Dilution Enthalpies and Enthalpic Pairwise Self-Interactions of

Article pubs.acs.org/jced

Dilution Enthalpies and Enthalpic Pairwise Self-Interactions of Nicotinamide and Isonicotinamide in (Dimethylformamide + Water) and (Dimethyl Sulfoxide + Water) Mixed Solvents at 298.15 K Nan Chen, Zhao-Peng Jia, Hua-Qin Wang, Li-Yuan Zhu, and Xin-Gen Hu* College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou 325035, Zhejiang P. R. China ABSTRACT: The dilution enthalpies of nicotinamide (NA) and isonicotinamide (INA) in (dimethyl sulfoxide (DMSO) + water) and (dimethylformamide (DMF) + water) mixed solvents (M1 and M2) at 298.15 K have been determined, respectively, using an isothermal titration calorimeter (MicroCal ITC200). On the basis of the McMillan-Mayer theory, enthalpic pairwise self-interaction coefficients (hxx) of NA and INA in both M1 and M2 aqueous mixed solvents (mole fractions of cosolvents xcos = 0 to 0.10) have been calculated. It was found that the values of hxx are all large negative, with the relative magnitudes hxx(NA) < hxx(INA) < 0 in both M1 and M2, and hxx (in M1) > hxx (in M2) for both NA and INA, and that all of them increase monotonously with the concentrations of cosolvents (both DMF and DMSO). It implies that an intense exothermic effect accompanies with the pairwise hydrophilic−hydrophilic self-interactions, in which the meso-isomer (NA) behaves as a stronger molecular associator than the para-isomer (INA).

1. INTRODUCTION As we all know, amide compounds have a very important position in biology and chemistry. Nicotinamide (NA) is the derivative of vitamin B3, serving as an important functional group of coenzymes NAD+ and NADP+.1,2 NAD+, NADP+, and their reduced state molecules (NADH, NADPH) are widespread in the biological redox systems.3−5 In addition to the direct interest in biology,6−8 researches on NA and its derivatives or isomers (e.g., isonicotinamide (INA)) focused on electrochemistry,9 coordination chemistry,10 structural chemistry,11,12 pharmacology,13,14 and molecular interaction thermodynamics in solutions.15−17 Because of the structural and biochemical importance of combination between pyridine-ring and carboxamide moieties (Scheme 1), investigations on NA, INA, and its derivatives or analogues are ongoing.18−20

one carbonyl group (>CO) or sulfoxide group (>SO), they can interact strongly with water and other organic molecules through hydrophobic and hydrophilic interactions.21−28 Calorimetry is an effective method for exploring the energetics of molecular interactions in solutions.29−35 We have carried out a series of calorimetric investigations on pairwise self-interactions of small organic nonelectrolytes, including some chiral and achiral organic compounds of biological interest.17,36−46 In this paper, we choose NA and INA as the solutes, and DMF and DMSO as the cosolvents of aqueous mixed solvents rich in water, namely (DMF + water) and (DMSO + water) mixtures, in order to study their enthalpic pairwise self-interactions in the ternary aqueous solutions (solute + water + cosolvent).

2. MATERIALS AND METHODS 2.1. Materials. NA and INA were purchased from J&K Company, with mass fraction purity ≥ 98 % (see Table 1). They were used without further purification except drying in a vacuum desiccator over P2O5 for 72 h. DMF (Sigma-Aldrich, anhydrous, mass fraction >99.8%) and DMSO (Sigma-Aldrich, anhydrous, mass fraction ≥99.9%) were dried by 0.4 nm molecular sieves for 24 h before use. The two mixed solvents (M1 = (DMF + water) and M2 = (DMSO + water)), with the mole fraction of cosolvent xcos = 0 to 0.10, were prepared by weight using an electronic balance (Sartorius BSA224S, with a precision of 0.1 mg). All solutions (solute + pure water or mixed solvent) were also prepared by mass (Sartorius LE225D, with a precision of 0.01 mg). The errors of molalities (m) and

Scheme 1. Structures of Nicotinamide (NA) and Isonicotinamide (INA)

DMF and DMSO are typical polar aprotic solvents, with larger dielectric constants and dipole moment. Both of them have a wide application in the fields of biology, medicine, chemistry, and materials, etc. As they bear two methyl groups and © 2014 American Chemical Society

Received: May 20, 2014 Accepted: June 20, 2014 Published: June 30, 2014 2324

dx.doi.org/10.1021/je500447r | J. Chem. Eng. Data 2014, 59, 2324−2335

Journal of Chemical & Engineering Data

Article

Table 1. Provenance and Purities of the Samples Used chemical name

source

density/g·cm−3

initial mass fraction purity

purification method

final mass fraction purity

method of analysis

nicotinamide (NA) isonicotinamide (INA) dimethyl sulfoxide (DMSO) N,N-dimethyllformamide (DMF)

J&K J&K Sigma-Aldrich Sigma-Aldrich

1.400 1.204 1.100 0.948

≥ 0.98 ≥ 0.98 0.99 0.99

drying drying redistillied redistillied

0.991 0.992 0.998 0.999

HPLC HPLC GC GC

mole fractions (x) are estimated to be ± 0.00001 mol·kg−1, ± 0.0001, respectively. The Milli-Q water (Millipore Elix5/Milli-Q Academic system, product water resistivity ρ ≈ 15 MΩ·cm at 298.15 K) was used in the preparations of all solutions. 2.2. Methods. Dilution enthalpies were determined at 298.15 K by an isothermal titration calorimeter (MicroCal ITC200), which requires only a sample of 40 μL (one-sixth of that needed by VP-ITC, the early ITC type of MicroCal). All solutions were degassed carefully by ultrasonic method before experiments. The sample cell (reaction cell) was loaded with 200 μL of solvent (pure water or aqueous mixed solvent), and the 40 μL syringe was filled with sample solution (containing NA or INA as solute), which was prepared exactly by the same solvent as loaded in the reaction cell. Therefore, in the titrating process, the solvents both in the cell and the syringe are not changed in composition. A whole titration run consisted of consecutive injections of 2 μL volume and 5 s duration each, with an interval of 2 min between them (the (N − 1)th and the Nth injections). The heat effect (ΔH(mN‑1, mN)) per injection was determined by automatic peak integration of thermal power (P) versus time (t) curve recorded. The thermal effect relating to the friction in the injection was considered to be negligible. Though in most instances it is reasonable to ignore the volumetric change of solution in the cell before and after mixing, it is necessary to pay attention to the small deviation introduced concomitantly. Every sample was determined for three times in the same experimental condition, and the average heat effect (ΔH̅ (mN‑1,mN)) was used to calculate the corresponding dilution enthalpy (ΔH(mN‑1 → mN)), ΔH(mN ‐ 1 → mN ) = ΔH̅ (mN ‐ 1 , mN )/np

(see also Supporting Information). The equation necessary for the regression analysis is as follows, ΔH(mN − 1 → mN ) = 2hxx m1N − [hxx (m1 + m0) + hxxx m02] + ···

where mN (N = 1, 2, 3, ...) represents the molality of the solution containing solute X and solvent Y in the measuring cell of ITC, and m0 (mN−1, N = 1) is the initial molality of titrant solution in the syringe. From eq 4, enthalpic selfinteraction coefficients like hxx, hxxx, etc. can be evaluated by linear regression of ΔH(mN‑1 → mN) versus N. In fact, only the enthalpic pairwise interaction coefficient (hxx) is usually analyzed as its physical meaning is clearer and more accessible.

