CHAPTER 4

Chemomechanical Polymers
HANS-JÖRG SCHNEIDER* AND KAZUAKI KATO

FR Organische Chemie, Universität des Saarlandes, D 66041 Saarbrücken/

Germany

4.1 Introduction
Chemomechanical polymers are intelligent materials that respond to external
chemical stimuli by changing their mechanical properties, in particular their
shape. In most cases these materials are polymeric gels, in which exposure to
chemical compounds leads to volume changes. Chemomechanical polymers
thus provide an intriguing way to new actuator and also sensor systems, which
can operate without any additional measuring devices, including transducers or
transmitters, and also without external power supply.1 An important aspect for
future uses is the possible miniaturisation of such devices, which can go down
to the nanoscale, taking advantage then also of high speed and energy-saving
property of such systems. Most promising applications involve self-sustained
systems for drug delivery,2 for artificial muscles,3 or for machines driven by
chemical interactions. In polyelectrolyte gels swelling and contraction can be
induced by pH gradients; these can also be produced electrically (as in elect-
rodialysis), thus allowing the design of both pH-operated and microelectroma-
chines.4 Several chemomechanical elements in particular for pH sensing have
been already described.5 Although science must go a long way until the
efficiency of biological actuators such as the myosin-actin complex can be
approximated with completely artificial systems, the first steps in this direction
have been taken. Other chapters in this monograph illustrate the development
of, e.g., molecular machines on a molecular level, until now confined mostly to
observation in solution, but also recent combinations of natural and artificial
polymers for ATP-driven macroscopic movements.
The presence of suitable binding sites in smart synthetic polymers opens the
way to highly selective molecular recognition also for endogenic substances,
such as specific metal ions, amino acids, peptides, nucleotides, carbohydrates
including glucose. This allows construction of, e.g., drug-release devices that

100
Chemomechanical Polymers 101

Figure 4.1 Size increase of a water-saturated chemomechanical hydrogel film piece

(1.1
0.9
0.4 mm) induced by a 0.25 mM solution of a dipeptide (gly-gly
in the presence of Cu(II) ions, pH 4.5; see Section 4.8).

are triggered by the level of such effector compounds in the body; selective
uptake of, e.g., toxic compounds could also be operated this way. Supramo-
lecular chemistry has in the last years developed hundreds of synthetic hosts for
all kind of desired ligands.6 Until now these receptors have been mostly used in
solution, but in principle can be implemented in functional materials such as
chemomechanical polymers. Due to the necessarily statistical nature of syn-
thetic polymers with sufficient flexibility structural insights are more difficult,
but are also of lesser importance than characterisation of their performance as
smart materials. The present chapter aims to highlight principles and recent
development in the field of chemomechanical polymers, with an emphasis on
the function of these intelligent materials, on their performance in the presence
of different chemical stimuli, and to a lesser degree on the underlying structural
and mechanical properties. Figure 4.1 visualises with one example how the
interaction of a peptide in less than 0.25 mM concentration can trigger an about
20-fold volume increase of the already water-saturated chemomechanical hy-
drogel. It will be discussed below how the sensitivity of chemomechanical
polymers can be further enhanced by miniaturisation of the polymer particles
and by increasing the affinity of effectors to the host units. Of course solvents,
in particular water alone, lead in the first place to sizeable swelling of gels,
reaching, e.g., water content of up to 99%. We will always characterise the
chemomechanical changes on materials, which have been exposed already to
the medium under the same condition, but without the chosen chemical
effector.

4.2 Chemomechanical Polymers Triggered by pH

Until recently most of the known chemomechanical materials are those that
change their mechanical property, in particular their shape, by changes of the
acidity of the surrounding medium. Generally, all polymers bearing ionisable
groups show expansion upon ionisation, e.g., the many gels containing ami-
nogroups will swell at lower pH. The historical starting point of this can be seen
in a contribution by Katchalsky, Kuhn and others7, who described – albeit in
102 Chapter 4
COOH
COOH
COOH COO- COO-
NaOH -OOC COO-
COOH
COO-
COOH
COO- COO-
COOH COOH

Scheme 4.1 Model for the viscosity increase by deprotonation of polyacrylic acid.

