The hydration effect on the uracil frequencies: an experimental and

quantum chemical study

M.A. Palafox
*
, N. Iza
1
, M. Gil
2
Departamento de Qu mica-F sica I, Facultad de Ciencias Qu micas, Universidad Complutense, Madrid 28040-ES, Spain
Received 21 September 2001; revised 2 January 2002; accepted 4 January 2002
Abstract
This work describes the performance of different quantum chemical theoretical methods in calculating the vibrational
frequencies of uracil and some derivatives, and the effect of hydration on the uracil frequencies. The Raman spectra of
polycristalline uracil with different water contents are discussed. To correct the deciency of the theoretical quantum chemical
methods, several procedures are described in detail. Two of them are new. For these new procedures, scaling factors and scaling
equations were determined at different levels. With them, a signicant reduction in the error of the predicted frequencies was
obtained over the one-factor scaling standard procedure. A comparison of the cost/effective method and procedure of scaling
was carried out on uracil molecule. Scale factors transferred from uracil to related molecules provided an a priori prediction of
fundamental frequencies and intensities, permitting several corrections to be proposed for earlier assignments. q 2002 Elsevier
Science B.V. All rights reserved.
Keywords: Uracil; Hydration; Scaling; Vibrational frequencies
1. Introduction
The theoretical prediction of vibrational spectra has
become an important part of spectrochemical and
quantum chemical investigations. Unfortunately, an
experimental spectrum of a polyatomic molecule
can be difcult to assign, even when the identity of
the molecular species is certain, often because of the
complexity resulting from coupling of vibrational
modes, molecular interactions, aggregation state,
and other effects. However, the theory is today suf-
ciently accurate to improve the assignment of the
vibrational spectra. The problem is that the most accu-
rate quantum chemical methods are still too expensive
in computer time and memory to apply as a routine
research. Thus, one may be forced to work at a low
level, and consequently, one must expect a large error
in the calculated vibrational frequencies. This error
can be notoriously decreased with the use of transfer-
able empirical parameters, also called scale factors.
The scale factor is therefore designed to correct the
calculated harmonic frequencies to be compared with
the anharmonic frequencies found by experiment.
These scale factors appear as a consequence of the
deciency of the theoretical approach and potentially
allow us to obtain, with greater accuracy, the vibra-
tional frequencies from procedures of only modest
computational cost, thus making possible the wide-
spread application to molecules of moderate size.
Journal of Molecular Structure (Theochem) 585 (2002) 6992
0166-1280/02/$ - see front matter q 2002 Elsevier Science B.V. All rights reserved.
PII: S0166-1280(02)00033-7
www.elsevier.com/locate/theochem
* Corresponding author. Tel.: 134-91-394-4272; fax: 134-91-
394-4135.
E-mail addresses: alcolea@quim.ucm.es (M.A. Palafox),
nereaiza@eucmax.ucm.es (N. Iza), mangil@eucmax.ucm.es
(M. Gil).
1
Tel.: 134-91-394-4281.
2
Tel.: 134-91-394-4274.
Also the introduction of scaling factors is capable of
accounting for many different factors that are usually
not even considered in theory, such as anharmonicity,
Fermi resonance, hydrogen bonding, solvent effects,
etc., and therefore, remarkably reduces the risk in the
assignment.
Considering as a rst approach that the values of
the force constants and the frequencies are close
among similar molecules and characteristic groups,
two kinds of transferable empirical parameters can
be established. Consequently, two procedures appear
frequently in the bibliography to get accurate frequen-
cies: to scale the force constants, previous to calculate
the frequencies, or to scale directly the frequencies.
The rst procedure, developed by Pulay et al. [1
4], involves the rescaling of the force constant matrix.
The off-diagonal force constants F
ij
are scaled by
C
i
C
j

