Catalytic nanoreactors for ester hydrolysis

Article abstract of DOI:10.1016/j.molcata.2010.09.002

Hydrolysis of 4-nitrophenyl benzoate (PNPB) in the presence of ionene nanoreactors was studied comparing the ionenes, poly[(dimethyl)-2-hydroxy propanodiyl chloride] (2-OH-33R1), poly[(methylbutyliminium)-2-hydroxy propanodiyl chloride] (2-OH-33R4) and poly[(methyloctyliminium)-2-hydroxy propanodiyl chloride] (2-OH-33R8). Methyl orange incorporation and study of viscosity showed that increase of the side chain length of the ionene enhances the ability to form globular hydrophobic microdomains. Catalytic hydrolysis of PNPB follows the order 2-OH-33R8 2-OH-33R4 > 2-OH-33R1, and 2-OH-33R8 has the lowest pK_a that may reflect its higher hydrophobicity, which apparently influences the ionene nanoreactor reactivity. A lower pK_a indicates easier deprotonation of the alkoxide group, which participates more effectively in the reaction and the 2-OH-33R8 functionalized ionene acts as a specially effective catalytic homogeneous nanoreactor.

Full text of DOI:10.1016/j.molcata.2010.09.002

Journal of Molecular Catalysis A: Chemical 332 (2010) 7–12
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Journal of Molecular Catalysis A: Chemical
journal homepage: www.elsevier.com/locate/molcata
Editor’s Choice paper
Catalytic nanoreactors for ester hydrolysis
Alexanders T.N. Berlamino, Elisa S. Orth, Renata S. Mello, Michelle Medeiros, Faruk Nome∗
Departamento de Química, INCT-Catálise, Universidade Federal de Santa Catarina, Florianópolis, SC 88040-900, Brazil
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 7 June 2010
Received in revised form 25 August 2010
Accepted 2 September 2010
Available online 21 September 2010
Hydrolysis of 4-nitrophenyl benzoate (PNPB) in the presence of ionene nanoreactors
was studied comparing the ionenes, poly[(dimethyl)-2-hydroxy propanodiyl chloride] (2-
OH-33R1),
poly[(methylbutyliminium)-2-hydroxy
propanodiyl
chloride]
(2-OH-33R4)
and
poly[(methyloctyliminium)-2-hydroxy propanodiyl chloride] (2-OH-33R8). Methyl orange incor-
poration and study of viscosity showed that increase of the side chain length of the ionene enhances
the ability to form globular hydrophobic microdomains. Catalytic hydrolysis of PNPB follows the order
2-OH-33R8 ꢀ 2-OH-33R4 > 2-OH-33R1, and 2-OH-33R8 has the lowest pKa that may reflect its higher
hydrophobicity, which apparently influences the ionene nanoreactor reactivity. A lower pKa indicates
easier deprotonation of the alkoxide group, which participates more effectively in the reaction and the
2-OH-33R8 functionalized ionene acts as a specially effective catalytic homogeneous nanoreactor.
© 2010 Elsevier B.V. All rights reserved.
Keywords:
Ester hydrolysis
Ionenes
Nanoreactors
1. Introduction
mer backbone separated by different numbers (x, y) of methylene
groups. The hydrophobicity of these compounds is determined by
The design of efficient nanoreactors based on the mimicking of
enzymatic reactions has been of increasing interest and resulted
in the design of efficient models, ranging from a simple molecular
structures [1–5] to more complex macromolecules (polymeric [6]
and dendrimeric [7]), which combine different functionalities that
resemble polysoaps and natural enzymes [8–11]. Polysoaps are a
class of polymers which comprise features of polyelectrolytes and
micelles, thus forming well-organized structures which depend
on electrostatic and hydrophobic forces and allow the binding of
organic substrates and ionic reactants [12]. A typical polysoap is
obtained when polyvinylpyridine is alkylated with ethyl and dode-
cyl bromides [13], and this class of compounds can accelerate many
reactions [13,14], resembling the well established rate effects of
micelles. The alkaline hydrolysis of 4-nitrophenyl hexanoate in the
presence of the copolymer formed from 4-vinyl-N-ethylpyridinium
bromide and 4-vinyl-N-dodecylpyridinium bromide (8 × 10−4 M,
expressed as monomeric units) is accelerated by up to 14-fold, com-
pared to reaction in absence of the polysoap [13]. Micellar catalysis
acceleration (dodecyltrimethylammonium bromide) of the same
reaction proceeds with a factor of less than 3, at a much higher
concentration (0.02 M) [15].
the number of the methylene group in the spacers and the size of
the side chain segment, forming polysoaps aggregates, which in
many aspects are similar to micelles [16–18].
