Journal of Molecular Liquids 143 (2008) 75–80

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Journal of Molecular Liquids

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Thermodynamic studies on the interactions of phenyl salicylate in protic solvents atdifferent temperatures

Muhammad Javed Iqbal ⁎, Mansoora Ahmed ChaudhryDepartment of Chemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan

⁎ Corresponding author. Tel.: +92 51 90642143; fax: +E-mail address: mjiqauchem@yahoo.com (M.J. Iqbal)

0167-7322/$ – see front matter © 2008 Elsevier B.V. Aldoi:10.1016/j.molliq.2008.05.014

A B S T R A C T

A R T I C L E I N F O

Article history:

Phenyl salicylate (PS) is emp Received 23 February 2008Received in revised form 15 May 2008Accepted 28 May 2008Available online 6 June 2008

Keywords:Phenyl salicylatePartial molar volumeActivation parametersViscosity B-coefficient

loyed as a nervous system depressant as well as an intestinal antiseptic owing toits antibacterial activity upon hydrolysis in the small intestine. The study of changes in its physico-chemicalproperties in different solvents may be helpful in understanding the mechanism of the drug action atphysiological body temperatures. The partial molar quantities, namely, apparent molar volume (Vϕ), partialmolar volume (Vm°), thermal expansion coefficient (α2) and partial molar expansivity (E20) of phenyl salicylatein various protic solvents (i.e. methanol, ethanol, 1-propanol, 2-propanol, 1-butanol and 2-butanol atT=293.15 K–313.15 K have been determined. The density and viscosity data in a molality range of 9.4×10−3–3.1×10−2 mol/kg are obtained with the help of commercially available vibrating tube densimeter andviscometer, respectively. The variation in the volumetric parameters resulting due to changes in temperatureand the nature of solvents are explained on the basis of the drug–solvent hydrogen bonding, dielectricconstant and dipole moments of the solvents used. The viscosity data is analyzed by the Jones–Dole equationand the derived viscosity B-coefficient is interpreted in terms of drug–solvent interactions. The molar Gibbsfree energy ΔG2

0#, enthalpy ΔH20# and entropy ΔS2

0# of activation for viscous flow in various protic solvents aredetermined using the transition state theory of solutions.

© 2008 Elsevier B.V. All rights reserved.

1. Introduction

Drug-macromolecular interactions are subjects of intensive studiesrelating to the physiological media such as blood and intra- or extra-cellular fluids. The mechanisms of these molecular processes are notyet clearly understood because of difficulty in carrying out directstudies of physiological media. One of the well recognized approachesto the study of the molecular interactions in fluids is the use ofvolumetric properties which are generally regarded as suitableparameters for the interpretation of drug–solvent interactions in thesolution phase. The partial molar volume of solute includes itsstructural volume in a solvent and volume change of the solvent dueto solvation of the solute. Also, it provides some useful informationabout various interactions occurring in solutions.

As a therapeutic class, non-steroidal anti-inflammatory drugs(NSAIDs) exhibit analgesic, anti-inflammatory, antipyretic and plateletinhibitory properties. However, these drugs exhibit serious side effectssuch as gastrointestinal toxicities, gastric mucosal ulcerations andhemorrhage [1]. Study of the volumetric properties of NSAIDs hasbeen the subject of interest because they are the most widelyprescribed medications in the world. The viscometric methods arealso used to investigate the solute–solvent interactions that correlatewith the structure making–breaking property of a drug.

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l rights reserved.

This work is a continuation of the systematic investigation of thevolumetric aspects of biochemical processes involving NSAID drug-macromolecular interactions in various solvents [2,3]. A survey of theliterature on this subject reveals that the volumetric properties ofphenyl salicylate (PS) with the above mentioned solvent systems arenot available and that the viscosity measurements of drugs are notvery common. The main focus of this investigation is on thedetermination of the apparent molar volumes (Vϕ), partial molarvolumes (Vm°), partial molar expansivity (E20), viscosity B-coefficientsand thermal expansion coefficient (α2) using precise density andviscosity data of PS solutions in the protic solvents. In order to obtain acomprehensive volumetric description, various protic solvents, i.e.methanol, ethanol, 1-propanol, 2-propanol, 1-butanol and 2-butanol,in a temperature range of 293.15 K–313.15 K have been employed. Theexpansibility data of PS is believed to be beneficial for the study ofliving systems under different physiological conditions such as feveror hypothermia. The data could be used for describing the so-calledcompactness or packing of solute–solvent molecules in solvatedstructures. Also, the values of the viscosity B-coefficient and thepartial molar volume have been used to obtain the free energies ofactivation for viscous flow, ΔG2

0#, of PS in different solvents using thetransition state theory of solutions. The results are rationalized interms of different types of interactions.

