NMR studies of chemical exchange amongst five conformers of a ten-memberedring compound containing two amide bonds and a disulfide

This paper presents experimental measurements which provide a very detailed picture of the free energy surface of a molecule. The compound, N,N'-dimet hyl-N,N'-(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 whic h is bonded to the nitrogen of an N-methylamide linkage. The amides are the n connected, through a methylene group, to a disulfide linkage, which forms the bottom of the ring. The conformations can be classified according to t he stereochemistry of the amide bond. The lowest energy conformer, C, has o ne amide in the Z geometry and one in the E geometry. Conformer B, 0.9 kJ m ol(-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 lineshap e 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 (Delta G(double dagger) at 300 K) of 72 kJ mol(-1), and the barrier from C to D ta n 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, w hich is a ring flip process, is 70 kJ mol(-1). Although the disulfide can i nvert when one amide is Z and the other is E (this process converts conform er 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 exte nsion of the lineshape exchange measurements to lower temperatures, so that the Gibbs' free energies above could be separated into entropy and enthalp y contributions. For the C to A process, Delta H-double dagger = 72 +/- 1 k J mol(-1) and Delta S-double dagger = 0 within experimental error. For the C to D process, Delta H-double dagger = 86 +/- 1.5 kJ mol(-1) and Delta S-d ouble dagger = 19 +/- 4 J K-1. For the A to B process, Delta H-double dagge r = 84 +/- 1.2 kJ mol(-1) and Delta S-double dagger = 22 +/- 4 J K-1. For t he A to E process, Delta H-double dagger = 74 +/- 1 kJ mol(-1) and Delta S- double dagger = 11 +/- 3 J K-1.