Experimental and theoretical vibrational study of N-carbamoyl-L-proline

Article abstract of DOI:10.1016/j.molstruc.2018.05.006

The infrared and Raman spectra of N-carbamoyl-L-proline, C₆H₁₀N₂O₃ [(2S)-1-carbamoylpyrrolidine-2-carboxylic acid] were obtained and interpreted with the help of DFT calculations. Six relatively stable molecular conformers were predicted by theory, being one of these similar to the conformer present in the crystal whose X-ray study was already known. The vibrational study was based in that conformer. The experimental vibrational data and assignments were used as basis for the definition of the Scaled Quantum Mechanics (SQM) force field for the molecule. The Potential Energy Distribution (P.E.D.), which revealed the complex nature of many molecular vibrations, and a set of internal force constants were calculated from this SQM force field.

Full text of DOI:10.1016/j.molstruc.2018.05.006

Accepted Manuscript
Experimental and theoretical vibrational study of N-carbamoyl-L-proline
L.E. Fernández, G.E. Delgado, L.V. Maturano, R.M. Tótaro, E.L. Varetti
PII:
S0022-2860(18)30562-3
10.1016/j.molstruc.2018.05.006
MOLSTR 25178
DOI:
Reference:
To appear in: Journal of Molecular Structure
Received Date: 13 December 2017
Revised Date: 2 May 2018
Accepted Date: 3 May 2018
Please cite this article as: L.E. Fernández, G.E. Delgado, L.V. Maturano, R.M. Tótaro, E.L. Varetti,
Experimental and theoretical vibrational study of N-carbamoyl-L-proline, Journal of Molecular Structure
(2018), doi: 10.1016/j.molstruc.2018.05.006.
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ACCEPTED MANUSCRIPT
Experimental and theoretical vibrational study of N-carbamoyl-L-proline
L. E. Fernández a, G. E. Delgado b, L. V. Maturano a R. M. Tótaro c and E. L. Varetti d, *
,
a Instituto de Química Física, Facultad de Bioquímica, Química y Farmacia, Universidad
Nacional de Tucumán, San Lorenzo 456, 4000 S. M. de Tucumán, Argentina.
b Laboratorio de Cristalografía, Facultad de Ciencias, Departamento de Química, Universidad
de Los Andes, Mérida 5101, Venezuela.
c Facultad de Agronomía y Zootecnia, Universidad Nacional de Tucumán, Avda. Roca 1900,
4000 S. M. de Tucumán, Argentina.
d Centro de Química Inorgánica (CEQUINOR, CONICET-UNLP), Facultad de Ciencias
Exactas, Universidad Nacional de La Plata, C. Correo 962, 1900 La Plata, Argentina.
Abstract
The infrared and Raman spectra of N-carbamoyl-L-proline, C6H10N2O3 [(2S)-1-
carbamoylpyrrolidine-2-carboxylic acid] were obtained and interpreted with the help of DFT
calculations. Six relatively stable molecular conformers were predicted by theory, being one
of these similar to the conformer present in the crystal whose X-ray study was already known.
The vibrational study was based in that conformer. The experimental vibrational data and
assignments were used as basis for the definition of the Scaled Quantum Mechanics (SQM)
force field for the molecule. The Potential Energy Distribution (P.E.D.), which revealed the
complex nature of many molecular vibrations, and a set of internal force constants were
calculated from this SQM force field.
Keywords: N-carbamoyl-L-proline; molecular structure; vibrational spectra; force field;
DFT calculation
---------------------------------------------------------------
* Author to whom correspondence should be sent (e-mail address:
varetti@quimica.unlp.edu.ar).
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1. Introduction
The N-carbamoyl derivates have interesting biotechnological applications as, for example,
the production of optically pure amino acids by the enzymatic kinetic resolution technique [1-
3]. They are also used in the preparation of N-carboxyanhydride precursors in peptide
synthesis [4]. These compounds are also of great importance in the pharmaceutical industry;
for instance, N-carbamoyl-L-glutamic acid is used in the treatment of patients with N-
acetylglutamate synthase deficiency, a urea cycle disorder [5,6,7]. The N-carbamoyl amino
acids are used as precursors in the synthesis of hydantoins, which possess clinically useful
activities; in fact, hydantoins can be used as anticonvulsants, antiepileptic, antiarrhythmics,
antimicrobial, and potential anticancer agents. They also have other biological properties as
herbicides and fungicides [8-13].
The crystal structure of N-carbamoyl-L-proline was determined by X-ray diffraction [14],
as part of the structural study of synthesized derivatives [14-18]. However, no information is
known about the vibrational properties of the title compound. Therefore, this substance has
been synthesized and the FTIR and Raman spectra have been measured and analysed with the
aid of the theoretical calculations. A complete assignment of the observed bands is proposed
in the present work.
2. Experimental details
