Volumetric, Viscometric, and 1H NMR Studies on Caffeine

Article Cite This: J. Chem. Eng. Data XXXX, XXX, XXX-XXX

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Volumetric, Viscometric, and 1H NMR Studies on Caffeine, Theophylline, and Theobromine in Aqueous Solutions of MgCl2 at Temperatures T = (288.15 to 318.15) K and at Pressure p = 101.3 kPa Tarlok S. Banipal,* Aashima Beri, and Parampaul K. Banipal Department of Chemistry, Guru Nanak Dev University, Amritsar, Punjab 143005, India S Supporting Information *

ABSTRACT: Apparent molar volumes (V2,ϕ) and viscosity Bcoefficients for xanthine drugs (caffeine, theophylline, and theobromine) in aqueous (0.09999−0.99989) mol·kg−1 MgCl2 solutions have been determined from measured densities ρ and viscosities η, respectively at T = (288.15 to 318.15) K and at pressure p = 101.3 kPa. These studies indicate the decrease in solubilization of xanthine drugs with increasing ionic strengths of MgCl2 solutions. The results have also been interpreted in terms of structure making/breaking ability of solutes. Spectroscopic studies also support that hydrophilic− ionic interactions are greater at lower concentrations of MgCl2, which descend and finally become weaker at higher concentrations of MgCl2. This type of behavior may also be understood in terms of a large dehydration effect.

1. INTRODUCTION Drugs have been an important class of osmolytes. They enter the human body to stimulate certain receptors, ion channels, and act on enzymes.1 The methylxanthines belong to the category of psychoactive drugs.2,3 They are the purine alkaloids and found in most human body tissues and fluids.4,5 Caffeine (CAF), theophylline (TPY), and theobromine (TBR) are closely related methylxanthines but show distinct pharmacological activities.6 Among all the psychoactive drugs, CAF is the best known pharmacologically active substance. Almost all of CAF comes from dietary sources (tea, coffee, and other energy drinks).7−10 CAF is also used in combination11−15 for the cure of headache and pain.16,17 The high amounts of CAF may have serious side effects such as trembling, nausea, nervousness, and seizures and mutation effects.18,19 Theophylline (TPY) and theobromine (TBR) also have medicinal values as antiinflammatory agents.20−22 In the brain, CAF takes the place of adenosine and orders neurons to work more rapidly.23,24 CAF extends its use as a stimulant and also as an antidepressant.25 Solvent media for the physicochemical reactions that occur in our body contain water. A number of salts/electrolytes are available in biological fluid. It is difficult to understand the solute−solvent interactions directly since they can be affected by the presence of cosolutes.26 Thus, in biological systems, interactions with the electrolytes are very important to understand the solvation behavior of drugs. To understand the activity of drugs in aqueous solutions of electrolytes, different physicochemical properties such as density and viscosity have been used as tools. Biologically, interactions of CAF with Mg2+ ions may be understood in terms of inhibitory effect of CAF at adenosine receptors which is decreased by Mg2+ ions as shown in Scheme 1.27 CAF may © XXXX American Chemical Society

raise magnesium absorption and urinary magnesium excretion.28,29 Interactions of CAF with electrolytes, metal ions, and nonelectrolytes have been studied in the literature.30−33 Scheme 1. Inhibitory Effect of Mg2+ on Caffeine27

Therefore, in continuation of our studies on the interactions of xanthine drugs with electrolytes,34 the studies on the interactions of xanthine drugs with MgCl2 in aqueous solution will be very useful from the biological point of view. We present here the densities and viscosities of xanthine drugs in aqueous (0.09999−0.99989) mol·kg−1 MgCl2 solutions at T = (288.15 to 318.15) K and at p = 101.3 kPa. The influence of concentration and temperature on various parameters has been discussed in terms of interactions occurring in these solutions. These studies have also been supplemented with 1H NMR spectroscopic data. Received: June 8, 2017 Accepted: October 9, 2017

A

DOI: 10.1021/acs.jced.7b00520 J. Chem. Eng. Data XXXX, XXX, XXX−XXX

Journal of Chemical & Engineering Data

Article

Table 1. Provenance and Purity of the Chemicals Used

a

As reported by the suppliers. bMass fraction purity as obtained from HPLC analysis. Notation: M = molecular weight and w = mass fraction purity.

2. EXPERIMENTAL SECTION 2.1. Materials. Provenance and the mass fraction purity of the solutes are given in Table 1. The solutes have been used without prior treatment but have been dried in vacuo over anhydrous CaCl2 before use. To check the purity, HPLC analyses of these solutes have been carried out which have been reported elsewhere.34 2.2. Equipment and Procedures. Deionized, double distilled, and degassed water obtained from Ultra UV/UF Rions laboratory water system with a specific conductance less than 1.3 × 10−4 Sm−1 was used for the preparation of all the stock solutions. The solutions were prepared on mass basis using a Mettler balance (model AB265-S) with a precision of ±0.01 mg. The standard uncertainty in the molality is ±2.8 × 10−5 mol·kg−1. 2.2.1. Density. To measure the solution densities ρ vibratingtube digital densimeter (model DMA 60/602, Anton Paar, Austria) attached with a constant temperature bath (model Julabo F-25) having a temperature stability within ±0.01 K was used. The calibration procedure of the densimeter was accomplished using dry air and pure water.35 Its working was checked by determining the densities of aqueous solutions of NaCl at 298.15 K, which agreed well with the literature values.36,37 The standard uncertainty in the density, u(ρ) is ±4 kg·m−3 (by taking 1% uncertainty in density due to impurity in samples). 2.2.2. Viscosity. A suspended level Micro-Ubbelohde capillary viscometer placed vertically in a constant temperature bath (model MC 31A Julabo/Germany) having a temperature stability within ±0.01 K has been used for the determination of solution viscosity η. Flow time measurements have been made using an automatic efflux time measurement unit (SCHOTT AVS 350) with a resolution of ±0.01 s. The viscometer was cleaned, dried, and calibrated with deionized, double distilled and degassed water. To calibrate the viscometer, the efflux time data for water were noted at T/K = (288.15, 298.15, 308.15 and 318.15). The final efflux time is the average of at least six readings. The standard uncertainty in viscosity, u(η) on an average is ±0.012 mPa·s (by taking 1% uncertainty in the viscosity of water used for calibration). The working of the apparatus was checked by measuring the viscosities of aqueous

solutions of glycine at T = 298.15 K which agree well with the literature values.38 Viscosities of pure water have been taken from the literature.39 The conversion of molalities into molarities was accomplished by using density data. 2.2.3. 1H Nuclear Magnetic Resonance (NMR) Spectroscopy. 1H NMR spectra were obtained using Bruker (AVANCEIII, HD 500 MHz spectrometer) at a probe temperature of 298.15 K. Being that D2O was the lock solvent, the center of the HDO signal (4.650 ppm) was considered as the internal reference for the other nuclei. NMR specta of CAF (20 mM), TPY (20 mM), and TBR (5 mM) in the absence, as well as in the presence, of aqueous solution of MgCl2, (0.09999− 0.99989) mol·kg−1 were studied in 9:1 (w/w) H2O−D2O solution. The chemical shifts (δ) in ppm were studied for the pure as well as for mixtures.

