1,9-Pyrazoloanthrone as a Colorimetric and ``Turn-On'' Fluorometric Chemosensor: Structural Implications

A colorimetric and ``turn-on'' fluorescent chemosensor based on 1,9-pyrazoloanthrone specifically for cyanide and fluoride ion detection shows a remarkable solid state reaction when crystals of tetrabutylammonium cyanide and fluoride are brought in physical contact with 1,9-pyrazoloanthrone. X-ray crystal structures of 1,9-pyrazoloanthrone and complexes have been determined, and the ion sensing activity (detection limit of 0.2 and 2 ppb) has been inferred based on spectroscopic and structural features.

Designing Ternary Co-crystals with Stacking Interactions and Weak Hydrogen Bonds. 4,4 `-Bis-hydroxyazobenzene

Three ternary co-crystals of the title compound are reported. The design strategy hinges on the identification of a robust synthon with O-H center dot center dot center dot N hydrogen bonds in a binary co-crystal. Construction of this module allows the tuning of pi center dot center dot center dot pi stacking interactions and weak hydrogen bonds to incorporate the third component into the crystal structure. Screening of various co-formers showed that a delicate balance of electrostatics is required for stacking to favor the formation of ternaries. A C-H center dot center dot center dot N hydrogen-bonded motif was also found to occur repetitively in the ternary co-crystals. The directional nature of weak hydrogen bonds allows them to be used effectively in this study.

Symbiosis in Solid State Interconversion and Synthon Modularity in Hydroxybenzoic Acid-Hexamine Adducts

Systematic cocrystallization of hydroxybenzoic acids with hexamine using liquid-assisted grinding shows facile solid state interconversion among different stoichiometric variants. The reversible interconversion caused by varying both the acid and base components in tandem is shown to be a consequence of hydrogen-bonded synthon modularity present in all representative crystal structures. Among a total of 11 complexes, three are salts and eight are cocrystals. The insulated synthons appear as conserved tetrameric motifs in the structures, and the mechanism of interconversion is closely monitored by the synthon modularity. The interconversion is consistent with the theoretically computed stabilization energies of all the tetramers found in this series of cocrystals based on atoms in molecule calculations.

Mechanochemical Synthesis of Amide Functionalized Porous Organic Polymers

Two porous organic polymers decorated with the amide functionality were synthesized mechanochemically and their properties were compared with the ones prepared by conventional solution mediated method. All the POPs were subjected to gas and water vapor sorption studies. The mechanochemically synthesized POPs have less surface area and show moderate adsorption properties compared to the solution mediated POPs. The amide based POPs show remarkable stability in water and concentrated acids.

Solubility-Hardness Correlation in Molecular Crystals: Curcumin and Sulfathiazole Polymorphs

Curcumin and sulfathiazole exist as three and five polymorphs, respectively. We correlate solubility and mechanical properties in these polymorphic systems. It is seen that hardness (H) is inversely proportional to the solubility of a polymorph. H of the polymorphs is explained on the basis of slip planes in the crystal structure, the Schmid factor (m), and the relative orientation of molecules with respect to the nanoindenter direction. Effectively, H is a useful parameter (compared to melting point, T-m, and density, rho) that correlates well with the solubility of a polymorph. Such a correlation is helpful in systems like curcumin and sulfathiazole in which the Gibbs free energy of the polymorphs are close to one another. To summarize, a softer polymorph is more soluble.

First-Principles Study of Structure, Vibrational, and Elastic Properties of Stoichiometric and Calcium-Deficient Hydroxyapatite

Hydroxyapatite (HAp), a primary constituent of human bone, is usually nonstoichiometric with varying Ca/P molar ratios, with the well-known fact that Ca deficiency can cause marked reductions in its mechanical properties. To gain insights into the mechanism of this degradation, we employ first-principles calculations based on density functional theory and determine the effects of Ca deficiency on structure, vibrational, and elastic properties of HAp. Our simulation results confirm a considerable reduction in the elastic constants of HAp due to Ca deficiency, which was experimentally reported earlier. Stress-induced transformation of the Ca-deficient defected structure into a metastable state upon the application of stress could be a reason for this. Local structural stability of HAp and Ca-deficient HAp structures is assessed with full phonon dispersion studies. Further, specific signatures in the computed vibrational spectra for Ca deficiency in HAp can be utilized in experimental characterization of different types of defected HAp.

