Polymer concentration-controlled substrate specificity in solvolysis of p-nitrophenyl alkanoates catalyzed by 4-(dialkylamino)pyridine-functionalized polymer in aqueous methanol solution

Article abstract of DOI:10.1021/ja970407c

The substrate specificity in solvolysis reactions of p-nitrophenyl alkanoates 2 (n = 2-18) catalyzed by 4-(dialkylamino)pyridine-functionalized polymer 1 can be controlled by the concentration of 1 in 50:50 (v/v) methanol-aqueous phosphate buffer solution

Full text of DOI:10.1021/ja970407c

J. Am. Chem. Soc. 1998, 120, 883-887
883
Polymer Concentration-Controlled Substrate Specificity in Solvolysis
of p-Nitrophenyl Alkanoates Catalyzed by
4-(Dialkylamino)pyridine-Functionalized Polymer in Aqueous
Methanol Solution
Guang-Jia Wang* and Wilmer K. Fife*
Contribution from the Department of Chemistry, Indiana UniVersity-Purdue UniVersity at Indianapolis,
402 North Blackford Street, Indianapolis, Indiana 46202
ReceiVed February 7, 1997. ReVised Manuscript ReceiVed NoVember 3, 1997
Abstract: The substrate specificity in solvolysis reactions of p-nitrophenyl alkanoates 2 (n ) 2-18) catalyzed
by 4-(dialkylamino)pyridine-functionalized polymer 1 can be controlled by the concentration of 1 in 50:50
(v/v) methanol-aqueous phosphate buffer solution at pH 8.0 and 30 °C. Below 1.0 × 10-5 unit mol L-1
,
macromolecule 1 exhibits substrate specificity for 2 (n )14). As the concentration of 1 increases to 2.5 ×
10-5 unit mol L-1, the substrate preference changes from 2 (n ) 14) to 2 (n ) 12). The substrate specificity
changes again from 2 (n ) 12) to 2 (n ) 10) when the concentration of 1 increases further to 7.5 × 10-5 unit
mol L-1. The control of substrate specificity by polymer catalyst concentration is believed to be unprecedented
for catalysis of ester solvolysis.
Introduction
the 4-(dialkylamino)pyridine functionality and a bis(trimethyl-
ene)disiloxane backbone (Scheme 1).7 The tris(hydroxymethyl)-
methylammonium ion as a salting-in ion induces the same
substrate specificity for 2 (n ) 6) in aqueous Tris buffer solution
that is obtained with cholesterol esterase for the same hydrolysis
reaction.8 The addition of salting-out agent NaCl induces a
substrate specificity change from 2 (n ) 14) to 2 (n ) 12) in
50:50 (v/v) methanol-aqueous phosphate buffer solution.7c
However, control of substrate specificity by the concentration
of catalyst has not been reported to date for catalysis of
solvolysis reactions.
In this report we describe the first example of substrate
specificity controlled by a polymer catalyst concentration in
solvolysis reactions of 2 (n ) 2-18) catalyzed by 1 in 50:50
(v/v) methanol-aqueous phosphate buffer solution. By chang-
ing the concentration of 1, we are able to change the substrate
preference in 1-catalyzed solvolysis of 2 (n ) 2-18) in
methanol-water medium. These results are unprecedented for
catalysis of ester solvolysis. Furthermore, we report a detailed
kinetic characterization of the effects of polymer concentration
on the 1-catalyzed solvolysis of 2 (n ) 10-16) in different
The hydrophobic effects, which are a principal force in
determining the structures of proteins and nucleic acids and the
binding of substrates to enzymes, play a pivotal role in many
chemical phenomena in aqueous solution. Small-molecule
amphiphiles are well-known to form aggregates of various
morphologies in aqueous solution.1 Depending on the copoly-
mer composition and the surrounding medium, amphiphilic
macromolecules can also form aggregates with multiple mor-
phologies.2 Extensive studies have shown that the increase of
hydrophobic effects of amphiphilic macromolecules, i.e., the
increase in ratio of hydrophobic to hydrophilic components and
the addition of salting-out agents, leads to changes of aggregate
morphology from spheres to rods, and to vesicles in appropriate
solvents.2,3 4-(Dialkylamino)pyridine-functionalized polymers
have been regarded as useful and simple model systems for
obtaining a better understanding of the origins of enzymic
efficiency and selectivity.4-6 Recently, we have reported ion-
induced substrate specificity in solvolysis of p-nitrophenyl
alkanoates 2 (n ) 2-18) catalyzed by polymer 1 containing
(1) (a) Kaler, E. W.; Murthy, A. K.; Rodriguez, B. E.; Zasadzinski, J.