3. RESULTS AND DISCUSSION 3.1. Apparent Molar Volumes. The ρ values for CAF, TPY, and TBR in I (ionic strength of MgCl2) = (0.29997− 2.99967) mol·kg−1 of MgCl2 solutions have been determined at T = (288.15, 298.15, 308.15 and 318.15) K and at p = 101.3 kPa. The ρ values of aqueous MgCl2 solutions are in good agreement with the literature40−42 as shown in Figure S1 [given as, Supporting Information]. The variation of ρ values for the solutions of the studied solutes with the molality of solute in aqueous MgCl2 solutions and temperature has been shown in Figure 1a (the representative plots of ρ versus molality mA for CAF in I = 0.29997 mol·kg−1 as a function of temperature are given in Figure 1a). Figure 1a has been divided into different color regions, and these color zones further vary with temperature T as well as with molality mA. In the present study, apparent molar volumes V2,ϕ have been determined from the experimentally measured densities using the relation V2, ϕ = {M /ρ} − {(ρ − ρ0 )/(mA ρρ0 )}

(1)

where M and mA are the molar mass and molality of the solutes, ρ and ρo are the densities of solution and solvent (MgCl2 + H2O), respectively. The ρ and V2,ϕ values for the studied solutes in aqueous solutions of MgCl2 as a function of mA, I, and T are given in Table 2. The V2,ϕ values of the solutes are positive and decrease with the molality of solute (the B



Article

strength of MgCl2. A similar type of behavior has been reported34 in the presence of aqueous solutions of NaCl but with lesser magnitude of V2,ϕ ° . The partial molar volumes of transfer, ΔtrV2,ϕ ° at infinite dilution from water to aqueous solutions of MgCl2 have been determined as Δtr V 2,° ϕ = V 2,° ϕ (in aqueous MgCl2 solutions) − V 2,° ϕ (in H 2O)

The values of ΔtrV2,ϕ° are free from solute−solute interactions but rather provides information about solute−cosolute interactions.45 The values of V°2,ϕ for these solutes in water have been taken from our previous paper.34 The positive values of ΔtrV2,ϕ ° have been observed for the solutes over the range of ionic strength of aqueous solutions of MgCl2 studied. The values of ΔtrV°2,ϕ [Figure 2(a−c)] are positive and decrease with increase in ionic strength of MgCl2 at all temperatures. The values of ΔtrV2,ϕ ° increase with temperature in the case of TPY and TBR while the reverse trend is observed in the case of CAF. The observed positive values of ΔtrV2,ϕ decrease in the following order: TBR > TPY > CAF. The solutes are embedded with both hydrophilic (polar) and hydrophobic (nonpolar) parts. Probably, interactions of these solutes with aqueous MgCl2 (ions) may either be hydrophilic−ionic or hydrophobic−ionic. The ΔtrV2,ϕ ° values can be explained in terms of these interactions using the cosphere overlap model.48 The positive contribution to ΔtrV°2,ϕ values is due to the overlap of hydrophilic−ionic hydration cospheres that releases some water molecules to the bulk water and hence the net volume increase. However, the negative contribution to ΔtrV2,ϕ ° values are due to the overlap of hydrophobic−ionic hydration cospheres, which results in net volume decrease. The resultant overlap is concentration and temperature specific. The present study indicates that hydrophilic−ionic interactions (positive ΔtrV2,ϕ ° values) dominate over the hydrophobic−ionic interactions. Volumetric virial coefficient (Sv) are more negative in water as compared to in the presence of a cosolute. It means the magnitude of hydrophobic interactions are less in water.49 The addition of an inorganic electrolyte in the water+drug system causes hydrophobic interactions to increase at high concentration. Hydrophobic interactions are greater in the presence of aqueous NaCl than MgCl2 as observed from the transfer volumes. CAF is more hydrophobic than the other two solutes. Therefore, maximum hydrophobic interactions are observed in the case of CAF. Sharma and Paul reported the salting out effect of CAF molecules in salt solution, as they have observed strong interactions of salt ions with CAF at higher temperatures.50,51 When a solute, for example, a drug, is dissolved in water, it becomes hydrated/solvated according to its hydrophilicity or hydrophobicity. Upon the addition of another solute, such as an electrolyte, into this (water+drug) system, the solubility of the drug may increase or decrease, depending upon the nature of the electrolyte, because of its salting-in/salting-out effect. The positive and negative transfer volume gives information about the salting-in/salting-out effect.40 In the present study, the greater magnitude of positive ΔtrV°2,ϕ at low ionic strength shows the salting-in effect, and the comparatively lesser magnitude of ΔtrV2,ϕ ° at high ionic strength indicates that salting-in-effect decreases with ionic strength. Thus, a high concentration of aqueous MgCl2 solutions would decrease the solubilization of the studied solutes. This may be understood as Mg2+ ions are highly hydrated in water, therefore as the

Figure 1. (a) Representative plot of density ρ versus molality mA for caffeine in aqueous MgCl2 solution, I = 0.29997 mol·kg−1, as a function of temperature T. (b) Apparent molar volume V2,ϕ versus molality mA for theophylline in aqueous MgCl2 solution, I = 0.29997 mol·kg−1, as a function of temperature T. [The density ρ increases with the molality of caffeine in aqueous MgCl2 solution and decreases with temperature as shown in panel a from change in color from blue to orange. The apparent molar volume V2,ϕ decreases with the molality of theophylline in aqueous MgCl2 solution and increases with temperature as shown in panel b].

representative plots of V2,ϕ versus molality mA for TPY in I = 0.29997 mol·kg−1 as a function of temperature are given in Figure 1b). 3.2. Partial Molar Volumes. At infinite dilution, apparent molar volume becomes equal to partial molar volume. Generally, partial molar volumes, at infinite dilution, V2,ϕ ° , have been calculated using Masson’s equation (eq 2) given below in the case of electrolytes. V2, ϕ = V 2,° ϕ + Sv(mA )1/2

However, in the case of nonelectrolytes, modified to eq 3. V2, ϕ = V 2,° ϕ + SvmA

(2) 43

(4)

eq 2 has been (3)

Our solutes are nonelectrolytes. Thus, we have used eq 3 to calculate partial molar volume, V2,ϕ ° . Sv is the experimental slope which characterizes the volumetric virial coefficient. It signifies the pairwise interaction between the solvated species. The negative sign of Sv may be due to the dominance of a hydrophobic type of interactions.44−47 The values of V2,ϕ ° and Sv have been given in Table S1(Supporting Information). The V°2,ϕ values are positive in aqueous solutions of MgCl2 and are higher than the corresponding values in water reported earlier.34 The V2,ϕ ° values also increase with temperature. However, the V2,ϕ ° values decrease with the increase in ionic C



Article

Table 2. Densities ρ and Apparent Molar Volumes V2,ϕ of Xanthine Solutes in Aqueous MgCl2 Solutions from T = (288.15 to 318.15) K and p = (101.3 kPa) T/K = 288.15

