Hydrogen-bonded network structure of water in aqueous solution of sulfobetaine polymers

Article abstract of DOI:10.1021/jp020185r

Poly(N,N-dimethylaminopropyl methacrylamide) (poly(DMAPMA)) was incubated with 1,3-propanesultone and 1,4-butanesultone to afford polymers with various contents of N,N-dimethyl-N-(3-sulfopropyl)-3a?2-methacrylamidopropanaminium inner salt residues and N,N-dimethyl-N-(4-sulfobutyl)-3a?2-methacrylamidopropanaminium inner salt residues, respectively. The structure and hydrogen bonding of water in an aqueous solution of the sulfobetaine polymers were analyzed using the contours of the O-H stretching in the polarized Raman spectra. With an increase in the content of the sulfobetaine residue, the relative intensity of the collective band (C value) corresponding to a long-range coupling of the O-H stretching in the aqueous polymer solutions became larger and approached the C value of pure water. The number of hydrogen bonds disrupted because of the presence of one monomer residue (N value) for the polymers with a large sulfobetaine content was a small positive value and comparable to those for neutral polymers such as poly(ethylene glycol) and poly-(N-vinylpyrrolidone). This is in significant contrast with the largely positive N values for the precursor polymer (poly(DMAPMA)), and ordinary polyelectrolytes such as sodium polyethylenesulfonate, poly-L-lysine hydrobromide, sodium polyacrylate, and poly(acrylic acid). The N value for a small molecular weight zwitterionic compound, 3-aminopropanesulfonic acid, was also slightly positive, which is consistent with the tendency observed for the sulfobetaine polymers. The present results clearly indicate that the zwitterionic polymers do not significantly disturb the hydrogen-bonded network structure of water, probably because of the counteraction of the electrostriction effect by the proximity between the anionic and cationic groups.

Full text of DOI:10.1021/jp020185r

J. Phys. Chem. B 2002, 106, 11391-11396
11391
Hydrogen-Bonded Network Structure of Water in Aqueous Solution of Sulfobetaine
Polymers†
Hiromi Kitano,* Makoto Imai, Kurao Sudo, and Makoto Ide
Department of Chemical and Biochemical Engineering, Toyama UniVersity, Toyama 930-8555, Japan
ReceiVed: January 18, 2002; In Final Form: July 8, 2002
Poly(N,N-dimethylaminopropyl methacrylamide) (poly(DMAPMA)) was incubated with 1,3-propanesultone
and 1,4-butanesultone to afford polymers with various contents of N,N-dimethyl-N-(3-sulfopropyl)-3′-
methacrylamidopropanaminium inner salt residues and N,N-dimethyl-N-(4-sulfobutyl)-3′-methacrylamidopro-
panaminium inner salt residues, respectively. The structure and hydrogen bonding of water in an aqueous
solution of the sulfobetaine polymers were analyzed using the contours of the O-H stretching in the polarized
Raman spectra. With an increase in the content of the sulfobetaine residue, the relative intensity of the collective
band (C value) corresponding to a long-range coupling of the O-H stretching in the aqueous polymer solutions
became larger and approached the C value of pure water. The number of hydrogen bonds disrupted because
of the presence of one monomer residue (N value) for the polymers with a large sulfobetaine content was a
small positive value and comparable to those for neutral polymers such as poly(ethylene glycol) and poly-
(N-vinylpyrrolidone). This is in significant contrast with the largely positive N values for the precursor polymer
(poly(DMAPMA)), and ordinary polyelectrolytes such as sodium polyethylenesulfonate, poly-L-lysine
hydrobromide, sodium polyacrylate, and poly(acrylic acid). The N value for a small molecular weight
zwitterionic compound, 3-aminopropanesulfonic acid, was also slightly positive, which is consistent with the
tendency observed for the sulfobetaine polymers. The present results clearly indicate that the zwitterionic
polymers do not significantly disturb the hydrogen-bonded network structure of water, probably because of
the counteraction of the electrostriction effect by the proximity between the anionic and cationic groups.