1=2
; F
ij
C
i
C
j

1=2
F
th
ij
where C
i
and C
j
are the
scale factors for F
ii
and F
jj
. These scale factors are
transferable among similar molecules and certainly
improve the agreement between computed and experi-
mental frequencies. Some of the molecules studied
with this procedure were recently collected [5,6].
The second procedure is based on the transferabil-
ity of the scale factors derived directly from the
frequencies themselves. The scaling of the frequen-
cies is carried out in the bibliography with a uniform
scale factor, which is common for the same level of
computation [7]. However, the error obtained in the
frequencies is still too large for this procedure to be
used as routine. As an alternative, the main purpose of
the present paper is to describe two new procedures
for scaling, i.e. with a scaling equation and with speci-
c scale factors for each mode determined in a simpler
and similar molecule.
We believe that the introduction of scaling factors
for the frequencies themselves is preferable to the
more indirect approach of scaling the force constants
[8,9]. First, the frequencies are physically observable
and the force constants are not. Second, the denition
of the force constant matrix is not unique because the
number of matrix elements is usually much larger than
the number of known frequencies. The third argument
in favor of our procedure is the pragmatic observation
that we could be primarily interested in only a few
major characteristic frequencies and not in the whole
spectrum.
In a previous paper, the scale factors and scale
equations for benzene derivatives were determined
[10]. The present work presents a study of the uracil
molecule. The essential biological importance of
uracil and its derivatives has motivated a number of
recent reviewed studies of the structure and spectro-
scopy of these molecules, which are now analyzed
with better procedures of scaling. The performance
of these procedures is analyzed in several examples:
in the hydration of uracil with different number of
water molecules, and in the molecules of 5-uoro-
uracil, 5-bromouracil, 5-methyluracil, 5-nitrouracil,
1-methyluracil, 2-thiouracil, 3-methyluracil, and 1,3-
dimethyluracil.
A clear prediction of the vibrational spectra of
uracil is essential in the analyses of the spectra of its
more complex derivatives, such as nucleosides and
nucleotides and their polymers, which play an impor-
tant role in biochemical processes frequently moni-
tored by means of vibrational spectroscopy. The use
of these new procedures of scaling makes it possible
to resolve the ambiguous assignment of some bands of
the spectra of uracil and to derive specic scale factors
and scale equations to be used in their derivatives and
in wateruracil complexes.
Special attention has been paid to the hydration due
to the biological functions of nucleic acids are depend
on their interactions with surrounding water. This
interaction takes place through both hydrophilic and
hydrophobic sites forming two hydration shells,
clearly described in the bibliography. In the present
study, the hydration of uracil from polycrystalline
samples with different water contents was carried
out by Raman spectroscopy. Until the present time,
the hydration of the solid phase has been performed
by lms as a function of the relative humidity. For the
rst time, the present manuscript shows the procedure
and the Raman spectral features obtained when small
amounts of water are added to the polycrystalline
solid. However, the spectral changes due to the hydra-
tion of the solid cannot be only attributed to the base
water interactions, but to structural modications of
the crystalline lattice.
2. Experimental
A `Dilor Modular XY Laser Raman' spectrometer
equipped with multichannel detection and an Ar
1
M.A. Palafox et al. / Journal of Molecular Structure (Theochem) 585 (2002) 6992 70
laser at 50 mW power with the 514.5 nm excitation
line was used. Integration time was 2 s at room
temperature and 1000 accumulations were made.
Spectral data for the 4000400 overall region were
collected in three ranges. Different water amounts
were added to 8 mg uracil samples. The hydrated
samples were weighted and sealed in capillary tubes
to record the Raman spectra.
2.1. Computational methods
The keywords OPT and FREQ, for optimization
and frequency calculations, respectively, with the
gaussian98 [11] program package, were used. The
TIGHT criterion of convergence was employed. The
frequency calculations were carried out at the same
level of the respective optimization process, and with
their nal results.
Ab initio calculations [12], with wave functions
based HartreeFock (HF) and second-order Mller
Plesset perturbation theory (MP2) [13,14], and
density functional theory methods (DFT) [15] were
performed with several basis sets, from 6-31G
p
to 6-
31111G(2d,p), but the 6-3111G(2d,p) was estab-
lished for the comparisons. The results obtained
with this basis set will be referred to by the notations,
HF, MP2, B3LYP, etc. The choice of these basis sets
is based on the consideration that, in order to obtain
reliable properties of hydrogen-bonded complexes,
the addition of polarization and diffuse functions to
the basis set is necessary [16].
In DFT, the hybrid methods with the Becke (B) [17]
and the Becke's three-parameter (B3) [18,19]
exchange functionals were used in combination with
the correlation functionals of Lee, Yang and Parr
(LYP) [20], Perdew 86 (P86) [21], and Perdew and
Wang 91 (PW91) [22,23].
3. Results and discussion
3.1. Geometry optimization
3.1.1. Non-hydrated form
Crystalline uracil is constituted by four molecules
of C
s
point symmetry per unit cell. The four molecules
are arranged into two hydrogen-bonded dimers. The
effect of hydrogen-bonded dimer formation in the
uracil crystal is clearly reected in the structural
results, particularly in the unequal length of the carbo-
nyl bonds.
The experimental data reported by electron diffrac-
tion (ED) [24] and by X-ray [25,26] agree well with
the predicted ground state geometries, especially by
B3LYP; bond lengths were found to be approximately
0.02 A

