Volumetric, Viscometric and Spectroscopic Approach to Study the

Article pubs.acs.org/jced

Volumetric, Viscometric and Spectroscopic Approach to Study the Solvation Behavior of Xanthine Drugs in Aqueous Solutions of NaCl at T = 288.15−318.15 K and at p = 101.325 kPa Tarlok S. Banipal,* Aashima Beri, Navalpreet Kaur, and Parampaul K. Banipal Department of Chemistry, Guru Nanak Dev University, Amritsar 143005, Punjab, India S Supporting Information *

ABSTRACT: The densities (ρ), viscosities (η), and 1H nuclear magnetic resonance (NMR) studies for caffeine, theophylline, and theobromine in water and in aqueous solutions of 0.10, 0.25, 0.50, 0.75, and 1.00 mol·kg−1 sodium chloride over a temperature range T = 288.15−318.15 K and at p = 101.325 kPa have been carried out using vibrating-tube digital densimeter, micro-Ubbelohde type capillary viscometer, and Bruker (AVANCE-III, HD 500 MHz) NMR spectrometer, respectively. From the density and viscosity data, apparent molar volume (V2,ϕ), partial molar volume at infinite dilution (V2,ϕ0), viscosity B-coefficient, corresponding transfer (ΔtrV2,ϕ0 and ΔtrB) and other related parameters have been calculated. The trends in transfer parameters reveal the dominance of hydrophilic−ionic interactions at lower molalities of NaCl while hydrophobic−ionic interactions at higher molalities of NaCl. The expansibilities and dB/dT data show the structurebreaking behavior of theophylline and theobromine in water and in aqueous solutions of NaCl. However, behavior of caffeine is exceptional. The increase in chemical shift (δ) values with increasing molalities of NaCl also signifies the predominance of solute−cosolute interactions over the dehydration process. The results have further been discussed and rationalized in terms of various interactions. Biological fluid consists of a wide range of components like sugars, polymers, alcohols, amino acids, peptides, proteins, electrolytes, and so forth.21 However, inorganic electrolytes such as NaCl, CaCl2, and MgCl2 are the essential components of biological fluid.22 They play important role in living cells, seawater, soils and effect the stability of biomolecules. They have their utility in maintaining the osmolarity and also the electrolytic balance of the body. Sodium chloride (NaCl) occurs mainly in the extracellular fluid23 and is vital for human life. The occurrence of Na+ is 92% of the total positive ions and Cl− is 68% of total negative ions.24 It is used as an important constituent in food, cosmetics, and also in pharmaceutical industry.25 To understand the solutes actions in the biological fluids, it is important to study their physicochemical properties at the molecular level.26 Therefore, combined study of thermodynamic, transport and spectroscopic properties of these solutes in the presence of aqueous NaCl solutions (cosolute) may help to understand the various solute−solvent interactions occurring in the mixed systems. Also the effect of solutes on the structure of water in the presence of electrolyte cannot be studied but assessed from the derived properties parameters such as apparent molar volumes (V2,ϕ), partial molar volume (V2,ϕ0), partial molar expansibilities (∂V2,ϕ0/

1. INTRODUCTION Xanthine based drugs such as caffeine (CAF), theophylline (TPY), and theobromine (TBR) have importance both in pharmacy and food industry.1−5 It is of particular interest to study these solutes because they are present in many daily used beverages. CAF (1,3,7-trimethylxanthine), TPY (1,3-dimethylxanthine) and TBR (3,7-dimethylxanthine) belong to the family of methylxanthines6 which differ in the positions of CH3 substituents. They are natural purine alkaloids present in tea leaves, coffee,7 cocoa seeds, and in food and beverages made from them.8−11 CAF being addictive in nature reduces drowsiness and the Food and Drug Administration (FDA) has recognized it as a safe (GRAS) substance.12 TBR also has its food value as its name originated from the Greek word “food of the gods”.13 Despite their tremendous importance as a food constituent, they also carry their pharmacological value. CAF is used for treatment of asthma and migraines14 and to influence various body systems including the central nervous system (CNS), gastrointestinal, cardiovascular, respiratory, and renal systems.15 In combination, CAF and TPY are used in premature infants for the remedy of neonatal apnea.16 TBR and TPY are useful as bronchodilators, diuretics, and also as vasodilators. They are preferred to prevent and treat respiratory disorders like asthma.17,18 These are the most frequently ingested solutes in the world but even then their physicochemical properties are poorly understood.19,20 © XXXX American Chemical Society

Received: March 30, 2016 Accepted: October 31, 2016

A

DOI: 10.1021/acs.jced.6b00273 J. Chem. Eng. Data XXXX, XXX, XXX−XXX

Journal of Chemical & Engineering Data

Article

Table 1. Chemicals with Their Structure, Molecular Formula, Molar Mass (M), Source, CAS Number, Mass Fraction Purity (w), and Analysis Methods

a

As reported by the suppliers. bMass fraction purity as obtained from HPLC analysis.

±0.01s. The average of six readings at least has been used as the final efflux time for calculations. The viscometer was calibrated with double distilled water at different temperatures. The accuracy of the apparatus was checked by measuring viscosities of L-glycine at 298.15 K which agreed well with the literature values.31 The standard uncertainties in the viscosities are ±0.012 mPa·s (by considering 1% uncertainty in viscosity for water that is used for the calibration of apparatus). Densities and viscosities for pure water were taken from the literature.32−35 1 H spectroscopic studies have been performed using Bruker AVANCE-III, HD 500 MHz spectrometer at 298.15 K. The center of HDO signal (4.650 ppm) has been considered as the internal reference for the other nuclei to establish the chemical shifts for the studied solutes being D2O as the lock solvent. NMR specta of CAF, TPY, and TBR in the absence as well as in the presence of aqueous NaCl solutions have been studied in 9:1 (w/w) H2O−D2O solution.

∂T)P, viscosity B-coefficients, and so forth. 1H NMR studies provide information about the effect of electrolyte on the local environment of the solute protons in water as well as in the presence of aqueous NaCl solutions. So we planned to carry out the physicochemical properties of CAF, TPY, and TBR (solutes) in water and in aqueous solutions of NaCl at different molalities and temperatures.

