Absolute Configuration of Pharmaceutical Research Compounds Determined by X‐ray Powder Diffraction

Schlesinger, Carina; Tapmeyer, Lukas; Gumbert, Silke D.; Prill, Dragica; Bolte, Michael; Schmidt, Martin; Saal, Christoph

doi:10.1002/anie.201713168

Cited by 14 publications

(11 citation statements)

References 20 publications

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“…To tackle this issue, we decided to study some co-crystals and salts with the two techniques that allow their full characterization: X-ray diffraction and solid-state NMR (SSNMR). The latter, well established in pharma science, has been used as a complementary technique to probe the short-range local structure, helping the positioning of light atoms, such as hydrogens [60][61][62][63], and in particular to study packing interactions, such as hydrogen bonds (HBs), and even establish their relative strength [62,64].…”

Section: Discerning Co-crystals From Salts By X-ray Diffraction and Smentioning

confidence: 99%

The Lisbon Supramolecular Green Story: Mechanochemistry towards New Forms of Pharmaceuticals

et al. 2020

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This short review presents and highlights the work performed by the Lisbon Group on the mechanochemical synthesis of active pharmaceutical ingredients (APIs) multicomponent compounds. Here, we show some of our most relevant contributions on the synthesis of supramolecular derivatives of well-known commercial used drugs and the corresponding improvement on their physicochemical properties. The study reflects, not only our pursuit of using crystal engineering principles for the search of supramolecular entities, but also our aim to correlate them with the desired properties. The work also covers our results on polymorphic screening and describes our proposed alternatives to induce and maintain specific polymorphic forms, and our approach to avoid polymorphism using APIs as ionic liquids. We want to stress that all the work was performed using mechanochemistry, a green advantageous synthetic technique.

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Section: Discerning Co-crystals From Salts By X-ray Diffraction and Smentioning

confidence: 99%

The Lisbon Supramolecular Green Story: Mechanochemistry towards New Forms of Pharmaceuticals

et al. 2020

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“…The preparation of active pharmaceutical ingredients in an anionic form would permit an improvement in their physicochemical and biological properties, such as their solubility, lipophilicity, or toxicity. 11,39 The nalidixic anion, a wellknown antibiotic ingredient used in the treatment of urinary-tract infections, when tested under the standard conditions gave the target product 58 in 86% yield. Moreover, the naproxen anion, a widely used nonsteroidal antiinflammatory ingredient, was amenable to this condensation reaction.…”

Section: -24mentioning

confidence: 99%

General and Greener Synthesis of Diverse Functional Organic Salts through Schiff Base Chemistry

Shi

et al. 2019

Synlett

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We report a greener and more-general organic method for the synthesis of functional organic salts containing organic anions through a Schiff base reaction between readily available aldehydes and simple aminoguanidinium salts. This reaction is operationally simple, free of metal salts, and forms water as the sole byproduct. The broad scope and good functional-group compatibility of this method permit its use to provide ready access to a library of more than 70 distinct organic salts, including those of heterocyclic anions, complex pharmaceutical anions, and polyanions, which are difficult to obtain through classical inorganic methods. Moreover, choosing different aldehydes and organic anions provides a convenient method for modulating or improving the functional properties of the designed organic salts, such as their melting points, fluorescence, and energetic properties. We therefore expect that this method will open new opportunities for the discovery and functionalization of a wide variety of organic salts and functional materials.

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“…For that, structural information is needed and is conventionally obtained from X-ray diffraction. The particular use of powder X-ray diffraction (PXRD) for structure determination of inorganic/organic and pharmaceutical systems has been exploited in several studies [1,9,10,11,12,13,14,15]. This approach revealed to be a powerful tool, especially for systems in which the crystallization into single crystal is limited or difficult.…”

Section: Introductionmentioning

confidence: 99%

Insight into the Structure and Properties of Novel Imidazole-Based Salts of Salicylic Acid

et al. 2019

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The preparation of new active pharmaceutical ingredient (API) multicomponent crystal forms, especially co-crystals and salts, is being considered as a reliable strategy to improve API solubility and bioavailability. In this study, three novel imidazole-based salts of the poorly water-soluble salicylic acid (SA) are reported exhibiting a remarkable improvement in solubility and dissolution rate properties. All structures were solved by powder X-ray diffraction. Multiple complementary techniques were used to solve co-crystal/salt ambiguities: density functional theory calculations, Raman and 1H/13C solid-state NMR spectroscopies. In all molecular salts, the crystal packing interactions are based on a common charged assisted +N-H(SA)⋯O−(co-former) hydrogen bond interaction. The presence of an extra methyl group in different positions of the co-former, induced different supramolecular arrangements, yielding salts with different physicochemical properties. All salts present much higher solubility and dissolution rate than pure SA. The most promising results were obtained for the salts with imidazole and 1-methylimidazole co-formers.

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Absolute Configuration of Pharmaceutical Research Compounds Determined by X‐ray Powder Diffraction

Cited by 14 publications

References 20 publications

The Lisbon Supramolecular Green Story: Mechanochemistry towards New Forms of Pharmaceuticals

The Lisbon Supramolecular Green Story: Mechanochemistry towards New Forms of Pharmaceuticals

General and Greener Synthesis of Diverse Functional Organic Salts through Schiff Base Chemistry

Insight into the Structure and Properties of Novel Imidazole-Based Salts of Salicylic Acid

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