J. Chem.

Thermodynamics 38 (2006) 1515–1522

www.elsevier.com/locate/jct

Thermochemical study of two anhydrous polymorphs of caffeine

Susana S. Pinto, Hermı́nio P. Diogo *

Centro de Quı́mica Estrutural, Complexo Interdisciplinar, Instituto Superior Técnico, 1049-001 Lisboa, Portugal

Received 14 February 2006; received in revised form 21 April 2006; accepted 26 April 2006
Available online 11 May 2006

Abstract

The mean values of the standard massic energy of combustion of caffeine in phase I (or alpha) and in phase II (or beta) measured by
static-bomb combustion calorimetry in oxygen, at T = 298.15 K, are Dcu (C8H10O2N4, I) = (21823.27 ± 0.68) J Æ g1 and Dcu
(C8H10O2N4, II) = (21799.96 ± 1.08) J Æ g1, respectively.
The standard (p = 0.1 MPa) molar enthalpy of formation in condensed phase for each form was derived from the corresponding
standard molar enthalpies of combustion as, Df H m ðC8 H10 O2 N4 ; cr; IÞ ¼ ð340:6  2:3Þ kJ  mol1 and Df H m ðC8 H10 O2 N4 ; cr; IIÞ
¼ ð345:1  2:3Þ kJ  mol1 .
The difference between the standard enthalpy of formation of the two polymorphs in condensed phase was also evaluated by using
reaction-solution calorimetry. The obtained result, 2.04 ± 0.25 kJ Æ mol1, is in agreement, within the uncertainty, with the difference
between the molar enthalpies of formation obtained from combustion experiments (4.5 ± 3.2) kJ Æ mol1, which can be considered as
an internal test for consistency of the results.
A value for the standard enthalpy of formation of caffeine in the gaseous state was proposed: Df H m ðC8 H10 O2 N4 ; gÞ ¼
ð229:7  6:1Þ kJ  mol1 , estimated from the values of the standard enthalpies of formation of both crystalline forms obtained in this
work, and the data on standard enthalpies of sublimation collected from the literature.
 2006 Elsevier Ltd. All rights reserved.

Keywords: Caffeine; Enthalpy of combustion; Enthalpy of formation; Differential scanning calorimetry; Solution calorimetry; Thermochemistry

1. Introduction lated by the Federal Food and Drug Administration

Caffeine (3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-
dione), chemical structure shown in figure 1, commonly
designed as 1,3,7,trimethylxantine (CAS 58-08-2), is a com-
ponent of coffee beans, tea leaves, and other plants includ-
ing rubiacea and theacea [1].
Pharmacologically, caffeine belongs to a group of stim-
ulants called xanthines and is listed as an active ingredient
in some stimulants, cold remedies, and various pain killers.
It is actually the most used psychoactive drug with an esti-
mated average consumption of 250 mg/day per capita [2].
Caffeine is also extensively used as a food additive regu-
*
Corresponding author. Tel.: +351 21 841 9232; fax: +351 21 8464455/
57.
E-mail addresses: susanapinto@ist.utl.pt (S.S. Pinto), hdiogo@ist.
utl.pt (H.P. Diogo).
(FDA) and European Community.
The crystalline hydrate of caffeine is known to be non-
stoichiometric in terms the number of water molecules
coordinated [3]. This hydrate is converted to a b-anhydrous
phase (sometimes referred as form II) under ambient tem-
perature and atmospheric pressure conditions which, in
turn, changes enantiotropically to a trigonal phase a-anhy-
drous caffeine (form I) at 155 C. Finally, an isotropic
liquid can be obtained heating this phase at 237 C (see fig-
ure 2).
Different polymorphs of a given substance often exhibit
different physical properties like solubility, dissolution rate,
crystal form, and bioavailability or therapeutic benefit. The
incomplete characterisation of the polymorphic forms of
organic compounds is probably at the origin of the fre-
quent discrepancies that are observed in the reported ther-
modynamic data obtained in different laboratories, namely

