Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 103 (2013) 110

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Spectrochimica Acta Part A: Molecular and

Biomolecular Spectroscopy
journal homepage: www.elsevier.com/locate/saa

IR, Raman and SERS spectra of propantheline bromide

C. Baraldi a, G. Freguglia a, A. Tinti b, M. Sparta c, A.N. Alexandrova c, M.C. Gamberini a,
a

Department of Pharmaceutical Sciences, Institute of Pharmacy, University of Modena and Reggio Emilia, via Campi n. 183, 41100 Modena, Italy
Department of Biochemistry, University of Bologna, via Belmeloro 8/2, 40126 Bologna, Italy
c
Department of Chemistry and Biochemistry, University of California, Los Angeles, 607 Charles E. Young Drive East, Los Angeles, CA 90095-1569, USA
b

h i g h l i g h t s

g r a p h i c a l a b s t r a c t

" Characterization of I and II

"

"
"

"

propantheline bromide polymorphic

forms.
FT-IR, Raman and hot stage Raman
microscopy studies and their
vibrations assignments.
DSC thermograms and X-ray powder
diffraction data.
SERS spectrum in a silver colloid: the
drug is adsorbed through the oxygen
atom.
Quantum mechanical calculations of
the most and least stable
conformers.

a r t i c l e

i n f o

Article history:
Received 6 December 2011
Received in revised form 6 August 2012
Accepted 27 October 2012
Available online 7 November 2012
Keywords:
Propantheline bromide
FTIR/ATR spectroscopy
Raman microscopy
Hot stage Raman microscopy (HSRM)
Surface enhanced Raman spectroscopy
(SERS)

a b s t r a c t
The two known propantheline bromide polymorphs (form I and form II) were studied and characterized
by a multianalytical approach. In the present work, the identication of propantheline bromide polymorphic forms through vibrational IR spectroscopies are presented and for the rst time Raman microscopy
and hot stage Raman microscopy (HSRM) studies are reported. Finally, quantum mechanical calculations
were performed. For assisting the assignment of the experimental picks, the two IR spectra of the most
and least stable representatives of a set of 56 conformers are calculated and studied.
DSC thermograms data, are also reported. The surface enhanced Raman scattering (SERS) spectrum was
also recorded in a silver colloid; it could be inferred that propantheline bromide is adsorbed on silver colloid through the oxygen atom with the molecular plane perpendicular to the metal surface.
2012 Elsevier B.V. All rights reserved.

Introduction
It is well known that in many cases for the same chemical composition different crystal structures show different crystal packing
and/or different conformations. Differences in physico-chemical
properties of various solid forms can be observed: density, hardness,
tabletability, refractive index, melting point, melting enthalpy,
vapor pressure, solubility, dissolution rate and other thermodynamic and kinetic properties.
Corresponding author. Tel.: +39 59 205 5157; fax: +39 59 205 5131.
E-mail address: mariacristina.gamberini@unimore.it (M.C. Gamberini).
1386-1425/$ - see front matter 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.saa.2012.10.070

Otherwise implications on the absorption of the active drug

from its dosage form can cause differences in solubility [1]. This
can inuence the absorption of the active drug from its dosage
form [2], by affecting the dissolution rate and, in conclusion, the
bioavailability of a given drug.
In fact, for a new drug approval, US Food and Drug Administration (FDA) guidelines state that for a drug substance, appropriate
analytical procedures need to be used for detecting polymorphs,
hydrates and amorphous forms [3]. During the various processing
steps of a drug development it is very important to control drug
crystal forms, because polymorph interconversions, solvation/
desolvation, hydrates formations, and changes in cristallinity can

C. Baraldi et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 103 (2013) 110

alter the pharmaceutical formulation, and nal bioavailability.

