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Ashwini Nangia

Bio: Ashwini Nangia is an academic researcher from University of Hyderabad. The author has contributed to research in topics: Hydrogen bond & Crystal structure. The author has an hindex of 63, co-authored 299 publications receiving 13057 citations. Previous affiliations of Ashwini Nangia include Yale University & National Chemical Laboratory.


Papers
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TL;DR: In this article, the authors reviewed several novel examples of pharmaceutical cocrystals from the past decade and analyzed the enhanced solubility profiles of cocrystal profiles, showing that the peak dissolution for pharmaceutical cocystals occurs in a short time (<30 min), and high-solubility is maintained over a sufficiently long period (4-6 h) for the best cases.
Abstract: The current phase of drug development is witnessing an oncoming crisis due to the combined effects of increasing R&D costs, decreasing number of new drug molecules being launched, several blockbuster drugs falling off the patent cliff, and a high proportion of advanced drug candidates exhibiting poor aqueous solubility. The traditional approach of salt formulation to improve drug solubility is unsuccessful with molecules that lack ionizable functional groups, have sensitive moieties that are prone to decomposition/racemization, and/or are not sufficiently acidic/basic to enable salt formation. Several novel examples of pharmaceutical cocrystals from the past decade are reviewed, and the enhanced solubility profiles of cocrystals are analyzed. The peak dissolution for pharmaceutical cocrystals occurs in a short time (<30 min), and high solubility is maintained over a sufficiently long period (4–6 h) for the best cases. The enhanced solubility of drug cocrystals is similar to the supersaturation phenomenon ...

818 citations

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TL;DR: The existence and nature of C−H···F−C interactions in crystalline fluorobenzenes 1−3 and 7−10 are discussed in this paper, where the authors compare the C−F−O/C−H−N interactions in these four crystal structures.
Abstract: The existence and nature of C−H···F−C interactions in crystalline fluorobenzenes 1−3 and 7−10 are discussed. These compounds were chosen because they contain only C, H, and F atoms; this is necessary in the evaluation of the weak acceptor capabilities of the C−F group. All of these compounds are liquids at room temperature, and single crystals for X-ray diffraction were grown in situ. The analysis of the C−H···F interactions that are found in all of these crystal structures takes the form of comparisons with related C−H···O/C−H···N analogues. Fluorobenzene, 1, bears a close relationship to pyridinium fluoride, pyridine 1-oxide, and benzonitrile at the level of individual interactions, showing that the character of the structure-determining intermolecular interactions in these four crystal structures are the same. Similarly, 1,4-difluorobenzene, 3, and 1,4-benzoquinone are related, the C−H···F interactions in the former playing the same structural role as the C−H···O interactions in the latter. A compariso...

637 citations

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TL;DR: Organic molecules with flexible torsions and low-energy conformers have a greater likelihood of exhibiting polymorphism because (1) different conformations lead to new hydrogen-bonding and close-packing modes and (2) the tradeoff reduces the total energy difference between alternative crystal structures.
Abstract: Polymorphs are different crystalline modifications of the same chemical substance. When different conformers of the same molecule occur in different crystal forms, the phenomenon is termed conformational polymorphism. Occasionally, more than one conformer is present in the same crystal structure. The influence of molecular conformation changes on the formation and stability of polymorphs is the focus of this Account. X-ray crystal structures of conformational polymorphs were analyzed to understand the interplay of intramolecular (conformer) and intermolecular (lattice) energy in the crystallization and stability of polymorphs. Polymorphic structures stabilized by strong O−H···O/N−H···O hydrogen bonds, weak C−H···O interactions, and close packing were considered. 4,4-Diphenyl-2,5-cyclohexadienone (1) and bis(p-tolyl) ketone p-tosylhydrazone (3) are prototypes of C−H···O and N−H···O hydrogen-bonded structures. Distance−angle scatter plots of O−H···O and C−H···O hydrogen bonds extracted from the Cambridge St...

456 citations

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TL;DR: Some prominent examples of drug cocrystals which exhibit variable hardness/softness and elasticity/plasticity depending on coformer selection, improvement of solubility and permeability in the same cocrystal, increase of the melting point for solid formulation, enhanced color performance, photostability and hydration stability, and a longer half-life are highlighted.