longer than expected, except for the C4yO

length which were about 0.03 A

shorter, Table 1ac.

The angles are also in good accordance to the experi-
mentals, with an error of ca. 18.
At the bottom of Table 1ac, the calculated rota-
tional constants, the total energy, and the zero-point
vibrational energy (ZPE) for each system are also
included. The ZPE values can be scaled with the scal-
ing factor of 0.970.
3.1.2. Hydrated form
To simulate theoretically the hydration effects three
procedures have been suggested [29]: (i) empirical
scaling of the quantum mechanical force constants
of the isolated molecule [30], (ii) use of solvation
cavity techniques [31], or (iii) modeling of the
solvated compound by a molecular complex with
water [32]. From a strict theoretical point of view,
the last method may be preferred, provided that size
of the considered complex is not too large, and thus it
is the method followed in the present work.
Firstly, we have tried with one water molecule in
three positions, complexes AC, Table 1ac, making
two simultaneous H-bonds to an amino hydrogen and
to a carbonyl oxygen. Small difference of energy
appears among these conformations, the most stable
one being the complex A. A lengthening of the NH
and CyO bonds by ,0.01 A

have been also observed

under hydration.
With one intermolecular hydrogen bond have been
reported [33] another form, the O
water
bonded to the
H11 atom, and a weak interaction of the H
water
with the
O10 atom. This form is less stable than the other ones
and thus it is not shown in Table 1ac.
Finally, we have reproduced the hydration with
three water molecules, starting the optimization with
the molecules placed in the positions accord to the
complexes AC. However, the optimum nal result
obtained by HF, B3LYP and B3PW91 is that shown in
Table 1ac, with the two water molecules in a dimer
form and forming a cycle (complex D). Other forms,
although less stable, can be obtained (complexes E
M.A. Palafox et al. / Journal of Molecular Structure (Theochem) 585 (2002) 6992 71
M
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(
2
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0
2
)
6
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2
7
2
Table 1a
Equilibrium geometries of the non-hydrated uracil and hydrated with one or three water molecules. Bond lengths in A

