Polymer conformation in mixed aqueous-polar organic solvents

European Polymer Journal 46 (2010) 324–335

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Polymer conformation in mixed aqueous-polar organic solvents Eleftheria Antoniou, Paschalis Alexandridis * Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York (SUNY), Buffalo, NY 14260-4200, USA

a r t i c l e

i n f o

Article history: Received 1 August 2009 Received in revised form 27 September 2009 Accepted 5 October 2009 Available online 9 October 2009 Keywords: Water-soluble polymer Polysaccharide Viscosity Solvent quality Dextran

a b s t r a c t The conformation of the common polysaccharide dextran has been investigated in mixed solvents at two different temperatures using viscosity measurements. In particular we considered binary mixtures of water with the polar organic solvents glycerol, formamide, dimethylsulfoxide, or ethanol. The intrinsic viscosity of dextran T500 in the different systems has been determined, and the solvent effects, as manifested in variations of the dextran intrinsic viscosity and coil radius, have been correlated to the surface tension and the fractional solubility parameters of the solvent mixture. The coil dimension changes observed in the different solvent mixtures are consistent with expectations from water– cosolvent–dextran interactions, especially as they pertain to hydrogen bonding. Ó 2009 Elsevier Ltd. All rights reserved.

1. Introduction Solvents can have a great impact on the conformation of polymers [1–4]. Depending on the interactions between the polymer and the solvent molecules, a polymer may dissolve fully or phase separate. In a good solvent, polymer coils swell and expand, whereas in marginal solvent conditions they contract to their unperturbed dimensions. Addition of another solvent in a polymer solution can greatly enhance or reduce the polymer miscibility. This is especially the case when the main solvent is water. Polymers dissolved in mixtures of water with polar organic solvents are widely used in applications such as coatings, paints and inks, pharmaceutics, personal care products, and protein processing [5,6]. In many such multi-component products, e.g., pharmaceutics, the mixed solvents serve to enhance the solubility of substances that have too low solubility in neat solvents [7–9]. At the same time, these solvents affect the solubility, conformation and function of the polymers which are typically incorporated in the formulations for reasons such as viscosity control, colloidal stability, or delivery of actives.

* Corresponding author. E-mail address: [email protected] (P. Alexandridis). 0014-3057/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.eurpolymj.2009.10.005

Motivated by the fundamental and practical considerations outlined above, our research group has been active in the study of solution properties of water-soluble polymers in single and mixed organic solvents [4,10–12]. The polysaccharide dextran is a water-soluble polymer that offers the advantages of being biocompatible and biodegradable [13]. Mainly used as plasma volume expander in clinical applications, dextran also serves as a rheology modifier in food, drink, cosmetics, pharmaceutical, coating, paint, photographic, and agricultural products. Several studies of dextran in pure solvents have been reported [14–18], but there is a dearth of information on dextran in mixed solvents. Only Mahapatra et al. [19] has published data of dextran fractions in mixtures of water and polar solutes (NaOH, KOH, urea, glycine, and glucose). In this work we investigate solution properties of dextran in binary mixtures of water and polar organic solvents such as formamide, glycerol, dimethylsulfoxide (DMSO), and ethanol. We are interested in the conformation of dextran as affected by the addition of a good or a bad solvent, or the variation of temperature. We use viscosity measurements to obtain the polymer intrinsic viscosity, coil radius, and coil volume, and we discuss these properties in terms of the quality of the mixed solvent. In order to interpret our results in mixed solvents we sought literature information concerning water–cosolvent interactions.

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The solvents examined in this work have been identified utilizing the polymer–solvent interaction parameter v12 and the free energy of interfacial interaction DG121. Dextran is a hydrophilic, monopolar, neutral polymer. As an electron donor, dextran manifests a strong, Lewis acid–base (AB) repulsion (DGAB > 0) in water, also an electron donor [20]. The v12 interaction parameters (Table 1) were determined following procedures in Hansen [21]. A polymer dissolves in a solvent when the v12 value is lower than 0.5. On the basis of v12 parameters close or lower than 0.5, dextran is expected to dissolve in glycerol, formamide, and DMSO. The value of the dextran–ethanol v12 parameter was significantly higher than 0.5, which indicates that ethanol is a bad solvent for dextran. The free energy of interfacial interaction, DG121, when positive, suggests that molecules of type (1) will repel each other in solvent (2) and will spontaneously dissolve in it [20]. If DG121 is negative, then molecules (1) will attract each other in solution, and will thus tend to precipitate from the solvent (2). According to the DG121 values resulting from the van Oss method [20] (Table 1), dextran is expected to dissolve in formamide, DMSO or water (where the DG121 values are positive), but not in ethanol or glycerol (negative DG121 values). These two different approaches (by Hansen [21] and van Oss [20]) concur that formamide, DMSO and water are good solvents for dextran, while ethanol is a bad solvent. Glycerol appears to be a good solvent for dextran if we use the v12 data and a bad solvent if we use the DG121 values. However, the v12 value of glycerol 0.491 is very close to the limit of 0.5, and the DG121 = 2.11 is relatively close to 0 in comparison to the 9.66 DG121 value for ethanol. Clearly, glycerol is expected a better solvent for dextran than ethanol. To our best knowledge, this is the first time that the conformation of dextran is being reported in mixed solvents. Moreover, we have successfully correlated here the dextran coil dimensions to properties (surface tension and fractional solubility parameters) of the solvent mixtures. A few studies have attempted to correlate dextran solution behavior to solvent properties in single solvents [22], but none in mixed solvents.

the T500 dextran fraction, with weight average (Mw) and number average (Mn) molecular weights 500,000 and 191,500 respectively, purchased from Amersham Biosciences AB (now part of GE Healthcare, Uppsala, Sweden) and Pharmcosmos A/S (Holbaek, Denmark). Dimethylsulfoxide (DMSO) and glycerol (purified grade, 99% min) were obtained from Fisher Scientific (Fair Lawn, NJ). Formamide (molecular biology grade) was purchased from VWR International (West Chester, PA) and ethanol from Decon Labs, Inc. (King of Prussia, PA). The water used was purified with a Milli-Q system. Two solvents were mixed to create a binary solvent mixture of desired vol.% composition. Samples were prepared individually for every dextran concentration by dissolving appropriate amount of polymer in a given binary solvent mixture. The samples remained under stirring for at least one day at room temperature and then equilibrated at 20° or 40 °C for at least an hour before the measurements were conducted at the same temperature. 2.2. Methods