The temperature range of 293.15 K–313.15 K is chosen in order toobtain greater relevance of the present data to the macromolecules incertain biological systems (such as mammals) operating near the

Scheme 1. Structure of phenyl salicylate.

Fig. 1. Apparent molar volume (Vϕ) of phenyl salicylate in methanol as a function ofmolality (m) at T=293.15 K to 313.15 K.

76 M.J. Iqbal, M.A. Chaudhry / Journal of Molecular Liquids 143 (2008) 75–80

physiological temperatures. The purpose of this study is to attempt toclarify the contribution of hydrogen bonding to the partial molarvolume of drug (PS) in various organic solvents.

2. Experimental

2.1. Materials

Phenyl salicylate (99%) of molar mass 214.22 g mol−1 was suppliedby Aldrich. The structural formula of phenyl salicylate was shown inScheme 1. The solvents used were methanol (99.8%, Sigma-Aldrich),ethanol (99.8%, Merck), 1-propanol (99.0%, Fluka), 2-propanol (99.7%,Lab Scan Asia), 1-butanol (99.0% Fluka) and 2-butanol (99.0% Fluka).The measured values of the density of the solvents were comparablewith the literature values (except for ethanol) as shown in Table 1therefore they were used without further purification. Ethanol was,however, subjected to further purification [4], but a sample ofmaximum purity could not be achieved hence the data in ethanolsolutions may not be very reliable. Solutions were prepared by weightin a molality range of 6.9×10−3–3.1×10−2 mol kg−1. The resolution ofthe balance is 10−2 mg and it has an accuracy of ±0.2 mg. The ex-periments were carried out at 293.15, 298.15, 303.15, 308.15, 310.15and 313.15 K.

2.2. Density and viscosity measurement

Density measurements were performed by an automated vibratingtube densimeter (Anton Paar DMA5000) with an uncertaintyof ±1×10−6 g/cm3 which was calibrated with doubly distilled water,toluene and cyclohexane in the temperature range investigated here.The temperature of the densimeter cell was calibrated using a Pt 100thermocouple with a resistance R°=100 Ώ at T=273.15 K, connectedto a multimeter (Keithley 2000). The resolution of the temperaturemeasurements is 0.1 mK. The total uncertainty of the temperaturemeasurements was estimated to be about +540 K at T=293.15 K,

Table 1Comparison of the values of density with the literature [8] data of some standardcompounds (at 293.15 K) and the dielectric constant and dipole moment of the solventsused (at 298.15 K)

Solvents Densityρ/g cm−3

Dielectric constant Dipole moment

Literature [8] Experimental

Water 0.99820 0.99812 78.6 ~Toluene 0.8669 0.86652 ~ ~Cyclohexane 0.7785 0.77875 ~ ~Methanol 0.79170 0.79141 32.7 1.70Ethanol 0.7923 0.79710 24.5 1.691-Propanol 0.8035 0.80404 20.5 1.682-Propanol 0.7855 0.78519 19.3 1.671-Butanol 0.8098 0.80962 17.3 1.662-Butanol 0.80637 0.80726 16.0 1.65

−15,700 K at T=298.15 K, +13700 K at T=303.15 K, − 8130 K atT=308.15 K and +5420 K at T=313.15 K.

The solution viscosities were measured using a commerciallyavailable viscometer (Anton Paar SVM3000) with an accuracy of±0.001 K. Uncertainty of viscosity measurements was ±0.0001 mPa s.

3. Theory and data evaluation

3.1. Density

The density data retrieved for the phenyl salicylate (PS) in theprotic solvents is used for the calculation of the apparent molarvolume (Vϕ), partial molar volume (Vm° ), thermal expansion coefficient(α2) and partial molar expansivity (E20) are given below:

The apparent molar volume, Vϕ is calculated from the density datausing the following equation

V/ ¼ 1000 ρo−ρð Þmρρo

þM2

ρð1Þ

where ρo=density of pure component 1 (solvent) and ρ=densityof solution of molality m of phenyl salicylate having molar mass M2.

