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.

A Comparative Study of a High-Pressure Polymorph of I2O5 and its Ambient-Pressure Modification.

A hitherto unknown modification of I2O5 was obtained from high-pressure/high-temperature syntheses in a Walker-type multianvil device at 8 GPa and 250 °C. HP-I2O5 crystallizes in the monoclinic crystal system in the space group P21/c (no. 14) with the unit cell parameters a = 12.0612(3) Å, b = 4.8613(2) Å, c = 6.9585(2) Å, ß = 100.10(1)° (at 173 K), and four formula units per cell. The single-crystal structure data are accompanied by powder X-ray diffraction data at ambient and elevated temperatures. Furthermore, DFT calculations were carried out to investigate the phase transition between the ambient-pressure polymorph NP-I2O5 to the newly synthesized high-pressure phase.

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.

The Role of Inverted Ligand Field in the Electronic Structure and Reactivity of Octahedral Formal Platinum (IV) Complexes.

Platinum complexes are ubiquitous in chemistry and largely used as catalysts or as precursors in drug chemistry, thus a deep knowledge of their electronic properties may help in planning new synthetic strategies or exploring new potential applications. Herein, the electronic structure of many octahedral platinum complexes is drastically revised especially when they feature electronegative elements such as halogens and chalcogens. The investigation revealed that in most cases the five d platinum orbitals are invariably full, thus the empty antibonding orbitals, usually localized on the metal, are mainly centered on the ligands, suggesting a questionable assignment of formal oxidation state IV. The analysis supports the occurrence of the inverted ligand field theory in all cases with the only exceptions of the Pt-F and Pt-O bonding. The trends for the molecular complexes are mirrored also by the density of states plots of extended structures featuring octahedral platinum moieties in association with chalcogens atoms. Finally, the oxidative addition of a Se-Cl linkage to a square platinum complex to achieve an octahedral moiety has been revised in the framework of the inverted ligand field.

In Situ X-ray Diffraction Studies on the Reduction of V2 O5 and WO3 by Using Hydrogen.

The reduction of metal oxides with hydrogen is widely used for the production of fine chemicals and metals both on the laboratory and industry scale. In situ methods can help to elucidate reaction pathways and to gain control over such synthesis reactions. In this study, the reduction of WO3 and V2 O5 with hydrogen was investigated by in situ X-ray powder diffraction with regard to intermediates and the influence of heating rates and hydrogen flow rates. Mixtures of V4 O9 , V6 O13 and VO2 in two modifications were identified as intermediates on the way to phase-pure V2 O3 . None of the intermediates occurs in a single phase and therefore cannot be prepared this way. In contrast, the intermediates of the WO3 reduction, H0.23 WO3 and W10 O29 , appear consecutively and can be isolated. For both reactions, the heating and flow rates have little influence on the formation of intermediates.

Cocrystal Synthesis through Crystal Structure Prediction.

Crystal structure prediction (CSP) is an invaluable tool in the pharmaceutical industry because it allows to predict all the possible crystalline solid forms of small-molecule active pharmaceutical ingredients. We have used a CSP-based cocrystal prediction method to rank ten potential cocrystal coformers by the energy of the cocrystallization reaction with an antiviral drug candidate, MK-8876, and a triol process intermediate, 2-ethynylglyclerol. For MK-8876, the CSP-based cocrystal prediction was performed retrospectively and successfully predicted the maleic acid cocrystal as the most likely cocrystal to be observed. The triol is known to form two different cocrystals with 1,4-diazabicyclo[2.2.2]octane (DABCO), but a larger solid form landscape was desired. CSP-based cocrystal screening predicted the triol-DABCO cocrystal as rank one, while a triol-l-proline cocrystal was predicted as rank two. Computational finite-temperature corrections enabled determination of relative crystallization propensities of the triol-DABCO cocrystals with different stoichiometries and prediction of the triol-l-proline polymorphs in the free-energy landscape. The triol-l-proline cocrystal was obtained during subsequent targeted cocrystallization experiments and was found to exhibit an improved melting point and deliquescence behavior over the triol-free acid, which could be considered as an alternative solid form in the synthesis of islatravir.

On the Importance of Halogen and Chalcogen Bonds in the Solid State of Nucleic Acids: A Combined Crystallographic and Theoretical Perspective.

In this work, intra- and intermolecular halogen and chalcogen bonds (HlgBs and ChBs, respectively) present in the solid state of nucleic acids (NAs) have been studied at the RI-MP2/def2-TZVP level of theory. To achieve this, a Protein Data Bank (PDB) survey was carried out, revealing a series of structures in which Br/I or S/Se/Te atoms belonging to nucleobases or pentose rings were involved in noncovalent interactions (NCIs) with electron-rich species. The energetics and directionality of these NCIs were rationalized through a computational study, which included the use of Molecular Electrostatic Potential (MEP) surfaces, the Quantum Theory of Atoms in Molecules (QTAIM), and Non Covalent Interaction plot (NCIplot) and Natural Bonding Orbital (NBO) techniques.