3. RESULTS AND DISCUSSION We have testified the accuracy of apparatus and method in use carefully in our previous work.38,39 The systematic errors were found to arise mainly from either the different calorimetric principles or the different calorimeter types. In general, we think that ITC is an accurate and effective method for the determination of dilution enthalpy of solution. The experimental values of ΔH(mN‑1 → mN) are listed in Tables 2, corresponding to the data in pure water, M1 and M2 mixed solvents, respectively. As an example, the typical titration curve of NA in M1 (DMF + water) mixed solvent (xDMF = 0.09569) at 298.15 K, and the fitting plot of ΔH(mN‑1 → mN) versus N are illustrated together in Figure 1. For each of the studied systems, the values of ΔH(mN‑1 → mN) are all positive and depend linearly on N with square of the correlation coefficient (R2) better than 0.95, just in line with the expected result according to eq 4. The slopes and intercepts obtained by the linear regression were used to calculate hxx and hxxx, and only the values of hxx are collected in Tables 3 and 4 for subsequent discussion. 3.1. Enthalpic Discrimination of Position Isomerization. NA and INA are meta- and para- position isomers each other. The C−N bond in amide group is well-known to be of the nature of partial double bond, with separation of charge to a certain extent, as a result of resonance interactions between the carbonyl group and the lone pair of electrons on nitrogen.49 In the present case, because of the meta- and paraisomerization of amide group on the pyridine ring, the possible pyridine-amide resonant structures lead to a considerable difference in the π-electron donating abilities from pyridine ring to amide group.50 The crystal structure and electron distribution studies show that the electrostatic properties of NA depend on its molecular conformation.51 Owing to the rotation of amide group with respect to the pyridine plane, the asymmetric electrostatic potential field is observed above and below the pyridine-ring, and the positive potential peak at the C4 atom of the pyridine ring extends to the CO-group side of the plane.51 The asymmetric potential is considered to be

(1)

where N indicates the number of injections, and np is the moles of solute in each injection volume (Vinj = 2 μL), which can be calculated as follows: np = 109Vinjdsolb0

(2)

in which dsol and b0 are the density (kg·m−3) and the concentration (mol·kg−1) of the initial solution in the syringe, respectively, and the latter is defined specially in term of mols of solute per kg of solution. From the McMillan−Mayer framework,47 the thermodynamic formula commonly used to deal with the excess enthalpy of a binary or ternary solution containing solute X and solvent Y (Y = pure water or aqueous mixed solvent) can be expressed as follows, HE(m x ) = hxx m x + hxxx m x2 + ...

(4)

(3)

in which, hxx, hxxx, and so forth are known as pairwise, triplet, and higher order enthalpic interaction coefficients, respectively. To evaluate these coefficients, dilution enthalpies of a binary solution (X+Y) are needed. The method of measuring dilution enthalpy by ITC was proposed first by Fini and Castagnolo48 2325



Article

Table 2. Experimental Dilution Enthalpies of Nicotinamide (NA) and Isonicotinamide (INA) in Pure Water, (DMSO + Water) and (DMF + Water) Mixed Solvents of Various Mole Fractions at T = (298.15 ± 0.01) K and under p = (101.35 ± 0.01) kPaa N

3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 xDMSO 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 xDMSO 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

mN‑1

mN

ΔH(mN‑1→mN)

mol·kg−1

mol·kg−1

J·mol−1

N

(mN−1)

(mN)

(ΔH(mN‑1→mN))

