hydrophilic and hydrophobic copolymer systems based on acrylic derivatives of pyrrolidone and...

Hydrophilic and Hydrophobic Copolymer Systems Based onAcrylic Derivatives of Pyrrolidone and Pyrrolidine

NIEVES GONZALEZ, CARLOS ELVIRA, JULIO SAN ROMAN

Departamento de Quımica Macromolecular, Instituto de Ciencia y Tecnologıa de Polımeros, National Research Council(CSIC) c/Juan de la Cierva 3, 28006 Madrid, Spain

Received 3 September 2002; accepted 12 November 2002

ABSTRACT: This article deals with the synthesis of hydrophilic methacrylic monomersderived from ethyl pyrrolidone [2-ethyl-(2-pyrrolidone) methacrylate (EPM)] and ethylpyrrolidine [2-ethyl-(2-pyrrolidine) methacrylate (EPyM)] and their respective homopoly-mers. For the determination of their reactivity in radical copolymerization reactions, bothmonomers were copolymerized with methyl methacrylate (MMA), the reactivity ratiosbeing calculated by the application of linear and nonlinear mathematical methods. EPMand MMA had ratios of rEPM � 1.11 and rMMA � 0.76, and this indicated that EPM withMMA had a higher reactivity in radical copolymerization processes than vinyl pyrrolidone(VP; rVP � 0.005 and rMMA � 4.7). EPyM and MMA had reactivity ratios of rEPyM � 1.31and rMMA � 0.92, and this implied, as for the EPM–MMA copolymers, a tendency to formrandom or Bernoullian copolymers. The glass-transition temperatures of the preparedcopolymers were determined by differential scanning calorimetry (DSC) and were found toadjust to the Fox equation. Total-conversion copolymers were prepared, and their behaviorin aqueous media was found to be dependent on the copolymer composition. The swellingkinetics of the copolymers followed water transport mechanism case II, which is the mostdesirable kinetic behavior for a swelling controlled-release material. Finally, the differentstates of water in the hydrogels—nonfreezing water, freezing bound water, and unboundfreezing water—were determined by DSC and found to be dependent on the hydrophilicand hydrophobic units of the copolymers. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A:Polym Chem 41: 395–407, 2003Keywords: hydrogels; acrylic derivatives; pyrrolidone; pyrrolidine; copolymerization;amphiphilic polymers

INTRODUCTION

Polymeric hydrogels are materials with the abil-ity to absorb certain amounts of water because oftheir hydrophilic nature. This hydrophilic charac-ter makes some of them biocompatible in applica-tions as biomaterials such as contact lenses,1

drug release systems,2 and wound dressings.3

Polymers such as poly(vinyl pyrrolidone) (PVP)have been widely used in commercial applica-

tions, but the monomer of this particular polymerhas poor reactivity in radical copolymerizationreactions.4 In this sense, it is interesting to syn-thesize new hydrophilic monomers with chemicalstructures and properties similar to those of PVP,including solubility in water (like the homopoly-mer) and improved reactivity in radical copoly-merization reactions, to easily design and preparecopolymer systems with a controlled hydrophilic–hydrophobic balance that can be applied in thefield of biomedicine.

The properties of polymeric hydrogels areknown to be influenced not only by the equilib-rium water content (WC) but also by the state of

Correspondence to: C. Elvira (E-mail: celvira@ictp. csic.es)Journal of Polymer Science: Part A: Polymer Chemistry, Vol. 41, 395–407 (2003)© 2002 Wiley Periodicals, Inc.

395

water in the gels.5 On the basis of various ther-modynamic properties of water absorbed by hy-drophilic polymers, several authors6–8 have pro-posed that water is present in three states inhydrophilic polymer matrices: (1) nonfreezablebound water (is directly bound to the polymer,which does not melt), (2) freezable bound water(interacts with water molecules through hydro-gen bonding, forming a second water layer, andmelts at temperatures lower than 0 °C), and (3)free water (forms water clusters that melt at 0°C). Studies of the different states of water givevaluable information concerning the sorption, dif-fusion, and permeation properties of molecularspecies in hydrophilic polymers. The swelling ki-netics of polymeric hydrogels give information notonly about the amount of water absorbed by thepolymer but also about the water transport mech-anism, which can be determined by the analysisproposed by Peppas et al.,3 which indicates pos-sible applications for analyzed hydrogels.