2. EXPERIMENTAL SECTION The specifications of the chemicals used are given in Table 1. These chemicals were used without further treatment but stored in vacuum desiccator over CaCl2 (anhydrous) at room temperature for 48 h before use. The purity of these solutes was analyzed using UHPLC - NEXERA (SHIMADZU, Asia Pacific limited) with C18G column (4.6 × 150 mm), porosity 5 μm; mobile phase, water/methanol/orthophosphoric acid (79.9/ 20/0.1); injected volume, 20 μL; speed, 1.0 mL min−1. UV detection was observed at 210 nm and the column was operated at 30 °C. The mass fraction purity obtained was more than 0.95. All the solutions were freshly prepared in double distilled, degassed water obtained from Ultra UV/UF Rions lab water system having a specific conductance less than 1.3 × 10−4 Sm−1. The solutions were prepared on gravimetric basis using a Mettler balance (model: AB265-S) having a precision of ±0.01 mg. The solution densities have been measured using the vibrating-tube digital densimeter (model: DMA 60/602, Anton Paar, Austria). The temperature of the densimeter cell was controlled within ±0.01 K. The calibration of the densimeter was done using dry air and pure water,27 and its accuracy was checked by measuring the densities of aqueous NaCl solutions at 288.15−318.15 K, which agree well with the literature values28−30 (Supporting Information, Figure S1) The standard uncertainty in the density is ±0.01 kg·m−3 (by taking 1% uncertainty in density due to impurity in samples). Viscosity measurements have been carried out with an Micro-Ubbelhode capillary viscometer using a constant temperature bath (model MC 31A Julabo/Germany) having temperature stability within ±0.01 K. Flow time measurements have been performed using an automatic digital viscosity measuring unit (SCHOTT AVS 350) with a resolution of

3. RESULTS AND DISCUSSION 3.1. Apparent Molar Volumes. The densities, ρ, of the CAF, TPY and TBR in water and in mB, (molality of NaCl in water) = 0.1, 0.25, 0.5, 0.75, and 1.0 mol·kg−1, have been measured at T = 288.15, 298.15, 308.15 and 318.15 K. As it can be observed from Table 2, the ρ values increase with the molality of the solute in water as well as in aqueous NaCl solutions and decrease with the rise of temperature. The ρ values for CAF in water are in good agreement with the literature36−41 values (Figure S2), whereas no density values are available for comparison in case of TPY and TBR. Apparent molar volumes, V2,ϕ, for the studied solutes have been determined from the experimentally measured densities using the relation:42 ⎧ M ⎫ ⎧ (ρ − ρo ) ⎫ ⎬ V2, ϕ = ⎨ ⎬ − ⎨ ⎩ ρ ⎭ ⎩ (mA ρρo ) ⎭ ⎪

⎪

⎪

⎪

(1)

where M and mA are the molar mass and molality of the solutes, ρo is the density of solvent (H2O or NaCl + H2O) and ρ is the density of solution, respectively. The ρ and V2,ϕ values for the solutes in water and in aqueous solutions of NaCl as a function B


a

C

141.30 141.28 141.25 141.23 141.21 141.17 141.07 141.02

140.04 140.00 139.96 139.88 139.77 139.74 139.68 139.63

(ρo = 1009.78 kg·m−3) 1.009933 1.010035 1.010147 1.010229 1.010575 1.010748 1.011102 1.011307

(ρo = 1019.738 kg·m−3) 1.019897 1.019995 1.020098 1.020208 1.020534 1.020779 1.021065 1.021296

0.00294 0.00491 0.00705 0.00863 0.01530 0.01862 0.02539 0.02931

0.00303 0.00491 0.00686 0.00896 0.01515 0.01980 0.02524 0.02961

142.56 142.50 142.42 142.35 142.23 142.20 142.10 142.05

0.00307 0.00499 0.00606 0.00881 0.01539 0.01939 0.02550 0.02882

(ρo = 999.129 kg·m−3)c,d 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

V2,ϕ × 106 (m3·mol−1) Caffeine in Water

T/K = 298.15

ρ × 10−3 (kg·m−3)

V2,ϕ × 106 (m3·mol−1)

(ρo = 999.875 kg·m−3) 0.999991 1.000069 1.000153 1.000216 1.000496 1.000649 1.000959 1.001039

(ρo = 994.175 kg·m−3) 0.994295 0.994371 0.994445 0.994521 0.994781 0.994939 0.995182 0.995316

153.38 153.34 153.30 153.24 153.14 153.09 153.00 152.95

154.77 154.75 154.69 154.63 154.52 154.49 154.33 154.32

155.67 155.62 155.59 155.52 155.37 155.34 155.23 155.10

(ρo = 990.244 kg·m−3)c,d 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

T/K = 318.15

ρ × 10−3 (kg·m−3)

(ρo = 1009.78 kg·m−3) 1.009900 1.009975 1.010053 1.010137 1.010384 1.010569 1.010788 1.010963

V2,ϕ × 106 (m3·mol−1)

T/K = 308.15

ρ × 10−3 (kg·m−3)

(ρo = 997.047 kg·m−3)c,d (ρo = 994.063 kg·m−3)c,d 0.997304 143.94 0.994303 147.65 0.997399 143.79 0.994390 147.61 0.997504 143.71 0.994488 147.59 0.998060 143.48 0.995013 146.99 0.998576 143.13 0.995497 146.62 0.998853 143.05 0.995759 146.49 0.999101 142.92 0.996001 146.14 0.999619 142.58 0.996484 145.91 b mB = 0.10 mol·kg−1 (ρo = 1001.12 kg·m−3) (ρo = 998.046 kg·m−3) 1.001265 146.81 0.998179 150.88 1.001356 146.77 0.998263 150.81 1.001446 146.73 0.998346 150.76 1.001537 146.69 0.998431 150.69 1.001849 146.60 0.998718 150.63 1.002039 146.57 0.998894 150.55 1.002329 146.49 0.999163 150.42 1.002487 146.46 0.999309 150.39 mB = 0.25 mol·kg−1 (ρo = 1007.289 kg·m−3) (ρo = 1003.48 kg·m−3) 1.007431 145.24 1.003610 149.54 1.007526 145.20 1.003698 149.50 1.007629 145.15 1.003792 149.45 1.007706 145.11 1.003863 149.41 1.008029 145.03 1.004159 149.34 1.008189 144.99 1.004306 149.31 1.008520 144.83 1.004608 149.22 1.008712 144.75 1.004784 149.13 mB = 0.50 mol·kg−1 (ρo = 1017.14 kg·m−3) (ρo = 1013.81 kg·m−3) 1.017286 144.26 1.013944 148.43 1.017377 144.21 1.014028 148.40 1.017471 144.17 1.014114 148.37 1.017573 144.12 1.014207 148.33 1.017873 144.04 1.014482 148.26 1.018098 143.99 1.014691 148.11 1.018362 143.94 1.014935 148.00 1.018574 143.90 1.015131 147.94

V2,ϕ × 106 (m3·mol−1)

T/K = 288.15

ρ × 10−3 (kg·m−3)

(ρo = 1003.328 kg·m−3) 1.003485 1.003584 1.003682 1.003782 1.004121 1.004327 1.004669 1.004816

0.00510 0.00695 0.00902 0.01993 0.02992 0.03531 0.04008 0.04992

mA (mol·kg−1)