The Telluraboranes closo-TeB5 Cl5 and closo-TeB11 Cl11 with Exceptionally Long Body Diagonals: Synthetic and Bonding Motifs for Innovative Octahedral and Icosahedral Geometries.

Six-vertex closo-TeB5 Cl5 (1) and twelve-vertex closo-TeB11 Cl11 (2) telluraboranes have been prepared via co-pyrolysis of B2 Cl4 with TeCl4 in vacuo at temperatures between 360 °C and 400 °C. Both compounds are sublimable, off-white solids, and they have been characterized by one- and two-dimensional 11 B NMR and high-resolution mass spectroscopy. Both ab initio/GIAO/NMR and DFT/ZORA/NMR computations support octahedral and icosahedral geometries for 1 and 2, respectively, as expected due to their closo-electron counts. The octahedral structure of 1 has been confirmed by single-crystal X-ray diffraction on an incommensurately modulated crystal. The corresponding bonding properties have been analyzed in terms of the intrinsic bond orbital (IBO) approach. 1 is the first example of a polyhedral telluraborane with a cluster size smaller than 10 vertices.

Atoms-In-Molecules' Faces of Chemical Hardness by Conceptual Density Functional Theory.

The chemical hardness concept and its realization within the conceptual density functional theory is approached with innovative perspectives, such as the electronegativity and hardness equalization of atoms in molecules connected with the softness kernel, in order to examine the structure-reactivity equalization ansatz between the electronic sharing index and the charge transfer either in the additive or geometrical mean picture of bonding. On the other hand, the maximum hardness principle presents a relation with the chemical stability of the hardness concept. In light of the inverse relation between hardness and polarizability, the minimum polarizability principle has been proposed. Additionally, this review includes important applications of the chemical hardness concept to solid-state chemistry. The mentioned applications support the validity of the electronic structure principles regarding chemical hardness and polarizability in solid-state chemistry.

Quantum Materials Discovery by Combining Chemical and Physical Design Principles.

Exploratory quantum materials discovery remains crucial to progress in material science. Due to the grand challenges that we are facing in predicting these materials and their properties from scratch, chemical design principles remain a key ingredient for the discovery of new materials. Chemical heuristics, structure, bonding, as well as global and local symmetries are at the very foundation of materials properties. In this regard, in this research, we aim to identify functional materials by composition-structure-property understanding. Materials discovery consists of a subset of methods and design principles that go hand in hand until a desired material or property is realized. However, materials synthesis is still far from a rational design approach. Rather, materials, and especially metastable materials, have to be accessed and synthesized in an exploratory, laboratory-intensive fashion. At the same time, quantum materials discovery is a vibrant highly active field of research that has seen various leaps of progress in recent years, and that holds the promise for many more in the coming years. Here, we lay out how we are discovering new materials and new materials physics in our and other chemical physics, or physical chemistry research groups, and how chemistry and chemical synthesis play a crucial role in this process.

SpeedMixing: Rapid Tribochemical Synthesis and Discovery of Pharmaceutical Cocrystals without Milling or Grinding Media.

We present SpeedMixing, a rapid blending technology, as an approach for fast mechanosynthesis and discovery of model pharmaceutical cocrystals through rapid spinning in the absence of bulk solvents and milling/grinding media. Syntheses of pharmaceutical cocrystals based on the active pharmaceutical ingredients (APIs) carbamazepine, dihydrocarbamazepine, and nicotinamide demonstrate SpeedMixing as a method for rapid, scalable, as well as controllable and selective synthesis of cocrystals, cocrystal polymorphs and stoichiomorphs, including the discovery of an unexpected methanol solvate of the archetypal cocrystal of carbamazepine and saccharin, which has eluded extensive screens over 20 years.

Strong Nonlinearity Induced by Coaxial Alignment of Polar Chain and Dense [BO3 ] Units in CaZn2 (BO3 )2.

Discovery of new efficient nonlinear optical (NLO) materials with large second-order nonlinearity for the short-wave ultraviolet spectral region (λPM ≤266 nm, PM=phase-matching) is still very challenging. Herein, a new beryllium-free borate CaZn2 (BO3 )2 with Sr2 Be2 B2 O7 (SBBO) double-layered like configuration was rationally designed, which not only preserves the structural merits but also eliminates the limitations of the SBBO crystal. CaZn2 (BO3 )2 shows a large PM second harmonic generation (SHG) reponse of 3.8×KDP, which is 38 times higher than that of its barium analogue. This enhancement mainly originates from the 1 [Zn2 O6 ]∞ polar chains with a large net dipole moment and [BO3 ] units with a high NLO active density. Our findings show the great significance of the [ZnO4 ] tetrahedra introduced strategy to design beryllium-free SBBO-type NLO crystals and also verify the feasibility of using simple non-isomorphic substitution to induce giant second-order nonlinearity enhancement.

Atom Transfer Radical Polymerization in the Solid-State.