Industrial processes such as spray drying and lyophilization may
lead to the emergency of amorphous forms, causing a decreased
stability and an increased hygroscopicity of the crystalline product.
Furthermore, processing stresses, like drying, grinding, milling, wet
granulation, oven drying and compaction, are reported to accelerate pharmaceutical solids phase transitions, i.e. polymorphs transitions [4].
The degree of polymorphic interconversion will depend on the
relative stability of the phases in question and on the type and degree of mechanical processing applied. It is often desirable to
choose the most stable polymorphic form of the drug in the beginning, and to control the crystal form and the distributions in size
and shape of the drug crystals during the entire process of development. The appearance of a metastable form during processing, and
its presence in the nal dosage form, frequently lead to instability
of the drug release due to phase transformations. Sometimes, on
the contrary, the metastable form can be used, if it has better
bioavailability [5].
The propantheline, or 2-propanaminium, N-methyl-N-(1-methylethyl)-N-[2-[(9H-xanthene-9-ylcarbonyl)oxy]ethyl]-bromide (Fig. 1),
a quaternary ammonium salt, is a cholinergic muscarinic receptor
antagonist. Although infrequently used in clinic, it can be employed
as an antispasmodic in reducing gastrointestinal motility [6].
Commercially available in capsules, it may be also used in treating
rhinitis, urinary incontinences and peptic ulcer diseases. In USA, it is
marketed in tablets too.
Literature reports the existence of two prophantheline bromide
polymorphic forms: the stable form I and metastable form II,
which, upon heating above 100 C, becomes the stable form I [7].
From the literature, a liquid chromatographic procedure permitted an identication of the stated content of propantheline bromide commercial tablets, which appeared to be composed of only
60% of this compound mixed with closely related impurities, such
as xanthone, 9-hydroxypropantheline, methyl xanthanoate and
methyl 9-hydroxyxanthanoate. It was evident that the presence
of 9-hydroxypropantheline bromide in tablets most probably arose
from a carryover during the synthesis of propantheline bromide
[8,9].
In the present work, the identication of propantheline bromide
polymorphic forms through vibrational IR and Raman spectroscopies are reported. The spectroscopic data and their attributions,
complete the propantheline bromide polymorphs knowledge.
Room temperature as well as hot-stage micro-Raman spectra heat-

Fig. 1. Propantheline bromide structure.

ing until 160 C were collected. In addition, some attributions of

signicant IR and Raman bands are reported for the rst time. Also
DSC was used to characterize and identify both polymorphs.
Surface enhanced Raman scattering (SERS) spectroscopy is a
well-established and highly effective technique that enables to observe Raman scattering from species present at trace concentrations [10,11]. It is a useful tool in surface chemistry because of
its high sensitivity and potential in providing useful information
regarding metaladsorbate interactions [12,13]. In this paper, the
SERS spectra of propantheline bromide are reported for the rst
time.
Materials and methods
Compounds
The basic propantheline bromide was a commercial sample
from SigmaAldrich (Italy), corresponding to form I and studied
as reported in the following.
Preparation of polymorphs
Form I. Commercial propantheline bromide (0.40 g) was dissolved in acetone (2 ml) and heated to 80 C for 510 min.
Form II. Commercial propantheline bromide (0.40 g) was dissolved in i-propanol (10 ml), heated to 83 C and set aside for
undisturbed crystallization at room temperature.
Methods
IR with attenuated total reection (FT-IR/ATR)
The spectra were recorded with a VERTEX 70 (Bruker) FT-IR
spectrophotometer, equipped with a deuterium triglycine sulfate
(DTGS) detector. Setting parameters: resolution 4 cm 1; apodization weak. The spectral range was 4000600 cm 1 with 32 scans
for each spectrum. The ATR spectra were recorded using the Elmer
Golden-Gate accessory.
Raman microscopy and hot stage Raman microscopy (HSRM)
The Raman spectra were recorded with a confocal Labram
instrument (Jobin Yvon-Horiba) equipped with a HeANe laser at
632.8 nm and a CCD detector (254  1024), cooled by Peltier effect.
The spectra were recorded in backscattering after focalisation in
several positions within a small area (ca. 100 lm  100 lm) of
the sample. The maximum power employed was 5 mW and the
recording time for good signal-to-noise ratio was 100200 s. Furthermore, GRAMS/AI 7.02 was used for the elaboration of the
spectra.
The hot-stage Raman analysis was carried out by coupling directly the Raman microscope with a hot stage.
Surface enhanced Raman spectroscopy (preparation of the silver
colloid)
The aqueous silver colloid used in the SERS experiments was
prepared by reduction of silver nitrate (Aldrich, 99.998% purity)
by sodium citrate (Aldrich, 99% purity), following the Lee-Meisel
method [14,15]. One milliliter of a 2  10 4 M aqueous solution
of the title compound was added to an equal volume of the silver
colloid. Colloid aggregation was induced by addition of 35 ml of a
1 M aqueous solution of NaCl (Aldrich, 99.999% purity). For the
aqueous solutions 18 MX/cm water was used.
One drop of the nal colloid mixture was placed on a glass slide
and the Raman spectrum was recorded with the instrument cited
above. The power employed was 0.62 mW and the recording time
was 10 s.

