Enabling Superprotonic Phase Transitions in Solid Acids via Supramolecular Complex Formation: The Case of Crown Ethers and Alkali Hydrogen Sulfates

This investigation, combining both structural and spectroscopic analyses, sheds light on the intricate relationship between conduction properties and the initiation of dynamic motions within the anhydrous crystalline materials of 18-crown-6·KHSO4 (1) and 18-crown-6·RbHSO4 (2) and proves how the formation of supramolecular complexes is pivotal for inducing solid–solid transitions, leading to superprotonic phases, i.e., crystalline solids exhibiting an enhanced ability to conduct protons, as elucidated through impedance spectroscopic measurements. This multifaceted approach deepens our understanding of the phenomenon and sets the stage for further exploration and application in solid-state protonic conductors

Preparation, stabilisation, isolation and tableting of valsartan nanoparticles using a semi-continuous carrier particle mediated process

This work investigated the technical feasibility of preparing, stabilizing and isolating poorly water-soluble drug nanoparticles via a small-scale antisolvent precipitation process operating in semi-continuous mode. Specifically, a novel semi-continuous process was demonstrated for the carrier particle mediated production, stabilization and isolation of valsartan nanoparticles into a solid form using montmorillonite clay particles as the carrier. The semi continuous process operated robustly for the full duration of the experiment (~16 min) and steady-state conditions were reached after ~5 min. Nanoparticles of valsartan (51 ± 1 nm) were successfully prepared, stabilized and isolated with the help of montmorillonite (MMT) or protamine functionalized montmorillonite (PA-MMT) into the dried form by this semi-continuous route. The dissolution profile of the isolated valsartan nanocomposite solids was similar to that of valsartan nanocomposite solids produced via the corresponding laboratory scale batch mode process, indicating that the product quality (principally the nanoscale particle size and solid-state form) is retained during the semi-continuous processing of the nanoparticles. Furthermore, tablets produced via direct compression of the isolated valsartan nanocomposite solids displayed a dissolution profile comparable with that of the powdered nanocomposite material. PXRD, DSC, SSNMR and dissolution studies indicate that the valsartan nanoparticles produced via this semi-continuous process were amorphous and exhibited shelf-life stability equivalent to > 10 months

Pseudopolymorphism Driven by Stoichiometry and Hydrated/Anhydrous Reagents: The Riveting Case of Methyl Gallate·l‑Proline

Among GRAS molecules, α-amino acids have been extensively used to produce molecular salts and cocrystals of APIs thanks to their nontoxicity, ready availability, cheapness, and their zwitterionic nature. Here we report on the use of both anhydrous and hydrated l-proline (Pro and Pro·H2O, respectively) with methyl gallate (MG) to selectively obtain by mechanochemical methods anhydrous and hydrated cocrystals: MG·Pro2 and MG2·Pro2·H2O, respectively. The two new forms were characterized by means of single-crystal and powder X-ray diffraction (SCXRD and PXRD), solid-state nuclear magnetic resonance (SSNMR), DSC, and TGA. Interestingly, the choice of the starting material together with the stoichiometry drives the formation of the cocrystal toward either the anhydrous or the hydrate form: the anhydrous form could be obtained only on starting from anhydrous Pro, whereas the hydrate could be obtained with Pro·H2O or with Pro by matching the correct stoichiometry. An energy framework analysis allowed us to rationalize this peculiar water uptake behavior in terms of both the relative interaction strengths of proline–proline, proline–water, and proline–methyl gallate pairs and packing features

Cortisone and cortisol break hydrogen-bonding rules to make a drug–prodrug solid solution

Multidrug products enable more effective therapies and simpler administration regimens, provided that a stable formulation is prepared, with the desired composition. In this view, solid solutions have the advantage of combining the stability of a single crystalline phase with the potential of stoichiometry variation of a mixture. Here a drug–prodrug solid solution of cortisone and cortisol (hydrocortisone) is described. Despite the structural differences of the two components, the new phase is obtained both from solution and by supercritical CO2 assisted spray drying. In particular, to enter the solid solution, hydrocortisone must violate Etter’s rules for hydrogen bonding. As a result, its dissolution rate is almost double