In this article, we describe the synthesis of themethacrylic derivatives of ethyl pyrrolidone[2-ethyl-(2-pyrrolidone) methacrylate (EPM)] andethyl pyrrolidine [2-ethyl-(2-pyrrolidine) methac-rylate (EPyM)], their respective radical homopo-lymerization, and their copolymerization withmethyl methacrylate (MMA), paying special at-tention to the reactivity ratios of the preparedmonomers and vinyl pyrrolidone (VP). The pre-pared copolymers were studied in terms of thethermal transitions [glass-transition tempera-ture (Tg)] and their behavior in aqueous media,with the equilibrium hydration degree, swellingkinetics, and different states of water in the co-polymers calculated by differential scanning cal-orimetry (DSC).

EXPERIMENTAL

Reagents

N-(2-Hydroxyethyl)-2-pyrrolidone (EP; Fluka) andN-(2-hydroxyethyl)-2-pyrrolidine (EPy; Fluka) wereused as received. Methacryloyl chloride (Fluka)and triethylamine (Scharlau) were distilled andfreshly used (bp � 99 and 89 °C, respectively).2,2�-Azobisisobutyronitrile (AIBN) was purifiedby fractional crystallization from ethanol (mp� 104 °C). Dimethylformamide (DMF) was dis-tilled (bp � 154 °C) and dried over molecularsieves. Other reagents were used without purifi-cation.

Monomer Synthesis

Both EPM and EPyM were synthesized with sim-ilar procedures. To solutions of 10 g of EP (0.0774mol) or 10 g of EPy (0.0868 mol) in chloroform(CDCl3; 75 mL) with 10.7 (0.0774 mol) or 12.1 mL(0.0868 mol) of triethylamine, respectively, solu-tions of 0.116 or 0.130 mol of methacryloyl chlo-ride, respectively, in 25 mL of CDCl3 were addeddropwise at 0 °C under an atmosphere of N2 withmagnetic stirring. After 6 h of reaction, the solu-tions were washed four times with aqueousNaOH (5 wt %) and dried over anhydrousNa2SO4, and the solvent was then removed underreduced pressure. The isolated products were pu-rified by column chromatography with tetrahy-drofuran as an eluent. The yield was 70% for bothsyntheses.

Polymerization

EPM and EPyM were homopolymerized at 60 °Cin a thermostatic bath with AIBN ([I] � 1.5� 10�2 mol L�1) as a radical initiator and DMF([Mo] � 1.0 mol L�1) as a solvent. Copolymeriza-tion reactions of the prepared monomers withMMA were performed under the same experimen-tal conditions. The monomer solutions were pre-pared with feed compositions between 20/80 and80/20 for both EPM–MMA and EPyM–MMA, andthe reaction time was adjusted to reach an overallcopolymer conversion of less than 10 wt % todetermine the corresponding reactivity ratios.High-conversion copolymers were also preparedfor studies in aqueous media. All experimentswere carried out in Pyrex ampules under an oxy-gen-free N2 atmosphere and after the desiredtime were precipitated in a large excess of ethylether, filtered off, and vacuum-dried at room tem-perature over phosphorus pentoxide.

Characterization of the Products

The synthesized monomers EPM and EPyM andtheir corresponding homopolymers were charac-terized with 1H and 13C NMR and Fourier trans-form infrared (FTIR). Copolymer systems, bothlow-conversion and high-conversion, were charac-terized by 1H NMR spectroscopy to determinetheir composition, as described in the Results andDiscussion section. In all cases, the composition ofthe prepared copolymers at high conversions wassimilar to that of the monomer feed, with a devi-ation of �3 wt %.

