Enthalpies and heat capacities of solution of racemic N-methyl-substituted glycolurils in water at T = (278.15 to 313.15) K

Article abstract of DOI:10.1016/j.tca.2015.09.023

The molar enthalpies of solution of racemic (with enantiomer ratio of 1:1) 2-monomethyl-, 2,6-dimethyl-, and 2,4,6-trimethylglycolurils (2-MMGU, 2,6-DMGU and 2,4,6-TMGU, respectively) in water were measured calorimetrically in the temperature range between (278.15 and 313.15) K and at p = 99.6 kPa. Derived from experimental data, the standard (at infinite dilution) molar enthalpic characteristics of the dissolution process are positive by sign and increase with rising temperature as well as in a sequence of 2,4,6-TMGU < 2,6-DMGU < 2-MMGU. In the same way, the standard heat capacity of solution decreases distinctly, leading to the conclusion that the effect of hydrophobic hydration is more pronounced for the more N-methylated solute. It was suggested that, despite the presence of hydrophobic moieties (N-sited methyl groups) in the molecules considered, a hydrophilic constituent (via H-bonding) seems to be the predominant one in the total enthalpy effect of a solute hydration.

Full text of DOI:10.1016/j.tca.2015.09.023

Thermochimica Acta 620 (2015) 59–64
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Thermochimica Acta
journal homepage: www.elsevier.com/locate/tca
Enthalpies and heat capacities of solution of racemic
N-methyl-substituted glycolurils in water at T = (278.15 to 313.15) K
Evgeniy V. Ivanov , Dmitriy V. Batovb,c
a,∗
a
Laboratory of Thermodynamics of Solutions of Non-electrolytes and Biologically Active Substances, G.A. Krestov Institute of Solution Chemistry, Russian
Academy of Sciences, 1 Akademicheskaya Str., 153045 Ivanovo, Russian Federation
b
Incorporated Physical and Chemical Center of Solutions, G.A. Krestov Institute of Solution Chemistry, Russian Academy of Sciences, 1 Akademicheskaya
Str., 153045 Ivanovo, Russian Federation
c
Ivanovo’s State University of Chemistry and Technology, 7 Sheremetevsky Ave., 153000 Ivanovo, Russian Federation
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 12 May 2015
Received in revised form
The molar enthalpies of solution of racemic (with enantiomer ratio of 1:1) 2-monomethyl-, 2,6-dimethyl-,
and 2,4,6-trimethylglycolurils (2-MMGU, 2,6-DMGU and 2,4,6-TMGU, respectively) in water were mea-
sured calorimetrically in the temperature range between (278.15 and 313.15) K and at p = 99.6 kPa.
Derived from experimental data, the standard (at infinite dilution) molar enthalpic characteristics of
the dissolution process are positive by sign and increase with rising temperature as well as in a sequence
of 2,4,6-TMGU < 2,6-DMGU < 2-MMGU. In the same way, the standard heat capacity of solution decreases
distinctly, leading to the conclusion that the effect of hydrophobic hydration is more pronounced for the
more N-methylated solute. It was suggested that, despite the presence of hydrophobic moieties (N-sited
methyl groups) in the molecules considered, a hydrophilic constituent (via H-bonding) seems to be the
predominant one in the total enthalpy effect of a solute hydration.
2
2 September 2015
Accepted 27 September 2015
Available online 30 September 2015
Keywords:
Enthalpy of dissolution
Water
2
2
2
-Monomethylglycoluril
,6-Dimethylglycoluril
,4,6-Trimethylglycoluril
© 2015 Elsevier B.V. All rights reserved.
1
. Introduction
It is known that some representatives of the cyclic N-alkyl-
ture. It is caused by the structure features of these molecules.