2. Materials and methods

We performed viscosity measurements at both 20° and 40 °C for dextran T500 in mixtures of water with one of the following polar organic solvents: glycerol, formamide, DMSO and ethanol. The viscosity of dilute dextran solutions was determined using Cannon Fenske Routine type viscometers [23] for transparent Newtonian fluids (aqueous solutions of up to 30 wt.% dextran exhibit Newtonian flow characteristics according to [17]). Different sizes of viscometers were used depending on the viscosity range of the samples. The viscometer was placed inside a constant temperature bath to ensure that the measurements were taken under constant temperature (controlled to within ±0.1 °C). The efflux times were reproducible to ±0.1% (each measurement was repeated three times) and were measured with an accuracy of ±0.1 s. The kinematic viscosity g is calculated by multiplying the efflux time with the viscometer calibration constant (supplied by the manufacturer, Cannon Instrument Co., State College, PA). The viscosity data analysis procedure has been presented elsewhere [24]. Briefly, focusing on data in the dilute regime, we obtain the intrinsic viscosity for dextran and extract the coil dimensions using the Einstein viscosity relation (see below).

2.1. Materials

2.3. Intrinsic viscosity

Dextran, a polysaccharide biopolymer consisting of glucose units, is the subject of this investigation. We consider

The intrinsic viscosity values of dextran in different solvents and at different temperatures are determined using

Table 1 Surface tension, c, surface tension apolar component, cLW, surface tension polar component, cAB, electron-acceptor parameter of the surface tension, c+, electron-donor parameter of the surface tension c, according to van Oss [20], free energy of interfacial interaction, DG121, estimated with the van Oss [20] procedure for the single solvents used in this study, and Flory–Huggins parameter, v12, estimated using the Hansen [21] procedure and data. Solvent

c

cLW

cAB

c+

c

DG121

v12

Dimethylsulfoxide Formamide Glycerol Ethanol Water Dextran T70 Dextran T150

44.0 58.0 64.0 22.4 72.8 55.5 42.0

36.0 39.0 34.0 18.8 21.8 41.8 42.0

8.0 19.0 30.0 2.6 51.0 13.7 0.0

0.50 2.28 3.92 0.02 25.50 1.00 0.00

32.0 39.6 57.4 68.0 25.5 47.2 55.0

4.51 6.67 2.11 9.66 41.24

0.500 0.419 0.491 0.696

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the Huggins (1) and Kramer (2) equations [25,26] by plotting gsp/C and ln(grel)/C, respectively, against the polymer concentration, and subsequently extrapolating to zero polymer concentration (infinite dilution).

gsp =C ¼ ½g þ k0 ½g2 C 00 ðln grel Þ=C ¼ ½g  k ½g2C

ð1Þ ð2Þ

grel is the relative viscosity (grel = g/g0, g and g0 are the kinematic viscosity of the solution and the pure solvent, respectively, in mPa s or cSt), gsp is the specific viscosity (gsp = grel  1), k0 and k00 are the Huggins and Kramer constants, respectively, and C is the concentration (g/dl) of the polymer solution. A straight line is obtained when the data are plotted according to Eqs. (1) and (2) (see Fig. 1(b)), with [g] being the intercept. The intrinsic viscosity values extracted from our experiments are presented in Table 2. 2.4. Hydrodynamic coil radius The increase in viscosity of a dilute dispersion of uniform, rigid non-interacting spheres can be expressed by the Einstein viscosity relation (Eq. (3)) [23,26]:

g ¼ gð1 þ 2:5UÞ

ð3Þ

where U represents the volume fraction of the spheres in the solution. Relative viscosity, grel, data versus dry polymer weight fraction are presented in Fig. 1(a). The volume fraction occupied by the polymer coils in solution is much higher than the dry polymer weight fraction because they are swollen with solvent. Starting from Eq. (3) we can derive an equation to determine the hydrodynamic coil radius, Rcoil (for derivation refer to [24]):

Rcoil ¼ ½3½g  M w =10p  N AV 1=3 ðcmÞ

ð4Þ

where NAV is Avogadro’s number. The Rcoil and corresponding hydrodynamic coil volume, Vcoil (=(4/3)pRcoil3), values for dextran T500 in different solvent systems are reported in Table 2. 2.5. Overlap concentration The overlap concentration, C*, marks the crossover between the dilute regime and the concentration regime where polymer coils overlap [27]. [g] can be used to estimate C* [28]:

C  ¼ 2:5=½g

ð5Þ

C* can also be estimated from a grel versus C plot by defining the point where the linear fits of the dilute and semidilute regime viscosity data intersect. The C* values reported in Table 2 were estimated using Eq. (5) since this is more objective than the intercept method; however both methods give consistent results.

(a) 32 28 24

η rel

20 16

3. Results

12

Experimental information on the solution structure of dextran dissolved in aqueous-polar organic (formamide, glycerol, dimethylsulfoxide, or ethanol) solvent mixtures, as affected by temperature, is presented here. Dextran adopts a random coil conformation in water and in polar organic solvents such as ethylene glycol [29], formamide [18], and DMSO [30], as attested by analysis of viscosity [16,18] and small angle X-ray scattering data [31]. We recently investigated the conformation of dextran T500 in the single solvents water, formamide, DMSO, and ethanolamine [18]. We found that the ability of a solvent to increase [g] and expand the dextran coils increases in the order: water < ethylene glycol < formamide < dimethylsulfoxide < ethanolamine. The magnitude of the intrinsic viscosity, [g], can be considered as a measure of solvent quality: the greater the [g], the better the solvent [18]. The coil radius, Rcoil, in the solvent systems used in this work is calculated through [g] using Eq. (4). In the sections that follow we discuss the solvent and temperature effects primarily in terms of the dextran coil dimensions, Rcoil and Vcoil. [g] and Rcoil data for dextran T500 in the four solvent systems of water mixed with formamide, glycerol, DMSO, or ethanol are plotted against the organic solvent content in the mixture in Figs. 2 and 3 (see also Table 2). We observe three trends: the dextran [g] and Rcoil increase (positive slope), decrease (negative slope), or change non-

8 4 0

0.02

0.04

0.06

0.08

0.1

weight fraction

nsp/c (dl/g) and ln(η rel)/c

(b) 0.7

25% Glycerol 25% Formamide

0.6

25% DMSO 0.5

25% Ethanol 0.4

0.3

0.2 0

0.2

0.4

0.6

0.8

1

1.2

1.4

1.6

C (g/dl) Fig. 1. (a) grel versus polymer (dry) weight fraction, U, and (b) specific viscosity (filled symbols) and log of relative viscosity over concentration (open symbols) plotted and linearly fitted versus the concentration, C, of dextran T500 in aqueous-polar organic mixed solvents at 20 °C: 25 v/v% of () glycerol, (d) formamide, (N) dimethylsulfoxide, or (j) ethanol in water.