The N-carbamoyl-L-proline was prepared by the reaction of L-proline and potassium
cyanate in acid medium at 60 °C. The same sample was used in the crystallographic study
[14] and in the present work.
The IR spectra of the substance in KBr pellets were run on a Perkin-Elmer GX FTIR
instrument at room temperature in the range 4000-400 cm-1, with a resolution of 2 cm-1.
The Raman spectra were obtained with the Bruker FRA 106 accessory mounted in a Bruker
IFS66 FTIR instrument, using 1064 nm light from a Nd-YAG laser for sample excitation, with
a resolution of 2 cm-1.
The used spectroscopic techniques, IR and Raman, should give the same frequencies for
each mode of vibration of the N-carbamoyl-L-proline molecule, which have no symmetry
elements (point group C1). However, both techniques are complementary regarding the
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relative intensity of bands: weak bands in IR could appear strong in Raman and vice versa,
facilitating the measurement of frequencies.
3. Computational details
A theoretical structural study was performed on the isolated molecule using B3LYP/6-
31G(d,p) approximations, in order to obtain information about the different conformers. All
calculations were made using the Gaussian 03 set of programs [19].
Optimized geometries and vibrational properties of the conformer present in the crystal
lattice were calculated using the B3LYP/6-311++G(d,p) combination. That combination
turned out to be the one that best adjusts to the experimental values, after analyzing the results
obtained from some exploratory calculations using the B3LYP and B3PW91 functional with
different basis sets.
The Cartesian force constants obtained by the calculation were transformed to the natural
(local symmetry) coordinates as defined by Fogarasi et al. [20] using the corresponding B
matrix [21] calculated with a standard program. Then, this force field was scaled following the
formalism of Pulay et al. [22], according to which the diagonal force constants are multiplied
by scale factors fi, fj,… and the corresponding interaction constants are multiplied by (fi.fj)1/2,
adjusting these factors in order to reproduce as well as possible the experimental frequencies.
This procedure generates a SQM (Scaled Quantum Mechanics) force field. No anharmonicity
corrections of the frequencies were made because of the lack of necessary experimental data.
The SQM force field was obtained with the FCARTP program developed by Collier [23],
whereas the atomic displacement vectors corresponding to each molecular vibration were
visualized by means of the Moldraw program [24]. The resulting SQM force field was used to
calculate the Potential Energy Distribution (P.E.D.) of the molecule, which represents the
contribution of each main force constant to the different vibrational modes.
The relative Raman intensities included in Table 4 are calculated from the Raman
activities given by the Gaussian program using the following expression, as reported in the
literature [25]:
Ii = f ( νexc - νi )4 Si / νi [1 – exp (- h c νi / k T) ]
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where νexc is the Raman excitation frequency (in cm-1), νi is the ith. vibrational mode, Si is
the corresponding Raman scattering activity, h, c and k are fundamental constants, T is the
absolute temperature and f is an arbitrary constant defined to give the 100 value to the
largest Raman intensity. The calculations were made with νexc = 9398.5 cm-1 (1064 nm) and
T = 293 K.
4. Results and discussion
4.1 Molecular geometry
The N-carbamoyl-L-proline molecule can exist in a variety of conformations on the
potential energy surface, with a number of local minima defined by the relative position of the
carboxyl and ureide groups, which can rotate with respect to the pentagonal ring.
The existence of possible stable conformers was investigated by varying the dihedral
angles that define the positions of the mentioned functional groups, using the B3LYP/6-
31G(d,p) approximation for the calculations. The results of these calculations showed the
existence of six conformers. The corresponding optimized structures without geometry
constraints are depicted in Fig. 1. The frequencies calculated for the six cases were all real
(positive) confirming that they correspond to minima in the potential energy surface.
The most stable structure predicted for the molecule (conformer I, Fig. 1) does not
correspond to the conformer present in the crystal lattice (conformer V, Fig. 1). In fact, the
three relatively more stable structures investigated (conformers I, II and III) include the
formation of different intramolecular hydrogen-bonds, which are detailed in Table 1. The
molecule existing in the crystal, however, has an structure stabilized by three intermolecular