Due to rigidity of the heterocyclic core and cis-fusion of the five-
membered rings, these glycoluril-derivatives adopt a conformation
of a “half-open book” or “gull-wings” [2,3]. Because of this, they
contain the asymmetric conjugate C C atoms. Beginning only
with the N-ethyl-substituted chiral glycolurils, the diastereotropic
methylene protons are defining a stereochemical nature of their
molecules [1]. Given this, 2-monomethylglycoluril (2-MMGU) or
2,4,6-trimethylglycoluril (2,4,6-TMGU) is crystallized as a racemate
with the equimolecular ratio of R-(+)- and S-(−)-enantiomers [4,5].
At the same time 2,6-dimethylglycoluril (2,6-DMGU) forms the
conglomerate (or mixture of homochiral crystals) which is capa-
ble of spontaneous separation into enantiomers with the ratio of
1:1 [1,6].
As we mentioned above, the racemic and enantiomeric forms
possess somewhat differing characteristics in a crystalline state
(although, according to the 1H NMR spectra, the geometries of a
glycoluril-derivative in homo- and heterochiral crystals are similar
[6]). Surely, it would be interesting to compare the thermodynamic
hydration effects for the specified molecular forms. Meanwhile,
taking into account the fact that the segregation of each racemate
into enantiomers (in the sufficient quantity for experiments) is
often a laborious and/or high-priced route for now, we have ana-
lyzed here the some thermodynamic characteristics of dissolution
substituted derivatives of urea have the pronounced physiological
or biological activity. The bicyclic bisureas of an octane series, being
2
,4,6,8-tetraazabicyclo[3.3.0]octane-3,7-diones or glycolurils (see
in Fig. 1), take up a special place among them. These compounds
serve as a basis to design the promising drugs [1]. However the
lack of reliable data on their thermodynamic properties in both
crystalline and dissolved states does not allow identifying the
peculiarities of hydration of pharmacophore (hydrophobic and
proton-donor/acceptor) centers of the molecules in question. In
many ways these peculiarities are due to the ability of chiral
glycoluril (as a racemate) is divided into two {R-(+) and S-(−)}
enantiomers, whose thermodynamic and physic-chemical charac-
teristics are somewhat different from each other. Herewith one of
enantiomers is usually the more bioactive compared to the racemic
form.
It should be noted in this connection that none of the three
methyl-substituted compounds studied is a diastereomeric mix-
∗ Corresponding author.
E-mail addresses: evi@isc-ras.ru, evi ihrras@mail.ru (E.V. Ivanov).
http://dx.doi.org/10.1016/j.tca.2015.09.023
0
040-6031/© 2015 Elsevier B.V. All rights reserved.

6
0
E.V. Ivanov, D.V. Batov / Thermochimica Acta 620 (2015) 59–64
Fig. 1. The schematically simplified molecular structures of the studied chiral glycolurils with the atom’s numeration: (a) 2-mohomethylglycoluril, (b) 2,6-dimethylglycoluril,
and (c) 2,4,6-trimethylglycoluril.
(
hydration) for the titled compounds being in the racemic form
procedure [1,4,5,11,12] based on the regioselective cyclocondensa-
tion of N-methyl-substituted urea derivative (puriss grade, Aldrich)
with the 4,5-dihydroxyimidazolidin-2-one or its mono-N-methyl-
derivative (during the 2,4,6-TMGU synthesis [4]). The last two
monocyclic compounds were prepared by the reaction of glyoxal,
being taken as a 40% aqueous solution (Acros, pure grade), with
urea or mono-N-methylurea [4,5]. Herewith the racemic nature of
2-MMGU and 2,4,6-TMGU was confirmed by the results of studying
of a solution optical activity (rotation) using a Polamat A polarime-
ter. According to the polarimetry data, the synthesized sample of
(± )-2,6-DMGU was optically inactive (i.e., it had a enantiomer ratio
of 1:1), too. The preparations were additionally recrystallized from
absolute ethanol (EtOH: Fluka, puriss) followed by slow precipita-
only. A consideration of similar properties of their enantiomers as
solutes will be our separate task in the future.
