Impact of chirality on the amorphous state of conglomerate forming systems: a case study of N-acetyl-α-methylbenzylamine.

The present work aims at addressing the issue of molecular handedness in glassy and liquid states and its impact on heterogeneous equilibrium. For this purpose, we evaluated the glass forming ability (GFA), crystallization propensity, molecular mobility and hydrogen bonding structure of a chiral conglomerate forming system, N-acetyl-α-methylbenzylamine (Nac-MBA), at various enantiomeric excesses (ees) using experimental and computational techniques. We revealed that the rich relaxational landscape (Debye (D), α, ßJG and ϒ) and the temperature dependence of the time scale of each process were insensitive to chirality. The most remarkable impact of chirality was expressed on the GFA and the recrystallization of heterochiral arrangements. In fact the GFA increases with decreasing ee, while the crystallization propensity increases with increasing ee. The counter enantiomer acted as a disruptor of crystallization and favored the glass formation upon cooling. The molecular dynamics simulation (MDS) results on the architecture of chiral sequences showed that homochiral sequences were more favorable when compared to heterochiral ones in the liquid state. However, this predisposition to form homochiral sequences in the liquid state was not the precursor of the future crystalline structure, since the liquid or the glassy system recrystallizes as heterochiral sequences. As per our understanding the crystallization was mostly controlled by the mean free migration path of an enantiomer to build homochiral or heterochiral sequences. In the present case, it seems that the mean free migration path achieved by an enantiomer for heterochiral sequences is shorter compared to homochiral arrangements in such a way that the crystallization of the metastable racemic compound is kinetically more favorable.

Molecular mobility of amorphous N-acetyl-α-methylbenzylamine and Debye relaxation evidenced by dielectric relaxation spectroscopy and molecular dynamics simulations.

The present work focusses on the molecular mobility characterization of amorphous N-acetyl-α-methylbenzylamine (Nac-MBA) by Broadband Dielectric Relaxation Spectroscopy (DRS) coupled with Fast Scanning Calorimetry (FSC) and Molecular Dynamics (MD) simulations covering over 12 decades in the frequency range. This study reveals another example of a secondary amide that shows a very intense Debye-like contribution (almost 90% of the global dielectric intensity) in addition to the structural α-relaxation and secondary Johari-Goldstein ß-relaxation. The D- and α-relaxations are separated by about one decade (in frequency) and their relaxation times follow a near parallel temperature evolution (Vogel-Fulcher-Tammann-Hesse). The micro-structure of Nac-MBA has been investigated from MD simulations. It is shown that the intense Debye-like process emanates from the formation of linear intermolecular H-bonding aggregates (precursors of the crystalline structure) generating super-dipole moments.

Impact of chirality on the Glass Forming Ability and the crystallization from the amorphous state of 5-ethyl-5-methylhydantoin, a chiral poor glass former.

The investigation of the glassy state of 5-ethyl-5-methylhydantoin (i.e. 12H, a chiral Active Pharmaceutical Ingredient) was attempted by Differential Scanning Calorimetry (DSC) and Fast Scanning Calorimetry (FSC). This compound exhibits a high crystallization propensity for every enantiomeric composition. Nevertheless, glassy states of pure enantiomer or mixtures between enantiomers were successfully reached by FSC at cooling rates of: 1000 °C/s and 300 °C/s respectively, even though limitations on the sampling reproducibility were evidenced due to FSC sample size. The Glass Forming Ability (GFA) was proven to increase with the counter-enantiomer content. From the glassy state, pure enantiomer displayed a more pronounced crystallogenic character (with a crystallization occurring 36 °C below Tg during ageing) than that of the mixture between enantiomers. Ageing of amorphous 12H promotes a strong nucleation behavior in both samples but enantiopure 12H crystallizes upon ageing while scalemic 12H evolves towards the metastable equilibrium. Finally, potential new phase equilibria (previously not reported) in the enantiomeric phase diagram could have been highlighted by FSC by recrystallization from the amorphous state.

Correlated and cooperative motions in segmental relaxation: Influence of constitutive unit weight and intermolecular interactions.

This work clarifies the notion of correlated and cooperative motions appearing during the α-relaxation process through the role of the molecular weight of the constitutive units and of the interchain dipolar interactions. By studying amorphous copolymers of poly(ethylene-co-vinyl acetate) with different vinyl acetate contents, we show that the correlated motions are not sensitive to the interchain dipolar interactions, in contrast to the cooperative motions, which increase with a strengthening of the intermolecular interactions for this sample family. Concerning the influence of the molecular weight m_{0}, the notion of "correlated motions" seems to be equivalent to the notion of "cooperative motions" only for low m_{0} systems.