Kinetic study on the interactions of cyclodextrins with organic phosphates and thiophosphates

Article abstract of DOI:10.1246/bcsj.82.76

α-Cyclodextrin (α-CD) and 6-O-α-D-glucopyranosyl-β- cyclodextrin (G1-β-CD) affected the rates of phenol release from a few dimethyl(nitrophenyl) phosphates and the corresponding thiophosphates in aqueous alkaline solutions. Curvefitting analysis of change

Full text of DOI:10.1246/bcsj.82.76

76
Bull. Chem. Soc. Jpn. Vol. 82, No. 1, 76–80 (2009)
© 2009 The Chemical Society of Japan
Kinetic Study on the Interactions of Cyclodextrins
with Organic Phosphates and Thiophosphates
Takuya Nagata, Kenta Yamamoto, Keisuke Yoshikiyo, Yoshihisa Matsui, and Tatsuyuki Yamamoto*
Faculty of Life and Environmental Science, Shimane University, 1060 Nishikawatsu, Matsue 690-8504
Received July 14, 2008; E-mail: tyamamot@life.shimane-u.ac.jp
¡-Cyclodextrin (¡-CD) and 6-O-¡-D-glucopyranosyl-¢-cyclodextrin (G1-¢-CD) affected the rates of phenol release
from a few dimethyl(nitrophenyl) phosphates and the corresponding thiophosphates in aqueous alkaline solutions. Curve-
fitting analysis of changes in the rate constants with CD concentrations showed that both ¡-CD and G1-¢-CD form not
only 1:1 but also 2:1 (host:guest) complexes with the phosphates and thiophosphates. In 1:1 complexes, phenol release
from the phosphates was mostly accelerated, and that from the thiophosphates was decelerated. In 2:1 complexes, the
reactions both of the phosphates and thiophosphates were strongly retarded. Binding constants and rate constants
determined showed significant host and substrate specificities.
A number of organophosphorus compounds have been
analogs such as 2S, O,O-dimethyl O-3-nitrophenyl thiophos-
phate (3S) and their corresponding phosphates (2O and 3O) as
guests (Figure 1). G1-¢-CD was selected as a host instead of
native ¢-CD, since the water solubility of ¢-CD is too low for
us to observe consecutive formation of 1:1 and 2:1 complexes.
The water solubility of G1-¢-CD is about 50 times greater than
that of ¢-CD.10
developed as pesticides. Among them, O,O-dimethyl O-(3-
methyl-4-nitrophenyl) thiophosphate (fenitrothion, 1S) is one
of the most widely used insecticides. The compound is
chemically or biochemically converted to the corresponding
phosphate (1O), which acts as an acetylcholinesterase inhib-
itor.1 Cyclodextrins (CDs) are cyclic oligomers composed of
six (¡-CD), seven (¢-CD), eight (£-CD), or more ¡-D-
glucopyranose units and have the shapes of hollow truncated
cones. They are able to accommodate a variety of organic
molecules, including organophosphorus compounds, within
their interior cavities to form inclusion complexes. According
to van Hooidonk et al.,2 ¡-CD is a simple and good model for
the inhibition of acetylcholinesterases by organophosphorus
insecticides. Mochida et al.3 showed that CDs accelerate the
cleavage of organic phosphates but decelerate that of corre-
sponding thiophosphates in alkaline solutions. Vico et al.4 also
showed that ¢-CD inhibits the alkaline hydrolysis of 1S.