396 GONZALEZ, ELVIRA, AND SAN ROMAN

FTIR spectra were recorded on NaCl disks forthe monomers and on KBr pellets for the corre-sponding homopolymers with a PerkinElmer 457spectrometer at room temperature. The FTIR sig-nals for the monomers were as follows: (1) EPM(�, cm�1), 1720 (CAO), 1685 (CAO cycle), 1642(CH2AC), 1316 (CH2ON), and 1165 (OOCH2),and (2) EPyM (�, cm�1), 1720 (CAO), 1631(CH2AC), 1316 (CH2ON), and 1169 (OOCH2).

NMR spectra were recorded in CDCl3-d solu-tions on a Varian XLR-300 spectrometer at 45 °C.1H NMR (300 MHz) spectra were performed with5% (w/v) solutions, whereas 13C NMR spectrawere performed with 25% (w/v) solutions, withthe spectrometer operating at 75.5 MHz. 1H NMRspectra for both the monomers and homopolymersare shown later in Figure 2, whereas the 13CNMR signals were as follows: (1) EPM (�, ppm),174.8 (CAO cycle), 167.0 (CAO), 126.6 (CH2AC),62.4 (OOCH2), 47.5 (CH2ON�), 41.6 (CH2ON�cycle), 30.9, 18.4 (CH2 cycle), and 18.6 (�-CH3),and (2) EPyM (�, ppm), 167.4 (CAO), 125.8(CH2A), 63.9 (OOCH2), 54.8 (CH2ON�), 54.4(CH2ON� cycle), 23.6 (CH2 cycle), and 18.4 (�-CH3).

The average molecular weights of the preparedpolymers were determined by size exclusion chro-matography (SEC) with poly(methyl methacry-late) (PMMA) standards. Number-average molec-ular weights of 34,000 for poly(EPM) and 39,000for poly(EPyM) were obtained. According to theobtained SEC curves, the polydispersities (weight-average molecular weight/number-average mo-lecular weight) of the analyzed samples were 2.2

and 2.4, respectively, with symmetric SEC dia-grams approaching a Gaussian distribution.

Preparation of the Films

Homopolymer and copolymer films (from high-conversion copolymers) were prepared by the slowevaporation of solutions of 0.5 g of the polymers in3 mL of CDCl3 poured into Teflon molds (20 mmin diameter and 8 mm thick). The films wereeasily separated from the Teflon molds andsoaked in water solutions for 24 h at room tem-perature. Then, the films were exhaustively driedunder reduced pressure until constant weightswere attained, with an average thickness of 200–300 �m.

Swelling Behavior

The study of the hydration degree was followedgravimetrically by the measurement of theweight with the time of the films immersed in 10mL of phosphate buffer solutions at pH 7.4 at 37°C. Measurements were taken until the equilib-rium hydration degree was reached, which wasconsidered accomplished when three consecutivemeasurements gave the same value.

DSC: The Tg Values and the State of Water

The Tg values of the corresponding homopolymersand prepared copolymers were determined with aPerkinElmer DSC-7 calorimeter. Measurements

Figure 1. Scheme of the synthesis of monomers EPM and EPyM.

HYDROPHILIC AND HYDROPHOBIC COPOLYMER SYSTEMS 397

and calibration were carried out at a heating rateof 10 °C min�1. Tg was taken as the midpoint ofthe transition region. Samples (�15–20 mg) wereintroduced into an aluminum pan, heated at 450K, compressed, and quenched to room tempera-ture before the experiments were performed.However, the determination of the amount of wa-ter was performed on swollen films (20 mg) withdifferent known hydration degrees. After the ap-propriate weight of the sample was reached, thefilm was placed in an aluminum pan, cooled withliquid nitrogen to �40 °C, and then heated at 2.5°C min�1 to 30 °C. The calibration of the instru-ment with pure water yielded 333.34 J g�1 as theenthalpy of fusion of water, and this value wasused to calculate the weights of water in various

states. The contents of free freezing water (Wff)and freezable bound water (Wbf) were determinedfrom the direct integration of the endothermicpeaks. The content of nonfreezing water (Wnf) wascalculated by the subtraction of the total freezingwater (Wtf) from the different WCs. The equationsrelating the different types of water are as fol-lows:

