Chemistry Reference
In-Depth Information
charge concentrations as vertices are typically characterized by less negative or
even positive Laplacian values and represent the positions where a nucleophile will
attack with highest probability. The
2
(
r
) value at the (3,+1) critical point with
higher and positive Laplacian thus provides a measure for the electrophilicity of the
atomic center to which it is related and can be used to discuss trends.
Test computations for a smaller model system 8 consisting of the epoxide and
the carboxylate substituent (Fig.
13
left-hand side) reveal that the orientation of the
carboxylate group influences the
r
r
2
(
r
) values at the (3,+1) critical points signifi-
cantly (Fig.
14
). The values computed for the geometry taken in the E64c-cathepsin
B complex differ from the corresponding values in the solvent since the enzyme
-inhibitor interactions lead to additional distortions in the epoxide ring (Table
17
).
The inhibitor adopts different geometries in different surroundings. To distinguish
between the direct influence of the environment on the ED and more indirect effects
r
r
Fig. 13 Potential energy curve for the rotation of the carboxylate group by the torsional angle y.
The computations were performed for the substituted epoxide 8
Fig. 14 Variation of the
Laplacian value of 8 (Fig.
13
)
at the (3,+1) critical point at
the
a
(
red
) and
b
center (
blue
)
as a function of the torsional
angle y. The computations are
performed for a polar solvent.
In the solvent, the equilibrium
geometry is found for
y
ΒΌ
55
. The
black line
is the
difference between the
Laplacians values of the
a
and
b
centers. The
crosses
depict
the values obtained for the
protein structure