Apparent molar volume Vϕ is plotted against the molality (m) indifferent protic solvents i.e. methanol, ethanol, 1-propanol, 2-propanol, 1-butanol and 2-butanol in accordance with the followingequation

V/ ¼ V∘m þ Svmþ Svvm2 þ N ð2Þ

where Sv and Svv are the semi-empirical parameters, whichdepend on solvent, solute and temperature, and Vm° is the partialmolar volume of solute molecule in the specific solvent. Only the firstparameter of this equation i.e. partial molar volume Vm° is consideredto be sufficient to represent the data adequately. The values of Vm° andcorrelation coefficients are estimated by the least-square fitting of theapparent molar volume data in the Eq. (2).

The partial molar expansivity (E20) is then calculated from thevalues of Vm° using the following relation:

E02 ¼ AV∘mAT

� �p

ð3Þ

Table 2Values of the apparent molar volume (Vϕ) for phenyl salicylate in methanol solutions at temperature ranging from T=293.15–313.15 K

T/K m ⁎10−3 (mol/kg−1) ρ (g/cm3) σ ⁎10−6 (cm3/mol) Vϕ (cm3/mol) T/K m ⁎10−3 (mol kg−1) ρ (g/cm3) σ ±10−6 (cm3/mol) Vϕ (cm3/mol)

313.15 0.0 0.775103 310.15 0.0 0.7752039.4 0.775975 2.08 126.60 9.4 0.776095 2.05 123.17

12.6 0.776245 3.00 128.83 12.6 0.776364 1.69 126.3815.7 0.776479 2.05 134.75 15.7 0.776599 2.00 132.7018.8 0.776721 1.08 137.26 18.8 0.776851 1.55 134.6922.0 0.776905 1.50 143.32 22.0 0.777045 1.50 140.3725.1 0.777100 1.00 147.65 25.1 0.777233 1.25 145.5331.4 0.777332 2.55 161.40 31.4 0.777521 2.50 156.81

308.15 0.0 0.777113 303.15 0.0 0.7818679.4 0.778039 3.00 117.44 9.4 0.782801 1.50 114.69

12.6 0.778305 3.05 122.46 12.6 0.783071 1.00 119.9315.7 0.778565 1.52 126.08 15.7 0.783351 2.00 122.0318.8 0.778771 2.08 133.12 18.8 0.783591 1.08 126.8222.0 0.778935 3.00 136.94 22.0 0.783831 1.69 130.2325.1 0.779225 3.50 139.72 25.1 0.784021 2.00 135.9731.4 0.779515 2.08 152.05 31.4 0.784331 2.08 147.95

298.15 0.0 0.786602 293.15 0.0 0.7914159.4 0.787541 2.00 112.45 9.4 0.792381 1.00 108.20

12.6 0.787831 1.69 115.75 12.6 0.792671 1.69 111.3515.7 0.788099 0.00 119.94 15.7 0.792965 2.00 113.8318.8 0.788369 1.08 122.54 18.8 0.793223 1.08 118.4822.0 0.788601 2.50 127.13 22.0 0.793445 1.55 124.3625.1 0.788801 0.00 132.59 25.1 0.793665 2.00 128.3231.4 0.789121 2.08 144.25 31.4 0.794045 2.08 137.76

77M.J. Iqbal, M.A. Chaudhry / Journal of Molecular Liquids 143 (2008) 75–80

Since the changes in the solution structure are very sensitive totemperature variations the value of E20 provides a sensitive criterionfor the detection of solute–solvent interactions.

The partial molar volume Vm° data is used for evaluation of theisobaric thermal expansion coefficient (α2) of the solute using thefollowing equation

α2 ¼ 1V∘m

AV∘mAT

� �¼ E02

V∘mð4Þ

The transfer volume [5], ΔVm° [6] of the solute from solvent I tosolvent II is defined by the following equation

ΔV∘m ¼ V∘m IIð Þ−V∘m Ið Þ ð5Þ

where Vm° (II) is the partial molar volume of the solute in water andVm° (I) is the partial molar volume of the solute in various organicsolvents.