Seen in this light, the thermochemical study of aqueous
solutions of N-alkyl-substituted glycolurils seems to be very infor-
mative. Previously [7–9], the enthalpy-related characteristics of
solution and hydration of achiral unsubstituted glycoluril (GU), 2,4-
dimethylglycoluril (2,4-DMGU) and 2,4,6,8-tetramethylglycoluril
(
2,4,6,8-TMGU, or the pharmaceutical mebicar) in water have been
discussed. In this work, we report data on the molar enthalpies
of solution, ꢀsol
1
m
2
H
, of chiral (racemic with enantiomer’s ratio of
:1) 2-MMGU, 2,6-DMGU and 2,4,6-TMGU in water (Fig. 1). The
calorimetric experiments were performed at T = (278.15, 279.15,
2
88.15, 298.15, 308.15, and 313.15) K and p = (99.6 ± 0.08) kPa. The
tion through the addition of diethyl ether (Et O: Fluka, ACS reagent)
2
m
2
experimental ꢀ
H
values were used to compute the standard
to give purer products. The compounds purified were then repeat-
edly dried in vacuo at T ≈ 320 K for 2,4,6-TMGU and T ≈ 370 K for
2-MMGU or 2,6-DMGU to constant mass. The final mass-fraction
purity of each of the glycolurils compared was from 0.992 to 0.995
sol
o
2
(
at infinite dilution) molar enthalpies, ꢀ H , and heat capacities,
sol
o
p,2
o
2
ꢀsol
C
= (∂ꢀ H /∂T) , for the process of dissolution/hydration
sol
p
of these three heterocyclic compounds.
(see Table 1), as determined using a high performance liquid chro-
matography (HPLC) based on the ECOM setup.
2
. Experimental
The “authenticity” of the racemic samples after synthesis was
established also using their 1H NMR data. The measurements were
carried out on a Bruker AM 300 spectrometer in DMSO-d6 (relative
to TMS as the internal standard) at T = 300 K. Being derived by such
way, the chemical shifts, ı/ppm, and coupling constants, J/Hz, were
A detail description of compounds employed in the calori-
metric measurements is given in Table 1. All N-methyl-substituted
glycolurils were laboratory-synthesized in accordance with the
Table 1
Sample description.
Characteristics
2-Monomethylglycoluril
2,6-Dimethylglycoluril
2,4,6-Trimethyglycoluril
Abbreviated name
IUPAC (CAS) name
2-MMGU
1-Methyl-
2,6-DMGU
1,3-Dimethyl-
2,4,6-TMGU
1,3,4-Trimethyl-
tetrahydroimidazo[4,5-
d]imidazole-2,5(1H,3H)-dione
2,4,6-Trimethyl-2,4,6,8-
tetraazabicyclo[3.3.0]-octane-
3,7-dione
tetrahydroimidazo[4,5-
d]imidazole-2,5(1H,3H)-dione
2-Methyl-2,4,6,8-
tetraazabicyclo[3.3.0]-octane-
3,7-dione
tetrahydroimidazo[4,5-
d]imidazole-2,5(1H,3H)-dione
2,6-Dimethyl-2,4,6,8-
tetraazabicyclo[3.3.0]-octane-
3,7-dione
Other agreed-upon name
(
being used in the organic
synthesis)
CAS RN
28889-54-5
17754-76-6
263403-90-3
Molecular formula
Molar mass/(g mol−1),
according to [10]
C5H8N4O2
156.1443
C6H10N4O2
170.1712
C7H12N4O2
184.1980
a
a
a
Melting point, Tmp/K
534.8 ± 0.2
550.2 ± 0.2
365.7 ± 0.2
(
533.2 ± 2 [5,12])
(542.2 ± 1 [1])
(400.2 ± 1 [4])
a
a
a
Standard enthalpy of fusion,
34.1 ± 0.5
24.4 ± 0.5
20.1 ± 0.5
o
2
−1
ꢀ
fusH /(kJ mol
)
Source
Original synthesis, being performed by Dr. A.N. Kravchenko with co-workers (N.D. Zelinsky Institute of Organic Chemistry
of the RAS, Moscow, Russia)
Initial mass fraction purity
Purification method
>0.95
≥0.95
≥0.95
The recrystallization from absolute EtOH with the addition of Et2O
Final mass fraction purity
Analysis method
∼0.995
∼0.993
∼0.992
HPLC
HPLC
HPLC
a
The reported uncertainty corresponds to expanded uncertainty, UT(H) (at the 0.95 level of confidence).