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Table 2 Intrinsic viscosity [g], hydrodynamic coil radius Rcoil, hydrodynamic coil volume Vcoil, and overlap concentration C*, for dextran T500 in single and mixed solvents, calculated using the viscosimetric data obtained in this work at 20 °C and 40 °C. The reported solvent compositions are vol.% (the remainder vol.% is water). Solvent

20 °C

100% Dimethylsulfoxide 85% Dimethylsulfoxide 70% Dimethylsulfoxide 50% Dimethylsulfoxide 25% Dimethylsulfoxide 100% Formamide 85% Formamide 70% Formamide 50% Formamide 25% Formamide 100% Glycerol 25% Glycerol 20% Glycerol 15% Glycerol 100% Ethanol 30% Ethanol 25% Ethanol 15% Ethanol 100% Water

40 °C

[g]H (dl/g)

Rcoil (nm)

Vcoil (10 nm )

C (g/dl)

[g]H (dl/g)

Rcoil (nm)

Vcoil (103 nm3)

C* (g/dl)

0.792 0.691 0.621 0.471 0.478 0.669 0.627 0.605 0.588 0.511 – 0.545 0.523 0.523 – 0.285 0.327 0.405 0.491

18.5 17.6 17.0 15.5 15.6 17.4 17.1 16.9 16.7 15.9 – 16.3 16.1 16.1 – 13.1 13.7 14.8 15.7

26.5 22.8 20.6 15.6 15.9 22.1 20.9 20.2 19.5 16.8 – 18.1 17.5 17.5 – 9.4 10.8 13.6 16.2

3.2 3.6 4.0 5.3 5.2 3.7 4.0 4.1 4.3 4.9 – 4.6 4.8 4.8 – 8.8 7.7 6.2 5.1

0.743 0.643 0.566 0.460 0.461 0.591 0.574

18.1 17.2 16.5 15.4 15.4 16.7 16.6

24.8 21.3 18.8 15.3 15.3 19.5 19.2

3.4 3.9 4.4 5.4 5.4 4.2 4.4

0.53 0.463 – 0.520 0.498 0.491 –

16.1 15.4 – 16.0 15.8 15.7 –

17.5 15.3 – 17.1 16.5 16.2 –

4.7 5.4 – 4.8 5.0 5.1 –

0.322 0.394 0.457

13.7 14.6 15.4

10.8 13.0 15.3

7.8 6.4 5.5

3

3

*

20

0.8

DMSO

19

0.7 18

Formamide

(nm)

Glycerol

coil

0.5

R

[η ] (dl/g)

0.6

DMSO

17

Glycerol

Formamide

16 15

0.4 14

0.3

Ethanol

13

Ethanol

20°C

20°C 12

0.2 0

20

40

60

80

100

cosolvent v/v%

0

20

40

60

80

100

cosolvent mole%

Fig. 2. Dependence of dextran T500 intrinsic viscosity, [g], on the content (v/v%) of polar organic solvent (glycerol, formamide, dimethylsulfoxide, or ethanol) in aqueous solvent mixtures at 20 °C.

Fig. 3. Dependence of dextran T500 coil radius, Rcoil, on polar organic solvent (glycerol, formamide, dimethylsulfoxide, or ethanol) content (mol%) in aqueous solvent mixtures at 20 °C.

linearly, depending on the organic solvent added in the aqueous solution. More specifically, the dextran T500 coils expand from 15.7 nm in water to 17.4 and 16.3 nm with addition of formamide (up to 100 v/v%) and glycerol (up to 25 v/v%), respectively. These are cases where the quality of the mixed solvent increases with cosolvent content. Higher Rcoil values indicate more expanded coils and consequently smaller C* (from 5.1 in plain water to 3.7 in 100 v/v% formamide and 4.6 g/dl in 25 v/v% glycerol). Addition of formamide expands the dextran coil linearly over the 0–100 v/v% formamide range. Glycerol is a rather viscous solvent (dextran dissolved very slowly in pure glycerol) and that is why we examined mixed solvents containing only up to 25 v/v% glycerol. An assessment of solvent quality by comparing the dextran dimensions at 25 v/v% cosolvent shows the aqueous glycerol mixture to be a better solvent for dextran

compared to aqueous formamide mixture. The Rcoil versus mole% content plot (Fig. 3) shows steeper slopes than a Rcoil versus v/v% plot. In order to achieve a 5% increase of the dextran Rcoil from its value in 100% water solutions we need to add approximately either 11 mol% (33% v/v%) glycerol or 23 mol% (42 v/v%) formamide. Glycerol as a cosolvent increases the solvent quality of water more than formamide. A non-linear trend is observed in DMSO–water mixtures. The solvent power remains roughly constant up to approximately 50 v/v% DMSO in the mixture, as reflected in a small variation in the dextran coil radius. Above 50 v/v% DMSO, the dextran T500 coils expand to Rcoil values (18.5 nm) that are much higher than those in pure water or formamide, thus the solvent quality increases significantly. From Figs. 2 and 3 we see that 35 mol% (68 v/v%) DMSO needs to be added to an aqueous dextran solution

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in order to achieve a 5% increase in Rcoil. Recall that we need 23 and 11 mol% of formamide and glycerol, respectively, to effect the same change. The addition of ethanol (a bad solvent for dextran according to v12 > 0.5 and DG121 < 0 (Table 1)) had the opposite effect on Rcoil from the cosolvents examined above (good solvents). The dextran coils contract considerably when up to 30 v/v% ethanol is added to water: Rcoil decreases from 15.7 to 13.1 nm. 4.5 mol% ethanol is enough to decrease the dextran Rcoil by 5%. Correspondingly ethanol decreases significantly the solvent power of water. Our experiments indicated that dextran did not dissolve in aqueous mixtures containing more than 35 v/v% ethanol, presumably because the ethanol–water mixed solvent becomes a non-solvent for dextran at these conditions. The effect of water and ethanol when added to formamide solutions of dextran is depicted in Fig. 4. The formamide solvent quality, as reflected in Rcoil, decreased upon water addition; ethanol addition decreased the quality of formamide even more than water. Water is not as good a solvent as formamide for dextran, and ethanol is a non-solvent, consistent with expectations from the v12 and DG121 data. No significant difference in the relative Rcoil change has been observed when plotting the data versus volume or mole%. We now turn our attention to the effects of temperature on dextran conformation. With increasing temperature the dextran coils contract ([g] and Rcoil decrease, and C* increases) in all the mixed solvent systems examined. The same has been observed for dextran in single solvents [16,18]. A 20 °C temperature increase has a rather small effect on the dextran T500 coil dimensions: a change of the Vcoil up to 10% was observed (Table 2). From a comparison of the Rcoil and [g] values at 20° and 40 °C (Table 2) we observe that the temperature increase affected the dextran coil dimensions in different ways, depending on the mixed solvent that dextran was dissolved into. In aqueous mixtures of formamide, heating had the same effect on the dextran Rcoil over the whole range of compositions examined. The dextran coils in aqueous DMSO mixtures of up to 50 v/v% DMSO content were not affected by the temperature change. Above 50 v/v% DMSO, the temperature