Fig. 2. The transfer volumes of phenyl salicylate from water to alcohols plotted againstdifferent temperatures ranging from T=293.15 K to 313.15 K.

3.2. Viscosity

The concentration dependence [5] of the viscosity of phenylsalicylate solutions in different alcohols can be interpreted in terms ofthe Jones–Dole equation

ηr−1C1=2 ¼ ψ ¼ Aþ BC1=2 ð6Þ

where ηr=η /ηo and η and ηo are viscosities of the solution and solventrespectively. C is the molal concentration. The linear plots for ψ versusC1/2are obtained for phenyl salicylate in all the solvents and viscosityA- and B-coefficients are obtained using the least square method. Asignifies the solute–solute interaction and B accounts for thecontribution arising from size of the solute and molar volume of thesolvent in addition to contribution due to solute–solvent interactionsand estimates the order or disorder introduced by the addition of asolute into a solvent.

The viscosity data is also analyzed on the basis of the transitionstate theory of solutions [6] calculated from the following equation

ΔG0#2 ¼ ΔG0#

1 þ RTV01

B− V01−V

02

� �� � ð7Þ

where ΔG20# is the contribution per mole of the drug to the free

energy of activation for viscous flow of solution and ΔG10# is the free

Table 3Transfer volumes (ΔVm° ) for phenyl salicylate in various organic solvents and at differenttemperatures in the range T=(293.15 To 313.15) K

Solvents ΔVm° (cm3/mol)

293.15 K 298.15 K 303.15 K 308.15 K 310.15 K 313.15 K

Methanol 67.93 65.96 62.07 58.65 54.79 53.03Ethanol 28.29 25.60 23.60 21.99 21.11 18.911-Propanol 15.95 14.52 13.28 12.14 11.54 10.422-Propanol 5.34 3.77 1.83 −0.30 −0.58 −1.231-Butanol 13.90 13.08 12.80 11.88 10.23 8.442-Butanol −1.83 −3.29 −4.97 −7.49 −8.99 −10.87

Scheme 2. Interaction of primary alcohol with phenyl salicylate.

78 M.J. Iqbal, M.A. Chaudhry / Journal of Molecular Liquids 143 (2008) 75–80

energy of activation per mole of the solvent, V10 (=M /ρ) is the partial

molar volume of the solvent and V20 (=Vm°) is the partial molar volume

of the solute. The value of ΔG10# is calculated from the following

relation;

ΔG0#1 ¼ RTln

η0V01

hNA

� ð8Þ

where, h is Planck's constant and NA is Avogadro's number.According to the thermodynamic relations [6], themolar activation

enthalpy ΔH20# and the molar activation entropy ΔS2

0# of a solute canbe calculated from Eqs. (9) and (10)

ΔH0#2 ¼ A ΔG0#

2 =T� �

=A 1=Tð Þp ð9Þ

ΔS0#2 ¼ ΔH0#2 −ΔG0#

2

� �=T ð10Þ

4. Results and discussion

Fig. 1 shows the apparent molar volume of phenyl salicylate (PS) inmethanol as a solvent over the temperature range (293.15–313.15) K.The apparent molar volume of PS in the solvent methanol increaseswith the solute concentration at a constant temperature as shown inTable 2. A behavior similar to this has been observed in all the other

Table 4Values of partial molar volume Vm°, isobaric thermal expansion coefficient α2 and partial molar

T (K) Vm° (cm3.mol−1) α2 (K 10−3) E20 (cm3 mol−1.K−

Methanol293.15 93.860 8.25 0.775298.15 97.680 7.93303.15 100.14 7.74308.15 102.94 7.52310.15 107.80 7.19313.15 109.74 7.06

1-Propanol293.15 145.84 2.15 0.314298.15 147.46 2.13303.15 148.93 2.10308.15 150.33 2.08310.15 151.05 2.07313.15 152.35 2.06

1-Butanol293.15 147.89 1.98 0.293298.15 148.90 1.97303.15 149.41 1.96308.15 150.59 1.95310 .15 152.36 1.92313.15 154.33 1.89

Water293.15 161.79 0.3034 0.0491298.15 161.98 0.3031303.15 162.21 0.3027308.15 162.47 0.3022310.15 162.59 0.3019313.15 162.77 0.3017

solvents used in the present study. The apparent molar volume isconsidered to be a sum of the geometric volume of the solute and thevolume change of the solvent due to its interaction with the solute.