C. Baraldi et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 103 (2013) 110

Computational details
Ab initio quantum mechanical calculations were carried out to
assist the interpretation of the experimental spectra.
A total of 56 conformers of the propantheline cation, as found in
the PubChem BioAssay database [16] were optimized using Density Functional Theory (TPSS functional [17] with the addition of
an empirical dispersion correction [18] in conjunction with the
def2-SVP basis set [19]). To account for the effect of the solvent,
the Conductor-like Screening Model (COSMO) continuum solvation
model was used [20].
The level of theory employed did not allow for a more detailed
analysis of the results, hence only the features that were independent on the conformers and or unequivocally assigned were discussed. It would be possible to have a qualitative and
quantitative prediction of the spectra by computing the phonons
within the periodic boundary condition on a set of possible molecular crystals identied with extensive molecular dynamic or Monte
Carlo sampling, even if this goes beyond the scope of this article.
For each optimized structure, vibrational modes and intensities
were calculated within the harmonic approximation, and the absence of imaginary frequencies conrmed that all structures are local minima on the potential-energy surface.
The computed harmonic vibrational frequencies were then
scaled by a factor of 0.9741 to account for anharmonicity as described in Ref. [21].
The calculated IR spectra have been broadened with a Lorentzian function having a half-width at half-maximum (HWHM) equal
to 10 cm 1. All the calculations were performed using Turbomole
suite of programs [22].

Differential scanning calorimetry (DSC)

The thermal behavior of the samples was studied by a Perkin Elmer Pyris 6 DSC instrument under dry nitrogen purge over the 35
200 C temperature range. The instrument was calibrated with an
indium sample (99.99% pure), having a melting point of 156.6 C
and a melting enthalpy of 28.4 J/g. The Pyris Manager software
was used to extrapolate onset value temperatures and melting enthalpy for each thermal event.

Results and discussion

Characterization of polymorphic forms
Infrared and Raman spectra
The IR spectra in 36002600 cm 1, 18001100 cm 1 and
1100600 cm 1 spectral ranges are shown in Fig. 2 (form I) and
Fig. 3 (form II). A good agreement with the spectra reported by Borka
[7] was found. Attributions of the signicant bands are listed in
Table 1.
From the analysis of the spectra, some observations can be
drawn. In the 26001800 cm 1 IR region, signicant bands were
not observed. The broad shape of two bands at about 3390 and
3201 cm 1 (form I) and 3479 and 3405 cm 1 (form II), is characteristic of the OH stretching modes. As reported in literature, the
appearance of signals due to the OH groups, not present in propantheline structure, is attributable to closely related impurities with
OH groups linked in position nine in xanthene ring [9]. The band at
about 3479 cm 1, (form II), is probably due to a weak intermolecular hydrogen bonding. In the case of the form I, an intramolecular
hydrogen bond between the OH group and the C@O ester or the
ether oxygen could explain the broad pick at 3201 cm 1 [23]. Other
peaks due to the OH group of this impurity could not be observed
as the in-plane OAH bending or deformation is coupled to the adjacent CH2 or CH wagging and gives rise to some broad and weak IR