20 19

R

coil

(nm)

18 17

Water

16

Ethanol

15 14 13

20°C 12 0%

20%

40 %

60%

80%

change had an effect on Rcoil comparable to that in formamide solutions. In aqueous ethanol mixtures we observe that the effects of temperature on dextran dimensions diminish as the ethanol content increases. Overall, the solvent effect that we observe on the coil dimensions of dextran T500 is more significant (resulting up to 33% Vcoil change in reference to the dextran Vcoil in pure water) than the temperature effect. 4. Discussion It is important to rationalize in terms of interactions between solvent molecules and polymer segments the changes in the dextran coil dimensions in mixed solvents when the solvent composition and temperature vary. In Section 4.1.1 we look into the molecular structure of each of the mixed solvent systems examined in this work, and we consider how the hydrogen bonding structure of water is affected by the addition of organic solvents (glycerol, formamide, DMSO, ethanol). In the same section, we assess qualitatively the conformation of dextran in each mixed solvent system and we support the findings quantitatively by invoking the number of H-bonding sites available per unit volume. In Section 4.1.2 we examine possible correlations of the coil dimensions of dextran to properties of the mixed solvent system like surface tension and fractional solubility parameters. Finally, in Section 4.2 we discuss effects of temperature. 4.1. Solvent effects 4.1.1. Molecular structure In assessing the solvation of solutes (in this case dextran) in mixed solvents, the mutual interactions of the solvents have to be taken into account. It is therefore of interest to consider the properties of the solvent mixtures, first in the absence of any solutes and then in their presence. Water, ethanol, glycerol, and formamide are all protic, hydrogen bond donor (donor groups: –O–H or >N–H) strongly associated solvents [32,33]. Dimethylsulfoxide is an aprotic, highly dipolar H-bond acceptor solvent (acceptor group: S@O). 4.1.1.1. Formamide–water mixtures. The intermolecular structure of the formamide–water mixture has been discussed in terms of H-bond network properties. Formamide forms hydrogen bonds with water and can thus be classified as a hydrophilic ‘‘structure breaking” solute. Formamide–formamide hydrogen bonding is stronger than formamide–water bonding, which, in turn, is stronger than water–water bonding [34]. This suggests that formamidelike structure is prevalent in the water–formamide mixture over the whole range of concentrations. Water–formamide mixtures can be regarded as ideal solutions in that the local composition of the solvent shells shows a random component arrangement [34].

100%

cosolvent v/v% Fig. 4. Dependence of the dextran T500 coil radius, Rcoil, on the cosolvent (water or ethanol) content (vol.%) in formamide mixtures.

4.1.1.2. Glycerol–water mixtures. The solution structure of glycerol depends on the strong hydrogen-bonding of neighboring molecules. Since each glycerol molecule has

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effectively three donor and three acceptor sites there is a high probability that all molecules are interlinked by a number of hydrogen bonds. Glycerol interacts favorably with water and strengthens the H-bond network of the mixed solvent. In mixtures with high water content (<0.15 M fraction or <40 v/v% glycerol), the average number of H-bonds/water from first hydration shell interactions increases compared to bulk water [35]. At around molar fraction xglyc  0.15, the bulk water pool is depleted and the H-bonding in the first hydration shell is disrupted. Above xglyc  0.22 (50 v/v%) the total number of H-bonds per water molecule decreases, and glycerol–glycerol interactions dominate in the solvation shell over glycerol–water interactions [35]. 4.1.1.3. DMSO–water mixtures. Dimethyl sulfoxide, (CH3)2SO, is an aprotic dipolar solvent that finds biological applications as a protein cryoprotector and as a drug carrier across membranes [36]. A powerful base and hydrogen-bond acceptor, it strongly interacts with hydrogenbond donors like water [32,33]. The partial negative charge on the DMSO oxygen atom favors hydrogen bond formation with water (one DMSO molecule can form four hydrogen bonds simultaneously with neighboring molecules), giving rise to a strongly non-ideal behavior [37]. This non-ideality is reflected in positive deviations of the viscosity and density as well as negative deviations of the heats of mixing (exothermic reaction), which reach a maximum at 60–70 vol.% or 30–40 mol% of DMSO in water [36]. The solvated DMSO is hydrogen bonded to two water molecules, with bonds that are longer lived compared to water–water hydrogen bonds. The nearest neighbor tetrahedral structure of water is preserved in the mixture with DMSO. 1DMSO–2water complexes predominate over 2DMSO–1water complexes for water-rich mixtures (water mole fractions >0.5 or volume fractions >0.2), whereas the opposite is true for DMSO-rich mixtures. The water–water bonds are depleted as the DMSO H-bonding sites replace the water hydrogens with increasing concentration [36]. 4.1.1.4. Ethanol–water mixtures. The ethanol–water system is known to exhibit non-ideal behavior in properties such as partial molar volumes and adiabatic compressibility [38] that are structural in origin. When ethanol is added to water (dilute region, below 0.18 M fraction or 42 v/v% ethanol), clusters form between ethanol and water molecules, and the arrangement of water molecules becomes much more ordered. The hydrogen bonds of water exhibit a maximum strength at molar fraction xeth  0.08, and remain nearly constant up to xeth  0.2. The hydration shells around ethanol become more rigid when two or more ethanol molecules are close together compared to when ethanol molecules are independently surrounded by water [39]. In the 0.1 < xeth < 0.18 region, water molecules with locally enhanced structures are orientationally ordered around an ethanol molecule but do not form rigid cages [39]. The behavior of the excess partial molar quantities in the concentrated region of 0.18 < xeth < 1.0 is very different (ethanol molecules now form chainlike clusters as in pure ethanol) than that in the region of 0 < xeth < 0.18 (where the water structure was maintained) [39]. This is

