diastereomers or enantiomers - THE ANSWER



 On the question of comparing the energies of "diastereomers", I
 followed
 the few publicly-posted answers and then the subsequent summary by Matthew
 Stahl.  Although this discussion is now several days old, I believe that
 there is  something else to contribute;  I do not usually post answers
 publically but in this case I think there would be interest.
 Let us be very careful:
 Suppose that our molecule has a single asymmetric centre; if we invert
 at that centre and obtain the "enantiomer", then we have an
 energetically
 equivalent structure.  That much we are all agreed upon.  This should
 hopefully be irrespective of the force-field. One hopes that the Hamiltonian
 is symmetric w.r.t. inversion of all particle coordinates
 [(x,y,z,) -> (-x,-y,-z)] and in any case, as has been pointed out, this
 operation preserves inter-particle distances.  [By way of an aside, although
 the traditional way of obtaining an enantiomer, is to 'reflect' in a plane,
 as is well known, a reflection operation is the composite of inversion through
 a center and a 2-fold rotation - neither of which alter the energy.]
 But, what happens if 2 chiral centres are present?  (One may refer to a standard
 text-book of  organic chemistry, e.g., March, if one is not familiar with the
 terms enantiomer and 'diastereomer'.)  There are 4 possible isomers (assuming
 that the two centres do not contain identical sets of substituents).
 Now,  let us write them schematically:
      V           V                     V             V
      |           |                     |             |
    U-C-W       W-C-U                 U-C-W         W-C-U
      |           |                     |             |
    X-C-Z       Z-C-X                 Z-C-X         X-C-Z
      |           |                     |             |
      Y           Y                     Y             Y
      A           A'                    B             B'
 Note that A and A' are enantiomers,   as are B and B'.
 But the relationship of, say, A and B, is that they are diastereomers.
 "diastereomers are stereoisomers which are not enantiomers."
 For all 4 of these structures, the 'bonded' interactions are the same, and
 on that basis they will have identical energies.   But it is the non-bonded
 interactions which discriminate.  Note that the molecules A and A', in the
 configurations shown all have V---Y, W---Z and U---X  _non-bonded_ interactions,
 whereas the pair B and B' have   V---Y, U---Z and W---X non-bonded matches.
 (You can 'rotate' each of the C(XYZ) or C(UVW) centres but you can't get the
 same set of triple pair-wise interactions.)
 It is thus to be expected that the relative energies of diastereomers will
 depend upon the nature of the force-field used.  Thus a very crude model,
 which does not contain the longer-range, non-bonded interactions will not
 distinguish energetically between diastereomers.
 The message is thus that, when more than one chiral centre is present,
 inversion at a single centre introduces changes in long-range pair-wise
 interactions which may well bea manifested in changes in the potential
 energy.
 Richard Bone
 ================================================================================
 R. G. A. Bone.
 Molecular Research Institute,
 845 Page Mill Road,
 Palo Alto,
 CA 94304-1011,
 U.S.A.
 Tel. +1 (415) 424 9924 x110
 FAX  +1 (415) 424 9501
 E-mail  rgab(-(at)-)purisima.molres.org