J. Phys. Chem. 1980,84,1345-1346
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Thermodynamic Properties of Caffeine Crystal Forms Attllio CesBro* and Giorglo Starec Laboratorb di Chimica delle Macromolecole Istltuto dl Chimica, Universitg di Trieste, Trieste, Italy (ReceivedJuly 5, 1979)
Evidence is given showing for the first time the existence of two anhydrous crystalline forms of caffeine. Some thermodynamic properties have been measured by calorimetry and by volumetry on the two different anhydrous forrns and on the hydrated form. Introduction Aqueous solution properties of caffeine have been extensively studied1-3 to understand the aggregation phenomenon of purinelike compounds and as a model for base interaction in nucleic acids. Unfortunately very little is known about the physicochemical properties of the crystal forms of caffeine and many other purinelike mole~ules,~ despite the fact that the crystal state is assumed as a reference in many thermodynamic calculations. The present work is intended to fill this gap of knowledge and takes its origin from the observation that heats of solution, AH:, of caffeine in water depend on the method of c r y ~ t a l l i z a t i o n .Experiments ~~~~~ showing the existence of different anhydrous crystalline forms of caffeine are lacking. The hydrated crystalline form loses 1 mol of water/mol of caffeine at 359 K,3 and its two-dimensional X-ray crystallographic structure has been determined by Sutor? No such data have been determined for anhydrous caffeine. Experimental Section Caffeine (C. Erba, Italy) was recrystallized twice from a saturated aqueous solution. Slow cooling produces long white needles of appreciable size. Fast cooling produces a larger yield, which has been used to get anhydrous powder (at ca. 350 I()as starting material for the sublimation and preparation of the crystals. The temperature-dependent calorimetric measurements have been carried out by using a Perkin-Elmer DSC-1B differential scanning calorimeter. The amount of sample used in each run was in the range 10-40 mg. The total caffeine content in the slightly wet, hydrated crystals was determined by weighing the sample capsule after the dehydration as well as by dissolving the caffeine in a known volume of water and measuring the UV absorbance at 272 nm.' The method wed for the heat capacity determination consisted of measuring the difference between the heat absorbed by the sample and that absorbed by the empty pan during scanning steps of about 10 K. Calibrations of the instrument temperature in the range 300-500 K and of the thermal response have been made with pure grade standards. Heats of solution of caffeine P and of the hydrated form in water at 308 K hiave been carried out by using an LKB 10700 batch microcalorimeter as previously de~cribed.~ Results The sublimation of caffeine at high temperature (T 2 450 K) under atmospheric pressure gives a crystal form (hereafter designated as caffeine P ) which presents no transition peak in differential scanning calorimetry (DSC) analysis but the fusion peak. Caffeine crystals kept in the oven at a temperature of 393 K slowly transform into a new crystal species (caffeine a)which gives a distinct DSC transition peak at 426 K (a P transition) and an X-ray -+
0022-3654/80/2084-1345$0 1.OO/O
TABLE I: Heat Capacity Data of Caffeine p no. cp Y cal deg- mol-' av temp, K of runs temp step, K 300.0-31 1.5 31 1.5-3 23.0 323.0-334.5 334.5-346.0 346.0-357.5 357.5-369.0 369.0-380.5 380.5-392.0
305.75 317.25 328.75 330.25 351.75 363.25 374.75 386.25
42.20 f 0.70 43.37 f 0.70 44.63 f 0.60 45.50 1. 0.80 46.90 f 0.80 48.00 * 0.90 49.25 f 0.80 50.54 f 0.33
6 6 5 5 8 7 7 7
TABLE 11: Enthalpy Data transition h+P ff'P p +liq
AH,:(p) AH, (h)
temp, K
AH, kcal mol-'
359 426 512 308 308
2.20 f 0.10 0.94 f 0.06 5.60 i: 0.30 4.17 f 0.10 6.05 f 0.10
runs 3 5 4 8 10
TABLE 111: Calorimetric Dataa on Caffeine Crystals and Caffeine Aqueous Solution temp, K property
298
308
359
426
512 ~
AHS"( P 1 AHS"(h) AH(h+!3
3.40 4.17 5.02 6.05 1.62 1.88
2.2 0.94
AH(ff+P) AHCo-tlis)
5.60 1.15 1.9od AH,"^ -3.2 CP(P) 41.4 clJp 50b CP (m=o) 120b a Units are kcal mol" for all AH data, and cal deg-' mol-' for Cp data. Calculated from AH^" and C p ( p ) . Heat of dimerization. At 313 K. Azfdfi(msat+m=o)
powder diffraction pattern different from that of the P form, produced either by sublimation or by direct dehydration of the hydrated form. The results of the heat capacity experiments are shown in Table I; the number of runs and the mean deviations are also given. Each average value is calculated as Cp(T+ AT/2) = AH(T (T+ AT))/AT
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which can be used if C, is a linear function of the temperature; in the present case the more nearly correct chord-area plot would give the same results. The equation for the temperature dependence of C, is C, = 41.4 + 0.104(T - 298) cal deg-' mol-l and has been extrapolated to 298 K on the basis of its observed linearity. Table I1 shows the results of the determination of the heats of transition at the equilibrium temperature as measured by differential scanning calorimetry. A complete 0 1980 American Chemical Society
1346
The Journal of Physical Chemistty, Vol. 84,
No. 11, 1980
TABLE IV: Density D a t a form CY
(solid)
p (solid) h (solid) solvated (aqueous, m = 0 )
d, g/cm3
V,
cm3/mol 1.60 i: 0.01 129 1.446 f 0.002 134.2 1.448 i: 0.006 146.3 144.2