329

evidence that ethanol–water mixtures, while macroscopically homogeneous, are not homogeneous at a microscopic level. 4.1.1.5. Dextran in mixed solvents. Using the literature information on water-polar organic solvent molecular interactions summarized above, we attempt here to rationalize the solvation behavior of dextran in the mixed solvents studied. The dextran coil radius increases linearly when glycerol is added to the aqueous solution (Fig. 3). Glycerol–water mixed solvents have more readily available H-bonding sites to offer compared to the H-bonding sites available in pure water, since the lifetime of the H-bonds in pure water is longer than the lifetime of the H-bonds among glycerol–glycerol or glycerol–water molecules [40]. So upon glycerol addition the dextran dimensions expand more in the less dense H-bonded network. A similar behavior is observed with formamide addition. Water H-bonds are replaced by water–formamide and formamide–formamide H-bonds which, even though are stronger than the water–water ones [34], interact more readily with the dextran H-bonding sites because the H-bonds between the formamide molecules have the shortest lifetimes [41]. Dextran coils dissolve better in formamide than in water [18] probably because the formamide–formamide H-bond life time is shorter than the water–water H-bond lifetime. The non-linear increase of the dextran coil radius in DMSO + water can be interpreted in terms of non-ideal mixing. The dextran conformation in DMSO–water mixtures can be described as follows: Dextran is initially faced with the dense hydrogen-bonded water network. Addition of DMSO results in 1DMSO–2H2O complexes which are Hbonded with bonds that are longer lived than the water– water ones, while the first molecular coordination shells in bulk water become more structured with the increase of DMSO (main difference between the formamide–water and DMSO–water mixed solvents). Dextran continues to face a strongly H-bonded network, so it keeps its conformation unchanged or slightly contracts. Upon further (>60 v/v%) DMSO addition, 2DMSO–1H2O complexes predominate, so dextran can H-bond with DMSO molecules more easily. Dextran, a hydrogen bond donor, interacts more readily with excess DMSO, a hydrogen-bond acceptor, than with water, a donor, thus [g] and Rcoil increase. In the binary solvent mixtures discussed above, both components were good solvents for dextran. When ethanol (bad solvent) is added to water (good solvent), coil contraction is observed, indicating that the aqueous solvent becomes worse. In the region up to 26 v/v% ethanol in water, a structural enhancement of the hydrogen bonded aqueous network occurs, which is more difficult for dextran to break. In the more concentrated regime (>26 v/v%) the ethanol molecules form chainlike clusters [39] as those in pure ethanol. We observed that dextran does not dissolve in aqueous mixtures containing more than 35 v/v% ethanol. This reflects the dominance in these mixtures of the non-solvent nature of ethanol. 4.1.1.6. Dextran–mixed solvent interactions. On the basis of the (qualitative) discussion above, we can argue that the coil dimension changes observed in the different solvent

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mixtures are consistent with expectations from water– cosolvent–dextran interaction, especially as they pertain to hydrogen bonding. In order to support the above findings quantitatively, we estimated the H-bonding density, i.e., the number of H-bonding sites available per solvent unit volume (nm3) (Table 3), using the H-bonding density of the individual solvents, the volume compositions of the mixed solvents, and assuming volume additivity. We attempt to rationalize the dextran solvation in the mixed solvents examined here by employing the dependence of the coil dimensions on the cosolvent content (mol%) and the number of H-bonding sites available to hydrogen-bond in the solution. We note that the coil radius versus cosolvent mole fraction content plots (Fig. 3) show steeper (up or down) slopes than those plotted versus cosolvent volume fraction. Such a comparison may help decouple volume effects from the effect of molecules in terms of the number of H-bonds. Water has a very small molecular volume (18 cm3/mol). Per unit volume (1 nm3), water has approximately 67 Hbonding groups (H and OH), double the number of H-bonds per unit volume of the other solvents that we used (Table 3). This reflects the dense H-bonded network of water. Upon addition of glycerol, formamide, DMSO or ethanol, the number of H-bonding sites per unit volume would change according to the volume change and the number of H-bonding groups that each solvent has to offer. For the glycerol, formamide and DMSO cosolvent cases, we found (using the data of Table 2) that 33, 40, and 69 v/ v%, respectively, would need to be added to aqueous dextran solutions in order to achieve a 5% Rcoil change. The number of H-bonds per nm3 was 53, 52, and 44 for the aqueous glycerol (33 v/v%), formamide (40 v/v%), and DMSO (69 v/v%) mixed solvents, respectively. Glycerol and formamide offer a similar number of H-bonding sites per nm3 (recall that both are protic H-bond donors). DMSO, as a H-bond acceptor, apparently interacts more efficiently (at a 15% lower HB density) with dextran which is a H-bond donor. Ethanol had a more pronounced effect on the aqueous solvent, causing a 5% decrease in Rcoil upon only a 10 v/v% addition. We know that ethanol can further enhance the very dense H-bonded network of water. So a small decrease of the number of the H-bonding sites per nm3 from 66 in pure water to 58 in 15 v/v% ethanol is sufficient for a 5% Rcoil decrease. It emerges from the above discussion that the solvent H-bond densities which contribute to a certain Rcoil change are approximately the same for mixtures of good solvents for dextran. The H-bonding density being a function of the solvent volume, it would seem appropriate to also consider the number of H-bonds needed to effect a certain change of

