Synperiplanar to antiperiplanar conformation changes as
underlying the mechanism of Debye Process in supercooled
Ibuprofen
K. Adrjanowicz1, K. Kaminski2,3, M. Dulski2, P. Wlodarczyk4, G. Bartkowiak1,5, L. Popenda1,
S. Jurga1,6, J. Kujawski7, J. Kruk7, M.K. Bernard7 and M. Paluch2
1
NanoBioMedical Centre, Adam Mickiewicz University, ul. Umultowska 85, 61-614 Poznan, Poland
2 Institute
3
of Physics, University of Silesia, ul. Uniwersytecka 4, 40-007 Katowice, Poland
Institute of Experimental Physics, University of Leipzig, Linnestr. 5, 04103 Leipzig, Germany
4 Institute
5
of Non Ferrous Metals, ul. Sowinskiego 5, 44-100 Gliwice, Poland
Faculty of Chemistry, Supramolecular Chemistry, Adam Mickiewicz University, ul. Umultowska 89b, 61-614 Poznan,
Poland
6 Department of Macromolecular Physics, Adam Mickiewicz University, ul. Umultowska 85, 61-614 Poznan, Poland
7 Department
of Organic Chemistry, Poznan University of Medical Sciences, ul. Grunwaldzka 6, 60-780 Poznan, Poland
Supplementary Materials
1. Chemical synthesis of racemic methyl ester of ibuprofen
To 10 ml of methanol in a 100 ml round bottom flask, equipped with a condenser (with a
calcium chloride guard tube), was added 1 g of racemic ibuprofen and 0.0.5 ml concentrated
sulphuric acid. The reaction mixture was refluxed for 10 h (TLC control using
benzene:chloroform 9:1 as mobile phase). After 10 h of refluxing the reaction mixture was
poured into 125 ml distilled water and extracted with n-hexane (3x25 ml) to remove the acid.
Combined organic were washed with saturated sodium bicarbonate solution (3x25 ml) to
remove acid. Organic layers were dried over anhydrous sodium sulphate and solvent was
evaporated to afford a colorless liquid ester with characteristic odor. The method given above
is described in details in paper by Ramachandran, G.; Ananthanarayan, L. Indian J.
Biotechnol. 2008, 7, 94-98.
2. Chemical purity verification (NMR studies)
NMR spectra were recorded at room temperature in CDCl3 as solvent on Varian VNMRS-400
MHz and Agilent 800 MHz spectrometers. 1H chemical shifts are reported in ppm relative to
1
TMS (δH = 0.0 ppm) as internal standard. Data are presented as follows: chemical shift,
multiplicity (s = singlet, d = doublet, q = quartet, m = multiplet and/or multiple resonances),
coupling constants (Hz), integration, and assignment. The 1H NMR spectrum of ibuprofen
methyl ester (Supplementary Fig. 1) showed no changes upon heating the compound to 80 °C
for ca 15 minutes and cooling it back to room temperature. Synthesized methyl ester of
ibuprofen is also chemically stable upon storage at room temperature (no changes in NMR
spectra were observed with time).
1
H NMR (400 MHz, CDCl3): δH 0.90 (s, 6H, 2xCH3, isopropyl), 1.48 (d, J = 7.3 Hz, 3H,
CH(CH3)COOCH3), 1.79-1.90 (m, 1H, CH(CH3)2), 2.44 (d, J = 7.0 Hz, 2H, CH2), 3.65 (s, 3H,
COOCH3), 3.70 (q, J = 7.2 Hz, 1H, CH(CH3)COOCH3), 7.08-7.11 (m, 2H, Ar), 7.18-7.21 (m,
2H, Ar).
3. Dielectric studies
(a) Fitting procedure
Dielectric loss spectra of methyl ibuprofen were fitted by 2 Havriliak-Negami (HN) functions
with DC-conductivity term [S. Havriliak, S. Negami, Polymer 1967, 8, 161]. Our fitting
procedure (none parameters were fixed) leads to the conclusion that D-relaxation process in
methylated derivative of ibuprofen is, indeed, Debye-like. As illustrated in Supplementary
Fig. 2 satisfactory fits were obtained with HN=0.98 and HN=0.85 at 227 K. At higher
temperatures, D-relaxation is even fitted with HN=0.98 and HN=0.9 (215K). These values
are not perfectly equal 1, but rather close to 1, which is certainly related with the fact the
amplitude of -process in methyl ibuprofen ester is very high (definitely much higher than for
ibuprofen), but the amplitude of D-relaxation remains very low, see Supplementary Fig. 3.
Therefore, any deviation from HN = HN = 1, can be related with experimental difficulty in
determining the correct values of the shape parameters for such a weak-intense process.
(b) Comparison of the D-relaxation in ibuprofen and methyl ibuprofen ester
As reported by Bras et al. for ibuprofen D-relaxation time closely follows the alpha process
over a very wide temperature and frequency domain. However, from Figure 3.(b) one can
conclude that in the case of methyl ibuprofen ester D-process does not follow any more the
VFT behavior, unlike the -process. We would like to remind here that the amplitude of process for methyl ester is much higher than that for ibuprofen, but same time they
compounds have very weak amplitude of D-relaxation. Therefore, it is very difficult to
2
determine for methyl ibuprofen ester D(T) dependence in much extended temperature range
and unambiguously state that its temperature dependence of D-relaxation times follows or not
the VFT behavior. In addition, by plotting on the same graph dielectric loss curves for
ibuprofen and methyl ibuprofen ester (Supplementary Fig. 4) we get a very important finding
that the maximums of D-relaxation peaks for ibuprofen and methyl ibuprofen are located
approximately in close vicinity of each other, which indicates that in this case the separation
between D- and - relaxations is not strongly affected by the hydrogen bonds and both
processes are indeed somehow connected.
3
Supplementary Fig. 1. 1H NMR spectrum of racemic methyl ester of ibuprofen
COOCH3
H 3C
H 3C
CH3
1.80
1.60
1.40
1.20
1.00
3.60
0.80
3.40
3.20
3.00
2.80
2.60
2.40
7.227.207.187.167.147.127.107.087.06
4
7.5
7.0
6.5
6.0
5.5
5.0
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0
Me-IBU
-relaxation
0.1
K
HN=0.85
21
5
K
0.01
22
7
Eps"
for D-relaxation at 227 K
HN=0.98
1E-3
10-2
D-relaxation
10-1
100
101
102
103
104
105
106
107
Freq. / Hz
Supplementary Fig.2. Dielectric loss spectra of methyl ibuprofen ester at 227 and 215 K. Solid
lines are HN fits
5
Eps''
IBU
T=263 K
-relaxation
0.01
D-relaxation
HN=0.92
HN=1.0
1E-3
101
102
103
104
105
106
107
Freq. [Hz]
Supplementary Fig. 3. Dielectric loss spectra of ibuprofen at 263 K. Solid lines are HN fits.
6
T=263 K, IBU (vertically shifted)
T=227 K, Me-IBU
0.1
D-relaxation
-relaxation
0.01
Eps''
Me-IBU
D-relaxation at 227 K
HN=0.98
IBU
D-relaxation at 263 K
HN=0.92
HN=0.85
HN=1.0
1E-3
10-1
100
101
102
103
104
105
106
107
Freq. [Hz]
Supplementary Fig. 4. Comparison of dielectric loss curves for ibuprofen and methyl ester of
ibuprofen measured at different temperatures but having approximately the same . Solid lines
represents HN fits.
7