solution – already in 1950 the reversible viscosity increase of polyacrylic acid

(PA) under basic condition. This can be ascribed primarily to a chain unfolding
produced by loss of hydrogen bonds that can materialise with protonated
carboxylic groups, and by a chain-elongating repulsion between the carboxy-
late anions at higher pH (Scheme 4.1).
Almost countless polymer gels have since then been described that exhibit
shape changes at different pH values,8 often described as phase transitions,9
which may involve a multitude of states.9,10 The theory of pH-induced polymer
swelling was developed already in the late 1980s.11 Particularly gels containing
randomly distributed both positively and negatively charged groups can exhibit
more than two, either collapsed or swollen, phases; they may exibit maximum
swelling at two different pH values, which depend on the relative pK values.12
For example, chitosan-polyacrylic acid gels exhibit three maximum expansions
at pH 3, pH 6 and pH 8.13 A heuristic description has been proposed9 between a
loose swollen state, which is stable at lower temperatures, and a shrunken,
collapsed state, which results, e.g., from temperature increase. In the swollen
state a target molecule – i.e. a drug – is believed to adsorb preferentially by
single contacts with loose receptor sites of the polymer network, whereas in the
shrunken state multipoint interactions can lead to higher affinity. Therefore,
the chemomechanical effect is a function of the applied temperature.
Gels have also been used with imprinting techniques, in which a target
molecule serves for generation of complementary binding cavities.14,15 After
imprinting, polymerisation and the following substrate release in the swollen
state a collapsed state can retain sufficient memory to bind a ligand with
increased selectivity, although the effects until now were rather modest.10,16
Thus, a thermosensitive gel showed concentration-dependent swelling induced
only by the compound that was used for imprinting gel such as adrenaline or
ephedrine.17
Hydrogels from phosphorylcholine and polymethacrylic acid and esters also
allow pH-dependent drug release; they form networks that, in line with the
measured expansions, with the modulus and with FT-IR spectra, show swelling
only at higher pH, ascribed as in Scheme 4.1 to the formation of the intramo-
lecular crosslinks by hydrogen bonds with carboxyl groups.18 In some gels
undergoing phase transitions within a narrow range of temperature and also of
pH values there is no stable intermediate between a swollen and a collapsed
state.19,20
With microgels derived from poly(methacrylic acid /nitrophenyl acrylate) the
pH range of the swelling response is proportional to the solution pK(a)s of their
Chemomechanical Polymers 103

protonation, ion pairing,

CONH N NH2 cation- π, metal chelating
H

C-H-π, vdWaals,
CONH
lipophil.
H
CONH N NH2 protonation ,ion pairing,
cation-π, metal chelating

OH OH
CH2 CH
O O
O O CH2
n
HO HO
NH2 NH2 NH2
n n

protonation,ion pairing, protonation,ion pairing,

hydrogen bonds hydrogen bonds
II III
Scheme 4.2 Structures of some chemomechanical polymers (I: poylmethacrylic acid
with supramolecular binding functions, II: chitosan, III: polyallylamine).

functional groups.21 Bicomponent fibrous hydrogel membranes from poly

(vinyl alcohol)/poly(acrylic acid) exhibit pH-dependent swelling in two directions
of the material.22 Chitosan II (Scheme 4.2) itself forms a gel by using simple
inorganic or organic acids.23 Although such gels slowly dissolve under acidic
conditions24 in the absence of a crosslinker,25 the chitosan gels themselves, are
under close to neutral conditions, stable enough for many applications. Semi-
interpenetrating hydrogel networks of chitosan and polyacrylamide show
increased swelling below pH ¼ 7.26 Poly(ethylene oxide) grafted methacrylic
acid and acrylic acid hydrogels were studied as a drug carrier for the protection
of insulin from the acidic environment of the stomach.27 Copolymers contain-
ing and galactosamine glutamate forming fiber hydrogel show under acidic
conditions dense packing and shrinking.28 Similarly, semi-interpenetrating
networks of crosslinked copolymer acrylamide/acrylic acid polyallylamine
can serve as an effective pH-stimulated drug-delivery system, as investigated
by equilibrium and oscillatory swelling techniques.29 Two-component cross-
linked chitosan derivatives show swelling at pH 7.4 and above due to ionisation
of the carboxylic acid groups in the gel.30 Strong temperature dependence of
pH-triggered hydrogels composed of poly(2-ethyl-2-oxazoline) and chitosan
was reported.31 Microgels from poly(methacrylic acid-co-nitrophenyl acrylate)
were selectively derivatised with carboxylic acid, glutamic acid, hydroxamic
acid, sulfonic acid, and ethanol functional groups, yielding pH- and NaCl-
induced swelling response and drug loading, proportional to the solution
pK(a)s of their functional groups.21 Polyallylamine (PAH, III, Scheme 4.2),
after crosslinking, exhibits a sharp swelling at pH 7, although its pK value of
104 Chapter 4
9.732 would suggest a jump at higher pH; this behaviour was explained by
counteracting ion pairing with the special hydroxyphenylsulfonate used in this
study.33 In contrast to most other ionic hydrogels the pH-stimulated PAH
polymers III show a very slow reverse contraction after swelling.34
The hydrogel I derived from reaction of poly(methyl)methylacrylate
(PMMA), diethylenetriamine and dodecylamine (Scheme 4.2) provides both
pH-sensitive and lipophilic binding groups; it seems to be the only known gel
that displays a symmetric pH profile above and below pH 7 (Figure 4.2).35
Xanthan-chitosan gels were reported to be sensitive not only to high pH with a
maximum swelling at pH 10, but to some degree also at pH 0, where, however,
the gel dissolves in the course of swelling.36
The chemomechanical response to varying pH depends strongly on the ionic
strength of the medium (Figure 4.2(b)).37 Independent measurements indicate
that similar expansions as, e.g., at pH 2 and 12 in the presence of salts
(Figure 4.2(a)) occur with e.g., related sodium chloride concentrations alone
at neutral pH; thus, the lower and higher pH effects are also due to increased
stronger ionic strength by the necessary acid or base concentrations at such
pH values.35b In accord with this, one found that polysaccharide-derived gels