mol·kg−1

mol·kg−1

J·mol−1

NA and INA in Pure Water INA, m0 = 0.16772 mol·kg−1 NA, m0 = 0.18001 mol·kg−1 0.002 67 0.004 43 947.46(0.09) 3 0.002 49 0.004 12 812.66(0.11) 0.004 43 0.006 17 925.40(−0.12) 4 0.004 12 0.005 74 792.95(0.03) 0.006 17 0.007 89 901.35(0.17) 5 0.005 74 0.007 35 775.11(0.03) 0.007 89 0.009 59 873.91(0.06) 6 0.007 35 0.008 93 749.53(0.42) 0.009 59 0.011 28 853.77(0.04) 7 0.008 93 0.010 50 733.88(0.30) 0.011 28 0.012 94 833.12(0.23) 8 0.010 50 0.012 06 716.10(0.27) 0.012 94 0.014 59 814.19(0.03) 9 0.012 06 0.013 59 700.45(0.23) 0.014 59 0.016 23 793.91(0.23) 10 0.013 59 0.015 11 684.41(0.35) 0.016 23 0.017 84 774.19(0.11) 11 0.015 11 0.016 62 667.55(0.19) 0.017 84 0.019 44 757.20(0.02) 12 0.016 62 0.018 10 653.02(0.32) 0.019 44 0.021 02 740.16(0.06) 13 0.018 10 0.019 58 638.32(0.18) 0.021 02 0.022 58 723.68(0.01) 14 0.019 58 0.021 03 625.31(0.22) 0.022 58 0.024 12 703.82(0.07) 15 0.021 03 0.022 47 609.66(0.16) 0.024 12 0.025 64 688.54(−0.03) 16 0.022 47 0.023 89 596.40(0.24) 0.025 64 0.027 15 671.40(−0.05) 17 0.023 89 0.025 29 582.05(0.23) 0.027 15 0.028 64 656.49(−0.20) 18 0.025 29 0.026 68 569.61(0.14) 0.028 64 0.030 11 640.68(−0.16) 19 0.026 68 0.028 05 556.60(0.23) 0.030 11 0.031 57 625.31(−0.22) 20 0.028 05 0.029 40 537.71(1.00) NA in (DMSO + Water) Mixed Solvents = 0.0121, m0 = 0.17692 mol·kg−1 xDMSO = 0.0250, m0 = 0.17502 mol·kg−1 0.002 62 0.004 35 866.62(−0.28) 3 0.002 59 0.004 30 795.13(−0.01) 0.004 35 0.006 06 845.82(0.16) 4 0.004 30 0.005 99 777.79(−0.04) 0.006 06 0.007 75 823.69(0.03) 5 0.005 99 0.007 67 761.58(0.06) 0.007 75 0.009 43 802.72(0.10) 6 0.007 67 0.009 32 739.51(−0.10) 0.009 43 0.011 08 777.19(0.12) 7 0.009 32 0.010 96 722.97(−0.15) 0.011 08 0.012 72 759.93(0.29) 8 0.010 96 0.012 58 704.81(0.00) 0.012 72 0.014 35 742.86(0.10) 9 0.012 58 0.014 19 690.04(0.00) 0.014 35 0.015 95 728.98(−0.06) 10 0.014 19 0.015 77 674.06(−0.06) 0.015 95 0.017 54 712.68(−0.15) 11 0.015 77 0.017 34 658.20(−0.02) 0.017 54 0.019 11 695.22(−0.02) 12 0.017 34 0.018 90 643.17(−0.03) 0.019 11 0.020 66 682.31(−0.21) 13 0.018 90 0.020 43 628.82(−0.02) 0.020 66 0.022 19 667.69(−0.22) 14 0.020 43 0.021 95 615.89(−0.06) 0.022 19 0.023 71 650.15(−0.35) 15 0.021 95 0.023 45 600.46(−0.02) 0.023 71 0.025 21 635.04(−0.07) 16 0.023 45 0.024 93 586.63(0.11) 0.025 21 0.026 69 620.22(−0.07) 17 0.024 93 0.026 39 571.64(0.04) 0.026 69 0.028 15 607.40(0.04) 18 0.026 39 0.027 84 560.89(0.08) 0.028 15 0.029 60 592.39(−0.17) 19 0.027 84 0.029 27 546.84(−0.09) 0.029 60 0.031 03 577.88(−0.01) 20 0.029 27 0.030 69 533.99(0.07) = 0.0391, m0 = 0.17351 mol·kg−1 xDMSO = 0.0546, m0 = 0.17673 mol·kg−1 0.002 57 0.004 27 739.29(0.11) 3 0.002 62 0.004 35 691.77(0.12) 0.004 27 0.005 94 720.45(−0.15) 4 0.004 35 0.006 05 675.67(−0.03) 0.005 94 0.007 60 703.78(0.00) 5 0.006 05 0.007 74 659.34(0.11) 0.007 60 0.009 24 680.64(−0.55) 6 0.007 74 0.009 42 637.34(0.09) 0.009 24 0.010 87 662.28(−0.27) 7 0.009 42 0.011 07 623.96(−0.01) 0.010 87 0.012 48 648.47(−0.33) 8 0.011 07 0.012 71 608.48(0.16) 0.012 48 0.014 07 634.50(−0.21) 9 0.012 71 0.014 33 596.28(0.01) 0.014 07 0.015 64 619.98(−0.20) 10 0.014 33 0.015 93 582.72(0.14) 0.015 64 0.017 20 605.32(−0.25) 11 0.015 93 0.017 52 569.39(0.04) 0.017 20 0.018 73 592.60(−0.16) 12 0.017 52 0.019 08 556.96(0.06) 0.018 73 0.020 26 580.17(−0.19) 13 0.019 08 0.020 63 544.36(0.18) 0.020 26 0.021 76 568.23(−0.15) 14 0.020 63 0.022 17 533.62(0.13) 0.021 76 0.023 25 553.57(−0.17) 15 0.022 17 0.023 68 519.69(0.13) 0.023 25 0.024 72 541.94(−0.09) 16 0.023 68 0.025 18 508.86(0.13) 0.024 72 0.026 17 529.35(−0.01) 17 0.025 18 0.026 66 497.45(0.13) 0.026 17 0.027 60 517.71(−0.04) 18 0.026 66 0.028 12 487.34(0.10) 0.027 60 0.029 02 508.24(0.13) 19 0.028 12 0.029 57 477.20(−0.02) 0.029 02 0.030 42 497.04(−0.04) 20 0.029 57 0.030 99 465.79(0.03) 2326



Article

Table 2. continued mN‑1 N 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

mol·kg

ΔH(mN‑1→mN)

mN −1

mol·kg

−1

xDMSO = 0.0714, m0 = 0.17342 mol·kg 0.002 57 0.004 26 0.004 26 0.005 94 0.005 94 0.007 60 0.007 60 0.009 24 0.009 24 0.010 86 0.010 86 0.012 47 0.012 47 0.014 06 0.014 06 0.015 63 0.015 63 0.017 19 0.017 19 0.018 73 0.018 73 0.020 25 0.020 25 0.021 75 0.021 75 0.023 24 0.023 24 0.024 71 0.024 71 0.026 16 0.026 16 0.027 59 0.027 59 0.029 01 0.029 01 0.030 41

(mN−1)

−1

N

J·mol −1

xDMSO = 0.0121, m0 = 0.16372 mol·kg−1 0.002 43 0.004 03 0.004 03 0.005 61 0.005 61 0.007 17 0.007 17 0.008 72 0.008 72 0.010 26 0.010 26 0.011 77 0.011 77 0.013 27 0.013 27 0.014 76 0.014 76 0.016 22 0.016 22 0.017 68 0.017 68 0.019 11 0.019 11 0.020 53 0.020 53 0.021 93 0.021 93 0.023 32 0.023 32 0.024 69 0.024 69 0.026 05 0.026 05 0.027 38 0.027 38 0.028 71 xDMSO = 0.0391, m0 = 0.17731 mol·kg−1 0.002 63 0.004 36 0.004 36 0.006 07 0.006 07 0.007 77 0.007 77 0.009 45 0.009 45 0.011 11 0.011 11 0.012 75 0.012 75 0.014 38 0.014 38 0.015 99 0.015 99 0.017 58 0.017 58 0.019 15 0.019 15 0.020 71 0.020 71 0.022 24 0.022 24 0.023 76 0.023 76 0.025 27 0.025 27 0.026 75 0.026 75 0.028 22 0.028 22 0.029 67 0.029 67 0.031 10

mol·kg

−1

(ΔH(mN‑1→mN))