summary of known direct and derived calorimetric properties of caffeine in solid state and in aqueous solution is reported in Table IIL3 The densities of the crystals determined with the floating method is a tetrachloromethane-heptane mixture are reported in Table IV. The value of 1.23 g/cm3 given by the “Handbook of Chemistry and Physics’’8is inconsistent with any of the three crystal forms. The values of the respective molar volumes and that of the partial molar volume of caffeine in water ( Vo)are also reported in Table IV. Discussion From the calorimetric data pertinent to caffeine crystals and its aqueous solution, the value of the molar heat capacity of the hydrated crystal, C,(h) (=50 f 10 cal deg-’ mol-’), and that of the solvated solute at the limit of infinite dilution, Cpo (=118 f 10 cal deg-l mol-’), have been evaluated. The experimental value of 41.4 cal deg-’ mol-’ for the anhydrous /3 crystal is significantly smaller than the value of 59 cal deg-’ mol-’ calculated by adding three methylene contributions to the C, value of ~ a n t h i n e . ~ When either atomic contributions or group contributiondo are used, a value of ca. 74 cal deg-’ mol-’, almost twice that found for the crystal, can be evaluated for the ideal gas molecule, showing that the molecular packing must contribute in a large extent to these discrepancies. Similarly, both C (h) and the A&-.,, indicate that the water molecule in the Rydrated crystal is firmly bound within the caffeine frame. It is found that the AI&.,, is very close, at the three temperatures 298, 308, and 359 K, to the values of the enthalpy of fusion of ice, at the respective temperatures. This coincidence has received the greatest attention in the case of water clathrates,’l and with some approximation it could well reflect the major contribution of the hydrogen bonds also for the present structure. Unfortunately, detailed information about the molecular packing of caffeine in the two forms CY and /3 is not available. Very preliminary crystallographic results show that the /3 structure possesses a threefold symmetry axis (parallel to the c axis of the needles) with an estimated distance between caffeine planes of about 3.4 A along this axis, The fact that the hydrated crystal produces at the transition temperature the p form, and not the more stable (11form, suggests that the relative orientation of caffeine
Cesgro and Starec
molecules in these crystals may be similar. A more stable structure with symmetry Czhas been predicted for caffeine dimers.12 It may be inferred that the more compact and energetically favorable CY form is in fact obtained with the Cz symmetry between stacked molecules. The calculated entropy for the transition CY /3 (AS‘ = 2.2 eu) is thus very close to the value 2.17 eu predicted for a simple orderdisorder solid transition with a ratio of the number of states N 2 / N l= 3.13 This interpretation is consistent with the preliminary X-ray crystallographic data, which show the presence of an orientational disorder in the /3 crystals, and with the observed higher molar volume. In the absence of volumetric data on liquid caffeine, the limiting value at infinite dilution of the apparent molar volume of the solvated (aqueous) caffeine ($VoE Y”)3 is reported in Table IV for the purpose of comparison. It may be useful to recall that the concentration dependence of $ V, the apparent molar volume, has been successfully interpreted on the basis of the multiple association of the ~ o l u t e . ~ * ’ ~ The above discussion is obviously speculative but consistent with the available set of data. The properties described may also provide for a better understanding of the phenomenon of the aggregation of polar noneletrolyte solute molecules in water, a process which is still often attributed to the peculiar behavior of the solvent.
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Acknowledgment. A.C. is grateful to Dr. J. H. Stern for helpful discussion and to the Department of Chemistry of the University of California, Irvine, for the kind hospitality during the time when this paper was prepared. The work was supported by a grant from the Italian CNR. References and Notes (1) S. J. Gill, M. Downing, G. F. Sheats, 6iochemlstty,8, 272 (1967). (2)J. H. Stem, J. A. Devore, S. L. Hansen, and 0. Y a w , J. phys. Chem., 78, 1922 (1974). (3) A. Ceslro, E. Russo, and V. Crescenri, J. Phys. Chem., 80, 335 (1976). (4) P. 0.P. Ts’o in “Fine Structure of Proteins and Nucleic Acids”, 0 . D. Fasman and S. N. Tlmasheff, Eds., Marcel Dekker, New York, 1970,Chapter 2. (5) J. H. Stern and E. Lowe, J . Chem. Eng. Data, 23, 341 (1978). (6)J. Sutor, Acta Ctysfallogr., 11, 453 (1956). (7)The extinction coefficient of caffeine in water depends on concentration, a phenomenon due to association. In the ran e lo-‘ changes smoothly from 9930 to 9900 L mol-’ cm-’.M, (8) R. C. Weast, Ed., “Handbook of Chemistry and Physics”, Chemical Rubber Publishing Co., Cleveland, Ohio, 1971,p C-228. (9)J. H. Stern and R. Beenlnga, J. Phys. Chem., 79, 582 (1975). (10)J. D. Cox and 0. Pitcher, “Thermochemistry of Organic and Organometallic Compounds”, Academic Press, London, 1970. (11) D. W. Davidson in “Water-A ComprehensiveTreatise”, Vol. 2,F. Franks, Ed., Plenum Press, New York, 1973,Chapter 3. (12) J. N. Kikkert, 0 . R. Kelly, T. Kurucsev, 6 @ ~ o ! ~ m r12, s , 1459 (1973). (13) E. F. Westrum and J. P. McCullough in “Physics and Chemistry of the Organic Solid State”, Vol. 1, D. Fox, M. M. Labes, and A. WeIssberger, Eds., Intersclence, New York, 1963, Chapter 1. (14)A. CesHro, J . Solution Chem., 5 , 319 (1976).