T/K = 298.15

T/K = 308.15

T/K = 318.15

mA

ρ·10−3

V2,ϕ·106

ρ·10−3

V2,ϕ·106

ρ·10−3

V2,ϕ·106

ρ·10−3

V2,ϕ·106

mol·kg−1

kg·m−3

m3·mol−1

kg·m−3

m3·mol−1

kg·m−3

m3·mol−1

kg·m−3

m3·mol−1

a

Caffeine I = 0.00c mol·kg−1 (ρo = 997.047 kg·m−3) 0.997304 143.94 0.997399 143.79 0.997504 143.71 0.998060 143.48 0.998576 143.13 0.998853 143.05 0.999101 142.92 0.999619 142.58 b I = 0.29997 mol·kg−1 (ρo = 1004.61 kg·m−3) 1.004722 158.49 1.004786 158.43 1.004856 158.36 1.004929 158.33 1.004961 158.23 1.005307 158.15 1.005498 158.13 1.005685 158.05 I = 0.74997 mol·kg−1 (ρo = 1015.321 kg·m−3) 1.015431 157.59 1.015494 157.55 1.015566 157.50 1.015630 157.39 1.015671 157.31 1.016020 157.16 1.016218 157.13 1.016375 157.06 I = 1.49985 mol·kg−1 (ρo = 1032.22 kg·m−3) 1.032321 156.59 1.032381 156.55 1.032447 156.45 1.032513 156.39 1.032549 156.35 1.032874 156.24 1.033075 156.15 1.033189 156.12 I = 2.24982 mol·kg−1 (ρo = 1048.21 kg·m−3) 1.048162 154.58 1.048225 154.54 1.048293 154.51 1.048354 154.46 1.048386 154.43 1.048704 154.35 1.048917 154.31 1.049044 154.22 I = 2.99967 mol·kg−1 (ρo = 1062.645 kg·m−3) 1.062744 152.56 1.062811 152.48 1.062862 152.43 1.062933 152.40 b

0.00510 0.00695 0.00902 0.01993 0.02992 0.03531 0.04008 0.04992

(ρo = 999.129 kg·m−3) 0.999404 140.20 0.999505 140.06 0.999619 139.92 1.000215 139.61 1.000769 139.22 1.001071 139.01 1.001338 138.83 1.001886 138.64

0.00316 0.00497 0.00697 0.00902 0.00991 0.01969 0.02509 0.03033

(ρo = 1006.865 kg·m−3) 1.006984 155.60 1.007053 155.58 1.007128 155.55 1.007206 155.50 1.007240 155.48 1.007611 155.40 1.007818 155.26 1.008022 155.07

0.00314 0.00494 0.00701 0.00882 0.00996 0.01992 0.02555 0.02999

(ρo = 1017.79 kg·m−3) 1.017910 154.53 1.017978 154.50 1.018056 154.45 1.018125 154.38 1.018168 154.35 1.018543 154.29 1.018759 154.13 1.018929 154.04

0.00299 0.00476 0.00671 0.00866 0.00973 0.01928 0.02519 0.02853

(ρo = 1034.95 kg·m−3) 1.035067 153.68 1.035131 153.63 1.035203 153.53 1.035274 153.47 1.035314 153.41 1.035666 153.26 1.035883 153.21 1.036007 153.14

0.00294 0.00480 0.00681 0.00859 0.00954 0.01892 0.02519 0.02888

(ρo = 1050.837 kg·m−3) 1.050943 151.90 1.051011 151.80 1.051085 151.70 1.051151 151.60 1.051187 151.53 1.051531 151.48 1.051764 151.32 1.051903 151.20

0.00291 0.00488 0.00634 0.00842

(ρo = 1065.458 kg·m−3) 1.065566 149.59 1.065639 149.56 1.065694 149.46 1.065772 149.38

D

(ρo = 994.063 kg·m−3) 0.994303 147.65 0.994390 147.61 0.994488 147.59 0.995013 146.99 0.995497 146.62 0.995759 146.49 0.996001 146.14 0.996484 145.91

(ρo = 990.244 kg·m−3) 0.990464 151.99 0.990545 151.80 0.990637 151.65 0.991121 151.11 0.991571 150.69 0.991812 150.57 0.992025 150.52 0.992483 150.03

(ρo = 1001.625 kg·m−3) 1.001728 161.48 1.001787 161.44 1.001852 161.41 1.001919 161.35 1.001948 161.29 1.002268 161.20 1.002445 161.16 1.002616 161.14

(ρo = 997.848 kg·m−3) 0.997940 164.86 0.997995 164.79 0.998054 164.77 0.998115 164.72 0.998143 164.59 0.998435 164.50 0.998598 164.43 0.998759 164.27

(ρo = 1012.53 kg·m−3) 1.012632 160.60 1.012690 160.53 1.012757 160.42 1.012816 160.34 1.012853 160.31 1.013175 160.19 1.013359 160.09 1.013503 160.03

(ρo = 1008.92 kg·m−3) 1.009012 163.69 1.009065 163.57 1.009126 163.55 1.009180 163.45 1.009215 163.36 1.009512 163.19 1.009681 163.09 1.009815 163.02

(ρo = 1029.55 kg·m−3) 1.029626 159.49 1.029681 159.41 1.029741 159.37 1.029802 159.35 1.029835 159.29 1.030132 159.21 1.030316 159.17 1.030420 159.15

(ρo = 1026.01 kg·m−3) 1.026101 162.56 1.026151 162.48 1.026207 162.42 1.026262 162.38 1.026293 162.28 1.026564 162.23 1.026734 162.13 1.026832 162.00

(ρo = 1045.263 kg·m−3) 1.045354 157.61 1.045411 157.58 1.045473 157.54 1.045528 157.50 1.045558 157.47 1.045848 157.43 1.046042 157.38 1.046158 157.30

(ρo = 1041.401 kg·m−3) 1.041483 160.69 1.041535 160.63 1.041592 160.58 1.041643 160.49 1.041670 160.45 1.041935 160.40 1.042112 160.33 1.042220 160.21

(ρo = 1059.402 kg·m−3) 1.059492 155.69 1.059553 155.63 1.059599 155.53 1.059664 155.48

(ρo = 1055.251 kg·m−3) 1.055334 158.52 1.055390 158.46 1.055432 158.43 1.055491 158.37 DOI: 10.1021/acs.jced.7b00520 J. Chem. Eng. Data XXXX, XXX, XXX−XXX


Article

Table 2. continued T/K = 288.15 ρ·10

a

mA

mol·kg

−1

T/K = 298.15

−3

V2,ϕ·10

−3

m ·mol

kg·m

6

−1

3

−3

0.00942 0.01809 0.02282 0.02892

(ρo = 1065.458 kg·m ) 1.065810 149.31 1.066136 149.19 1.066314 149.12 1.066543 149.05