0021-9614/$ - see front matter  2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.jct.2006.04.008
1516 S.S. Pinto, H.P. Diogo / J. Chem. Thermodynamics 38 (2006) 1515–1522
O tempered at 110 C, to avoid as much as possible the con-
CH3
H3C
N
N residual moisture, when the sample was cooled to ambient
O N
N low level of form I [8]. This fact leads Gavezzotti and co-
CH3
FIGURE 1. Caffeine molecule.
phase II (or β) phase I (or α) Isotropic liquid
______________|__________________|___________________
155οC 237οC
FIGURE 2. Schematic phase diagram of caffeine.
heats of formation, heats of solution, and heats of sublima-
tion. According to Henck et al. it is presumed that more
than 50% of active ingredients of pharmaceutical products
show at least two polymorphic forms [4]. It is thus very
important, particularly to the pharmaceutical industry, to
be able to achieve an unambiguous characterisation of
the solid phases, namely because the bioavailability of
polymorphic forms can be different, and since the ratio
yield/energetic must be maximised on economic grounds.
The wide academic and industrial importance of the caf-
feine molecule [5] contrasts with the lack of reliable exper-
imental values for the standard enthalpy of combustion
and standard enthalpy of formation for the two anhydrous
polymorphic forms. The present work is precisely a contri-
bution to the thermodynamic characterisation of the pure
phases of anhydrous caffeine, using combustion calorime-
try and solution calorimetry.
Nevertheless, as far as we known, the only two values
for the enthalpy of combustion of caffeine reported in the
literature in 1891 and 1893 (presumably for phase II) have
merely a historic significance [6,7]. The first paper, pub-
lished by Stohmann and Langbein, does not indicate the
origin and the purity of the sample used and no calorimet-
ric details were given. The second one is the average of only
two combustion measurements and the sample character-
isation was only based on nitrogen determination. In addi-
tion, no Washburn corrections were applied by the authors
to the above results.
2. Experimental
2.1. Sample purification
2.1.1. Form II
Commercially obtained caffeine (USP grade from
Sigma) was recrystallised twice from distilled water, dried
in vacuum (p  1.5 Æ 103 Pa) for 24 h at 80 C, and then
tamination with form I. A schlenck tube, under an inert
atmosphere, was used to prevent the adsorption of any
temperature. Greisser refers that is improbable to obtain
crystallographic pure form II without adulteration with a
workers to argue that up to now, the failure to obtain an
ordered crystal phase, for the lower temperature form of
this molecule, is a consequence of its molecular features,
namely the existence of an orientational disorder [9]. On
the other hand, the structure of the high temperature form
(I) was derived from X-ray powder diffraction measure-
ments recorded at 278 K, and it is believed that could be
greatly disordered [8,10,11].
2.1.2. Form I
Caffeine phase I was prepared by heating the phase II
above the melting temperature (ca. 240 C) inside a
schlenck tube (under a nitrogen flush) to avoid sublima-
tion, quenched to ca. 0 C, by using a ethanol/N2 mixture,
and then warmed to ambient temperature. The pellets for
the combustion experiments were made quickly and kept,
under inert atmosphere, inside a refrigerator (5 C) for a
maximum period of 24 h. Due to its metastability, at room
temperature, the process was repeated whenever necessary,
for example, if a systematic tendency in the specific energy
of combustion was observed on successive combustion
runs. Although, Epple et al. [12] and Descamps and co-
workers [10,13], based on time- and temperature-resolved
X-ray powder diffraction, and kinetic studies made by
Lehto and Laine [14] by using isothermal microcalorime-
try, confirm that, at room temperature, the conversion
form I ! form II is very slow.
2.2. Apparatus
The elemental analysis was made with a Fisions Instru-
ments EA1108 apparatus, with typical claimed accuracy
errors of ±0.3% for carbon and nitrogen and ±0.1% for
hydrogen.
The FT-IR spectra were obtained in a Shimadzu, model
8400S spectrophotometer calibrated with polystyrene film.
The differential scanning calorimetry (DSC) measure-
ments were acquired with a temperature-modulated TA
Instruments Inc. model 2920 MTDSC, in the conventional
mode. A helium purge rate 30 cm3/min was employed for
all experiments. The samples were previously encapsulated
in seal aluminium pan and weighted (±107 g) on a
Mettler UMT2 ultra-micro balance. The baseline was cali-
brated by scanning the temperature range of the experi-
ments with an empty pan. The temperature calibration
was performed acquiring the onset of the endothermic
melting peak of several calibration standards, at a heating
rate of 10 K Æ min1: n-decane (Tm = 246.49 K), n-octade-
cane (Tm = 301.39 K), hexatriacontane (Tm = 349.09 K),
indium (Tm = 429.75 K), and tin (Tm = 505.08 K). The
 S.S. Pinto, H.P. Diogo / J. Chem. Thermodynamics 38 (2006) 1515–1522
enthalpy scale was also calibrated using indium (fusion
enthalpy, Dlcr H m ¼ 28:71 J  g1 ) [15].
The 1H n.m.r. spectra were obtained in a Varian 300
MHZ spectrometer.
The gas-chromatography/mass spectrometry (GC/MS)
analysis was carried out on an Agilent 6890 gas chromato-
graph joined to an Agilent 5973N mass detector.
X-ray diffraction measurements were made with a Phil-
lips PW 1710-type angle dispersive powder diffractometer.
The diffractograms were obtained with Ni-filtered Cu Ka-
radiation (k = 0.15418 nm, voltage 40 kV, current 30 mA)
over the range 5 6 2h 6 32 with scan speed of 1 (2h/
min) and step size 0.016 of 2h.
The combustion calorimetric experiments were achieved
using a micro-combustion calorimeter previously described
[16]. The energy equivalent of the calorimeter and its stan-
dard deviation, e0 = (1895.27 ± 0.33) J Æ K1, were deter-
mined from the combustion of benzoic acid (B.D.H.
thermochemical standard) whose standard massic energy
of combustion under the certificate conditions was
(26433 ± 4) J Æ g1. n-Hexadecane (Aldrich, mass fraction
0.99) was used as a combustion aid only for experiments on
phase I. The analysis of the HNO3(aq), formed from traces
of atmospheric N2 initially present inside the bomb, was
made with a Dionex 4000i ion chromatography apparatus
[16b].
The reaction-solution calorimeter and the general oper-
ating procedure used in the experiments have been
described in a previous publication [17]. The calorimeter
consisted basically of a transparent Dewar vessel closed
by a lid, which supported a stirrer, a quartz crystal ther-
mometer probe, a resistor for electrical calibration, and