(mN) mol·kg

−1

J·mol−1 −1

xDMSO = 0.0900, m0 = 0.17691 mol·kg 619.90(−0.14) 3 0.002 62 0.004 35 606.93(−0.55) 4 0.004 35 0.006 06 590.50(−0.16) 5 0.006 06 0.007 75 573.53(0.54) 6 0.007 75 0.009 42 555.68(−0.09) 7 0.009 42 0.011 08 545.44(−0.48) 8 0.011 08 0.012 72 534.03(−0.29) 9 0.012 72 0.014 34 522.29(−0.37) 10 0.014 34 0.015 95 510.88(−0.30) 11 0.015 95 0.017 53 498.62(−0.32) 12 0.017 53 0.019 10 488.58(−0.18) 13 0.019 10 0.020 65 478.21(−0.08) 14 0.020 65 0.022 19 466.55(−0.18) 15 0.022 19 0.023 70 457.16(−0.12) 16 0.023 70 0.025 20 446.14(−0.17) 17 0.025 20 0.026 68 437.83(−0.28) 18 0.026 68 0.028 14 427.95(−0.01) 19 0.028 14 0.029 59 418.17(0.09) 20 0.029 59 0.031 02 INA in (DMSO + Water) Mixed Solvents xDMSO = 0.02500, m0 = 0.16242 mol·kg−1 742.45(0.10) 3 0.002 41 0.003 99 725.84(0.10) 4 0.003 99 0.005 56 708.41(0.15) 5 0.005 56 0.007 11 689.59(−0.22) 6 0.007 11 0.008 65 668.87(0.33) 7 0.008 65 0.010 17 653.90(0.31) 8 0.010 17 0.011 68 639.89(0.24) 9 0.011 68 0.013 17 625.64(0.18) 10 0.013 17 0.014 64 610.66(0.38) 11 0.014 64 0.016 09 597.22(0.32) 12 0.016 09 0.017 53 585.04(0.27) 13 0.017 53 0.018 96 572.77(0.25) 14 0.018 96 0.020 37 558.56(0.38) 15 0.020 37 0.021 76 546.21(0.22) 16 0.021 76 0.023 13 534.08(0.42) 17 0.023 13 0.024 49 522.61(0.31) 18 0.024 49 0.025 84 511.24(0.35) 19 0.025 84 0.027 16 497.93(−0.09) 20 0.027 16 0.028 47 xDMSO = 0.0546, m0 = 0.17893 mol·kg−1 693.97(0.02) 3 0.002 65 0.004 40 678.08(0.08) 4 0.004 40 0.006 13 661.66(0.07) 5 0.006 13 0.007 84 637.85(−0.46) 6 0.007 84 0.009 53 625.00(−0.28) 7 0.009 53 0.011 21 610.01(−0.20) 8 0.011 21 0.012 87 597.50(−0.35) 9 0.012 87 0.014 51 583.66(−0.39) 10 0.014 51 0.016 13 570.15(−0.29) 11 0.016 13 0.017 73 557.28(−0.41) 12 0.017 73 0.019 32 546.20(−0.20) 13 0.019 32 0.020 89 534.37(−0.04) 14 0.020 89 0.022 44 520.98(0.02) 15 0.022 44 0.023 97 509.54(0.04) 16 0.023 97 0.025 49 498.12(0.18) 17 0.025 49 0.026 99 487.38(0.13) 18 0.026 99 0.028 47 470.98(−0.21) 19 0.028 47 0.029 93 465.74(0.31) 20 0.029 93 0.031 37

2327

591.42(−0.18) 578.34(0.14) 564.68(−0.12) 544.03(0.33) 533.31(−0.18) 520.11(0.16) 508.63(0.19) 497.86(0.19) 486.93(0.30) 475.75(0.17) 465.75(0.21) 456.99(0.10) 445.18(0.28) 436.17(0.28) 426.42(0.22) 417.27(−0.19) 407.33(−0.21) 398.91(−0.06)

690.05(−0.05) 675.51(−0.11) 659.72(−0.11) 638.13(0.28) 622.45(0.36) 609.46(0.27) 596.70(0.29) 583.00(0.22) 570.71(0.23) 555.52(−0.01) 545.62(0.16) 534.52(0.16) 521.25(0.21) 509.55(−0.03) 497.93(0.02) 487.40(−0.10) 465.31(2.54) 466.49(0.02) 641.95(0.14) 627.80(0.01) 613.79(0.21) 596.96(−0.28) 582.89(−0.33) 566.59(0.03) 554.71(−0.22) 541.03(−0.11) 529.26(−0.10) 518.38(−0.13) 507.74(−0.15) 497.20(−0.16) 484.58(−0.06) 474.42(0.14) 464.11(0.29) 447.06(1.99) 444.72(0.45) 434.59(0.33)



Article


3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

mol·kg

ΔH(mN‑1→mN)

mN −1

mol·kg

−1

xDMSO = 0.0714, m0 = 0.17752 mol·kg 0.002 63 0.004 37 0.004 37 0.006 08 0.006 08 0.007 78 0.007 78 0.009 46 0.009 46 0.011 12 0.011 12 0.012 77 0.012 77 0.014 39 0.014 39 0.016 00 0.016 00 0.017 59 0.017 59 0.019 17 0.019 17 0.020 73 0.020 73 0.022 27 0.022 27 0.023 79 0.023 79 0.025 29 0.025 29 0.026 78 0.026 78 0.028 25 0.028 25 0.029 70 0.029 70 0.031 13

(mN−1)

−1

N

J·mol −1

xDMF = 0.0128, m0 = 0.18131 mol·kg−1 0.002 69 0.004 46 0.004 46 0.006 21 0.006 21 0.007 94 0.007 94 0.009 66 0.009 66 0.011 36 0.011 36 0.013 04 0.013 04 0.014 70 0.014 70 0.016 34 0.016 34 0.017 97 0.017 97 0.019 58 0.019 58 0.021 17 0.021 17 0.022 74 0.022 74 0.024 29 0.024 29 0.025 83 0.025 83 0.027 35 0.027 35 0.028 85 0.028 85 0.030 33 0.030 33 0.031 79 xDMF = 0.0417, m0 = 0.18022 mol·kg−1 0.002 67 0.004 43 0.004 43 0.006 17 0.006 17 0.007 90 0.007 90 0.009 60 0.009 60 0.011 29 0.011 29 0.012 96 0.012 96 0.014 61 0.014 61 0.016 24 0.016 24 0.017 86 0.017 86 0.019 46 0.019 46 0.021 04 0.021 04 0.022 60 0.022 60 0.024 15 0.024 15 0.025 67 0.025 67 0.027 18 0.027 18 0.028 67 0.028 67 0.030 15 0.030 15 0.031 60

mol·kg

−1

(ΔH(mN‑1→mN))