Ionenes have found a variety of applications, such as fungicides
and bactericides [19,20], anticoagulants [21], antiheparinic agents
[22], flocculants [23] and corrosion inhibitors [24]. Most recently,
ionenes have been shown to have relevance as gene delivery agents
[8,25,26], because use of cationic polymers in non-viral gene deliv-
ery is of increasing interest due to safety considerations [27].
Ionenes may be functionalized with reactive groups, thus behav-
ing like a nanoreactor. We reported previously the hydrolysis of
benzoic anhydride mediated by micelles and ionene nanoreactors
[28]. In particular, the functionalized poly[(dimethyl)-2-hydroxy
propanodiyl chloride] (2-OH-33R1) gave up to 25-fold rate
enhancements, in contrast to the 5-fold rate enhancement
for the non-functionalized ionene poly[(dipropyliminium)-1,3-
propanediyl bromide] (33R3), showing the important participation
of the ionene alkoxy group.
In this study, we are interested in evaluating the effect of
the introduction of hydrophobic microdomains in 2-OH-33R1,
with ionene nanoreactors such as poly[(methylbutyliminium)-
An interesting class of polysoaps are the ionenes, which are
cationic polymers with quaternized nitrogen atoms in the poly-
2-hydroxy
propanodiyl
chloride]
(2-OH-33R4)
and
poly[(methyloctyliminium)-2-hydroxy propanodiyl chloride]
(2-OH-33R8). The effect of the increase in hydrophobicity is
analyzed by examining reduced viscosity, methyl orange incor-
poration, and kinetic effects. Alkaline hydrolysis of 4-nitrophenyl
benzoate is efficiently mediated by the functionalized ionenes
∗
Corresponding author. Tel.: +55 48 3721 6849; fax: +55 48 3721 6850.
E-mail address: faruk@qmc.ufsc.br (F. Nome).
1381-1169/$ – see front matter © 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.molcata.2010.09.002

8
A.T.N. Berlamino et al. / Journal of Molecular Catalysis A: Chemical 332 (2010) 7–12
which concentrate reagents and behave as catalytic homogeneous
nanoreactors.
2. Experimental
2.1. Materials
Fig. 1. Ratio of the absorbances of methyl orange at 372 nm (I1) and 464 nm (I2)
as a function of the ionene [2-OH-33R4], 0.02 M borate and pH = 9.40 (for data see
Table S.1).
Reactants, methylamine 40%, bromobutane 98% and bromod-
ecane were obtained from Merck. Methylbutylamine 99% and
diethylamine were from Aldrich and ␣-epichlorohydrin was from
Sigma. All these reactants were used as received. Other reactants
and solvents of analytical grade were used without further purifica-
tion. The ionene 2-OH-33R1 was prepared and purified as described
[23,28]. The syntheses of 2-OH-33R4 and 2-OH-33R8 are described
in the supplementary information.
464 nm. Aliquots of 10 ␮L of a stock solution 1 × 10−2 M of methyl
orange were added to a cuvette containing 2.0 mL of the desired
polyelectrolyte with known concentration, with a final dye con-
centration of 4.98 × 10−5 M.
3. Results and discussion
2.2. Potentiometric titration
3.1. Characterization of the ionene nanoreactors
The polymer concentrations in the stock solutions were deter-
mined by titration of the chloride counterion by using the
Mohr method. Standard solutions were 0.1 M silver nitrate and
silver chromate was the indicator. The concentration of poly-
mers, expressed as monomeric units, was 93.5 mM, 56.0 mM and
1.75 mM for 2-OH-33R1, 2-OH-33R4 and 2-OH-33R8, respectively.