0.00208 0.00285 0.00378 0.00479 0.00578 0.00699 0.00776 0.00934 0.00986

0.999241 0.999283 0.999333 0.999388 0.999443 0.999509 0.999551 0.999638 0.999667

126.30 126.15 126.11 126.05 125.91 125.85 125.79 125.68 125.58

0.00201 0.00412 0.00608 0.00794 0.00913 0.01018 0.01489 0.02067

1.006943 1.007025 1.007102 1.007175 1.007222 1.007264 1.007449 1.007676

140.51 140.47 140.42 140.35 140.29 140.22 140.19 140.10

0.00200 0.00406 0.00602 0.00806 0.00882 0.00990 0.01477 0.02056

1.017869 1.017948 1.018023 1.018103 1.018132 1.018174 1.018363 1.018592

140.06 139.97 139.95 139.83 139.80 139.74 139.64 139.34

0.00210 0.00371 0.00561 0.00772 0.00880 0.00993 0.01358 0.01731

1.035038 1.035100 1.035173 1.035254 1.035296 1.035340 1.035482 1.035630

138.45 138.36 138.26 138.23 138.14 138.09 137.93 137.76

0.00206 0.00391 0.00582 0.00749 0.00858 0.00944 0.01417 0.01957

1.050916 1.050988 1.051062 1.051128 1.051171 1.051204 1.051389 1.051600

136.42 136.34 136.29 136.22 136.18 136.12 136.08 136.01

0.00200 0.00374 0.00579 0.00783 0.00851

1.065537 1.065605 1.065686 1.065767 1.065794

134.54 134.50 134.42 134.35 134.30

ρ·10

T/K = 308.15

−3

V2,ϕ·10

−3

m ·mol

kg·m

6

−1

3

−3

(ρo = 1062.645 kg·m ) 1.062968 152.33 1.063266 152.25 1.063430 152.16 1.063642 152.05 Theophylline I = 0.00c mol·kg−1 0.997153 129.66 0.997192 129.62 0.997239 129.58 0.997291 129.50 0.997341 129.41 0.997404 129.33 0.997443 129.22 0.997526 129.11 0.997554 128.86 I = 0.29997 mol·kg−1 1.004680 144.68 1.004754 144.63 1.004823 144.58 1.004889 144.53 1.004931 144.47 1.004968 144.41 1.005135 144.36 1.005339 144.29 I = 0.74997 mol·kg−1 1.015391 144.06 1.015463 143.95 1.015530 143.91 1.015601 143.89 1.015628 143.83 1.015666 143.70 1.015838 143.51 1.016044 143.31 I = 1.49985 mol·kg−1 1.032292 142.60 1.032347 142.48 1.032412 142.42 1.032485 142.38 1.032522 142.30 1.032562 142.27 1.032687 142.22 1.032816 142.15 I = 2.24982 mol·kg−1 1.048134 140.44 1.048199 140.30 1.048266 140.20 1.048324 140.15 1.048363 140.09 1.048393 140.04 1.048559 139.97 1.048751 139.83 I = 2.99967 mol·kg−1 1.062715 138.66 1.062776 138.56 1.062848 138.49 1.062920 138.40 1.062944 138.34 E

ρ·10

T/K = 318.15

−3

V2,ϕ·10

−3

m ·mol

kg·m

6

−1

3

−3

ρ·10

−3

V2,ϕ·106

−3

m3·mol−1

kg·m

(ρo = 1059.402 kg·m ) 1.059696 155.45 1.059967 155.37 1.060117 155.26 1.060309 155.21

(ρo = 1055.251 kg·m−3) 1.055520 158.33 1.055770 158.21 1.055905 158.19 1.056081 158.13

0.994165 0.994204 0.994250 0.994300 0.994350 0.994410 0.994448 0.994528 0.994554

131.38 131.27 131.20 131.12 130.98 130.94 130.91 130.83 130.78

0.990343 0.990379 0.990423 0.990472 0.990519 0.990578 0.990614 0.990691 0.990716

133.62 133.52 133.43 133.36 133.29 133.23 133.20 133.12 133.00

1.001691 1.001760 1.001826 1.001888 1.001928 1.001963 1.002123 1.002317

147.20 147.07 146.97 146.88 146.70 146.68 146.44 146.38

0.997908 0.997973 0.998033 0.998091 0.998127 0.998161 0.998307 0.998489

149.98 149.88 149.79 149.71 149.65 149.51 149.45 149.26

1.012596 1.012662 1.012725 1.012791 1.012816 1.012851 1.013009 1.013201

146.84 146.76 146.70 146.55 146.47 146.42 146.33 146.09

1.008979 1.009040 1.009098 1.009159 1.009182 1.009215 1.009360 1.009535

149.65 149.61 149.58 149.43 149.35 149.29 149.23 149.10

1.029600 1.029650 1.029710 1.029777 1.029812 1.029849 1.029966 1.030088

145.24 145.21 145.17 145.14 145.06 144.97 144.86 144.70

1.026077 1.026123 1.026179 1.026240 1.026272 1.026305 1.026413 1.026526

148.41 148.34 148.24 148.11 148.07 148.00 147.83 147.62

1.045328 1.045387 1.045448 1.045501 1.045536 1.045564 1.045715 1.045888

143.48 143.41 143.34 143.31 143.25 143.19 143.12 143.05

1.041460 1.041513 1.041568 1.041616 1.041648 1.041673 1.041811 1.041968

146.66 146.59 146.56 146.54 146.48 146.41 146.28 146.19

1.059466 1.059522 1.059588 1.059654 1.059677

141.47 141.44 141.33 141.29 141.17

1.055310 1.055361 1.055421 1.055482 1.055503

144.56 144.39 144.35 144.21 144.13



Article


a

mA

mol·kg

−1

T/K = 298.15

−3

V2,ϕ·10

−3

m ·mol

kg·m

3

6

−1

ρ·10

T/K = 308.15

−3

V2,ϕ·10

−3

m ·mol

kg·m

ρ·10

6

−1

3

T/K = 318.15

−3

V2,ϕ·10

−3

m ·mol

kg·m

6

3

−1

ρ·10

−3

V2,ϕ·106

−3

m3·mol−1

kg·m

−1

0.00936 0.01399 0.01924

1.065829 1.066014 1.066222

134.20 134.07 134.00

1.062976 1.063140 1.063329

0.00051 0.00070 0.00090 0.00098 0.00123 0.00148 0.00183 0.00213

0.999157 0.999167 0.999177 0.999182 0.999195 0.999209 0.999228 0.999244

126.37 126.35 126.33 126.32 126.31 126.29 126.27 126.24

0.997073 0.997083 0.997093 0.997097 0.997110 0.997123 0.997141 0.997156

0.00049 0.00058 0.00079 0.00104 0.00118 0.00145 0.00182 0.00208

1.006884 1.006887 1.006895 1.006905 1.006911 1.006921 1.006936 1.006946

140.57 140.55 140.54 140.52 140.50 140.48 140.47 140.45

1.004628 1.004631 1.004639 1.004648 1.004652 1.004662 1.004675 1.004684

0.00048 0.00058 0.00079 0.00090 0.00125 0.00146 0.00173 0.00199

1.017811 1.017814 1.017822 1.017827 1.017840 1.017848 1.017859 1.017869

140.10 140.09 140.07 140.06 140.04 140.02 140.01 139.99

1.015339 1.015342 1.015350 1.015353 1.015366 1.015373 1.015382 1.015391

0.00047 0.00058 0.00079 0.00085 0.00127 0.00149 0.00179 0.00199

1.034976 1.034980 1.034988 1.034990 1.035006 1.035015 1.035026 1.035034

138.45 138.44 138.42 138.41 138.40 138.38 138.37 138.34

1.032237 1.032240 1.032248 1.032250 1.032264 1.032272 1.032282 1.032289

0.00045 0.00058 0.00079 0.00086 0.00120 0.00144 0.00183 0.00204

1.050854 1.050859 1.050867 1.050870 1.050883 1.050893 1.050907 1.050916

136.48 136.45 136.44 136.42 136.41 136.40 136.38 136.36

1.048079 1.048083 1.048090 1.048093 1.048104 1.048113 1.048126 1.048133

0.00049 0.00058 0.00079 0.00087 0.00111 0.00151 0.00174

1.065478 1.065481 1.065490 1.065493 1.065503 1.065519 1.065528

134.03 134.02 134.01 134.00 133.98 133.96 133.94

1.062662 1.062665 1.062673 1.062676 1.062684 1.062698 1.062706

I = 2.99967 mol·kg 138.22 138.17 137.95 Theobromine I = 0.00c mol·kg−1 129.26 129.25 129.23 129.21 129.20 129.18 129.15 129.10 I = 0.29997 mol·kg−1 145.03 145.01 145.00 144.98 144.96 144.95 144.92 144.90 I = 0.74997 mol·kg−1 144.01 143.99 143.97 143.95 143.93 143.91 143.89 143.87 I = 1.49985 mol·kg−1 142.33 142.31 142.29 142.27 142.25 142.23 142.21 142.20 I = 2.24982 mol·kg−1 140.71 140.69 140.68 140.67 140.64 140.62 140.61 140.57 I = 2.99967 mol·kg−1 138.33 138.31 138.30 138.28 138.27 138.26 138.23 F