the polymer coil volume. Eleven and 30 v/v% glycerol and formamide aqueous mixtures cause a 5% change in Vcoil from its value in water, contributing approximately 62 and 56 H-bonds per nm3, respectively. 65% DMSO in water contributes 45 H-bonds/nm3 (reflecting the impact of electron donicity as discussed above). Similarly to the Rcoil case, the H-bond densities that contribute to a 5% Vcoil change are approximately the same for mixtures of good solvents for dextran. On the basis of the above discussion, we can argue that the H-bonding density can be a useful indicator of dextran solvation in single or mixed good solvents for dextran. Hydrogen bonding interactions appear to be important for the interpretation of the experimental findings. In order to validate the significance of this observation, we consider next solvent interaction properties. 4.1.2. Dextran structure – solvent property correlations In solvent mixtures, solute molecules may be preferentially solvated by a certain component of the mixture. Therefore, the use of mixed solvents entails knowledge of their properties as a function of the composition. Some physical, chemical and thermodynamic properties of certain mixed solvents have been measured [33], and equations have been generated to estimate solvent properties in terms of composition [5]. In order to rationalize the solubility of dextran in mixed solvents, we use here solvent properties such as surface tension and Hansen solubility parameters, and examine their relationship to dextran solution properties. 4.1.2.1. Surface tension. The surface tension, r, expresses the energy per unit area of the surface of a liquid relative to vacuum, in principle, or relative to air saturated with the vapors, in practice [33]. We previously found that dextran coil dimension changes correlate to the surface tension values of the (single) solvents where dextran is dissolved [18]. We thus decided to examine if such a correlation between [g] (and Rcoil) and r exists also in the case of binary solvent mixtures. According to Marcus [5], for aqueous mixtures at 25 °C, the dependence of r on the cosolvent composition is given as r = 71.8(1  x) + rcosolventx + x(1  x)f(x) mN m1, where in general f(x) = r0/[1  r1(1x)], except in some cases (which include aqueous mixtures of ethanol and DMSO, of interest here) where f(x) = r0 + r1(1  2x) + r2(12x)2 + r3(1  2x)3, with x being the cosolvent mole fraction, and r0, r1, r2, r3 fitting parameters specific for each cosolvent (provided in [5]). Fig. 5 shows the dextran [g] plotted versus the surface tension of the aqueous mixed solvent systems studied here, calculated with the above method.

Table 3 Molecular volume, number of hydrogen bonds (HB) per molecule, and number of HB per unit volume (nm3) of the single solvents used in this study. Solvent

Vm 103 nm3/molecule

# of HB/molecule

# of HB/nm3

Dimethylsulfoxide Formamide Glycerol Ethanol Water

118 66 122 97 30

4 2 3 1 2

33.79 30.27 24.65 10.30 66.92

(S@O) (CO, NH3) (OH) (OH) (H, OH)

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The [g] and Rcoil of dextran increase while r decreases for solvents like formamide, glycerol and DMSO that enhanced the solvent quality of water. In cases where the solvent power of water decreased, i.e., upon addition of ethanol, [g] and Rcoil decreased when surface tension decreased. Recall that surface tension describes cohesive forces between the solvent molecules. For the first case it is possible that the weaker the cohesive forces between the solvent molecules, the easier for dextran to break them and form hydrogen bonds with the solvent. The slope observed in Fig. 5 is the same with that observed previously in the case of dextran dissolved in single solvents [18]. For the case of aqueous ethanol mixtures that do not follow the same monotonic relationship as the other solvent mixtures, dextran coils do not expand probably because the ethanol molecules enhance the water structure around the polymer coil. Having established a connection between dextran solution conformation and cohesive energies (manifested in r) of the mixed solvents considered in this work, we will now test how our data correlate to the solvent Hansen solubility parameters, which also express cohesive forces. 4.1.2.2. Fractional solubility parameters. According to Hansen [21], the Hildebrand solubility parameter of a given (single) solvent, d, can be ascribed to three distinct contributions: dD due to dispersion forces, dP due to polar dipole– dipole forces, and dH due to hydrogen bonding. The solubility behavior is determined by the relative amounts of the three component forces (dispersion, polar, and hydrogen bonding) that contribute to the total d value. d is related to the three contributions through Eq. (6):

d2 ¼ d2D þ d2P þ d2H

ð6Þ

In order to capture the solubility behavior of polymers in the mixed solvents of interest here, we employed the fractional solubility parameters (FSPs), fD, fP, fH, that have been used in, e.g., the coating industry to describe the miscibility regime of hydrocarbons and ethanol [21]. The FSPs, also called Teas parameters, are obtained from the HSPs normalized by the sum of the three parameters (Eq. (7)).

[η ] (dl/g)

0.9 0.8

DMSO

0.7

85% DMSO

Formamide

70% DMSO

0.6 0.5

50% DMSO

0.4 0.3 0.2 30

85% Formamide 70% Formamide 50% Formamide 25% Glycerol 25% Formamide 15, 20% Glycerol Water 25% DMSO

15% Ethanol 25% Ethanol 30% Ethanol

40

50

60

70

80

σ Fig. 5. Intrinsic viscosity, [g] of dextran T500 plotted versus the surface tension, r, of the single and mixed solvents at 20 °C. The dotted line is a linear fit to the data indicated by the filled symbols.

fD ¼ 100dD =ðdD þ dP þ dH Þ fP ¼ 100dP =ðdD þ dP þ dH Þ

ð7Þ

fH ¼ 100dH =ðdD þ dP þ dH Þ The sum of fD, fP, and fH is 100. The fractional solubility parameters of mixed solvents are determined by calculating the volume-wise contributions of the solubility parameters of the individual components of the mixture (reported in Table 4). The Teas graph of the FSPs of the aqueous formamide, glycerol, DMSO and ethanol mixed solvents is shown in Fig. 6. A benefit of such a ternary diagram is that all three parameters are presented onto a two-dimensional plot, something that permits us to observe and evaluate the relative positions of the FSPs of the solvent mixtures compared to the FSPs of dextran. In general, polymers dissolve in solvents that have similar solubility parameters to the polymer [21]. We can see in Fig. 6 that the FSP values of formamide and DMSO and their mixtures with water are rather close to those of dextran and away from those of ethanol. In the same diagram, the FSPs of the aqueous glycerol mixed solvents with increasing glycerol content moved towards the FSP values for pure ethanol, which are away from those for dextran. The FSP values of water and its mixtures with ethanol are also rather different than those of dextran. We can identify in Fig. 6 a range of FSP values where good solvents for dextran can be found. The location of this range with respect to the apexes of the ternary diagram points to the higher relative importance in dextran solubility of the hydrogen bonding, fH, and the polar, fP, fractional solubility parameters over the dispersion parameter, fD. The solvent systems that fall outside this range are the relatively bad solvents (e.g., ethanol) for dextran. We note that Fig. 6 compares only the FSPs of the solvent mixtures to those of dextran. The possible impact of the solvent FSPs to the dextran Rcoil can be revealed when the coil radius of dextran is plotted as a function of the fractional solubility parameters of each of the different mixed solvent systems used in this work (Figs. 7 and 8). Rcoil changes while the mixed solvent FSPs change toward the cosolvent FSPs, with the addition of the good solvents, glycerol, formamide, or DMSO, or the bad solvent, ethanol. In water–formamide mixtures, when the formamide content increased, the dextran Rcoil increased as fD and fP increased and as fH decreased, approaching the pure formamide FSP values (Fig. 7(a)). In the case of aqueous glycerol solvents (Fig. 7(b)), Rcoil increased when fD increased and fH decreased towards the glycerol FSP values

