How to easily replace the independent atom model - the example of bergenin, a potential anti-HIV agent of traditional Asian medicine.
Bergenin, which has been isolated from a variety of tropical plants, has several pharmacological applications in traditional Asian medicine. Its electron-density distribution was obtained from a room-temperature low-resolution X-ray data set measured with point detection making use of multipole populations from the invariom library. Two refinement models were considered. In a first step, positional parameters and ADPs were refined with fixed library multipoles (model E1). This model was suitable to be input into a second refinement of multipoles (model E2), which converged smoothly although based on Cu Kalpha room-temperature data. Quantitative results of a topological analysis of the electron density from both models were compared with Hartree-Fock and density-functional calculations. With respect to the independent atom model (IAM) more information can be extracted from invariom modelling, including the electrostatic potential and hydrogen-bond energies, which are highly useful, especially for biologically active compounds. The reliability of the applied invariom formalism was assessed by a comparison of bond-topological properties of sucrose, for which high-resolution multipole and invariom densities were available. Since a conventional X-ray diffraction experiment using basic equipment was combined with the easy-to-use invariom formalism, the procedure described here for bergenin illustrates how it can be routinely applied in pharmacological research.
Dittrich
Birger
B
Institut für Anorganische Chemie, Georg-August-Universität Göttingen, Tammanstrasse 4, D-37077 Göttingen, Germany.
Weber
Manuela
M
Kalinowski
Roman
R
Grabowsky
Simon
S
Hübschle
Christian B
CB
Luger
Peter
P
D019380:Anti-HIV Agents / Q000737:chemistry*; D001578:Benzopyrans / Q000737:chemistry*; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D008518:Medicine, East Asian Traditional; D008958:Models, Molecular; D008968:Molecular Conformation; D055672:Static Electricity
D019380:Anti-HIV Agents; D001578:Benzopyrans; C006741:bergenin