E.V. Ivanov, D.V. Batov / Thermochimica Acta 620 (2015) 59–64
61
Table 2
found to be the following: 2.61 (s, 3Н, Me), 5.14 (d, 1H, CH, J = 8.2),
o
2
Standard molar enthalpies of dissolution, ꢀsolH , of the studied glycoluril-
derivatives in water at different temperatures, T, and p = 99.6 kPa.
5
1
.20 (d, 1H, CH, J = 8.2), 7.25 (s, 1H, NH), 7.27 (s, 1H, NH), 7.44 (s,
H, NH) for 2-MMGU and 2.61 (s, 6H, 2Me), 5.10 (s, 2H, 2CH), 7.52
a
T/K
m/{mol (kg H2O)−
}
1
b
Nc
ꢀsolHo ± ıH /(kJ mol−1)d
(
s, 2H, 2NH) for 2,6-DMGU. These results, being presented graph-
ically (in the form of spectrograms) as a Supplementary material
Figs. S1 and S2), are in good agreement with those existing in the
literature [1,5,12]. As for 2,4,6-TMGU, we have presented here the
2
2
-Monomethylglycoluril
(
278.15
0.0057–0.0091
0.0075–0.0109
0.0136–0.0154
0.0117–0.0141
0.0125–0.0145
0.0103–0.0153
4
5
4
4
4
5
23.00 ± 0.04
23.05 ± 0.03
23.44 ± 0.06
24.00 ± 0.08
24.76 ± 0.08
25.19 ± 0.08
2
79.15
288.15
98.15
1
13
relevant H NMR and C NMR data for this glycoluril-derivative in
DMSO-d6 at T = 300 K for the first time (earlier [4], the data on ı in
CDCl3 at the same temperature were published only). The results
also were provided as a Supplementary material, in the form of
detailed NMR-spectrograms (see Figs. 3S and 4S).
2
308.15
313.15
2
,6-Dimethylglycoluril
278.15
0.0062–0.0075
0.0052–0.0055
0.0050–0.0059
0.0101–0.0109
0.0043–0.0068
0.0048–0.0050
4
4
4
4
4
4
11.92 ± 0.04
12.02 ± 0.04
12.94 ± 0.12
13.88 ± 0.06
14.93 ± 0.03
15.40 ± 0.09
In Table 1, data on melting point, Tmp, and standard molar
279.15
288.15
o
2
enthalpy of the fusion (melting), ꢀfusH , for the investigated
2
3
3
98.15
08.15
13.15
glycoluril-derivatives are shown together with values, being found
in other sources. The results of thermal analysis of the samples were
derived from heating curves in the melting region using a mul-
tipurpose differential scanning calorimeter DSC 204 F1 Phoenix
2
2
2
,4,6-Trimethylglycoluril
78.15
79.15
0.0077–0.0095
5
4
5
4
5
4
3.28 ± 0.06
3.40 ± 0.06
4.63 ± 0.09
5.91 ± 0.13
7.32 ± 0.08
7.98 ± 0.06
(
Netzsch-Gerätebau GmbH, Germany). As follows from data of
0.0066–0.0073
0.0048–0.0071
0.0058–0.0086
0.0051–0.0078
0.0049–0.0075
Table 1, our values of Tmp are in fairly good agreement with the
results reported by other authors, perhaps, with the exception of
the quantity for 2,4,6-TMGU. We believe that it may be mainly
due to differences in details of the experimental procedure. Unfor-
tunately, there is no information on ways of the preparing and
thermal testing the 2,4,6-TMGU sample in the work [4], whereas
288.15
298.15
3
3
08.15
13.15
a
The expanded uncertainties, U, do not exceed: U(m) = ± 0.0001 mol kg−1
,
U(T) = ± 0.001 K and U(p) = ± 0.8 kPa (level of confidence = 0.95).
b
c
m
2
The molality range in which the ꢀsolH values were averaged.
