determining step is significantly lower and the overall stabilization energy is larger than for 2-alkyl-5(4H)-oxazolones. The implications of these results with respect to coupling and racemization of urethane-protected amino acids in peptide synthesis are outlined

Benzotriazole Complexes with Amines and Phenol: Cooperativity Mediated by Induction Effects in the Crystal State

Benzotriazole forms complexes of different stoichiometries with amines and phenols. Four of them have been characterized by single-crystal X-ray diffraction. The trends of donor−acceptor hydrogen-bond distances between corresponding molecular entities in the different complexes are related to induction-mediated cooperativity effects

Circular Dichroism Spectrum of a Peptide 3₁₀-Helix

Circular Dichroism Spectrum of a Peptide 310-Heli

Circular Dichroism Spectrum of a Peptide 3₁₀-Helix

Circular Dichroism Spectrum of a Peptide 310-Heli

Reactive Intermediates in Peptide Synthesis: First Crystal Structures and <i>ab Initio</i> Calculations of 2-Alkoxy-5(4<i>H</i>)-oxazolones from Urethane-Protected Amino Acids

The structures of the 2-alkoxy-5(4H)-oxazolones derived from 2,2,6,6-tetramethyl-4-[(benzyloxycarbonyl)amino]-1-oxypiperidine-4-carboxylic acid and 2,2,6,6-tetramethyl-4-[(9‘-fluorenylmethoxycarbonyl)amino]-1-oxypiperidine-4-carboxylic acid have been solved by single-crystal X-ray diffraction. The overall geometry of their oxazolone ring compares well with that of 2-alkyl-5(4H)-oxazolones. However, the bond distance from C2 to the exocyclic O(2) atom is shorter than expected for a (sp2)C−O single bond, thus suggesting a significant involvement of a O(2) lone pair in the electron delocalization of the CN π-system. These two structures represent the first examples of 2-alkoxy-5(4H)-oxazolones in the crystal state. Ab initio molecular orbital calculations have been performed on (4S)-2-methoxy-4-methyl-5(4H)-oxazolone and (4S)-2,4-dimethyl-5(4H)-oxazolone [as simple models for 2-alkoxy- and 2-alkyl-5(4H)-oxazolones, respectively, derived from the chiral protein amino acid l-Ala] both in the neutral and deprotonated state. The calculated geometries of the 2-alkoxy- and 2-alkyl-5(4H)-oxazolone systems at the MP2/6-31+G(d,p) level agree well with those experimentally determined in the crystal state. The calculated energetics of deprotonation show only modest differences between the two systems. Conversely, a theoretical investigation of the reaction of model oxazolones with ammonia as a nucleophile indicates that for 2-alkoxy-5(4H)-oxazolones the activation energy of the rate-determining step is significantly lower and the overall stabilization energy is larger than for 2-alkyl-5(4H)-oxazolones. The implications of these results with respect to coupling and racemization of urethane-protected amino acids in peptide synthesis are outlined

β‑Aminocarbonates in Regioselective and Ring Expansion Reactions

The reactivity of β-aminocarbonates as anisotropic electrophiles has been investigated with several phenols. Products distribution shows that the regioselectivity of the anchimerically driven alkylation reaction depends on the nucleophiles. The results suggest that in the presence of nucleophiles that are also good leaving groups, the reaction takes place under thermodynamic control favoring the attack on the most sterically hindered carbon of the cyclic aziridinium intermediate. Furthermore, when an enantiomerically pure pyrrolidine-based carbonate was used, the reaction with phenols proceeds via a bicyclic aziridinium intermediate leading to the stereoselective synthesis of optically active 3-substituted piperidines via ring expansion reaction. These results were confirmed both by NMR spectroscopy and X-ray diffraction analysis

First Rigid Peptide Foldamers with an Alternating Cis−Trans Amide Sequence. An Oligomeric Building Block for the Construction of New Helices, Large-Ring Cyclic Correlates, and Nanotubes

As part of a program evaluating homochiral and heterochiral amino- and carboxylic acid-substituted γ-lactams as conformationally constrained dipeptide building blocks, we have synthesized by the solid-phase technique and assessed by X-ray diffraction the crystal-state structure of the terminally blocked homotrimer from (2S,4R)-4-amino-5-oxopyrrolidine-2-carboxylic acid, characterized by a unique, alternating cis−trans amide sequence. Using computer modeling, we also showed that the rigid conformation of the trimer can be exploited as a template to construct novel linear oligopeptide foldamers and large-ring cyclic correlates with self-recognizing properties

Flat Peptides

We have synthesized by solution methods the first homopeptide series, pBrBz-(ΔAla)n-OMe (n = 1−6), based on a Cα,β-didehydro-α-amino acid, to determine the preferred conformation of this residue, characterized by an sp2 α-carbon atom and the smallest side chain. To this aim, we have exploited FTIR absorption and 1H NMR techniques in solution and X-ray diffraction in the crystal state. Our investigation shows that a multiple, consecutive, fully extended conformation (2.05-helix) largely predominates for all oligomers in deuteriochloroform solution and occurs in the crystal state for the monomer, dimer, and trimer as well. These peptide molecules are completely flat, including the amino acid side chains, and form planar sheets. This novel peptide structure is stabilized by two types of intramolecular H-bonds, Ni−H···OiC‘i (typical of the 2.05-helix) and Cβi+1−H···OiC‘i (characteristic of ΔAla peptides). The results obtained are compared with those of the oligopeptides based on the related Cβ-substituted, Cα,β-didehydro-α-amino acid residues