Guest Inclusion Crystal structures of Macrocyclic Boronic Esters

Macrocyclic compound has been attracting increasing attention because of their application for guest absorption and storage, guest selectivity, and reaction environment, which would utilize void space in the compound. Recently, such macrocyclic compound, boronic esters, has found to be formed as dynamic self-assembly of organic molecules through solvent dependent dynamic covalent bond formation between racemic polyol and planar 1,4-benzen(boronic acid)[1]. Thus, it is important to determine the crystal structure of the macrocyclic boronic esters with incorporated guest molecule to reveal the features of the compounds. In this study, structures of boronic ester of 1,4- naphthalene(boronic acid) (1) are presented and compared. The boronic ester with toluene guest molecule crystalized in monoclinic system, C2/c, Z=4, V=5099.7(6) Å3. As expected, toluene molecule was accommodated within a ring sandwiched by two naphthalene rings suggesting π-π interaction (ca. 3.6 Å separations). It is interesting that other structures of 1 with 1,4-dicyanobenzene, chloroform, and THF also have isomorphic structures to 1 with toluene. It clearly shows the guest inclusion ability of this boronic ester by weak intermolecular interactions. In the crystal structures, the boronic ester aligned along b-axis forming one-dimensional stacking with channel structure filled with guest molecules. Also, 1 with chloroform has a pseudo-polymorph phase (P21/c, V=5780.8(13) Å3) that has two additional chloroform molecules inside and outside of the ring; however, it also shows similar one-dimensional stacking structure with channel, implying this boronic ester has an easily stacking molecular shape. Although, the molecules have similar [2+2] ring structure, dihedral angle between two facing naphthalene rings is different in 1 with toluene, which is smaller as 14.1⁰ than 22 to 24⁰ in other structures. It may indicate a flexibility of the macrocyclic ring.

Dehydration mechanism of Ciprofloxacin Hydrochloride hydrate crystal

Active pharmaceutical ingredients (APIs) often exist in different crystalline forms such as hydrate and polymorph, which show different pharmaceutically important physicochemical properties such as crystal color, solubility, stability, dissolution rate and bioavailability. Moreover, crystalline phase transformation is induced by environmental changes such as heating and humidity. Thus, mechanistic investigation based on crystal structures is essential. Ciprofloxacin Hydrochloride (CIP) is fluoroquinolone antimicrobials with potent activity against a broad spectrum of bacteria. From TG/DTA and XRD-DSC measurement, the sesqui-hydrate form dehydrates to anhydrate form I at 140 °C and then transforms to another anhydrate form II at 172 °C. The single crystals of sesqui-hydrate form and anhydrous II were obtained by recrystallization from water and methanol, respectively. However, anhydrate I could not be obtained as single crystal, so the powder crystal form was accomplished by dehydration of hydrate form at 140 °C at vacuum heating condition, and the crystal structure was analyzed by ab-initio powder crystal structure analysis technique using synchrotron X-ray diffraction data. The crystal structure of anhydrous form I was partly related to the hydrate in the packing, i.e., both show one-dimensional chain and two-dimensional sheet structure. However, in anhydrous II, only one-dimensional chain structure was retained. Interestingly, the colors of powder crystal of hydrate and anhydrate I were white, meanwhile, anhydrate II appeared as yellow crystalline powder. The color changes may be explained from their molecular conformation . The torsion angle between flouroquinolone and piperazine of hydrate, anhydrate form I (white) and anhydrate form II (yellow) was 145.71°, 136.28° and 108.65°, respectively. Thus, the large difference in anhydrate II might affect the conjugation in aromatic group slightly and resulted in the color change.

Hydration and Dehydration Transformation Mechanism of Cefaclor Pseudopolymorphs

Hydration/dehydration phase transitions of active pharmaceutical ingredients (API) are often accompanied with changes of physicochemical properties, such as solubility, stability, and bioavailability. Therefore, three dimensional structural investigation of the hydration / dehydration mechanism of API is important for pharmaceutical research and development. By relative humidity control, Cefaclor hydrate crystal dehydrates non-stoichiometrically from dihydrate to anhydrous form A. Unexpectedly, its monohydrate form transformed into new 1.9 hydrate by slurry treatment (methanol / water) which dehydrated into another anhydrous form B through hemihydrate by heating. In this study, these hydration and dehydration presudo-polymorphic transitions of Cefaclor are investigated by the crystal structure analyses. Crystal structures of anhydrous and partially dehydrated forms were determined by structure determination from powder diffraction data technique because such dehydration phase transitions were resulted in a disintegration of single crystal form. In the first dehydration route, hydrates and the anhydrous form A have similar crystal structure, which is referred as `isomorphic desolvation'. Interestingly, the anhydrous form A has void spaces which corresponds to the water molecule position in the hydrate form. Thus, in hydration / dehydration phase transitions, water molecules move in and out of the void without changing the crystal structures, and the anhydrous form A can hydrate even in low R.H. condition. In the second route, the 1.9 hydrate, hemihydrate and the anhydrate form B have three crystallographically independent molecules forming similar T-shape building block pattern. There are tunnel spaces along b axis between the blocks. In the hydration / dehydration process, the blocks slide each other to open and close the channel. This mechanism explains another non-stoichiometric dehydration in this route.