Biomedical subjects

Y-H Kiang

Publications and source records attributed to Y-H Kiang.

4 recordsLinked to original sources

PubMed2004

Crystal structure and surface properties of an investigational drug--a case study.

In this study we investigate the correlations between the single crystal structure, the crystal habitat and morphology, and surface energetics of an investigational pharmaceutical compound. Crystal structure of this investigational pharmaceutical solid has been solved from single crystal X-ray analysis. Crystallographic data are as follows: triclinic, P1 (no. 1), a = 6.1511 (8) A, b = 13.5004 (18) A, c = 17.417 (2) A, alpha = 68.259 (2) degrees, beta = 80.188 (2) degrees, gamma = 82.472 (2) degrees, V = 1320.2 (3) A(3), Z = 2. The external morphology of this crystalline solid was predicted by molecular modelling using attachment energies to be thin-plate like with a dominant face (001). The predicted morphology was confirmed by scanning electron micrographs (SEM) and the Miller Index of the dominant face was complemented by X-ray powder diffraction (XRPD) method. The microscopic layering structures of crystals and surface stability of the dominant faces were investigated using atomic force microscopy (AFM). Contact angle measurement showed that the surface of the dominant face is hydrophilic as predicted from crystal structure.

Crystallization↗

PubMed2003

Ab initio structure determination of rofecoxib from powder diffraction data using molecular packing analysis method and direct space method.

Crystal structures of a COX-II inhibitor, rofecoxib (Vioxx) were solved ab initio from X-ray powder diffraction pattern using both molecular packing analysis and direct space methods. The X-ray powder pattern was indexed into a tetragonal cell. Packing energies were generated and analyzed in eight most frequently found tetragonal space groups. The two space groups with the lowest total energy, P4(1)2(1)2 and P4(3)2(1)2, were used for direct space method with a Monte-Carlo/Simulated Annealing searching algorithm. Structural solutions obtained from direct space method were evaluated using molecular packing energy analysis. The structures solved ab initio from this work were compared to the single crystal structure deposited in the Cambridge Structural Database.

Crystallization↗

PubMed2003

Structure determination of enalapril maleate form II from high-resolution X-ray powder diffraction data.

The crystal structure of polymorphic Form II of enalapril maleate, a potent angiotensin-converting enzyme inhibitor, was determined from high-resolution X-ray diffraction data using the direct space method. Enalapril maleate Form II crystallizes in space group P2(1)2(1)2(1), Z = 4, with unit cell parameters a = 33.9898(3) A, b = 11.2109(1) A, c = 6.64195(7) A, and V = 2530.96(5) A(3). By treating the molecules as rigid bodies and using the bond lengths and angles obtained from the X-ray single crystal structures of Form I, which were solved almost 20 years ago, the total degrees of freedom of enalapril maleate were reduced from 25 to 12. This reduction in total degrees of freedom allowed the simulated annealing to complete within a reasonable computation time. In the crystal structure of Form II, the crystal packing, hydrogen-bonding pattern, and conformation of enalapril maleate resemble those in the structure of Form I. The crystal packing and conformation of enalapril maleate in the two polymorphic forms may explain the similarity of the thermal properties, (13)C nuclear magnetic resonance, Fourier transform infrared, and Raman spectra of Forms I and II. In both structures, the conformations of the main peptide chains, which are considered responsible for binding the active angiotensin-converting enzyme sites, remain largely unchanged. Lattice energy calculation showed that Form II is slightly more stable than Form I by 3.5 kcal/mole.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2002

Structure rationalization and topology prediction of two-distinct-component organic crystals: the role of volume fraction and interface topology.

We consider here small-length-scale crystal structures with two clearly different molecular components (e.g., hydrophobic and hydrophilic). Using a perspective developed by studies on large-length-scale block copolymers and liquid crystals, we focus on the crystalline interface between the two components. We examine four types of two-component crystals: aromatic ammonium carboxylates, aromatic oligo(ethylene oxides), cyclohexylammonium carboxylates, and ether-thioether compounds. Of the 111 crystal structures found in the Cambridge Structure Database (CSD), 108 adopt one of the five generic topologies found in diblock copolymers: spheres, columns, perforated layers, layers, and bicontinuous structures. As in diblock copolymers, a key factor controlling the interfacial topology is shown to be the volume ratio of the two components. When the volume fraction of one component is less than 30% of the whole, more than five-sixths of the examined crystal structures are of columnar or spherical type. For volume fractions between 40 and 50% more than three-quarters are of lamellar or bicontinuous type. We use this model to predict the topologies of small-length-scale two-component crystals. We predict the crystal topolgies of six new crystal structures: three are predicted to be columnar, and the other three, lamellar or bicontinuous. The crystal structures of these systems were then determined by single-crystal X-ray methods. Five of the structures form in topologies consistent with the predictions: three in columns and two in layers. The remaining one forms as a perforated layer instead of the predicted columnar structure. Such predictive accuracy is consistent with the statistics of the CSD investigation.

Journal Article↗