Pharmaceutical materials and polymorphism
A palladium catalyst supported by Si-Thiol, which was a commercially available mercaptopropyl-modified and TMS-passivated amorphous silica, was synthesized and characterized by SEM、TEM、aberration-corrected STEM-HAADF、XRD、FTIR and XPS. Statistical analysis reveals that the catalytic Pd species in Si-Thiol consist of dominant atom clusters (< 2nm), small amount of single atoms (ca. 0.1nm), and trace amount of nanoparticles (< 5nm). Suzuki coupling reaction shows that the catalyst synergistically plays full functions of what the corresponding homogeneous catalyst can offer. It is believed that the atom clusters dominate the total activity and sever as the key active site for Suzuki coupling. The outcomes of the reaction are greatly affected by choice of solvents, and Pd/Si-Thiol is demonstrated to be reusable over multiple times without noticeable loss of activity.
Polymorphs can be viewed as material phases with identical elemental composition but different molecular or crystal structures. Thermodynamically, polymorphs would constitute local minima in the energy landscape with the thermodynamically stable form being the absolute minimum at a given temperature and pressure. A renewed interest in polymorphism from both industry and academia is due to better recognition of the effects that polymorphism has on the activity, manufacturability, and stability of the drug products. Recent efforts include investigating the chemical transformations and unusual degradation of sodium warfarin (Coumadin®, registered trademark of Bristol Myers Squibb).
Hui-Yin (Harry) Li, Rui Liu, Carl Behrens, and Chaoying Ni, Chapter 7 Industrial Application of Chiral Technologies, Wiley, 2011, 253-296.
Xiazhang Li, Zuogang Huang, Andrew Herzing, Hui-Yin (Harry) Li, David C. Martin, Chaoying Ni, Si-Thiol supported atomic-scale palladium catalyst for Suzuki coupling reaction, manuscript prepared and under revision.