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Hemoglobin

Hemoglobin. 4 polypeptide chains A conjugated protein Contains HEME units (prosthetics) The heme binds O 2. The Heme group. porphyrin + iron(II). heme group. Allosteric Interactions. Binding of oxygen results in a conformational change. Deoxy Hb + O 2 Oxy Hb.

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Hemoglobin

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  1. Hemoglobin • 4 polypeptide chains • A conjugated protein • Contains HEME units (prosthetics) • The heme binds O2

  2. The Heme group porphyrin + iron(II) heme group

  3. Allosteric Interactions • Binding of oxygen results in a conformational change Deoxy Hb + O2 Oxy Hb • Conformational change makes binding additional O2 molecules easier (“cooperative binding”) • Hemoglobin is used primarily to bind and transport oxygen • MYOGLOBIN is used to store the oxygen

  4. http://www3.interscience.wiley.com:8100/legacy/college/boyer/0471661791/structure/HbMb/hbmb.htmhttp://www3.interscience.wiley.com:8100/legacy/college/boyer/0471661791/structure/HbMb/hbmb.htm http://upload.wikimedia.org/wikipedia/commons/0/07/Hb-animation2.gif

  5. Myoglobin, Mb • Similar to Hb, but only one peptide chain • Stores O2 • Binds O2 more strongly than Hb

  6. Affinity of Hb & Mb for oxygen

  7. When Working Out... • You produce lots of CO2 and lactic acid in muscles HbO2 + acid HbH+ + O2 HbO2 + CO2 HbCO2 + O2 • H+ and CO2 can bind to hemoglobin, making oxygen more available!!

  8. Chlorophyll

  9. 1 . L i g a n d E x c h a n g e D i s s o c i a t i v e D P P h 3 W ( C O ) W ( C O ) P h P W ( C O ) 6 5 3 5 A s s o c i a t i v e P P h P P h P P h 3 3 3 C l B r - C l O C I r C l O C I r O C I r B r B r P P h P P h P P h 3 3 3 R a d i c a l C h a i n P P h R 3 R e ( C O ) H R e ( C O ) P h P R e ( C O ) 5 5 3 4 - C O R - H H P h P R e ( C O ) 3 5

  10. d6 metal-silylene complexes Bond lengths29SiNMR shifts Cr-Si = 232.9 pm 136.9 ppm Mo-Si = 247.1 pm 119.3 ppm W-Si = 247.1 pm 97.7 ppm • Monosubstituted complex is observed, but disubstituted is the major product. Schmedake, T. A., Haaf, M. P., Paradise, B. J., Millevolte, A. J.; Powell, D., West, R.;.J. Organomet. Chem. 2001, 636, 17

  11. CO stretching frequencies • If L is a good s-donor and/or poor p-acceptor, the CO shift • If L is a poor s-donor and/or good p-acceptor, the CO shift s-donor / p-acceptor Schmedake, T. A., Haaf, M. P., Paradise, B. J., Millevolte, A. J.; Powell, D., West, R.;.J. Organomet. Chem. 2001, 636, 17

  12. CO stretches for Mo series Approximate trend for s-donor/p-acceptor ratios: N-heterocyclic carbenes > PR3 > PPh3 ~ 1 > 2 > P(OR)3 > P(OAr)3 Schmedake, T. A., Haaf, M. P., Paradise, B. J., Millevolte, A. J.; Powell, D., West, R.;.J. Organomet. Chem. 2001, 636, 17

  13. 2 . O x i d a t i v e A d d i t i o n - R e d u c t i v e E l i m i n a t i o n C H P P h 3 3 P P h 3 C H C l 3 O C I r C l O C I r C l P h P 3 C l P P h 3 I r ( I I I ) I r ( I ) P h O O + ( O C ) F e 4 ( O C ) F e C H P h C H 4 3 3 F e ( I I ) F e ( 0 )

  14. 3 . S i g m a B o n d M e t a t h e s i s H C H H 3 2 Z r C H Z r 4 H C H 3 M C H M C H 3 3 H H H H +

  15. 4 . M i g r a t o r y I n s e r t i o n R C l C l H Z r Z r C C H H H 2 R C p v i a C l C p Z r H R