On the other hand, Kamiya et al.5 examined interactions of
CDs with organophosphorus pesticides from the viewpoint
of environmental chemistry. Recently, Luo et al.6 reported
toxicological studies on CD complexes with O,O-dimethyl
O-4-nitrophenyl thiophosphate (methyl parathion, 2S). Com-
putational studies with molecular dynamics were also reported
on the interactions of CDs with a few organophosphorus
pesticides.7,8 It is noteworthy that all the above works assumed
that CDs form only 1:1 (host:guest) inclusion complexes with
organophosphorus compounds. However, Yamamoto et al.9
have isolated ¢-CD complexes with 2S with molar ratios not
only 1:1 but also 2:1 (host:guest). Recently, we also found that
an effect of 6-O-¡-D-glucopyranosyl-¢-CD (G1-¢-CD) on the
alkaline hydrolysis of 1S is difficult to explain by simple 1:1
complexation but is explicable by consecutive formation of 1:1
and 2:1 complexes. The present study was undertaken to
examine the generality of consecutive formation of 1:1 and 2:1
complexes between CDs and organophosphorus compounds,
using ¡-CD and G1-¢-CD as hosts and 1S, 1O, and their
Results and Discussion
Stoichiometry. The rate of phenol release from 1S was
measured by following the appearance of the absorption due to
CH
3
X
P
H CO
3
O
NO
2
H CO
3
X = S, 1S
X = O, 1O
X
H CO
3
P
O
NO
2
H CO
3
X = S, 2S
X = O, 2O
NO
2
X
H CO
3
P
O
H CO
3
X = S, 3S
X = O, 3O
Figure 1. Structures and abbreviations of organophos-
phorus compounds examined.
Published on the web January 14, 2009; doi:10.1246/bcsj.82.76

T. Nagata et al.
Bull. Chem. Soc. Jpn. Vol. 82, No. 1 (2009)
77
12
10
8
b
a
0.5
0
−0.5
−1
6
4
2
0
0
0.05
0.1
0.15
0.2
0
20
40
60
80
100
[G1-β-CD] / mmol dm-3
[OH-] / mol dm-3
Figure 3. The plots of kun ( ) and kobsd ( ) vs. OHÕ
concentration for a 20 mmol dmÕ3 G1-¢-CDÍ1O system
Figure 2. The plots of Åkobsd vs. G1-¢-CD concentration
for 1S (a) and 1O (b) in 0.20 and 0.05 mol dmÕ3 NaOH,
respectively, at 308 K and Ic = 0.65 mol dmÕ3. A solid line
was obtained by curve-fitting analysis upon an assumption
of consecutive 1:1 and 2:1 complexation. A dotted line
was obtained upon an assumption of simple 1:1 complex-
ation. The kun values were 1.22 © 10Õ3 sÕ1 for 1S and
2.73 © 10Õ3 sÕ1 for 1O.
at 308 K and Ic = 0.65 mol dmÕ3
.
et al.2 have shown that ¡-CD accelerates the cleavage of a few
organophosphorus compounds in aqueous alkaline solutions,
and the acceleration is due to the nucleophilic attack of the
alkoxide ion derived from ¡-CD on the phosphates. Thus, the
acceleration of the cleavage of 1O by G1-¢-CD in a 1:1
complex will also be due to the nucleophilic attack of the
alkoxide ion on the phosphate group of 1O. On the other hand,
the deceleration observed for a 2:1 complex will be brought
about by the second G1-¢-CD molecule, which pulls apart the
phosphate group from the alkoxide ion and also protects the
phosphate group from nucleophilic attack of the hydroxide ion
from bulk solution by steric hindrance.
In order to learn the detailed roles of the alkoxide and
hydroxide ions in the reaction of 1O, the reaction rates were
measured at various alkaline concentrations in the absence and
in the presence of 20 mmol dmÕ3 G1-¢-CD (Figure 3). The plot
of the rate constants (kun) for free 1O vs. OHÕ concentrations
gave a good straight line passing through the point of origin.