Tautomeric Preference and Conformation Locking in Fenobam, Thiofenobam, and Their Analogues: The Decisive Role of Hydrogen Bond Hierarchy

The crystal and molecular structures of the potential antidepressant drug fenobam and its derivatives are examined in terms of the preferred form among the two possible tautomeric structures. In this study, chemical derivatization has been utilized as a means to ``experimentally simulate'' the tautomeric preference and conformational variability in fenobam. Eight new derivatives of fenobam have been synthesized, and structural features have been characterized by single-crystal X-ray diffraction and NMR spectroscopy. The specific tautomeric preference found in all of these compounds and their known crystal forms have been construed in terms of the stabilizing intramolecular N-H center dot center dot center dot O and N-H center dot center dot center dot S hydrogen bonding. The hierarchy of intramolecular hydrogen bonds evidenced as the preference of the C-H center dot center dot center dot O hydrogen bond over C-H center dot center dot center dot N and that of the C-H center dot center dot center dot N hydrogen bond over C-H center dot center dot center dot S explains the two distinct conformations adopted by fenobam and thiofenobam derivatives. The relative energy values of different molecular conformations have been calculated and compared.

Cu-II-Azide Polynuclear Complexes of Three Different Building Clusters with the Same Schiff-Base Ligand: Synthesis, Structures, Magnetic Behavior, and Density Functional Theory Studies

Three copper-azido complexes Cu-4(N-3)(8)(L-1)(2)(MeOH)(2)](n) (1), Cu-4(N-3)(8)(L-1)(2)] (2), and Cu-5(N-3)(10)(L-1)(2)](n) (3) L-1 is the imine resulting from the condensation of pyridine-2-carboxaldehyde with 2-(2-pyridyl)ethylamine] have been synthesized using lower molar equivalents of the Schiff base ligand with Cu(NO3)(2)center dot 3H(2)O and an excess of NaN3. Single crystal X-ray structures show that the basic unit of the complexes 1 and 2 contains Cu-4(II) building blocks; however, they have distinct basic and overall structures due to a small change in the bridging mode of the peripheral pair of copper atoms in the linear tetranudear structures. Interestingly, these changes are the result of changing the solvent system (MeOH/H2O to EtOH/H2O) used for the synthesis, without changing the proportions of the components (metal to ligand ratio 2:1). Using even lower proportions of the ligand, another unique complex was isolated with Cu-5(II) building units, forming a two-dimensional complex (3). Magnetic susceptibility measurements over a wide range of temperature exhibit the presence of both antiferromagnetic (very weak) and ferromagnetic exchanges within the tetranuclear unit structures. Density functional theory calculations (using B3LYP functional, and two different basis sets) have been performed on the complexes 1 and 2 to provide a qualitative theoretical interpretation of their overall magnetic behavior.

Tracing a Crystallization Pathway of an RT Liquid, 4-Fluorobenzoyl Chloride: Metastable Polytypic Form as an Intermediate Phase

When quenched with liquid N-2, a room temperature liquid, 4-fluorobenzoyl chloride, generates a new crystalline form that appears to be polytypic to the previously reported form. The structural and energetic correlations between these forms trace a crystallization pathway of the compound.