, bond angles in degrees. The calculated values are with the 6-

3111G(2d,p) basis set
Bond
lengths
Calc.
B3LYP
Exp.
RX
a
Angles Calc.
B3LYP
Exp.
RX
Bond
lengths
Calc.
B3LYP
Bond
angles
Calc.
B3LYP
Interatomic
angles
Calc.
B3LYP
Bond
lengths
Calc.
B3LYP
Bond
angles
Calc.
B3LYP
Interatomic
angles
Calc.
B3LYP
N1C2 1.3906 1.371 NC2N 113.13 114.0 N1C2 1.3803 NC2N 114.14 N1H O13 144.65 N1C2 1.3844 NC2N 114.27 N3H O13 142.86
C2N3 1.3805 1.377 C2NC4 127.88 126.7 C2N3 1.3746 C2NC4 127.51 C2yO H15 109.02 C2N3 1.3714 C2NC4 127.01 C2yO H15 109.34
N3C4 1.4093 1.371 N3C4C5 113.68 115.5 N3C4 1.4115 N3C4C5 113.47 H7 OH15 83.69 N3C4 1.4091 N3C4C5 113.97 H9 OH15 84.10
C4C5 1.4554 1.430 C4CyC 119.83 118.9 C4C5 1.4530 C4CyC 119.76 O8 H15O 144.47 C4C5 1.4574 C4CyC 119.90 O8 H15O 143.72
CyC 1.3443 1.340 N3C2yO 124.18 CyC 1.3460 N3C2yO 122.97 C2N1H O 26.21 CyC 1.3430 N3C2yO 124.30 C2N3H O 24.93
N1C6 1.3722 1.359 C4N3H 116.38 N1C6 1.3699 C4N3H 116.45 N1H OH14 114.91 N1C6 1.3740 C4N3H 117.69 N3H OH14 114.94
C2yO 1.2120 1.215 N3C4yO 120.22 119.2 C2yO 1.2243 N3C4yO 120.05 N1H OH15 7.43 C2yO 1.2238 N3C4yO 120.43 N3H OH15 7.79
C4yO 1.2146 1.245 C4C5H 118.24 C4yO 1.2148 C4C5H 118.26 C2yO H15O 1.33 C4yO 1.2141 C4C5H 118.17 C2yO H15O 4.73
RC
b
: A 3896 3884
c
m (Debye): 4.518 RC
b
: A 3693 m (Debye): 3.910 RC
b
: A 2213 m (Debye): 5.079
B 2021 2023 Total En (AU): 2414.955648 B 978 Total En (AU): 2491.431475 B 1346 Total En (AU): 2491.428063
C 1331 1331 ZPE (kJ/mol): 227.614 C 774 ZPE (kJ/mol): 293.125 C 838 ZPE (kJ/mol): 292.351
a
Refs. [24,26].
b
Calculated rotational constants in MHz.
c
Experimental, Refs. [27,28].
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)
5
8
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(
2
0
0
2
)
6
9

9
2
7
3
Table 1b
Equilibrium geometries of the non-hydrated uracil and hydrated with one or three water molecules. Bond lengths in A

