Electron densities of bexarotene and disila-bexarotene from invariom application: a comparative study.

Peter Luger, Manuela Weber, Christian Hübschle, Reinhold Tacke

Freie Universität Berlin, Institut für Chemie und Biochemie/Anorganische Chemie, Fabeckstr. 36a, D-14195 Berlin, Germany. luger@chemie.fu-berlin.de

Organic & biomolecular chemistry 2013 Apr 14

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By the application of the invariom formalism, which provides aspherical atomic scattering factors, the electron densities of the RXR-selective retinoid agonists bexarotene (1a) and disila-bexarotene (1b) were derived from their known low resolution (d = 0.76 Å) crystal structures. The density distributions allowed us to make a comparison of the electronic properties of these pharmacologically relevant compounds. Differences were found to be restricted to relatively small regions in the terminal six-membered rings of the tetrahydronaphthalene and tetrahydrodisilanaphthalene fragments. In total, the replacement of two carbon atoms in 1a by silicon atoms (→1b) does neither influence the electronic structures nor the pharmacological properties (RXR receptor activation) significantly. It should be noted that the almost completely software supported invariom formalism can yield electronic information for biologically interacting systems with moderate effort. This offers interesting possibilities for drug research, in that steric and electronic information can be combined for the analysis of intermolecular recognition and interaction on an atomic scale. This approach is also valuable for the design and development of silicon-containing drugs using the carbon/silicon switch strategy.

Citation

Peter Luger, Manuela Weber, Christian Hübschle, Reinhold Tacke. Electron densities of bexarotene and disila-bexarotene from invariom application: a comparative study. Organic & biomolecular chemistry. 2013 Apr 14;11(14):2348-54