Stepwise Crystallization: Illustrative Examples of the Use of Metalloligands Cu-6(mna)(6)](6-) and (Ag-6(Hmna)(2)(mna)(4)](4-) (H(2)mna=2-Mercapto Nicotinic Acid) in the Formation of Heterometallic Two- and Three-Dimensional Assemblies with brucite, pcu, and sql Topologies

Three new inorganic coordination polymers, {Mn(H2O)(6)]-Mn-2(H2O)(6)](Cu-6(mna)(6)]center dot 6H(2)O}, 1, {Mn-4(OH)(2)(H2O)(10)] (Cu-6(mna)6]center dot 8H(2)O}, 2, and {Mn-2(H2O)(5)]Ag-6(Hmna)(2)(mna)(4)]center dot 20H(2)O}, 3, have been synthesized at room temperature through a sequential crystallization route. In addition, we have also prepared and characterized the molecular precursor Cu-6(Hmna)(6)]. Compounds 1 and 3 have a two-dimensional structure, whereas 2 has a three-dimensional structure. The formation of 2 has been achieved by minor modification in the synthetic composition, suggesting the subtle relationship between the reactant composition and the structure. The hexanudear copper and silver duster cores have Cu center dot center dot center dot Cu and Ag center dot center dot center dot Ag distances close to the sum of the van der Waals radii of Cu1+ and Ag1+, respectively. The connectivity between Cu-6(mna)(6)](6-) cluster units and Mn2+ ions gives rise to a brucite related layer in 1 and a pcu-net in 2. The Ag-6(Hmna)(2)(mna)(4)](4-) cluster in 3, on the other hand, forms a sql-net with Mn2+. Compound 1 exhibits an interesting and reversible hydrochromic behavior, changing from pale yellow to red, on heating at 70 degrees C or treatment under a vacuum. Electron paramagnetic resonance studies indicate no change in the valence states, suggesting the color change could be due to changes in the coordination environment only. The magnetic studies indicate weak antiferromagnetic behavior. Proton conductivity studies indicate moderate proton migrations in 1 and 3. The present study dearly establishes sequential crystallization as an important pathway for the synthesis of heterometallic coordination polymers.

Polymorphism and Phase Transformation Behavior of Solid Forms of 4-Amino-3,5-dinitrobenzamide

We report the preparation, analysis, and phase transformation behavior of polymorphs and the hydrate of 4-amino-3,5-dinitrobenzamide. The compound crystallizes in four different polymorphic forms, Form I (monoclinic, P2(1)/n), Form II (orthorhombic, Pbca), Form III (monoclinic, P2(1)/c), and Form IV (monoclinic, P2(1)/c). Interestingly, a hydrate (triclinic, P (1) over bar) of the compound is also discovered during the systematic identification of the polymorphs. Analysis of the polymorphs has been investigated using hot stage microscopy, differential scanning calorimetry, in situ variable-temperature powder X-ray diffraction, and single-crystal X-ray diffraction. On heating, all of the solid forms convert into Form I irreversibly, and on further heating, melting is observed. In situ single-crystal X-ray diffraction studies revealed that Form II transforms to Form I above 175 degrees C via single-crystal-to-single-crystal transformation. The hydrate, on heating, undergoes a double phase transition, first to Form III upon losing water in a single-crystal-to-single-crystal fashion and then to a more stable polymorph Form I on further heating. Thermal analysis leads to the conclusion that Form II appears to be the most stable phase at ambient conditions, whereas Form I is more stable at higher temperature.

Stable Crystalline Salts of Haloperidol: A Highly Water-Soluble Mesylate Salt

Haloperidol, an antipsychotic drug, was screened for new solid crystalline phases using high throughput crystallization in pursuit of solubility improvement. Due to the highly basic nature of the API, all the solid forms with acids were obtained in the form of salts. Eleven crystalline salts in the form of oxalate (1:1), benzoate (1:1), salicylate (1:1 and 1:2), 4-hydroxybenzoate (1:1), 4-hydroxybenzoate ethyl acetate solvate (1:1:1), 3,4-dihydroxybenzoate (1:1), 3,5-dihydroxybenzoate (1:1), mesylate (1:1), besylate (1:1), and tosylate (1:1) salt were achieved. There is an insertion of carboxylate or sulfonate anion into the hydrogen bonding pattern of haloperidol. The salts with the aliphatic carboxylic acids were found to be more prone to form salt hydrates compared with aromatic carboxylate salts. All the salts were subjected to solubility measurement in water at neutral pH. There was no direct correlation observed between the solubility of the salt and its coformer. All the salts are stable at room temperature as well as after 24 h slurry experiment except the oxalate salt, which showed an unusual phase transformation from its hydrated form to the anhydrous form. A structureproperty relationship was examined to analyze the solubility behavior of the solid forms.

