Chemistry Reference
In-Depth Information
Fig. 16 Orientation of E64d (Loxistatin) in crystals of the pure compound [
135
]
values at the (3,+1) critical points. In difference to E64c, the C
a
carbon atom is the
stronger electrophilic center in E64d. This is in line with the experimental result
that the
-reaction for ester-substituted epoxides [
136
,
137
]. This changed electrophilicity of C
a
and C
b
as compared to E64c can be
explained by the substitution of the negatively charged carboxylate of E64c which
had a strong influence on the epoxide ring by a neutral ester substituent in E64d.
Going from gas phase to a polar solvent, the computed value of the Laplacian
increases by about 20-25% while an additional rise of 10-15% is obtained for the
environment inside of the crystals of E64d (Fig.
17
). This shows that also in this
case a polar solvent provides a much better approximation of a crystal environment
than the gas phase.
For the E64c-enzyme complex, the total effects are much stronger but a consid-
erable part results from the heavily distorted ring structure and the orientation of the
carboxylate group. If the geometry taken within the protein-inhibitor complex is
also adopted for the polar solvent environment, the Laplacian values obtained for
solvent (Fig.
15
p/s) and protein environment [Fig.
15
p/s(S
1
)], respectively, differ
by 20% (
a
-attack is faster than the
b
b
-center) and about 50% (
a
-center). This shows that the influence of the
crystal environment on the
b
-center of E64d is similar to the influence of the protein