The rate constant at [OHÕ] = 0.1 mol dmÕ3 was about twice
that at [OHÕ] = 0.05 mol dmÕ3, indicating that phenol release
from free 1O is brought about by the nucleophilic attack of the
hydroxide ion from bulk solution. On the other hand, the plot
of the rate constants (kobsd) in the presence of 20 mmol dmÕ3
G1-¢-CD vs. OHÕ concentrations gave a hyperbolic curve: The
kobsd values at low OHÕ concentrations were larger than the
corresponding kun values, but those at high OHÕ concentrations
were smaller than the corresponding kun values. The 1O
molecule included within the G1-¢-CD cavity is subject to
nucleophilic attack by the alkoxide ion derived from G1-¢-CD,
together with the attack by the hydroxide ion from bulk
solution.3 Although the pKa value of G1-¢-CD is not known, it
will virtually be equal to that of native ¢-CD (pKa = 12.09 at
303 K and 11.91 at 313 K12). Therefore, the G1-¢-CD molecule
will almost completely be ionized to give the alkoxide ion
at any OHÕ concentrations above 0.05 mol dmÕ3 (pH ca. 12.7).
Then, the rate constants for the nucleophilic attack by the
alkoxide ion are regarded as constant at OHÕ concentrations
above 0.05 mol dmÕ3. On the other hand, the rate constants for
the attack on the included 1O by the hydroxide ion from bulk
solution will be smaller than those for free 1O, owing to steric
the corresponding phenoxide ion at 410 nm in 0.20 mol dmÕ3
NaOH at 308 K. Changes in absorbance with time obeyed good
first-order kinetics with respect to 1S in both the absence and
presence of ¡-CD or G1-¢-CD. Figure 2a shows the plot of
differences (Åkobsd) between the rates in the presence (kobsd
)
and in the absence (kun) of G1-¢-CD vs. G1-¢-CD concen-
trations (c0). As have already been reported for a ¢-CDÍ1S
system,3 the phenol release was significantly decelerated by the
addition of G1-¢-CD. However, the curve-fitting analysis of
the relationship between Åkobsd and c0 upon an assumption
of simple 1:1 complexation of G1-¢-CD with 1S gave an
unsatisfactory correlation coefficient of 0.9836, and the
calculated curve (dotted line) was apparently ill-fitted to the
observed data. Then, the relationship between Åkobsd and c0
was analyzed by an equation derived by Tee and Du11 for such
a case that 1:1 complexation is followed by 2:1 (host:guest)
complexation. The obtained curve (solid line) was well-fitted to
the data with a correlation coefficient of 0.9998, suggesting that
not only 1:1 but also 2:1 complexes are formed in solution.
More clear results were obtained for a G1-¢-CDÍ1O system
in 0.05 mol dmÕ3 NaOH at 308 K (Figure 2b). The rate (kobsd
)
of phenol release increased with an increase in c0 up to
ca. 20 mmol dmÕ3, whereas it decreased above 25 mmol dmÕ3
G1-¢-CD. At c0 ² 80 mmol dmÕ3, the kobsd value became
smaller than kun (Åkobsd < 0, deceleration). Similar results have
been reported by Tee and Du,11 who examined the cleavage
of aryl alkanoates by ¡-CD in basic aqueous solution. They
found that the cleavage of 4-carboxy-2-nitrophenyl hexanoate,
for example, is accelerated at low ¡-CD concentrations but
decelerated at high ¡-CD concentrations. They concluded
that ¡-CD consecutively forms 1:1 and 2:1 complexes, and 1:1
complex accelerates, whereas 2:1 complex decelerates, the
cleavage. The curve-fitting analysis of our data upon the same
assumption, in fact, gave a well-fitted curve (solid line in
Figure 2b) with a correlation coefficient 0.9996. van Hooidonk

78
Bull. Chem. Soc. Jpn. Vol. 82, No. 1 (2009)
Complexes of Cyclodextrins with Phosphates
2
1.5
1
1
0
−1
−2
−3
−4
−5
0.5
0
−0.5
−1
−1.5
−2
0
20
40
60
80
100
0
20
40
60
80
100
[G1-β-CD] / mmol dm-3
[α-CD] / mmol dm-3
Figure 4. The plots of Åkobsd vs. G1-¢-CD concentration
for 1O in 0.03 ( ) and 0.20 mol dmÕ3 ( ) NaOH at 308 K
and Ic = 0.65 mol dmÕ3. Solid lines were obtained by
curve-fitting analysis upon an assumption of consecutive
1:1 and 2:1 complexation. The kun values were 1.75 © 10Õ3
and 10.09 © 10Õ3 sÕ1 in 0.03 and 0.20 mol dmÕ3 NaOH,
respectively.