Navigating the Complex Solid Form Landscape of the Quercetin Flavonoid Molecule

Quercetin, a naturally occurring bioflavonoid substance widely used in the nutraceutical and food industries, exists in various solid forms that can have different physicochemical properties, thus impacting this compound’s performance in various applications. In this work, we will clarify the complex solid-form landscape of this molecule. Two elusive isostructural solvates of quercetin were obtained from ethanol and methanol. The obtained crystals were characterized experimentally, but the crystallographic structure could not be solved due to their high instability. Nevertheless, the desolvated structure resulting from a high-temperature treatment (or prolonged storage at ambient conditions) of both these two labile crystals was characterized and solved via powder X-ray diffraction and solid-state nuclear magnetic resonance (SSNMR). This anhydrous crystal structure was compared with another anhydrous quercetin form obtained in our previous work, indicating that, at least, two different anhydrous polymorphs of quercetin exist. Navigating the solid-form landscape of quercetin is essential to ensure accurate control of the functional properties of food, nutraceutical, or pharmaceutical products containing crystal forms of this substance

Selective Synthesis of a Salt and a Cocrystal of the Ethionamide–Salicylic Acid System

Herein is presented a rare example of salt/cocrystal polymorphism involving the adduct between ethionamide (ETH) and salicylic acid (SAL). Both the salt and cocrystal forms have the same stoichiometry and composition and are both stable at room temperature. The synthetic procedure was successfully optimized in order to selectively obtain both polymorphs. The two adducts’ structures were thoroughly investigated by means of single-crystal X-ray diffraction, solid-state NMR spectroscopy, and density functional theory (DFT) calculations. From the solid-state NMR point of view, the combination of mono- and multinuclear experiments (1H MAS, 13C and 15N CPMAS, 1H-{14N} D-HMQC, 1H–14N PM-S-RESPDOR) provided undoubted spectroscopic evidence about the different positions of the hydrogen atom along the main N···H···O interaction. In particular, the 1H–14N PM-S-RESPDOR allowed N–H distance measurements through the 1H detected signal at a very high spinning speed (70 kHz), which remarkably agree with those derived by DFT optimized X-ray diffraction, even on a natural abundance real system. The thermodynamic relationship between the salt and the cocrystal was inquired from the experimental and computational points of view, enabling the characterization of the two polymorphs as enantiotropically related. The performances of the two forms in terms of dissolution rate are comparable to each other but significantly higher with respect to the pure ETH

Tuning Carbon Dioxide Adsorption Affinity of Zinc(II) MOFs by Mixing Bis(pyrazolate) Ligands with N‑Containing Tags

The four zinc­(II) mixed-ligand metal–organic frameworks (MIXMOFs) Zn­(BPZ)x(BPZNO2)1–x, Zn­(BPZ)x(BPZNH2)1–x, Zn­(BPZNO2)x(BPZNH2)1–x, and Zn­(BPZ)x(BPZNO2)y(BPZNH2)1–x−y (H2BPZ = 4,4′-bipyrazole; H2BPZNO2 = 3-nitro-4,4′-bipyrazole; H2BPZNH2 = 3-amino-4,4′-bipyrazole) were prepared through solvothermal routes and fully investigated in the solid state. Isoreticular to the end members Zn­(BPZ) and Zn­(BPZX) (X = NO2, NH2), they are the first examples ever reported of (pyr)­azolate MIXMOFs. Their crystal structure is characterized by a three-dimensional open framework with one-dimensional square or rhombic channels decorated by the functional groups. Accurate information about ligand stoichiometric ratio was determined (for the first time on MIXMOFs) through integration of selected ligands skeleton resonances from 13C cross polarized magic angle spinning solid-state NMR spectra collected on the as-synthesized materials. Like other poly­(pyrazolate) MOFs, the four MIXMOFs are thermally stable, with decomposition temperatures between 708 and 726 K. As disclosed by N2 adsorption at 77 K, they are micro-mesoporous materials with Brunauer–Emmett–Teller specific surface areas in the range 400–600 m2/g. A comparative study (involving also the single-ligand analogues) of CO2 adsorption capacity, CO2 isosteric heat of adsorption (Qst), and CO2/N2 selectivity in equimolar mixtures at p = 1 bar and T = 298 K cast light on interesting trends, depending on ligand tag nature or ligand stoichiometric ratio. In particular, the amino-decorated compounds show higher Qst values and CO2/N2 selectivity vs the nitro-functionalized analogues; in addition, tag “dilution” [upon passing from Zn­(BPZX) to Zn­(BPZ)x(BPZX)1–x] increases CO2 adsorption selectivity over N2. The simultaneous presence of amino and nitro groups is not beneficial for CO2 uptake. Among the compounds studied, the best compromise among uptake capacity, Qst, and CO2/N2 selectivity is represented by Zn­(BPZ)x(BPZNH2)1–x

Tuning Carbon Dioxide Adsorption Affinity of Zinc(II) MOFs by Mixing Bis(pyrazolate) Ligands with N‑Containing Tags