Table 2. Densities, ρ, and Apparent Molar Volumes, V2,ϕ, of Xanthine Solutes in Water and in aqueous NaCl Solutions from T = 288.15−318.15 K and p = 101.325 kPa

Journal of Chemical & Engineering Data Article


a

D

0.00206 0.00295 0.00426 0.00471 0.00631 0.00691 0.00839 0.00888 0.00998

1.003433 1.003479 1.003546 1.003569 1.003651 1.003682 1.003758 1.003783 1.003841

0.999241 0.999283 0.999333 0.999388 0.999443 0.999509 0.999551 0.999638 0.999667 128.87 128.81 128.80 128.74 128.72 128.64 128.61 128.58 128.47

126.30 126.15 126.11 126.05 125.91 125.85 125.79 125.68 125.58

136.55 136.51 136.47 136.43 136.36 136.32 136.28 136.22

(ρo = 1039.16 kg·m−3) 1.039321 1.039423 1.039512 1.039630 1.039990 1.040204 1.040533 1.040678

0.00302 0.00489 0.00654 0.00869 0.01531 0.01923 0.02527 0.02791

0.00208 0.00285 0.00378 0.00479 0.00578 0.00699 0.00776 0.00934 0.00986

138.53 138.45 138.36 138.33 138.24 138.13 138.03 137.91

0.00291 0.00502 0.00672 0.00890 0.01528 0.01843 0.02518 0.02930

V2,ϕ × 106 (m3·mol−1)

1.001217 1.001260 1.001323 1.001345 1.001421 1.001451 1.001522 1.001545 1.001599

0.997153 0.997192 0.997239 0.997291 0.997341 0.997404 0.997443 0.997526 0.997554

(ρo = 1036.18 kg·m−3) 1.036331 1.036426 1.036509 1.036618 1.036951 1.037150 1.037454 1.037589 129.66 129.62 129.58 129.50 129.41 129.33 129.22 129.11 128.86 mB = 0.10 mol·kg−1 132.77 132.64 132.48 132.31 132.24 132.15 132.14 132.12 132.00

0.998140 0.998180 0.998240 0.998261 0.998334 0.998361 0.998429 0.998452 0.998502

0.994165 0.994204 0.994250 0.994300 0.994350 0.994410 0.994448 0.994528 0.994554

134.89 134.82 134.79 134.72 134.69 134.64 134.61 134.56 134.53

131.38 131.27 131.20 131.12 130.98 130.94 130.91 130.83 130.78

145.00 144.96 144.94 144.89 144.83 144.81 144.73 144.67

146.79 146.75 146.71 146.66 146.61 146.59 146.51 146.48

0.994264 0.994302 0.994359 0.994379 0.994448 0.994475 0.994539 0.994561 0.994610

0.990343 0.990379 0.990423 0.990472 0.990519 0.990578 0.990614 0.990691 0.990716

(ρo = 1028.31 kg·m−3) 1.028435 1.028514 1.028583 1.028673 1.028950 1.029115 1.029368 1.029480

137.54 137.47 137.42 137.37 137.33 137.28 137.23 137.15 137.08

133.62 133.52 133.43 133.36 133.29 133.23 133.20 133.12 133.00

149.53 149.41 149.33 149.30 149.23 149.15 149.11 149.04

151.44 151.36 151.29 151.22 151.19 151.07 151.04 150.94

V2,ϕ × 106 (m3·mol−1)

T/K = 318.15

ρ × 10−3 (kg·m−3)

(ρo = 1018.94 kg·m−3) 1.019058 1.019144 1.019214 1.019303 1.019563 1.019694 1.019970 1.020141

V2,ϕ × 106 (m3·mol−1)

T/K = 308.15

ρ × 10−3 (kg·m−3)

mB = 0.75 mol·kg−1 (ρo = 1023.12 kg·m−3) 142.62 1.023251 142.60 1.023346 142.53 1.023423 142.49 1.023521 142.44 1.023809 142.38 1.023951 142.30 1.024257 142.25 1.024443 mB = 1.00 mol·kg−1 (ρo = 1032.47 kg·m−3) 140.74 1.032608 140.63 1.032695 140.56 1.032770 140.47 1.032870 140.37 1.033174 140.32 1.033355 140.27 1.033634 140.21 1.033756 Theophylline in Water

Caffeine in Water

T/K = 298.15

ρ × 10−3 (kg·m−3)

(ρo = 1026.12 kg·m−3) 1.026263 1.026366 1.026450 1.026558 1.026871 1.027027 1.027360 1.027564

V2,ϕ × 106 (m3·mol−1)

T/K = 288.15

ρ × 10−3 (kg·m−3)

(ρo = 1029.45 kg·m−3) 1.029604 1.029717 1.029807 1.029924 1.030264 1.030434 1.030795 1.031019

mA (mol·kg−1)

Table 2. continued



1.009887 1.009931 1.009999 1.010042 1.010107 1.010113 1.010163 1.010231 1.010266

1.019842 1.019894 1.019944 1.019998 1.020047 1.020093 1.020145 1.020179 1.020251

1.029569 1.029614 1.029670 1.029704 1.029752 1.029815 1.029846 1.029925 1.029981

1.039270 1.039309 1.039375 1.039410 1.039456 1.039522 1.039563 1.039615 1.039675

0.999157 0.999167

0.00208 0.00291 0.00422 0.00505 0.00631 0.00671 0.00773 0.00909 0.00979

0.00200 0.00301 0.00397 0.00501 0.00595 0.00682 0.00781 0.00846 0.00982

0.00229 0.00313 0.00421 0.00485 0.00576 0.00695 0.00755 0.00902 0.01006

0.00216 0.00288 0.00413 0.00480 0.00566 0.00691 0.00767 0.00865 0.00977

0.00051 0.00070

Table 2. continued

E

126.37 126.35

124.70 124.65 124.58 124.48 124.35 124.32 124.29 124.27 124.22

125.78 125.72 125.68 125.60 125.53 125.45 125.40 125.29 125.16

126.71 126.69 126.67 126.66 126.59 126.57 126.53 126.49 126.35

127.66 127.59 127.53 127.51 127.48 127.45 127.38 127.26 127.21

0.997073 0.997083

1.036285 1.036321 1.036382 1.036414 1.036457 1.036518 1.036556 1.036604 1.036659

1.026230 1.026271 1.026323 1.026354 1.026398 1.026456 1.026485 1.026557 1.026608

1.017235 1.017283 1.017328 1.017378 1.017422 1.017464 1.017511 1.017542 1.017607

1.007388 1.007428 1.007491 1.007530 1.007591 1.007610 1.007660 1.007725 1.007760

129.26 129.25

mB = 0.25 mol·kg−1 131.93 131.89 131.81 131.75 131.65 131.63 131.53 131.50 131.41 mB = 0.50 mol·kg−1 131.30 131.28 131.26 131.25 131.23 131.21 131.18 131.17 131.14 mB = 0.75 mol·kg−1 129.76 129.73 129.70 129.67 129.66 129.61 129.57 129.55 129.46 mB = 1.00 mol·kg−1 128.40 128.37 128.36 128.34 128.29 128.26 128.21 128.17 128.13 Theobromine in Water