bands in the 14401220 cm 1 region [23]. Hence, they fall in a

crowded spectral range.
The asymmetric and symmetric CAH aromatic stretching bands
fall at 3067, 3038, 3004 cm 1 (form I) and give very weak signals at
3069, 3042 and 3022 cm 1 for the polymorph II. The stronger and
sharper CH aliphatic stretchings are detectable at 2968 cm 1 (form
I) and 2992, 2969, 2923 and 2851 cm 1 (form II).
In the 18001100 cm 1 range the IR spectrum of the form I
(Fig. 2b) shows a typical band at 1729 cm 1 assignable to the
C@O stretching of the esteric group. The C@O stretching splitting
(17391727 cm 1) is characteristic of the form II spectrum
(Fig. 3b) compared to the form I.
Two medium-intensity bands can be observed at about 1480
and 1456 cm 1 for both polymorphs. They can be attributed to
the CH2 scissoring which overlapped with the CH3 asymmetric
bending.
Two form I characteristic bands are detected at 1250
1235 cm 1. The rst broad and very strong band is identied as
CAOAC asymmetric stretching of the ester group, while the second
one can be attributed to the asymmetric stretching mode of
CAOAC ether group [24]. These very intense bands are observed
at 1260 and 1220 cm 1 for the form II, while the out of plane
C@O wag [23] shifts from 713 cm 1 to 709 cm 1 (Fig. 3b).
In the IR spectra, there are several bands attributable to the isopropylic group. The characteristic i-propyl skeletal stretching
vibrations are observed at 1171 and 1157 cm 1; the bands at 959
and 912 cm 1, together with the shoulder at 899 cm 1, are attributable to the CAC skeletal stretching, and additionally a weak
deformation mode is identiable at 837 cm 1. The form II IR spectrum shows (Fig. 3b) a strong and characteristic band at
1166 cm 1, associated with a weak peak and a shoulder at 1196
and 1148 cm 1, respectively. Thus, a medium and broad band at
905 cm 1 replaces the sharp peak at 912 and its shoulder at
899 cm 1, both attributable to the CAC skeletal stretching modes.
In the 1100100 cm 1 spectral region (Fig. 2c), a strong band at
1038 cm 1, shifted at 1032 for the form II, can be observed. This band
is assigned to the CAOAC symmetric stretching of the ester group.
The xanthene ring shows a characteristic series of bands. The
C@C aromatic stretching vibrations fall at 1602 and 1575 cm 1
for both polymorphs and other ring stretching ring modes are
detectable at 1302, 1212 and 1097 cm 1 (1304, 1212 and
1097 cm 1, form II), whereas the peaks due to its deformation were
recorded at 939 cm 1 and 937 cm 1 for the forms I and II, respectively [25]. The weak bands at 870 and 854 cm 1, shifted at 866
and 852 cm 1 for the second form, are assigned to the out of plane
CAH deformation in the xanthene ring.
Finally, for polymorph I, it can be observed at 758746 cm 1 a
characteristic doublet attributable not only to the out of plane
CAH aromatic bending but also to CH2 rocking and ring breathing
mode. Instead, the weak aromatic CAH out of plane deformations
fall at 668661 cm 1 (form I) and 664 cm 1 (form II). The splitting
of the band at 758 cm 1 is characteristic of the form II, with a
shoulder at 770 cm 1 and two strong bands at 753 and
744 cm 1. The medium intensity band at 630 cm 1, absent in the
form II, is principally due to the out of plane deformation of the
xanthene ring.
The IR spectra enable to identify the I and II polymorphs, particularly through their typical bands at 1729, 12501235, 11711157,
1038, 758746, 713, 630 cm 1 and 17391727, 1260, 1166, 1032,
753744, 709 cm 1, respectively.
Micro-Raman analyses were also performed to discriminate between the polymorphic forms. This technique allows to obtain
spectra without any sample preparation. Micro-Raman spectra of
the forms I and II in the 36002600 cm 1, 18001100 cm 1 and
1100150 cm 1 ranges are shown in Figs. 2 and 3ac. Some main
bands and their assignments are summarized in Table 1.

C. Baraldi et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 103 (2013) 110

Fig. 2. FT-IR/ATR and micro Raman spectra of propantheline bromide (form I) in the range 36002600 cm
spectrum) or 140 cm 1 (Raman spectrum) (c).