(mN) mol·kg

−1

J·mol−1 −1

592.90(0.01) 578.16(0.27) 566.50(0.07) 549.01(−0.26) 537.08(−0.42) 522.60(−0.09) 511.71(−0.03) 500.90(−0.07) 489.00(0.01) 479.32(0.10) 470.08(0.10) 460.59(−0.07) 449.96(0.02) 440.62(−0.08) 430.98(−0.03) 420.05(−0.04) 412.57(−0.10) 403.01(0.13) NA in (DMF + Water) 709.37(−0.05) 693.45(0.01) 675.67(0.28) 654.96(−0.03) 639.59(0.04) 624.27(0.00) 610.57(−0.02) 596.46(0.01) 582.42(0.05) 569.21(−0.09) 556.81(0.06) 544.39(0.07) 529.95(0.15) 517.93(0.08) 506.73(0.13) 495.48(0.35) 483.78(0.39) 472.43(0.23) 443.45(−0.21) 434.71(−0.12) 425.44(−0.1) 412.05(0.04) 401.99(−0.12) 392.78(−0.13) 384.08(−0.09) 375.65(−0.06) 368.09(0.30) 360.26(0.18) 352.70(0.23) 345.60(0.12) 336.72(0.17) 330.18(0.05) 321.22(0.09) 315.39(−0.02) 309.82(−0.37) 301.73(0.07)

2328

xDMSO = 0.0900, m0 = 0.17834 mol·kg 3 0.002 64 0.004 38 4 0.004 38 0.006 11 5 0.006 11 0.007 81 6 0.007 81 0.009 50 7 0.009 50 0.011 17 8 0.011 17 0.012 82 9 0.012 82 0.014 46 10 0.014 46 0.016 07 11 0.016 07 0.017 67 12 0.017 67 0.019 25 13 0.019 25 0.020 82 14 0.020 82 0.022 36 15 0.022 36 0.023 89 16 0.023 89 0.025 40 17 0.025 40 0.026 89 18 0.026 89 0.028 37 19 0.028 37 0.029 83 20 0.029 83 0.031 27 Mixed Solvents xDMF = 0.0265, m0 = 0.17570 mol·kg−1 3 0.002 61 0.004 32 4 0.004 32 0.006 02 5 0.006 02 0.007 70 6 0.007 70 0.009 36 7 0.009 36 0.011 01 8 0.011 01 0.012 64 9 0.012 64 0.014 25 10 0.014 25 0.015 84 11 0.015 84 0.017 42 12 0.017 42 0.018 98 13 0.018 98 0.020 52 14 0.020 52 0.022 04 15 0.022 04 0.023 55 16 0.023 55 0.025 03 17 0.025 03 0.026 51 18 0.026 51 0.027 96 19 0.027 96 0.029 40 20 0.029 40 0.030 82 xDMF = 0.0581, m0 = 0.20453 mol·kg−1 3 0.003 03 0.005 03 4 0.005 03 0.007 01 5 0.007 01 0.008 96 6 0.008 96 0.010 90 7 0.010 90 0.012 81 8 0.012 81 0.014 71 9 0.014 71 0.016 58 10 0.016 58 0.018 44 11 0.018 44 0.020 27 12 0.020 27 0.022 08 13 0.022 08 0.023 88 14 0.023 88 0.025 65 15 0.025 65 0.027 40 16 0.027 40 0.029 14 17 0.029 14 0.030 85 18 0.030 85 0.032 54 19 0.032 54 0.034 21 20 0.034 21 0.035 86

537.09(0.40) 526.87(0.28) 511.33(0.62) 498.90(−0.33) 485.16(0.24) 472.41(0.57) 461.66(0.71) 453.52(1.15) 442.43(0.84) 432.75(0.77) 424.69(0.94) 416.17(0.91) 405.67(0.80) 397.49(0.97) 384.43(−0.10) 380.53(1.14) 372.40(1.05) 363.46(0.98)

543.75(0.16) 533.34(0.10) 519.54(0.14) 502.80(0.28) 492.69(0.04) 481.37(−0.02) 470.97(0.03) 460.52(−0.01) 449.11(0.04) 439.22(0.03) 430.39(−0.15) 420.47(0.07) 410.02(0.05) 401.90(0.06) 391.43(0.05) 383.86(−0.07) 376.04(0.10) 367.32(0.18) 407.46(0.03) 399.87(−0.01) 391.23(0.12) 381.18(−0.12) 371.42(−0.02) 361.84(0.10) 354.35(0.11) 346.34(0.09) 337.97(0.01) 330.64(0.06) 323.96(0.05) 316.91(0.15) 309.24(0.03) 302.31(−0.10) 296.19(0.15) 289.73(0.05) 283.41(−0.01) 277.75(0.04)



Article


3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

mol·kg

ΔH(mN‑1→mN)

mN −1

mol·kg

−1

xDMF = 0.0763, m0 = 0.24851 mol·kg 0.003 68 0.006 11 0.006 11 0.008 51 0.008 51 0.010 89 0.010 89 0.013 24 0.013 24 0.015 57 0.015 57 0.017 87 0.017 87 0.020 15 0.020 15 0.022 40 0.022 40 0.024 63 0.024 63 0.026 83 0.026 83 0.029 01 0.029 01 0.031 17 0.031 17 0.033 30 0.033 30 0.035 40 0.035 40 0.037 48 0.037 48 0.039 54 0.039 54 0.041 57 0.041 57 0.043 58

(mN−1)

−1

N

J·mol −1

xDMF = 0.0128, m0 = 0.17801 mol·kg−1 0.002 64 0.004 38 0.004 38 0.006 10 0.006 10 0.007 80 0.007 80 0.009 48 0.009 48 0.011 15 0.011 15 0.012 80 0.012 80 0.014 43 0.014 43 0.016 05 0.016 05 0.017 64 0.017 64 0.019 22 0.019 22 0.020 78 0.020 78 0.022 32 0.022 32 0.023 85 0.023 85 0.025 36 0.025 36 0.026 85 0.026 85 0.028 32 0.028 32 0.029 78 0.029 78 0.031 21 xDMF = 0.0417, m0 = 0.18652 mol·kg−1 0.002 77 0.004 59 0.004 59 0.006 39 0.006 39 0.008 17 0.008 17 0.009 94 0.009 94 0.011 69 0.011 69 0.013 41 0.013 41 0.015 12 0.015 12 0.016 82 0.016 82 0.018 49 0.018 49 0.020 14 0.020 14 0.021 78 0.021 78 0.023 40 0.023 40 0.025 00 0.025 00 0.026 58 0.026 58 0.028 14 0.028 14 0.029 68 0.029 68 0.031 21 0.031 21 0.032 71

mol·kg

−1

(ΔH(mN‑1→mN))