(a)
80
[%]

0.05M phosphate buffer

70
60
50
Expansion length

40 0.5M NaCl
30
20
10
0
0 1 2 3 4 5 6 7 8 9 1011121314
pH
(b)
220
[%]

200
180
160 d
140
Expansion length

120 c
100
80 b
60 a
40
20
0
0 2 4 6 8 10 12 14
pH

Figure 4.2 (a) Size changes of a PMMA-derived hydrogel (I, Scheme 4.1) as function
of pH; calculated maximum volume change 390%; in 0.05 M phosphate
buffer (circles), and in 0.5 M sodium chloride (triangles).; (b) pH expansion
profiles at different salt concentrations; in 0.5 M (K–a), 0.05 M (n–b), and
0.025 M (,c) sodium chloride solution, respectively, and in water with
very dilute HCl or NaOH (m–d).35
Chemomechanical Polymers 105
decrease the swelling with an increase in the ionic strength of the salt solutions,
due to a charge-screening effect for monovalent cations, as well as due to ionic
crosslinking by multivalent cations.38
Unspecific salt effects are often due to changes of the ionic strength,39 as
shown, e.g., with beta-hairpin peptides that self-assemble into hydrogel nano-
structures consisting of semiflexible fibrillar assemblies.40 Circular dichroism
spectroscopy indicates in absence of salt unfolded peptides; an increased ionic
strength screens electrostatic interactions between charged amino acids within
the peptide with subsequent beta-hairpin formation. Adsorption affinities for
various substrates decrease by orders of magnitude with increasing salt con-
centration.41 A moderate selectivity with respect to different alkali salts is seen
with the hydrogel I, as illustrated in Scheme 4.3.35b The partially reversed
effects in presence of, e.g., sodium phosphate will be discussed below in the
context of cooperativity effects. It should be noted that reverse contraction
after expansion of ionic polymers always needs treatment with another salt or
buffer as replacement of the gegenion neutralising the charge of the backbone.
Anion effects can to some degree be selective also without introduction of
selective binding groups into gels. An alternative used not for chemomechanical
properties but for sensing of different phosphate derivatives rests on fluorescent
artificial receptors that upon guest binding can dynamically change the location
between aqueous cavity and hydrophobic fibers provided under semiwet con-
ditions of a supramolecular hydrogel, as observed by confocal laser scanning
microscopy.42 As found recently, swelling of chitosan II is not only a function
of pH, but also of the acids used. Expansion stimulated by acetic acid starts
already at pH 6.2, which is close to the pKa of chitsoan. In contrast, acids such
as hydrochloric acid or phosphoric acid expand at lower pH (Figure 4.3).45 The
particular effect of the polyvalent phosphoric acid can be tentatively ascribed to
the ionic crosslinking counteracting the expansion.25 Ionic crosslinking with
concomitant gel contraction exists only in the presence of anions, while free
acids, formed depending on their pK values, allow expansion. Monocarboxylic

100
80
60
[%] volume

40
20
0
-20
-40
NaCl NaBr NaI NaNO3 Na2SO4 NaH2PO4

Scheme 4.3 Volume changes ([%]) induced by different anions on the PAA-derived
polymer I; [NaX] ¼ 0.10 M; left bars (always expansion): in pure water,
pH 7.3; right bars (partially contraction): in presence of 0.02 M phos-
phate buffer, pH 7.0.35b
106 Chapter 4
160
hydrochloric acid
140
acetic acid
120 phosphoric acid

100
[%] length

80

60

40

20

-20
1 2 3 4 5 6 7 8 9
pH

Figure 4.3 pH profiles of expansion of chitosan film in the presence of different acids;
(K) 0.1 M hydrochloric acid, (J) 0.1 M acetic acid and (.) 0.1 M phos-
phoric acid; starting with gel at pH 7.

Table 4.1 Volume expansions of chitosan gel II triggered by different acids at

pH 5.*1
Acid pKa [%] length Acid pKa [%] length

Hydrochloric acid – 0  1.5 Oxalic acid 1.23, 4.19 3  1.5

(0.1 M) (10 mM)
Acetic acid (0.1 M) 4.75 850  7.4 Malonic acid 2.83, 5.69 40  3.0
(10 mM)
Phosphoric acid 2.12, 7.21, 3  0.6 Succinic acid 4.16, 5.16 760  3.0
(0.1 M) 12.67 (10 mM)
Sulfuric acid 1.92 23  1.5 Glutaric acid 4.34, 5.41 790  3.0
(0.1 M) (10 mM)
Benzoic acid 4.19 640  9.0 Tartaric acid 2.98, 4.34 26  4.5
(20 mM) (10 mM)
Cyclohexanoic acid – 1020  3.0
(50 mM)
*1
All at pH 7  0.2; deviations [%] from triplicate measurements; 30 mM phosphate buffer was used only in case
of sulfuric acid.