The transfer volumes ΔVm° of PS from water to alcohols (Fig. 2) iscalculated according to Eq. (5) and their values at temperatures rangingfrom T=(293.15 to 313.15) K are listed in Table 3. The value of ΔVm° ispositive for all the solvents investigated here with the exception of 2-butanol and 2-propanol at higher temperatures. This trend can bediscussed in terms of higher solvation of the drug molecule in variousorganic solvents than in the aqueous medium implying a solvophobiccharacter of the drug. An examination of the transfer volume dataindicates that ΔVm° is the highest for methanol and the lowest for 2-butanol at all the temperatures investigated here. The positive ΔVm°change from water to various organic solvents can be explained byassuming a decreased electrostriction of the solvents around the drug.The ΔVm° values for 2-butanol and for 2-propanol (at higher tempera-tures) are negative indicating that solvophobic–solvophilic interaction isdominant. Based on the co-sphere overlap model, solvophobic–solvophilic interaction results in a break up of solvent structure andthus results in a negative transfer volume value. Fig. 2 shows thedependence of the transfer volume on temperature. The decrease in themagnitude ofΔVm° with temperature increments can be attributed to anenhanced thermal agitation and weakening of various interactions.

The calculated values of the partial molar volume Vm° are shown inTable 5. The positive values of Vm° in all the solvents suggest a strongsolute–solvent interaction that promotes the structure making effectof the studied drug. Thus the values of viscosity B-coefficient given inTable 5 are also in support of the behavior noted for the partial molarvolume of PS as discussed above.

In case of pure alcohols, the strength of the intermolecular hydrogenbonding decreases with the increase in their chain length due to anelectron-donating effect of alkyl groups [7]. The extent of the hydrogenbonding decreases due to an increase in the steric hindrance of bulkieralkyl groups. The branched structure of secondary alcohols, i.e. 2-propanol and 2-butanol, causesweakening their hydrogen bonds due to

expansivity E20 of phenyl salicylate in alcohols at temperatures from 293.15 to 313.15 K

1) Vm° (cm3. mol−1) α2 (K 10−3) E20 (cm3.mol−1 K)

Ethanol133.50 3.63 0.485136.38 3.57138.61 3.49140.48 3.45141.48 3.43143.86 3.37

2-Propanol156.45 2.90 0.455158.21 2.87160.38 2.83162.77 2.79163.17 2.78166.00 2.74

2-Butanol163.62 3.04 0.498165.27 3.01167.18 2.98169.96 2.93171.53 2.90173.65 2.86

Scheme 3. Interaction of a secondary alcohol with phenyl salicylate.

79M.J. Iqbal, M.A. Chaudhry / Journal of Molecular Liquids 143 (2008) 75–80

steric hindrance. On the other hand, methanol, ethanol, 1-propanol and1-butanol are primary alcohols with linear alkyl chains. For this reason,methanol has the highest hydrogen bonded structure and 2-butanol theweakest amongst the solvents investigated in this work.

It is well known that the formation of H-bond results in a decreasein the partial molar volume due to shortening of the inter-atomicdistance. When the drug interacts with the solvents, intra-molecularH-bonding breaks and only the intermolecular H-bonding predomi-nates. The partial molar volume of PS in ethanol, within the studiedtemperature range, is large as compared to that in methanol. Primaryalcohol interacts with PS molecule via H-bonding that largelycontributes to the observed values of Vm° as shown in Scheme 2 andTable 4. Large value of Vm° in 2-propanol as compared to 1-propanolas shown in Table 3 is due to comparatively favorable packing of1-propanol molecules into the spaces created by the solute PS. Thesolvent 2-propanol experiences steric hindrance by the bulky (CH3)2CHgroup and is also less acidic than 1-propanol due to its higher electronreleasing tendency than that of the (C3H7) group [7].