(mN) mol·kg

−1

J·mol−1 −1

394.93(0.01) 386.88(0.01) 378.40(0.00) 367.80(−0.21) 359.61(−0.10) 350.66(−0.04) 343.03(−0.14) 335.27(−0.16) 327.29(−0.26) 319.93(−0.08) 313.06(−0.23) 306.74(−0.04) 299.48(0.14) 293.31(0.17) 286.01(−0.02) 280.02(0.00) 274.46(−0.07) 265.86(0.57) INA in (DMF + Water) 642.94(−0.47) 628.05(−0.39) 613.03(−0.42) 592.97(−0.55) 579.14(−0.51) 565.25(−0.61) 553.41(−0.61) 540.32(−0.62) 528.09(−0.65) 515.63(−0.60) 504.52(−0.58) 492.80(−0.56) 480.34(−0.65) 470.26(−0.62) 459.00(−0.61) 449.61(−0.42) 439.19(−0.49) 428.76(−0.45) 421.64(0.06) 410.40(0.04) 402.50(0.14) 389.73(0.09) 380.53(−0.14) 371.84(0.02) 363.52(−0.09) 354.79(0.01) 346.44(0.09) 338.23(0.07) 331.49(−0.14) 323.85(0.05) 315.93(−0.17) 308.96(0.03) 301.58(−0.10) 294.52(−0.07) 287.64(−0.06) 280.73(−0.10)

2329

xDMF = 0.0957, m0 = 0.25962 mol·kg 3 0.003 85 0.006 38 4 0.006 38 0.008 89 5 0.008 89 0.011 37 6 0.011 37 0.013 83 7 0.013 83 0.016 26 8 0.016 26 0.018 67 9 0.018 67 0.021 05 10 0.021 05 0.023 40 11 0.023 40 0.025 73 12 0.025 73 0.028 03 13 0.028 03 0.030 31 14 0.030 31 0.032 56 15 0.032 56 0.034 78 16 0.034 78 0.036 98 17 0.036 98 0.039 16 18 0.039 16 0.041 30 19 0.041 30 0.043 43 20 0.043 43 0.045 52 Mixed Solvents xDMF = 0.0265, m0 = 0.17612 mol·kg−1 3 0.002 61 0.004 33 4 0.004 33 0.006 03 5 0.006 03 0.007 72 6 0.007 72 0.009 38 7 0.009 38 0.011 03 8 0.011 03 0.012 67 9 0.012 67 0.014 28 10 0.014 28 0.015 88 11 0.015 88 0.017 46 12 0.017 46 0.019 02 13 0.019 02 0.020 56 14 0.020 56 0.022 09 15 0.022 09 0.023 60 16 0.023 60 0.025 09 17 0.025 09 0.026 57 18 0.026 57 0.028 02 19 0.028 02 0.029 46 20 0.029 46 0.030 89 xDMF = 0.0581, m0 = 0.19054 mol·kg−1 3 0.002 82 0.004 68 4 0.004 68 0.006 52 5 0.006 52 0.008 35 6 0.008 35 0.010 15 7 0.010 15 0.011 93 8 0.011 93 0.013 70 9 0.013 70 0.015 44 10 0.015 44 0.017 17 11 0.017 17 0.018 88 12 0.018 88 0.020 57 13 0.020 57 0.022 24 14 0.022 24 0.023 89 15 0.023 89 0.025 52 16 0.025 52 0.027 14 17 0.027 14 0.028 73 18 0.028 73 0.030 31 19 0.030 31 0.031 86 20 0.031 86 0.033 40

346.31(−0.07) 338.52(0.18) 330.46(0.20) 322.10(−0.10) 313.85(−0.02) 306.06(0.02) 299.65(0.08) 292.58(0.04) 285.29(0.13) 278.77(0.12) 272.72(0.33) 266.41(0.44) 259.46(0.49) 253.83(0.58) 247.56(0.67) 242.60(0.56) 237.51(0.63) 230.50(−0.78)

503.49(−0.14) 492.37(−0.10) 481.10(−0.23) 467.23(0.36) 456.64(0.21) 444.12(−0.32) 434.51(−0.32) 425.35(−0.40) 415.52(−0.41) 406.46(−0.38) 399.16(0.01) 390.13(−0.23) 380.21(−0.29) 372.29(−0.10) 363.65(−0.30) 355.40(−0.35) 347.76(−0.33) 339.90(−0.05) 350.89(−0.12) 342.98(−0.03) 334.11(−0.05) 323.86(0.00) 316.56(0.24) 309.51(0.22) 302.30(0.25) 295.68(0.06) 288.75(0.12) 281.96(0.05) 276.43(0.19) 270.07(0.10) 263.07(0.17) 257.47(0.17) 251.44(0.19) 245.88(−0.13) 241.03(0.08) 235.62(−0.29)



Article


mol·kg

ΔH(mN‑1→mN)

mN −1

mol·kg

−1

xDMF = 0.0763, m0 = 0.25441 mol·kg 0.003 77 0.006 26 0.006 26 0.008 71 0.008 71 0.011 15 0.011 15 0.013 55 0.013 55 0.015 94 0.015 94 0.018 29 0.018 29 0.020 63 0.020 63 0.022 93 0.022 93 0.025 21 0.025 21 0.027 47 0.027 47 0.029 70 0.029 70 0.031 91 0.031 91 0.034 09 0.034 09 0.036 24 0.036 24 0.038 37 0.038 37 0.040 48 0.040 48 0.042 56 0.042 56 0.044 61

(mN−1)

−1

N

J·mol −1

387.77(−0.05) 378.47(0.06) 369.89(−0.04) 360.27(0.10) 350.51(−0.14) 341.23(−0.01) 334.04(−0.06) 326.32(−0.16) 318.94(−0.15) 311.86(−0.06) 305.92(0.01) 298.94(−0.06) 289.89(−0.02) 285.51(0.06) 279.01(0.13) 272.94(0.12) 267.40(−0.11) 261.75(−0.24)

3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

mol·kg

−1

(ΔH(mN‑1→mN))

(mN) mol·kg

−1

xDMF = 0.0957, m0 = 0.27662 mol·kg 0.004 10 0.006 80 0.006 80 0.009 48 0.009 48 0.012 12 0.012 12 0.014 74 0.014 74 0.017 33 0.017 33 0.019 89 0.019 89 0.022 43 0.022 43 0.024 94 0.024 94 0.027 42 0.027 42 0.029 87 0.029 87 0.032 30 0.032 30 0.034 69 0.034 69 0.037 07 0.037 07 0.039 41 0.039 41 0.041 72 0.041 72 0.044 01 0.044 01 0.046 27 0.046 27 0.048 51

