Page 61 - Visions of the Future Chemistry and Life Science

50 J. M. GOODMAN

Figure 3.4. Pentane. The diagram shows the four minimum-energy conformations
of pentane. The global minimum is on the far left. Reflection and rotation of some
of these geometries would generate more structures, but nothing with a different
energy. Pentane is a simple molecule. More complicated molecules have many
more conformations. Bryostatin 2 and PM-toxin A have so many minimum-energy
conformations that to list them all would be a major undertaking and would
require a large library to store the result.

in energy (a few tens of kilojoules) than the global minimum. For bryosta-
tin, there are probably many more accessible conformations. Simply being
able to calculate the energy of one of these molecules is a long way from
understanding its structural properties, which will require many energy
calculations.
In addition to finding the minima for each intermediate in a synthesis,
it is also necessary to be able to analyse reactivity. This is a more difficult
problem than conformation searching, because it is now possible for bonds
to break. The range of movements available to the molecule is far larger,
and it is also necessary to consider which bond will break most easily, and
what factors are present which will drive the reaction forwards. If there are
many competing reactions, then these calculations may have to be very
precise in order to distinguish between them.
This problem is made easier because the different reactions have
similar starting points, so the question of the most favourable reaction
only requires the comparison of similar systems, and this is a great advan-
tage. It is easy to compare two pieces of string to find which is longer, but
only if the strings have similar conformations. If one is straight, and the
other tied in knots, it may be very hard. Even if both strings are untangled,
then it may still be hard to decide which is longer, if they have very similar
lengths. Comparing possible reaction pathways is usually like comparing
two pieces of string which are both untangled, or, at least, tangled in much
the same way. However, the energy differences between processes may be
very small compared with the total energy of the system, and so it may be
hard to decided which will be preferred.
Analysing structure, conformation and reactivity means that the mol-