A. N. Science 1989, 245, 1371. (b) Safran, S. A.; Pincus, P.; Andelman, D.
Science 1990, 248, 354. (c) Brasher, L. L.; Herrington, K. L.; Kaler, E. W.
Langmuir 1995, 11, 4267. (d) Sein, A.; Engberts, J. B. F. N. Langmuir
1995,11, 455. (e) Ravoo, B. J.; Engberts, J. B. F. N. Langmuir 1994, 10,
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(b) Mathias, L. J.; Cei, G. Macromolecules 1987, 20, 2645. (c) Cei, G.;
Mathias, L. J. Macromolecules 1990, 23, 4127.
(6) (a) Fife, W. K.; Rubinsztajn, S.; Zeldin, M. J. Am. Chem. Soc. 1991,
113, 8535. (b) Jackson, P. L.; Rubinsztajn, S.; Fife, W. K.; Zeldin, M.;
Gorenstein, D. G. Macromolecules 1992, 25, 7078. (c) Rubinsztajn, S.;
Zeldin, M.; Fife, W. K. Macromolecules 1991, 24, 2682. (d) Rubinsztajn,
S.; Zeldin, M.; Fife, W. K. Macromolecules 1990, 23, 4026. (e) Fife, W.
K. Trends Polym. Sci. 1995, 3, 214. (f) Wang, G. J.; Fife, W. K. Langmuir
1997, 13, 3320.
(7) (a) Wang, G. J.; Ye, D.; Fife, W. K. J. Am. Chem. Soc. 1996, 118,
12536. (b) Wang, G. J.; Fife, W. K. Macromolecules 1996, 29, 8587. (c)
Wang, G. J.; Fife, W. K. Angew. Chem., Int. Ed. Engl. 1997, 36, 1543.
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S0002-7863(97)00407-1 CCC: $15.00 © 1998 American Chemical Society
Published on Web 01/22/1998

884 J. Am. Chem. Soc., Vol. 120, No. 5, 1998
Wang and Fife
Scheme 1
compositions of methanol-aqueous phosphate buffer solution,
which provides significant new insight into the mechanism of
catalytic ester solvolysis.
Experimental Section
Materials and Reagents. Synthesis of the poly(siloxane-bis-
(trimethylene)) supported 4-(dialkylamino)pyridine (1) has been de-
scribed previously.6c p-Nitrophenyl alkanoates 2 (n ) 2-18) and 1,4-
dioxane were purchased from Sigma Chemical Co. Methanol and
aqueous buffer (0.05 M H2PO4-/HPO42-, pH 8.0) solution were used
as received from Aldrich and Fisher. Stock solutions (2.5 × 10-2 M)
of p-nitrophenyl alkanoates 2 (n ) 2-18) were prepared in 1,4-dioxane.
The fresh catalyst solutions for kinetic experiments were made up in
methanol-aqueous phosphate buffer solution.
Kinetic Measurements. The cuvette was filled with 2.5 mL of a
fresh solution containing catalyst in methanol-aqueous buffer (0.05
M H2PO4-/HPO42-, pH 8.0) solution and the solution was equilibrated
for 10 min at 30 °C in the thermostated cell compartment of a Hewlett-
Packard Model 8450 spectrophotometer. A fresh stock solution (5 µL)
of p-nitrophenyl alkanoates 2 (n ) 2-18, 2.5 × 10-2 M) in dioxane
was added by microsyringe. The reaction mixture was quickly mixed
by shaking and the absorbance at 400 nm was recorded as a function
of time. The reactions were performed for 4-5 half-lives and the
pseudo-first-order rate constants (kobsd) were obtained as slopes of plots
of ln[A∞/(A∞ - At)] vs time, where A∞ and At are the absorbance at
infinite time and time t, respectively. The first-order rate constants
(kobsd) represent the average of three runs and experimental error is
less than (5%.
Figure 1. Pseudo-first-order rate constants (kobsd) for the solvolysis of
p-nitrophenyl alkanoates 2 (n ) 2-18, 5.0 × 10-5 M) catalyzed by 1
as a function of alkanoate chain length (n) in 50:50 (v/v) methanol-
aqueous buffer (0.05 M H2PO4-/HPO42-, pH 8.0) solution at 30 °C:
(b) 7.5 × 10-5 unit mol L-1 1; (9) 2.5 × 10-5 unit mol L-1 1; (2) 5.0
× 10-6 unit mol L-1 1.