acids such as benzoic or cyclohexanoic acid behave like acetic acid, whereas
dicarboxylic acids exhibit a dependence on the chain length separating the
carboxylic groups: glutaric and succinic acid, having similar pK values as the
monoacids, behave like these, whereas oxalic, tartraric and malonic acid with
their low pK values, due to the proximity of the carboxylgroups, lead to
reduced chemomechanical effects, again ascribed to counteracting crosslinking
with the anions, in analogy to phosphate (Table 4.1).
Chemomechanical Polymers 107
Chitosan obtained by ionic crosslinking with either triphosphate TPP or
polyphosphate PP was found to swell at degrees that depend on the mode of
preparation. The swelling at high pH was ascribed to deprotonation of the
chitosan amine groups with disruption of the crosslinking salt bridges. How-
ever, if the gels with TPP or PP were prepared at pH 6.8 the pH-induced
swelling was small, whereas gels prepared at pH 1.2 showed large swelling
above pH 8.25 In PAH III gels, crosslinked with glutardialdehyde, iodide
induces larger contraction compared to chloride. It was concluded that the
higher polarisability of iodide ions result in enhanced ion-pair formation and
thereby decreased osmotic pressure with a collapse of the gel.34

4.3 Particle-size Effects and Kinetics

Swelling kinetics are mostly controlled by effector diffusion, described by
Fick’s laws. Expansion of xanthan-chitosan-derived gels upon pH change
seems to be mainly controlled by the diffusion of mobile ions, except that at
pH values below 10 the degree of ionisation during swelling also may affect the
swelling rate.43,44 Figure 4.4 illustrates that with the PA-derived polymer I the
kinetics of both expansion and the fully reversible contractions follow pseudo-
first–order equations, the same holds for the corresponding ab- and desorption
of the effectors.35
The size and shape of the polymer particles used have a distinct influence on
the expansion and contraction of the chemomechanical materials. The rate of
volume changes depend on the effector concentration gradients, the speed of
effector diffusion into the particles, and therefore also on the surface to volume
ratio. Thus, film pieces of chitosan gel II show, with histidine and acetic acid
as effector rates, which increase with the surface to volume ratio S/V
(Figure 4.5).45
Another, until now often overlooked, influence of the polymer particle size
on the volume change is due to the effect, that smaller particles may need a
smaller amount of effector for saturation.46 The possible sensitivity increase

30 105
25 1.0M 100
0.7M
size change factor (%)

contraction (%)

20 0.2M 95
15 90
0.05M
10 85

5 80

0 75
70
0 20 40 60 0 20 40 60
Time / min depletion time (min)

Figure 4.4 Kinetics of expansion and desorption (action of AMP on polymer I, least
square fit to first-order equation.35b
108 Chapter 4
120

100

[%] length 80

60

40
S/V = 34.6
S/V = 12.2
20
S/V = 10.0

0
0 10 20 30 40 50 60 70 80
time (min)

Figure 4.5 Expansion kinetics, and surface to volume S/V effects with chitosan;
elongation induced by 50 mM L-histidine and 0.1 M acetic acid, in 30 mM
phosphate buffer at pH 5.0. Approximate ‘‘half-life’’ time t1/2 for 50% of
the maximum expansion: t1/2 ¼ 42, 32 and 3 min for S/V ¼ 10.0, 12.2 and
34.6, respectively.

with the decrease of a particle volume has been described in the context of
sensor miniaturisation.47 The sensitivity increase, however, holds only as long
as the affinity of an effector towards the sensing material is so high that all, or
nearly all, effector molecules are absorbed, independent of the external effector
concentration. As long as the affinity is high enough one can indeed observe
that the effector concentration that is required to reach a certain volume change
is a function of the used chemomechanical particle size (Figure 4.6).46

4.4 Water Uptake and Release

Dry hydrogels take up much water (up to 99%, e.g., in the case of polyallyla-
mine45); conversion from neutral to ionic condition invariably will lead to the
uptake of more water needed for solvation of both the cationic and anionic sites
(Scheme 4.4(a)). Exposure of the swollen polymer to different effectors in
aqueous solution can also lead to significant additional weight and volume
increase (Scheme 4.4(b)) due to the necessary solvation of the effector. Alter-
natively, effector absorption can lead to water release with concomitant con-
traction as consequence of, e.g., counteracting ionic crosslinking (Scheme
4.4(c)). It is known that water transport through gels is significantly affected
by the pH of the environment.48 Chitosan hydrogels grafted with lactic or
glycolic acid were characterised by FT-IR and differential scanning calorimetry
(DSC), and the presence of three different water types was proposed.49 Car-
boxymethylcellulose gels showed water uptake as a function of the used
crosslinking; after sulfating the gels are pH sensitive. The water uptake of such
Chemomechanical Polymers 109
0,12