Introduction
The physical properties of polymer systems in all concentra-
tion regions from dilute aqueous solutions to hydrated solids
The anomalous physical properties of liquid water (for
example, the heat capacity, the heat of solidification, and the
heat of vaporization are the largest among ordinary liquids) can
be ascribed to hydrogen bonding between the oxygen atom of
the water molecule and hydrogen atom of a neighboring water
molecule.1 A nonlinear bent structure of water molecules,
furthermore, makes a fluctuated hydrogen-bond network in the
liquid state. Vibrational spectroscopic methods (VSs) including
Raman spectroscopy have been very often used to analyze the
so-called V structure (vibration-averaged structure) of water
reflecting orientation of water molecules,2 because these meth-
ods utilize smaller observation times (τ ) 10-13-10-14 s) than
the relaxation times of the rotational rearrangement (τR) of water
molecules in the liquid phase (τ ) 10-11-10-12 s). Furthermore,
the average lifetime of the hydrogen bond between water
molecules (on the order of 10-12 s) is larger than the vibrational
relaxation time of chemical bonds used as a probe in the VSs.
Therefore, the VSs can detect not only the rotational rearrange-
ment of water molecules but also the changes in the hydrogen-
bonded networks between water molecules. On the other hand,
other techniques (differential scanning calorimetry (DSC), X-ray
diffraction, dielectric dispersion, and NMR), which utilize larger
observation times (τ = 101, 101, 100-10-11, and 10-6-10-11
s, respectively) compared with the τR or the lifetime of hydrogen
bond between water molecules, can detect the state of water
based on the diffusion property of the water molecule. Therefore,
these techniques cannot directly detect the changes in the water
structure.
are very often determined by the interaction between water and
the polymer chain. The thermodynamic properties of water in
polymer solutions have been analyzed by NMR,3 DSC,4 and
other techniques.5 However, as mentioned above, it is difficult
to reveal the hydrogen-bonded network structure of water using
these methods. We have been interested in the analyses of the
structure of water in aqueous polymer solutions from a Raman
scattering of water attributable to the O-H stretching vibration
band (2800-3800 cm-1).6,7 It was pointed out that the number
of hydrogen bonds disrupted because of the presence of one
monomer residue (N value) of a polyelectrolyte with an ionic
group in the side chain (sodium poly-L-glutamate, poly-L-lysine
hydrobromide, and sodium polyacrylate with a small Mw value,
etc.) was much larger than those for neutral polymers (poly-
(ethylene glycol) and poly(N-vinylpyrrolidone)).6b,e,f Moreover,
the N value for the polymer with an ionizable group in the side
chain (poly(acrylic acid) (HPAA), for example) was smaller than
those for the polyelectrolytes with a fully ionized group and
larger than those for neutral polymers.6b
Quite recently, it was found that a zwitterionic polyelectrolyte,
poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC), did
not disturb the hydrogen-bond network structure of water.6f To
examine the possibility that zwitterionic polymers in general
do not significantly affect the structure of water, we examined
the polarized Raman scattering of the O-H stretching vibration
band of water in an aqueous solution of another kind of
zwitterionic polymer, a sulfobetaine polymer with various
degrees of quaternization.
† Partly presented at the 49th Polymer Symposium of the Society of
Polymer Science, Japan, at Tohoku University in September 2000.
* To whom correspondence should be addressed. Tel: +81-76-445-6868.
Fax: +81-76-445-6703. E-mail: kitano@eng.toyama-u.ac.jp.
About fifty years ago, the properties of an aqueous solution
of zwitterionic polymers prepared by the free radical copolym-
erization of cationic and anionic comonomers were studied.8a,b
10.1021/jp020185r CCC: $22.00 © 2002 American Chemical Society
Published on Web 10/05/2002

11392 J. Phys. Chem. B, Vol. 106, No. 43, 2002
Kitano et al.