Theophylline in Water

0.994088 0.994097

1.032571 1.032606 1.032665 1.032696 1.032737 1.032796 1.032832 1.032879 1.032933

1.023225 1.023264 1.023314 1.023343 1.023385 1.023440 1.023468 1.023536 1.023585

1.013901 1.013946 1.013990 1.014038 1.014081 1.014121 1.014166 1.014196 1.014258

1.003574 1.003611 1.003670 1.003708 1.003765 1.003783 1.003829 1.003891 1.003922

131.91 131.90

130.38 130.33 130.31 130.18 130.13 130.12 130.08 130.07 129.99

132.20 132.18 132.14 132.12 132.09 132.03 132.01 131.98 131.85

133.59 133.57 133.43 133.42 133.37 133.35 133.26 133.25 133.23

134.79 134.77 134.76 134.73 134.70 134.68 134.65 134.62 134.60

0.990268 0.990277

1.028407 1.028439 1.028496 1.028526 1.028565 1.028621 1.028656 1.028701 1.028753

1.019040 1.019077 1.019124 1.019152 1.019192 1.019245 1.019271 1.019337 1.019383

1.009867 1.009910 1.009952 1.009998 1.010039 1.010077 1.010120 1.010149 1.010210

0.999965 1.000001 1.000057 1.000093 1.000148 1.000166 1.000211 1.000271 1.000301

133.39 133.37

132.81 132.74 132.62 132.55 132.53 132.52 132.51 132.42 132.32

134.82 134.79 134.74 134.70 134.60 134.53 134.46 134.37 134.33

135.93 135.86 135.81 135.77 135.70 135.65 135.62 135.53 135.41

137.04 137.03 136.99 136.91 136.88 136.79 136.66 136.61 136.55



F

1.009804 1.009817 1.009824 1.009830 1.009841 1.009856 1.009871 1.009884

1.019767 1.019776 1.019783 1.019792 1.019800 1.019811 1.019828 1.019836

0.00048 0.00074 0.00088 0.00098 0.00120 0.00152 0.00181 0.00206

0.00056 0.00075 0.00089 0.00104 0.00120 0.00142 0.00175 0.00191

1.029478 1.029485 1.029496 1.029498 1.029512 1.029530 1.029544 1.029551

1.003352 1.003366 1.003372 1.003379 1.003388 1.003400 1.003418 1.003425

0.00049 0.00077 0.00089 0.00102 0.00120 0.00146 0.00182 0.00195

0.00053 0.00068 0.00088 0.00093 0.00120 0.00155 0.00182 0.00195

0.999177 0.999182 0.999195 0.999209 0.999228 0.999244

0.00090 0.00098 0.00123 0.00148 0.00183 0.00213

Table 2. continued

126.33 126.32 126.31 126.30 126.29 126.26 126.25 126.22

127.40 127.39 127.38 127.36 127.35 127.34 127.32 127.31

129.00 128.99 128.98 128.97 128.96 128.95 128.91 128.89

130.42 130.41 130.40 130.39 130.38 130.37 130.35 130.32

126.33 126.32 126.31 126.29 126.27 126.24

1.026146 1.026153 1.026163 1.026165 1.026178 1.026195 1.026208 1.026215

1.017167 1.017176 1.017183 1.017190 1.017198 1.017209 1.017225 1.017232

1.007312 1.007324 1.007330 1.007335 1.007346 1.007361 1.007375 1.007387

1.001142 1.001156 1.001161 1.001167 1.001176 1.001188 1.001204 1.001211

0.997093 0.997097 0.997110 0.997123 0.997141 0.997156

mB =

mB =

mB =

mB =

129.23 129.21 129.20 129.18 129.15 129.10 0.10 mol·kg−1 133.77 133.76 133.74 133.73 133.72 133.70 133.67 133.66 0.25 mol·kg−1 132.37 132.36 132.35 132.33 132.32 132.30 132.27 132.23 0.50 mol·kg−1 130.51 130.50 130.49 130.47 130.45 130.44 130.42 130.39 0.75 mol·kg−1 129.60 129.58 129.56 129.54 129.53 129.51 129.49 129.46

Theobromine in Water

1.023144 1.023150 1.023159 1.023161 1.023174 1.023190 1.023202 1.023207

1.013835 1.013843 1.013849 1.013856 1.013863 1.013873 1.013888 1.013895

1.003501 1.003512 1.003519 1.003523 1.003533 1.003547 1.003560 1.003571

0.998067 0.998079 0.998084 0.998090 0.998098 0.998109 0.998124 0.998130

0.994107 0.994111 0.994123 0.994135 0.994152 0.994167

133.37 133.36 133.35 133.33 133.32 133.31 133.30 133.27

134.45 134.44 134.43 134.41 134.40 134.38 134.37 134.36

135.89 135.87 135.85 135.84 135.83 135.82 135.81 135.78

137.48 137.47 137.46 137.45 137.43 137.42 137.41 137.38

131.88 131.87 131.86 131.84 131.82 131.79

1.018963 1.018969 1.018978 1.018979 1.018991 1.019006 1.019018 1.019023

1.009804 1.009811 1.009817 1.009824 1.009830 1.009840 1.009854 1.009860

0.999895 0.999906 0.999911 0.999916 0.999925 0.999938 0.999950 0.999961

0.994195 0.994207 0.994212 0.994217 0.994224 0.994235 0.994250 0.994255

0.990287 0.990291 0.990303 0.990314 0.990331 0.990346

135.78 135.76 135.75 135.74 135.73 135.71 135.69 135.66

137.25 137.24 137.22 137.21 137.20 137.19 137.17 137.15

138.69 138.68 138.66 138.65 138.64 138.62 138.61 138.59

139.74 139.72 139.70 139.69 139.67 139.66 139.65 139.61

133.35 133.32 133.31 133.29 133.28 133.25



Article

mA is the molality of solute in water or water + NaCl. bmB is the molality of NaCl in water. cReference 32. dReference 33. 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) = 0.01 kg·m−3, u(V2,ϕ) = 0.03 to 1.27 × 10−6 m3·mol−1 (0.68 level of confidence).

of mA, mB, and T are given in Table 2. The V2,ϕ values of the studied solutes are positive and decrease with the molality of solute (the representative plots of ρ and V2,ϕ versus molality, mA, for CAF and TPY in water as a function of temperature are given in Figure 1a,b, respectively). These observed trends in V2,ϕ with increasing solute concentration have also been rationalized in terms of self-association of solutes in aqueous solutions.37−43

Figure 1. Representative plot of (a) density, ρ versus molality, mA, for caffeine in water as a function of temperature, T. (b) Apparent molar volume, V2,ϕ, versus molality, mA, for theophylline in water as a function of temperature, T (The density, ρ, increases with the molality of caffeine in water and decreases with temperature as shown in the figure from change in color from blue to orange. The apparent molar volume, V2,ϕ, decreases with the molality of theophylline in water and increases with temperature as shown in figure from change in color from blue to orange.)