Concentration of AMP [M]

0,10

0,08

0,06

0,04

0,02

0,00
0 5 10 15 20 25
initial particle length [mm]

Figure 4.6 Effector AMP concentration needed for a certain expansion (here 35% in
volume) as a function of the polymer particle size (variable length, with
constant width and thickness; in 0.02 M phosphate buffer, pH ¼ 7.0).
Volume expansions of up to 300% are possible under the working con-
ditions with the smaller particle, but not with the larger ones.46

(a) (b)
NH + NH + A B B A
G G
NH HX A B B A G
NH - -
X X
NH NH B A B G
A
+ A B
NH B
NH + A
: water

pH > 8 pH > 5
(c)

A
A
A
G A
G
G
A A
A A

Scheme 4.4 (a) Water uptake as result of pH change with concomitant charge
increase, (b) water uptake as result of complexation with guest G, and
(c) water release as result of, e.g., ionic cross-linking with guest G.

gels was studied by FT-IR spectra; hydrogen-bond formation between the

chains was proposed to explain the correlation found between water uptake
properties and the chemical composition of the gels.50 Albumin gels showed at
the isoelectric point a minimum of swelling, and expansion above and below
this.51 In crosslinked chitosan/polyether hydrogels the total water content and
the amount of bound water is related to the pH values of the environment; the
diffusion coefficient from the kinetics is correlated with the water state of the
110 Chapter 4
35
total
30 Effector
25 Expansion

20
15
10
5
0
pH11 pH1.8 Cu(OAc)2+L Cu(OAc)2 AMP

Scheme 4.5 Weight increase compared to expansion. Values scaled per mg of wet
polymer, in mg of total weight increase due to water and effector, and in
mg increase due to effector alone (upper limit as estimated from absorp-
tion measurements and complexometry); volume expansion Dv (from
1 mm3 wet), average from length and width increase. Weight increase is
within the error due to water-content increase.35b

swollen hydrogel, and likely is related to the relative composition of bound and
nonbound water.52 Hydrogels from fluorenyl-ala-ala dipeptides release 40%
water upon addition of the known strong binding ligand vancomycin.53
Scheme 4.5 shows the weight increase which accompanies the effector
absorption with the PA polymer I; independent measurements of water content
before and after expansion establish that the weight increase is almost entirely
due to water uptake. At the same time the scheme illustrates the abovemen-
tioned water uptake by protonation and deprotonation at low and high pH; in
comparison to pH 7 there is a water content increase by a factor of f ¼ 26  1.
The swelling induced by other effectors reflects the need of these molecules
inside the gel for the effector solvation, leading to a expansion that goes far
beyond the weight and volume increase needed by the effector alone; in line
with this, the swelling increases with the size of structurally related effectors.35b
It has long been known that in supramolecular complex formation, in partic-
ular with ion pairing, solvation differences before and after complex formation
play a major role, leading also to distinct dynamic differences between water
inside and outside supramolecular cavities.54 With chemomechanical hydrogels
the water uptake accompanying solvation becomes directly measurable.

4.5 Concentration Profiles

Unless abrupt phase transitions9,10,19 occur one may expect saturation-type of
profiles as a function of the effector concentration until all the binding sites of a
chemomechanical polymer are occupied. Figure 4.7 illustrates with polymer I
that such isotherm-like curves can be observed, unless the cooperativity effects
discussed below play a role. The curves present only approximately normal
Chemomechanical Polymers 111
16
14
12

[%]
10

Exp. length 8
6
4
2
0

0.00 0.02 0.04 0.06 0.08 0.10 0.12

AMP [M]

Figure 4.7 Expansion (length) as function of AMP concentration; polymer A, film

size 5.0
2.0
0.4 mm, pH 7.0. Lower trace (J), in the absence of buffer;
upper trace (K), in the presence of 0.02 M NaH2PO4 buffer.35b

saturation isotherms, but allow an affinity towards the polymer to be inferred

that resembles apparent association constants of related host–guest complexes
in aqueous solution. Thus, the apparent binding constant K, e.g., for AMP
under the conditions in Figure 4.7 amounts to about 20 M1, roughly compa-
rable to K values reported in homogeneous solution for the interaction of AMP
and ethylenediamine-type host compounds.55 From the first part of the par-
ticularly discontinuous concentration profiles with transition-metal ions56 and
the maximum expansions reached there one can estimate affinities that are, as
expected, much higher, e.g., for Cu(II) ions with an apparent K value around
105 to 106 M1. However, the profiles not only depend on the presence of
additional salts or buffers, but also show a lag period before swelling begins
(Figure 4.7). In contrast, UV-vis measurements show, as expected, absorption
already at low concentrations, which are too low for an expansion. The
expansion starts at a concentration at which presumably the effector starts to
move inside the gel after first saturating the surface.35b