SCHEME 1: Preparation of Sulfobetaine Vinyl
Afterward, zwitterionic polymers based on carboxybetaine
monomer units were also investigated.8c,d In the past 10 years,
preparation and characterization of sulfobetaine polymers have
been extensively studied.9,10 It was found that zwitterions in
the sulfobetaine polymers remain in their diionic form over a
broader pH range than the carboxybetaine polymers.9h
Monomer (SPB)
Furthermore, the anomalous properties of aqueous solution
of sulfobetaine polymers (so-called “anti-polyelectrolyte” be-
havior as described below) have been fascinating many re-
searchers: By taking into account the large solubility of sulfo-
betaine derivatives in salt solutions, for example, researchers
prepared super-adsorbent gels, which can swell at high elec-
trolyte concentrations, by the copolymerization of the sulfobe-
taine monomer with other hydrophilic comonomers.9d,e,f Poly-
styrene latex particles were also prepared at high electrolyte
concentration (1.0 M NaCl) by using sulfobetaine macromon-
omers.10c
SCHEME 2: Preparation of Polymeric Sulfobetaines
Meanwhile, zwitterionic compounds are characterized by
having excellent dermatological properties. They also exhibit
low eye irritation and are frequently used in shampoos and other
cosmetic products.11 Carboxybetaine derivatives, for example,
are widely used in cleansing compositions, fabric conditioner,
hair and skin cosmetic compositions,12 etc. Similarly, sulfobe-
taine surfactants reduce the skin irritation of other surfactants,13
and therefore, they are widely used as skin-compatible dish-
washing detergents with good foaming properties.14 Further-
more, sulfobetaine derivatives are used as a component in
various cosmetics (reducing agent for permanent wave, condi-
tioning and hair washing composition, etc.). As previously
pointed out,6f the phosphobetaine polymer, PMPC, also has a
large biocompatibility (no thrombus formation).15 Quite recently,
it was reported that zwitterionic self-assembled monolayers
(SAMs) resist the nonspecific adsorption of various proteins
from an aqueous buffer.16 There is a possibility that the structure
of water at the interface of the zwitterionic SAMs plays an
essential role in the adsorption behavior of proteins.
and 3-mercaptopropionic acid (MPA, 900 mg) as the initiator
and chain transfer reagent, respectively. After evaporation of
the solvent, the obtained polymer was dissolved in water and
purified by ultrafiltration using Amicon membranes (YM-10
(exclusion limit, 104) and YM-50 (5 × 104)) to obtain a fraction
between 104 and 5 × 104 daltons. The purified polymer was
finally lyophilized (poly(DMAPMA), 353 mg). The weight-
average and number-average molecular weights (Mw and Mn)
of poly(DMAPMA) were determined to be 1.54 × 104 and 1.22
× 104 (Mw/Mn ) 1.26) by gel permeation chromatography
(GPC) (Waters HPLC system; column, Wako Gel G-40, Wako
Pure Chemicals; mobile phase, acetate buffer (0.5 M, pH 4.06))
using pullulan standards (Showa Denko, Tokyo, Japan).
Poly(DMAPMA) (100 mg) dissolved in THF (20 mL) was
incubated with 1 or 2 equiv of 1,3-propanesultone in a tightly
sealed round-bottomed small flask at 30 °C for 24 h.9,10 After
evaporation, the oily mixture was dissolved in water and
repeatedly passed through an ion-exchange column (Amberlite
IRA96SB, 2 × 20 cm) to remove the ionic impurities. The
polymer solution was further dialyzed against pure water for 3
days in a seamless cellulose dialysis tube (molecular cutoff,
13 000; Wako Pure Chemicals) and finally lyophilized (poly-
(N,N-dimethyl-N-(3-sulfopropyl)-3′-methacrylamidopropanamin-
ium inner salt), PSPB) (Table 1). Similarly, poly(DMAPMA)
was incubated with 1,4-butanesultone in THF to give poly(N,N-
dimethyl-N-(4-sulfobutyl)-3′-methacrylamidopropanaminium in-
ner salt) (PSBB) with various degrees of quaternization (DQ)
(Table 1). The degree of quaternization (DQ) of the polymeric
As mentioned above, the unique properties of sulfobetaine
polymers might be strongly related to the interaction of the
zwitterionic polymers with water. Therefore, Raman spectros-
copy would be an excellent technique to explore the structure
of water in aqueous solution of sulfobetaine polymers.
Experimental Section
Materials. N,N-Dimethylaminopropyl methacrylamide
(DMAPMA) was obtained from Aldrich, Milwaukee, WI. 1,3-
Propanesultone and 1,4-butanesultone were obtained from Wako
Pure Chemicals, Osaka, Japan. The other reagents were com-
mercially available. Milli-Q grade water was used for the
preparation of the sample solutions.
Sulfobetaine Vinyl Monomer (Scheme 1). N,N-Dimethy-
laminopropyl methacrylamide (DMAPMA, 3.2 mL) was dis-
solved in diethyl ether (20 mL), and 1,3-propanesultone (2.15
g) was added. The solution mixture was incubated at room
temperature for 1 day. The obtained white precipitates were
collected by filtration and, after being washed with acetone,
dried in vacuo (N,N-dimethyl-N-(3-sulfopropyl)-3′-methacry-
lamidopropanaminium inner salt, SPB) (4.45 g, yield 86%). 1H
NMR (D2O) δ 1.93 (s, 3H), 2.05 (m, 2H), 2.20 (m, 2H), 2.97
(t, 2H), 3.11 (s, 6H), 3.36 (m, 4H), 3.47 (m, 2H), 5.47 (s, 1H),
and 5.71 (s, 1H).