The absorption spectra of methyl orange has been proven to
be a useful tool to investigate the nature of the hydrophobic
environment in macromolecules because a non-polar environ-
ment significantly shifts ꢀmax to shorter wavelengths [30]. The
absorption spectra of methyl orange changes as a function of con-
centration of the 2-OH-33R4 polyelectrolyte, with the absorbances
increasing at 372 nm and decreasing at 464 nm as a function of the
increase of [2-OH-33R4]. Fig. 1 shows that the intensity ratio of
the absorption peaks has a large variation in ionene concentrations
below 5 × 10−4 M, with a rather small change at higher concentra-
tions. The small absorbance changes may be attributed to the partial
incorporation of methyl orange in the ionene domain, with a sig-
nificant shift to smaller wavelengths developing when the cationic
polyelectrolytes are added to the solution. The observed effect of
the 2-OH-33R4 on the spectra of the dye is suggestive of the induced
formation of hydrophobic microdomains at low concentrations of
polysoaps, and consistent with the assumption of Wang and Eng-
berts [31], that the dye nucleates the formation of new aggregates.
When methyl orange is added to the more hydrophobic 2-
OH-33R8, even for the lowest concentration of ionene, there is
a significative shift of ꢀmax from 464 nm to 390 nm, indicating
that the dye is totally incorporated in the ionene microdomains
(Table 1).
2.3. Kinetics
Reactions were followed in aqueous solution, at constant
pH, by UV–vis spectrometry measuring the appearance of p-
nitrophenolate ion at 400 nm. All reactions were in 0.01 M borate
buffer and first order rate constants, kobs, were not affected by this
dilute buffer [29]. The reactions were carried out in quartz cuvettes
with a final volume of 3.0 mL and 50 ␮M of PNPB. Temperature
was maintained at 25 ◦C with a thermostatted water-jacketed cell
holder. First order rate constants, kobs, were calculated from linear
plots of ln(A – At) against time for at least 90% reaction with an
∞
iterative least-squares program and correlation coefficients were
>0.999 for all kinetic runs. Ionene solutions were prepared with
deionized H2O (Milli-Q system, Millipore).
2.4. Viscosity
Viscosities of aqueous solutions of the ionenes 2-OH-33R8
and 2-OH-33R4 were carried out in an Ostwald viscometer at
25 ◦C. The initial ionene solution (1.18 × 10−2 M of 2-OH-33R8 and
3.27 × 10−2 M of 2-OH-33R4) was progressively diluted with water,
and the viscosity measured after each dilution. Standard solutions
of water, ethanol, acetone and chloroform were used to calibrate
the instrument.
3.2. Reduced viscosity
The concentration dependences of the reduced viscosity of the
ionenes 2-OH-33R4 and 2-OH-33R8 in water are shown in Fig. 2.
As expected for ionenes with R groups between methyl and butyl,
the experimental behavior observed for 2-OH-33R4 is typical of
polyelectrolytes, with the reduced viscosity increasing significantly
as a function of the decrease in polymer concentration [32]. The
observed effect is consistent with the fact that in solution, in
the absence of salt, polyelectrolytes are in their elongated shape,
2.5. Dye incorporation
The absorption spectra of methyl orange in a borate solution
(2 × 10−2 M) were determined at pH 9.4, and showed a maximum at

A.T.N. Berlamino et al. / Journal of Molecular Catalysis A: Chemical 332 (2010) 7–12
9
Table 1
ꢀmax of methyl orange as a function of 2-OH-33R8 concentration.
104 [monomer] (M)
ꢀmax (nm)
0.000
0.510
1.100
1.800
2.800
3.560
6.700
9.333
18.6
464
390
392
390
390
392
390
390
390
390
46.60
presenting high values of hydrodynamic volume. This is a conse-
quence of the fact that with decreasing concentration of the ionene,
the polymer expands because charges on the backbone are less
shielded by counterions which increases repulsion. Probably, upon
addition of salt, chains collapse into random coils due to charge
screening of counter ions.
Conversely, as shown in Fig. 2, the more hydrophobic 2-OH-
33R8 ionene behaves as a polysoap, with the reduced viscosity
profile as a function of concentration being much less dependent on
polymer concentration, consistent with a compact globular shape,
corroborating results of dye incorporation.
