Thermodynamic properties and enhancement of diamagnetism in nitrogen doped lutetium hydride synthesized at high pressure.

Nitrogen doped lutetium hydride has drawn global attention in the pursuit of room-temperature superconductivity near ambient pressure and temperature. However, variable synthesis techniques and uncertainty surrounding nitrogen concentration have contributed to extensive debate within the scientific community about this material and its properties. We used a solid-state approach to synthesize nitrogen doped lutetium hydride at high pressure and temperature (HPT) and analyzed the residual starting materials to determine its nitrogen content. High temperature oxide melt solution calorimetry determined the formation enthalpy of LuH1.96N0.02 (LHN) from LuH2 and LuN to be -28.4 ± 11.4 kJ/mol. Magnetic measurements indicated diamagnetism which increased with nitrogen content. Ambient pressure conductivity measurements observed metallic behavior from 5 to 350 K, and the constant and parabolic magnetoresistance changed with increasing temperature. High pressure conductivity measurements revealed that LHN does not exhibit superconductivity up to 26.6 GPa. We compressed LHN in a diamond anvil cell to 13.7 GPa and measured the Raman signal at each step, with no evidence of any phase transition. Despite the absence of superconductivity, a color change from blue to purple to red was observed with increasing pressure. Thus, our findings confirm the thermodynamic stability of LHN, do not support superconductivity, and provide insights into the origins of its diamagnetism.

Tale of Two Polymorphs: Investigating the Structural Differences and Dynamic Relationship between Nirmatrelvir Solid Forms (Paxlovid).

Two anhydrous polymorphs of the novel antiviral medicine nirmatrelvir were discovered during the development of Paxlovid, Pfizer's oral Covid-19 treatment. A comprehensive experimental and computational approach was necessary to distinguish the two closely related polymorphs, herein identified as Forms 1 and 4. This approach paired experimental methods, including powder X-ray diffraction and single-crystal X-ray diffraction, solid-state experimental methods, thermal analysis, solid-state nuclear magnetic resonance and Raman spectroscopy with computational investigations comprising crystal structure prediction, Gibbs free energy calculations, and molecular dynamics simulations of the polymorphic transition. Forms 1 and 4 were ultimately determined to be enantiotropically related polymorphs with Form 1 being the stable form above the transition temperature of ∼17 °C and designated as the nominated form for drug development. The work described in this paper shows the importance of using highly specialized orthogonal approaches to elucidate the subtle differences in structure and properties of similar solid-state forms. This synergistic approach allowed for unprecedented speed in bringing Paxlovid to patients in record time amidst the pandemic.

Accelerated Development of Pharmaceuticals Past, Present, and Future.

This paper reviews the accelerated development of pharmaceuticals, exploring past, present, and future perspectives. It provides a historical overview of early strategies used to expedite development, beginning with initiatives from the 1990s. The work of Gardner and Byrn in accelerated development analysis during this era is highlighted. The narrative progresses to the 2000s, discussing the emergence of PK/PD in accelerating pharmaceutical development. The paper further examines case studies in the accelerated development field, including the INDIGO and Chorus programs. It concludes with an analysis of the current state of the field, referencing the NIPTE conference, which focused on the industrial perspective of accelerated development. Additionally, the paper outlines strategies for the rapid development of Solid Lipid Nanoparticle manufacturing and vaccine production.

Where do the Fluorine Atoms Go in Inorganic-Oxide Fluorinations? A Fluorooxoborate Illustration under Terahertz Light.

The substitution of fluorine atoms for oxygen atoms/hydroxyl groups has emerged as a promising strategy to enhance the physical and chemical properties of oxides/hydroxides in fluorine chemistry. However, distinguishing fluorine from oxygen/hydroxyl in the reaction products poses a significant challenge in existing characterization methods. In this study, we illustrate that terahertz (THz) spectroscopy provides a powerful tool for addressing this challenge. To this end, we investigated two fluorination reactions of boric acid, utilizing MHF2 (M=Na, C(NH2)3) as fluorine reagents. Through an interplay between THz spectroscopy and solid-state density functional theory, we have conclusively demonstrated that fluorine atoms exclusively bind with the sp3-boron but not with the sp2-boron in the reaction products of Na[B(OH)3][B3O3F2(OH)2] (NaBOFH) and [C(NH2)3]2B3O3F4OH (GBF2). Based on this evidence, we have proposed a reaction pathway for the fluorinations under investigation, a process previously hindered due to structural ambiguity. This work represents a step forward in gaining a deeper understanding of the precise structures and reaction mechanisms involved in the fluorination of oxides/hydroxides, illuminated by the insights provided by THz spectroscopy.

Exploring High-Pressure Polymorphism in Carbonic Acid through Direct Synthesis from Carbon Dioxide Clathrate Hydrate.

Carbon dioxide (CO2) is widespread in astrochemically relevant environments, often coexisting with water (H2O) ices and thus triggering a great interest regarding the possible formation of their adducts under various thermodynamic conditions. Amongst them, solid carbonic acid (H2CO3) remains elusive, yet being widely studied. Synthetic routes followed for its production have always been characterised by drastic irradiation on solid ice mixtures or complex procedures on fluid samples (such as laser heating at moderate to high pressures). Here we report about a simpler yet effective synthetic route to obtain two diverse carbonic acid crystal structures from the fast, cold compression of pristine clathrate hydrate samples. The two distinct polymorphs we obtained, differing in the water content, have been deeply characterised via spectroscopic and structural techniques to assess their composition and their astonishing pressure stability, checked up to half a megabar, also highlighting the complex correlations between them so to compile a detailed phase diagram of this system. These results may have a profound impact on the prediction and modelisation of the complex chemistry which characterises many icy bodies of our Solar System.

Paracetamol Inclusion in Mechanically Interlocked Nanocages.

The solid-state synthesis and fast crystallization under kinetic control of poly-[n]-catenanes self-assembled of mechanically interlocked metal organic cages (MOCs) is virtually unexplored. This is in part, due to the lack of suitable crystals for single crystal X-ray diffraction (SC-XRD) analysis which limits their progress as advanced functional materials. Here we report the unprecedented inclusion of paracetamol in the cavities of amorphous materials constituted of M12L8, interlocked MOCs synthesized by mechanochemistry under kinetic control. Full structure determination of a low-crystallinity and low-resolution powders of the M12L8 poly-[n]-catenane including paracetamol has been carried out combining XRD data and Density Functional Theory (DFT) calculations using a multi-step approach. Each M12L8 cage contains six paracetamol guests which is confirmed by thermal analysis and NMR spectroscopy. The paracetamol loading has been also carried out by the instant synthesis method using a saturated paracetamol solution in which TPB and ZnI2 self-assemble immediately (i. e., 1-5 seconds) encapsulating ~7 paracetamol molecules in the M12L8 nanocages under kinetic control also giving a good selectivity. Benzaldehyde has been included in the M12L8 cages using amorphous M12L8 polycatenanes showing that the icosahedral cages can serve as potential nanoreactors for instance to study Henry reactions in the solid-state.