How to easily replace the independent atom model - the example of bergenin, a potential anti-HIV agent of traditional Asian medicine

Acta Crystallogr B. 2009 Dec;65(Pt 6):749-56. doi: 10.1107/S0108768109046060. Epub 2009 Nov 16.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / chemistry*
  • Benzopyrans / chemistry*
  • Crystallography, X-Ray
  • Hydrogen Bonding
  • Medicine, East Asian Traditional
  • Models, Molecular
  • Molecular Conformation
  • Static Electricity

Substances

  • Anti-HIV Agents
  • Benzopyrans
  • bergenin