The value ofVm° is large in 2-butanol as compared to that in 1-butanolin the studied temperature range. The difference in theVm° values of PS in1-butanol and 2-butanol is most likely due to the difference in thestructure and the solvation pattern of the two solvents (Schemes 2and 3). For instance,1-butanol with a linear chain shows self association[8] to a much greater extent as compared to 2-butanol. The number ofdrugmolecules that show favorable packingof 1-butanolmolecules intothe spaces createdby the solute PS are greater as compared to those in 2-butanol because of the extent to which drug molecules are bonded toone another in 1-butanol as compared to that in 2-butanol. It results inlarger partial molar volume for phenyl salicylate in 2-butanol than in 1-butanol. Secondary alcohol interacts via H-bonding with the solute(phenyl salicylate)molecule as shown in Scheme3. Partialmolar volumeof PS increases with an increase in temperature due to the release ofsome solvent molecules from the loose solvation layers of the solute inthe solution.

Table 5Viscosity B-coefficients and activation parameters of phenyl salicylate in alcohols at differen

T/K B (dm3mol−1) ΔG10# (kJmol−1) ΔG2

0# (kJmol−1) ΔH20# (kJmol−1) ΔS2

0# (kJmol−1 K−1)

Methanol293.15 0.484 9.991 42.40 269.42 0.7744298.15 0.404 9.963 37.50 0.7779303.15 0.302 9.928 30.30 0.7887308.15 0.262 9.906 25.60 0.7912310.15 0.232 9.903 22.30 0.7967313.15 0.185 9.890 21.80 0.7970

1-Propanol293.15 0.301 14.933 28.00 180.86 0.5245298.15 0.295 14.919 27.10 0.5249303.15 0.226 14.892 25.00 0.5251308.15 0.150 14.670 22.31 0.5256310.15 0.114 14.493 21.00 0.5260313.15 0.105 14.452 20.05 0.5268

1-Butanol293.15 0.231 15.373 25.33 82.29 0.2289298.15 0.204 15.315 24.55 0.2291303.15 0.184 15.269 23.90 0.2293308.15 0.127 15.205 21.55 0.2295310 .15 0.094 15.188 20.00 0.2297313.15 0.092 15.156 19.05 0.2299

The values for the dielectric constant and the dipole moment canbe used in the quantitative characterization of solvent polarity [8]. Thevalue of Vm° of drug solution decreases in various solvents when thedielectric constant and the dipole moment are increased as shown inTable 4. This indicates that by increasing solvent polarity, the solute–solvent interactions are decreased.

The values of isobaric thermal expansion coefficient (α2) for all thesystems investigated here are shown in Table 4. The values of α2 arefound to decreasewith temperature increase showing the significance ofsolvent–hydroxyl group interactions in the solution properties of thedrugmolecule. Thedensityof the solution and, consequently, thevalueofα2 are noted to decreasewith an increase in temperature. Comparativelyhigher value of α2 in methanol is due to stronger H-bonding betweenmethanol and the drugmolecule and the lowest α2 value in 1-butanol isdue to a weak H-bonding between 1-butanol and the drug.

The values of partial molar expansivity (E20) reflect the solvent–solvent interactions (i.e. attractive and orientational short range forces)and it is believed that thenon specific solvent–solvent and solute–soluteinteractions are the fundamental forces that determine the volumetricbehavior of the solute (PS) in the solvents. The values of E20 in differentorganic solvents are listed in Table 4. E20 is considered to be an importantand sensitive indicator of solute–solvent interactions. E20 values areusually employed in interpreting the structure making or breakingproperties of various solutes. Positive values of E20 show the structuremaking property of the drug. Thus the values of viscosity B-coefficientsof PS solutions also support such a behavior of E20 (Table 5). Highest valueof Eϕ0 in methanol is due to a stronger H-bonding between the drugmolecule and the solvent (methanol) and lowest value for 1-butanol isdue to less hydrogen bonding betweendrugmolecule and the solvent asshown in Schemes 2 and 3.

4.1. Viscosity

Fig. 3 shows a representative plot of the viscosity (ψ) of phenylsalicylate solutions in methanol versus the square root of concentra-tion (C1/2) over the temperature range analyzed in this study. Similarshape plots have been obtained all the other solvents employed here.The values of the viscosity A-coefficients in all the solvents are close tozero representing very weak solute–solute interactions and thereforehave not been reported in Table 5.