hydrogen-bonds which have donor-acceptor distances something smaller than those which
appear in the isolated conformers, as can be seen in Table 1.
A set of the selected optimized structural parameters recalculated at the B3LYP/6-
311++G(d, p) level for the conformer V are summarized in Table 2 together with the
crystallographic measured values [14]. As can be seen, there is an acceptable agreement
between the theoretical and experimental values. However, a rather large difference (0.086 Å)
appears between the experimental and calculated C3-C4 distance, a discrepancy which we
cannot explain at this time. Other differences in Table 2 can be justified taking into account
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that the calculation was performed on the isolated molecule while the experimental data
correspond to molecules that interact in the crystalline structure.
4.2 Vibrational analysis
The infrared and Raman spectra obtained for N-carbamoyl-L-proline are shown in Figs. 2
and 3, along with the corresponding calculated spectra with the B3LYP/6-311++G(d,p)
combination. The frequencies used to plot the theoretical spectra were calculated using the
SQM force field, which corresponds to the conformer V existing in the crystal, as discussed
before.
N-carbamoyl-L-proline was studied in its crystalline form, a fact which can in principle
modify the number and activity of the bands expected for the molecular vibrations. However,
there is no clear evidence that this effect appears in the vibrational spectra obtained and
therefore the interpretation of the experimental data was based on the isolated molecule.
The N-carbamoyl-L-proline molecule has C1 symmetry and their 57 normal modes of
vibration are all active in the infrared and Raman spectra. The frequencies of the bands
observed in the infrared and Raman spectra are collected in Table 3.
The assignment of the experimental bands was performed by comparison with the
calculated frequencies and the visualization of the atomic displacement vectors corresponding
to each vibrational mode. In some cases, an observed band was assigned to two normal modes
of vibration very close in frequency, according to the obtained values in the theoretical
calculation.
Some comments can be made regarding the assignment of bands appearing in the spectra to
the different modes of vibration, as follows:
OH and NH2 stretching modes.
The OH stretching mode and NH2 stretching modes are strongly affected by the
anharmonicity, so the calculated (harmonic) and experimental (anharmonic) values differ by
approximately 300 cm-1. After applying the scaled force field method, the obtained
frequencies are closer to the experimental values, with differences smaller than 20 cm-1, as
shown in Table 4.
The region of the infrared spectrum of N-carbamoyl-L-proline between 3500-2800 cm-1 is
complicated due to the broad bands originated by the hydrogen-bonds in the crystal. In
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addition, the formation of hydrogen-bonds causes displacement of the bands of the functional
groups involved to lower frequencies, as expected. Hence, the band in the IR spectrum located
at 3420 cm-1 is assigned to the OH stretching mode, whereas the bands at 3349 and 3235 cm-1
are assigned to the antisymmetric and symmetric NH2 stretching modes, respectively.
CH stretching and deformation modes.
Four bands in the range 2994 to 2885 are assigned to the antisymmetric and symmetric
stretching modes of the three CH2 groups, as detailed in Table 4. Besides, the Raman band at
2968 cm-1 is assigned to the C-H stretching mode.
The three CH2 deformation modes generate the band with an intense component at 1457 cm-
1 in infrared and 1446 cm-1 in Raman.
C=O stretching and rocking modes.
The intense bands in the IR spectrum at 1687 and 1657 cm-1 are assigned to the C=O
stretching modes of the carboxyl and ureide groups, respectively, according to the calculated
frequencies and the corresponding atomic displacements associated with each vibration. The
same arguments locate the in-plane and out-of-plane C=O rocking vibrations in the 771-567
cm-1 range.
Ring modes.
Nine vibrational modes are associated to the five-member ring which appears in the
molecule: five stretchings, two ring bendings and two ring torsions. The atomic displacements
associated with each vibration and the calculated frequencies allowed the assignment of these
modes to the corresponding bands, as detailed in Table 4, but the potential energy distribution
shows that these ring modes are in some cases strongly mixed with the carbamoyl and
carboxyl groups vibrations.
The rest of the bands observed in the vibrational spectra were assigned according to the
frequencies predicted by calculation and the visualization of the normal modes of vibration, as
