Molecular, Solid-State and Surface Structures of the Conformational Polymorphic Forms of Ritonavir in Relation to their Physicochemical Properties

Purpose Application of multi-scale modelling workflows to characterise polymorphism in ritonavir with regard to its stability, bioavailability and processing. Methods Molecular conformation, polarizability and stability are examined using quantum mechanics (QM). Intermolecular synthons, hydrogen bonding, crystal morphology and surface chemistry are modelled using empirical force fields. Results The form I conformation is more stable and polarized with more efficient intermolecular packing, lower void space and higher density, however its shielded hydroxyl is only a hydrogen bond donor. In contrast, the hydroxyl in the more open but less stable and polarized form II conformation is both a donor and acceptor resulting in stronger hydrogen bonding and a more stable crystal structure but one that is less dense. Both forms have strong 1D networks of hydrogen bonds and the differences in packing energies are partially offset in form II by its conformational deformation energy difference with respect to form I. The lattice energies converge at shorter distances for form I, consistent with its preferential crystallization at high supersaturation. Both forms exhibit a needle/lath-like crystal habit with slower growing hydrophobic side and faster growing hydrophilic capping habit faces with aspect ratios increasing from polar-protic, polar-aprotic and non-polar solvents, respectively. Surface energies are higher for form II than form I and increase with solvent polarity. The higher deformation, lattice and surface energies of form II are consistent with its lower solubility and hence bioavailability. Conclusion Inter-relationship between molecular, solid-state and surface structures of the polymorphic forms of ritonavir are quantified in relation to their physical-chemical properties.

Fluid-like elastic response of superionic NH3 in Uranus and Neptune

Nondipolar magnetic fields exhibited at Uranus and Neptune may be derived from a unique geometry of their icy mantle with a thin convective layer on top of a stratified nonconvective layer. The presence of superionic H2O and NH3 has been thought as an explanation to stabilize such nonconvective regions. However, a lack of experimental data on the physical properties of those superionic phases has prevented the clarification of this matter. Here, our Brillouin measurements for NH3 show a two-stage reduction in longitudinal wave velocity (Vp) by ∼9% and ∼20% relative to the molecular solid in the temperature range of 1,500 K and 2,000 K above 47 GPa. While the first Vp reduction observed at the boundary to the superionic α phase was most likely due to the onset of the hydrogen diffusion, the further one was likely attributed to the transition to another superionic phase, denoted γ phase, exhibiting the higher diffusivity. The reduction rate of Vp in the superionic γ phase, comparable to that of the liquid, implies that this phase elastically behaves almost like a liquid. Our measurements show that superionic NH3 becomes convective and cannot contribute to the internal stratification.

Low-Temperature Chlorite Geothermometry and Related Recent Analytical Advances: A Review

Chlorite, a 2:1:1 phyllosilicate, has all the required attributes to form the basis of a geothermometer: this mineral is ubiquitous in metamorphic, diagenetic, and hydrothermal systems with a broad field of stability and a chemical composition partly dependent on temperature (T) and pressure (P) conditions. These properties led to the development of a multitude of chlorite thermometers, ranging from those based on empirical calibrations (linking T to AlIV content) to thermodynamic or semi-empirical models (linking T to chlorite + quartz + water equilibrium constant). This present study provides an overview of these geothermometers proposed in the literature for low-temperature chlorite (T < 350 °C), specifying the advantages and limitations of each method. Recent analytical developments that allow for circumventing or responding to certain criticisms regarding the low-temperature application of thermometers are also presented. The emphasis is on micrometric and nanometric analysis, highlighting chemical intracrystalline zoning—which can be considered as evidence of a succession of local equilibria justifying a thermometric approach—and mapping ferric iron content. New perspectives in terms of analysis (e.g., Mn redox in Mn-chlorite) and geothermometer (molecular solid-solution model, oxychlorite end-member) are also addressed.

Dynamics of a [2]rotaxane wheel in a crystalline molecular solid

A highly crystalline material comprised of [2]rotaxanes shows large amplitude motion of the interlocked macrocycle as evidenced by variable-temperature (VT) 2H solid-state nuclear magnetic resonance (SSNMR).

Magnetism, dielectrics and ion conduction in two polymorphs of a heteroleptic bis(dithiolato)nickelate molecular solid

A new heteroleptic compound [triethylpropylammonium][Ni(dmit)(mnt)] with two crystal polymorphs, which show different magnetic and dielectric properties, has been reported.