Figure 5. The plots of Åkobsd vs. ¡-CD concentration for
1O ( ), 2O ( ), and 3O ( ) in 0.05 mol dmÕ3 NaOH at
308 K and Ic = 0.65 mol dmÕ3. Solid lines were obtained
by curve-fitting analysis upon an assumption of consec-
utive 1:1 and 2:1 complexation. The kun values were
2.73 © 10Õ3 sÕ1 for 1O, 4.33 © 10Õ3 sÕ1 for 2O, and
2.60 © 10Õ3 sÕ1 for 3O.
hindrance. Hence, the kobsd values at high OHÕ concentrations
become smaller than the corresponding kun values. Figure 4
shows the plots of Åkobsd versus c0 for a G1-¢-CDÍ1O system
in 0.03 and 0.20 mol dmÕ3 NaOH. The plot for a G1-¢-CDÍ1O
system in 0.03 mol dmÕ3 NaOH was similar to that in
0.05 mol dmÕ3 NaOH: The Åkobsd value increased at low
concentrations, whereas it decreased at high concentrations of
G1-¢-CD. On the other hand, the Åkobsd value for the system in
0.20 mol dmÕ3 NaOH decreased even at low concentrations of
G1-¢-CD, indicating that the included 1O is less reactive than
the free 1O in such a strong basic solution. The plot also shows
that the extent of retardation by G1-¢-CD is more pronounced
at high G1-¢-CD concentrations than that at low G1-¢-CD
concentrations, suggesting that 1O included in a 2:1 complex is
more effectively protected from the attack of OHÕ in bulk
solution than that in a 1:1 complex. The curve-fitting analysis
of these data based on the consecutive formation of 1:1 and 2:1
complexes gave well-fitted curves (solid lines).
In order to examine the generality of consecutive formation
of 1:1 and 2:1 complexes between CDs and organophosphorus
compounds, we also used 2O, 2S, 3O, and 3S as substrates and
¡-CD as well as G1-¢-CD as hosts. Every combination of the
host and substrate showed the consecutive formation of 1:1 and
2:1 complexes between them. The effects of ¡-CD on the rates
of phenol release from 1O, 2O, and 3O are shown in Figure 5
as examples. The curves (solid lines) obtained by calculation
were well-fitted to the observed data with correlation coef-
ficients of about 0.999. Thus, it is evident that the consecutive
formation of 1:1 and 2:1 complexes is general, at least, in ¡-
CD and G1-¢-CD complexation with dimethyl(nitrophenyl)
phosphates and thiophosphates. Hamai13 showed that, in the
2:2 inclusion complex of £-CD with 1-chloronaphthalene in
alkaline solution, the primary hydroxy-group sides of the CD
cavities face each other. Unfortunately, there is no experimental
evidence showing how the 2 molecules of CD are bound to
dimethyl(nitrophenyl) phosphates and thiophosphates in our
2:1 complexes at the present stage of investigation.