Wtf � Wff � Wfb (1)

Wnf � WC � Wtf (2)

In eqs 1 and 2, all the quantities (with corre-sponding subscripts) denoting the different types

Table 1. Copolymer Compositions and ConditionalProbabilities for the Radical Copolymerization ofEPM and EPyM with MMA in a DMF solution at 60°C with AIBN as an Initiator and Corresponding Tg

Values of the Prepared Copolymers

FEPM

(feed)fEPM

(Copolymer) PEM PME WEPM Tg (°C)

0.00 0.00 1.00 0.00 0.00 1140.20 0.23 0.78 0.25 0.37 1050.40 0.45 0.57 0.47 0.62 830.60 0.63 0.37 0.66 0.77 770.80 0.83 0.18 0.84 0.91 701.00 1.00 0.00 1.00 1.00 57

FEPyM

(feed)fEPyM

(Copolymer) PEM PME WEPyM Tg (°C)

0.00 0.00 1.00 0.00 0.00 1140.20 0.22 0.75 0.21 0.34 870.40 0.47 0.53 0.42 0.62 650.60 0.62 0.34 0.62 0.75 410.80 0.85 0.16 0.81 0.91 301.00 1.00 0.00 1.00 1.00 27

Table 2. Reactivity Ratios of the Free-RadicalPolymerization of EPM–MMA and EPyM–MMA inDMF at 60 °C with AIBN as a Radical Initiator

Methoda rEPM rMMA rEPyM rMMA

FR 1.2 0.82 1.5 1.06KT 1.13 0.75 1.4 0.96TM 1.11 0.76 1.31 0.92

a FR � Fineman–Ross; KT � Kelen–Tudos; TD � Tidwell–Mortimer.

Figure 2. 1H NMR spectra of (A) EPM and (B) EPyMand their corresponding homopolymers prepared byradical polymerization at 60 °C with AIBN ([I] � 1.5� 10�2 mol L�1) as a radical initiator and DMF ([Mo]� 1.0 mol L�1) as a solvent.


of water are calculated as weights relative to thetotal weight of the swollen hydrogel and are ex-pressed finally as percentages. The content ofmaximum nonfreezing water (bound water) wasdetermined by extrapolation from the plot of theDSC melting enthalpy of the gel versus the dif-ferent WCs of the hydrogels, taken as the WCs ina hydrogel at zero enthalpy of fusion.

RESULTS AND DISCUSSION

Synthesis and Characterization of the Monomersand Homopolymers

The methacrylic monomers derived from EP andEPy were synthesized in good yields by the reac-tion of the hydroxyl group with methacryloyl chlo-ride to give the corresponding methacrylic esters(see Fig. 1). The synthesis of EPM was initiallydescribed by Iskander et al.,9 and we followed asimilar procedure. Figure 2 shows the 1H NMRspectra of the synthesized monomers and theircorresponding homopolymers with the assign-ments of the signals. 13C NMR and FTIR assign-ments are shown in the Experimental section.The radical polymerization was carried out ac-

cording to the experimental conditions, reachingconversions of 85% for poly(EPM) and 83% forpoly(EPyM) after 24 h.

Kinetic Treatment and StatisticalCopolymerization Data

Copolymerization experiments at various co-monomer feed compositions (see Table 1) werecarried out in solution and at low conversions(�10 wt %) to satisfy the general copolymeriza-tion equation and to calculate the correspondingreactivity ratios. The copolymer compositionswere obtained by 1H NMR spectroscopy, with ananalysis of the intensities of the signals assignedto the protons OCH2OO (4.1 ppm) andONOCH2O (3.5 ppm) of EPM units, OCH2OO(4.1 ppm) of EPyM units, and OOOCH3O (3.6ppm) of MMA units. For the system EPM–MMA,theOOOCH3O signal from MMA overlapped theONOCH2O signal from EPM, so the well-sepa-rated signal at 4.1 ppm, corresponding toOOCH2O of EPM, was set as a reference, withthe value of two protons and the value of fourprotons of the two EPM groups bonded to N sub-tracted from the integral value of the signal at

Figure 3. Composition diagram of the prepared copolymers EPM–MMA and EPyM–MMA.


about 3.6 ppm to calculate the value of OOCH3from MMA units.