Fig. 3. Observed rate constants as a function of KOH concentration for the alkaline
hydrolysis of PNPB, in the presence of 1.82 × 10−2 M 2-OH-33R1 (᭹); 1.48 × 10−2
M
2-OH-33R4 (ꢁ) and 6.73 × 10−5 M 2-OH-33R8 (ꢀ). The points are experimental (for
data see Tables S.7–S.9) and the solid line calculated according to Eq. (2).
3.3. Alkaline hydrolysis of PNPB in the presence of ionenes
The catalytic effect of functionalized ionene nanoreactors in the
alkaline hydrolysis of PNPB was examined, initially, as a function
of the concentration of hydroxide ion, data presented in Fig. 3, and
the results show that the rate constant increases as a function of
the concentration of added KOH showing a typical saturation-like
profile with a reactivity order of 2-OH-33R8 > 2-OH-33R4 > 2-OH-
33R1.
The experimental results shown in Fig. 3 for the alkaline hydrol-
ysis of PNPB in the presence of the functionalized ionenes can
be accounted by the reactions of (i) hydroxide ion in the aque-
ous phase ([HOw−]); (ii) hydroxide ion which concentrates in the
ionene domain ([HOp−]) and (iii) alkoxide in the backbone of the
ionene ([ROp−]), formed by ionisation of the 2-hydroxy substituent
of the polysoap as a function of the increase in basicity in the ionene
Scheme 1. Equilibrium reactions of the ionenes involving the hydroxide species in
the aqueous phase ([HOw−]) and in the ionene domain ([HOp−]) and the alkoxide in
the backbone of the ionene ([ROp−]).
for the ionenes can be estimated by means of Eq. (1).
Ka = KwKe
(1)
−
domain. The interactions between HOw−, HOp and ROp, are given
In order to obtain Ke from the kinetic profile shown in Fig. 3, the
data were fitted with Eq. (2),
in Scheme 1, where Ke is the deprotonation equilibrium of the
ionene alkoxide by hydroxide ion (Scheme 1), and the pKa values
kmaxKe[OH−]w
1 + Ke[OH−]w
kobs
=
(2)
where kmax corresponds to first order rate constant in the presence
of the ionene nanoreactor and most probably contains contribu-
−
tions of both HOp and ROp−. The solid lines in Fig. 3 represent the
theoretical values calculated obtained by using Eqs. (1) and (2) and
Table 2 summarizes the obtained rate and equilibrium constants.
The value of kmax is slightly higher for 2-OH-33R8, and decrease
with decreasing hydrophobicity of the ionenes. The pKa values for
the 2-OH-33R1 and 2-OH-33R4 ionenes are identical. The slightly
smaller value obtained for 2-OH-33R8 is consistent with a more
compact structure, where some electrical potential builds up and
helps to concentrate hydroxide ion in the surface of the ionene.
Table 2
Calculated values of kmax, Ke and pKa for the PNPB hydrolysis in the presence of
2-OH-33R1, 2-OH-33R4 and 2-OH-33R8.
Ionene
kmax (s−1
)
Ke (M−1
)
pKa
2-OH-33R1
2-OH-33R4
2-OH-33R8
0.041
0.046
0.059
120
123
160
11.9
11.9
11.8
Fig. 2. Concentration dependence with the reduced viscosities for ionenes 2-OH-
33R4 (ꢀ) and 2-OH-33R8 (ꢁ) in water (for data see Tables S.2 and S.3).

10
A.T.N. Berlamino et al. / Journal of Molecular Catalysis A: Chemical 332 (2010) 7–12
Table 3
Calculated values of kXO
ꢀ
ꢁ
w
−
p[XO−]KS and k
−
HO− for the PNPB hydrolysis in the
HO
presence of 2-OH-33R1, 2-OH-33R4 and 2-OH-33R8.
ꢀ
ꢁ
w
Polymer
103 kXO
−
p[XO−]KS (M−1 s−1
)
104 kHO
−
HO− (s−1
)
2-OH-33R1a
2-OH-33R4a
2-OH-33R8b
8.60
14.60
5.30
5.19
5.20
7000
a
Calculated using Eq. (4).
Calculated using Eq. (3).
b
([HOw−]) or in the ionene domain ([HOp−]), or reaction with the
alkoxide ion of the ionene ([ROp−]).