Kinetic Parameters. Kinetic parameters determined for the
alkaline hydrolyses of the organic phosphates and thiophos-
phates in the presence of ¡-CD and G1-¢-CD are shown in
Table 1, where k1 and k2 are the rate constants for 1:1 and 2:1
complexes, respectively, and K1 and K2, the binding constants
for 1:1 and 2:1 complexes, respectively. A few notable features
were found in the obtained parameters: First of all, the k2/kun
values were always smaller than the k1/kun values, implying
that the 2:1 complexes of the phosphates and thiophosphates
are less reactive than the 1:1 complexes. The substrates will be
effectively protected by the second CD molecules in the 2:1
complexes from the nucleophilic attack of the hydroxide
ion from bulk solution by steric hindrance. It is also notable
that the k1/kun values for the phosphates, except a ¡-CDÍ1O
system, were larger than 1, whereas those for the thiophos-
phates were smaller than 1. This tendency was especially clear
when G1-¢-CD was used as a host. The binding constants K1
for G1-¢-CDÍthiophosphate systems were much larger than
those for G1-¢-CDÍphosphate systems, suggesting that the
thiophosphates are too deeply included within the cavity of
G1-¢-CD to be attacked by the alkoxide ion derived from
the secondary hydroxy groups of G1-¢-CD, as well as by the
hydroxide ion from bulk solution. The electronegativity of
sulfur is less than that of oxygen, and the atomic radius of
sulfur is larger than of oxygen. Therefore, the thiophosphates
are more hydrophobic than the corresponding phosphates. On
the other hand, the phosphates are less deeply included within
the G1-¢-CD cavity and susceptible to the nucleophilic attack
by the alkoxide ion and the hydroxide ion from bulk solution.
In this context, it is interesting that the k1/kun value for a ¡-
CDÍ3O system was the largest among systems examined. 3O
has a m-nitrophenyl group. It is well known that the cleavage of

T. Nagata et al.
Bull. Chem. Soc. Jpn. Vol. 82, No. 1 (2009)
79
Table 1. Kinetic (k1/kun and k2/kun)a) and Equilibrium (K1 and K2) Parameters for Complexes of CDs with
Organic Phosphates and Thiophosphates in NaOH Solution (Ic = 0.65 mol dmÕ3) at 308 K
Compound
[OHÕ]
/mol dmÕ3
k1/kun
k2/kun
K1
/molÕ1 dm3
K2
/molÕ1 dm3
rb)
¡-Cyclodextrin
1S
2S
3S
1O
2O
3O
0.20
0.20
0.20
0.05
0.05
0.05
0.49
0.95
1.00
0.66
2.54
6.51
0.00
0.00
0.26
0.00
0.05
0.08
21
5
4
44
22
7
11
61
47
9
31
41
0.9961
0.9994
0.9946
0.9990
0.9992
0.9987
G1-¢-Cyclodextrin
1S
2S
3S
1O
2O
3O
0.20
0.20
0.20
0.05
0.05
0.05
0.44
0.32
0.34
1.68
2.23
1.06
0.00
0.01
0.04
0.00
0.33
0.11
1300
750
640
48
11
7
33
33
57
7
25
31
0.9998
0.9993
0.9998
0.9996
0.9980
0.9980
a) kun = 1.22 © 10Õ3 sÕ1 (1S), 1.78 © 10Õ3 sÕ1 (2S), 1.24 © 10Õ3 sÕ1 (3S), 2.73 © 10Õ3 sÕ1 (1O),
4.33 © 10Õ3 sÕ1 (2O), and 2.60 © 10Õ3 sÕ1 (3O). b) Correlation coefficient.
m-nitrophenyl acetate in an alkaline solution is greatly
accelerated by ¡-CD, since the alkoxide ion of ¡-CD and the
acyl carbonyl of the substrate lie close together in their
inclusion complex.14 Thus, the phosphate group of 3O will also
lie close to the ¡-CD alkoxide ion in a 1:1 complex. Only a
¡-CDÍ1O system showed weak deceleration by 1:1 complex-
ation: No clear reasoning is possible at the present stage of
investigation. The K1 values for the ¡-CD complexes with
thiophosphates were smaller than those for the corresponding
phosphate complexes, suggesting that the thiophosphates are
more shallowly included within the ¡-CD cavity than the
phosphates. Probably, the relatively bulky thiophosphate group
will retard deep inclusion within the small cavity of ¡-CD. In
such cases, the reaction sites of the thiophosphates locate at the
outside of the ¡-CD cavity and too far apart from the alkoxide
ion of ¡-CD to be attacked. The weak or no deceleration
observed for 2S (k1/kun = 0.95) or 3S (k1/kun = 1.00) implies
that the ¡-CD cavity hardly hinders the attack of the hydroxide
ion from bulk solution on the complexed thiophosphates.