1.059705 1.059855 1.060029

141.13 141.10 140.92

1.055529 1.055667 1.055825

144.09 144.00 143.87

0.994088 0.994097 0.994107 0.994111 0.994123 0.994135 0.994152 0.994167

131.91 131.90 131.88 131.87 131.86 131.84 131.82 131.79

0.990268 0.990277 0.990287 0.990291 0.990303 0.990314 0.990331 0.990346

133.39 133.37 133.35 133.32 133.31 133.29 133.28 133.25

1.001640 1.001643 1.001649 1.001657 1.001661 1.001669 1.001681 1.001689

149.48 149.46 149.45 149.43 149.42 149.41 149.39 149.37

0.997862 0.997864 0.997870 0.997877 0.997881 0.997889 0.997899 0.997907

152.35 152.34 152.33 152.32 152.30 152.28 152.26 152.23

1.012547 1.012550 1.012557 1.012560 1.012571 1.012578 1.012586 1.012595

147.38 147.37 147.36 147.34 147.33 147.32 147.30 147.28

1.008934 1.008937 1.008943 1.008946 1.008957 1.008963 1.008971 1.008979

149.66 149.65 149.64 149.63 149.62 149.60 149.57 149.55

1.029548 1.029551 1.029558 1.029560 1.029573 1.029579 1.029589 1.029595

145.88 145.87 145.86 145.85 145.84 145.82 145.80 145.77

1.026031 1.026034 1.026040 1.026042 1.026054 1.026060 1.026069 1.026075

148.17 148.15 148.13 148.11 148.10 148.09 148.08 148.04

1.045277 1.045281 1.045287 1.045290 1.045300 1.045307 1.045319 1.045326

144.45 144.44 144.42 144.41 144.40 144.38 144.36 144.35

1.041414 1.041418 1.041424 1.041426 1.041435 1.041442 1.041453 1.041459

146.76 146.75 146.73 146.71 146.69 146.66 146.65 146.64

1.059417 1.059419 1.059426 1.059429 1.059436 1.059448 1.059455

142.59 142.58 142.57 142.56 142.54 142.52 142.51

1.055265 1.055267 1.055273 1.055276 1.055282 1.055294 1.055300

145.55 145.53 145.51 145.50 145.48 145.47 145.46



Article


a

mA

mol·kg

−1

0.00202

T/K = 298.15

−3

V2,ϕ·10

−3

m ·mol

kg·m

1.065539

3

6

−1

133.92

ρ·10

T/K = 308.15

−3

V2,ϕ·10

−3

m ·mol

kg·m

1.062716

ρ·10

6

−1

3

V2,ϕ·10

−3

m ·mol

kg·m

I = 2.99967 mol·kg 138.21

T/K = 318.15

−3

6

3

−1

ρ·10

−3

V2,ϕ·106

−3

m3·mol−1

kg·m

−1

1.059464

142.48

1.055308

145.44

a

mA is the molality of solute in water34 or water + MgCl2. bI is the ionic strength of MgCl2 in water. cData reported in ref 34. Standard uncertainties, u are u(T) = 0.01 K, u(p) = 0.5 kPa, u(m) = 2.8 × 10−5 mol·kg−1, u(ρ) = 4 kg·m−3, u(V2,ϕ) = 0.05 to 1.3 × 10−6·m3·mol−1 (0.68 level of confidence).

Figure 2. Partial molar volume of transfer, at infinite dilution, ΔtrV2,ϕ ° and viscosity B-coefficients of transfer ΔtrB versus square root of ionic strength √I of aqueous MgCl2 solutions of (a/A) caffeine, (b/B) theophylline, (c/C) theobromine at ◆, 288.15 K; ■, 298.15 K; ▲, 308.15 K; ●, 318.15 K.

of divalent ions are higher than in the monovalent ions. Mg2+ ions also have the catalytic role to facilitate the binding of RNA with TPY as compared to Na+ ions.55 3.3. Partial Molar Expansibilities. To evaluate the effect of temperature on V2,ϕ ° values, the partial molar expansibilities, VE° (VE° = ∂V2,ϕ ° /∂T)P and their second-order derivatives, (∂2V°2,ϕ/∂T2)P have been determined by the method of leastsquares using the following equation:

concentration increases, they decrease the free water available for hydrating the nonelectrolyte solutes (CAF, TPY, and TBR).52 The Mg2+ ions electrostrict a greater number of water molecules in aqueous solution as compared to Na+ ions due to their small ionic radii, and thus for CAF, TPY, and TBR, ΔtrV°2,ϕ values are greater in the case of MgCl2 in comparison to that in NaCl.34 In other words, MgCl2 being a 2:1 electrolyte ° to a greater extent than the 1:1 influences the ΔtrV2,ϕ electrolyte (NaCl). Therefore, the overall results give a hint that the solubility of the studied drugs is greater in the aqueous solution of MgCl2 than NaCl. Nafisi et al. reported53,54 that divalent ions show strong interactions with TPY and weak interactions with CAF as the association constants in the case

V 2,° ϕ = a + b(T − Tref ) + c(T − Tref )2

(5)

where a, b, and c are constants, T is the temperature in Kelvin and Tref = 303.15 K, that is, the mean temperature over the range covered. The values of these constants have been G



Article

Table 3. Pair, VAB, and Triplet, VABB, Interaction Coefficients of Xanthine Solutes in Aqueous NaCl and MgCl2 Solutions from T = (288.15 to 318.15) Ka T/K = 288.15 solutes

VAB·106

VABB·106

T/K = 298.15 VAB·106

T/K = 308.15

VABB·106

T/K = 318.15

VAB·106

VABB·106

VAB·106

VABB·106

5.83 7.44 8.95

−4.91 −5.33 −6.05

7.49 7.88 10.98

−5.94 −5.56 −7.17

13.64 15.96 16.64

−4.52 −5.19 −5.42

12.85 16.52 17.46

−4.35 −5.31 −5.61

b

caffeine theophylline theobromine

4.73 4.34 6.59

−4.42 −3.52 −4.91

5.36 5.81 7.31

caffeine theophylline theobromine

15.30 14.41 14.62

−5.00 −4.79 −4.91

14.53 14.96 15.69

NaCl −4.73 −4.42 −5.31 MgCl2 −4.78 −4.95 −5.19

Standard deviations in VAB/m3·mol−2·kg and VABB/m3·mol−3·kg2 lie in the range of (3.17 to 9.16)·106 m3·mol−2·kg and (2.48 to 5.04)·106 m3·mol−3· kg2, respectively (0.68 level of confidence). bThe interaction coefficients in the presence of NaCl have been calculated from the data reported earlier.34 a

reported in Table S2 (Supporting Information). The (∂V°2,ϕ/ ∂T)P values are positive for the studied solutes except for CAF at a certain ionic strength of MgCl2 (Table S3, Supporting Information). Except for CAF, the (∂V°2,ϕ/∂T)P values decrease with temperature. However, (∂V°2,ϕ/∂T)P values do not follow any particular pattern with I values. Hepler56 used the general thermodynamic equation: {(∂CP°,2/∂P)T = −T (∂ 2V 2,° ϕ/∂T 2)P }