Table 1. Summary of the Effect of Concentration of 1 on the
Substrate Specificity of 1-Catalyzed Solvolysis of 2 (n ) 2-18) in
Aqueous Methanol Solution at 30 °Ca
concn of 1 (unit mol L-l)b
substrate specificity
5.0 × 10-6
1.0 × 10-5
2.5 × 10-5
5.0 × 10-5
7.5 × 10-5
l.0 × 10-4
2 (n ) 14)
2 (n ) 14)
2 (n ) 12)
2 (n ) 12)
2 (n ) 10)
2 (n ) 10)
a 2, 5.0 × 10-5 M. b In 50:50 (v/v) methanol-aqueous buffer (0.05
M H2PO4-/HPO42-, pH 8.0) solution.
unit mol L-l (Table 1). At 5.0 × 10-6 unit mol L-1, the
macromolecule 1 exhibits a preference for 2 (n ) 14). As the
concentration of 1 increases to 1.0 × 10-5 unit mol L-1, the
substrate preference is still for 2 (n ) 14) (Table 1). However,
when the concentration of 1 increases to 2.5 × 10-5 unit mol
L-1, the substrate specificity changes from 2 (n ) 14) to 2 (n
) 12) (Figure 1). For 5.0 × 10-5 unit mol L-1, the substrate
specificity also favors 2 (n ) 12) (Table 1). As the concentra-
tion of 1 increases further to 7.5 × 10-5 unit mol L-1, the
substrate specificity changes again from 2 (n ) 12) to 2 (n )
10). The latter substrate specificity is also observed for 1.0 ×
10-4 unit mol L-1 1 (Table 1). Apparently, the substrate
specificity for the 1-catalyzed solvolysis of 2 is controlled by
the concentration of 1 in 50:50 (v/v) methanol-aqueous
phosphate buffer solution. Although both enzymes and synthetic
catalysts exhibit substrate specificity for the same solvolysis
reactions,5,8-10 we are not aware of any catalytic systems that
show substrate specificity controlled by the concentration of
catalyst for catalysis of ester solvolysis.
Results and Discussion
The macromolecule 1 is an amphiphilic polymer containing
distinct hydrophobic and hydrophilic regions. The catalytic
center of macromolecule 1 is the 4-(dialkylamino)pyridine group
and the hydrophobic association of substrate to catalyst in the
reaction medium is responsible for the rate enhancements
observed in the 1-catalyzed solvolysis reaction of 2.4-7
We have measured pseudo-first-order rate constants for the
1-catalyzed solvolysis of 2 (n ) 2-18) with different concen-
trations of 1 as a function of alkanoate chain length in 50:50
(v/v) methanol-aqueous phosphate buffer solution at pH 8.0
and 30 °C. The results are presented in Figure 1 and Table 1.
Without 1, the solvolysis rate of 2 (n ) 2-18) is very slow
and no substrate specificity is observed in methanol-water
solution. In fact, an increase of the alkanoate chain length in
2 causes small decreases in the solvolysis rates. The rates for
1-catalyzed solvolysis of 2 (n ) 2-18) increase significantly
with increasing concentration of 1. Surprisingly, we find that
macromolecule 1 demonstrates different substrate preferences
as its concentration increases from 5.0 × 10-6 to 1.0 × 10-4
Furthermore, we find that the solutions of 1 show appreciable
turbidity when the concentration of 1 is increased beyond 1.0
(9) Marshall, T. H.; Akgun, A. J. Biol. Chem. 1971, 246, 6019.
(10) Bhattacharya, S.; Snehalatha, K. Langmuir 1995, 11, 4653.

