Handbook of Solvents - George Wypych - ChemTech - Ventech!

878 Tsuneo Yamane
[ ( kcat Km) ( kcat Km)
] ( )
log / / / = log γ / γ + constant [14.4.3.3]
1 2 1 2
The correlation was unexpectedly high as seen in Figure 14.4.3.2, 15 implying that the
change of substrate specificity of enzyme in organic solvent stems to a large extent from the
energy of desolvation of the substrate.
(2b) Enantioselectivity
Changes in enantioselectivity in various organic solvents was first discovered by Sakurai et
al. 17 Later Fitzpatrick and Klibanov studied enantioselectivity of subtilisin, Carsberg in the
transesterification between the sec-phenethyl alcohol (a chiral alcohol) and vinyl butyrate
to find that it was greatly affected by the solvent. Only the correlations with εor with D gave
good agreements. 18 The enzyme enantioselectivity was inversed by changing solvents. 19
Nakamura et al. studied lipase (Amano AK from Pseudomonas sp.)-catalyzed
transesterification of cis- and trans-methylcycolhexanols with vinyl acetate in various organic
solvents, and investigated the effect of solvent on activity and stereoselectivity of the
lipase. 20 They correlated their stereoselectivity with good linearity (except for dioxane and
dibutyl ether) by the following two-parameter equation (Figure 14.4.3.3):
( ε 1) ( 2ε 1)
E = a − / + + bV + c
[14.4.3.4]
m
where ε and V m are dielectric constant and molar volume of the solvent, respectively, and a,
b, and c are constants which
should be experimentally determined.
Bianchi et al. also reported
that for the resolution of
antitussive agent, Dropropizine,
using both hydrolysis in aqueous
buffer and transesterification
techniques in various organic solvents,
by a lipase (Amano PS
from Pseudomonas cepacia), E
depended very much on organic
solvents (Table 14.4.3.3), with the
highest E value (589) in n-amyl
alcohol and the lowest one (17) in
water. 21 In this case, however,
there was no correlation between
Figure 14.4.3.3. Linear relationship between f(ε, V m) and E for
lipase-catalyzed transesterification of cis- and trans-4-methylcyclohexanols
with vinyl acetate in various organic solvents. For the
organic solvents 1 through 18, refer to Ref. 20. [Adapted, by permission,
from K. Nakamura, M. Kinoshita and A. Ohno, Tetrahedron,
50, 4686(1994)].
the enantioselectivity and the
physico-chemical properties of
the solvents such as logP or ε.