J·mol−1 −1

340.72(−0.05) 332.94(0.13) 325.11(−0.03) 315.87(0.00) 307.90(−0.20) 301.03(0.00) 294.63(0.00) 287.93(0.07) 281.68(0.01) 275.81(0.01) 269.62(0.04) 264.25(−0.15) 257.75(−0.13) 252.32(0.00) 246.82(−0.07) 241.82(−0.16) 235.00(0.59) 231.60(0.08)

a

The atmospheric pressure was determined by a Fortin barometer (FM-52, Russell Scientific Instruments). The errors of molalities (m) and mole fractions (x) are estimated to be ± 0.00001 mol·kg−1, ± 0.0001, respectively. The values in parentheses are the evaluated relative deviations (δ) between experimental and calculated values of ΔH(mN‑1 → mN), denoted here respectively by ΔH(exptl) and ΔH(calcd), δ = 10{[ΔH(exptl) − ΔH(calcd)]/ΔH(exptl)}, in which the values of ΔH(calcd) were calculated according to eq (4) in section 2 of the text. The combined standard uncertainties of ΔH(exptl), u(ΔH(exptl)), were determined to be ± 0.05 J· mol−1.

Table 3. Enthalpic Pairwise Self-Interaction Coefficients (hxx) of Nicotinamide (NA) and Isonicotinamide (INA) in Pure Water and (DMF + Water) Mixed Solvents of Various Mole Fractions at T = (298.15 ± 0.01) K and under p = (101.35 ± 0.01) kPaa

Table 4. Enthalpic Pairwise Self-Interaction Coefficients (hxx) of Nicotinamide (NA) and Isonicotinamide (INA) in Pure Water and (DMSO + Water) Mixed Solvents of Various Mole Fractions at T = (298.15 ± 0.01) K and under p = (101.35 ± 0.01) kPaa

hxx/J·kg·mol−2c

hxx/J·kg·mol−2c

xDMFb

NA

INA

xDMSOb

NA

INA

0.0000 0.0128 0.0265 0.0417 0.0581 0.0763 0.0957

−5296 (±31) −3830 (±23) −2960 (±25) −2315 (±11) −1891 (±9) −1515 (±12) −1309 (±16)

−4763 (±23) −3529 (±18) −2718 (±13) −2207 (±17) −1774 (±14) −1456 (±18) −1160 (±7)

0.0000 0.0121 0.0250 0.0391 0.0546 0.0714 0.0900

−5296 (±31) −4765 (±9) −4426 (±29) −4116 (±25) −3779 (±26) −3414 (±31) −3215 (±19)

−4763 (±23) −4409 (±7) −4089 (±9) −3799 (±28) −3453 (±24) −3142 (±19) −2875 (±31)

a

a

The atmospheric pressure was determined by a Fortin barometer (FM-52, Russell Scientific Instruments). bThe errors of mole fractions (xDMF) are estimated to be ± 0.0001. cThe values of hxx were calculated by least-squares fitting according to eq (4) in section 2 of the text, and the values in parentheses are the evaluated mean deviations for three independent determinations of hxx, σ = ± (∑i 3= 1|hxx(i) − h̅xx|)/3. The combined standard uncertainties of hxx, u(hxx), were determined from the experimental and fitted uncertainties to be ± 35 J· kg· mol−2.

The atmospheric pressure was determined by a Fortin barometer (FM-52, Russell Scientific Instruments). bThe errors of mole fractions (xDMSO) are estimated to be ± 0.0001. cThe values of hxx were calculated by least-squares fitting according to eq (4) in section 2 of the text, and the values in parentheses are the evaluated mean deviations for three independent determinations of hxx, σ = ± (∑i3= 1|hxx(i)−h̅xx|)/3. The combined standard uncertainties of hxx, u(hxx), were determined from the experimental and fitted uncertainties to be ±35 J· kg· mol−2.

(picolinamide, PA).52 Besides the presence of intermolecular hydrogen bonding, there exist other nonbonding interactions such as hydrophobic interaction in aqueous solutions, since both NA and INA molecules contain hydrophobic groups. For their processes of self-association in aqueous solutions, various hydrophilic and hydrophobic interactions between functional groups compete with each other to achieve finally a thermodynamic balance. As a thermodynamic probe for the measurement of interplays between two solvated solutes, the enthalpic pairwise interaction coefficient (hxx) is sensitive to the subtle variation in competition equilibrium among complex interactions

+

related to the stereospecificity of hydride transfer in NAD / NADH oxidoreduction.51 In condensed phases, both NA and INA molecules can participate in the formation of intermolecular hydrogen bonding, through the −NH2 and −CO groups, as well as the sp2-hybridized N atom on pyridine ring, all of which are able to serve as proton acceptors or donors.52,53 The infrared spectra of the room-temperature crystals reflect that intermolecular interactions in the condensed phase, particularly H-bond interactions, are stronger in INA than the ortho-isomer 2330



Article

Figure 1. (a) Typical ITC curve of nicotinamide (NA) in (DMF + water) mixed solvents (xDMF = 0.09569) at T = (298.15 ± 0.01) K and under p = (101.35 ± 0.01) kPa. (b) Experimental values of ΔH(mN‑1 → mN) of in (DMF + water) mixed solvent (xDMF = 0.09569) as a function of injection number N at T = (298.15 ± 0.01) K and under p = (101.35 ± 0.01) kPa, with the square of correlation coefficient R2 = 0.9992, and the standard deviation of regression SD = 1.6, fitting according to eq (4) in section 2 of the text.

