Page 60 - Visions of the Future Chemistry and Life Science

World champion chemists 49

force fields. Once the energy has been found, it is possible to calculate the
preferred shape of the molecule, by finding alterations to the shape of the
molecule which lower the total energy. This process of altering the struc-
ture and recalculating the energy is continued until all small changes to
the structure lead to an increase in energy. The shape that the molecule has
now reached is called a minimum energy conformation. This requires
many calculations of the energy of the structure.
This does not solve the problem of synthesis. A minimum energy con-
formation is the lowest energy point in the immediate vicinity, but it may
not be the lowest energy geometry available to the molecule. The lowest
energy point of all is called the global minimum. There can only be one
global minimum for any molecule, but there may be very many local
minima. These are geometries for which any small change will increase the
energy of the structure, but for which larger changes may lead to a decrease
in energy, so they must be higher in energy than the global minimum. This
can be compared with a mountainous landscape. Only one point can be the
lowest point of all, the global minimum, but there may be many points
from which every direction you choose to walk will be up hill.
For a molecule containing several alcohol groups, some conformations
may have particular alcohols tucked into the centre of the molecule. This
may be helpful, if it means that these alcohols will not react, and others in
the molecule may do so. But will each conformation be accessible? One
way to assess this is to make a list of all the minima on the surface, and to
examine the properties of each. The higher energy minima will be less
likely to be occupied that the lower energy minima, and this difference can
be quantified. This process, called conformation searching, requires many
minimisations, each of which requires many energy calculations, and so
multiplies the total time required for the analysis. This leaves out all of the
parts of the landscape between the minima, and this can be a problem.
There are ways of taking these into account, but they are even more time
consuming.
A simple molecule is illustrated in Figure 3.4. This is pentane, a chain
of five carbon atoms, with hydrogen atoms ensuring that each carbon
makes four connections to its surroundings. Pentane has four minimum
energy conformations, as illustrated. The conformation analysis is
straightforward, but pentane is a simple molecule. It is not easy to assess
accurately the number of conformations accessible to PM-toxin, but the
answer is certainly well into four figures, for structures only slightly higher