The reactivity ratios were determined with thelinearization methods proposed by Fineman andRoss10 and Kelen and Tudos11 and with the non-linear least-squares analysis of Tidwell and Mor-timer12 exhibited in Table 2. The Tidwell–Mor-timer method provides the most probable reactiv-

ity ratio values, as checked by the ellipticaldiagram13 of the 95% confidence limit of the reac-tivity ratios of the EPM–MMA and EPyM–MMAcopolymerization reactions. In this sense, thecomonomer pair EPM–MMA had the reactivityratios rEPM � 1.11 and rMMA � 0.76; in compari-son with VP–MMA14,15 (rVP � 0.005 and rMMA� 4.7), the methacrylic derivative of EP showed a

Figure 4. Variation of the molar fraction of (A) EPM- and (B) EPyM-centered triadswith the molar fractions of EPM and EPyM in the respective copolymers.


higher reactivity with MMA in radical copolymer-ization processes, which is an interesting charac-teristic for the preparation of copolymer systems

with a controlled hydrophilic–hydrophobic bal-ance with applications in the field of biomedicine.However, comonomers EPyM and MMA had the

Figure 5. Three-dimensional diagrams of the instantaneous copolymer molar frac-tion as a function of the conversion and initial feed molar fraction for the (A) EPM–MMA and (B) VP–MMA copolymer systems.


reactivity ratios rEPyM � 1.31 and rMMA � 0.92,which implied, as for the EPM–MMA copolymers,that the propagating species ending in EPM orEPyM were slightly more reactive toward them-selves than to MMA molecules, and MMA-endingpropagating species reacted slightly more towardEPM and EPyM species than toward its ownMMA monomer. In light of the reactivity ratioproducts, this would lead to a tendency to formrandom or Bernoullian copolymer systems, as canbe observed in Figure 3, which shows the averagecomposition diagram of the prepared copolymers.The conditional probabilities Pij, defined as theprobability for the addition of monomer units j toradical i ends, were calculated statistically fromthe Tidwell–Mortimer values of the reactivity ra-tios and are collected in Table 1. The statisticaldiagrams of EPM- and EPyM-centered triadswere determined according to the classical Mayo–Lewis model.16

Figure 4 shows the variation of the molar frac-tion of EPM- and EPyM-centered triads with thecopolymer composition for copolymers preparedat low conversions, M being the MMA units in thecopolymer and E being the hydrophilic units, ei-ther EPM or EPyM. The molar fraction of MEMalternating triads of EPM–MMA and EPyM–

MMA copolymer systems decreased with the Econtent, being predominant until E molar frac-tions of 0.47 and 0.43, respectively, from whichvalues the EEE homotriad molar fraction startedto increase, being predominant in the E high mo-lar fractions in both copolymer systems. Thesedata indicate that the probability of finding con-secutive E units along the macromolecules washigh at E molar fractions higher than 0.5. Thisanalysis contributes to explaining the copolymerbehavior in aqueous media, as discussed later in astudy of these properties. According to the reac-tivity ratio values, the average compositional tri-ads could be expect not to change noticeably withthe conversion degree, as can be observed in thethree-dimensional diagrams of Figure 5, whichrepresent the instantaneous copolymer molarfraction as a function of the conversion and initialfeed molar fractions for the EPM–MMA and VP–MMA copolymer systems obtained by the applica-tion of an algorithm of the integrated solution ofthe Mayo–Lewis equation.17 Figure 5(a) repre-sents the system EPM–MMA, in which it can beobserved that the evolution with the conversion ofa 0.5 EPM initial molar fraction (bold line) led toa similar EPM instantaneous copolymer molarfraction over the entire conversion range,

Figure 6. Variation of 1/Tg versus the monomer weight fraction in the copolymersystems EPM–MMA and EPyM–MMA.


whereas for the VP–MMA system [Fig. 5(b)], a 0.5VP initial molar fraction (bold line) at a low con-version led to copolymers rich in MMA units,causing the formation of VP blocks at high con-versions. The same behavior could be expected forthe system EPyM–MMA.