an ampoule breaking system. The assembled vessel was
immersed in a thermostatic water bath whose temperature
was controlled at 298 ± 103 K by a Tronac PTC-40 unit.
In a typical experiment a thin walled glass ampoule (vol-
ume ca. 2.5 ml) was weighed to ±105 g on a Mettler
AT201 balance, filled with the sample using an apparatus
to maintain the inert atmosphere [18] and sealed with a
torch. The two resulting pieces (closed ampoule + part of
the neck) were weighed and the mass of sample obtained
by subtracting the mass of the empty ampoule.
2.3. Sample characterisation
The results of elemental analysis (average of two inde-
pendent runs) show acceptable agreement with theoretical
values for carbon, hydrogen, and nitrogen for both
samples:
For C8H10O2N4 calculated: C, 49.48; H, 5.19; N 28.85.
Found (phase I): C, 49.67; H, 5.28; N 28.85.
Found (phase II): C, 49.68; H, 5.25; N 28.89.
The GC/MS of the purified caffeine, dissolved in dichlo-
romethane, indicates a purity better than 99.9% and the
MS of the peak shows a parent ion at m/z = 194. This
1517
defragmentation pattern is in excellent accordance with
the NIST Data Base [19].
The melting peak of caffeine in phase I was characterised
by DSC, and it was found that the onset temperature is
Ton = 509.6 K and the temperature of the maximum is
Tmax = 510.2 K at a heating rate of 10 K/min (see figure
3). The corresponding enthalpy of fusion was found to be
Dlcr H m ðC8 H10 O2 N4 Þ ¼ 21:9 kJ  mol1 , which is in agree-
ment with the literature values which span in a range of
3.4 kJ/mol, from 20.1 to 23.5 kJ/mol [11,20,21].
DSC was also used to characterise the conversion
between polymorphs. Muller and Greisser [8] pointed out
that the purity of stable form II can be estimated based
on the experimental value obtained by DSC for the
enthalpy of transition form II ! form I. These authors cor-
related the amount of phase I as an impurity present in
phase II with the enthalpy of phase transition observed
at ca. 155 C in a DSC experiment [8] (figure 4). For a pure
sample of phase II a value of DHtrans (II ! I) = 4.025
± 0.006 kJ/mol can predicted. The DSC result for our sam-
ple gives DHtrans (II ! I) = 4.02 ± 0.03 kJ/mol (20.71 J/g)
which indicates a phase purity better than 99.9%. The dif-
fraction patterns obtained on our samples of phase I are
very close those published by Descamps and co-workers
[11,13]. Furthermore, for phase II, a characteristic peak
(2h = 28.4) is observed, which is absent in form I. This
X-ray powder diffractogram of phase II is in accordance
to one reported by Laine et al. [22] and Descamps and
co-workers [11]. The 1H n.m.r. spectra, in CDCl3 solution,
obtained in a 300 MHz spectrometer, agrees very well with
that reported in reference [23]: 1H n.m.r. (CDCl3/TMS):
d = 7.50 (m, CH, 1H), 4.01 (d, CH3, 3H), 3.55 (s, CH3,
3H), 3.37 (s, CH3, 3H). Finally, the FT-IR spectra were
obtained for both phases of caffeine, and it was found that
all the individual vibrational bands reported by York et al.
[3] are detected in the spectrum of form II carried out in the
present work.
0
-5
-10
Heat Flow
-0.4
-15 -0.6
-0.8
-20 -1
-1.2
-25 -1.4
-1.6
-30
365 415 465
T /K
-35
300 340 380 420 460 500
T /K
FIGURE 3. DSC scan of caffeine at a heating rate of 10 K/min. The inset
shows the thermal event relative to phase transition (II ! I).
1518 S.S. Pinto, H.P. Diogo / J. Chem. Thermodynamics 38 (2006) 1515–1522
105
85
% of phase II
65
45
25
5 tion depicted in the following equation:
0.5 1.5 2.5 3.5
Htrans (kJ/mol)
FIGURE 4. Relationship between the DHtrans (II ! I) and the percentage
of form II (data from Muller and Greisser [8]).
3. Results and discussion
Appendix A presents the detail of the calorimetric pro-
cedures and data treatment. Individual values of the stan-
dard massic energy of combustion of anhydrous caffeine
form I and form II are indicated in tables A1 and A2,
and the mean values are:
Dc u ðC8 H10 O2 N4 ; IÞ ¼ ð21823:27  0:68Þ J  g1
and
Dc u ðC8 H10 O2 N4 ; IIÞ ¼ ð21799:96  1:08Þ J  g1 ;
where the uncertainty quoted represents the standard devi-
ation of the mean. All presented molar quantities are based
on the 2001 standard atomic masses [24]. The Dcu values
obtained in this work, and above indicated, refer to the
reaction:
C8 H10 O2 N4 ðcr; I or IIÞ þ 19=2 O2 ðgÞ ¼
8 CO2 ðgÞ þ 5 H2 OðlÞ þ 2 N2 ðgÞ
and lead, respectively, to the molar values:
Dc U m ðC8 H10 O2 N4 ; IÞ ¼ ð4237:87  1:98Þ kJ  mol1 ;
Dc H m ðC8 H10 O2 N4 ; IÞ ¼ ð4236:63  1:98Þ kJ  mol1 ;
and to
Dc U m ðC8 H10 O2 N4 ; IIÞ ¼ ð4233:35  2:00Þ kJ  mol1 ;
Dc H m ðC8 H10 O2 N4 ; IIÞ ¼ ð4231:89  2:00Þ kJ  mol1 ;
both at T = 298.15 K. The symbols Dc U m and Dc H m
denote, respectively, the standard energy and the standard
molar enthalpy of combustion. As recommended, the
uncertainties quoted represent twice the overall standard
deviation of the mean and include the contributions from
the calibration with benzoic acid and from the energy of
combustion of n-hexadecane in the case of phase I. From
the Dc H m ðC8 H10 O2 N4 ; IÞ and Dc H m ðC8 H10 O2 N4 ; IIÞ
values indicated above, together with Df H m ðCO2 ; gÞ ¼
ð393:51  0:13Þ kJ  mol1 [25] and Df H m ðH2 O; lÞ ¼
ð285:830  0:040Þ kJ  mol1 [25], the following values of
the standard formation enthalpies at 298.15 K were
derived:
Df H m ðC8 H10 O2 N4 ; cr; IÞ ¼ ð340:6  2:3Þ kJ  mol1
and
Df H m ðC8 H10 O2 N4 ; cr; IIÞ ¼ ð345:1  2:3Þ kJ  mol1 :
From these standard enthalpies of formation at
298.15 K of the anhydrous phases of caffeine we conclude
that the enthalpy of reaction associated to the transforma-
4.5
C8 H10 O2 N4 ðcr; IIÞ ¼ C8 H10 O2 N4 ðcr; IÞ ð2Þ
at the same temperature is DrH = (4.5 ± 3.2) kJ Æ mol1.
0
Let us note that this value of DrH0 agrees, within the
uncertainty interval, with that obtained by DSC
(4.02 ± 0.03 kJ Æ mol1) at the transition temperature
(155 C = 388.15 K). In order to check the internal consis-
tency of this result, we chose a different estimation method,
based on the measurement of the dissolution enthalpies of
both phases of anhydrous caffeine in the same solvent. We
thus measured the enthalpy associated with the dissolution
process of each phase of caffeine (200–500 mg) in 125 ml of
a mixture of ethanol/chloroform (60:40), where this partic-
ular solvent mixture was chosen since the dissolution pro-
cess was found to be reasonably fast. Tables B1 and B2
show the results of five and six independent runs carried
out on phase I and phase II, respectively. The values of
the dissolution enthalpies are Dsol H m ¼ ð11:89  0:20Þ kJ
mol1 for phase I and (13.93 ± 0.15) kJ Æ mol1 for phase
II. Given that the final state of the dissolution of each
polymorph in the solvent mixture is identical, the difference
between those values of the dissolution enthalpy,
