1 / 26

NMR Shielding and Antimalarial Drugs Angel C. de Dios Georgetown University

NMR Shielding and Antimalarial Drugs Angel C. de Dios Georgetown University. 13. CARB-NMR Day 2006. Chloroquine Resistance, 2002. http://www.cdc.gov/ travel/diseases/maps. Antimalarial Drugs. Red Blood Cell Hemoglobin Digestion. Heme. Hemozoin.

neviah
Download Presentation

NMR Shielding and Antimalarial Drugs Angel C. de Dios Georgetown University

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. NMR Shielding and Antimalarial Drugs Angel C. de Dios Georgetown University 13 CARB-NMR Day 2006

  2. Chloroquine Resistance, 2002 http://www.cdc.gov/ travel/diseases/maps

  3. Antimalarial Drugs Red Blood CellHemoglobin Digestion Heme Hemozoin Pagola, S.; Stephens, P. W.; Bohle, D. S.; Kosar, A. D.; Madsen, S. K. Nature, 404, 307 (2000) Leed, A.; DuBay, K.; Ursos, L. M. B.; Sears, D. N.; de Dios, A. C.; Roepe, P. D. Biochemistry, 41, 10245 (2002)

  4. Amodiaquine Chloroquine Quinine Casabianca, L. B.; de Dios, A. C. J. Phys. Chem. A,108 (40), 8505 -8513, (2004)

  5. J. Phys. Chem. A,108 (40), 8505 -8513, 2004 Quinine carbon 8

  6. Casabianca, L. B.; de Dios, A. C. J. Phys. Chem. A,108 (40), 8505 -8513, (2004)

  7. Interactions between drug molecules Casabianca, L. B.; de Dios, A. C. Magn. Reson. Chem., 44, 276-282 (2006)

  8. Solution structures of drug-heme complex Leed, A.; DuBay, K.; Ursos, L. M. B.; Sears, D. N.; de Dios, A. C.; Roepe, P. D. Biochemistry, 41, 10245 (2002) de Dios, A.C.; Casabianca, L.B.; Kosar, A.; Roepe, P.D. Inorg. Chem., 43, 8078-8084, (2004)

  9. Biochemistry,41 (32), 10245 -10255, (2002)

  10. Chemical shifts and p electron density Search for a Quantitative Structure-Activity Relationship (QSAR) Experimental Chemical Shift* I II Carbon Difference 2 165.5 152.2 -13.3 3 119.8 119.4 -0.4 4 147.9 137.5 -10.4 5 125.3 126.4 1.1 6 128.4 127.8 -0.6 7 125.1 129.8 4.7 8 129.4 120.8 -8.6 9 126.4 128.9 2.5 10 146.7 140.9 -5.8 1,8-bis(2-isopropyl-4-quinolyl)naphthalene Tumambac, G. E.; Wolf, C. J. Org. Chem.69, 2048 (2004) Tumambac, G. E.; Wolf, C. J. Org. Chem. 70, 2930 (2005)

  11. Ramsey’s Equations for Calculating Chemical Shielding Ramsey, N. F. Phys. Rev. 1950, 78, 699-703. de Dios, A.C. Prog. NMR Spectrosc.1996, 29, 229-278.

  12. Shielding Tensors in Aromatic Rings

  13. Strub, H.; Beeler, A. J.; Grant, D. M.; Michl, J.; Cutts, P. W.; Zilm, K. W. J. Am. Chem. Soc., 105, 3333, (1983)

  14. Calculated Shielding Differences Casabianca, L.B.; Faller, C.M. Faller; de Dios, A.C. J. Phys. Chem. A, 110, 234-240, (2006)

  15. Quinine

  16. Maps of 11 “-electron density” B A B A

  17. Heme

  18. Heme-Drug

  19. Heme-Drug Solution Structures Electron-Rich Electron-Poor Leed, A.; DuBay, K.; Ursos, L. M. B.; Sears, D. N.; de Dios, A. C.; Roepe, P. D. Biochemistry41, 10245 (2002) de Dios, A. C.; Casabianca, L. B.; Kosar, A. D.; Roepe, P. D. Inorg. Chem. 43, 8078 (2004)

  20. Substituted Aminoquinolines Log K values from Kaschula, C. H.; Egan, T. J.; Hunter, R.; Basilico, N.; Parapini, S.; Taramelli, D.; Pasini, E.; Monti, D. J. Med. Chem.45, 3531 (2002)

  21. Solid State NMR Studies de Dios, A.C.; Tycko, R.; Ursos, L.M.B.; Roepe, P.D. J. Phys. Chem. A,107 (30), 5821 -5825, (2003)

  22. de Dios, A.C.; Tycko, R.; Ursos, L.M.B.; Roepe, P.D. J. Phys. Chem. A,107 (30), 5821 -5825, (2003)

  23. de Dios, A.C.; Tycko, R.; Ursos, L.M.B.; Roepe, P.D. J. Phys. Chem. A,107 (30), 5821 -5825, (2003)

  24. de Dios, A.C.; Tycko, R.; Ursos, L.M.B.; Roepe, P.D. J. Phys. Chem. A,107 (30), 5821 -5825, (2003)

  25. de Dios, A.C.; Tycko, R.; Ursos, L.M.B.; Roepe, P.D. J. Phys. Chem. A,107 (30), 5821 -5825, (2003)

  26. Acknowledgements Alison Leed • National Institutes of Health • Georgetown University • Luce Foundation • ARCS Foundation Prof. Paul Roepe, PhD Lyann Ursos, PhD Leah Casabianca Prof. Christian Wolf, PhD Caitlyn Faller Devin Sears, PhD Kateri DuBay NIH (Robert Tycko’s group)

More Related