Tg’s

The Tg’s of the homopolymers poly(EPM) andpoly(EPyM) (see Table 1) were lower than Tg of

PMMA, with values of 60 and 27 °C, respectively.These lower Tg values with respect to PMMAcould be attributed to the higher flexibility of thelonger side chains of the prepared homopolymers.However, the higher Tg of poly(EPM) with respectto that of poly(EPyM) could be attributed to thestiffness of the cyclic amide and to the tautomer-ism of this chemical group. Table 1 shows the Tgexperimental values of EPM–MMA and EPyM–MMA copolymers and the molar and weight frac-tions of the monomers in the feed and in the

Figure 7. Swelling isotherms (37 °C) of films prepared from (A) EPM–MMA copoly-mers and (B) poly(EPyM) and EPyM–MMA copolymers.


copolymer systems. Figure 6 shows the diagramsof 1/Tg versus the weight fraction of EPM andEPyM. The straight lines correspond to the appli-cation of the Fox equation based on the free-vol-ume theory.18 The experimental points of bothcopolymer systems adjusted to the straight lines,indicating that Tg’s of the prepared copolymerscorresponded approximately to the averageweight values of the homopolymers.

Swelling Behavior

The homopolymer derived from EP [poly(EPM)]was found to be soluble in water, whereas poly-(EPyM) was found to be soluble under an acidicpH because the cyclic amine could be protonated.For this reason, MMA total-conversion copoly-mers rich in EPM and EPyM were prepared tostudy the swelling behavior in phosphate buffersolutions at pH 7.4 of systems with a controlledhydrophilic–hydrophobic balance. Copolymers ofEPM–MMA with a composition of about 50 wt %did not absorb water, and the studies were per-formed in systems with 65–86 wt % EPM in thesecopolymer systems. However, EPyM–MMA copol-ymers exhibited a similar behavior, the equilib-rium hydration degree for 50 and 68 wt % EPyMbeing low (ca. 30%) in comparison with that of thehomopolymer poly(EPyM), about 260% (see Fig.7). This low equilibrium hydration degree in bothcopolymeric systems was consistent with the al-ternating triad analysis, in which the MEM alter-

nating triad molar fractions (hydrophobic–hydro-philic–hydrophobic units) were predominant un-til 0.47 and 0.43, values which correspond to 63and 60 wt % EPM and EPyM, respectively. Fromthose values, EEE triads (hydrophilic units)started to predominate, and this indicated thatthe accessibility of water molecules for swellingthe corresponding copolymers was easier whenEEE triads predominated.

After immersion in buffer solutions at pH 7.4,the films were readily swollen up to an extensiondepending on the chemical composition. The val-ues of the equilibrium hydration degree (H%) aresummarized in Table 3, and the swelling iso-therms at 37 °C are exhibited in Figure 7. Theabsorption of water depended on the copolymercomposition, and H% was reached faster forEPM–MMA copolymers (ca. 1 h) than for EPyM–MMA systems (ca. 4 h). The dependence of H% onthe composition is plotted in Figure 8, in which itcan be observed that for EPM–MMA copolymers,H% started to increase rapidly when the compo-sitions were higher than 65 wt % EPM (H% � 10)up to H% � 200 for the system with 86 wt % EPM,whereas in the EPyM–MMA copolymers, the in-crease in H% with respect to the EPyM composi-tion was lower but similar, ranging from H% � 30for 50 wt % in the copolymer to 190% for 95 wt %.