The number of independent measurements of ꢀsolH2
ıH is the half-width of a 95% confidential interval for ꢀsolH .
in our case, the most accurate method of measuring tmp was
m
.
o
2
d
o
2
employed. It is worthy of noticing also the fact that the ꢀfus
H
value decreases with sequential increasing the number of methyl
groups on the N(2)-, N(4)-, and N(6)-sited positions in a gly-
coluril’s molecule. Going from 2-MMGU to 2,6-DMGU and further
to 2,4,6-TMGU, this tendency becomes decreasingly pronounced
interaction is to be weaker than the interaction between solute
molecules in their own crystal substance. Indeed, since the stan-
dard state is understood as the state of a hypothetically ideal
solution or gas phase [16,17], the hydration of a solute can be iden-
tified with the condensation of 1 mol of its gaseous (monomeric)
(
see Table 1).
After and before experiments, each glycoluril’s sample was
stored in a light-proof vacuum dessicator over P O5. The water (of
2
natural isotope composition) was deionized and then twice dis-
tilled in a Pyrex-glass apparatus up to electrical conductivity of
1
molecules in an infinitely large amount of a solvent [18].
−
6
−1
.
1
.5 × 10 S cm
o
As the temperature rises, the ꢀsol
H
values become increas-
m
2
2
The molality-dependent molar enthalpies of solution, ꢀsol
H
,
o
ingly positive (see in Table 2). Interestingly, ꢀsol
the same manner as it is observed in the case of changing ꢀfus
H
decreases in
2
of the glycolurils compared were measured using an ampoule-type
o
H
2
sealed microcalorimeter with isothermal shell. The setup was fit-
(Table 1) on going from 2-MMGU to 2,6-DMGU and further to 2,4,6-
3
ted with a 60 cm titanium vessel. The procedure for experimental
TMGU. It would be more “thermodynamically justified”, if a similar
measurements and testing the microcalorimeter were detailed pre-
o
correlation existed between ꢀ H and the molar enthalpy of sub-
m
2
sol
2
viously [13,14]. Four to five measurements of ꢀsol
m were performed at each temperature.
H
at different
o
o
limation, ꢀsub
H
(or hydration, ꢀhydrH ). But, due to the problem
2
2
of decomposition of glycoluril’s samples during their heating, we
o
2
were unable to derive the reliable information on ꢀsub
H
(using
the Knudsen’s effusion mass-spectrometric method [19]).
3
. Results and discussion
Such a distribution in the dissolution enthalpies (Table 2) is not
surprising. Here, the point is that the hydrophobicity of a solute
becomes increasingly pronounced in a sequence of 2-MMGU < 2,6-
DMGU < 2,4,6,8-TMGU (i.e., with the increase in the number of
methyl groups in a glycoluril’s molecule). When the specified
glycoluril-derivatives are subjected to dissolution in water, the
given circumstance should be manifested in the relative strength-
ening of hydrophobic constituent of a solute hydration.
The results of calorimetric measurements indicated that the
m
2
ꢀsol
H
values within the measurement error do not depend on
m at all the temperatures chosen. As a consequence, the values of
o
2
m
ꢀsolH were calculated as average-weighted |ꢀ H |av in the stud-
sol
2
m
2
ied range of m. The procedure for calculating |ꢀ H |av is described
sol
∞
previously [14,15]. The temperature-dependent data on ꢀ
H
sol
2
are tabulated in Table 2.