Preparation of Polymeric Sulfobetaine (Scheme 2). Sul-
fobetaine polymers were prepared by the method of Lee and
Tsai.9a N,N-Dimethylaminopropyl methacrylamide (DMAPMA,
12.0 g) was polymerized in tetrahydrofuran (THF, 100 mL) at
70 °C for 8 h using 2,2′-azobisisobutyronitrile (AIBN, 120 mg)
1
sulfobetaine was estimated by H NMR measurements.
Raman Spectroscopy. The O-H stretching Raman spectra
of water between 2500 and 4000 cm-1 in various aqueous poly-

Hydrogen-Bonded Network Structure of Water
J. Phys. Chem. B, Vol. 106, No. 43, 2002 11393
TABLE 1: Preparation of Polymeric Sulfobetaines
polymer
poly(DMAPMA) (mg)
sultone (mg)
solvent (mL)
time (h)
temp (°C)
yield (mg)
DQe (%)
1/[η]f (g/dL)
PSPB-1
PSPB-2
PSPB-3
PSBB-1
PSBB-2
PSBB-3
PSBB-4
100
100
100
100
200
200
220
140a (2 equiv)
290a (4 equiv)
290a (4 equiv)
160b (2 equiv)
640b (4 equiv)
640b (4 equiv)
700b (4 equiv)
20c
20c
20d
20c
20c
20d
20d
24
24
24
24
24
24
24
30
40
40
30
40
40
40
86
114
83
66
89
95
63
68
83
91
15.3
27.5
40.8
11.1
19.6
30.3
40.9
98
183
189
175
a 1,3-Propanesultone. b 1,4-Butanesultone. c THF. d CH3CN. e The degree of quaternization (DQ ) (m/n) × 100. See Scheme 2). f In water at
25 °C.
Figure 2. Reduced viscosity vs concentration of sulfobetaine polymers
at 25 °C in water: (b) poly(DMAPMA) (precursor); (4) PSPB-1; (9)
PSPB-2; (3) PSPB-3.
various kinds of aqueous polymeric sulfobetaine solutions at
25 °C was determined using an Ubbelohde dilution type
viscometer (type 0B; Kusano, Tokyo, Japan).
Figure 1. Raman spectra of O-H stretching region: (a) I| (solid) and
I
(broken) spectra of pure water at 25 °C (I /FO-H spectrum is also
shown by the dotted line); (b) the collective band of pure water.
Results and Discussion
meric sulfobetaine solutions were recorded on a NR-1100 spec-
trophotometer (Japan Spectroscopic, Co., Tokyo, Japan; light
source, argon laser 488.0 nm) with a spectral resolution of 5
cm-1. The details of the measurements were described else-
where.6,7
A. Viscosity Behavior of Polymeric Sulfobetaine Solution.
It has been widely accepted that, in aqueous polyelectrolyte
solutions, a decrease in the polymer concentration results in an
increased Debye length and, consequently, the increase in the
electrostatic repulsion between the charged groups within the
polymer chain induces expansion of the polymer chain.20
However, highly precise viscometric measurements showed that,
even for an infinitely diluted solution, polyelectrolyte molecules
such as sodium poly(styrenesulfonate) do not completely stretch
out.21
The viscosity behavior of sulfobetaine-type polymers prepared
with 1,3-butanesultone (PSPBs) are shown in Figure 2. The
reduced viscosity (ηsp/φ) for an aqueous solution of polymeric
sulfobetaine with a large DQ value (PSPB-2 and PSPB-3)
decreased with the decrease in the polymer concentration. This
is in good contrast with the increase of ηsp/φ with the decrease
in the concentration of the precursor polymer, poly(DMAPMA),
which is the typical viscosity behavior of the aqueous solution
of ordinary polyelectrolytes.
As exemplified in Figure 1, the component of the O-H
stretching band of water centered at 3250 cm-1 was highly
polarized and diminished in the spectra at a perpendicular
position.17 The polarized O-H stretching band of water, which
is called the “collective band”, is ascribed to the H2O molecule
executing ν1 vibrations all in phase with each other but the vibra-
tional amplitude varying from molecule to molecule in water
clusters, which are strongly hydrogen-bonded.18 Theoretical
calculations of a random network model,19 which is character-
ized by the fluctuated defects in water-water hydrogen bonds
in a distorted tetrahedral network, support the interpretation.