  16. 4 . M i g r a t o r y I n s e r t i o n

  17. 5 . M e t a l H y d r i d e E l i m i n a t i o n P P h 3 H C O C 3 2 B r P d P P h 3 P P h C O C H 3 2 3 + B r P d H P P h 3 6 . N u c l e o p h i l i c A t t a c k o n C o o r d i n a t e d L i g a n d s P P h P P h O H 3 3 2 O H P h P P d P h P P d 3 3 C l C l

  18. 7 . T r a n s m e t a l l a t i o n P h P P h P 3 3 P d + P d B u S n + B r S n B u 3 3 P h P P h P B r 3 3 8 . C l e a v a g e o f C - M b o n d s b y e l e c t r o p h i l e s + H H Z r H

  19. Cross-Coupling Reactions

  20. The Stille Reaction palladium catalyst eletrophilic organic substrate X = halide or sulfonate stannane (transfer agent) alkyl = Me or Bu Milstein, D.; Stille, J. K. J. Am. Chem. Soc.1979, 101, 4992

  21. Relative transfer rates alkyl allyl ~ benzyl aryl vinyl alkynyl “PdL2” L = neutral ligand slow fast X = I, Br, OTf Milstein, D.; Stille, J. K. J. Am. Chem. Soc.1979, 101, 4992

  22. Advantages of the Stille Reaction • Tolerate a variety of functional groups • Largely insensitive to sterics on organic electrophile • Reactants are generally stable to air and moisture • Highly catalytic (turnover ~ 20,000) • A diverse array of functionalized organostannanes are readily available

  23. Limitations of the Stille Reaction • Tin compounds are toxic • Tin compounds are difficult to separate from products • Bulky vinyl stannanes don’t transfer efficiently • Alkyl groups on stannane are difficult to transfer selectively • Palladium catalyst can decompose before coupling is complete

  24. Putative Mechanism Casado, A. L.; Espinet, P. J. Am. Chem. Soc., 1998, 120, 8978

  25. Stille Coupling to Aryl Chlorides • P(t-Bu)3 ligand enhances the reactivity of Pd catalyst • Addition of fluoride activates the organotin reagent • Reaction appears to be general Littke, A. F.; Fu, G. C. Angew. Chem, Int. Ed. Engl.1999, 38, 2411

  26. Entry R % yield 1 2 3 4 5 82 98 87 94 82 Littke, A. F.; Fu, G. C. Angew. Chem. Int. Ed. Engl.1999, 38, 2411

  27. Selective Alkyl Transfer Vedejs, E.; Haight, A. R.; Moss, W. O. J. Am. Chem. Soc.1992, 114, 6556

  28. One Pot Stille Coupling Alternate Conditions: Maleczka, R. E.; Terstiege, I. J. Org. Chem.1998, 63, 9622

  29. One Pot Stille Coupling Alkyne Product Bu3SnH stepwise 89% 43% 87% 65% 51% 59% Maleczka, R. E.; Terstiege, I. J. Org. Chem.1998, 63, 9622

  30. Carbonylative Coupling Knight, S. D.; Overman, L. E.; Pairaudeau, G. J. Am. Chem. Soc. 1993, 115, 9293

  31. Tandem Stille Couplings Antonelli, E.; Rosi, P.; Lo Sterzo, C.; Viola, E. J. Organomet. Chem. 1999, 578, 210

  32. Tandem Stille Couplings Nicolaou, K. C.; Xu, J.; Murphy, F.; Barluenga, S.; Baudoin, O.; Wei, H.; Gray, D. L.; Ohshima, T. Angew. Chem. Int. Ed.1999, 38, 2447

  33. Nicolaou, K. C.; Xu, J.; Murphy, F.; Barluenga, S.; Baudoin, O.; Wei, H.; Gray, D. L.; Ohshima, T. Angew. Chem. Int. Ed.1999, 38, 2447

  34. The Suzuki Reaction Boronic acid Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457

  35. Suzuki

  36. Suzuki with boronic esters

  37. Heck Coupling JACS, 2002, 124, 6552

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