To understand a situation with enthalpy effects of dissolu-
Data of Table 2 point out the fact that the process of dissolution
tion more clearly, heat capacity changes in the specified process,
of all three glycoluril-derivatives in water is endothermic over
the whole temperature range of interest. A positive sign at ꢀsol
o
p,2
ꢀsol
C
, for all aqueous glycoluril-derivatives under study, must
o
H
2
be considered, too. We have attempted to do it below.
suggests that the total energy released during the formation of
heterocomponent H bonds and from hydrophobic hydration of a
solute (the exothermic contribution) does not replace all of the
energy spent to destroy a glycoluril’s crystal lattice and to form
the cavity in the solvent (the endothermic contribution). The
latter process is accompanied by the disturbance of the hydrogen-
bonded network of water in the nearest environment of the
solute glycoluril-derivative. In other words, the glycoluril–water
1
Here, the point is that the evaporation or sublimation process at standard state
can be identified with the opposite process of condensation where the solute is
postulated to be solvated in its own environment. Hence the sign and quantity of
the standard enthalpy of dissolution are being determined by the difference between
solute–solvent and solute–solute interactions [18].

6
2
E.V. Ivanov, D.V. Batov / Thermochimica Acta 620 (2015) 59–64
The analysis of data in Table 2 has shown that the dependence
o
2
of ꢀsolH vs. T for 2,6-DMGU and 2,4,6-TMGU can be approximated
by a simple linear equation [9,15]
o
2
o
2
o
p,2
ꢀsolH (T) − ꢀ H (Â) = ꢀsolC (T − Â),
(1)
sol
where  = 298.15 K is the “reference temperature”. In fitting of this
equation, a least-squares method was employed with choosing the
degree, for which all the coefficients are significant with respect to
their own 95% confidence limit.
o
p,2
The form of Eq. (1) assumes that the ꢀsol
C
values,
−
1
−1
being equal to (99.5 ± 1.9) J mol
K
for 2,6-DMGU and
−1
K for 2,4,6-TMGU in H O, do not depend
−1
(
134.4 ± 2.3) J mol
2
on the current value of T within the temperature range chosen.
o
2
In the case of (H O + 2-MMGU), the ꢀsolH − T function is non-
2
linear and the corresponding data of Table 2 can be adequately
described by a least square method applied to model (1) with the
o
2
additional quadratic term: (∂ꢀsol
C
/∂T) (T − Â) . The following
p,2
p
o
p,2
temperature-dependent ꢀsol
C
values for 2-MMGU in water
have been derived in such way (ıCp = ± 1.3 J mol−
1
K ): 33.9
−1
(
(
278.15 K), 35.5 (279.15 K), 50.1 (288.15 K), 66.4 (298.15 K), 82.6
o
308.15 K), and 90.7 (313.15 K). Assuming the ꢀsub
not change in the temperature range studied, the ꢀsol
H
value does
2
o
C
value is
p,2
numerically equal to a change in the standard molar heat capacity
Fig. 2. The correlation between the standard molar heat capacities of the glycoluril-
derivatives studied in water and the number of N-sited methyl groups in the solute
molecules at 298.15 K.
o
of glycoluril hydration, ꢀhydr
C
.
p,2
ꢀ
ꢁ
o
p,2
∼
o
p,2
According to [20], a large and positive ꢀsol
C
= ꢀhydrC
reflects structural changes in the solvent induced by increas-
ing energy fluctuations (due to increasing the number of shorter
water–water H bonds) in the nearest vicinity of nonpolar groups.
Given this, one can confirm that the effect of hydrophobic hydra-
tion of a solute is to be more pronounced in the aqueous medium
molecules, two bound to each of carbonyls, one to each of nitro-
gen protons. The HC CH bridging group can form H bonds with
two other water molecules [8,24,25]. Unlike the trans-configured
containing 2,4,6-TMGU. Herewith, using the data [7,21], we have
2
,6-DMGU, both methyls of 2,4-DMGU are located in the same
o
obtained ꢀsol
C
for achiral 2,4,6,8-TMGU (mebicar) to be equal to
p,2
five-membered ring, predetermining the stereochemically achiral
nature of this molecule. Hence two unsubstituted NH groups are
in the adjacent ring, a situation being characteristic for the concur-
−1
−1
(
168.7 ± 8.4) J mol
K that is almost 2.5 times greater than the
corresponding value for 2-MMGU at 298.15 K. In the given con-
o
p,2
text, of special interest is the fact that the ꢀsol
C
(Â) quantity
rent hydration of urea and its 1,3-dimethyl-derivative [26]. Seen
o
2
varies virtually in proportion to the number of methyl-substituents,
in this light, the less pronounced changes in ꢀsol
H
of 2,4-DMGU
N , within a series of 2-MMGU < 2,6-DMGU < 2,4,6-TMGU < 2,4,6,8-
depending on T may be caused by the decreasing steric hindrances
for the solute–solvent interactions through C O···H and N···H O-
bonding.