3.2. Partial Molar Volumes. At infinite dilution, apparent molar volume becomes equivalent to partial molar volume. The partial molar volume at infinite dilution, V2,ϕ0, has been evaluated for solutes by fitting the following equation to the corresponding data as follows44 V2, ϕ = V2, ϕ 0 + SvmA

(2)

where Sv is the experimental slope. The Sv values are found to be negative for the studied solutes in water as well as in aqueous NaCl solutions. The values of V2,ϕ0 and Sv are given in Table S1 (Supporting Information). The negative Sv values give information about solute−solute interactions but interestingly the Sv values decrease in the presence of aqueous NaCl solution

a

0.00041 0.00068 0.00089 0.00098 0.00120 0.00147 0.00174 0.00190

Table 2. continued

1.039178 1.039192 1.039203 1.039208 1.039219 1.039233 1.039247 1.039255

125.51 125.50 125.48 125.47 125.46 125.44 125.42 125.41

1.036200 1.036213 1.036223 1.036228 1.036238 1.036252 1.036265 1.036272

mB = 1.00 mol·kg−1 128.68 128.66 128.64 128.63 128.62 128.61 128.59 128.58

Theobromine in Water

1.032488 1.032500 1.032510 1.032514 1.032524 1.032536 1.032548 1.032555

132.42 132.41 132.39 132.38 132.37 132.36 132.34 132.32

1.028328 1.028339 1.028348 1.028352 1.028362 1.028374 1.028385 1.028392

134.54 134.53 134.52 134.51 134.49 134.47 134.46 134.44


G



Article

owing to dominating solute−cosolute interactions. The V2,ϕ0 values of CAF in water are in good aggrement with the literature.37,41,45 However, no V2,ϕ0 data are available for TPY and TBR in aqueous solutions for comparison. For the studied solutes, V2,ϕ0 values are positive in water as well as in aqueous solutions of NaCl and increase with temperature. However, in aqueous NaCl solutions, the V2,ϕ0 values first increase at lower molalities of NaCl and then start decreasing at higher molalities. This may be due to the presence of both hydrophilic and hydrophobic groups in the solutes structures and thus these solutes show different hydration pattern. As mentioned in the literature,46 the higher the molality of aqueous NaCl solutions, the greater is the association between the CAF molecules, which reduce the accessibility of CAF hydrophilic groups for water molecules. In other words, the addition of salt causes an exclusion of water from the CAF hydrophilic sites, and hydrophobic sites tend to be more hydrated. This shows that there exists a competition between hydrphobic self-association and hydrophilic hydration. Thus, at low molalities of aqueous NaCl solutions, hydrophilic−ionic interactions are more feasible whereas at higher molalities of aqueous NaCl solutions, these interactions become weaker. The partial molar volumes of transfer, ΔtrV2,ϕ0 at infinite dilution from water to aqueous solutions of NaCl have been determined as Δtr V2, ϕ 0 = V2, ϕ 0 (in aqueous NaCl solutions) − V2, ϕ 0 (in H 2O) (3)

Both positive and negative ΔtrV2,ϕ0 values have been observed for the solutes over the concentration range of NaCl studied. The ΔtrV2,ϕ0 values for the studied solutes [Figure 2] after passing through maxima in the lower concentration region, start decreasing with the rise of molalities of NaCl at all temperatures. In all the cases, ΔtrV2,ϕ0 values increase with temperature. The observed positive ΔtrV2,ϕ0 values at lower molalities of aqueous NaCl solution decrease in the following order: TBR > TPY > CAF. In the studied systems, various possible interactions are (1) hydrophilic−ionic interactions among polar groups of the solutes and ions (Na+ and Cl−) of the cosolute and (2) hydrophobic−ionic interactions between the nonpolar parts of solutes and ions of the cosolute. First type of interactions contribute positively to V2,ϕ0 values and second type of interactions contribute negatively to V2,ϕ0 values in accordance with cosphere overlap model.47 The overlap of cospheres of hydrophilic−ionic or ionic−ionic species results in positive change in volume due to the effect of “electrostriction” and decrease in water H-bonded network of molecules in the solvation sphere. Moreover the overlap of two hydrophilic hydration cospheres release some water molecules to the bulk water and hence results in positive volume change. However, the overlap of hydrophobic−ionic hydration cospheres results in negative volume change. Thus, the positive ΔtrV2,ϕ0 values suggest the predominance of hydrophilic−ionic interactions and negative ΔtrV2,ϕ0 values indicate the predominance of hydrophobic−ionic interactions. The positive ΔtrV2,ϕ0 values over the significant concentration range of NaCl for the studied solutes suggest the predominance of type (1) interactions at lower molalities while at higher molalities of NaCl type (2) interactions dominate. It may also be noted that the ΔtrV2,ϕ0 values become negative at 298.15 K at mB ≈ 0.8 mol·kg−1 for TBR, mB ≈ 0.6 mol·kg−1 for TPY, and mB ≈ 0.45 mol·kg−1 for CAF. This shows that the hydrophobic character decreases in the following order: CAF > TPY > TBR. This hydrophobicity behavior is well supported with the observations made by

Figure 2. Partial molar volume of transfer at infinite dilution, ΔtrV2,ϕ0, and viscosity B-coefficients of transfer, ΔtrB, versus molalities, mB, of aqueous NaCl solution of (a/A) caffeine (b/B) theophylline (c/C) theobromine at blue diamond, 288.15 K; black square, 298.15 K; green triangle, 308.15 K; red circle, 318.15 K.