Poly(2-vinylnaphthalene) was synthesized in the solid-state by ball milling a mixture of the corresponding monomer, a Cu-based catalyst, and an activated haloalkane as the polymerization initiator. Various reaction conditions, including milling time, milling frequency and added reductant to accelerate the polymerization were optimized. Monomer conversion and the evolution of polymer molecular weight were monitored over time using 1 H NMR spectroscopy and size exclusion chromatography, respectively, and linear correlations were observed. While the polymer molecular weight was effectively tuned by changing the initial monomer-to-initiator ratio, the experimentally measured values were found to be lower than their theoretical values. The difference was attributed to premature mechanical decomposition and modeled to accurately account for the decrement. Random copolymers of two monomers with orthogonal solubilities, sodium styrene sulfonate and 2-vinylnaphthalene, were also synthesized in the solid-state. Inspection of the data revealed that the solid-state polymerization reaction was controlled, followed a mechanism similar to that described for solution-state atom transfer radical polymerizations, and may be used to prepare polymers that are inaccessible via solution-state methods.

Three-Step Spin State Transition and Hysteretic Proton Transfer in the Crystal of an Iron(II) Hydrazone Complex.

A proton-electron coupling system, exhibiting unique bistability or multistability of the protonated state, is an attractive target for developing new switchable materials based on proton dynamics. Herein, we present an iron(II) hydrazone crystalline compound, which displays the stepwise transition and bistability of proton transfer at the crystal level. These phenomena are realized through the coupling with spin transition. Although the multi-step transition with hysteresis has been observed in various systems, the corresponding behavior of proton transfer has not been reported in crystalline systems; thus, the described iron(II) complex is the first example. Furthermore, because proton transfer occurs only in one of the two ligands and π electrons redistribute in it, the dipole moment of the iron(II) complexes changes with the proton transfer, wherein the total dipole moment in the crystal was canceled out owing to the antiferroelectric-like arrangement.

[Ge2 S5 (S2 )]4- , A NLO-Active Unit Leading to an Asymmetric Structure Discovered in Li2 Cs4 Ge2 S5 (S2 )Cl2 : An Experimental and Theoretical study.

Metal-centered MS4 tetrahedra are fundamentally important building blocks for the structural construction of infrared (IR) nonlinear optical (NLO) mateirals, because they have a large effect on properties like second-harmonic generation, birefringence, band gap, etc. Therefore, rational design and selection of these tetrahedra could effectively help synthesize new materials and give satisfactory properties. In this work, we reported a new NLO-active [Ge2 S5 (S2 )]4- unit composed of two corner-shared GeS4 tetrahedra with a nonpolar covalent S-S bond, discovered in a new compound of Li2 Cs4 Ge2 S5 (S2 )Cl2 . To the best of our knowledge, this [Ge2 S5 (S2 )]4- unit has never been discovered. [Ge2 S5 (S2 )]4- units have intrinsic asymmetric features and lead to the whole structure being noncentrosymmetric (NCS). Further, real-space atom-cutting methods reveal that they make almost all the contribution to the second-harmonic generation response (SHG) for Li2 Cs4 Ge2 S5 (S2 )Cl2 . All of the above indicate that the [Ge2 S5 (S2 )]4- unit is a new functional unit and a good choice for designing new IR NLO materials.

Reversible Encapsulation of Xenon and CH2 Cl2 in a Solid-State Molecular Organometallic Framework (Guest@SMOM).

Reversible encapsulation of CH2 Cl2 or Xe in a non-porous solid-state molecular organometallic framework of [Rh(Cy2 PCH2 PCy2 )(NBD)][BArF4 ] occurs in single-crystal to single-crystal transformations. These processes are probed by solid-state NMR spectroscopy, including 129 Xe SSNMR. Non-covalent interactions with the -CF3 groups, and hydrophobic channels formed, of [BArF4 ]- anions are shown to be important, and thus have similarity to the transport of substrates and products to and from the active site in metalloenzymes.

Endohedral gallide cluster superconductors and superconductivity in ReGa5.

We present transition metal-embedded (T@Gan) endohedral Ga-clusters as a favorable structural motif for superconductivity and develop empirical, molecule-based, electron counting rules that govern the hierarchical architectures that the clusters assume in binary phases. Among the binary T@Gan endohedral cluster systems, Mo8Ga41, Mo6Ga31, Rh2Ga9, and Ir2Ga9 are all previously known superconductors. The well-known exotic superconductor PuCoGa5 and related phases are also members of this endohedral gallide cluster family. We show that electron-deficient compounds like Mo8Ga41 prefer architectures with vertex-sharing gallium clusters, whereas electron-rich compounds, like PdGa5, prefer edge-sharing cluster architectures. The superconducting transition temperatures are highest for the electron-poor, corner-sharing architectures. Based on this analysis, the previously unknown endohedral cluster compound ReGa5 is postulated to exist at an intermediate electron count and a mix of corner sharing and edge sharing cluster architectures. The empirical prediction is shown to be correct and leads to the discovery of superconductivity in ReGa5. The Fermi levels for endohedral gallide cluster compounds are located in deep pseudogaps in the electronic densities of states, an important factor in determining their chemical stability, while at the same time limiting their superconducting transition temperatures.