Proline Zwitterion Dynamics in Solution, Glass, and Crystalline State

Abstract

Raman and Raman optical activity spectra of L- and D-proline zwitterionic (PROZW) forms were recorded for H(2)O and D(2)O solutions in a wide frequency range and analyzed with respect to the motion of the proline ring and rotation of the carbonyl group. The solution spectra were additionally compared to Raman scattering of glass and crystalline powder proline. Solution and glass spectral band broadenings are similar and reveal information about the extent of internal molecular motion. Two distinct but equally populated flexible forms were found in the glass and the solution. The equal population is consistent with NMR data, temperature, and concentration dependencies. The molecular flexibility is reduced significantly in the crystal, however, where only one conformer is present. Consequently, the crystal bands are narrow and exhibit minor frequency shifts. The spectra were interpreted with the aid of density functional theory computations involving both continuum and explicit solvent. A two-dimensional potential energy surface pertaining to the five-member ring puckering coordinates was constructed and used for dynamical averaging of spectral properties. Comparison of the computed and experimental bandwidths suggests that the puckering is strongly correlated with the carbonyl rotation. An averaging over these two motions produces similar results. The interpretation of the Raman experiments with the aid of the simulation techniques also indicates that the environment modulates properties of the hydrophobic part of the molecule indirectly by interacting with the ionic group. Such behavior may be important for the reactivity and biological activity of proline-containing peptides and proteins.

Molecular dynamics with restrictions derived from optical spectra

“…7,11,12 By comparison of the computed and experimental Raman and ROA spectral shapes not only the equilibrium structure but also an important knowledge about molecular flexibility and multiconformational states could be acquired. [13][14][15] Even more objective information can be gained from a numerical spectra decomposition, 16 as a complement to the traditional visual comparison of the theoretical spectra with the experiment.…”

Comparison of Quantitative Conformer Analyses by Nuclear Magnetic Resonance and Raman Optical Activity Spectra for Model Dipeptides

“…11 On the other hand, flexible and polar molecules are particularly difficult to model. 9,10,[12][13][14][15] However, a detailed spectral analysis as outlined in the present paper yields conformer ratios of model dipeptides that fit benchmark NMR data very well indeed.…”

“…13 The region below ∼800 cm -1 is severely affected by flexibility of the molecules, such as rotation of the functional NH 3 , CH 3 , and CO 2 groups, 9 and perhaps also by oscillations of the backbone parameters ( Figure 4). Within the range of ∼1550-1700 cm -1 the signal is considerably broadened by an interaction of the polar NH x + and CO 2-groups with the solvent.…”

“…[50][51][52] The approximately equally populated "north" and "south" conformers were predicted on simple models; the detailed conformer distribution, however, varies according to the attached residues. 39,[53][54][55] By ROA, an equal conformer ratio was predicted for polyproline 10 and proline zwitterion, 13 based particularly on the ring deformation (observed at ∼850-1000 cm -1 ) and C-H bending (∼1300-1400 cm -1 ) proline modes. The present results are thus in agreement with the previous findings but expand them about the more quantitative information of the conformer ratios.…”

“…The IR spectra can be found in the Supporting Information and were used for an additional control of the transition assignments. The 1 H and 13 C NMR spectra of all four peptides were measured on a Bruker AVANCE 600 instrument ( 1 H at 600.13 MHz; 13 C at 150.92 MHz) in D 2 O with dioxane as internal reference (σ H ) 3.75; σ C ) 69.3) at three temperatures (278, 300, and 322 K).…”