The four zinc­(II) mixed-ligand metal–organic frameworks (MIXMOFs) Zn­(BPZ)x(BPZNO2)1–x, Zn­(BPZ)x(BPZNH2)1–x, Zn­(BPZNO2)x(BPZNH2)1–x, and Zn­(BPZ)x(BPZNO2)y(BPZNH2)1–x−y (H2BPZ = 4,4′-bipyrazole; H2BPZNO2 = 3-nitro-4,4′-bipyrazole; H2BPZNH2 = 3-amino-4,4′-bipyrazole) were prepared through solvothermal routes and fully investigated in the solid state. Isoreticular to the end members Zn­(BPZ) and Zn­(BPZX) (X = NO2, NH2), they are the first examples ever reported of (pyr)­azolate MIXMOFs. Their crystal structure is characterized by a three-dimensional open framework with one-dimensional square or rhombic channels decorated by the functional groups. Accurate information about ligand stoichiometric ratio was determined (for the first time on MIXMOFs) through integration of selected ligands skeleton resonances from 13C cross polarized magic angle spinning solid-state NMR spectra collected on the as-synthesized materials. Like other poly­(pyrazolate) MOFs, the four MIXMOFs are thermally stable, with decomposition temperatures between 708 and 726 K. As disclosed by N2 adsorption at 77 K, they are micro-mesoporous materials with Brunauer–Emmett–Teller specific surface areas in the range 400–600 m2/g. A comparative study (involving also the single-ligand analogues) of CO2 adsorption capacity, CO2 isosteric heat of adsorption (Qst), and CO2/N2 selectivity in equimolar mixtures at p = 1 bar and T = 298 K cast light on interesting trends, depending on ligand tag nature or ligand stoichiometric ratio. In particular, the amino-decorated compounds show higher Qst values and CO2/N2 selectivity vs the nitro-functionalized analogues; in addition, tag “dilution” [upon passing from Zn­(BPZX) to Zn­(BPZ)x(BPZX)1–x] increases CO2 adsorption selectivity over N2. The simultaneous presence of amino and nitro groups is not beneficial for CO2 uptake. Among the compounds studied, the best compromise among uptake capacity, Qst, and CO2/N2 selectivity is represented by Zn­(BPZ)x(BPZNH2)1–x

Tuning Carbon Dioxide Adsorption Affinity of Zinc(II) MOFs by Mixing Bis(pyrazolate) Ligands with N‑Containing Tags

The four zinc­(II) mixed-ligand metal–organic frameworks (MIXMOFs) Zn­(BPZ)x(BPZNO2)1–x, Zn­(BPZ)x(BPZNH2)1–x, Zn­(BPZNO2)x(BPZNH2)1–x, and Zn­(BPZ)x(BPZNO2)y(BPZNH2)1–x−y (H2BPZ = 4,4′-bipyrazole; H2BPZNO2 = 3-nitro-4,4′-bipyrazole; H2BPZNH2 = 3-amino-4,4′-bipyrazole) were prepared through solvothermal routes and fully investigated in the solid state. Isoreticular to the end members Zn­(BPZ) and Zn­(BPZX) (X = NO2, NH2), they are the first examples ever reported of (pyr)­azolate MIXMOFs. Their crystal structure is characterized by a three-dimensional open framework with one-dimensional square or rhombic channels decorated by the functional groups. Accurate information about ligand stoichiometric ratio was determined (for the first time on MIXMOFs) through integration of selected ligands skeleton resonances from 13C cross polarized magic angle spinning solid-state NMR spectra collected on the as-synthesized materials. Like other poly­(pyrazolate) MOFs, the four MIXMOFs are thermally stable, with decomposition temperatures between 708 and 726 K. As disclosed by N2 adsorption at 77 K, they are micro-mesoporous materials with Brunauer–Emmett–Teller specific surface areas in the range 400–600 m2/g. A comparative study (involving also the single-ligand analogues) of CO2 adsorption capacity, CO2 isosteric heat of adsorption (Qst), and CO2/N2 selectivity in equimolar mixtures at p = 1 bar and T = 298 K cast light on interesting trends, depending on ligand tag nature or ligand stoichiometric ratio. In particular, the amino-decorated compounds show higher Qst values and CO2/N2 selectivity vs the nitro-functionalized analogues; in addition, tag “dilution” [upon passing from Zn­(BPZX) to Zn­(BPZ)x(BPZX)1–x] increases CO2 adsorption selectivity over N2. The simultaneous presence of amino and nitro groups is not beneficial for CO2 uptake. Among the compounds studied, the best compromise among uptake capacity, Qst, and CO2/N2 selectivity is represented by Zn­(BPZ)x(BPZNH2)1–x