Another notable point of data shown in Table 1 is that there
are several cases in which the K2 values are larger than the
K1 values. This fact suggests that the second CD molecule
interacts not only with part of a substrate molecule but also
with the first CD molecule, probably by hydrogen bonding.
1H NMR Spectroscopy. The solubilities of the examined
phosphates and thiophosphates in D2O were too low for us to
record their 1H NMR spectra. However, 2S was soluble enough
for NMR measurement in a 1:1 (v/v) mixture of D2O with
dimethyl sulfoxide-d6. The chemical shifts (¤) for the protons
of 2S (3.1 mmol dmÕ3) in the solvent were significantly
changed by the addition of ¡-CD and G1-¢-CD. For example,
changes (Ť) in chemical shifts for the ortho protons of the
p-nitrophenyl group of 2S were 0.027 and Õ0.019 when ¡-CD
(50 mmol dmÕ3) and G1-¢-CD (21 mmol dmÕ3) were added,
respectively. On the other hand, the Ť values for the methyl
protons of 2S were only 0.003 and Í0.005 for ¡-CD and G1-¢-
CD, respectively. Significant upfield shifts of the C(3)- and
C(5)-Hs of ¡-CD and G1-¢-CD were also observed by the
addition of 2S. These results suggest that the p-nitrophenyl
group of 2S interact with ¡-CD and G1-¢-CD more strongly
than the methoxy groups of 2S.
Conclusion
¡-CD and G1-¢-CD form not only 1:1 but also 2:1
complexes with the organic phosphates and thiophosphates
examined in aqueous alkaline solutions. In 1:1 complexes,
phenol release from the phosphates was mostly accelerated, and
that from the thiophosphates was decelerated. In 2:1 com-
plexes, the reactions both of the phosphates and thiophosphates
were strongly retarded.
Experimental
Apparatus. The absorption and NMR spectra were recorded
using a Shimadzu UV-2100 UV/Vis spectrophotometer and a
JEOL Model JNM-A400 FT NMR spectrometer (400 MHz),
respectively. The mass spectra were recorded using a Waters
Quattro Micro tandem quadrupole MS system with positive ion
electrospray ionization (ESI).
Materials. The ¡-CD and G1-¢-CD were kindly supplied by
Ensuiko Sugar Refining Co., Ltd. They were dissolved in water,
treated with activated charcoal, and lyophilized to dryness before
use. Reagent-grade m-nitrophenol (m-NP) and m-chloroperbenzoic
acid (m-CPBA) were purchased from Wako Pure Chemical
Industries, Ltd. The potassium salt of m-NP was prepared by
neutralization of m-NP with aqueous KOH, followed by lyo-
philization. Reagent-grade O,O-dimethyl chlorothiophosphate was
purchased from Sigma-Aldrich and used without further purifica-
tion. Silica gel 60 (Merck, 0.040Í0.063 mm) was used for column
chromatography.
1S was extracted from MEP water-dispersible powder (MEP
40%, Nihon Nohyaku Co., Ltd.) and purified as follows: An
aliquot of the MEP powder was suspended in aqueous NaCl (10%)
solution and extracted twice with dichloromethane. The organic

80
Bull. Chem. Soc. Jpn. Vol. 82, No. 1 (2009)
Complexes of Cyclodextrins with Phosphates
layer was dried over Na2SO4, filtered, and evaporated in vacuo at
40 °C to dryness. The residue was suspended in hexane and
chromatographed on a 3.0 © 50 cm silica gel column with hexane,
followed by hexane/ether (3:1 v/v), as eluents. The hexane/ether
fractions were assayed by an UV spectrophotometer. Fractions
which gave absorption at 265 nm were combined and evaporated to
afford a yellow-brown liquid, which was identified to be 1S by
1H NMR spectroscopy and mass spectroscopy.