2.04 ± 0.25 kJ Æ mol1, can be identified with the enthalpy
of reaction (2). It is to be noted that this value is inside
the confidence interval of the enthalpy of the same reaction
ð1Þ
calculated as the difference of the formation enthalpies of
the crystalline phases (4.5 ± 3.2 kJ Æ mol1), which tells in
favour of a good internal consistency of the thermody-
namic data obtained in the present work. Due to its
destructive character and time consuming the combustion
calorimetry is not a first choice technique to determine
the expected small difference between the standard enthal-
pies of formation of polymorphs. However, this technique
offers an interesting way to validate the values supplied by
other thermal techniques.
Several values of the enthalpy of sublimation of the two
anhydrous phases of caffeine, at different temperatures, are
reported in the literature [26]. The most recent values were
reported by Greisser et al. [27]: Dgcr H m ðC8 H10 O2 N4 ; IÞ
¼ 104:8  0:2 kJ  mol1 at T = 439 K and Dgcr H m ðC8 H10
O2 N4 ; IIÞ ¼ 113:6  0:2 kJ  mol1 at T = 369 K, where
the uncertainties denote the standard deviation of the
mean. The enthalpy of sublimation at 298.15 K for phase
I and phase II of caffeine can be calculated from the
reported values at a different T by using [28]:
 S.S. Pinto, H.P. Diogo / J. Chem. Thermodynamics 38 (2006) 1515–1522
Dgcr H m ð298:15 KÞ ¼ Dgcr H m ðT Þ þ Dgcr C p;m ð298:15  T Þ;
where Dgcr C p;m
represents the difference between the molar
heat capacity of gaseous and crystalline caffeine for each
phase. Since no experimental values of Dgcr C p;m for the
two anhydrous forms of caffeine are presently available in
the literature, we decided to estimate those values on the
basis of a prediction method proposed by Chickos et al.
[29]. This method uses an empirical equation (see equation
(4)) that was derived from a huge set of experimental values
relative to a large number of organic molecules:
Dgcr C p;m =ðJ  K1  mol1 Þ ¼ 0:75  0:15 C p;m ðcrÞ;
where C p;m
ðcrÞ is the molar heat capacity, at T = 298.15 K,
of the crystalline phase. The published C p;m values of the
crystalline phases of anhydrous caffeine [10,20] refer to
temperatures different from 298.15 K, so that the values
at this temperature were obtained by fitting and extrapolat-
ing the reported values. From the obtained values:
Cp;m ðC8 H10 O2 N4 ; cr; IÞ ¼ 267:2 J  K1  mol1 at 298:15 K
and
Cp;m ðC8 H10 O2 N4 ; cr; IIÞ ¼ 173:4 J  K1  mol1 at 298:15 K
we calculated, using equation (4), Dgcr C p;m ðC8 H10
O2 N4 ; cr; IÞ ¼ ð40:8  33:0Þ J  K1  mol1 for phase I
and Dgcr C p;m ðC8 H10 O2 N4 ; cr; IIÞ ¼ ð26:8  33:0Þ J  K1 
mol1 for phase II, both at T = 298.15 K. The uncertainty
of ±33.0 J Æ K1 Æ mol1 quoted above was obtained con-
sidering the standard deviation of the empirical coefficients
of equation (4) [29]. Finally, introducing these values in
equation (3) leads to:
Dgcr H m ðC8 H10 O2 N4 ; IÞ ¼ 110:5  4:7 kJ  mol1 at 298:15 K;
and
Dgcr H m ðC8 H10 O2 N4 ; IIÞ ¼ 115:52:3 kJ  mol1 at 298:15 K:
It should stressed that Greisser et al. [27] reported the
values of 115 kJ Æ mol1 and 119 kJ Æ mol1 for the stan-
dard enthalpy of sublimation at T = 298.15 K for phase I
and phase II, respectively, without indication of the uncer-
tainty associated.
Finally, the results obtained in this work for the stan-
dard enthalpy of formation in condensed phase for each
polymorph of caffeine, together with the values of the stan-
dard enthalpy of sublimation ðDgcr H m Þ, allow the determi-
nation of the standard enthalpy of formation of caffeine
in the gaseous phase, Df H m ðgÞ. From the values relative
to phase I we obtained Df H m ðC8 H10 O2 N4 ; gÞ ¼ ð230:1
5:2Þ kJ  mol1 , while the value Df H m ðC8 H10 O2 N4 ; gÞ ¼
ð229:6  3:3Þ kJ  mol1 was obtained using the thermo-
dynamic properties of phase II. The very good agreement
between these values is again another evidence for the
internal consistency of the results presented in this work.
1519
We suggest to consider the average between those values
ð3Þ as the best value of the standard enthalpy of formation
of caffeine in gaseous state: Df H m ðC8 H10 O2 N4 ; gÞ ¼
ð229:7  6:1Þ kJ  mol1 .
4. Concluding remarks
In this work we have prepared and characterised by ele-
mental analysis, X-ray powder diffraction, DSC, GC-MS,
and FT-IR two phases of anhydrous caffeine (I or a, and
II or b). By using static-bomb combustion calorimetry in
oxygen the standard massic energies of combustion and
ð4Þ the standard enthalpies of combustion were determined.
From these values, the corresponding standard molar
enthalpies of formation were derived for both condensed
phases. Combining these data with literature values for the
standard enthalpies of sublimation allowed the estimation
of the standard enthalpy of formation in the gaseous phase.
Different approaches were used to test the internal consis-
tency of the results. The first one used reaction-solution cal-
orimetry for determining of enthalpy of solution of each
phase of caffeine in a mixture of ethanol/chloroform
(60:40). From these measurements it was found that the dif-
ference between the enthalpies of solution of the two crystal-
line polymorphs at room temperature is (2.04 ± 0.25)
kJ Æ mol1 which is comparable to (4.02 ± 0.03 kJ Æ mol1)
obtained by DSC at 155 C (328.15 K), and to (4.5 ± 3.2)
kJ Æ mol1 obtained by combustion calorimetry at 298.15
K. This agreement within the uncertainty interval, obtained
by three independent calorimetric techniques, is an indica-
tion of the reliability of the enthalpies of formation obtained
for the two polymorphs in condensed phase.
The values of the standard enthalpies of formation, in
condensed phase, obtained in this work, together the corre-
sponding standard enthalpies of sublimation, allowed the
suggestion of a value for the standard enthalpy of formation
of caffeine in the gaseous state: Df H m ðC8 H10 O2 N4 ; gÞ
¼ ð229:7  6:1Þ kJ  mol1 . This result is relevant, for
example, for computational energetic screening studies on
drug discovery development [30]. Finally, it should be
stressed that an accurate determination of enthalpies of com-
bustion and formation of a solid demands the knowledge of
the purity of phase of the used material.
Acknowledgements
The authors are indebted for Prof. Moura Ramos for
very useful discussions. A grant (SFRH/BD/12330/2003)
from Fundação para a Ciência e a Tecnologia is gratefully
acknowledged by S.S. Pinto.
Appendix A. Details on the calorimetric combustion
experimental procedures and data treatment
In a typical calorimetric experiment, a pellet of caf-
feine with a diameter of ca. 4 mm was placed in a platinum
1520 S.S. Pinto, H.P. Diogo / J. Chem. Thermodynamics 38 (2006) 1515–1522