overlap of hydration spheres of solute and cosolute molecules.61 3.5. Viscosity and Viscosity B-Coefficients. From the flow time measurements, the η values of the studied solutes have been calculated using the following expression: η /ρ = At − B /t

where A and B are viscometer constants, (A = 0.0000321483 mPa·m3·kg−1, B = 0.019563 mPa·m3·s2·kg−1). The uncertainty in η values occurring due to the viscometric constant, density measurement, and flow time measurement and the uncertainty in the viscosity of calibrated water comes out to be 0.012 mPa· s. The η values for the solutions of MgCl2 are in line with the literature values40 as shown in Figure S2 (Supporting Information). The η values of solutes increase with the molality of solute mA as well as with the ionic strength of cosolute I (Table 4) and decrease with the temperature, T (representative plot of η vs molality mA for TBR in I = 0.29997 mol·kg−1 as a function of temperature is given in Figure 3). Using the Jones− Dole empirical equation,62 the viscosity data were fitted by the method of least-squares expressing the relative viscosities, ηr (ηr= η/ηo, where ηo and η are the viscosity of solvent and the solution, respectively) of solution as a function of concentration of solutes. The complete form of the Jones−Dole equation used in the case of electrolytes63 is

(6)

to determine the capacity of solute as a structure-maker or structure-breaker in solution. It concerns the degree of structure on the overall basis. It has been mentioned that (∂2V2,ϕ ° /∂T2)P should be negative for the structure-breaking and positive for the structure-making solute. The negative values of (∂2V°2,ϕ/∂T2)P for the studied solutes in aqueous solutions of MgCl2 suggest that these solutes act as structure-breaking solutes except for CAF up to I = 2.24982 mol·kg−1. However, at I = 2.99967 mol·kg−1, CAF is a structure-breaker, which shows that the behavior is concentration or ionic strength specific. Structure-making and structure-breaking concepts provide some qualitative information about solutions but this has also been regarded as a conventional view.57 3.4. Interaction Coefficients. The McMillan-Mayer equation58 has been considered to calculate interaction coefficients from the transfer volume ΔtrV2,ϕ ° of the studied solutes as follows: 2

Δtr V 2,° ϕ = 2VAB·mB + 3VABB·mB + ...

(8)

ηr = η /ηo = 1 + AC1/2 + BC

(7)

(9)

A-coefficient describes the impact of charge−charge interactions on the viscosity of a solution and B-coefficient characterizes the ion−solvent interactions. The modified form of Jones−Dole equation used in the case of nonelectrolytes is given below.

where A stands for solute and B for cosolute, VAB and VABB are the volumetric pair and triplet interaction coefficients, respectively, which are given in Table 3. VAB values are positive and VABB values are negative in the presence of both NaCl (VAB and VABB have been calculated from the data published earlier34) and MgCl2. Magnitude of VAB is greater in case of MgCl2 than NaCl. Whereas the magnitude of VABB is greater in the case of NaCl than MgCl2 at higher temperatures in all the cases. Higher VAB values are due to stronger hydrophilic−ionic interactions, and more negative VABB values are due to stronger hydrophobic−ionic interactions.59,60 Thus, there are stronger hydrophobic−ionic interactions in the case of NaCl than that of MgCl2 at higher temperatures. Therefore, salting-out is greater in the case of NaCl. The higher values for VAB (positive values) in comparison to VABB (negative values) for the studied solutes in both the salts at all the temperatures suggest the predominance of pairwise interactions which occur due to the

ηr = η /ηo = 1 + BC

(10)

The A-coefficient values are negligible in the case of nonelectrolytes as there are no charge−charge interactions. C is the molarity (calculated from density and molality data). The B-coefficient45 indicates the structure of solvent in the vicinity of the solute molecules. The B-coefficient values of the studied solutes are positive in water and in aqueous solutions of MgCl2 (Table S4). These values decrease with the concentration of cosolute but increase with the temperature. The B-coefficients of transfer, ΔtrB for the studied solutes, from water to aqueous MgCl2 solutions have been evaluated using equation H



Article

Table 4. Viscosities η of Xanthine Solutes in Water and in Aqueous MgCl2 Solutions from T = (288.15 to 318.15) K, and at Pressure p = (101.3 kPa)a η/mPa·s mA/mol·kg−1

T/K = 288.15

0.00508 0.00693 0.00900 0.01986 0.02978 0.03533 0.03983 0.04953

ηo= 1.138 mPa·s 1.140 1.142 1.144 1.147 1.152 1.154 1.156 1.162

0.00316 0.00497 0.00697 0.00902 0.00991 0.01969 0.02509 0.03033

ηo= 1.210 mPa·s 1.213 1.213 1.214 1.216 1.220 1.222 1.223 1.224

0.00314 0.00494 0.00701 0.00882 0.00996 0.01992 0.02555 0.02999

ηo= 1.250 mPa·s 1.253 1.255 1.256 1.257 1.260 1.262 1.263 1.264

0.00299 0.00476 0.00671 0.00866 0.00973 0.01928 0.02519 0.02853

ηo= 1.355 mPa·s 1.358 1.359 1.361 1.363 1.365 1.367 1.369 1.370

0.00294 0.00480 0.00681 0.00859 0.00954 0.01892 0.02519 0.02888

ηo= 1.445 mPa·s 1.447 1.448 1.449 1.451 1.453 1.456 1.458 1.459

0.00291 0.00488 0.00634 0.00842 0.00942

ηo= 1.534 mPa·s 1.537 1.539 1.541 1.542 1.544

T/K = 298.15 Caffeine I = 0.00b mol·kg−1 ηo= 0.890 mPa·s 0.895 0.896 0.896 0.900 0.905 0.907 0.910 0.914 I = 0.29997 mol·kg−1 ηo= 0.934 mPa·s 0.936 0.938 0.939 0.942 0.943 0.946 0.947 0.948 I = 0.74997 mol·kg−1 ηo= 0.981 mPa·s 0.984 0.986 0.987 0.989 0.992 0.993 0.994 0.995 I = 1.49985 mol·kg−1 ηo= 1.072 mPa·s 1.075 1.076 1.079 1.080 1.083 1.085 1.086 1.087 I = 2.24982 mol·kg−1 ηo= 1.147 mPa·s 1.150 1.151 1.152 1.154 1.155 1.157 1.161 1.162 I = 2.99967 mol·kg−1 ηo= 1.214 mPa·s 1.218 1.220 1.220 1.222 1.225