Table 4 Hildebrand (d) and Hansen (dD, dP and dH) solubility parameters of the single solvents and polymer used in this study. Solvent

d

dD

dP

dH

Dimethylsulfoxide Formamide Glycerol Ethanol Water Dextran

26.7 36.7 36.2 26.5 47.8 38.6

18.4 17.2 17.4 15.8 15.5 24.3

16.4 26.2 12.1 8.8 16.0 19.9

10.2 19.0 29.3 19.4 42.3 22.5

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(represented by the dashed lines). In the DMSO aqueous mixed solvents, the dextran coil remained effectively unchanged up to 50% DMSO (Fig. 7(c)). The Rcoil started increasing with fD and fP increase and fH decrease above 60 vol.% DMSO. The Rcoil increase with fH decrease and fP increase can be attributed to a decrease in the cohesive forces due to H-bonding and polar forces. fH and fP appear relatively more important than fD. Addition of ethanol (bad solvent) to water caused the Rcoil of dextran to decrease while the fH values decreased and the fD values increased towards the FSP values of pure ethanol (Fig. 7d)). It is instructive to plot the variation of dextran Rcoil against each of the three FSP properties for all the mixed solvent systems that we considered in the same figure (Fig. 8). For the majority of the solvent systems the dextran Rcoil increases as the fD and fP values increase, and as the fH values decrease. The polar solubility parameter, dP, from which fP has been calculated, is a function of dipole moment [21]. It appears that the higher the dipole moment of the solvent molecules, the stronger the interactions between dextran and solvents, consequently, the dextran coils expand. fH, on the other hand, expresses cohesive forces, similarly to dH and r [18]. Lower fH values indicate

fP

0

100

10

90

20

80

30

70

40

60

50

50 100% Formamide

60

40 100% DMSO

70 80

30 100% Water

100% Ethanol 100% Glycerol

20

90

10

100

fH

0

0

10

20

30

40

50

60

70

80

90

100

fD

Fig. 6. Teas graph of the fractional solubility parameters (FSP) fD, fP, and fH of mixtures of water with the polar organic solvents glycerol (D), formamide (h), DMSO (s) or ethanol (e). The FSPs of dextran are represented with an asterisk. The solid line encloses the range of FSPs where solvent mixtures are good solvents for dextran.

(a)

(b)

20 19

19

18

18 100% Formamide 85% Formamide 50% Formamide coil

17

25% Formamide 100% Water

25% Glycerol 15% Glycerol 100% Water

16

R

R

coil

17 16

20

15

15 f

f

14

14

D

f

f

P

13

13

f

f

H

12 10

20

30

40

50

10

60

20

30

40

50

f

D

19

f

100% DMSO

18

coil

17

100% Water 25% DMSO

f

H

70% DMSO

16

100% Water

15

15% EtOH

14

25% EtOH

R

coil

P

18

85% DMSO

17

R

60

(d) 20

19

15

H

f

20

16

P

12

f

(c)

D

50% DMSO

f

14

D

f

P

13

f

13

H

12 10

20

30

40

f

50

60

12 10

30% EtOH

20

30

40

50

60

f

Fig. 7. Rcoil of dextran T500 at 20 °C plotted versus the (+) dispersion, fD, (e) polar, fP, and (d) hydrogen bonding, fH, fractional solubility parameters of binary mixtures of water with the polar organic solvents (a) formamide, (b) glycerol, (c) dimethylsulfoxide, and (d) ethanol. The dashed lines in plots (b) and (d) indicate the fP, fD, and fH values (in order of appearance) of pure glycerol and ethanol, respectively.

E. Antoniou, P. Alexandridis / European Polymer Journal 46 (2010) 324–335

(a) 20 19 DMSO

R

coil

(nm)

18 17 16

85% DMSO Formamide 85% Formamide 70% Formamide 70% DMSO 50% Formamide 25% Glycerol 15, 20% Glycerol 25% Form Ethylene glycol Water 25% DMSO 50% DMSO

15

15% Ethanol

14

25% Ethanol 30% Ethanol

13

y = 13.954 + 0.093559x R= 0.65566

12 10

20

30

f

40

50

60

D

(b) 20 19 DMSO 85% DMSO

17

15

15% Ethanol

14

25% Ethanol

13

25% Formamide 25% DMSO

16

Formamide 85% Formamide 70% Formamide 50% Formamide

70% DMSO 25% Glycerol 15, 20% Glycerol Ethylene glycol Water

50% DMSO

R

coil

(nm)

18

30% Ethanol

y = 13.911 + 0.09033x R= 0.76664

12 10

20

30

f

40

50

60

4.2. Temperature effects

19 DMSO

18

coil

(nm)

85% DMSO

R

express cohesive forces, but it is reassuring since the HSP and r data originate from different sources and methods. The Rcoil data of the water–ethanol mixed solvents do not follow the monotonic dependence on FSPs followed by the rest of the mixed solvents studied in this work. Recall that dextran does not dissolve in ethanol since v12 > 0.5 and DG121 < 0, and the water solvent quality decreased with ethanol addition. The fact that data for water–ethanol solvent systems fall out of these trends, suggests that hydrogen bonding is not sufficient to interpret interactions in such systems (possibly due to the hydrophobic/associating nature of ethanol). In Fig. 8 we identify correlations between Rcoil and FSPs (fD, fP, and fH), with the dependence of Rcoil on fH emerging as the more pronounced (attesting to the importance of hydrogen bonding interactions between dextran and the mixed solvents). A correlation between Rcoil and the hydrogen bonding solubility parameter dH was established in previous work on dextran in the single solvents water, ethylene glycol, formamide, DMSO, or ethanolamine [18], which is similar to the correlation between Rcoil and fH discussed above. At the same time, in single solvents there was no clear relation between Rcoil and the polar HSP, dP, and the Rcoil variation was not connected to any significant change in the solvent dispersion solubility parameter, dD, whereas in the mixed solvents there is some correlation between Rcoil and fP or fD.