In the 36002600 cm 1 spectral region, the OH stretching vibrations were not detected with the Raman technique (Fig. 2a), because the OAH stretching exhibits a very weak scattering. The
OAH bending intensities in the Raman spectra are also mediumto-weak [23].

(a), 18001100 cm

(b) and from 1100 to 600 cm

(IR

Several bands, referable to CH stretching modes, can be seen in

the region of 30902800 cm 1. The aliphatic CH stretchings are recorded between 2980 and 2900 cm 1, whereas the aromatic ones
are in the region of 30903000 cm 1. The characteristic C@C aromatic ring vibrations are recorded at about 1600 cm 1, particularly

C. Baraldi et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 103 (2013) 110

Fig. 3. FT-IR/ATR and micro Raman spectra of propantheline bromide (form II) in the range 36002600 cm
spectrum) or 140 cm 1 (Raman spectrum) (c).

(a), 18001100 cm

(b) and from 1100 to 600 cm

(IR

C. Baraldi et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 103 (2013) 110

Table 1
IR, Raman and SERS experimental spectral dataa (cm

), calculated data (cm

) and band assignments for propantheline bromide.

IR form I

IR form II

3390w, broad
3201w
3067vw3038vw
3004vw

1602w

3479w
3405w
3069vw
3042vw
3022vw
2992vw
2969vw
2923vw
2851vw
1739s
1727vvs
1602w

1575w

1575w

1480vs
1456vs

1480vs
1456vs

1302m
1250vvs

1304m
1260vvs

1235vs
1212vs
1171m

1220s
1212s
1196w

1157m

1166s

1162w

1164w

1159w

1157w

1114m
1097m

1117m
1097m

1124vw

1125vw

1124w
1102vvw

1123sh

1038s

1032s

1037vs

1037vvs

1034vs

2968w

1729vvs

Raman form I

Raman form II

Aqueous
Raman

SERS

Calculated

Assignmentb

mOH

3067m
3025sh

3062w, br

3060m, br

3125
3065vw

mCH ar

2981w
2939w, br

2983m
2939m, br

3053
2953vw

mCH al

1732w

2988m, br
2956m, br
2911w, sh
2866vvw, sh
1733w

1717vs

mC@O

1625vw
1605m

1628vvw
1608m

1602vw

mC@C (ring)

1581w
1558w
1470w
1456w
1453s
1447m
1424m
1377w
1345w
1258vw
1241mw
1229vvs

mring

3093sh
3072m3064m
3047w3006m
2971m
2944w2916w

1744vvw,
br
1605s

1466w, br

1465w, br
1451vw

1462vvw,
br

1312w
1267w
1255w
1222m

1314w

1312m

1615w
1603w
1586m
1487s
1468s
1443s

1372m, br

1229m

1222vs

1282m
1254vw
1221m, br

1195mw

dCH al + mring

dCH al
mip ring
dip ring + masCOC (ester)

masCOC (ether) + dCH2

mXR
mCAC skeletal i-pro + dipCH ar + msCOC
(ether)