already mentioned. However, for many vibrational modes a simple description is not possible,
as shown by the Potential Energy Distribution (Table 4). In fact, in some complex vibrations
several coordinates are involved.
The proposed assignment of the bands observed in the vibrational spectra was used as basis
for the calculation of the SQM force field (see Computational details). The Cartesian force
constants given by the Gaussian calculation were transformed to the set of natural internal
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coordinates defined in Table S1 (Supplementary material). The resulting force field was then
scaled with the Pulay et al. methodology [22] in order to reproduce the experimental
frequencies as best as possible. The scale factors obtained in such procedure are listed in
Table S2 (Supplementary material).
The experimental, theoretical and SQM frequencies and the corresponding RMSD (Root
Mean Square Deviation) values are shown in Table 4. As can be seen, the RMSD value
resulting from the comparison between experimental and calculated frequencies, which was
initially 93 cm-1, decreases to 11 cm-1 after the force field scaling procedure.
The SQM force field was used to calculate the Potential Energy Distribution (P.E.D.) of the
N-carbamoyl-L-proline molecule, which represents the contribution of each main force
constant (associated with a given natural internal coordinate), to the different normal modes of
vibration. Table 4 shows the P.E.D values considering contributions ≥ 10%.
The SQM force field was used to calculate a set of internal force constants for the N-
carbamoyl-L-proline molecule. A selection of these force constants are collected in Table S3
(Supplementary material).
5. Conclusions
N-carbamoyl-L-proline, C6H10N2O3, (2S)-1-carbamoylpyrrolidine-2-carboxylic acid, was
synthetized and its FTIR and Raman spectra were obtained.
A series of DFT calculations allowed the determination of six possible molecular
conformers for N-carbamoyl-L-proline, most of which are more stable than the (ideally
isolated) conformer which appears in the crystal. However, the conformer located in the
crystal lattice is clearly stabilized by the formation of three intermolecular hydrogen-bonds.
The frequencies corresponding to the normal modes of vibration and the molecular force
field were also calculated. The theoretical results and the experimental vibrational data were
used to define a Scaled Quantum Mechanics (SQM) force field for the molecule. The Potential
Energy Distribution calculated with the SQM force field revealed the complex nature of many
molecular vibrations. A set of internal force constants for N-carbamoyl-L-proline was also
calculated from the SQM force field.
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Acknowledgements
Research grants from the following institutions from Argentina are gratefully acknowledged:
CONICET (Consejo Nacional de Investigaciones Científicas y Técnicas), UNLP (Universidad
Nacional de La Plata) and CIUNT (Consejo de Investigaciones de la Universidad Nacional de
Tucumán). From Venezuela: FONACIT (Fondo Nacional de Ciencia, Tecnología e
Innovación) and CDCHT-ULA (Consejo de Desarrollo Científico y Humanístico).
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Table 1.- Intramolecular hydrogen-bonds geometry for conformers I, II and III;
intermolecular hydrogen-bonds geometry in the crystal (Å, degrees).
D-H----A
D-H
0.997
1.015
1.012
H----A
1.673
2.078
2.126
D----A
2.644
2.997
3.014
D-H----A
163.1
Conformer I
O15-H16----O18
Conformer II
N19-H20----O14
Conformer III
N19-H20----O15
149.4
145.3
Crystal a
O15-H16----O
N19-H21----O
N19-H20----O
a Data from ref. 14.
0.82
0.86
0.86
1.73
2.08
2.13
2.536(3)
2.914(4)
2.901(3)
167
165
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Table 2.-Selected experimental and optimized geometric parameters for N-carbamoyl-L-proline
(
For atom numbering see Figure 1 (conformer V).
Bond length (Å)
C13=O14
C13-O15
O15-H16
C13-C2
Exp.a
Calc.b
1.204
1.353
0.969
1.530
1.224
1.387
1.373
1.008
1.546
1.538
1.538
1.469
1.456
Bond angles (º)
O14=C13-O15
O14=C13-C2
C13-O15-H16
C13-C2-C3
Exp.a
124.0(3)
121.0(3)
-
Calc.b
123.1
123.5
107.0
111.3
114.8
122.2
115.5
122.3
119.8
113.2
103.6
113.5
103.8
102.7
119.6
126.4
103.7
113.3
1.215(3)
1.300(3)
0.82 c
1.513(4)
1.265(3)
1.327(4)
1.337(4)
0.86 c
112.5(3)
113.2(2)
119.4(3)
119.3(3)
121.4(3)
-
C17=O18
C17-N19
C17-N12
N19-H20,21
C2-C3
C13-C2-N12
N12-C17=O18
N12-C17-N19
O18=C17-N19
C17-N19-H20
C17-N19-H21
C2-C3-C4
1.542(5)
1.452(6)
1.503(5)
1.462(4)
1.455(4)
C3-C4
-
C4-C1
105.9(3)
113.9(3)
108.0(3)
102.3(3)
119.6(2)
126.4(3)
102.6(3)
115.0(2)
C1-N12
C2-N12-C1
N12-C2
C1-C4-C3
C3-C2-N12
C17-N12-C2
C17-N12-C1
N12-C1-C4
O15-C13-C2
a Ref. [14]; b B3LYP/6-311++G(d,p) approximation; c Fixed in the cristallographic study
(14).