SolVolysis of p-Nitrophenyl Alkanoates
J. Am. Chem. Soc., Vol. 120, No. 5, 1998 885
frozen aggregate.3 These considerations are also adopted in our
calculations. Interestingly, the values of DL and DS are almost
the same for both processes. The 3% difference between values
of DL and DS for the change from 2 (n ) 14) to 2 (n ) 12) and
the change from spheres to rods seems to be reasonable when
probable measurement error in the studies of morphological
structures by transmission electron microscopy is taken into
consideration.3 These results suggest that a parallel and
equivalent decrease in hydrophobic effects is involved in both
processes. Therefore, the substrate specificity changes that
accompany an increase in the concentration of 1 may be caused
by an energetically favorable matching of hydrophobicities of
substrate 2 and aggregates of 1 leading to enhanced stabilization
of 1‚2 complexes. We suggest that the substrate specificity
change from 2 (n ) 14) to 2 (n ) 12) may result from a change
of aggregate morphology of 1 from spheres to rods leading to
decreased hydrophobic binding and increased access of 1‚2
complexes to the nucleophilic medium that is optimum for 2
(n ) 12), whereas the specificity change from 2 (n ) 12) to 2
(n ) 10) may be attributed to further change of aggregate
morphology of 1 from rods to vesicles leading to further
decreased hydrophobic binding compensated by more rapid
turnover that is optimum for 2 (n ) 10). The matching of
hydrophobicities of substrate and aggregate of catalyst is
believed to be responsible for the molecular discrimination
described by the term hydrophobic interactions at active sites
of enzymes and catalysts in controlling substrate specificity for
biological and chemical catalysis. Moreover, we find that
increasing the concentration of 1 has a parallel effect on the
substrate specificity, as does increasing the concentrations of
NaCl in 50:50 (v/v) methanol-aqueous phosphate buffer
solution,7a,c which is consistent with the notion that the
hydrophobic effect is at work controlling the substrate specificity
in the 1-catalyzed solvolysis of 2 (n ) 2-18). We suggest
further that the distribution of both 1 and 2 among solution and
aggregate phases controlled by polymer concentration and
reaction medium may also be a major factor affecting the
solvolysis rates of 2 in methanol-aqueous phosphate buffer
solution.
Table 2. The Decrease of Length of Alkanoate Chain (DL) of 2
Associated with Substrate Specificity Changes from 2 (n ) 14) to 2
(n ) 12) and 2 (n ) 10) and the Decrease of Stretching of
Hydrophobic Chains (DS) of Amphiphilic Macromolecules
Associated with Aggregate Morphology Changes from Sphere to
Rod and Vesiclea
change of substrate
specificity
change of aggregate
morphology
b
DL
Dsc
2 (n ) 14) f 2 (n ) 14)
2 (n ) 14) f 2 (n ) 12)
2 (n ) 14) f 2 (n ) 10)
0%
14%
29%
sphere f sphere
sphere f rod
sphere f vesicle
0%
11%
29%
a Stretching of hydrophobic chains in aggregate morphology (ratio
of the core radius of aggregate to the hydrophobic chain end-to-end
distance in the unperturbed state): 1.40 for spheres, 1.25 for rods, and
1.00 for vesicles (see ref 3a,c). b DL ) (L2(n)14) - L2(n)12 or 10))/L2(n)14)
,
where L is the length of alkanoate chains of substrates. c DS ) (Ssphere
- Srod or vesicle)/Ssphere, where S is the stretching of hydrophobic chains
of aggregate morphology (Ssphere ) 1.40, Srod ) 1.25, and Svesicle
)
1.00).3a
× 10-4 unit mol L-1 in 50:50 (v/v) methanol-aqueous
phosphate buffer solution. These results suggest that changes
of the aggregate morphology of 1 from spheres to rods, and to
vesicles may accompany the increases of concentration of 1
-4
from 5.0 × 10-6 to 1.0 × 10
unit mol L-1 in 50:50 (v/v)
methanol-aqueous phosphate buffer solution.3 A phenomenon
well-known for small-molecule amphiphiles is that increases
of their concentrations are accompanied by the transition from
spherical micelles to micellar rods and vesicles in solution.11
Very recently, changes of aggregate morphology of polystyrene-
b-poly-2-vinylpyridine copolymers from spheres to rods, and
to vesicles have also been observed with increasing polymer
concentration.12 The continual changes in aggregate morphol-
ogy are governed solely by the polymer concentration in the
solutions.12 The stretching of hydrophobic chains of macro-
molecular amphiphiles is known to be greatest when they are
located within spherical aggregates, and stretching decreases
as the aggregate morphology changes from spheres to rods and
decreases further as vesicles are formed.3 Thus, spherical
aggregates tend to provide the strongest hydrophobic binding
to lipophilic substrates among the common aggregate morphol-
ogies in the reaction medium.