1034vs

976mw, br
959w
939m
912m
899sh

959w, br
937m
905m, br

870w
854w
758vvs
746vvs

866w
852w
770sh
753vvs
744vvs
709m

713m
668w
661w
630m

664w

914w
903w
889w
861w

918vvw
904w
894vw
858w

766vw
750s

761w
750s

672w
635vw, br

531vvw
520w
468vvw
459
417w
402ms
380m

294m
255m
224m
217m201m164m
149w
a

mCAC skeletal i-pro + dipCH

ar + msCACAO (ester)
dipCH ar

mXR + dCH al
msCOC (ester) + dCH al
dopCH ar

mCAC skeletal i-pro

615vvw

1164s
1161mw
1140mw
1110 mw
1092w
1072mw
1063w
1012m
977
910vw

903 m
890w

749vs

669w

661m
643m

620vvw

621vvw

537w
530vw
464vvw, br

527w

415vvw
397w
390sh

295vw
282vw
249vw, br
233w
185w166w

481w
469w
413w

925vw
900vvw

749m
733m

663s
652s
630m, sh
621m, sh
575m
533m

936mw

dopCH ar

mCAC i-pro

881
859w
801w
759mw
749mw
724w
717w
663w

dopCAH ar + CH2 rock in phase + mas

CAN + breath ring
dopC@O + dring + mas CAN
dopC@O + dop ring

590vvw
511vvw

dCOC (ester) + dopring

dipXR
mring + dCOC (ether)
d skeletal i-pro + cring

468m

465vw

dCAN

432ms426m
404m

443vw

dCNC + cring
dipXR
dring

392m

644w

dopCAH ar

395vw
386vw
339ms

dOCC + dipXR
dCC skeletal i-pro + dring

225m

sCH3 + mAgAO

290m

dopXR

Relative intensities: v = very; s = strong; m = medium; w = weak; sh = shoulder; and br = broad.

ip = in plane; op = out of plane; i-pro = isopropylic; ar = aromatic; al = aliphatic; and XR = xanthene ring.

Lattice vibrations

C. Baraldi et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 103 (2013) 110

there is a Raman-active intense band at 1605 cm 1 (form I), shifted

to 1608 cm 1 for the form II. In regards to the deformation modes
of the CAH groups, the CAH aliphatic bending is found at 1466 and
1037 cm 1 (form I) or 1465 and 1034 cm 1 (form II), whereas the
aromatic CAH in-plane deformation is noticed at 1124 (form I)
or 1125 (form II) cm 1.
Concerning the C@O symmetric stretching mode, its intensity is
considerably weaker as compared to the IR one, particularly for the
form I. The COC asymmetric stretching vibrations, in the Raman
spectra of the form II, fall at 1267 and 1255 cm 1 for the esteric
group, whereas, for the etheric group, an intense band at
1222 cm 1, shifted to 1229 cm 1 in the form II, is reported.
Among the characteristic bands assignable to the isopropylic
group, the skeletal stretchings at 1162 and 889 cm 1 (form I) and
1164 and 894 cm 1 (form II) are detected. The deformation modes
in the low wavenumber region fall at 520 and 294 cm 1, the latter
band being stronger and characteristic of the form I. For the form II,
a wavenumber shift at 530 and 295 cm 1 is present instead.
Some interesting features can be seen in the range of 1100
100 cm 1, as reported in Fig 2b. Some bands are almost the same
in wavelength and intensity for the two forms. In the Raman spectra the CAOAC symmetric stretching of the esteric group in the
ring is always strong and falls at 1037 and 1034 cm 1 for the forms
I and II, respectively. The weak deformation band due to the outof-plane bending of aromatic CAH falls at 766 cm 1 for the polymorph I, and at 761 cm 1 for the form II.
The strong band at 750 cm 1 remains substantially unchanged
for the two polymorphs, and this due to the CAN stretching and
ring breathing modes. Instead, the CAN deformation modes appear
at about 464 cm 1 (form II) and 468 cm 1 (form I).
The bands typical of the form I are found at 417, 402 and
380 cm 1, the rst one being attributable to the CANAC deformation and the second one to the xanthene ring deformations. These
bands are weak and shifted to 415 and 397 cm 1, and exhibiting a
shoulder at 390 cm 1 for the second polymorph.

A characteristic medium intensity band is observed at

255 cm 1, (249 cm 1 for II form) assignable to the torsion mode
of the xanthene ring.
Lattice vibrations, from strong to weak in intensity, can be noticed under 300 cm 1.
In summary, the polymorphs characterization through Raman
spectroscopy permitted to identify specic bands for the form I
(12671255, 1222, 520, 417402380, 294, and 255 cm 1) and
form the II (in particular at 1733, 1229, 669, 537530, 397, 295
282 and 185 cm 1).
Thermal analysis
Differential scanning calorimetry (DSC). According to Borkas results
[7,26], the conversion of the form II into the form I was observed at
temperature above 100 C with a successive fusion of the form I. A
further heating caused the decomposition of the moiety. The temperature program started from 35 and reached 200 C with the
heating rate of 2 C/min (different heating rates, 220 C/min, were
also tested). The form II showed an endothermic peak at 87.0 C
(15.44 J/g) due to the transition into the form I. An endothermic
peak caused by the melting of the form I was observed at
159.7 C (50.89 J/g), in agreement with the published data [27].
The thermogram study, conducted on a sample of the form I, with
the aforementioned temperature program, showed only the endothermic peak corresponding to the fusion of the form I at 159.5 C
(39.38 J/g).
Hot-stage Raman spectroscopy. Hot-stage measurements were carried out with the same DSC temperature program (2 C/min; 35
200 C temperature range). A specic characterization of DSC
events is possible by this technique: the conversion of II into I
and the successive melting were observed. From 35 C to 80 C,
the micro-Raman spectra correspond to the form II, whereas at
90 C and at 160 C the transformation into the form I and its melting occurred, respectively (Fig. 4.).