in solutions.54,55 The contributions of diverse interaction natures on the values of hxx are completely different and discriminably superimposable, which can be summarized as follows:17,56,57 I. The partial desolvation of solvated shells of solute molecules when they approach to each other, is an endothermic process and makes a positive contribution to hxx. II. The direct interactions between two approaching solute molecules, might be an endothermic (or exothermic) process and makes a positive (or negative) contribution to hxx, according to the nature of interacting groups on solute molecules. There are three such kinds of interactions potentially working between two approaching solute molecules in the solutions under study: (a) Hydrophilic−hydrophilic interactions: H-bonds between amide (−CONH2) and amide (−CONH2), amide (−CONH2) and the N atom on pyridine ring, etc. make negative contribution to hxx. (b) Hydrophilic−hydrophobic interactions: interactions between amide (−CONH2) and the rest moiety of pyridine ring except its N atom, the N atom on pyridine ring

and the rest moiety of pyridine ring except its N atom, etc. make a positive contribution to hxx. (c) Hydrophobic− hydrophobic interactions: mainly π−π interaction between two pyridine rings, which has the electron-deficient aromaticity in nature, makes a positive contribution to hxx. The hxx values of NA and INA in pure water at 298.15 K are −5296 J·kg·mol−2 and −4763 J·kg·mol−2, respectively (see Table 3 and 4). The large negative values of hxx manifest that the interaction type (a) is predominant in both of the binary solutions (NA+water, INA+water). The considerable difference (∼533 J·kg·mol−2) in hxx implies that the NA molecule has a stronger self-assembly ability by H-bonding with respect to INA. It would be much better to explain the order of hxx by means of the Abraham’s solute parameters,58 which are commonly used to characterize H-bond acidity and H-bond basicity of nonelectrolyte solutes. As is well-known, all the atoms in the pyridine ring are sp2-hybridized. The N atom donates its three hybridized electrons 2331



Article

Figure 2. Enthalpic pairwise self-interaction coefficients (hxx) of nicotinamide (NA) and isonicotinamide (INA) in (DMF + water) mixed solvents as a function of mole fraction (xDMF) at T = (298.15 ± 0.01) K and under p = (101.35 ± 0.01) kPa (black ■, NA; red ●, INA).

Figure 3. Enthalpic pairwise self-interaction coefficients (hxx) of nicotinamide (NA) and isonicotinamide (INA) in (DMSO + water) mixed solvents as a function of mole fraction (xDMSO) at T = (298.15 ± 0.01) K and under p = (101.35 ± 0.01) kPa (black ■, NA; red ●, INA).

to the ring system, and its extra electron pair lies in the plane of ring, projecting outward, contribute nothing to the aromatic system. However, because of the separation of the lone pair from the ringy aromatic system, the N atom behaves as an electron-withdrawing group, exhibiting a negative mesomeric (resonance) effect. On account of its ability as a relatively strong base, pyridine and its substituted derivatives are often involved in coordination complexes and H-bond interactions.59 In the case of pyridine/pyridinium systems, only the 2p-type electron in the N atom is weakly involved in mesomeric and π-electron delocalization due to H-bond formation.60 Investigation on the protonated homodimer of pyridine, [Pyr···H···Pyr]+, has shown that the hydrogen bond is linear and asymmetric, as a kind of proton-sharing or low-barrier hydrogen bonds, and the aromatic rings are oriented perpendicular to each other.61

An experimental and theoretical study of vibrational spectra indicated that the dihedral angles between the ring planes and the amide groups have a nonplanar environment for NA and INA molecules, clearly different from their ortho-isomer (PA) which has a planar environment.62 Both NA and INA are versatile for a varity of H-bond interactions, especially in the polymorphs of pharmaceutical cocrystals. It has been found that the crystal polymorphism of NA is simpler than that of INA,63 and that the structural outcome of the crystallization process of INA is directed by the association and self-association processes in solutions which are largely influenced by the H-bonding capacity of the solvent.64 The possible dominant configurations of pairwise self-interaction were proposed for INA in solutions, one is the head-to-tail dimer (amide-pyridine heterosynthon), and the other is head-to-head dimer (amide−amide homosynthon).64 2332



Article

Figure 4. Enthalpic pairwise self-interaction coefficients (hXX) of nicotinamide (NA) and isonicotinamide (INA) in (DMF + water) and (DMSO + water) mixed solvents as a function of mole fractions of cosolvents (xDMF, xDMSO) at T = (298.15 ± 0.01) K and under p = (101.35 ± 0.01) kPa, respectively (black ■, DMF; red ●, DMSO).

amplifying the difference between them stepwise (see Figure 4). The results manifest that (1) the interaction type (a), mainly intermolecular H-bonding, is always dominant over others in both of the mixed solvents under study; (2) the H-bond between a pair of NA molecules is always stronger than that of INA, due to the difference in resonance structures of meso- and para- isomers; (3) the comediation of DMSO in the pairwise self-interaction of hydrated solutes can compel more structured water to release from shells to bulky water, leading to less enhancement of the interaction type (I), because DMSO is a more powerful structure-breaker of water in view of its stronger ability of H-bonding with water as a receptor than DMF with water and water with itself;65−67 (4) Both DMF and DMSO are the competitors for water−water H-bonding, and the latter is stronger than the former since not only the base strength (donor number DN = 29.8) but also the acidity (acceptor number AN = 19.3) of liquid DMSO are higher than those of DMF.65

In the present case, taking into consideration that water is not only a strong H-bond acceptor but also a strong H-bond donor, we think that both of the configurations are likely prevailing. However, as the negatively charged N on the para-position in INA molecule is weakened with respect to its meso-isomer (NA), the ability of H-bonding is consequently attenuated, resulting in its less negative values of hxx (see Tables 3 and 4). 3.2. Solvent Effects on Enthalpic Pairwise SelfInteractions. The trends of hxx of NA and INA with the mole fraction of cosolvents (xDMF and xDMSO) in M1 and M2 mixed solvents are illustrated in Figure 2 and 3, respectively. Across the whole studied composition ranges of the two mixed solvents, the hxx coefficients of NA and INA are all large negative (∼103 J·kg·mol−2), keeping up the inequality hxx(NA) < hxx(INA) < 0. Moreover, for both of the solutes (NA and INA), the values of hxx in M1 are always larger than those in M2 (not in absolute value); that is, hxx(in M2) < hxx(in M1) < 0, and all of them increase gradually in positive direction with xcos, 2333



Article

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4. CONCLUSION We have determined dilution enthalpies of NA and INA in two aqueous mixed solvents containing highly polar aprotic cosolvents DMF or DMSO by ITC, respectively. Enthalpic pairwise self-interaction coefficients (hxx) of the two solutes have been calculated from the classical McMillan−Mayer approach and discussed from the point of view of competition equilibrium between hydrophilic and hydrophobic interactions. The enthalpic discrimination of position isomerization and the solvent effects of enthalpic pairwise self-interactions have been found, which are helpful to gain insight into the selfassociations of the two studied solutes of biochemical importance in complex aqueous solutions and the properties of the two studied mixed solvents. The results obtained might be applied to the research fields such as drug morphology and self-assembly in solutions.

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AUTHOR INFORMATION

Corresponding Author

*Tel: (+86)0577-86596022. E-mail: [email protected]. Funding

This work was financially supported by the National Natural Science Foundation of China (No. 21073132). Notes

The authors declare no competing financial interest.

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REFERENCES

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