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Table 3.-Observed bands in the infrared and Raman spectra of N-carbamoyl-L-proline
(units are cm-1).
IR a
Raman b
3420 s
3349 s
3235 s
2994 w
3338 (11)
3231 (11)
2991 (63)
2968 (63)
2954 (62)
2941 (76)
2885 (66)
2954 w
2941 w
2885 w
2720 w d
2498 w e
1944 w c
1687 vs
1657 vs
1542 vs
1465 s
1691 (50)
1642 (51)
1544 (50)
1472 (73)
1457 sh
1457 s
1448 s
1446 (83)
1361 (53)
1325 (59)
1307 (51)
1276 (67)
1247 (60)
1206 (53)
1168 (42)
1148 (48)
1095 (49)
1074 (56)
1041 (50)
1357 m
1314 s
1302 s
1274 m
1244 m
1201 m
1164 m
1147 m
1093 sh
1079 m
1048 m

ACCEPTED MANUSCRIPT
1034 m c
983 w
924 vw
917 vw
874 vw
824 vw
771 m
983 (47)
926 (62)
921 (62)
875 (93)
824 (53)
806 (53)
757 (48)
690 (57)
663 (48)
618 (42)
565 (43)
524 (39)
444 (100)
413 (48)
350 (42)
319 (41)
285 (58)
241 (50)
160 (57)
120 (120)
75 (633)
687 vw
666 vw
608 m
567 m
536 vw
446 m
a v, very; s, strong; m, medium; w, weak; sh, shoulder.
b Relative Raman intensities appear in parentheses.
c Unassigned bands.
d Tentatively assigned as 1357 cm-1 x 2 = 2714 cm-1.
e Tentatively assigned as 1244 cm-1 x 2 = 2488 cm-1.

ACCEPTED MANUSCRIPT
Table 4.- Experimental and calculated frequencies, infrared and Raman intensities and potential energy distribution for N-carbamoyl-L-proline.
Mode
ν1
Exp. a
3420
3349
3235
2994
2994
2968*
2954
2941
2941
2885
1687
1657
1542
Calc. b
3758
3696
3582
3114
3102
3101
3064
3054
3051
2981
1813
1739
1625
Calc. SQM c IR int. d Raman int. e
Main coordinate
P.E.D. (contributions≥ 10 %) f
100 S1
3400
3343
3242
3004
2992
2968
2955
2945
2942
2876
1683
1647
1553
0.177
0.088
0.065
0.050
0.053
0.016
0.084
0.004
0.053
0.144
0.862
1.000
0.400
41.7
17.5
58.2
43.6
77.5
54.4
86.1
38.0
78.1
100.0
26.5
33.8
11.0
O-H str.
100 S2
NH2 antisym. str.
NH2 sym. str.
CH2 antisym. str.
CH2 antisym. str.
C-H str.
ν2
100 S3
ν3
71 S4 + 21 S5
ν4
73 S5 + 14 S4
ν5
96 S6
ν6
62 S7 + 25 S8 + 11 S10
35 S8 + 27 S7 + 18 S9 + 16 S10
62 S9 + 14 S4
CH2 sym. str.
ν7
CH2 antisym. str.
CH2 sym. str.
ν8
ν9
70 S10 + 32 S8
85 S11
CH2 sym. str.
ν10
ν11
ν12
ν13
C=O str. (carboxyl)
C=O str. (ureide)
NH2 bend.
66 S12 + 17 S15 + 14 S48
48 S13 + 28 S46 + 11 S15

