NMR studies of chemical exchange amongst five conformers of a ten-membered ring compound containing two amide bonds and a disulfide[hair space]

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Alex D. Bain, Russell A. Bell, Daniel A. Fletcher, Paul Hazendonk, Rob A. Maharajh, Suzie Rigby and John F. Valliant


Abstract

This paper presents experimental measurements which provide a very detailed picture of the free energy surface of a molecule. The compound, N,N[hair space]′-dimethyl-N,N[hair space]′-(2,2′-dithiobisacetyl)ethylenediamine (a diamino–disulfide, DADS, chelate), is a symmetrical ten-membered ring compound. Five conformers with significant populations are observed in dimethylformamide solution at 300 K. The ring consists of a pair of methylene groups at the top, each of which is bonded to the nitrogen of an N-methylamide linkage. The amides are then connected, through a methylene group, to a disulfide linkage, which forms the bottom of the ring. The conformations can be classified according to the stereochemistry of the amide bond. The lowest energy conformer, C, has one amide in the Z geometry and one in the E geometry. Conformer B, 0.9 kJ mol–1 above C, has both amides Z. Two other Z,E conformations, labelled A and E, lie 3.1 and 3.5 kJ mol–1, respectively, above C. Finally, there is a Z,Z conformer, labelled D, which is 5.6 kJ mol–1 above C. NMR lineshape and selective-inversion measurements have permitted estimates of some of the barriers to interconversion amongst these conformers. The barrier from C to A, which involves an inversion of the disulfide, has a barrier (ΔG[hair space] at 300 K) of 72 kJ mol–1, and the barrier from C to D (an amide rotation) is 80 kJ mol–1. The barrier from A to B, also an amide rotation, is 78 kJ mol–1. Finally, the barrier to conversion of A to E, which is a ring flip process, is 70 kJ mol–1. Although the disulfide can invert when one amide is Z and the other is E (this process converts conformer C to A), the barrier to this process when both amides are Z is too high to be measured accurately. Selective-inversion NMR experiments allowed extension of the lineshape exchange measurements to lower temperatures, so that the Gibbs’ free energies above could be separated into entropy and enthalpy contributions. For the C to A process, ΔH[hair space]  = 72 ± 1 kJ mol–1 and ΔS[hair space]  = 0 within experimental error. For the C to D process, ΔH[hair space]  = 86 ± 1.5 kJ mol–1 and ΔS[hair space]  = 19 ± 4 J K–1. For the A to B process, ΔH[hair space]  = 84 ± 1.2 kJ mol–1 and ΔS[hair space]  = 22 ± 4 J K–1. For the A to E process, ΔH[hair space]  = 74 ± 1 kJ mol–1 and ΔS[hair space]  = 11 ± 3 J K–1.


