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

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

Legal notice
  • Legal notice:

    Copyright (c) Pielaszek Research, all rights reserved.
    The above materials, including auxiliary resources, are subject to Publisher's copyright and the Author(s) intellectual rights. Without limiting Author(s) rights under respective Copyright Transfer Agreement, no part of the above documents may be reproduced without the express written permission of Pielaszek Research, the Publisher. Express permission from the Author(s) is required to use the above materials for academic purposes, such as lectures or scientific presentations.
    In every case, proper references including Author(s) name(s) and URL of this webpage: http://science24.com/paper/23217 must be provided.

 

Related papers
  1. The comparison of the stability indicating  two HPLC methods and their application for the determination of bosentan in coated tablets 
  2. Elaboration of travoprost eye drops formulation.
  3. What modern crystallography can add to pharmaceutical research?
  4. Antiproliferative and cytotoxic effect of vitamin D3 and its derivatives on the selected cells with a higher proliferative potential
  5. Pharmaceutical  technologies  – why do they have to be innovative
  6. A novel convergent synthesis of the prostaglandin F analogues
  7. Comparative permeation studies of tacalcitol through the human skin from brand product versus generic product
  8. HPLC method for determination of the enantiomeric purity of a new ω chain aldehyde synthon used in the synthesis of travoprost
  9. Physicochemical characterization of sunitinib and its impurities
  10. Vitamin D analogs enhance the activity of imatinib mesylate in human non-small cell lung cancer model
  11. Colon cancer treatment with the use of vitamin D analogs and irinotecan 
  12. Synthetic Technologies of Pharmaceutical Substances
  13. The influence of (24R)-1,24- dihydroxyvitamin D3 on the anticancer activity of 5-fluorouracil in human colon cancer model
  14. The use of the hyphenated LC-MS/MS technique for the characterisation of impurity profile of Quetiapine during drug development
  15. A novel synthesis of 19-nor analogs of vitamin D
  16. The influence of novel analogs of vitamin D3 on the antiproliferative activity of cisplatin or doxorubicin on human promyelocytic leukaemia cell line HL-60 
  17. Isolation, structural elucidation and characterization of impurities in latanoprost
  18. New rosiglitazone salts
  19. New calcipotriol analogs, their toxicity and antitumor activity in vivo in comparison to the affinity with VDR and DBP
  20. High-yielded method of synthesis of voriconazole.
  21. Redox processes of dithiolated tetraazamacrocyclic complexes of Ni(II) and Cu(II) in solution and immobilized on gold electrodes
  22. Charge Density Studies of Tetraazamacrocyclic Complexes of Copper(II) and Nickel(II)
  23. Polimorphism of Active Pharmaceutical Ingredients
  24. Sigma Cutoff - and What Lies Behind
  25. ANTITUMOR EFFECT OF CISPLATIN OR FLUOROURACIL IN COMBINED TREATMENT WITH (24R)-1,24-DIHYDROXYVITA- MIN D3
  26. COMBINATION OF: IMATINIB, PRI-2191 AND CYTOSTATICS - THE ANTIPROLIFERATIVE EFFECTS ON HL-60 LEUKEMIA CELL LINE
  27. ANTIPROLIFERATIVE ACTIVITY IN VITRO OF DIASTEREOMERIC ANALOGUES OF VITAMIN D3 AGAINST NORMAL AND CANCER CELL LINES
  28. Fine-tuning of properties of bismacrocyclic dinuclear cyclidene receptors by N-methylation.

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
Google
 
Web science24.com
© 1998-2021 pielaszek research, all rights reserved Powered by the Conference Engine