4.6 Cooperativity and Logical Gate Functions

In solution supramolecular complexes have been already designed in such a
way that two different chemical entities are required in order to give a certain
response.57 Here, e.g., a fluorescence signal is only emitted (or quenched) from
a host–guest complex if the pH has a certain value, or if a second compound is
present. Such systems are either based on cooperativity between different guest
molecules, or on allosteric effects between two or more distinct binding and
conformationally coupled sites. As mentioned above, pH-induced swelling of a
chemomechanical polymer often depends also on, e.g., salt concentrations or
rather ionic strength, which may be considered as simple, although rather
112 Chapter 4
unselective cooperativity. Only recently has it been shown that with a chemo-
mechanical polymer bearing several recognition functions, such as I, can
selective response be materialised between several effectors58 (Scheme 4.6).
The cooperativity can be so strong that a volume change occurs with, e.g.,
peptides only if a certain metal cation is present (see Section 4.8). Such gel-
based logical AND gate systems require no spectroscopic detection and trans-
ducers, but communicate directly to the outside world.
The expansion stimulated on the functional polymer I by different effectors
depends markedly on the pH, thus representing an efficient macroscopic AND
gate system. Thus, the expansion magnitude induced by the nucleotides UMP
and AMP is reversed in going from pH 7 to pH 11 (Scheme 4.7).35
Logical AND gates in the sense of positive cooperativity are not only seen by
the influence of pH but also between different effectors. For example, with
polymer I the expansion induced by AMP reaches a distinct maximum only at a
certain concentration of phosphate anions as the second effector (Figure 4.8).58
With other effectors negative cooperativity has also been observed; e.g., the
presence of sodium salts distinctly lowers the expansion induced in polymer I
by zinc acetate (Figure 4.9).56 The ethylenediamine units in I allows chelation
and selective volume changes with transition-metal ions;59 as expected, low pH
values lead to a reversal of the expansions, since the ethylenediamine units
become protonated – another manifestation of cooperativity with pH. The

S M L

Scheme 4.6 Cooperativity effects with two guest molecules G1 and G2; S: small/tight;
M: medium/loose; L: large/loose network.

O NH2

N
NH N
O
O N O
N O N
HO P O
HO P O O HO P OH
O OH
OH
OH
OH OH
OH OH
at pH 7 : 45 75 < 10 vol%

at pH 11 : 28 60 < 10 vol%

Scheme 4.7 Expansions (in % volume) triggered by nucleotides UMP and AMP and
phosphate (0.1 M) at different pH values; chemomechanical polymer I.35
Chemomechanical Polymers 113

25

20

15 NaH2PO4/Na2HPO4+AMP
Expans.[%]

10

5
NaH2PO4/Na2HPO4 alone
0

0.00 0.05 0.10 0.15 0.20 0.25 0.30 0.35

NaH2PO4/Na2HPO4 [M]

Figure 4.8 Cooperativity between AMP and phosphate in the expansion with poly-
mer I. (Expansion given in one dimension).58

40

30
Size changing factor (%)

20

10

0 Zn(OAc)2 alone

-10
Zn(OAc)2 + 0.1MNaCl
-20
Zn(OAc)2 + 0.1M PhCO2Na
-30
0.00 0.05 0.10 0.15 0.20 0.25
Conentration of Zn(OAc)2 /M

Figure 4.9 Expansions with the chelating polymer I induced by zinc(II)acetate

with and without the presence of sodium choride or sodium benzoate
as the second effector.35b,56

critical effector concentration at which the expansion reaches a maximum has

been shown to correlate with the size of the polymer particle used, for the
reasons discussed above in the context of the relation between size and
sensitivity.46
114 Chapter 4

4.7 Selectivity with Organic Effector Molecules

The introduction of even simple receptor groups such as ethylenediamine
(‘‘ene’’) units and lipophilic alkyl chains in polymer I already leads to relatively
large differences in swelling by various organic compounds. They can be
understood and planned on the basis of interaction mechanisms known from
supramolecular chemistry. As indicated in Scheme 4.2 the ene units allow not
only metal chelation, and pH-dependent protonation but also hydrogen bond-
ing as well as N1 cation-p effects. That the latter play an essential role is
obvious from the large chemomechanical effects as long there are aryl units in
the effector molecule: the saturated cyclohexane-carboxylate has, within the
error, no effect in contrast to the almost isosteric benzoic acid (Scheme 4.8).35
That electrostatic attraction, or ion pairing with the cationic N1 sites in I is an
additional prerequisite for any size changes of the gel is clear from the inactivity
of electroneutral compounds. Finally, the alkyl groups introduced into polymer
I provide for lipophilic interaction, which varies between the different organic
moieties of the effectors. In consequence, not only nucleotides (see Scheme 4.7),
but even structural isomers such as different benzene dicarboxylicacids can be
distinguished (Scheme 4.8). Lipophilic interactions are also responsible for the
unique contraction of polymer I upon exposure to ammonium compounds
bearing longer alkyl chains; Scheme 4.9 illustrates the systematic change from
the usual expansion to shrinking.35 It should be borne in mind that small
expansion differences can be sufficient to switch, e.g., release of a drug from a
suitable container, on or off.
Another binding mechanism, often used in supramolecular complexes as well
as in nature, are stacking interactions between aromatic units.60 Introduction of
anthrhyl groups into chitosan II provided for large interaction sites with
aromatic effectors, although the substitution degree was low. With various
amino acids one found expansions that as expected increase with the lipophili-
city of the residues (Scheme 4.10).