ACCEPTED MANUSCRIPT
1472*
1465
1457
1448
1361*
1530
1502
1493
1435
1386
1478
1468
1449
1440
1371
0.005
0.011
0.015
0.594
0.009
14.8
18.6
30.6
6.8
76 S14
CH2 bend.
C17-N12 str.
CH2 bend.
CH2 bend.
CH2 wag.
ν14
ν15
ν16
ν17
ν18
33 S15 + 19 S31 + 13 S42+ 11 S14
47 S16 + 38 S17 + 13 S14
54 S17 + 46 S16
9.6
56 S18 + 24 S20 +15 S50 + 11 S25
22 S19 + 18 S50 + 17 S38 + 16 S27 + 15 S44
+ 15 S20
1357
1364
1362
0.029
3.9
C-OH str.
ν19
1325*
1325*
1314
1302
1274
1362
1351
1328
1300
1267
1337
1336
1314
1295
1252
0.050
0.014
0.006
0.026
0.009
5.1
4.4
64 S20 + 36 S21 + 32 S50 + 10 S29
70 S20 + 26 S50 + 21 S21
C-H def. in-plane
CH2 wag.
ν20
ν21
ν22
ν23
ν24
6.6
52 S22 + 16 S26 + 12 S18 + 10 S33
26 S23 + 14 S36 + 11 S20 + 14 S21
38 S24 + 17 S29 + 12 S20
CH2 wag.
17.0
32.9
C-H def. out-of-plane
CH2 twist.
27 S25 + 18 S36 + 16 S23 + 12 S18 + 13 S24
+ 10 S45
1244
1230
1234
0.081
21.4
C2-N12 str. (ring)
ν25
1244
1201
1164
1147
1093
1216
1195
1169
1144
1104
1227
1186
1166
1144
1104
0.008
0.099
0.217
0.091
0.104
10.4
9.8
18 S26 + 15 S34 + 14 S47 + 12 S29 + 12 S28 CH2 twist.
ν26
ν27
ν28
ν29
ν30
28 S27 + 19 S24 + 13 S26
21 S28 + 16 S23 + 12 S26
COH def.
NH2 rock.
13.1
17.3
9.4
18 S29 + 16 S27 + 15 S24 + 14 S19 + 13 S35 CH2 twist.
23 S28 + 15 S31 + 6 S30 CH2 rock.

ACCEPTED MANUSCRIPT
1079
1048
983
924
917
874
874
824
771
757*
687
666
608
567
567
536
446
413*
1079
1035
985
922
919
879
874
813
770
747
665
643
593
580
547
515
415
399
1074
1047
994
934
922
886
877
817
780
761
679
652
607
590
556
499
425
408
0.049
0.015
0.020
0.009
0.017
0.008
0.025
0.008
0.075
0.056
0.060
0.077
0.123
0.062
0.083
0.297
0.035
0.035
22.4
30.6
19.1
9.5
13 S31 + 13 S35 + 11 S30 + 11 S37
N19-C17 str.
ν31
ν32
ν33
ν34
ν35
ν36
ν37
ν38
ν39
ν40
ν41
ν42
ν43
ν44
ν45
ν46
ν47
ν48
24 S32 + 15 S33 + 15 S34
27 S33 + 22 S32
C1-C4 str. (ring)
C2-C3 str. (ring)
50 S34 + 15 S32
C3-C4 str. (ring)
43.8
27.3
35.4
27.1
6.6
18 S35 + 13 S36 + 11 S29
13 S26 + 13 S50 + 12 S35 + 12 S47 + 9 S36
26 S37 + 25 S45
CH2 rock.
C1-N12 str. (ring)
CH2 rock.
20 S38 + 17 S30 + 11 S19
96 S39
C2-C13 str.
C=O rock. out-of-plane (ureide)
C=O rock. out-of-plane (carboxyl)
COOH bend.
60.3
65.4
4.9
38 S40 + 13 S33 + 11 S43
23 S42 + 13 S43 + 6 S41
24 S42 + 11 S45 + 12 S47 + 12 S37
45 S43 + 16 S48
C=O rock. in-plane (ureide)
OH def. out-of-plane
C=O rock. in-plane (carboxyl)
Bend.’ (ring)
24.8
4.3
28 S44 + 18 S45 + 10 S41 + 12 S30
22 S45 + 16 S43 + 10 S48 + 10 S36
48 S46 + 30 S13 + 15 S49 + 11 S31
27 S47 + 21 S42
38.7
10.1
78.8
73.7
NH2 wag.
Bend. (ring)
29 S48 + 14 S44 + 11 S25
CONH2 bend.