I

T/K = 308.15

T/K = 318.15

ηo= 0.719 mPa·s 0.723 0.724 0.724 0.728 0.732 0.735 0.737 0.741

ηo= 0.596 mPa·s 0.599 0.600 0.601 0.606 0.609 0.611 0.613 0.617

ηo= 0.751 mPa·s 0.752 0.753 0.755 0.758 0.759 0.762 0.763 0.764

ηo= 0.624 mPa·s 0.625 0.626 0.627 0.629 0.632 0.634 0.636 0.637

ηo= 0.794 mPa·s 0.797 0.798 0.799 0.801 0.803 0.805 0.806 0.807

ηo= 0.659 mPa·s 0.662 0.663 0.665 0.667 0.668 0.670 0.670 0.671

ηo= 0.862 mPa·s 0.864 0.866 0.868 0.870 0.872 0.874 0.875 0.875

ηo= 0.715 mPa·s 0.717 0.718 0.720 0.722 0.724 0.726 0.728 0.729

ηo= 0.934 mPa·s 0.937 0.938 0.939 0.940 0.941 0.944 0.946 0.947

ηo= 0.762 mPa·s 0.765 0.766 0.767 0.768 0.770 0.772 0.773 0.775

ηo= 1.010 mPa·s 1.013 1.016 1.018 1.018 1.020

ηo= 0.814 mPa·s 0.817 0.819 0.821 0.822 0.824



Article

Table 4. continued η/mPa·s mA/mol·kg

−1

T/K = 288.15

0.01809 0.02282 0.02892

ηo= 1.534 mPa·s 1.547 1.549 1.552

0.00213 0.00284 0.00394 0.00519 0.00617 0.00689 0.00819 0.00921

1.139 1.139 1.140 1.140 1.141 1.141 1.142 1.142

0.00201 0.00412 0.00608 0.00794 0.00913 0.01018 0.01489 0.02067

1.210 1.211 1.212 1.213 1.214 1.215 1.216 1.217

0.00200 0.00406 0.00602 0.00806 0.00882 0.00990 0.01477 0.02056

1.251 1.251 1.252 1.253 1.254 1.255 1.256 1.257

0.00210 0.00371 0.00561 0.00772 0.00880 0.00993 0.01358 0.01731

1.356 1.357 1.357 1.358 1.359 1.360 1.360 1.362

0.00206 0.00391 0.00582 0.00749 0.00858 0.00944 0.01417 0.01957

1.446 1.447 1.448 1.449 1.450 1.450 1.451 1.452

0.00200 0.00374 0.00579 0.00783 0.00851 0.00936 0.01399 0.01924

1.535 1.536 1.537 1.538 1.538 1.539 1.540 1.541

T/K = 298.15 ηo= 1.214 mPa·s 1.227 1.230 1.233 Theophylline I = 0.00b mol·kg−1 0.891 0.892 0.892 0.892 0.893 0.893 0.894 0.895 I = 0.29997 mol·kg−1 0.934 0.935 0.936 0.937 0.937 0.939 0.940 0.941 I = 0.74997 mol·kg−1 0.980 0.981 0.983 0.984 0.985 0.986 0.987 0.988 I = 1.49985 mol·kg−1 1.072 1.073 1.074 1.075 1.076 1.077 1.078 1.079 I = 2.24982 mol·kg−1 1.149 1.150 1.151 1.151 1.152 1.153 1.153 1.155 I = 2.99967 mol·kg−1 1.215 1.216 1.217 1.217 1.219 1.220 1.220 1.223

J

T/K = 308.15

T/K = 318.15

ηo= 1.010 mPa·s 1.022 1.025 1.027

ηo= 0.814 mPa·s 0.826 0.829 0.831

0.719 0.720 0.720 0.721 0.722 0.722 0.723 0.723

0.597 0.597 0.598 0.598 0.599 0.599 0.599 0.600

0.750 0.751 0.752 0.754 0.755 0.755 0.756 0.757

0.624 0.625 0.625 0.627 0.627 0.628 0.629 0.630

0.795 0.795 0.796 0.797 0.797 0.798 0.800 0.801

0.658 0.659 0.660 0.661 0.663 0.664 0.664 0.665

0.863 0.864 0.864 0.865 0.866 0.866 0.868 0.869

0.715 0.716 0.717 0.718 0.719 0.719 0.720 0.721

0.936 0.937 0.937 0.938 0.939 0.939 0.940 0.941

0.763 0.764 0.765 0.765 0.766 0.767 0.768 0.769

1.011 1.012 1.013 1.014 1.015 1.015 1.016 1.017

0.815 0.816 0.816 0.818 0.818 0.819 0.820 0.821



Article

Table 4. continued η/mPa·s mA/mol·kg

−1

T/K = 288.15

0.00051 0.00070 0.00090 0.00098 0.00123 0.00147 0.00182 0.00212

1.138 1.139 1.139 1.139 1.139 1.139 1.139 1.139

0.00049 0.00058 0.00079 0.00104 0.00118 0.00145 0.00182 0.00208

1.210 1.210 1.210 1.210 1.210 1.210 1.211 1.211

0.00048 0.00058 0.00079 0.00090 0.00125 0.00146 0.00173 0.00199

1.250 1.250 1.250 1.250 1.250 1.250 1.251 1.251

0.00047 0.00058 0.00079 0.00085 0.00127 0.00149 0.00179 0.00199

1.355 1.355 1.355 1.355 1.355 1.355 1.356 1.356

0.00045 0.00058 0.00079 0.00086 0.00120 0.00144 0.00183 0.00204

1.445 1.445 1.445 1.445 1.445 1.445 1.446 1.446

0.00049 0.00058 0.00079 0.00087 0.00111 0.00151 0.00174 0.00202

1.534 1.534 1.534 1.534 1.534 1.535 1.535 1.535

T/K = 298.15 Theobromine I = 0.00b mol·kg−1 0.891 0.891 0.891 0.891 0.891 0.891 0.891 0.891 I = 0.29997 mol·kg−1 0.934 0.934 0.934 0.934 0.934 0.934 0.935 0.935 I = 0.74997 mol·kg−1 0.981 0.981 0.981 0.981 0.981 0.982 0.982 0.982 I = 1.49985 mol·kg−1 1.072 1.072 1.072 1.072 1.072 1.072 1.073 1.073 I = 2.24982 mol·kg−1 1.147 1.147 1.147 1.147 1.147 1.148 1.148 1.148 I = 2.99967 mol·kg−1 1.214 1.214 1.214 1.214 1.214 1.215 1.215 1.215

T/K = 308.15

T/K = 318.15

0.720 0.720 0.720 0.720 0.720 0.720 0.720 0.720

0.597 0.597 0.597 0.597 0.597 0.597 0.597 0.597

0.751 0.751 0.751 0.751 0.751 0.751 0.752 0.752

0.624 0.624 0.624 0.624 0.624 0.624 0.624 0.625

0.794 0.794 0.794 0.794 0.794 0.794 0.794 0.795

0.659 0.659 0.659 0.659 0.659 0.659 0.659 0.660

0.862 0.862 0.862 0.862 0.862 0.862 0.863 0.863

0.715 0.715 0.715 0.715 0.715 0.715 0.715 0.716

0.934 0.934 0.934 0.934 0.934 0.934 0.935 0.935

0.762 0.762 0.762 0.762 0.762 0.762 0.763 0.763

1.010 1.010 1.010 1.010 1.010 1.011 1.011 1.011

0.814 0.814 0.814 0.814 0.814 0.814 0.815 0.815

a mA is the molality of solute in water34 or water + MgCl2 (solvent). I is the ionic strength of MgCl2 in water. bData reported in ref 34. Standard uncertainties are u(T) = 0.01 K, u(p) = 0.5 kPa, u(m) = 2.8 × 10−5 mol·kg−1 and u(η) = 0.012 mPa·s (0.68 level of confidence).