The intensity of the collective band (Ic) observed around 3250
cm-1 was separated from the spectra using eq 1 (Figure 1).
Ic ) I| - I /FO-H
(1)
When the DQ value was small (PSPB-1), a slight increase in
ηsp/φ upon dilution was observed. A similar tendency was also
observed for another type of sulfobetaine polymers prepared
with 1,4-butanesultone (PSBBs) (data not shown). These results
were consistent with the previous reports: despite the sufficient
solubility of the monomer in water, it has been often pointed
out that polymeric sulfobetaines show “anti-polyelectrolyte
behaviors”, that is, a greatly enhanced solubility and an extensive
chain expansion upon increasing salt concentration.9,10
When the sulfobetaine monomer, N,N-dimethyl-N-(3-sulfo-
propyl)-3′-methacrylamidopropanaminium inner salt, was po-
lymerized, the product polymer (PSPB, DQ ) 100%) could not
be dissolved in pure water at all, which is in agreement with
the result by Lee and Tsai.9a,b This might be partly due to the
cyclization of the side chain to form an ion pair9a and partly
where the depolarization ratio, F, is an indicator of symmetry
of the vibration mode and is expressed by F ) I /I|, where I
and I| are the intensities of the spectra observed with the
polarizer oriented perpendicular and parallel to the incident laser
beam, respectively.
Because the intensities of the Raman spectra are not absolute,
the area of Ic was normalized by eq 2
C ) I (w) dw/ I (w) dw
(2)
∫
∫
c
|
where w is the Raman shift in cm-1
.
Viscometric Measurements. The reduced viscosity (ηsp/φ,
ηsp ) (η - ηo)/ηo, φ ) concentration of polymer in g/dL) for

11394 J. Phys. Chem. B, Vol. 106, No. 43, 2002
Kitano et al.
In a dilute solution, polymer coils are separated from each
other and the intermolecular interaction between the coils is
sufficiently weak that the solution can be described as a nonideal
gas. When the polymer concentration (φ) approaches a critical
value (φ*), the polymer coils begin to overlap and make a
pseudonetwork. In the concentration region (φ > φ*), the
polymer solutions are called “semidilute” solutions.26 Graessley
suggested a concentration criterion between the low- and high-
concentration regimes for random coils in a good solvent as 1
< φ[η] < 10.27 Therefore, the value of φ* can be roughly related
to the intrinsic viscosity [η] as stated in eq 3.
Figure 3. The relationship between the Cx/Cw value of water and the
concentration (pX, molar fraction of monomer unit) of sulfobetaine
polymers at 25 °C: (9) poly(DMAPMA) (precursor); (b) PSBB-2 (DQ
) 68%); (2) PSBB-3 (DQ ) 83%); (4) PSBB-4 (DQ ) 91%); (0)
HPAA.
φ* = 1/[η]
(3)
From the value of [η] for aqueous solutions of sulfobetaine
polymers at 25 °C, it was concluded that almost all the
sulfobetaine polymers examined here make dilute solutions at
pX ) 0.01 (for example, the φ* values of PSBB-2 and PSBB-3
were 19.6 g/dL (pX ) 0.013) and 30.3 g/dL (pX ) 0.021),
respectively). Only in the case of PSBB-1, the pX value of 0.01
was slightly larger than the φ* value (pX ) 0.008).
due to the stacking between the cationic and anionic groups of
neighboring monomer residues. Both phenomena would de-
crease the characteristics of the electrolytes, resulting in a
reduced solubility in water.
The cyclization of various kinds of sulfobetaine monomers
including SPB has not been reconfirmed by the NMR method
at present.22 Weers et al. examined the effect of the intramo-
lecular charge separation distance on the solution properties of
betaines and sulfobetaines using FT-IR and NMR.23 They
reported that no evidence could be seen for the intramolecular
ion-pair formation, indicating that in a polar medium such as
water, the distance between the charge sites monotonically
increases with the increasing number of methylene units in the
tether. Using a molecular orbital calculation (WinMOPAC 3.0,
Fujitsu Computer Chemistry Systems, Tokyo, Japan), however,
we found the sulfobetaine monomer residues examined in this
study to be able to be cyclized in water (unpublished results).
