1
122
Chemistry Letters Vol.32, No.12 (2003)
Inclusion Complex Formation and Hydrolysis of Lactones by Cyclodextrins
Ã
Yoshinori Takashima, Yoshinori Kawaguchi, Shinya Nakagawa, and Akira Harada
Department of Macromolecular Science, Graduate School of Science, Osaka University, Toyonaka, Osaka 560-0043
(Received September 9, 2003; CL-030843)
Cyclodextrins (CDs) have been found to form inclusion
complexes with lactones in aqueous solutions and/or in the solid
states; hydrolysis of lactones has been found to be suppressed or
promoted by CDs according to the combination of lactones and
CD.
In recent years, much attention has been focused on biode-
gradable polymers, such as poly(lactic acid) and poly("-capro-
lactone) from point of view of environmental protection. Previ-
ously, we found and reported that CDs form inclusion complexes
1
2
,3
with some aliphatic polyesters, such as poly("-caprolactone)
and poly(1,4-butylene adipate). Later, the others reported that
some other polyesters are included in CDs.
4
5
,6
In the course of the studies on the complex formation be-
tween CDs and polyesters, we found that hydrolysis of the poly-
esters is accelerated by CDs. CDs are known to accelerate hy-
drolysis of activated esters, such as p-nitrophenyl esters.
Accordingly, CDs have been studied as one of enzyme models
7
for a long time. However, there are few reports on hydrolysis
of alkyl esters by CDs. Therefore, we have decided to study in-
clusion complex formation of lactones (cyclic esters), which are
the starting monomers of above mentioned polyesters, with CDs
and hydrolysis of these lactones by CDs. We have prepared in-
clusion complexes of cyclodextrins with some lactones, and test-
ed their hydrolysis with CDs. We found that the hydrolysis of
some lactones has been promoted or retarded by CDs. Now we
report here that ꢀ-CD promoted hydrolysis of "-caprolactone
1
Figure 1. 400 MHz H NMR spectra of "-caprolactone in the
absence (a) and presence of ꢁ-CD (b), ꢀ-CD (c), and ꢂ-CD
d) in D2O. ["-CL] = 9.3 mM, [CD] = 11.7 mM.
(
("-CL) and ꢁ-CD suppressed its hydrolysis, although ꢂ-CD
1
has no effects. In addition, ꢀ-cyclodextrin suppressed hydrolysis
of ꢃ-valerolactone (ꢃ-VL) strongly, although ꢁ-CD did not show
any effects on hydrolysis of this lactone (Eq 1).
While we have been measuring the H NMR spectra of lac-
tones in the presence of CDs, we found that the spectra changed
with time. The time changes are different from each other be-
tween ꢁ-CD and ꢀ-CD. These differences have been found to
be due to hydrolysis of lactones to hydroxycarboxylic acids.
Figures 2and 3 show the degree of hydrolysis of "-CL and ꢃ-va-
lerolactone with various CDs as a function of time. The degree of
hydrolysis was determined by the sum of integrated values of
methylene proton adjacent to carbonyl carbon. When "-CL
was added onto dilute aqueous solutions of ꢁ-CD, the hydrolysis
of "-CL has been suppressed. When ꢀ-CD was used, the hydrol-
ysis was facilitated, although ꢂ-CD did not show any effects
(Figure 2).
Although ꢂ-CD did not show any effects, ꢁ-CD retarded hy-
drolysis of ꢃ-valerolactone and ꢀ-CD suppressed its hydrolysis
strongly.
The differences between the results with "-caprolactone and
those by ꢃ-valerolactone are due to the differences between the
relative sizes of CDs and the lactones. ꢃ-Valerolactone might fit
well in the ꢁ-CD and ꢀ-CD cavities so as to block the carbonyl
group of the ester. "-caprolactone and ꢃ-valerolactone is includ-
ed in the ꢂ-CD cavity so as to susceptible to attack by base or
acids.
O
O
CDs
r.t.
H
O
n
(1)
HO
O
n
(n = 1 or 2)
When "-caprolactone was added onto saturated aqueous so-
lution of ꢁ-CD, the solution became turbid and crystalline com-
plexes were formed. When the lactone was added onto ꢀ-CD so-
lution, some crystalline complexes were also obtained, although
ꢂ-CD did not give any complexes with this lactone at all.
1
Figure 1 shows the H NMR spectra of "-caprolactone in the ab-
sence and presence of CDs in D2O solutions at room tempera-
1
ture. Although ꢂ-CD showed small effects on the H NMR spec-
trum of lactone, the methylene peaks of the lactone shifted
toward lower magnetic fields on addition of ꢀ-CD and ꢁ-CD.
The spectral changes are even larger by ꢀ-CD than ꢁ-CD. These
results indicate that "-CL is included in both ꢁ-CD and ꢀ-CD,
and ꢀ-CD is more favorable for binding the lactone than ꢁ-CD.
Copyright Ó 2003 The Chemical Society of Japan