We have also examined the effects of polymer concentration
on the 1-catalyzed solvolysis of 2 (n ) 10-16) in different
compositions of methanol-aqueous phosphate buffer solution
at pH 8.0 and 30 °C in order to detect the relationships between
the rate of model reaction and changes of concentration of 1 in
the reaction medium. The data in Figure 2 on the pseudo-first-
order rate constants for the 1-catalyzed solvolysis of 2 (n )
10) as a function of concentration of 1 show that the solvolysis
rates increase strongly with an increase in the concentration of
1 in 45:55 and 50:50 (v/v) methanol-water but modestly with
an increase in the concentration of 1 in 55:45 and 60:40 (v/v)
methanol-water, and tend to level off at the later stage.
Strikingly, below 2.5 × 10-5 unit mol L-1 1, the order of
reactivity for 2 (n ) 10) is 45:55 > 50:50 > 55:45 > 60:40
(v/v) methanol-aqueous phosphate buffer solution. However,
above 5.0 × 10-5 unit mol L-1 1, the reactivity order is 50:50
> 45:55 > 55:45 > 60:40 (v/v) methanol-aqueous phosphate
buffer solution.
We have made an attempt to compare the decreases of alka-
noate chain length (DL) of 2 associated with substrate specificity
changes from 2 (n ) 14) to 2 (n ) 12) and 2 (n ) 10) with the
decreases of stretching of hydrophobic chains (DS) of am-
phiphilic macromolecules associated with aggregate morphology
changes from spheres to rods and vesicles3 (Table 2). As
indicated by Eisenberg et al.,3 the kinetics of exchange between
aggregates and single chains in solution are slow due to the
high viscosity of the insoluble chains within the aggregates of
polymers. On a reasonable time scale, the aggregates of poly-
mers may be regarded as “frozen” structures with no dynamic
equilibrium between aggregates and single chains.3 Therefore,
an application of theoretical models for such systems requires
the assumption that a dynamic equilibrium does exist at some
stage of aggregate formation even though the final result is a
(11) (a) Fendler, J. H. Membrane Mimetic Chemistry: Characterizations
and Applications of Micelles, Microemulsions, Monolayers, Bilayers,
Vesicles, Host Guest Systems, and Polyions; Wiley-Interscience: Chichester,
UK, 1982. (b) Lucassen-Reynders, E. H. Anionic Surfactants, Physical
Chemistry of Surfactant Action; Surfactant Series, Vol. 11; Dekker: New
York, 1981. (c) Hoffmann, H. AdV. Mater. 1994, 4, 116. (d) Buckingham,
S. A.; Garvey, C. J.; Warr, G. G. J. Phys. Chem. 1993, 97, 10236. (e)
Gamboa, C.; Sepulveda, L. J. Phys. Chem. 1989, 93, 5540.
The pseudo-first-order rate constants for the 1-catalyzed
solvolysis of 2 (n ) 12) as a function of the polymer
concentration in different compositions of methanol-aqueous
phosphate buffer solution are plotted in Figure 3. We find that
the pseudo-first-order rate constants increase by a factor of about
35 when the concentration of 1 is increased to 2.5 × 10-5 unit
mol L-1 and then stay at plateau values up to 1.0 × 10 -4 unit
(12) Li, Z.; Zhao, W.; Liu, Y.; Rafailovich, M. H.; Sokolov, J.; Khougaz,
K.; Eisenberg, A.; Lennox, R. B.; Krausch, C. J. Am. Chem. Soc. 1996,
118, 10892.

886 J. Am. Chem. Soc., Vol. 120, No. 5, 1998
Wang and Fife
Figure 4. Pseudo-first-order rate constants (kobsd) for the 1-catalyzed
solvolysis of 2 (n ) 14, 5.0 × 10-5 M) as a function of polymer
concentration in different compositions of methanol-aqueous buffer
(0.05 M H2PO4-/HPO42-, pH 8.0) solution at 30 °C: (4) in 45:55 (v/
v) CH3OH-H2O; (b) in 50:50 (v/v) CH3OH-H2O; (2) in 55:45 (v/v)
CH3OH-H2O; (9) in 60:40 (v/v) CH3OH-H2O.
Figure 2. Pseudo-first-order rate constants (kobsd) for the 1-catalyzed
solvolysis of 2 (n ) 10, 5.0 × 10-5 M) as a function of polymer
concentration in different compositions of methanol-aqueous buffer
(0.05 M H2PO4-/HPO42-, pH 8.0) solution at 30 °C: (4) in 45:55 (v/
v) CH3OH-H2O; (b) in 50:50 (v/v) CH3OH-H2O; (2) in 55:45 (v/v)
CH3OH-H2O; (9) in 60:40 (v/v) CH3OH-H2O.
