From rgab@purisima.molres.org Mon Apr 25 17:34:54 1994 Received: from purisima.molres.org for rgab@purisima.molres.org by www.ccl.net (8.6.4/930601.1506) id RAA00356; Mon, 25 Apr 1994 17:29:14 -0400 Message-Id: <199404252129.RAA00356@www.ccl.net> Received: by purisima.molres.org (1.37.109.4/16.2) id AA00505; Mon, 25 Apr 94 14:09:34 -0700 Date: Mon, 25 Apr 94 14:09:34 -0700 From: "R.G.A. Bone" To: chemistry@ccl.net Subject: 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@purisima.molres.org