References

  1. R. B. Maharajh, J. P. Synder, J. F. Britten and R. A. Bell, Can. J. Chem., 1997, 75, 140 CAS.
  2. K. Schwochau, Angew. Chem., Int. Ed. Engl., 1994, 33, 2258 CrossRef.
  3. D. Brenner, A. Davison, A. G. Jones and J. Lister-James, Inorg. Chem., 1984, 23, 3793 CrossRef CAS.
  4. D. Stepniak-Biniakiewicz, B. H. Chen and E. Deutsch, J. Med. Chem., 1992, 35, 274 CrossRef CAS.
  5. W. C. Klingensmith, A. R. Fritzberg, V. M. Spitzer, D. L. Johnson, C. C. Kuni, M. R. Williamson, G. Washer and R. Weil, J. Nucl. Med., 1984, 25, 42 Search PubMed.
  6. R. K. Hom and J. A. Katzenellenbogen, Nucl. Med. Biol., 1997, 24, 485 CrossRef CAS.
  7. A. Capretta, R. B. Maharajh and R. A. Bell, Carbohydr. Res., 1995, 267, 49 CrossRef CAS.
  8. D. Z. Avizonis, S. Farr-Jones, P. A. Kosen and V. J. Basus, J. Am. Chem. Soc., 1996, 118, 13031 CrossRef CAS.
  9. K. D. Kopple, K. K. Bhandary, G. Kartha, Y. S. Wang and K. N. Parameswaran, J. Am. Chem. Soc., 1986, 108, 4637 CrossRef CAS.
  10. K. D. Kopple, J. W. Bean, K. K. Bhandary, J. Briand, C. A. D'Ambrosio and C. E. Peishoff, Biopolymers, 1993, 33, 1093 CrossRef CAS.
  11. M. J. Blackledge, R. Bruschweiler, C. Griesinger, J. M. Schmidt and R. R. Ernst, Biochemistry, 1993, 32, 10960 CrossRef CAS.
  12. T. Shimizu, Y. Tanaka and K. Tsuda, Int. J. Peptide Protein Res., 1983, 22, 194 CAS.
  13. K. A. Carpenter, P. W. Schiller, R. Schmidt and B. C. Wilkes, Int. J. Peptide Protein Res., 1996, 48, 102 CAS.
  14. D. Kern, G. Kern, G. Scherer, G. Fischer and T. Drakenberg, Biochemistry, 1995, 34, 13594 CrossRef CAS.
  15. E. Pinet, J. M. Neumann, I. Dahse, G. Girault and F. Andre, Biopolymers, 1995, 36, 135 CAS.
  16. J. H. Viles, J. B. Mitchell, S. L. Gough, P. M. Doyle, C. J. Harris, P. J. Sadler and J. M. Thornton, Eur. J. Biochem., 1996, 242, 352 CAS.
  17. A. Lombardi, M. Saviano, F. Nastri, O. Maglio, M. Mazzeo, C. Isernia, L. Paolillo and V. Pavone, Biopolymers, 1996, 38, 693 CrossRef CAS.
  18. W. E. Stewart and T. H. Siddall, Chem. Rev., 1970, 70, 517 CrossRef.
  19. R. R. Fraser, G. Boussard, J. K. Saunders, J. B. Lambert and C. E. Mixan, J. Am. Chem. Soc., 1971, 93, 3822 CrossRef CAS.
  20. C. M. Deber, F. A. Bovey, J. E. Carver and E. R. Blout, J. Am. Chem. Soc., 1970, 92, 6191 CrossRef CAS.
  21. M. Ptak, Biopolymers, 1973, 12, 1575 CAS.
  22. K. W. Kim, F. Sugawara, S. Yoshida, N. Murofushi, N. Takahashi and R. W. Curtis, Biosci. Biotechnol. Biochem., 1993, 57, 787 CAS.
  23. D. Jiao, M. Barfield, J. E. Combariza and V. J. Hrubny, J. Am. Chem. Soc., 1992, 114, 3639 CrossRef CAS.
  24. V. Renugopalakrishnan and R. Walter, Z. Naturforsch., Teil A, 1984, 39, 495.
  25. Z. Lidert, Tetrahedron, 1981, 37, 967 CrossRef CAS.
  26. L. M. Jackman and F. A. Cotton, Dynamic Nuclear Magnetic Resonance Spectroscopy, Academic Press, New York, 1975 Search PubMed.
  27. F. A. L. Anet and A. J. R. Bourn, J. Am. Chem. Soc., 1967, 89, 760 CrossRef CAS.
  28. S. C. Cepas and M. North, Tetrahedron, 1997, 53, 16859 CrossRef CAS.
  29. D. M. Pawar and E. A. Noe, J. Am. Chem. Soc., 1996, 118, 12821 CrossRef CAS.
  30. J. Sandstrom, Dynamic NMR spectroscopy, Academic Press, London, 1982 Search PubMed.
  31. G. Binsch, J. Am. Chem. Soc., 1969, 91, 1304 CrossRef CAS.
  32. D. A. Kleier and G. Binsch, J. Magn. Reson., 1970, 3, 146 CAS.
  33. A. D. Bain and G. J. Duns, Can. J. Chem., 1996, 74, 819 CAS.
  34. M. Grassi, B. E. Mann, B. T. Pickup and C. M. Spencer, J. Magn. Reson., 1986, 69, 92 CAS.
  35. J. J. Led and H. Gesmar, J. Magn. Reson., 1982, 49, 444 CAS.
  36. D. R. Muhandiram and R. E. D. McClung, J. Magn. Reson., 1987, 71, 187 CAS.
  37. A. D. Bain and J. A. Cramer, J. Magn. Reson., 1993, 103 A, 217.
  38. A. D. Bain and J. A. Cramer, J. Magn. Reson., 1996, 118 A, 21.
  39. R. E. D. McClung and G. H. M. Aarts, J. Magn. Reson., 1995, 115 A, 145.
  40. A. D. Bain, G. J. Duns, F. Rathgeb and J. Vanderkloet, J. Phys. Chem., 1995, 99, 17338 CrossRef CAS.
  41. M. Vasques, G. Nemethyl and H. A. Scheraga, Chem. Rev., 1994, 94, 2183 CrossRef CAS.
  42. J. Jeener, B. H. Meier, P. Bachmann and R. R. Ernst, J. Chem. Phys., 1979, 71, 4546 CrossRef CAS.
  43. C. L. Perrin and T. Dwyer, Chem. Rev., 1990, 90, 935 CrossRef CAS.
  44. K. G. Orrell, V. Sik and D. Stephenson, Prog. Nucl. Magn. Reson. Spectrosc., 1990, 22, 141 CrossRef CAS.
  45. C. L. Perrin and R. E. Engler, J. Magn. Reson., 1990, 90, 363 CAS.
  46. C. L. Perrin and R. E. Engler, J. Magn. Reson., 1996, 123 A, 188.
  47. R. E. Engler, E. R. Johnston and C. G. Wade, J. Magn. Reson., 1988, 77, 377.
  48. S. F. Bellon, D. Chen and E. R. Johnston, J. Magn. Reson., 1987, 73, 168 CAS.
  49. A. N. Taha, S. M. Neugebauer Crawford and N. S. True, J. Am. Chem. Soc., 1998, 120, 1934 CrossRef CAS.
  50. R. A. Bell, D. W. Hughes, C. J. L. Lock and J. F. Valliant, Can. J. Chem., 1996, 74, 1503 CAS.
  51. A. D. Bain, G. J. Duns, S. Ternieden, J. Ma and N. H. Werstiuk, J. Phys. Chem., 1994, 98, 7458 CrossRef CAS.
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