Figure 5. Pseudo-first-order rate constants (kobsd) for the 1-catalyzed
solvolysis of 2 (n ) 16, 5.0 × 10-5 M) as a function of polymer
concentration in different compositions of methanol-aqueous buffer
(0.05 M H2PO4-/HPO42-, pH 8.0) solution at 30 °C: (4) in 45:55 (v/
v) CH3OH-H2O; (b) in 50:50 (v/v) CH3OH-H2O; (2) in 55:45 (v/v)
CH3OH-H2O; (9) in 60:40 (v/v) CH3OH-H2O.
Figure 3. Pseudo-first-order rate constants (kobsd) for the 1-catalyzed
solvolysis of 2 (n ) 12, 5.0 × 10-5 M) as a function of polymer
concentration in different compositions of methanol-aqueous buffer
(0.05 M H2PO4-/HPO42-, pH 8.0) solution at 30 °C: (4) in 45:55 (v/
v) CH3OH-H2O; (b) in 50:50 (v/v) CH3OH-H2O; (2) in 55:45 (v/v)
CH3OH-H2O; (9) in 60:40 (v/v) CH3OH-H2O.
phosphate buffer solution. But, the magnitude of catalytic
effects is 50:50 > 45:55 > 55:45 > 60:40 (v/v) methanol-
aqueous phosphate buffer solution over 2.5 × 10-5 unit mol
L-1 1.
The dependence of the pseudo-first-order rate constants on
the concentration of 1 for the 1-catalyzed solvolysis of 2 (n )
14) in different compositions of methanol-aqueous phosphate
mol L-1 in 50:50 (v/v) methanol-aqueous phosphate buffer
solution. Similar types of kinetic behavior for 2 (n ) 12) have
also been observed in 45:55, 55:45, and 60:40 (v/v) methanol-
aqueous phosphate buffer solution. Significantly, below 1.0 ×
10-5 unit mol L-1 1, the catalytic efficiency for 2 (n ) 12) is
45:55 > 50:50 > 55:45 > 60:40 (v/v) methanol-aqueous

SolVolysis of p-Nitrophenyl Alkanoates
J. Am. Chem. Soc., Vol. 120, No. 5, 1998 887
buffer solution is presented in Figure 4. The solvolysis reactions
exhibit rapid enhancements of the pseudo-first-order rate con-
stants at low concentrations of 1, followed by gradual levelling
off with increasing concentrations of 1. Finally, the rate con-
stants reach plateau values. It is noted that the reactivity order
of 2 (n ) 14) is 45:55 > 50:50 > 55:45 > 60:40 (v/v) metha-
nol-aqueous phosphate buffer solution below 5.0 × 10-6 unit
mol L-1 1, and the order of reactivity is 50:50 > 45:55 > 55:
45 > 60:40 (v/v) methanol-aqueous phosphate buffer solution
between 5.0 × 10-6 and 1.0 × 10-5 unit mol L-1 1 and 50:50
> 55:45 > 45:55 > 60:40 (v/v) methanol-aqueous phosphate
buffer solution above 1.0 × 10-5 unit mol L-1 1.
small with further increase in the concentration of 1. Interest-
ingly, the catalytic efficiency is found to be in the order 50:50
> 55:45 > 45:55 > 60:40 (v/v) methanol-aqueous phosphate
buffer solution in the concentration range of 1 investigated.
These results demonstrate that the substrate specificity of
catalysis of ester solvolysis can be controlled by the concentra-
tion of polymer catalyst in the reaction medium, and provide a
new approach to the control of chemical reactivity that can be
useful in understanding the fundamental basis of controlling
substrate specificity at the molecular level in biological and
chemical catalysis. The demonstration of polymer concentra-
tion-controlled substrate specificity establishes this system as a
potential guide to synthetic receptors which can mimic the
biological systems in terms of molecular recognition and
selective interactions with hydrophobic drugs.
Relevant plots of the pseudo-first-order rate constants vs
polymer concentrations for the 1-catalyzed solvolysis of 2 (n
) 16) in different compositions of methanol-aqueous phosphate
buffer solution are graphically shown in Figure 5. The sol-
volysis rates for 2 (n ) 16) increase rapidly with increasing
concentration of 1 up to 1.0 × 10-5 unit mol L-1. But the
effects of polymer concentration on the solvolysis rates are very
Acknowledgment. We thank the Office of Naval Research
for financial support of this work.
JA970407C