For the determination of the water transportmechanism, the initial swelling data were fit withthe following equation:19

Mt

Meq� ktn (3)

Table 3. Compositions of Copolymers EPM–MMAand EPyM–MMA and Their H% and n Values(Calculated from eq 3)

CopolymerEPM—MMAComposition H% n

86 200 1.03 � 0.0381 95 1.29 � 0.0565 10 1.02 � 0.04

CopolymerEPyM—MMAComposition H% n

100 260 0.79 � 0.0795 190 1.01 � 0.0283 80 0.79 � 0.0668 35 0.89 � 0.0550 30 0.82 � 0.06

Figure 8. Variation of the equilibrium hydration de-gree with the monomer (EPM or EPyM) weight fractionin the EPM–MMA and EPyM–MMA copolymers.


where Mt is the mass of the water uptake at timet, Meq is the equilibrium water uptake, and k andn are constants that are characteristic parame-ters of the specific system. A value of n � 0.5indicates Fickian diffusion, and n � 1 impliescase transport II; values of n between these limitsdefine anomalous or non-Fickian transport, inwhich both diffusion and polymer relaxation con-trol simultaneously the overall rate of water up-take. The values of diffusion exponents are pre-sented in Table 3 for a 95% confidence level. ForEPM–MMA copolymers, the n exponent was sim-ilar or near to unity, and this behavior is knownas case II transport; it indicates that the waterdiffusion through the polymers was much fasterthan the polymer–solvent relaxation, which cor-responded to the most desirable kinetic behaviorfor a swelling controlled-release material.

Bound and Nonbound Water in HydrogelsDetermined by DSC Experiments

Several techniques such as DSC, thermogravi-metric analysis, and dynamic thermal analysishave been used in the determination of the differ-ent states of water in polymeric hydrogels.20,21

DSC has proven to be a sensitive technique for

determining the state of water in hydrogels,22–24

allowing researchers to differentiate between Wnf(water that is strongly bound to the polymer),freezing and more loosely bound water (Wfb), andWff. Figure 9 shows a DSC thermogram of thecopolymer system EPM–MMA (81/19 w/w) withvarious unsaturated water uptakes from 18 to123%. At lower hydration degrees, all the waterpresent in the hydrogel was directly bound to thepolymer and could not be detected by DSC. Whenthe copolymer had higher hydration degrees,melting peaks appeared at �4 °C (assigned toWfb) and at 0 °C (assigned to the melting of Wff;see the hydration degrees of 18 and 34% in Fig. 9).At higher water uptakes (58 and 123%), both peakscollapsed, but the total freezable water could becalculated. Wfb and Wff were calculated by the inte-gration of the peaks and were divided by the en-thalpy of pure water, that is, 333.34 Jg�1. Wnf wasdetermined, as described in the Experimental sec-tion, by the application of eqs 1 and 2. The contentof maximum bound water limited the value of WCin the hydrogels at zero melting enthalpy. This ex-trapolated value was taken from the plot of the DSCmelting enthalpy of the gel versus the nonequili-brated WC in the hydrogels. (Fig. 10). Table 4 showsthe values of Wnf of the studied systems: the EPM–

Figure 9. DSC thermograms of EPM–MMA with 81 wt % EPM and different WCs.


MMA copolymers (81/19 and 65/35 w/w), the ho-mopolymer poly(EPyM), and EPyM–MMA (85/15w/w). The highest amount of Wnf corresponded tothe homopolymer derived from EPy, as the amountof hydrophilic groups in this macromolecular chainwas higher with respect to the studied MMA copol-ymers as the bound water sites decreased with anincreasing amount of hydrophobic units of MMA.

CONCLUSIONS

The methacrylic monomers derived from EP andEPy were synthesized in good yields (80%) and werecharacterized by spectroscopic techniques (NMRand FTIR). Radical polymerization reactions were

performed in solution to obtain the correspondinghomopolymers and copolymers with MMA. The de-termined reactivity ratios of the MMA copolymersshowed higher reactivity for the methacrylic deriv-ative of EP with respect to VP, with a tendency toform random copolymers in both EPM–MMA andEPyM–MMA systems. Poly(EPM) was a water-sol-uble polymer like PVP, whereas poly(EPyM) wassoluble at an acidic pH. High-conversion copolymerswere prepared, and systems were obtained with acontrolled hydrophilic–hydrophobic balance; theirequilibrium hydration degrees and an analysis byDSC of the different states of the hydration waterrevealed an intimate dependence with the copoly-mer compositions. The study of the swelling kinet-ics and the analysis of the water transport mecha-nism of the prepared hydrogels indicated possibleapplications in biomedicine as swelling controlled-release materials.

