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Experimental and theoretical charge density studies on a model analogue of vitamin D

Maura D. Malińska 1,  Andrzej Kutner 2,  Michał Chodyński 2,  Krzysztof Woźniak 1

1. University of Warsaw, Faculty of Chemistry, Pasteura1, Warsaw 02-093, Poland
2. Pharmaceutical Research Institute (IF), Rydygiera 8, Warszawa 01-793, Poland

Abstract
SYN1 (Fig. 1)  is used in the synthesis of  vitamin D analogues. For example calcipotriol, calcitriol and alfacalcidol are good examples of those analogues  that have undergone clinical trials with positive outcome [1,2]. The charge density analysis, and multipole-model based on Hansen-Coppens formalism [3] refinement of electron density, obtained from theoretical and experimental structure factors, shows interesting results.
SYN1 crystallizes in a general position in the orthorhombic P212121 space group. Molecules are packed  in layers, in 3D. The layers are joined by C-H---O hydrogen bond type contacts. There are two types of these bonds: the first one is situated between the oxygen atom from the  sulfo group, and hydrogen from the aromatic ring. The second one is situated between the carbonyl oxygen and methylene hydrogen. High resolution experiment allowed obtaining a multipole model of experimental electron density. Subsequently topological analysis was performed. This approach revealed some differences in the interaction energy for the examined interactions and allowed characterizing quantitatively the details of charge density distribution both, in the molecule, and in the crystal lattice. 

Fig 1. The molecular structure of SYN1 and atomic labeling. Thermal displacement ellipsoids are shown at the 50% probability level.

Fig 2. The contour plot of Laplacian of charge density. Plane is set through three atoms: O(2), C(15) and C(4).

[1] Fogh K., Kragballe K., Curr Pharm Des, 2000, 6, 961.

[2] Slatopolsky E., Brown A.J., Blood Purif, 2002, 20, 109.

[3] Hansen N.K., Coppens P., Acta Cryst., 1978, A34, 909.

 

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Presentation: Poster at VII Multidyscyplinarna Konferencja Nauki o Leku, by Maura D. Malińska
See On-line Journal of VII Multidyscyplinarna Konferencja Nauki o Leku

Submitted: 2010-04-28 19:00
Revised:   2010-04-29 16:42