412 citations

Journal ArticleDOI
TL;DR: In this paper, a modular expansion of carboxylic acid dimer in neutral cocrystals with pyridine type bases is shown, which results in a ternary cocrystal 12 sustained via O−H⋯N and O−O− hydrogen bonds, and the length of bipyridinium cation plays a role in the overall structure.
Abstract: Linear, zigzag tapes and flat, corrugated sheet structures are described in binary cocrystals 1–9 of some di- and tricarboxylic acids with 4,4′-bipyridine bases and isonicotinamide. Carboxylic acid⋯pyridine O–H⋯N, its proton transfer form N+–H⋯O−, carboxamide dimer N–H⋯O, and extended motifs are present in these crystal structures. Our results show modular expansion of carboxylic acid dimer in neutral cocrystals with pyridine type bases. Even as the structures of these aggregates can be understood from the molecular constituents in a straightforward manner, the nature of acid⋯pyridine synthon, i.e. neutral or ionic, is difficult to anticipate from their ΔpKa values. We modify the ΔpKa (pKa conjugate acid of pyridine base – pKa carboxylic acid) rule in COOH–pyridine cocrystals: ΔpKa 3.75 results in proton migration to the ionic interaction N+–H⋯O−. Proton transfer results in the assembly of a supramolecular 3-connected node of cyclohexane tricarboxylate and these anions form chair cyclohexane or parquet grid sheets in 10 and 11. The length of bipyridinium cation plays a role in the overall structure. A novel approach to three-component adducts is crystallization of 1,3cis,5cis-cyclohexane tricarboxylic acid with 4,4′-bipyridine and 4,4′-bipyridine-N-oxide bases of different strengths, which results in a ternary cocrystal 12 sustained via O–H⋯N and O–H⋯O− hydrogen bonds.

355 citations


Cited by
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10 Mar 1970

8,159 citations

Journal ArticleDOI
TL;DR: The hydrogen bond is the most important of all directional intermolecular interactions, operative in determining molecular conformation, molecular aggregation, and the function of a vast number of chemical systems ranging from inorganic to biological.
Abstract: The hydrogen bond is the most important of all directional intermolecular interactions. It is operative in determining molecular conformation, molecular aggregation, and the function of a vast number of chemical systems ranging from inorganic to biological. Research into hydrogen bonds experienced a stagnant period in the 1980s, but re-opened around 1990, and has been in rapid development since then. In terms of modern concepts, the hydrogen bond is understood as a very broad phenomenon, and it is accepted that there are open borders to other effects. There are dozens of different types of X-H.A hydrogen bonds that occur commonly in the condensed phases, and in addition there are innumerable less common ones. Dissociation energies span more than two orders of magnitude (about 0.2-40 kcal mol(-1)). Within this range, the nature of the interaction is not constant, but its electrostatic, covalent, and dispersion contributions vary in their relative weights. The hydrogen bond has broad transition regions that merge continuously with the covalent bond, the van der Waals interaction, the ionic interaction, and also the cation-pi interaction. All hydrogen bonds can be considered as incipient proton transfer reactions, and for strong hydrogen bonds, this reaction can be in a very advanced state. In this review, a coherent survey is given on all these matters.

5,153 citations

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TL;DR: In this paper, a two-dimensional mapping of the Hirshfeld surfaces of a molecular molecule is presented, which summarizes quantitatively the nature and type of intermolecular interaction experienced by a molecule in the bulk, and presents it in a convenient graphical format.
Abstract: We have recently described a remarkable new way of exploring packing modes and intermolecular interactions in molecular crystals using a novel partitioning of crystal space. These molecular Hirshfeld surfaces reflect intermolecular interactions in a novel visual manner, offering a hitherto unseen picture of molecular shape in a crystalline environment. The surfaces encode information about all intermolecular interactions simultaneously, but sophisticated interactive graphics are required in order to extract the information most efficiently. To overcome this we have devised a two-dimensional mapping which summarizes quantitatively the nature and type of intermolecular interaction experienced by a molecule in the bulk, and presents it in a convenient graphical format. The mapping takes advantage of the triangulation of the Hirshfeld surfaces, and plots the fraction of points on the surface as a function of the closest distances from the point to nuclei inside and outside the surface. In this manner all interaction types (for example, hydrogen bonding, close and distant van der Waals contacts, C–H⋯π interactions, π–π stacking) are readily identifiable, and it becomes a straightforward matter to classify molecular crystals by the nature of interactions, and to rapidly identify similarities and differences which can become obscured when examining crystal packing diagrams. These plots are a novel visual representation of all the intermolecular interactions simultaneously, and are unique for a given crystal structure and polymorph. Applications to a wide variety of molecular crystals and intermolecular interactions are presented, including polymorphic systems, as well as crystals where Z′ > 1.

2,646 citations

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TL;DR: Concentrating on recent advances, this article covers industrial aspects, inorganic materials, organic synthesis, cocrystallisation, pharmaceutical aspects, metal complexes, supramolecular aspects and characterization methods.
Abstract: The aim of this critical review is to provide a broad but digestible overview of mechanochemical synthesis, i.e. reactions conducted by grinding solid reactants together with no or minimal solvent. Although mechanochemistry has historically been a sideline approach to synthesis it may soon move into the mainstream because it is increasingly apparent that it can be practical, and even advantageous, and because of the opportunities it provides for developing more sustainable methods. Concentrating on recent advances, this article covers industrial aspects, inorganic materials, organic synthesis, cocrystallisation, pharmaceutical aspects, metal complexes (including metal–organic frameworks), supramolecular aspects and characterization methods. The historical development, mechanistic aspects, limitations and opportunities are also discussed (314 references).

2,102 citations