Perusal of Table 5 shows that the values of B for PS in all thesolvents are large and positive. When a solute is dissolved in a solvent,

t temperatures from 293.15 K to 313.15 K

B (dm3mol−1) ΔG10# (kJ mol−1) ΔG2

0# (kJmol−1) ΔH20# (kJmol−1) ΔS2

0# (kJmol−1 K−1)

Ethanol0.404 12.762 33.00 221.97 0.64460.324 12.731 29.99 0.64500.247 12.710 26.90 0.64600.177 12.526 23.90 0.64700.124 12.514 21.65 0.64750.117 12.493 21.42 0.6480

2-Propanol0.262 14.922 25.80 114.46 0.33630.230 14.811 24.96 0.33680.208 14.697 24.20 0.33710.137 14.582 21.95 0.33740.107 14.533 20.85 0.33780.095 14.463 19.51 0.3382

2-Butanol0.185 16.391 23.80 80.58 0.22540.175 16.220 23.05 0.22560.160 16.055 22.60 0.22590.110 15.895 21.00 0.22620.090 15.812 19.35 0.22650.089 15.705 18.55 0.2269

Fig. 3. Plot of viscosity (Ψ) versus the square root of phenyl salicylate concentration(C1/2) in methanol at different temperatures from T=293.15 K to 313.15 K.

80 M.J. Iqbal, M.A. Chaudhry / Journal of Molecular Liquids 143 (2008) 75–80

some of the solvent molecules are attached to the solute as a result ofthe solute–solvent interaction and thus increase the solution viscosity.Positive values of B-coefficients indicate the large size of movingparticles (i.e. increase in the viscosity of the solution), decreasing withincreasing temperature. This phenomenon can be attributed to thebreakup of the solvation shell due to the thermal motion. Decrease inthe values of B-coefficient with rise in temperature is owing to thestructure promoting tendency e (i.e. solvophobic and hydrogen bondmaking action of solvent) of the drug (PS) molecule. B-values arefound to be positive reflecting a certain degree of solute–solventinteraction [6] which may change with the nature of the alcoholicsolvent.

According to the transition state theory of solutions, every solventmolecule in one mole of solution must pass through the transitionstate and also interact more or less strongly with solutemolecules. It isevident from Table 5 that ΔG2

0# values are positive and larger thanΔG1

0# for solvophobic solutes indicating that the interactions betweenthe drug and the solvent molecules in the ground state are strongerthan in the transition state. Thus, the solvation in the transition state isunfavorable in free energy terms and decreases with the increase intemperature. In other words, formation of the transition state isaccompanied by the rupture and distortion of the intermolecularforces in the solvent structure. This indicates that PS behaves as asolvophobic structure maker. This conclusion is consistent with theresults deduced from the values of B and dB/dT.

The enthalpy and entropy of activation for viscous flow of PS invarious solvents over the temperature range studied are calculatedfrom Eqs. (9) and (10)respectively. The activation parameters havebeen calculated from the values of ΔG2

0# at temperature (293.15–313.15) K and are given in Table 5. The value of ΔS20# is associated withthe structural change in the solvation shell of the solute (drug) in theground to the transition state. Positive value of ΔS20# is an indicationthat the structure of the solvation shell in the transition state is lessordered than in the ground state. By changing the solvent, ΔS20# valuedecreases due to an enhanced ‘order’ in the solvation shell of the tran-sition state. The activation enthalpy ΔH2

0# is positive and decreaseswith change in the solvent. Positive values for ΔH2

0# indicate anendothermic process [9].

5. Conclusions

The apparent molar volume of phenyl salicylate drug solutionincreases with an increase in the drug concentration. The solvateddrug molecule interacts with the solvent molecules through aconstructive overlap of their solvation spheres. The H-bond formationresults in decreasing the partial molar volume due to shortening of theinteratomic distance. The values of the partial molar volume showa decreasing trend with an increase in the dipole moment andthe dielectric constant of the solvent. The partial molar expansivityincreases with an increase in hydrogen bonding. Thermal expan-sion coefficient decreases with an increase in temperature. ViscosityB-coefficient and various activation parameters are also affected.

Acknowledgements

The authors acknowledge a research grant by the Higher Edu-cation Commission (HEC) Pakistan under its Indigenous Scholarshipprogram.

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