C
TMGU (see Fig. 2).
o
Being depicted in Fig. 2, the ꢀsolC − N function have allowed
C
p,2
o
p,2
us to estimate the value of ꢀsol
C
(Â) for the unexplored GU (due
Previously [24,25], by using the millimeter-wave absorption and
C NMR spectroscopic studies of aqueous mebicar, it has been
13
to its very low solubility), i.e., for the case when N = 0. For this
C
concluded that two carbonyl oxygens form H bonds with four
water molecules according to a mechanism of “positive hydra-
tion”, whereas the hydrogen-bonding ability of nitrogen atoms
is sterically hindered. Herewith, at least two water molecules
incorporated in the hydration shell of a 2,4,6,8-TMGU molecule
purpose, we have expressed the given relation in an analytical form
o
p,20
−1 −1
K
) = 31.8(± 2.9) + 34.2(± 0.9) · NC.
ꢀsol
C
(Â)/(J mol
(2)
The first term in the right-hand side of Eq. (2) is the predicted
o
p,2
value of ꢀsol
C
for GU at  = 298.15 K, although this assumption
(probably about CH groups) retain their rotation mobility, as has
should be experimentally tested. The coefficient at NC repre-
sents the average-weighted value of the heat capacity increment
been observed for urea “negative hydration” [27]. Given this and the
fact that each of the glycoluril-derivatives considered here contains
ıCP (CH ) in the above-mentioned glycoluril’s series.
2
(1–3) NH groups, the hydrophilic (via hydrogen-bonding) inter-
In the first place, it is worth noting that, unlike the family of
actions are to be predominating in hydration of their molecules,
acyclic N-methyl-substituted ureas [22,23], the ıCP (CH ) contri-
2
although the hydrophobic constituent (around N-sited CH groups)
3
bution for each of the considered heterocyclic derivatives in an
aqueous medium was estimated to be the same (within the limit
of error), regardless of the stereochemical nature of a molecule
in the case of 2,4,6-TMGU seems to be significant.
This inference is confirmed by the enthalpy coefficients for pair-
wise 2–2 interactions, h22, which for the aqueous mebicar were
o
methylation. The second point of interest is a decrease in ꢀsol
C
by
p,2
−1
found to be ca. −2042 J kg mol [28]. In other words, by analogy
−
1
−1
(
9 ± 3) J mol
K at replacement of 2,6-DMGU by the equimolecu-
−1
[29]), the 2,4,6,8-
with hydrophilic urea (h22 ≈ −330 J kg mol
2
lar 2,4-DMGU [9]. The situation is more complicated here, because
each of glycoluril-derivatives compared contains two CH3 groups
attached to nitrogen atoms in different ways (Fig. 1). The hydration
sphere of these compounds most probably consists of eight water
TMGU molecules in an aqueous medium interact rather strongly
with each other to form solvent-separated pairs despite the pres-
ence of the four (as in 1,1,3,3-tetramethylurea) methyl groups.
Allowing for increase of the proton-donor ability in a sequence of
2
,4,6,8-TMGU < 2,4,6-TMGU < 2,6-DMGU < 2-MMGU, this fact indi-
cates that the hydrophilic component of hydration of the studied
glycoluril-derivatives generally dominates over the hydrophobic
2
In the case of aqueous 2,4-DMGU,ꢀsolCo (Â) = (90.4 ± 2.2) J mol−1
−1
K
[9].
p,2

E.V. Ivanov, D.V. Batov / Thermochimica Acta 620 (2015) 59–64
63
constituent and the given tendency is to be strengthened when the
NC in a molecule decreases.
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