New Multicomponent Sulfadimethoxine Crystal Forms: Sulfonamides as Participants in Supramolecular Interactions

Sulfadimethoxine (SDM) cocrystal formation was screened using coformers with cyclic amines, amide, carboxylic acid, and sulfonamide based moieties. Eight new multicomponent crystal forms were obtained by solution crystallization and liquid-assisted grinding techniques, showing a preference for the amine derivatives. Cocrystals were obtained with isonicotinamide (SDM:ISO) and 4,4′-bipyridine (SDM:BIP:ACE; SDM:BIP:H₂O), and molecular salts were synthesized with piperazine (SDM:PIP), 4,4′-trimethylenedipiperidine (SDM:TRI), and 1,4-diazabicyclo­[2.2.2]­octane (two anhydrous polymorphic forms (SDM:DABCO) and one hydrate (SDM:DABCO:H₂O)). The new forms were fully characterized by X-ray diffraction. Structural characterization shows the disruption of the typical <i>R</i>₂²(8) sulfonamide synthon, while the supramolecular arrangement is achieved through several new synthons. In cocrystals, the amide nitrogen N_sulfonamide behaves as the best donor and bonds to the O_acetamide of ISO, while with BIP the interaction is established with the N_BIP atom. In salts, charge assisted hydrogen bonds are established, predominantly with the amide nitrogen, the best acceptor, or the sulfonyl O atom, but there is a strong competition with the N atom of the pyrazine ring (N_pyrazine). Thermal behavior and physicochemical properties were assessed by thermogravimetric analysis, differential scanning calorimetry, variable temperature powder X-ray diffraction, and hot-stage microscopy techniques. As expected, the molecular salts reveal higher solubility in water than the cocrystals, an important aspect for the improvement of SDM performance

DataSheet1_Micro/mesoporous LTL derived materials for catalytic transfer hydrogenation and acid reactions of bio-based levulinic acid and furanics.docx

The biomass-derived platform chemicals furfural and 5-(hydroxymethyl)furfural (HMF) may be converted to α-angelica lactone (AnL) and levulinic acid (LA). Presently, LA (synthesized from carbohydrates) has several multinational market players. Attractive biobased oxygenated fuel additives, solvents, etc., may be produced from AnL and LA via acid and reduction chemistry, namely alkyl levulinates and γ-valerolactone (GVL). In this work, hierarchical hafnium-containing multifunctional Linde type L (LTL) related zeotypes were prepared via top-down strategies, for the chemical valorization of LA, AnL and HMF via integrated catalytic transfer hydrogenation (CTH) and acid reactions in alcohol medium. This is the first report of CTH applications (in general) of LTL related materials. The influence of the post-synthesis treatments/conditions (desilication, dealumination, solid-state impregnation of Hf or Zr) on the material properties and catalytic performances was studied. AnL and LA were converted to 2-butyl levulinate (2BL) and GVL in high total yields of up to ca. 100%, at 200°C, and GVL/2BL molar ratios up to 10. HMF conversion gave mainly the furanic ethers 5-(sec-butoxymethyl)furfural and 2,5-bis(sec-butoxymethyl)furan (up to 63% total yield, in 2-butanol at 200°C/24 h). Mechanistic, reaction kinetics and material characterization studies indicated that the catalytic results depend on a complex interplay of different factors (material properties, type of substrate). The recovered-reused solids performed steadily.</p

Packing Interactions and Physicochemical Properties of Novel Multicomponent Crystal Forms of the Anti-Inflammatory Azelaic Acid Studied by X‑ray and Solid-State NMR

The reactivity of the active pharmaceutical ingredient azelaic acid (AA) with carboxylic acid, alcohol, amine, and amide based co-formers was screened. Five new multicomponent crystal forms of AA were obtained by liquid assisted grinding and conventional solution methods. The obtained forms: (i) a co-crystal with 4,4′-bipyridine (AA:BIP, <b>1</b>), (ii) an anhydrous and an hydrated molecular salt with piperazine (AA:PIP, <b>2</b> and <b>3</b>), and (iii) two anhydrous molecular salts with morpholine (AA:MORPH, <b>4</b>) and 1,4-diazobicyclo­[2.2.2]­octane (AA:DABCO, <b>5</b>), were fully characterized by X-ray diffraction and solid-state (SS) NMR. In all new forms the carboxylic-carboxylic <i>R</i>₂²(8) homosynthon present in AA is broken, and NH₂···O_COOH or ⁺NH₂···O_COO- hydrogen bonds (HBs) become the fundamental pillars in the new supramolecular arrangements. The X-ray structure of <b>4</b> exhibits a static disorder in the hydrogen atoms engaged in an HB between two COOH moieties of AA. Density functional theory geometry optimization of the hydrogen positions followed by GIPAW-DFT calculations of ¹H chemical shifts showed that such disordered atoms refer to O···H···O hydrogens, roughly equidistant from both proton acceptor and donor atoms. ¹H SSNMR detected unusually strong HBs associated with such disordered hydrogens through the presence of ¹H resonances shifted to very high frequencies (up to <i>ca</i>. 20.1 ppm). These results clearly show the advantageous use of both X-ray diffraction and SSNMR techniques for structural elucidation. We concluded that the hydrated piperazine salt <b>3</b> readily converted to <b>2</b> at ambient RH and that their thermal behavior is strongly determined by both the supramolecular arrangement and strength of HB network. Piperazine salt <b>2</b> presents an improved aqueous solubility bestowing a promising opportunity to avoid the use of alcoholic solutions in the final formulations