Fig. 4. From the top HSRM spectra at 35508090160 C.

C. Baraldi et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 103 (2013) 110

Surface enhanced Raman spectroscopy

SERS is already regarded as a valuable method because of its
high sensitivity, which enables the detection and spectroscopic
study of even single molecules [11]. Vibrational information contained in a SERS spectrum is molecule-specic, and thus provides
for the characterization of adsorbatesurface interactions, e.g.,
and the orientation of the adsorbed species on metal surface. Relative bands intensities observed in SERS spectra are expected to
differ signicantly from those of normal Raman spectra owing to
specic surface selection rules. In addition, in literature, it is reported that vibrations involving groups close to silver surface are
enhanced [28].
SERS and aqueous propantheline bromide Raman spectra are
shown in Fig. 5 (without any linearization or baseline correction).
Some considerations can be carried out: when the difference between Raman bands in normal and SERS spectra does not exceed
5 cm 1, it is expected that the molecular plane lies perpendicular
to the silver surface [29]. This is the case of the molecule in discussion. In SERS, the presence or absence of the ring CH stretching
vibration is a reliable probe for the perpendicular or parallel orientation, respectively, of the ring on the surface [3033]. This peak,
located at 3064 (form I) and 3067 cm 1 (form II) in the normal solid state Raman spectra and at 3062 cm 1 in aqueous solution Raman spectrum, falls at 3060 cm 1 in SERS spectrum and suggests
that the ring may be in a position close to perpendicular to the silver surface, possibly a slightly tilted position since it is a weak
band [34].
The observation of which bands are intensied in the SERS spectrum, suggests that the i-propylic group is close to the metal surface. In fact, the presence and broadening of the CH aliphatic
bands, in particular the broad and mean peak at 2939 cm 1 attributable to masCH aliphatics vibrations and the medium band at
2983 cm 1 indicate an involvement of the isopropylic group in
the interaction with the substrate [32,35]. Furthermore, the
appearance of two modes, the rst at 1487 cm 1, attributable to
the dasCH3 and the second as a medium and broad band at
1372 cm 1, due to CH3 symmetric deformation, supports this
hypothesis. In addition, there is a signicant increase in intensity
of the band at 533 cm 1 (iso-propylic group deformation).
The total C@O stretching band is absent in the SERS spectrum
and the weakness of masCAO ester at 1254 cm 1 and the absence
of C@O deformation mode near 710 cm 1.