K



Article

MgCl2, which indicates the structure-breaking behavior of the solutes. Overall both the parameters, that is, (∂2V2,ϕ°/∂T2)P and dB/dT suggest the structure-breaking behavior of the solutes. It may further be noted that TPY and TBR act as structurebreakers in both aqueous solutions of MgCl2 and in aqueous NaCl solutions, whereas the behavior of CAF is anomalous. 3.6. Solvation. The solvation behavior of the solutes in aqueous MgCl2 solutions can be judged from the ratio of Bcoefficient to V°2,ϕ (B/V°2,ϕ). A ratio below 2.5 refers to unsolvated species while a higher value refers to a solvated spherical species.38 This ratio indicates the formation of the primary solvation sphere around the solute molecules.45 The B/ V°2,ϕ values of solutes are found to be greater in water as compared to that in the presence of a cosolute, indicating greater solvation of solutes (Table S6, given as Supporting Information) in water. This shows that aqueous MgCl2 solutions decrease the solvation of the studied solutes at high ionic strength. Solvation is greater in the MgCl2 solutions than in NaCl solutions as discussed earlier. Hence solvation of these solutes decreases with increase in concentration of electrolyte. 3.7. Spectroscopic Studies. The 1H NMR spectra have been obtained for the studied solutes in 9:1 (w/w) H2O−D2O water and in the presence of aqueous MgCl2 solutions at different ionic strengths, I = (0.29997−2.99967) mol·kg−1. Spectral 1H NMR peaks have been reported in a previous paper.34 Since the rapid proton exchange between OH and NH2/NH groups in the presence of D2O causes the proton signals of these disappear, only the proton signals of CH and CH3 of the solutes have been recorded. The chemical shifts of the solutes have been given in Table S7. For the given solutes, there is a sharp rise in the chemical shift values, δ at I ≈ 0.29997 mol·kg−1, and after that there is a constant decrease at other ionic strengths of aqueous MgCl2 solutions. In the case of CAF and TBR (8H) protons, positive change in δ has been observed. Whereas, in the case of TPY (1H, 3H) and TBR (3H, 7H), a change in chemical shift value of these protons becomes negative at I ≈ 2.24982 mol·kg−1. The 8H proton of TPY becomes negative at I ≈ 2.99967 mol·kg−1. The downfield/deshielded protons may be due to the dominance of hydrophilic−ionic interactions, and upfield/ shielded protons are the result of hydrophobic−ionic interactions. The order of magnitude of shift in the CAF protons is 1H > 3H > 7H > 8H which is same as observed in aqueous NaCl,34 while in the case of TPY and TBR the order is 8H > 3H ≥ 1H and 8 H > 7H ≥ 3H, respectively (Figure S3). Results show that the solute protons get deshielded at low ionic strengths of aqueous MgCl2 solutions. Deshielding decreases gradually after I ≈ 0.29997 mol·kg−1. This type of behavior is the cause of large dehydration effect of solutes. Deshielding of protons are more pronounced in CAF followed by TPY and TBR. However, in aqueous NaCl solutions, chemical shift values of the solutes continuously increase with the concentration.34 This may be due to small dehydration effect. As observed from the volumetric and viscometric studies in aqueous MgCl2 solutions, hydrophilic−ionic interactions decrease with increase in ionic strengths of aqueous MgCl2 solutions. These results also favor the spectroscopic results.

Figure 3. Plot of viscosity, η vs molality, mA, for theobromine in aqueous MgCl2 solution, I = 0.29997 mol·kg−1 as a function of temperature, T (the viscosity η increases with the molality of theobromine in aqueous MgCl2 solution and decreases with temperature as shown in the figure).

Δtr B = B‐coefficient(in aqueous MgCl2solutions) − B‐coefficient(in H 2O)

(11)

The B-coefficient values are higher in water than in the presence of aqueous MgCl2 solutions which result in negative ΔtrB values for the solutes at all temperatures and ionic strengths [Figure 2(A−C)]. The decrease of ΔtrB values with the ionic strength of MgCl2 shows that the hydrophilic−ionic interactions become progressively weaker with increasing ionic strength of MgCl2. The higher values of B-coefficients in the case of MgCl2 in comparison to that in the presence of NaCl34 indicate that stronger hydrophilic−ionic interactions exist in aqueous MgCl2 solutions more than in aqueous NaCl solutions for the studied solutes. The magnitude of ΔtrB values increase with temperature. Thus, both volumetric and viscometric studies show that hydrophilic−ionic interactions become weaker with the increase in ionic strength of MgCl2. Similar to the volume of transfer data, the plots of ΔtrB [Figure 2 (A− C)] have been made as a function of the square root of ionic strength. The linear fit provided the intercept as ΔtrB value at zero ionic strength at different temperatures, while the slopes provided the values of D-coefficients of the Jones−Dole equation. The D-coefficient is related to solute−solute interactions in the solution.64 The D-coefficient values are more negative at all the temperatures in the presence of NaCl (D-coefficient values have been calculated from the data published earlier34) than MgCl2 (Table S5). Therefore, solute− solute interactions are comparatively greater in the case of NaCl than MgCl2 which leads to more salting-out in the case of NaCl. The salting-out effect of electrolytes can also be understood using the Hofmeister’s series.65 According to this series, NaCl is a better salting-out agent than MgCl2. In our studies, it is also noted that NaCl is a better salting-out agent than MgCl2. The temperature dependence of the B-coefficient, that is, dB/dT is a better indicator of the structure-making/ breaking property of the solute. The dB/dT values in literature66 are positive for structure-breaking solutes and negative for structure-making solutes. The dB/dT values for the studied solutes are positive (Table S4) in aqueous solutions of

4. CONCLUSIONS The density and viscosity studies of CAF, TPY, and TBR were completed in aqueous MgCl2 solutions, I = (0.29997−2.99967) mol·kg−1, at temperatures T = (288.15 to 318.15) K and pressure p = 101.325 kPa. The negative Sv values are attributed L



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to the self-association of these solutes. It may be emphasized that the ΔtrV°2,ϕ values are higher at low I values for TBR followed by TPY and CAF. This signifies that the hydrophobic character follows the order CAF > TPY > TBR. From the transfer parameters of both the studies (volumetric and viscometric), it may be suggested that a competition exists between various interactions at low and high ionic strengths of aqueous MgCl2 solutions. Except in case of CAF up to I ≈ 2.24982 mol·kg−1, both the volumetric and viscometric studies suggest the structure-breaking behavior of these solutes in aqueous MgCl2 solutions. B/V2,ϕ ° values suggest that with increasing ionic strengths of aqueous MgCl2 solutions, solvation decreases. It may also be said that high ionic strengths of aqueous MgCl2 solutions would decrease the solubilization of these solutes. In the majority of the cases, the observed downfield shift at low ionic strength and significant decrease in the magnitude of downfield shift at high ionic strength of aqueous MgCl2 solutions also suggest greater dehydration behavior of the solutes. Thus, the results obtained from various techniques indicate that the xanthine drugs and MgCl2 in aqueous solutions interact through hydrophilic−ionic interactions via dehydration of solute molecules.

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.jced.7b00520. Tables: partial molar volumes at infinite dilution (V2,ϕ°) with experimental slope Sv; values of constants of equation 5 for xanthine solutes in aqueous MgCl2 solutions; partial molar expansibilities,(∂V2,ϕ°/∂T)P with their second-order derivatives (∂2V2,ϕ°/∂T2)P; viscosity B-coefficients and dB/dT values; D-coefficient values; B/ V2,ϕ° values; NMR chemical shifts, δ values. Figures: density and viscosity comparison of MgCl2 solutions with the literature values; change in chemical shift of different protons of xanthine solutes (PDF)

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

Tarlok S. Banipal: 0000-0002-6239-2543 Funding

A.B. is grateful to the Department of Science and Technology, New Delhi, for the award of Inspire Fellowship. Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS The authors are grateful to UPE-UGC scheme, New Delhi, India, for use of the NMR facility. REFERENCES

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