Clearly, the reactions of PNPB are mediated by the functionalized
ionenes in this study and Eq. (3), which is consistent with Scheme 2,
was used to fit the data in Fig. 4.
ꢀ
ꢁ
w
kHO
−
HO−
+ k
−
p[XO−]pKSCp
w
XO
kobs
=
(3)
1 + KSCp
In Eq. (3), [HO−]w is the hydroxide concentration in water
and [XO−]p corresponds to the sum of the equilibrium concen-
trations of hydroxide ([HO−]p) and alkoxide ([RO−]p) ions in the
ionene domain, defined as the molarity in the total solution. There-
Fig. 4. Observed rate constants as a function of 2-OH-33R1 (ꢀ), 2-OH-33R4 (ꢁ) and
2-OH-33R8 (᭹) concentration in alkaline hydrolysis of PNPB at pH = 10 (for data see
Tables S.4–S.6). The points are experimental and the solid line calculated according
to Eq. (3).
fore, the term kXO
−
p[XOp−] represents the contribution of both
kHO
−
p[HOp−] and kRO p[ROp−], which corresponds to the reactions
−
of hydroxide ion and alkoxide ions in the ionene domain, respec-
tively (Scheme 2). It is important to notice that at low ionene
concentration, 1 > KsCp, and Eq. (3) simplifies to the form shown
in Eq. (4).
Besides, pKa values in Table 2 show a behavior understandable
when predicting pKas for similar structures [33], and, for example,
(dimethylamino) methanol has a pKa of 14.87, for the acid dissocia-
tion of the OH group, hence the introduction of charged ammonium
ions and hydrophobic groups (to a lesser extent) in neighboring
positions results in a significant pKa decrease. Although under-
standing this charge effect is not simple, the higher reactivity
shown by the 2-OH-33R8 ionene may be due to both its lower pKa
and higher hydrophobicity.
The dependence of kobs with the ionene nanoreactor concentra-
tion (Cp) was also evaluated and the rate constant profile is shown in
Fig. 4 and, there is a linear dependence of the rate constant with Cp
for 2-OH-33R1 and 2-OH-33R4. Conversely, the more hydrophobic
2-OH-33R8 shows a non-linear behavior probably related to more
efficient binding of the substrate [34].
Moreover, compared to the reaction in the absence of ionenes
(k0 = 5.25 × 10−4 s−1, at pH 10), rate enhancements are 2- to 3-
fold for 2-OH-33R1 and 2-OH-33R4 and 15-fold for 2-OH-33R8.
These rate effects are significantly larger than those for the micel-
lar mediated reaction of phenyl benzoate, where a small 1.5-fold
rate increment was observed [35]. Besides, the effect is con-
sistent with previous studies [28] which showed that, in the
alkaline hydrolysis of benzoic anhydride, the rate constant in the
presence of a non-functionalized ionene (poly[(dipropyliminium)-
1,3-propanediyl bromide], 33R3) is accelerated with only 24% of the
efficiency of the corresponding catalysis by the functionalized lin-
ear ionene nanoreactor (2-OH-33R1). All these reactions are fully
consistent with Scheme 2, where alkaline hydrolysis of the sub-
strate involves reaction of hydroxide ion in the aqueous phase
ꢀ
ꢁ
w
kobs = kHO
−
HO−
+ k
−
p[XO−]pKSCp
(4)
w
XO
It follows that a plot of kobs versus Cp should be linear for low
values of Ks and/or Cp. Indeed, this linear behavior was observed
for the ionenes 2-OH-33R1 and 2-OH-33R4, and the data was fitted
with this simplified equation and the calculated values for slope and
intercepts are given in Table 3. With the more efficient 2-OH-33R8
ionene, a non-linear fit with Eq. (3) was necessary and calculated
ꢀ
ꢁ
w
values of kXO
−
p[XO−]KS and kHO
−
HO− from fit of the data are
also included in Table 3.