crucible (containing n-hexadecane in the experiments on
phase I) and weighed to 107 g in a Sartorius 4504 Mp8-
1 ultra-micro balance. The crucible with the sample was
adjusted to the sample holder in the bomb head. A volume
of 50 lL of deionised water from a Milipore system (con-
ductivity 60.1 lS) was introduced in the bomb body. The
stainless-steel bomb of 17.95 cm3 internal volume was
closed and purged twice by charging it with oxygen (Ar
Liquide N45, mass fraction >0.9995) at a pressure of
1.01 MPa and then venting the overpressure. The bomb
was then charged with oxygen at a pressure of 3.04 MPa
and transferred to the inside of the calorimeter proper.
The combustion of the sample was initiated by discharge
of a 2200 lF capacitor through a platinum wire (Johnson
Matthey; mass fraction: 0.9995) with a diameter of
0.05 mm.
The results of the calorimetric combustion experiments
are shown in tables A1 and A2, where m(C8H10O2N4) is
the mass of caffeine; m(aux) is the mass of n-hexadecane
used as combustion auxiliary; n(HNO3) is the amount of
substance of nitric acid formed in the bomb process; ei
and ef are the energy equivalents of the bomb contents in
the initial and final states of the bomb process, respectively;
Ti and Tf represent the initial and final temperatures of the
experiment; DTc is the contribution to the observed tem-
perature rise of the calorimeter proper due to the heat
exchanged with the surroundings and the heat dissipated
by the temperature sensor; DUign is the electrical energy
supplied for ignition of the sample; DUIBP is the internal
energy change associated with the bomb process under iso-
thermal conditions, at T = 298.15 K; DUR represents the
sum of all corrections necessary to reduce DUIBP to the
standard state; DU(HNO3) is the energy change associated
with the formation of nitric acid; DU(aux) and
DU(C8H10O2N4) are the contributions of n-hexadecane
and caffeine to the energy of the isothermal bomb process,
respectively; and, finally, Dcu (C8H10O2N4) is the standard
massic energy of combustion of caffeine.
The values of Ti, Tf, and DTc were calculated by using a
computer program based on the Regnault–Pfaundler
method [16a] and DUIBP was obtained from:
DU IBP ¼eo ðT i  T f þ DT c Þ þ ei ðT i  298:15Þþ
ef ð298:15  T f þ DT c Þ þ DU ign : ðA:1Þ