On the other hand, the rate constant kobsd at any CD concentration
is represented by:
kobsd ¼ kunðs=s0Þ þ k1ðx=s0Þ þ k2ðy=s0Þ
ð2Þ
or
ꢀkobsd ¼ ꢀk1x=s0 þ ꢀk2y=s0
ð3Þ
where kun and s are the rate constant and equilibrium concentration
for free substrate, respectively, k1, and x, those for 1:1 complex,
k2 and y, those for 2:1 complexes, Åkobsd = kobsd Õ kun, Åk1 =
k1 Õ kun, and Åk2 = k2 Õ kun. Thus, we determined the values of
K1, K2, Åk1, and Åk2 by a nonlinear least-squares curve-fitting
analysis of the change in Åkobsd with c0 using the software
Equatram-G available for numerical analysis.
2S was a stored sample used in previous work.3 3S was prepared
by the reaction of O,O-dimethyl chlorothiophosphate with potas-
sium m-nitrophenoxide in xylene.15 Crude 2S and 3S were purified
by column chromatography and identified as described above.
1O, 2O, and 3O were prepared by the reaction of corresponding
thiophosphates, 1S, 2S, and 3S, with m-CPBA.16 For example, a
solution of m-CPBA in chloroform was added to a solution of 1S
in chloroform cooled below 0 °C. After stirring overnight at room
temperature, the mixture was washed with 5% NaHCO3 aqueous
solution and then with water. The chloroform layer was dried over
Na2SO4, filtrated, and evaporated in vacuo at 40 °C to dryness. The
residue was dissolved in hexane/ethyl acetate (1:1 v/v) and
chromatographed on a 3.0 © 50 cm silica gel column with hexane/
ethyl acetate (1:1 v/v) as an eluent. Fractions which gave
absorption at 265 nm were combined and evaporated to dryness
to afford a yellow-brown liquid. The liquid was identified to be 1O
References
1
T. Kasagami, T. Miyamoto, I. Yamamoto, Pest Manag. Sci.
2002, 58, 1107.
2
a) C. van Hooidonk, J. C. A. E. Breebaart-Hansen, Recl.
Trav. Chim. Pays-Bas 1970, 89, 289. b) C. van Hooidonk, C. C.
Groos, Recl. Trav. Chim. Pays-Bas 1970, 89, 845. c) C. van
Hooidonk, J. C. A. E. Breebaart-Hansen, Recl. Trav. Chim. Pays-
Bas 1971, 90, 680.
1
by H NMR spectroscopy and mass spectroscopy.
3
K. Mochida, Y. Matsui, Y. Ota, K. Arakawa, Y. Date, Bull.
Chem. Soc. Jpn. 1976, 49, 3119.
R. V. Vico, E. I. Buján, R. H. de Rossi, J. Phys. Org. Chem.
2002, 15, 858.
Kinetics.
The alkaline hydrolyses of organic phosphates
and thiophosphates were carried out in 0.05 and 0.20 mol dmÕ3
NaOH, respectively, at 308 « 0.1 K. The ionic strengths (Ic) of
the solutions were maintained at 0.65 mol dmÕ3 with Na2SO4. The
reaction rates were measured by following the appearance of the
absorption due to the corresponding phenoxide anions at 410 nm
for 1S, 2S, 1O, and 2O and at 390 nm for 3S and 3O. In a typical
run, 2.00 mL of a base solution was pipetted into a pair of 1.00-cm
quartz cells, one of which was used as a reference cell, and
the other, as a sample cell, in a spectrophotometer. After thermal
equilibrium had been reached, 5 to 20 µL of a ca. 20 mmol dmÕ3
ester in methanol was added to the sample cell and the change in
absorbance was followed. The rate constants (kobsd) were deter-
mined by a nonlinear least-squares curve-fitting analysis of the
data according to the ordinary first-order rate equation. All the
reactions examined obeyed good first-order kinetics with respect
to substrates in both the absence and presence of ¡-CD and
G1-¢-CD.