Nishijo et al.48 This order is in consonance with increase in ΔtrV2,ϕ0 values for the three studied solutes. The solubility behavior of solutes in aqueous medium as well as in the presence of cosolute assumes a very important role in the biophysical chemistry. It may provide a deeper insight about the solute−solvent interactions. Solubility may either be amplified or reduced, depending on the nature and size of electrolyte (cosolute). Hofmeister ranked ions by their ability to solubilize, known as the Hofmeister series. This series assigns salting-out as the ability of salts to absorb water. It may be simplified as water gets attached to the ions of electrolyte and removes from the surface of solute molecules and reverse is true for the salting-in process.49 In the volumetric studies, the positive ΔtrV2,ϕ0 values signifies the salting-in at lower molalities of NaCl, whereas negative ΔtrV2,ϕ0 values at higher molalities of NaCl may be attributed to salting-out effect. Hence, high concentrations of NaCl would decrease the solubilization of these solutes.50 This shows that salting-in decreases with increasing concentration of NaCl after a particular concentration of NaCl and finally at higher concentrations of NaCl, salting-out comes in picture. 3.3. Partial Molar Expansibilities. To study the effect of temperature, the partial molar expansibilities, VE0 (VE0 = ∂V2,ϕ0/ ∂T)P and their second-order derivatives, (∂2V2,ϕ0/∂T2)P have been calculated by fitting the V2,ϕ0 data using the method of least-squares to the following equation H



Article

Table 3. Viscosities (η) of Xanthine Solutes in Water and aqueous NaCl Solutions from T = 288.15−318.15 K, and at pressure p = 101.325 kPa η/mPa·s mA (mol·kg−1)

288.15 T/K

0.00508 0.00693 0.00900 0.01986 0.02978 0.03533 0.03983 0.04953

ηo = 1.138 mPa·sb,c 1.140 1.142 1.144 1.147 1.152 1.154 1.156 1.162

0.00308 0.00500 0.00690 0.00883 0.01554 0.01940 0.02537 0.02881

ηo = 1.150 mPa·s 1.151 1.152 1.153 1.155 1.157 1.158 1.161 1.163

0.00296 0.00496 0.00711 0.00870 0.01567 0.01875 0.02510 0.02948

ηo = 1.160 mPa·s 1.159 1.161 1.162 1.164 1.167 1.168 1.171 1.173

0.00296 0.00479 0.00736 0.00913 0.01596 0.02068 0.02507 0.02882

ηo = 1.178 mPa·s 1.180 1.180 1.181 1.182 1.185 1.187 1.188 1.190

0.00299 0.00517 0.00691 0.00915 0.01573 0.01893 0.02501 0.03004

ηo = 1.214 mPa·s 1.216 1.217 1.217 1.218 1.220 1.221 1.223 1.225

0.00292 0.00682 0.00885 0.01031 0.01635 0.01886

ηo = 1.254 mPa·s 1.254 1.255 1.256 1.257 1.259 1.259

298.15 T/K

308.15 T/K

318.15 T/K

ηo = 0.719 mPa·sb,c 0.723 0.724 0.724 0.728 0.732 0.735 0.737 0.741

ηo = 0.596 mPa·sb,c 0.599 0.600 0.601 0.606 0.609 0.611 0.613 0.617

ηo = 0.728 mPa·s 0.728 0.729 0.731 0.732 0.734 0.735 0.739 0.740

ηo = 0.605 mPa·s 0.606 0.607 0.608 0.609 0.611 0.613 0.615 0.618

ηo = 0.740 mPa·s 0.740 0.742 0.743 0.744 0.745 0.747 0.749 0.750

ηo = 0.610 mPa·s 0.611 0.612 0.613 0.614 0.615 0.616 0.618 0.620

ηo = 0.756 mPa·s 0.757 0.758 0.758 0.759 0.761 0.763 0.764 0.765

ηo = 0.630 mPa·s 0.630 0.631 0.632 0.633 0.635 0.636 0.637 0.639

ηo = 0.780 mPa·s 0.782 0.782 0.783 0.784 0.784 0.785 0.787 0.789

ηo = 0.650 mPa·s 0.651 0.652 0.653 0.654 0.655 0.656 0.657 0.658

ηo = 0.812 mPa·s 0.812 0.813 0.814 0.814 0.816 0.816

ηo = 0.676 mPa·s 0.676 0.677 0.678 0.679 0.680 0.680

Caffeine/Water ηo = 0.890 mPa·sb,c 0.895 0.896 0.896 0.900 0.905 0.907 0.910 0.914 mB = 0.10 mol·kg−1 ηo = 0.901 mPa·s 0.902 0.903 0.904 0.905 0.907 0.909 0.912 0.915 mB = 0.25 mol·kg−1 ηo = 0.910 mPa·s 0.912 0.913 0.914 0.914 0.916 0.918 0.920 0.921 mB = 0.50 mol·kg−1 ηo = 0.932 mPa·s 0.932 0.933 0.934 0.936 0.937 0.939 0.941 0.942 mB = 0.75 mol·kg−1 ηo = 0.959 mPa·s 0.959 0.960 0.961 0.963 0.964 0.965 0.967 0.971 mB = 1.00 mol·kg−1 ηo = 0.991 mPa·s 0.991 0.993 0.994 0.994 0.996 0.996 I



Article

Table 3. continued η/mPa·s −1

mA (mol·kg )

288.15 T/K

298.15 T/K

308.15 T/K

318.15 T/K

Caffeine/Water 0.02520 0.02912

mB = 1.00 mol·kg−1 0.998 0.999 Theophylline/Water

1.261 1.262

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

0.00207 0.00296 0.00427 0.00473 0.00632 0.00692 0.00841 0.00890

1.151 1.151 1.151 1.152 1.153 1.153 1.153 1.154

0.00194 0.00287 0.00408 0.00482 0.00612 0.00673 0.00820 0.00887

1.160 1.161 1.161 1.162 1.162 1.163 1.163 1.164

0.00204 0.00306 0.00404 0.00511 0.00610 0.00695 0.00795 0.00861

1.178 1.179 1.180 1.180 1.180 1.181 1.181 1.182

0.00192 0.00295 0.00412 0.00506 0.00626 0.00716 0.00795 0.00894

1.214 1.215 1.215 1.216 1.216 1.216 1.217 1.217

0.00199 0.00313 0.00395 0.00518 0.00610 0.00706 0.00819 0.00951

1.254 1.254 1.254 1.255 1.255 1.255 1.256 1.256

mB =

mB =

mB =

mB =

mB =

0.891 0.892 0.892 0.892 0.893 0.893 0.894 0.895 0.10 mol·kg−1 0.902 0.902 0.902 0.903 0.903 0.903 0.904 0.905 0.25 mol·kg−1 0.910 0.911 0.911 0.912 0.912 0.912 0.913 0.913 0.50 mol·kg−1 0.932 0.932 0.933 0.933 0.934 0.934 0.934 0.934 0.75 mol·kg−1 0.959 0.960 0.960 0.960 0.961 0.961 0.961 0.962 1.00 mol·kg−1 0.991 0.992 0.992 0.992 0.993 0.993 0.993 0.994