, bond angles in degrees. The calculated values are with the 6-

311 1G(2d,p) basis set
Bond
lengths
Calc.
B3LYP
Bond
angles
Calc.
B3LYP
Interatomic
angles
Calc.
B3LYP
Bond
lengths
Calc.
HF
Calc.
B3LYP
Calc.
B3PW91
Bond
angles
Calc.
HF
Calc.
B3LYP
Calc.
B3PW91
Interatomic
angles
Calc.
HF
Calc.
B3LYP
Calc.
B3PW91
N1C2 1.3935 NC2N 113.44 N3H O13 143.19 N1C2 1.3656 1.3841 1.3794 NC2N 115.07 114.84 114.95 H9 O16H18 107.76 106.40 103.44
C2N3 1.3806 C2NC4 127.03 C4yO H15 111.17 C2N3 1.3628 1.3747 1.3702 C2NC4 126.23 126.12 126.10 O10 H21O19 166.83 170.65 170.68
N3C4 1.3971 N3C4C5 114.81 H9 OH15 82.64 N3C4 1.3766 1.3936 1.3883 N3C4C5 115.07 115.04 115.08 O16H18 O19 156.63 156.22 160.20
C4C5 1.4510 C4CyC 119.49 O10 H15O 145.79 C4C5 1.4547 1.4482 1.4448 C4CvC 118.75 119.44 119.33 H18 O19H21 93.72 94.75 94.21
CyC 1.3455 N3C2yO 124.33 C4N3H O 25.14 CyC 1.3279 1.3471 1.3463 N3C2vO 122.69 123.03 123.03 C2N1H O13 24.82 25.97 25.42
N1C6 1.3688 C4N3H 116.24 N3H OH14 113.61 N1C6 1.3624 1.3650 1.3601 C4N3H 117.76 118.09 118.11 N1H OH15 5.63 6.91 5.99
C2yO 1.2112 N3C4yO 120.61 N3H OH15 7.55 C2yO 1.1971 1.2243 1.2231 N3C4vO 120.85 121.02 121.04 C2yO H15O13 0.46 0.26 0.61
C4yO 1.2267 C4C5H 118.41 C4yO H15O 3.94 C4yO 1.1993 1.2293 1.2280 C4C5H 118.62 118.40 118.51 C4N3H9 O16 9.76 219.39 21.06
RC: A 2245 m (Debye): 4.496 RC
d
: A 1512 m
d
: 4.370
N1H O13 145.60 144.60 145.05 N3H9 O16H18 218.11 28.36 233.24
B 1337 Total En (AU): 2491.429168 B 536 En
d
: 2644.381119
C2vO H15 112.26 109.39 108.87 H9 OH18 O19 2.85 219.77 8.13
C 839 ZPE (kJ/mol): 292.701 C 397 ZPE
d
: 423.450
H7 OH15 83.96 82.60 81.91 O16H18 OH20 117.99 129.42 112.02
O8 H15O 139.82 145.99 147.23 O16H18 OH21 2.98 14.75 1.35
N3H O16 173.43 174.58 175.07 O10 H21O H18 3.06 5.80 21.72
C4vO H21 141.59 136.54 134.66 C4yO10 H21O 217.07 24.45 214.47
d
By B3LYP.
and F). The complex F was only obtained by us with
the AM1 semiempirical method. The existence of a
water dimer instead of water monomer leads to the
formation of linear H-bonds between water molecules
and uracil.
Uracil 12H
2
O, 14H
2
O, and 17H
2
O complexes
have been reported [33], which indicate the numerous
possibilities of reproduce the rst hydration shell,
with water dimer and trimer around uracil.
3.2. Characterization of the ring modes
The ring modes characterized at B3LYP/6-31G
pp
level in uracil molecule with their calculated frequen-
cies are plotted in Fig. 1. The atomic displacements
for each computed frequency are presented as XYZ
coordinates, in the standard orientation, which are
plotted to identify each vibration. Although cartesian
displacements for some planar ring modes have been
initially reported by Susi and Ard [34], no full char-
acterization appears in the bibliography of the ring
modes. These normal modes of uracil structure,
numbered from 1 to 30, are briey analyzed in para-
graphs hereafter.
It is interesting to observe in Fig. 1 that a few
skeletal ring modes retain a certain resemblance to
the pseudo normal modes of a hypothetical C
6
ring
and the skeletal modes of benzene, although the uracil
ring has no symmetry within the molecular plane. A
correlation between these modes has been reported
[34], although differing in several cases from our
results.
M.A. Palafox et al. / Journal of Molecular Structure (Theochem) 585 (2002) 6992 74
Table 1c
Equilibrium geometries of the non-hydrated uracil and hydrated with one or three water molecules. Bond lengths in A

, bond angles in degrees.