Obtaining Synthon Modularity in Ternary Cocrystals with Hydrogen Bonds and Halogen Bonds

Design of ternary cocrystals based on synthon modularity is described. The strategy is based on the idea of extending synthon modularity in binary cocrystals of 4-hydroxybenzamide:dicarboxylic acids and 4-bromobenzamide:dicarboxylic acids. If a system contains an amide group along with other functional groups, one of which is a carboxylic acid group, the amide associates preferentially with the carboxylic acid group to form an acidamide heterosynthon. If the amide and the acid groups are in different molecules, a higher multicomponent molecular crystal is obtained. This is a stable pattern that can be used to increase the number of components from two to three in a multicomponent system. Accordingly, noncovalent interactions are controlled in the design of ternary cocrystals in a more predictable manner. If a single component crystal with the amideamide dimer is considered, modularity is retained even after formation of a binary cocrystal with acidamide dimers. Similarly, when third component halogen atom containing molecules are introduced into these binary cocrystals, modularity is still retained. Here, we use acidamide and Br/I center dot center dot center dot O2N supramolecular synthons to obtain modularity in nine ternary cocrystals. The acidamide heterosynthon is robust to all the nine cocrystals. Heterosynthons may assist ternary cocrystal formation when there is a high solubility difference between the coformers. For a successful crystal engineering strategy for ternary cocrystals, one must consider the synthon itself and factors like shape and size of the component molecules, as well as the solubilities of the compounds.

Characterization of Interactions Involving Bromine in 2,2-Dibromo2,3-dihydroinden-1-one via Experimental Charge Density Analysis

Experimental and theoretical charge density analyses on 2,2-dibromo-2,3-dihydroinden-1-one have been carried out to quantify the topological features of a short CBr....O halogen bond with nearly linear geometry (2.922 angstrom, angle CBr....O = 172.7 degrees) and to assess the strength of the interactions using the topological features of the electron density. The electrostatic potential map indicates the presence of the s-hole on bromine, while the interaction energy is comparable to that of a moderate OH....O hydrogen bond. In addition, the energetic contribution of CH.....Br interaction is demonstrated to be on par with that of the CBr....O halogen bond in stabilizing the crystal structure.

Computational Study of the Formation of Short Centrosymmetric N-center dot center dot center dot S Supramolecular Synthon and Related Weak Interactions in Crystalline 1,2,4-Triazoles

A comprehensive analysis of the crystal packing and the energetic features of a series of four biologically active molecules belonging to the family of substituted 4-(benzylideneamino)-3-(4-fluoro-3-phenoxyphenyl)-1H-1,2,4-triazole-5-(4 H)-thione derivatives have been performed based on the molecular conformation and the supramolecular packing. This involves the formation of a short centrosymmetric R-2(2)(8) NH...S supramolecular synthon in the solid state, including the presence of CH...S, CH...O, CH...N, CH...F, CH...Cl, CF...FC, CCl...ClC, and CH...pi intermolecular interactions along with pp stacking to evaluate the role of noncovalent interactions in the crystal. The presence of such synthons has a substantial contribution toward the interaction energy (-18 to -20 kcal/mol) as obtained from the PIXEL calculation, wherein the Coulombic and polarization contribution are more significant than the dispersion contribution. The geometrical characteristics of such synthons favor short distance, and the population of related molecules having these geometries is rare as has been obtained from the Cambridge Structural Database (CSD). Furthermore, their interaction energies have been compared with those present in our molecules in the solid state. The topological characteristics of the NH...S supramolecular synthon, in addition to related weak interactions, CH...N, CH...Cl, CF...FC, and CCl...ClC, have been estimated using the quantum theory of atoms in molecules (QTAIM). In addition, an analysis of the Hirshfeld surface and associated fingerprint plots of these four molecules also have provided a platform for the evaluation of the contribution of different atom...atom contacts, which contribute toward the packing of the molecules in solids.