J

0.817 0.819

0.682 0.682

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

0.728 0.729 0.729 0.729 0.730 0.730 0.730 0.731

0.606 0.606 0.607 0.607 0.607 0.608 0.608 0.608

0.740 0.740 0.741 0.741 0.742 0.742 0.743 0.743

0.610 0.610 0.611 0.611 0.612 0.612 0.612 0.613

0.756 0.757 0.757 0.757 0.758 0.758 0.758 0.758

0.630 0.630 0.630 0.631 0.631 0.631 0.632 0.632

0.780 0.781 0.781 0.781 0.781 0.782 0.782 0.782

0.650 0.650 0.651 0.651 0.652 0.652 0.652 0.652

0.812 0.812 0.812 0.813 0.813 0.813 0.814 0.814

0.676 0.676 0.677 0.677 0.677 0.678 0.678 0.678



Article

Table 3. continued Theobromine/Water 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

0.00051 0.00066 0.00086 0.00099 0.00123 0.00149 0.00175 0.00213

1.150 1.150 1.150 1.150 1.151 1.151 1.151 1.151

0.00054 0.00071 0.00085 0.00094 0.00112 0.00151 0.00197 0.00211

1.160 1.160 1.160 1.160 1.161 1.161 1.161 1.161

0.00053 0.00074 0.00092 0.00106 0.00124 0.00155 0.00175 0.00193

1.179 1.179 1.179 1.179 1.179 1.179 1.179 1.179

0.00055 0.00070 0.00091 0.00095 0.00120 0.00160 0.00178 0.00201

1.214 1.214 1.214 1.214 1.214 1.214 1.215 1.215

0.00043 0.00071 0.00092 0.00102 0.00123 0.00153 0.00179 0.00197

1.254 1.254 1.254 1.254 1.254 1.254 1.254 1.254

mB =

mB =

mB =

mB =

mB =

0.891 0.891 0.891 0.891 0.891 0.891 0.891 0.891 0.10 mol·kg−1 0.901 0.901 0.901 0.901 0.901 0.902 0.902 0.902 0.25 mol·kg−1 0.910 0.910 0.910 0.910 0.910 0.911 0.911 0.911 0.50 mol·kg−1 0.932 0.932 0.932 0.932 0.932 0.932 0.932 0.932 0.75 mol·kg−1 0.959 0.959 0.959 0.959 0.959 0.959 0.960 0.960 1.00 mol·kg−1 0.991 0.991 0.991 0.991 0.991 0.991 0.992 0.992

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

0.728 0.728 0.728 0.728 0.728 0.728 0.729 0.729

0.606 0.606 0.606 0.606 0.606 0.606 0.606 0.606

0.740 0.740 0.740 0.740 0.740 0.740 0.741 0.741

0.610 0.610 0.610 0.610 0.610 0.610 0.611 0.611

0.756 0.756 0.756 0.756 0.756 0.757 0.757 0.757

0.630 0.630 0.630 0.630 0.630 0.630 0.630 0.630

0.780 0.780 0.780 0.780 0.780 0.780 0.780 0.781

0.650 0.650 0.650 0.650 0.650 0.650 0.650 0.650

0.812 0.812 0.812 0.812 0.812 0.812 0.812 0.812

0.676 0.676 0.676 0.676 0.676 0.676 0.676 0.676

a

mA is the molality of solute in water or water + NaCl (solvent). mB is the molality of NaCl in water. bReference 34. cReference 35. 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).

V2, ϕ 0 = a + bT + cT 2

(∂V2,ϕ0/∂T)P values increase with temperature both in water as well as in aqueous NaCl solutions while reverse trend with temperature is observed in case of TPY and TBR. However, the trend with the molality of cosolute is irregular.

(4)

where a, b, and c are constants and T is the absolute temperature. For the studied solutes the (∂V2,ϕ0/∂T)P values are positive (Supporting Information, Table S2). For CAF, K



Article

It has been reported that (∂2V2,ϕ0/∂T2)P should be negative for the structure-breaking and positive for the structure-making solute.51 For CAF, the positive values for (∂2V2,ϕ0/∂T2)P in water as well as in aqueous solutions of NaCl suggest that CAF acts as structure-making solute. However, the negative (∂2V2,ϕ0/ ∂T2)P values for TPY and TBR, both in water and in aqueous NaCl solutions, indicate their structure-breaking behavior. 3.4. Interaction Coefficients. McMillan−Mayer equation52 has been used to calculate interaction coefficients from the transfer volume ΔtrV2,ϕ0 of the studied solutes as follows Δtr V2, ϕ 0 = 2VABmB + 3VABBmB 2 + ...

difference is small at 318.15 K. No other data are available for comparison. However, overall comparison is good as these small differences are within standard uncertainty of ±0.012 mPa.s. Further no viscosity data are available for comparison in case of TPY and TBR. The viscosity data have been fitted by the method of least-squares using the Jones−Dole empirical equation,53 expressing the relative viscosities of solutions (treating them as nonelectrolytes) as a function of concentration η = 1 + Bc ηr = ηo (7)

(5)

where c is the molarity (calculated from molality and density data), B is the Jones−Dole coefficient, and ηr is the relative viscosity (where ηo and η are the viscosity of solvent and the solution, respectively). B-coefficient signifies the contribution arising from the size of the solute and molar volume of the solvent in addition to solute−solvent interactions. B-coefficient also relates to the order or disorder created by the addition of a solute in the solvent.54 The B-coefficient values for the studied solutes are positive in water as well as in aqueous NaCl solutions (Table S4). The B-values decrease with the molality of cosolute but increase with temperature. The B-coefficients of transfer, ΔtrB, for the studied solutes from water to aqueous NaCl solution have been evaluated using equation

where A stands for solute and B for cosolute, VAB and VABB are the volumetric pair and triplet interaction coefficients, respectively (Table S3). Positive values for VAB and negative values for VABB are observed for the studied solutes at all the temperatures. Positive values for VAB may be attributed to the presence of hydrophilic−ionic interactions, while the negative values for VABB suggest the presence of hydrophobic−ionic interactions. Comparing the magnitude of pair and triplet interaction coefficients, it has been observed that in all cases except CAF at 288.15 and 298.15 K, the magnitude of VAB is greater than VABB, hence suggesting the predominance of hydrophilic−ionic interactions over the hydrophobic−ionic interactions. However, there exists a competitive behavior between both kinds of interactions. 3.5. Viscosity and Viscosity B-Coefficients. The viscosities, η of the studied solutes have been calculated from the flow time measurements using the following expression η b = at − ρ t

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

(8)