B. Structure of Water in Aqueous Polymer Solutions. The
O-H stretching Raman band of liquid water gave a broad band
(Figure 1a) composed of several overlapping components, which
were attributed to the unperturbed O-H stretching band by the
intra- and intermolecular vibrational coupling of the O-H
oscillators.2b,24 The relative intensities of the collective bands
(C) are reduced by the decoupling of the O-H oscillators, (1)
when the stretching frequency of an O-H oscillator is quite
different from that of the O-H oscillator that is combined by
a hydrogen bond with the former one and (2) when the hydrogen
bond between the coupled O-H oscillators is broken by
translational or rotational rearrangement of the water molecules.17a
In pure water, the values of C at a certain temperature T (Cw-
(T)) are reduced with an increase in the temperature by intrinsic
hydrogen-bond defects caused by thermal motion.25
In aqueous solutions, water molecules interact with hydro-
philic or hydrophobic solutes and change their positions and
orientations in the hydration shell around the solutes. Conse-
quently, the intensities of the collective band of aqueous
solutions at a certain temperature T (Cx(T)) are reduced or
increased by breaking or enhancing the water-water hydrogen
bonding in comparison with those of pure water (Cw(T)) at the
same temperature. The probability, Pd, that an O-H oscillator
is excluded from the hydrogen-bonding network of water
molecules because of an unfavorable position or orientation is
defined as eq 4.
Cw(T) - Cx(T)
Pd )
(4)
Cw(T)
The C values of aqueous solutions of simple electrolytes17d and
polar substances were smaller than that of pure water at the
same temperature. This is caused, as mentioned above, by the
exclusion of the O-H oscillator of hydrating water (HOH‚‚‚
solute or H2O‚‚‚solute or both) from the collective O-H oscil-
lators of the water cluster. On the contrary, those of hydrophobic
substances such as tetra-n-butylammonium hydroxide17f (pX )
0.013) and tert-butyl alcohol17e (pX ) 0.04) were higher than
that of pure water because of an enhancement of the hydrogen
bond between water molecules in hydrophobic hydration shells
around the hydrocarbon moiety.28 These results show that the
vibrational band attributed to the O-H oscillators of water
cluster can be distinguished from that of the water hydrated to
solutes by using the polarized Raman spectroscopy and that this
method has an ability to detect the changes in the hydrogen-
bonded network structure of water even in dilute-semidilute
aqueous solutions (pX ) 0.01-0.05 (0.55-2.8 mol/L)).
C. Elucidation of N Values for Polymers. To elucidate the
effects of the properties of the monomeric unit of various
polymers, the number of hydrogen-bond defects introduced into
the hydrogen-bonded network structure of water per one
monomer unit of a polymer, N, was calculated from the defect
probability (Pd) using eq 5.
Next, the effect of various polymeric sulfobetaines on the C
value at the constant molar fraction of monomer units (pX
)
0.01) was examined. Figure 3 shows the effect of concentrations
of various sulfobetaine polymers on the Cx/Cw value, where Cx
and Cw are the C values for an aqueous polymer solution and
pure water, respectively. The Cx/Cw values for the polymer
solutions were slightly smaller than unity, and with an increase
in the degree of quaternization, the Cx/Cw value increased. In
precursor polymer solution, poly(DMAPMA), the Cx/Cw value
significantly decreased with an increase in the concentration,
whereas in the solution of PSBB-2, the Cx/Cw value more
gradually decreased. In the solution of PSBB-3, the Cx/Cw value
was always larger than those for the precursor polymer and the
PSBB-2. The Cx/Cw value of poly(acrylic acid) (HPAA)
decreased with an increase in the concentration much more
significantly than the precursor polymer. These results are due
to the difference in the disturbing effect of the polymers on the
structure of water.
N ) Pd/fX
(5)
where fX is the number of monomer units per one O-H
oscillator in a water molecule.6b,d-f, 29
Similar to small molecular solutes, ionized and polar groups
in water-soluble polymer chains and counterions may disturb
the hydrogen bond between the water molecules and raise the

Hydrogen-Bonded Network Structure of Water
J. Phys. Chem. B, Vol. 106, No. 43, 2002 11395
TABLE 2: The N Values for Various Polymersa
negative N values for PMPC are probably due to the small error
associated with separation of the collective band from the OH
stretching band, and therefore, they can be regarded as zero
approximately. Furthermore, the N value for PSBB seemed to
have the quite similar tendency as that for PSPB, despite a
difference in the distance between the quaternary ammonium
polymer
NaPES
N value
7.5b
8.1b
8.7d
3.4d
-1.1b
1.0b
0.9b
5.4
PLL‚HBr
NaPAAc
HPAAe
1
PMPC
and sulfonate groups. A recent H NMR study by El Seoud et
PEG
al. showed that a sulfobetaine surfactant, N,N-dimethyl-N-(3-
sulfopropyl)dodecylaminium inner salt, does not affect the state
of interfacial water because of the strong intermolecular
interactions between the head ions of neighboring molecules
in the micelles,31 which is consistent with the present results.