ACCEPTED MANUSCRIPT
350*
319*
285*
241*
160*
120*
-
392
302
268
212
154
118
82
370
310
275
217
158
119
83
0.145
0.009
0.009
0.009
0.004
0.008
0.012
0.008
0.002
25.2
18.8
93 S49 + 37 S46 + 18 S13
NH2 twist.
ν49
ν50
ν51
ν52
ν53
ν54
ν55
ν56
ν57
42 S50 + 40 S41 + 19 S55 + 16 S56
40 S51 + 26 S53 + 14 S40
C13-C2 rock.
22.8
C13-C2 rock.
13.3
47 S52 + 36 S53 + 14 S48 + 11 S55
40 S53 + 23 S51 + 17 S55 + 16 S50
85 S54 + 49 S55 + 40 S56
C17-N12 rock. in-plane
Torsion (ring)
11.5
36.7
Torsion around N12-C17
Torsion’ (ring)
355.8
724.6
844.6
86 S55 + 63 S56 + 12 S54
75*
72
72
42 S56 + 26 S57
C17-N12 rock. out-of-plane
Torsion around C2-C13
-
46
46
145 S57 + 57 S55 + 23 S56 + 19 S54
RMSD (cm-1)
93
11
a From the infrared spectrum except those marked: *From the Raman spectrum.
b From B3LYP/6-311++G(d.p) approximation.
c From Scaled Quantum Mechanics force field (see text).
d Relative absorption intensities normalized with the highest band absorbance equal to 1.0.
e Raman intensities calculated and normalized with the highest value (for frequencies larger than 100 cm-1) equal to 100 (see text).
f Potential Energy Distribution values. Coordinate numbers correspond to Table S1 (Supplementary material).

ACCEPTED MANUSCRIPT
Conformer I (0.0)
Conformer II (14.3)
Conformer III (16.8)
Conformer IV (20.2)
Conformer VI (27.0)
Conformer V (23.2)
Fig. 1. The most stable conformers of N-carbamoyl-L-proline. The relative energies
calculated at the B3LYP/6-31G(d,p) approximation (in kJ mol-1) are given in parentheses.

ACCEPTED MANUSCRIPT
1542
1657
1687
3420
IR exp.
1457
1302
1201
3349
3235
1079
608
567
2941
2994
771
2885
1647
IR calc. SQM
1449
1683
1553
1186
556
607
3400
3004
2876
3343
780
3242
4000
3500
3000
2500
2000
1500
1000
500
cm-1
Fig. 2. The experimental and calculated infrared spectra of N-carbamoyl-L-proline.

ACCEPTED MANUSCRIPT
2991
444
2941
Raman exp.
2885
1446
875
1276
1074
285
690
1642
1691
3231
3338
2992
2942
2876
Raman calc. SQM
425
877
3242
3343
679
1440
1252
1074
275
1647
1683
4000
3600
3200
2800
2400
2000
1600
1200
800
400
cm-1
Fig. 3. The experimental and calculated Raman spectra of N-carbamoyl-L-proline.

ACCEPTED MANUSCRIPT
AHPro – Highlights.
-
The infrared and Raman spectra of N-carbamoyl-L-proline were obtained and
interpreted with the help of DFT calculations.
-
-
The molecule have six relatively stable conformers in the potential energy surface.
The most stable conformer for the isolated molecule does not correspond to the
conformer present in the crystal lattice, which is stabilized by intermolecular
hydrogen-bonds.
-
-
An assignment of the infrared and Raman bands was made after the theoretical
calculation of the corresponding vibrational frequencies.
A Scaled Quantum Mechanics force field was calculated, which allowed the
definition of a Potential Energy Distribution and a set of internal force constants.