4
5
a) M. Kamiya, S. Mitsuhasi, M. Makino, Chemosphere
1992, 25, 1783. b) M. Kamiya, K. Nakamura, C. Sasaki,
Chemosphere 1994, 28, 1961. c) M. Kamiya, K. Nakamura,
Pestic. Sci. 1994, 41, 305. d) M. Kamiya, K. Nakamura, C. Sasaki,
Chemosphere 1995, 30, 653. e) M. Kamiya, K. Nakamura,
Environ. Int. 1995, 21, 299. f) S. Ishiwata, M. Kamiya, Chemo-
sphere 1999, 38, 2219. g) S. Ishiwata, M. Kamiya, Chemosphere
1999, 39, 1595. h) S. Ishiwata, M. Kamiya, Chemosphere 2000,
41, 701. i) M. Kamiya, K. Kameyama, S. Ishiwata, Chemosphere
2001, 42, 251.
6
a) Y. C. Luo, Q. R. Zeng, G. Wu, Z. K. Luan, R. B. Yang,
B. H. Liao, Bull. Environ. Contam. Toxicol. 2003, 70, 998. b) Q.
Zeng, B. Liao, Y. You, C. Liu, H. Tang, Bull. Environ. Contam.
Toxicol. 2003, 71, 668.
7
B. Manunza, S. Deiana, M. Pintore, C. Gessa, Glycocon-
Kinetic Determination of the Binding Constants and Rate
Constants of CyclodextrinÍSubstrate Complexes. As is shown
in Figure 2b for a G1-¢-CDÍ1O system as an example, the
observed first-order rate constant (kobsd) increased, approached
maximum, and then decreased as the CD concentration (c0)
increased. This behavior suggests that the rate process involves the
prior formation of not only 1:1 but also 2:1 (host:guest) inclusion
complexes of the CD with the substrate. In such a case, we can
derive eq 1:11
jugate J. 1998, 15, 293.
8
D. Churchill, J. C. F. Cheung, Y. S. Park, V. H. Smith, G.
vanLoon, E. Buncel, Can. J. Chem. 2006, 84, 702.
9
I. Yamamoto, K. Ohsawa, F. W. Plapp, Jr., J. Pestic. Sci.
1977, 2, 41.
10 Y. Okada, Y. Kubota, K. Koizumi, S. Hizukuri, T. Ohfuji,
K. Ogata, Chem. Pharm. Bull. 1988, 36, 2176.
11 O. S. Tee, X.-X. Du, J. Org. Chem. 1988, 53, 1837.
12 R. I. Gelb, L. M. Schwartz, J. J. Bradshaw, D. A. Laufer,
Bioorg. Chem. 1980, 9, 299.
13 S. Hamai, J. Mater. Chem. 2005, 15, 2881.
14 R. L. VanEtten, J. F. Sebastian, G. A. Clowes, M. L.
Bender, J. Am. Chem. Soc. 1967, 89, 3242.
K1K2c3 þ ðK1 þ 2K1K2s0 ꢀ K1K2c0Þc2
þ ð1 þ K1s0 ꢀ K1c0Þc ꢀ c0 ¼ 0
ð1Þ
where K1 and K2 are binding constants for 1:1 and 2:1 complexes,
respectively, c0 and s0, initial concentrations of CD and substrate,
respectively, and c, equilibrium concentration of CD.
15 W. Loremz, G. Schrader, Chem. Abstr. 1963, 58, 11402e.
16 T. Miyamoto, I. Yamamoto, J. Pestic. Sci. 1997, 2, 303.