Chemistry Reference
In-Depth Information
Challenging Problems in Charge Density
Determination: Polar Bonds and Influence
of the Environment
Bernd Engels, Thomas C. Schmidt, Carlo Gatti, Tanja Schirmeister,
and Reinhold F. Fink
Abstract The review focuses on the influence of environments on electron den-
sities (ED) and their Laplacians. This is of interest for many applications which uses
EDs measured at hand of crystals of a given ligand to predict its pharmaceutical
properties. This comprises for example the questions if the ligand fits into the active
center of an enzyme and how strong it binds to this active side. This widely used
approximation strongly rely on the assumption that the active side of the enzyme
influences the ED of the ligand the same way the crystal environment does. This is
not obvious since enzymes represent systems made to catalyze reactions. So one
could assume that the active sides influence the EDs of ligands in a special way to
prepare them for a given reaction. The review shows that this is indeed the case for
E64c. Its inhibition properties result since it reacts with cathepsin B and forms a
covalently bonded cathepsin B-E64c complex. It clearly comes out that the reac-
tion only takes place since the ED of the ligand is influenced in a way which is not
found in the respective crystals. Nevertheless, the review also shows that the above
mentioned approximation holds for AMCHA which serves as a model compound
for reversible inhibitors. In the last part the review shows in detail that the source
function can be used to study the influence of the environment in more detail. In the