P

(c) 20

17

Formamide 85% Formamide

70% DMSO

70% Formamide 50% Formamide 25% Glycerol 25% Formamide 15%, 20% Glycerol Ethylene glycol Water 50% DMSO 25% DMSO

16 15

15% Ethanol

14

25% Ethanol 30% Ethanol

13 y = 19.252 - 0.062903x R= 0.84168

12 10

333

20

30

f

40

50

60

H

Fig. 8. Rcoil of dextran T500 plotted versus (a) dispersion, fD, (b) polarity, fP, and (c) hydrogen bonding, fH, fractional solubility parameters of single and mixed solvents at 20 °C. The dotted lines are linear fits to all the data in each plot other than those of mixtures of water with ethanol.

weaker cohesive forces between the solvent molecules. Dextran therefore can break more easily these forces and form hydrogen bonds with the solvent molecules. We fitted the data of Fig. 8 linearly to identify a possible correlation for the case of mixed solvents for which both components are good solvents for dextran. Rcoil showed a dependence on each FSP, fD, fP, and fH. The more significant dependence, however, is noticed between Rcoil and fH, as attested by the higher correlation factor, R = 0.84 for the Rcoil versus fH plot, compared to R = 0.77 for fP and R = 0.66 for fD. The same dependence of Rcoil to fH is observed in Fig. 5 (where [g] is plotted versus r). This observation is not unexpected, since both parameters

Temperature effects are of general interest in polymer and colloidal systems. In this work we have an additional interest on temperature effects in order to validate the conclusion from the previous section that hydrogen bonding is an important interaction in the dextran-mixed solvent systems. Thus the effects of temperature on the polymer phase behavior and hydrogen bond interactions in the solvents are discussed here as they relate to the dextran coil dimensions. Dextran has been previously studied in single solvents such as water, ethylene glycol, formamide, and DMSO, and in all cases the solutions moved towards theta conditions upon temperature increase [18,22]. This reflects low critical solution temperature (LCST) behavior. Phase separation commences at the theta-point, characterized by the theta temperature, h. LCST polymers contract as temperature increases [42], and at the theta temperature the coils reach their unperturbed dimensions, where the polymer coil conformation is only due to its own molecular conformational constraints (not swollen by the presence of a solvent) [26]. Studies on water and organic solvents like formamide or glycerol [43–45] indicate that the structure of the solvent is not affected significantly by temperature, rather the hydrogen bonding stability is influenced (i.e., it decreases with temperature increase). In water the stability of the hydrogen bonds decreases with increasing temperature from 0 to 400 °C (at 300–400 °C they have disappeared completely) due to the increasing influence of the entropy loss associated with the formation of bonds [45,46]. In liquid formamide the number of hydrogen bonds is not

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significantly affected when temperature changes from 10° to 64 °C. The N. . .O distance decreases with increasing temperature; at low temperature (10 °C), the N, H, and O atoms of the hydrogen bond (N–H. . .O) are lined up, but, as the temperature increases, this hydrogen bond bends, causing a stronger and denser network [43]. We found in this study the dextran coil volume (reported in Table 2) to decrease when the temperature increases from 20° to 40 °C, with the aqueous formamide mixed solvent system being more affected (8–12%), and the aqueous ethanol and DMSO mixtures less (0 and 8% respectively), indicating that the solvent power of the aqueous mixed solvents decreases. Considering that hydrogen bonding is an important interaction between dextran and the solvent molecules, and that temperature increases weaken hydrogen bonding [43–45], it is reasonable that the dextran coil dimensions will be affected by the temperature increase. So the observed contraction of the dextran coils upon heating can be attributed to a decrease of the hydrogen bonds between the dextran and solvent molecules [15,18] and a relative increase of the interactions between the polymer segments. The dextran-mixed solvent systems move towards theta conditions with increasing temperature (coils contract), indicative of LCST behavior. We note that the dextran Vcoil in aqueous ethanol mixtures did not change significantly upon heating, which means that, regardless of the temperature effect on the H-bonded network stability of these mixtures, the dextran conformation was not affected. Recall that Rcoil data for water–ethanol mixtures are outliers from the correlations in Fig. 8, consistent with the observation that temperature (and its impact on hydrogen bonding) has little effect on the dextran coil dimensions. The polymer segments adopt a less expanded conformation in the solution (Rcoil decrease) and thus the intermolecular association within polymer segments is enhanced at higher temperatures. The solvent property correlations presented in the previous section and the temperature effects discussed above support hydrogen bonding as a main interaction between dextran and solvent molecules.

tension and the fractional solubility parameters of the solvent mixture. [g] and Rcoil increase while r decreases for the solvents formamide, glycerol, and DMSO that enhanced the solvent quality of water. Similar correlations exist between Rcoil and the hydrogen bonding, polar and dispersion components of the fractional solubility parameters of the solvent mixtures, with the stronger correlation being noticed between Rcoil and the hydrogen bonding fractional solubility parameter, fH. This observation is not unexpected, since both r and solubility parameters reflect cohesive forces. The lower the r and fH values, the weaker the cohesive forces between the solvent molecules, and the easier for dextran to break them and form hydrogen bonds with the solvent molecules, leading to [g] and Rcoil increase. Upon heating, the polymer segments adopt a less expanded conformation in the solution. This can be connected to the decreased H-bonding ability of the solvent molecules, resulting in enhanced intermolecular association between polymer segments. The temperature effect that we observe is not as significant as the solvent effect on the coil conformation of dextran. The coil dimension changes observed in the different solvent mixtures and upon varying the temperature are consistent with expectations from water–cosolvent–dextran interactions, especially as they pertain to hydrogen bonding. The same conclusion has been drawn also in the case of dextran dissolved in single solvents. In fact, we found the H-bonding density to be a useful indicator of dextran solvation in single or mixed good solvents. Hydrogen bonding thus emerges as an important interaction between dextran and its solvents. This is the first time that the conformation of dextran in mixed solvent systems has been reported. Mixed-solvent properties were successfully used to establish structure– property relationships. The findings reported here can be generalized to the solution behavior of other polysaccharides in single or mixed solvents, and facilitate polymer structure tuning with mixed solvents, and solvent selection or substitution. Acknowledgements

5. Conclusions The conformation of the common polysaccharide dextran has been investigated in mixed solvents at two different temperatures using viscosity measurements. Binary mixtures of water with each of the polar organic solvents glycerol, formamide, dimethylsulfoxide, and ethanol have been considered. The intrinsic viscosity of dextran T500 in the different systems has been experimentally determined and the coil radius calculated. The dextran coil radius increases linearly when the good solvent glycerol or formamide is added to the aqueous dextran system. A non-linear trend is observed for the dextran coil radius in DMSO–water mixtures, reflecting the DMSO–water mixing non-idealities (DMSO is a good solvent for dextran). Addition of ethanol (bad solvent for dextran) to water caused a significant decrease in Rcoil. The solvent effects, as manifested in the dextran intrinsic viscosity and coil radius, have been correlated to the surface

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