TABLE A1
Results of the calorimetric combustion experiments on anhydrous caffeine, form I (C8H10O2N4)
Experiment 1 2 3 4 5 6
m(C8H10O2N4, I)/mg 34.5575 28.2855 32.3060 41.1013 46.7722 21.1121
m(aux)/mg 2.3244 2.0540 2.2645 2.0841 2.2755 1.9331
n(HNO3) · 105/mol 3.25 3.60 2.75 3.10 3.60 3.40
ei/(J Æ K1) 1.180 1.172 1.177 1.186 1.194 1.162
ef/(J Æ K1) 1.232 1.214 1.226 1.247 1.263 1.194
Ti/K 298.23056 298.27753 298.09865 298.08960 298.06605 298.06228
Tf/K 298.72161 298.69530 298.58950 298.66552 298.70513 298.44299
DTc/K · 102 3.55 3.88 6.06 4.87 4.16 8.73
DUign/J 1.76 1.76 1.76 1.76 1.76 1.76
DUibp/J 862.12 716.83 814.10 998.00 1131.17 554.31
DU(HNO3)/J 1.94 2.15 1.64 1.85 2.15 2.03
DU(aux)/J 105.41 96.90 106.83 98.32 107.35 91.20
DUR/J 0.65 0.52 0.60 0.77 0.88 0.39
DU(C8H10O2N4, I)/J 754.12 617.26 705.03 897.06 1020.79 460.69
Dcu (C8H10O2N4, I)/(J Æ g1) 21822.18 21822.49 21823.50 21825.58 21824.72 21821.14