CO2H CO2H CO2H CO2H

at pH 7 : < 10 40 150 250 vol%

(conc. 1.0 mM)
CO2H CO2H CO2H
CO2H

CO2H
CO2H
at pH 7 : 0
120 170 320 vol%
vo
at pH 11 : 95 170 480 vol%
(conc. 0.1 M)

Scheme 4.8 Selectivity between different organic effector compounds. (0.02–0.05 M

phosphate buffer; the effects at pH 11 are corrected for difference
between pH 7 and pH 11 alone (390 vol%)).35a
Chemomechanical Polymers 115

300

200

100

-100

-200

-300

-400
Ethyl n-Butyl n-Pentyl n-Hexyl

Scheme 4.9 Volume changes changes [%]) of polymer I with peralkylammonium

hydroxides R4NOH (after correction for pH-induced change, pH 12.4 to
12.7).35b

H
N
+ NH

(CH )
CH CH CH
+ + + +
H N CH COOCH HN CH COOCH HN CH COOCH HN CH COOCH

1.3% 1.9% 17% 31%

Scheme 4.10 Volume expansions [%] on chitosan-anthrhyl polymer with different

amino acid esters; pH and salt effects deducted; (pH 5.0; 0.1 M
effector).64

Even without introduction of special recognition groups, some chemome-

chanical polymers can exhibit a moderate selectivity against special effector
compounds. Chitosan gel II for example shows expansion differences not only
between few carboxylic acids (see Table 4.1), but also between basic and
nonbasic amino acids, which for this purpose need not to be protected but
can be used in their native form. The largest expansions are observed with
histidine (Table 4.2); due to the chiral chitosan backbone one could expect also
some chiral discrimination, which is materialised with the most strongly inter-
acting histidine to a moderate, yet promising degree. The difference in swelling
depends on the acid anion with which it is competing, showing a preference for
the D-enantiomer over the L-form that amounts to 145% vs. 120% in the
presence of acetate; to 134% vs. 123% in the presence of benzoate, whereas no
difference was observed in the presence of chloride.
Even the simple polyallylamine III, crosslinked for gel formation, exhibits
some interesting selectivity. Using small-angle X-ray scattering (SAXS, Figure
4.10) it has been shown that incorporation of strongly bound salts such as
arylsulfonates leads to ordered structures, with distances between the polymer
116 Chapter 4
Table 4.2 Volume expansions of chitosan gel II triggered by basic amino acids
in presence of different acids.*1
Acid L-histidine L-lysine L-arginine control*2
0.07 M chloride 120  9.5 92 91 44  1
0.10 M acetate 86  4.5 69  3 56  8 586  5
0.10 M phosphate –3  2 –6  1 –6  1 0.9  0.3
0.10 M surfate –6  0.3 –3  1.5 –9  2.5 23  1.5
0.08 M benzoate 310  5 218  8.5 192  13 325  8
*1
All measured in 30 mM phosphate buffer at pH 5.0; deviations [%] from triplicate measurements;
expansion with other aminoacids such as ala, phe, trp:o10%.
*2
Expansion volume without amino acids.

Figure 4.10 SAXS patterns of collapsed gels derived from polyallylamine III in
various aromatic sodium salt solutions (0.07 M); taken with permission
from Ref. 34.

backbone that increase with the size of the guest molecules.34 Such effectors
lead to weight decrease of, e.g., 95%; re-swelling is possible by treatment with
an excess of weaker effectors such as NaCl that cause only 40% weight loss.
Recent studies reveal that the PAH polymer gel III allows even some isomeric
compounds to be distinguished (Scheme 4.11).45 Generally, ionic crosslinking
leads to a volume decrease with all kind of carboxylic acids, with significant
Chemomechanical Polymers 117
CO H CO H CO H CO H
H OH H OH
NO R
HO H HO H
HO H H OH
H OH H OH
m- and p- : - 95% R = H : - 50%
CO H CH OH
o- : - 55% R = OCH o- and p- : - 65%
- 95% - 35%
R = OH o- and p- : - 95%
R = Cl m- and p- : - 95%

Scheme 4.11 Volume change of PAH gel III in the presence of different acids
effectors (10 mM) at pH ¼ 7.45

NH3 NH3

Y Y

X X

X X

Y Y X = CH=CH2, NO2, OH etc.

NH3 NH3 Y = SO3-, CO2-etc.