PVPy
poly(DMAPMA)
PSPB-1
PSPB-2
PSPB-3
PSBB-1
PSBB-2
PSBB-3
3.8
3.2
1.8
3.8
It should be mentioned here that PMPC could be very easily
dissolved in water, whereas PSPB (DQ ) 100%) could not.
This might be due to the bulkiness around the phosphate and
quaternary ammonium groups in the MPC residue, which
inhibits the tight ionic association between the oppositely
charged groups. As for the sulfobetaine polymers, on the
contrary, the anionic sulfonate group might easily electrostati-
cally associate with the quaternary ammonium group, resulting
in a cross-linked network that can be regarded as a ring (in the
case of ion stacking within the residue) or a head-to-tail stacking
(in the case of ionic association between the neighboring
residues). These ionic associations might diminish the electro-
static hydration (electrostriction) and induce the precipitation
of the completely quaternized sulfobetaine polymer.
Such a disadvantageous ionic association can be weakened
by the introduction of hydrophilic comonomer residues between
the sulfobetaine monomer residues.9g,i,j McCormick et al., for
example, prepared amphoteric copolymers composed of sulfo-
betaine and carboxybetaine monomer residues and showed that
the electrolyte and pH responsiveness of the copolymers largely
depended on the monomer ratio.9h
In the case of 3-aminopropanesulfonic acid, which is also
zwitterionic at neutral pH, the N value was evaluated to be 0.7
at pX ) 0.01 and 25 °C. This value is consistent with the N
values for PSPB-3 and PSBB-3. Previously, it was reported that
the C values of aqueous amino acid solutions under neutral
conditions were slightly smaller than that of pure water and
almost constant despite the difference in hydrophobicity of the
side chain.32 In other words, when both R-amino and R-carboxyl
groups of amino acids are ionized (zwitterionic), the N value
for amino acids is slightly positive and independent of the
hydrophobicity of the side chain.
3.2
1.0
a In H2O at 25 °C and pX ) 0.01. The uncertainties of N values are
(1 at the most. b Reference 6f. c Sodium polyacrylate (Mw ) 5000) at
pX ) 0.05. d Reference 6b. e Poly(acrylic acid) (Mw ) 5000) at pX
)
0.05.
N value, whereas hydrophobic moieties such as hydrocarbon
chains may enhance the hydrogen bond and reduce the N value.
The exposure area of the chemical groups to water is also
important to the structure of water around them. The values of
N obtained for the dilute solutions of various polymers, in which
the hydrogen-bond defects are expected to be localized in the
hydration shell of polymer chains and their counterions, were
determined and are listed in Table 2.
The N values of ordinary polyelectrolytes with one kind of
ionic group (sodium polyacrylate,6b,f sodium poly(ethylene-
sulfonate), and poly-L-lysine HBr salt)6f are larger than those
of water-soluble electrically neutral polymers (PEG and PVPy),6b,f
indicating that ionic groups and the counterions of polyelec-
trolytes strongly disturb the structure of water in their hydration
shells (electrostriction). Previously, Tao et al. evaluated the N
value of an aqueous DNA solution to be around 30 using eq
5.29 Such a large N value could be attributed to both the
bulkiness and polar and ionic moieties of the nucleotide unit.
As shown in Table 2, the N values for electrically neutral
water-soluble polymers (PEG and PVPy) were very small. From
the use of time domain reflectometry, it was reported that oligo-
(ethyleneglycol)s (degree of polymerization, 4-7) dissolve in
water without much perturbation to the water structure,30 which
coincides with the present data.
D. The N Values for Sulfobetaine Polymers. Table 2 shows
that the N value for zwitterionic-type polyelectrolytes, PSPBs
and PSBBs, was a relatively small positive value and, with the
increase in the degree of quaternization, the N value decreased.
