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10.1A

Phosphates. pKa 1 : 2.1 pKa 2 : 7.2 pKa 3 : 12.3. actual charge at pH 7 ~ -1.5. pKa’s ~ 2, 7. 10.1A. phosphate monoesters. 10.1A. 10.1A. Bonding in phosphines (analogs of amines). electron configuration:. P. 10.1C. Electron configuration in phosphate. 4 s bonds - tetrahedral.

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10.1A

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  1. Phosphates pKa1: 2.1 pKa2: 7.2 pKa3: 12.3 actual charge at pH 7 ~ -1.5 pKa’s ~ 2, 7 10.1A

  2. phosphate monoesters 10.1A

  3. 10.1A

  4. Bonding in phosphines (analogs of amines) electron configuration: P 10.1C

  5. Electron configuration in phosphate 4 s bonds - tetrahedral 10.1C

  6. p bond delocalized 10.1C

  7. on esters, bridging oxygens don’t share p bonding charge spread over non-bridging oxygens 10.1C

  8. phosphoryl transfer reactions 10.1D

  9. example: 10.1D

  10. hydrolysis of phosphate ester: transfer of phosphate to water acceptor donor 10.1D

  11. 10.1D

  12. 10.1D

  13. 10.1D

  14. Proceeds with inversion (like SN2) 10.1D

  15. Is tetravalent state a TS? option 1 10.1E

  16. . . . or an intermediate? option 2 10.1E

  17. stable phosphorus pentavalent compound: sp3d hybridization: (notice this is not possible for SN2 reaction at carbon!) 10.1E

  18. another possibility (SN1-like): option 3 (we’ll treat as SN2-like (option 1) for simplicity) 10.1E

  19. Your friend ATP (the most important phosphoryl group donor) 10.2A

  20. abbreviations: 10.2A

  21. energy stored in ATP comes from phosphate anhydrides: 10.2A

  22. ‘spending’ an ATP to phosphorylate (activate) an alcohol: 10.2A

  23. making an organic-AMP adduct: 10.2A

  24. making an organic diphosphate: 10.2A

  25. separate the charges –release energy: 10.2A

  26. real reactions: kinases (phosphorylate alcohol groups) first step in glycolysis: 10.2B

  27. 10.2B

  28. now the 6-C sugar is ready to be broken into two 3-C sugars! (nature likes to keep molecules charged – why? 10.2B

  29. protein kinases (cell signaling) 10.2B

  30. making diphosphates: the 2-step method 10.2C

  31. The one-step method 10.2C

  32. now we’ve turned the alcohol into a good leaving group! (remember tosylates?) 10.2C

  33. phosphorylated carboxylates (making acyl phosphates) a simple acyl phosphate: 10.2D

  34. . . .or attack at the a-phosphate of ATP and make acyl-AMP 10.2E

  35. an interesting variation! 10.2E

  36. ATP synthase: uphill reaction! 10.2F

  37. minor sources of ATP regeneration 10.2F

  38. Hydrolysis of phosphates (transfer to water) protein phosphorylase 10.3

  39. what’s the mechanism? experimentally, result A is seen – it’s a phosphoryl transfer reaction 10.3

  40. sometimes transfer occurs with retention of configuration at P: is this an SN2??? 10.3

  41. no! It is the double displacement mechanism

  42. Phosphate diesters: eg. DNA, RNA why not citrate as a DNA linker? phosphates are thermodynamically labile, kinetically stable 10.4A

  43. RNA is much less stable than DNA! (uncatalyzed hydrolysis at pH 7 100 times faster) driving force of each step? 10.4A

  44. RNA is much less stable than DNA! (uncatalyzed hydrolysis at pH 7 100 times faster) step 1: entropy increases step 2: ring-strain relieved 10.4A

  45. The organic chemistry of genetic engineering DNA polymerase: 10.4B

  46. restriction endonucleases: 10.4B

  47. usually, a staggered cut: 10.4B

  48. DNA ligase: how is the leaving water activated?? 10.4B

  49. now its ready to leave 10.4B

  50. 10.4B

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