Figure 4.11 Model of a polyallylamine III-derived gel with substituted aromatic acids
as counterion spacers.

differences between natural glucoronic and glucaric acids. Surprisingly, benzoic

acids with suitable substituents also lead to large contractions of similar size as
the dicarboxylic acids, presumably as a result of stacking interactions between
the aryl rings in analogy to Figure 4.11. Nitrosubstituents have been shown to
interact strongly with other aromatic moieties by dispersive forces,61 which
would explain why the nitrobenzoic acids lead to particular sizeable contraction
as long as the nitrogroup is not too close to the anionic carboxylate center
(cf. Scheme 4.11, R ¼ o-NO2).

4.8 Ternary Complex Formation for Amino Acids

and Peptides as Effectors
The metal chelating groups in polymer I allow binding, in addition, also of
effectors that otherwise would not interact at all with the chemomechanical
polymer. It is known from solution chemistry that, e.g., Cu(II) or Zn(II) cations
118 Chapter 4

C tertiary site L
e.g. peptide C
addtl. lipophilic site L

B secondary site
B
e.g. Cu(II)

A primary site A
e.g.ene
Polyme

Scheme 4.12 Ternary complex formation.64

O O

N COO- N COO-
NH3+ NH3+ H
H
N
H
with Cu2+ 128% 145%
net : 17% 28%

Scheme 4.13 Examples of expansion (in one dimension) in ternary complexes; Cu(II)
and Effector 0.25 mM polymer I pH 4.5. Net: effect of Cu21 alone
deducted.64

form ternary mixed complexes with a number of chelating agents including

amino acids and peptides.62 Such cocomplexation has been used successfully in
supramolecular associations, e.g., for sensor application.63 The additional
interaction groups of polymer I (Scheme 4.12)64 provide for additional dis-
crimination with the amino acids side groups, which is visible in swelling
differences between different peptides (Scheme 4.13). With some special chelat-
ing agents the expansions reach a record 475% on top of the swelling produced
by the metal ion itself. Removal of the metal cations by decomplexing agents
leads to a reversible contraction of the swollen gel as a function of the
decomplexing agent chelating strength.

4.9 Selectivity by Covalent Interactions/

Glucose-triggered Size Changes
Several substrates of biological importance such as carbohydrates exert noto-
riously weak intermolecular interactions, particular in water. The most prac-
tical way to overcome this problem, e.g., for the glucose-responsive
supramolecular systems consists in the formation of boronic esters, for which
NMR studies in solution65 suggest crosslinking with two boronic residues
Chemomechanical Polymers 119

OH HO
B O
OH O
HO
O
CONH
OH Glucose B O
B R
OH O OH
B
CONH
R

Scheme 4.14 Boronic ester formation with glucose.

1.1

1
Contraction Fac

0.9

0.8

0.7
Fructose Galactose Glucose
0.6
0 5 10 15 20 25 30 35
Time (min)

Figure 4.12 Selective response of a boronic-ester equipped polymer to glucose over

fructose and galactose. Measurement under blood plasma condition with
all sugars at the 0.005 M concentration.69

(Scheme 4.14). The use of such esters for the determination of the configuration
of carbohydrates has long been known,66 but has been implemented into
sophisticated supramolecular sensing systems only during recent years.67,68 It
has been shown that this principle can be transferred to chemomechanical
polymers.69,70 Thus, reaction of poly(methyl methacrylate) with 3-amino-
phenylboronic acid, simultaneously processed with diethylenetriamine, do-
decylamine, and butylamine, yields a hydrogel, which after swelling in water
exhibits sizeable contraction with glucose, presumably due to the disappearance
of the negatively charged boronate anions (Figure 4.12). The response is
selective for glucose under blood plasma conditions with only 5 mM sugar
concentration, holding obvious promise for self-sustained delivery devices, e.g.,
for insulin release.71

4.10 Conclusions
On the basis of the now vast experience of supramolecular chemistry it will be
possible to develop polymers that are selectively stimulated by all kinds of
120 Chapter 4
possible molecules in the environment. Such selective polymers allow engi-
neering of actuator devices that can drive a micromachine or, e.g., deliver a
drug, entirely self-controlled. Asymmetric bilayers made from films of different
chemical nature and thereby different response to the environment can be
used for an increased macroscopic movements by bending of the film stripes.72
As discussed in Section 4.3, particle miniaturisation can enhance both the
speed and the sensitivity of response of a chemomechanical polymer. Coop-
erative effects between several different effectors can lead to high selectivity
under defined conditions, and allow stimulation by otherwise inactive com-
pounds. Biomacromolecules including proteins can also be used both as the
basis for chemomechanical polymers with active and selective recognition
sites, as well as effectors. Materials responsive to glucose have been already
developed on the basis of lectin, specifically of concanavalin,73 and also using
enzymes such as glucose oxidase.74 Grafting an antigen and the correspond-
ing antibody into a polymer network the binding of the free antigen can trigger
a gel-volume change.75 The biomimetic translation of selective molecular
recognition into the outside world with completely self-sustained and fully
automatic devices will be of particular significance for future biomedical
applications.

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