It is worth noting that the N values of PSPB-3 and PSBB-3
with a large DQ value (95% and 83%, respectively) were smaller
than that of poly(acrylic acid) (HPAA). HPAA has an ionizable
group (-COOH) in the side chain and is scarcely ionized under
neutral conditions. Therefore, the water structure in poly-
(DMAPMA), PSPBs, and PSBBs solutions should be more
significantly disturbed in comparison with that in HPAA solution
because the amount of ionic species in these polymers is much
larger than that in HPAA. Actually, the obtained results that
the N values of poly(DMAPMA), PSPBs and PSBBs with a
lower DQ value were larger than that of HPAA are not in
conflict with the general knowledge and our previous reports.
However, as mentioned above, the disturbing effects of PSPB-3
and PSBB-3 on the water structure were smaller than that of
the ordinary polyelectrolytes. This is in accordance with the
previous result that the zwitterionic polymer, poly(2-methacry-
loyloxyethyl phosphorylcholine) (PMPC), did not disturb the
structure of water (N ) -1.1 and -0.1 for PMPC 4.3 K (Mw
) 4300) and 8.3 K (Mw ) 8300), respectively).6f These slightly
Because zwitterionic compounds with a small molecular
weight did not disturb the structure of water, there might be
the same reason for the small N values evaluated for the
sulfobetaine polymer systems. The anionic sulfonate group and
cationic quaternary ammonium group, which are in close
proximity to each other in the SPB and SBB residues, might
counteract the electrostatic hydration. The partially negative
oxygen atom of the water molecule is toward the positively
charged ions in solution, whereas the negatively charged ions
attract the partially positive hydrogen atoms of water, creating
their hydration shells.33 When the cation and anion are in close
proximity, the orientation of the hydrating water might be largely
disturbed resulting in the collapse of electrostriction. The
hydrocarbon main chain in the sulfobetaine polymers might be
hidden behind the bulky zwitterionic groups from water.
Previously, Høiland reported that when hydration sheaths for
ionizable groups of a dicarboxylic acid are in close proximity
and overlapped, an additivity rule for the hydration of each
component is not applicable.34 His result supports the tendency
observed in this work.
As described in the Introduction, various kinds of sulfobe-
taine, carboxybetaine, and phosphobetaine derivatives have been

11396 J. Phys. Chem. B, Vol. 106, No. 43, 2002
Kitano et al.
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found to be dermatologically inert and blood-compatible.
Though many other factors affect the biocompatibility of poly-
meric materials in a complicated manner,35 the experimental
results obtained here seem to indicate that zwitterionic polymers
without disturbing the structure of the surrounding water have
a significant potential to show a good biocompatibility. One
should note here that the N value for gelatin (Mw ) 10 000)
was estimated to be 0 at 20 °C and 10 wt %.6d Because gelatin
is a highly biocompatible denatured protein with many cationic
and anionic charges (at least 11.4% of the amino acid residues
had an ionizable side chain), the N value obtained for gelatin
strongly supports the hypothesis proposed above.
Conclusion
The structure of water in various aqueous sulfobetaine poly-
mer systems could be analyzed using Raman spectroscopy to
obtain important information concerning the interaction between
water and the polymer chains. In contrast to ordinary polyelec-
trolytes with one kind of ionized group, polymeric sulfobetaines
had a very small disturbing effect on the structure of the
hydrogen-bonding network of water molecules in dilute solutions
because of the intra- and intertether proximity between the
oppositely charged groups. Namely, the weak disturbing effect
of sulfobetaine polymers on the water structure was due to the
intrinsic property of the zwitterionic sulfobetaine polymers
themselves and not due to the polymer-polymer coordination.
The usability of sulfobetaine polymers in biomedical fields was
strongly suggested.
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Acknowledgment. This research was supported by Grants-
in-Aid for Scientific Research (Grants 11167236, 12450381,
13022225, and 13555260) from the Ministry of Education,
Science, Sports and Culture. M.I. thanks the Saneyoshi Scholar-
ship Foundation, Tokyo, Japan, for its financial support. The
authors are indebted to the Research and Development Center,
Terumo Corporation, Nakai-Machi, Kanagawa, Japan, for its
financial support. The authors thank Mr. Ken Ichikawa of this
department for his technical assistance. The authors are also
grateful to Dr. Masaru Tanaka, Research Institute for Electronic
Science, Hokkaido University, for his helpful suggestion.
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