TABLE A2
Results of the calorimetric combustion experiments on anhydrous caffeine, form II (C8H10O2N4)
Experiment 1 2 3 4 5
m(C8H10O2N4, II)/mg 23.8140 38.1108 39.4286 44.2060 36.3405
n(HNO3) · 105/mol 3.5 5.24 5.0 4.70 4.76
ei/(J Æ K1) 1.160 1.175 1.178 1.183 1.174
ef/(J Æ K1) 1.189 1.223 1.228 1.241 1.219
Ti/K 298.22072 298.07941 298.11363 298.08107 298.10354
Tf/K 298.55794 298.58125 298.62242 298.64233 298.58312
DTc/K · 102 6.11 6.09 5.27 3.24 5.91
DUign/J 1.76 1.76 1.76 1.76 1.76
DUibp/J 521.69 834.49 863.25 967.30 795.78
DU(HNO3)/J 2.09 3.13 2.99 2.81 2.84
DUR/J 0.41 0.70 0.71 0.80 0.65
DU(C8H10O2N4, II)/J 519.19 830.66 859.55 963.69 792.29
Dcu (C8H10O2N4, II)/J Æ g1 21801.88 21795.92 21800.16 21799.98 21801.85
 S.S. Pinto, H.P. Diogo / J. Chem. Thermodynamics 38 (2006) 1515–1522 1521

