1 / 24

Nitroxide reduction consequences

Syntheses and Redox Properties of Sterically Shielded Nitroxides of Imidazoline, Imidazolidine, Pyrroline and Pyrrolidine Series. 2. Nitroxide reduction consequences. Spin probe decay Low molecular weight antioxidants depletion Toxicity. 3. How to increase the nitroxide lifetime.

Download Presentation

Nitroxide reduction consequences

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. Syntheses and Redox Properties of Sterically Shielded Nitroxides of Imidazoline, Imidazolidine, Pyrroline and Pyrrolidine Series

  2. 2 Nitroxide reduction consequences • Spin probe decay • Low molecular weight antioxidants depletion • Toxicity

  3. 3 How to increase the nitroxide lifetime • Delivery systems • Liposomes • Inclusion complexes • Bulky substituents

  4. 4 Reduction in the rat blood I.A.Kirilyuk, A.A.Bobko, I.A.Grigor’ev, V.V. Khramtsov, Org.Biomol.Chem., 2004, 2, 1025 Influence of bulky substituents Observed rates of reduction with ascorbate at pH 5.5. [nitroxide] 1 mM, [ascorbic acid] 100 mM L. Marx, R. Chiarelli, T. Guiberteau and A. Rassat, J. Chem. Soc. Perkin Trans. 1, 2000, 1181-1182. 0.027 s-1 0.0009 s-1

  5. 5 Syntheses of sterically shielded nitroxides

  6. 6 Organometallic Compounds Additions. pH-Sensitive Spin Probes pK 6.60 (37 °C) A. A. Bobko, T. D. Eubank, J. L. Voorhees, O. V. Efimova, I. A. Kirilyuk, S. Petryakov, D. G. Trofimiov, C. B. Marsh, J. L. Zweier, I. A. Grigor’ev, A. Samouilov, and V. V. Khramtsov, Magn. Reson. Med., 2012, 67, 1827-1836. D. A. Komarov, I. Dhimitruka, I. A. Kirilyuk, D. G. Trofimiov, I. A. Grigor’ev, J. L. Zweier, V. V. Khramtsov, Magn. Reson. Med., 2012, 68, 649–655.

  7. 7 Organometallic compounds additions. Limitations metallation low reactivity deoxygenation

  8. 8 Organometallic compounds additions. Nitroxides with tert-butyl group at α-carbon

  9. 9 Organometallic compounds additions. Nitroxides with tert-butyl group at α-carbon

  10. 10 Condensations 9% pK = 6.1 kred = 0.04 V. V. Yan’shole, I. A. Kirilyuk, I. A. Grigor’ev, S. V. Morozov, and Yu. P. Tsentalovich, Russian Chemical Bulletin, Vol. 59, No. 1, pp. 66—74.

  11. 11 1,3-Dipolar cycloaddition C. Sár, J. Jekő, K. Hideg, Synthesis, 2003, 9, 1367-1372 C. Sár, E. Ősz, J. Jekő, K. Hideg, Synthesis, 2005, 2, 255-259

  12. 12 Intramolecular 1,3-dipolar cycloaddition D. A. Morozov, I. A. Kirilyuk, D. A. Komarov, A. Goti, I. Yu. Bagryanskaya, N. V. Kuratieva, I. A. Grigor’ev. J. Org. Chem. 2012, 77 (23), pp. 10688-10698.

  13. 13 EPR spectra of pyrrolidine nitroxides 1 mM solutions in H2O+10%DMSO; spectrometer settings: modulation amplitude, 0.5 G; microwave power, 10 mW; time constant, 20 ms; sweep time, 40 s.

  14. 14 EPR line widths problem A.A. Bobko, I.A. Kirilyuk, N.P. Gritsan, D.N. Polovyanenko, I.A. Grigor’ev, V.V. Khramtsov, E.G. Bagryanskaya, ApplMagnReson (2010) 39:437–451.

  15. 15 Partly deuterated nitroxides R=CH3 (1/3); CD3 (2/3).

  16. 16 Paletta, J. T.; Pink, M.; Foley, B.; Rajca, S.; Rajca, A.; Synthesis and Reduction Kinetics of Sterically Shielded PyrrolidineNitroxides. Org. Lett. 2012, Vol.14, No.20, P. 5322-5325.

  17. 17 Mechanism of nitroxides reduction with ascorbate A.A.Bobko, I.A.Kirilyuk, I.A.Grigor’ev, J.L.Zweier, V.V.Khramtsov. FreeRadic. Biol. Med., 2007, V. 42, P. 404-412. k = 5*10-3 M-1c-1

  18. 18 Rate constants of nitroxides reduction with ascorbate 0.02 0.005

  19. 19 Rate constants of reduction with ascorbate, k1, M-1s-1 6.32±0.01 0.044±0.002 5.6±0.2 0.039±0.003 0.063±0.002 0.001 Paletta, J. T.; Pink, M.; Foley, B.; Rajca, S.; Rajca, A.; Synthesis and Reduction Kinetics of Sterically Shielded PyrrolidineNitroxides. Org. Lett. 2012, Vol.14, No.20, P. 5322-5325.

  20. 20 Rate constants of imidazolidine nitroxides reduction with ascorbate

  21. 21 Correlation between the rate constants of nitroxide reductionwith ascorbate(kAsc) and the coupling constants with 1-(tert-butoxycarbonyl)-ethyl radical (kc)

  22. 22 Rate constants of direct and reverse reactions A.A.Bobko, I.A.Kirilyuk, I.A.Grigor’ev, J.L.Zweier, V.V.Khramtsov. FreeRadic. Biol. Med., 2007, V. 42, P. 404-412.

  23. Hydrogen atom exchange 23 NR CPH-15N PСА-15N 0.04 0.02

More Related