ꢀ
ꢁ
w
The calculated constant kHO
−
HO− , included in Table 3, is
consistent with previously reported rate constants for the alka-
line hydrolysis of PNPB (1.95 × 10−4 s−1, pH 10, 33% acetonitrile in
water) [36]. Since the calculated values of pKa for the 2-OH-33R1,
2-OH-33R4 and 2-OH-33R8 are alike, within limits of experimen-
tal error, and the rate constants are only moderately affected by
addition of organic solvents (see above), changes in Ks must be
responsible for the observed dramatic increase in kXO
−
p[XO−]KS.
Thus, the results in Table 3 indicate that 2-OH-33R8 is a much bet-
ter catalyst, by factors of about 815- and 480-fold than 2-OH-33R1
and 2-OH-33R4, respectively. Clearly, the higher hydrophobicity of
2-OH-33R8, facilitates the incorporation of PNPB more effectively
in the ionene domains, promotes an increase in the association
constant Ks and, therefore, a significant increase in catalytic ability.
All studied ionenes showed important catalytic effects, proba-
bly due to their ability to concentrate hydroxide ions ([HOp−]) a
fact that is consistent with the similar pKa values (Table 2) and to
the fact that the alkoxide ion ([ROp−]) of the ionene is an effec-
tive nucleophile in the reaction. Recently, we reported the reaction
of 2-OH-33R1 with benzoic anhydride, and showed that alkoxide
attack occurs as shown in Scheme 3, which can be extended for
reactions with PNPB. Deprotonation of the alkoxide (Ke, Scheme 1)
is followed by two-step reactions (1) and (2), Scheme 3. In reactions
with benzoic anhydride, the second step (2) is rate-determining,
with breakdown of the acylated ionene intermediate taking about
6 h (in pH = 9). Similarly, in reactions of PNPB, the second step (2)
is expected to be rate-determining, but this fact is not important
Scheme 2. Reactions in the aqueous and ionene nanoreactor domains.

A.T.N. Berlamino et al. / Journal of Molecular Catalysis A: Chemical 332 (2010) 7–12
11
Scheme 3. Mechanism of PNPB hydrolysis in the presence of the ionene nanoreactors.
Fig. 5. Schematic of a small portion of a (A) polysoap molecule in aqueous solution where one can observe hydrophobic microdomains and free monomeric units, and (B)
normal polyelectrolyte.
since the kinetic experiment were performed using a large excess
of polymer and we only followed the p-nitrophenoxide liberation
(reaction (1) in Scheme 3).
hydrolysis compared to ionenes 2-OH-33R1 and 2-OH-33R4. Fur-
thermore, 2-OH-33R8 has a slightly lower pKa value and its lower
pKa may be a reflection of the higher hydrophobicity. The globular
shape of the 2-OH-33R8 nanoreactor turns the catalysis particularly
This result is not surprising since a p-nitrophenyl ester such as
PNPB is expected to be hydrolyzed faster than the alkylbenzoate
formed in the nanoreactor surface. These polysoaps are structurally
closer to dendrimers than micelles and, in principle, could show
turnover in reactions as do real catalysts in the presence of excess
substrate provided the rate limiting step is the hydrolysis of the
acylated nanoreactors 2-OH-33R1, 2-OH-33R4 and 2-OH-33R8.
The results suggest that alkaline hydrolysis of PNPB mediated
by ionenes can occur as shown in Fig. 5, where (A) is the reac-
tion in the presence of a polysoap which has the ability to form
hydrophobic microdomains, thus acting as a microreactor concen-
trating reactants, and (B) is reaction in the presence of a normal
polyelectrolyte.
effective by increasing the ability of the ionene to concentrate HO−
p
and RO− ions in the surface of the aggregates and, also binds the
p
ester substrate in the interfacial region, behaving, as a consequence,
like a catalytic homogeneous nanoreactor.
Acknowledgements
We thank INCT-Catálise and the Brazilian foundations CNPq,
CAPES and FAPESC for financial assistance.
Appendix A. Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.molcata.2010.09.002.
4. Conclusion
Hydrolysis of PNPB in the presence of ionene nanoreactors was
evaluated by comparing ionenes 2-OH-33R1, 2-OH-33R4 and 2-
OH-33R8. Methyl orange incorporation and viscosity experiments
showed that the increase of the ionene side chain promotes the
ability of the polymer to form globular hydrophobic microdomains.
This might explain the higher reactivity of 2-OH-33R8 toward PNPB
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