A critical role is traditionally assigned to transition states (TSs) and minimum energy pathways, or intrinsic reaction coordinates (IRCs), in interpreting organic reactivity. Such an interpretation, however, ignores vibrational and kinetic energy effects of finite temperature. Recently it has been shown that reactions do not necessarily follow the intermediates along the IRC. We report here molecular dynamics (MD) simulations that show that dynamics effects may alter chemical reactions even more. In the heterolysis rearrangement of protonated pinacolyl alcohol Me3C-CHMe-OH2+ (Me, methyl), the MD pathway involves a stepwise route with C-O bond cleavage followed by methyl group migration, whereas the IRC pathway suggests a concerted mechanism. Dynamics effects may lead to new interpretations of organic reactivity.

The interatomic distances in the crystalline specimen of 13C,15N doubly labeled peptides [1-13C]N-acetyl-Pro-[15N]Gly-Phe (I), N-acetyl-[1-13C]Pro-Gly-[15N]Phe (II), and [1-13C]N-acetyl-Pro-Gly-[15N]Phe (III) evaluated from rotational echo double resonance (REDOR) data were compared with those from X-ray diffraction studies and justify our novel approach. The minimization of B1 inhomogeneity was critical to obtain accurate distances, which were achieved by confinement of the samples in the central portion (50% of the total filling volume of the rotor). The effect of the finite length of the π pulse was found to be negligible as long as the pulse length is less than 10% of the rotor cycle. The 13C···15N distances obtained from 13C REDOR were thus 3.24 ± 0.05, 3.43 ± 0.05, and 4.07 ± 0.05 Å for I, II, and III, respectively. The REDOR-derived conformation of this peptide was β-turn type I, consistent with our X-ray diffraction study (orthorhombic crystal). The maximum deviation of the distances determined by NMR and X-ray diffraction is 0.08 Å despite the complete neglect of the dipolar interactions with the labeled nuclei of neighboring molecules and natural abundance nuclei. The precision and accuracy given by 13C REDOR experiments are on the order of ±0.05 Å. Distinction between the two types of β-turn forms including the β-turn type II found in the monoclinic crystal of this peptide whose interatomic distances are different by about 0.57 Å is made possible only by the very accurate REDOR measurement. Finally, we found that the three-dimensional structure of this peptide was well reproduced by a molecular dynamics simulation by taking into account all the intermolecular interactions in the crystals.

We have determined the three-dimensional structure of [13C,15N]-labeled Leu-enkephalin (Tyr-Gly-Gly-Phe-Leu) dihydrate (crystallized from aqueous methanol) on the basis of six sets of accurately determined 13C···15N interatomic distances by rotational echo double resonance (REDOR) and some additional constraints from 13C chemical shifts. This compound has not yet been refined by X-ray diffraction. Six kinds of [13C,15N]-doubly-labeled samples, in which the doubly-labeled positions are four-bonds apart (four samples) and five-bonds apart (two samples), were chemically synthesized. These labeled peptides (100%) and an isotopically diluted one with unlabeled samples (60% or 30%) were crystallized from aqueous methanol solution. 13C or 15N chemical shifts were carefully evaluated prior to and after every REDOR experiment in order to check that the crystalline polymorphs under consideration were not modified either by loss of or by freezing of motion of solvent molecules in the crystals. Accurate and precise interatomic distances (±0.10 Å) were obtained from REDOR factors of infinite dilution, which were extrapolated from the data of 100% and 30% isotopically diluted samples to eliminate dipolar contributions from the labeled nuclei of neighboring molecules in the crystals. These distance data were converted to a possible set of local torsion angles (φ i and ψ i ) in a peptide unit of the respective amino acid residue of interest using standard bond lengths and angles in a sequential manner. It turned out that a unique set of the torsion angles corresponding to the most appropriate three-dimensional structure was determined with reference to some additional constraints from the conformation-dependent displacements of 13C chemical shifts of certain peptide units. The three-dimensional structure thus obtained was finally subject to a calculation for energy minimization in order to ensure that the conformation obtained was at least at one of local minima. Finally, the biological consequence of the peptide structure thus determined is discussed.

Polarized Raman scattering measurements have been made of a single crystal of L‐tyrosine by the use of a Raman microscope with the 488.0‐nm exciting beam from an argon ion laser. The L‐tyrosine crystal belongs to the space group P212121 (orthorhombic), and Raman scattering intensities corresponding to the aa, bb, cc, ab and ac components of the crystal Raman tensor have been determined for each prominent Raman band. A similar set of measurements has been made of L‐tyrosine‐d4, in which four hydrogen atoms on the benzene ring are replaced by deuterium atoms. The effects of NH3 → ND3 and OH → OD on the Raman spectrum have also been examined. In addition, depolarization ratios of some bands of L‐tyrosine in aqueous solutions of pH 13 and pH 1 were examined. For comparison with these experimental results, on the other hand, ab initio molecular orbital calculations have been made of the normal modes of vibration and their associated polarizability oscillations of the L‐tyrosine molecule. On the basis of these experimental data and by referring to the results of the calculations, discussions have been presented on the Raman tensors associated to some Raman bands, including those at 829 cm−1 (benzene ring breathing), 642 cm−1 (benzene ring deformation), and 432 cm−1 (Cα‐Cβ‐Cγ bending). © 1998 John Wiley & Sons, Inc. Biospectroscopy 4: 61–71, 1998

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