The values of B-coefficient are higher in water than in the presence of cosolute resulting in negative ΔtrB values for the solutes at all temperatures and molalities of NaCl [Figure 2A− C]. The magnitude of ΔtrB at lower molalities of NaCl is less negative or close to zero while at higher molalities of NaCl, magnitude becomes more negative. This may be attributed to the presence of hydrophilic−ionic interactions at lower molalities of NaCl and hydrophobic−ionic at higher molalities of NaCl. The magnitude of ΔtrB increases with temperature for the studied solutes. The magnitude of ΔtrB values are higher in CAF as compared to TPY and TBR, which may be due to the presence of an additional methyl group in CAF. Comparing the transfer coefficients of volumetric and viscometric studies, it has been observed that the magnitude of ΔtrV2,ϕ0 values initially increase, and after passing through maxima the values starts decreasing and finally become negative. On the other hand, the observed ΔtrB values initially are less negative and become more negative at higher molalities of NaCl. Thus, both the studies show that there are competing hydrophilic−ionic and hydrophobic−ionic interactions, while at higher molalities of NaCl the hydrophobic−ionic interactions dominate. The temperature dependence of B-coefficient, that is, dB/dT provide better information about the structure-making/breaking property of the solute.55 The dB/dT values 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 water as well as in aqueous solutions of NaCl, which suggests the structure-breaking behavior of the solutes. A gradual decrease in the magnitude of dB/dT values with the molality of NaCl has been observed, suggesting the decrease in structure-breaking property of the studied solutes. The negative (∂2V2,ϕ0/∂T2)P and positive dB/dT values for TPY and TBR, both suggest the structure-breaking behavior. But this is not

(6)

where a and b are viscometer constants. The η values of aqueous NaCl solutions are in good agreement with the literature values (Figure S3). The η values increase with the molality of solute, mA, as well as with the molality of cosolute, mB, (Table 3) and decrease with the temperature, T, (a representative plot of η versus molality, mA for TBR in water as a function of temperature is given in Figure 3). The η values for CAF in water have been compared with the literature37 values (Figure S4). The comparison shows that the present values are slightly higher than those reported by Sinha et al. and the

Figure 3. Plot of viscosity, η versus molality, mA, for theobromine in water as a function of temperature, T. (The viscosity, η increases with the molality of theobromine in water and decreases with temperature as shown in the figure from change in color from blue to orange.) L



Article

Table 4. NMR Chemical Shifts, δ, of Xanthine Solutes in Water and in Aqueous NaCl Solutions at T = 298.15 K under p = 101.325 kPaa 1

solute protons

a

H NMR

δ/ppm

water

δ δ δ δ

H(1) H(3) H(7) H(8)

3.229 3.062 3.727 7.738

3.376 3.201 3.819 7.784

δ H(1) δ H(3) δ H(8)

3.213 3.404 7.868

3.240 3.430 7.903

δ H(3) δ H(7) δ H(8)

3.242 3.798 7.726

3.272 3.828 7.759

mB = 0.10 mol·kg

−1

mB = 0.25 mol·kg

−1

Caffeine 3.423 3.251 3.870 7.836 Theophylline 3.254 3.443 7.919 Theobromine 3.285 3.842 7.776

mB = 0.50 mol·kg−1

mB = 0.75 mol·kg−1

mB = 1.00 mol·kg−1

3.447 3.270 3.890 7.859

3.456 3.283 3.914 7.902

3.463 3.286 3.907 7.882

3.257 3.444 7.925

3.306 3.497 7.971

3.336 3.526 8.008

3.306 3.862 7.799

3.335 3.892 7.835

3.351 3.909 7.854

The standard deviation in the chemical shift values, δ is 3H > 7H > 8H, whereas in the case of TPY and TBR it is 8H > 1H ≈ 3H and 8H > 3H ≈ 7H, respectively (Figure 4a−c). Results show that the solute protons get deshielded in the presence of aqueous NaCl solution and this fact is more pronounced at higher molalities of the cosolute. Deshielding of protons is more in CAF as compared to TPY and TBR. As observed from the volumetric studies, the positive ΔtrV2,ϕ0 values that start decreasing in the higher concentration range are attributed to the dominance of hydrophobic−ionic interactions and these results are also in line with the spectroscopic results. However, volumetric and viscometric studies describe the global effect of

Figure 4. Change in chemical shift of different protons, Δδ, versus molality of NaCl, mB, of (a) caffeine, (b) theophylline, (c) theobromine.

cosolute on the bulk solution, while NMR studies mainly emphasize on the local environment of the solute molecule.

4. CONCLUSIONS The densities and viscosities of CAF, TPY, and TBR have been measured in water and in aqueous NaCl solutions, mB = 0.1, 0.25, 0.5, 0.75 and 1.0 mol·kg−1, at temperatures, T = 288.15 to 318.15 K and pressure, p = 101.325 kPa. The negative Sv values in the above-mentioned solutes are due to the self-association of these solutes in water as well as in aqueous NaCl solutions. It may be emphasized that the ΔtrV2,ϕ0 values become negative at 298.15 K at mB ≈ 0.8 mol·kg−1 for TBR, mB ≈ 0.6 mol·kg−1 for TPY and mB ≈ 0.45 mol·kg−1 for CAF. This shows that the hydrophobic character decreases in the following order: CAF > TPY > TBR. It may also be noted that high concentrations of NaCl would decrease the solubility of these solutes. By considering the transfer coefficients of both the studies, it may suggest the competition between hydrophilic−ionic and hydrophobic−ionic interactions and the absence of complete predominance of any one interaction. Except in case of CAF, M



Article

both the volumetric, (∂2V2,ϕ0/∂T2)P, and viscometric, dB/dT, studies suggest the structure-breaking behavior of these solutes in water as well as in aqueous NaCl solutions. B/V2,ϕ0 values suggest that with increasing molalities of aqueous NaCl solutions solvation decreases owing to the predominance of hydrophobic−ionic interactions. The observed downfield shift in the protons of the studied solutes in aqueous NaCl solutions also suggest the predominance of solute−cosolute interactions over the dehydration effect. Both volumetric and viscometric studies deal with the bulk macroscopic properties of solutes, while the NMR studies mainly focus on the local microscopic properties of solute. Both local and bulk properties suggest that solute−cosolute interactions are more predominant over the dehydration effect. Thus, the presence of the studied xanthine drugs in aqueous NaCl solutions, affect their thermodynamic, transport, and structural properties through hydrophobic−ionic interactions, which overpowers the effect of solute dehydration.

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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.6b00273. Partial molar volumes at infinite dilution, (V2,ϕ0) with experimental slope, Sv (Table S1), Partial molar expansibilities, (∂V2,ϕ0/∂T)P with their second-order derivatives, (∂2V2,ϕ0/∂T2)P (Table S2), pair, VAB, and triplet, VABB, interaction coefficients (Table S3), viscosity B-coefficients and dB/dT values, (Table S4), B/V2,ϕ0 values (Table S5). Density and viscosity comparison of NaCl solutions with the literature values [Figures S1 and S3]. Density and viscosity comparison of aqueous CAF solutions with the literature values [Figures S2 and S4] (PDF)

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS Authors are grateful to UPE-UGC scheme, New Delhi, India for NMR spectrometer. A.B. is grateful to the Department of Science and Technology, New Delhi for the award of Inspire Fellowship.

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REFERENCES

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Volumetric, Viscometric and Spectroscopic Approach to Study the

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