Instead, the medium-to-strong band at 1221 cm 1, attributed to

ether stretching, and the deformation of the OCC at 339 cm 1 are
suggestive of a possible interaction between the ether group and
the substrate. The appearance of the 225 cm 1 band in the SERS
spectrum, which may be due to AgAO stretching mode, could support this argument and suggest that the molecule is adsorbed
through the lone-pairs of the oxygen atoms with the molecular
plane tilted with respect to the colloidal silver surface.
Surface selection rules suggest that for a molecule adsorbed at
on the silver surface, its out-of-plane bending modes will be more
enhanced as compared to its in-plane bending modes, and vice versa when it is absorbed perpendicular to the surface [36]. Concerning the aromatic ring, the weakness of C@C (ring) stretching at
about 1600 cm 1 and the absence of the ring stretching modes
near 1312 and 1102 cm 1 (values from the aqueous spectrum), is
indicative of the weak interaction of the surface with the p electrons in the ring.
The intensity enhancement or the broadening of the band corresponding to the in-plane ring deformations (Table 1), such as
the 1123, 621 and 404 cm 1 bands, suggest the perpendicular
geometry of the molecule on the metal surface [37,38]. The absence of out-of-plane CAH modes near 760, 860 and 250 cm 1,
present in the solid state, conrms this hypothesis.
Finally, it has also been documented in literature [39] that when
a ring moiety interacts directly with a metal surface, in a at orientation, the ring breathing mode is broadening and red shifted by
10 cm 1 in the SERS spectrum. For the title compound, the ring
breathing mode at 1157 cm 1 (of a weak intensity), and
749 cm 1 (of a medium intensity), show a small no wavenumber
shift, respectively. This entails that the probability of direct ring
p-orbital to metal interaction should be low, in accordance to a
tilted position of the ring [37,38].
Computational results
The optimized structures were found to have very similar total
energy, in particular, the energy difference between the most and
least stable of the conformers accounts for only 7 kcal/mol.
Visual inspection of the calculated spectra suggested that only
the position and relative intensities of few modes are strongly
dependent on the conformation, whereas most of the features
are conserved. In Fig. 6, the calculated IR spectra for the two representatives of the set of conformers, namely the most and least sta-

Fig. 5. Aqueous (top) and SERS spectra of propantheline bromide.

C. Baraldi et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 103 (2013) 110

Fig. 6. Representative of the calculated IR spectra: the most (Structure A, red spectrum) and least (Structure B, black spectrum) of the conformers investigated.

ble, are reported. Given the approximation of our theoretical approach, we refrain from commenting features that are beyond
the expected accuracy.
The two spectra show remarkable similarities, especially for the
zones around 3000 cm 1 and 13001700 cm 1, on the other hand,
very few modes are found to strongly dependent on the conformation. In particular, the msCACAO (ester) mode is redshifted by
60 cm 1 when passing form the most stable conformer A to the
least stable B.
This mode was found to be the most sensitive to the exact conguration of the molecule and its frequency spans a range of almost 100 cm 1 (from 1100 to 1200 cm 1) when considering the
different conformations analyzed in this study.
We note that, due to the small energy difference computed for
the conformers, these calculations are not suited to determine
which conformers are more likely to resemble the congurations
assumed in the crystal structures. On the other hand, it was shown
that:
i. The shape and position of most of the intense bands characterizing the IR spectrum are conserved regardless of the
conformers.
ii. The position and intensity of the carbonyl stretching and msCACAO (ester) modes are the most sensitive to the exact
conguration.
Given these information, the calculated data for the most stable
gas phase conformer was used to assist the assignment of the
experimental picks as shown in Table 1.

Conclusions
In this research, a study of propantheline bromide polymorphic
forms was carried out. It was possible to clearly characterize and
discriminate the I and II forms by the use of different techniques
such as FTIR-ATR, Raman microscopy, XRPD, DSC, HSRM, and ab
initio calculations. The IR and Raman bands typical of the two polymorphs were identied.
In addition propantheline bromide SERS spectrum was studied
and rstly reported. It may be inferred that for propantheline bromide adsorbed on silver colloid, the molecule is adsorbed through
the oxygen atom with the molecular plane perpendicular to the
metal surface. The presence of the methyl modes in the SERS spectrum indicates the proximity of the methyl group to the metal surface whereas the presence of the bands attributable to ring
vibrations and in plane ring modes suggests a perpendicular orientation of the molecule on the silver surface.
A total of 56 local minima of the potential energy surface of the
propantheline cation were identied and characterized by means

of quantum mechanical calculations. The simulated spectra of the

conformers show that only a few modes (i.e. the carbonyl stretching and the msCACAO (ester)) are strongly dependent on the exact
conguration of the molecule. Although, the energies of the conformers were found to be too similar to suggest which conformation may be found in solid phase, it was possible to use the
calculated spectra of the most stable of the gas phase conformers
during the assignment of the experimental picks.

Appendix A. Supplementary material

Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.saa.2012.10.070.
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