The authors acknowledge the grant of reference CICYTMAT (2001-1618) and Programa Ramon y Cajal fortheir financial support.

REFERENCES AND NOTES

1. Franklin, V. J.; Bright, A. M.; Tighe, B. J. TrendsPolym Sci 1993, 1, 9–16.

Figure 10. Plot of the melting enthalpy (Hf) as a function of WC for EPM–MMAwith EPM weight fractions of 65 and 81%, EPyM–MMA with an EPyM weight fractionof 85 wt %, and poly(EPyM). Both Hf and WC are related to the dried polymer weight.

Table 4. Maximum Wnf Values in the EPM–MMAand EPyM–MMA Copolymers Determined byExtrapolation from Diagrams of the Enthalpy ofFusion versus the Hydration Degree

EPM (%)Maximum

Wnf (%) EPyM (%)Maximum

Wnf (%)

81 25 100 9165 15 83 58


2. Kim, S. W.; Petersen, R. V.; Feijen, J. In DrugDesign; Ariens, J., Ed.; Academic: New York, 1980;Vol 10, pp 193–250.

3. Peppas, N. A.; Korsmeyer, R. W. In Hydrogels inMedicine and Pharmacy; Peppas, N. A., Ed.; CRC:Boca Raton, FL, 1987; Vol. 3, pp 109–135.

4. Liu, Y.; Huglin, M. B.; Davis, T. P. Eur Polym J1994, 30, 457–463.

5. Ahmad, M. B.; Huglin, M. B. Polym Int 1994, 30,457–463.

6. Higuchi, A.; Iijima, T. Polymer 1985, 26, 1207–1211.

7. Quinn, F. X.; Kampff, E.; Smyth, G.; McBrierty, J.Macromolecules 1988, 21, 3191–3198.

8. Ping, Z. H.; Nguyen, Q. T.; Chen, S. M.; Zhou, J. Q.;Ding, Y. D. Polymer 2001, 42, 8461–8467.

9. Iskander, G. M.; Baker, L. E.; Wiley, D. E.; Davis,T. P. Polymer 1998, 39, 4165–4169.

10. Fineman, M.; Ross, S. D. J Polym Sci 1950, 5,259–265.

11. Kelen, T.; Tudos, F. J Macromol Sci Chem 1975, 9,1–27.

12. Tidwell, P. W.; Mortimer, G. G. A. J Polym Sci PartA: Gen Pap 1965, 3, 369–387.

13. Behnken, D. W. J Polym Sci Part A: Gen Pap 1964,2, 645.

14. Al-Issa, M. A.; Davis, T. P.; Huglin, M. B.; Rego,J. M.; Rehab, M. M. A.-M.; Yip, D. C. F.; Zakaria,M. B. Makromol Chem 1990, 191, 321–330.

15. Bork, J. F.; Coleman, L. E. J Polym Sci 1960, 43,413–421.

16. Mayo, F. R.; Lewis, F. M. J Am Chem Soc 1944, 66,1594–1601.

17. Gallardo, A.; Aguilar, M. R.; Abraham, G. A.; SanRoman, J. J. Educ Chemistry, submitted for publi-cation, 2002.

18. Fox, T. G. Bull Am Phys Soc 1956, 1, 123–130.19. Crank, J. The Mathematics of Diffusion; Claren-

don: Oxford, 1975; p 239.20. Ngui, M. O.; Mallapragada, S. K. J Appl Polym Sci

1999, 72, 1913–1920.21. Hatakeyama, T.; Nakamura, K.; Hatakeyama, H.

Thermochim Acta 1988, 123, 153–161.22. Liu, Y.; Huglin, M. B. Polym Int 1995, 37, 63–67.23. Hatakeyama, H.; Hatakeyama, T. Thermochim

Acta 1998, 308, 3–22.24. Vazquez, B.; San Roman, J.; Peniche, C.; Cohen,

M. E. Macromolecules 1997, 30, 8440–8446.


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