TABLE B1
Results of the reaction-solution calorimetric experiments relative to solution of caffeine phase I in a mixture of ethanol/chloroform (60:40)
m(C8H10O2N4)/mg n · 103/mol e/(J Æ K1) DTad/K Dsol H m =ðkJ  mol1 Þ
360.87 1.858 370.19 0.0562 11.202
389.81 2.007 349.48 0.0714 12.435
424.42 2.186 327.03 0.0812 12.149
498.49 2.567 339.52 0.0913 12.076
470.48 2.423 327.76 0.0877 11.870
ÆDsolHm/(kJ Æ mol1)æ = (11.89 ± 0.20) kJ Æ mol1

TABLE B2
Results of the reaction-solution calorimetric experiments relative to solution of caffeine phase II in a mixture of ethanol/chloroform (60:40)
m(C8H10O2N4)/mg n · 103/mol e/JK1 DTad/K Dsol H m =ðkJ  mol1 Þ
235.90 1.211 337.12 0.0517 14.358
327.65 1.687 316.93 0.070 13.174
190.37 0.980 334.73 0.0422 14.420
185.88 0.957 322.34 0.0408 13.752
287.10 1.478 327.25 0.0634 14.030
223.89 1.153 334.61 0.0462 13.399
hDsol H m =ðkJ  mol1 Þi ¼ ð13:93  0:15Þ kJ  mol1

The standard state corrections, DUR, were derived as rec- References

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JCT 06-34