The calculated values are with the 6-311 1G(2d,p) basis set
Bond lengths Calc. HF Bond. angles Calc. HF Interatomic angles Calc. HF Interatomic torsional angles Calc. HF
N1C2 1.3589 NC2N 115.58 N1H O13 147.75 C2N1H O13 5.63
C2N3 1.3527 C2NC4 126.26 C2yO H15 111.87 N1H OH15 26.66
N3C4 1.3893 N3C4C5 114.50 H7 OH15 84.32 C2yO H15O13 0.13
C4C5 1.4595 C4CyC 118.94 O8 H15O13 138.20 N3C2yO8 H18 12.19
CyC 1.3251 N3C2yO 123.00 C2O8 H18 136.99 C2yO8 H18O16 217.68
N1C6 1.3682 C4N3H 116.77 O8 H18O16 170.79 O8 H18O16 H21 2.66
C2yO 1.2087 N3C4yO 120.49 H18O16 H21 92.69 O8 H18O16H17 2122.66
C4yO 1.1891 C4C5H 118.49 O16 H21O19 152.47 C2N3H9 O19 0.99
RC: A 858 m: 4.788
N3H9 O19 175.50 N3H9 O19H20 2141.73
B 790 En: 2640.794842
H9 O19H21 109.25 H9 O19H21 O16 13.87
C 413 ZPE: 453.637
3.3. Frequency calculation
The frequencies and intensities of uracil, calculated
at different levels, is examined in Table 2. The rst
column refers to the numbers assigned to the calculated
vibration plotted in the centrum of the rings in Fig. 1,
and are given in increasing order of frequencies. For
simplicity, in the second column the assignments of
the non-hydrated form include only the contributions
of predominant modes. The columns with relative
intensities were obtained by dividing the computed
values by the intensity of the strongest line. The 9
11th columns collect the experimental wavenumbers
reported in Argon matrix [3542] and in gas phase
[35,43], while the last three columns show Raman
frequencies, in solid and with different water amounts.
M.A. Palafox et al. / Journal of Molecular Structure (Theochem) 585 (2002) 6992 75
Fig. 1. Characterization of the normal modes in uracil molecule by B3LYP/6-31G
pp
DFT method.
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2
7
6
Table 2
Calculated wavenumbers and intensities for the normal ring modes of uracil molecule and hydrated with some of the methods used (Abbreviations: n, stretch; b, bend; g, wag; sh,
shoulder; vs, very strong; s, strong; m, medium; w, weak; vw, very weak)
No. Characterization Non-hydrated
a
Infrared Uracil 1H
2
O
b
HF
freq.
MP2
c
freq.
B3P86
freq
B3LYP B3PW91
freq.
Ar matrix
d
Gas
e
Gas
f
B3LYP
Freq. Freq
b
I
g
Freq.
h
I Freq.
i
Freq.
j
1 Puckering N3 167 139 151 150 147 0 151 161 1 153 155
2 Puckering N1 179 161 171 170 165 0 171 185 w 185 w 172 0 166 167
3 d(OCNCO) 426 383 385 385 387 4 385 391 m 377 m 374 vw 404 1 407 410
4 g(CvCH12) 429 379 397 396 395 4 396 411 m 411 m 395 w 412 2 401 401
5 d(ring) 561 518 519 519 523 4 518 516.5 m 527 m 512 w 528 4 532 531
6 d(ring) 1d(CvO) 593 541 543 541 543 1 542 536.4 m 549 1 548 555
7 d
as
(ring) 1d(CvO) 609 560 560 558 560 1 559 559 w 588 w 574 1 567 565
8 g(N1H) 588 566 571 563 475 8 570 551.2 m 556 m 545 w 797 16 849 857
9 g(N3H) 730 698 693 687 677 14 692 662.1 s 633 m 659.5 w 673 3 554 562
10 g(C4vO) 1g(C5H) 803 782 732 729 728 2 731 718 w 717.4 vw 716 1 728 732
11 g(C2vO) 862 722 760 752 765 10 759 769 s 756.5 w 770 0 762 761
12 n(ring) 829 738 781 772 769 0 779 759.2 sh? 775 1 773 775
13 g(C5H) 1g(C4vO) 905 799 814 813 819 10 814 804 s 810 s 802 w 821 5 817 816
14 n(CC) 1d(NH) 1053 990 975 965 962 1 970 958.3 w 946 vw 952 w 971 1 981 982
15 g(C6H) 1110 930 971 970 972 0 973 963 w 974 w 972 sh 979 0 970 972
16 d(NCC) 1076 999 994 990 994 1 993 982 w 999 w? 990 sh 998 1 998 997
17 n(ring) 1d(C5H) 1175 1113 1098 1091 1086 1 1097 1073 w 1089 s? 1082 m 1096 0 1087 1092
18 n(CN) 1d(C6H, N1H) 1306 1236 1210 1198 1191 14 1209 1184 vs 1172 s 1206 5 1204 1205
19 d(C5H) 1d(NH) 1347 1273 1240 1231 1227 1 1237 1217.4 w 1228 m 1244 5 1228 1230
20 d(N3H) 1d(CH) 1530 1413 1388 1382 1382 3 1387 1359.3 vw 1360 m 1356 sh 1388 3 1454 1457
21 n(CN) 1d(N3H) 1554 1436 1417 1407 1406 20 1415 1388.7 vs 1380 s 1387 s 1437 4 1421 1393
22 d(C6H) 1d(NH) 1557 1449 1428 1422 1423 3 1426 1399.6 vs 1396 ms 1400 s 1415 9 1402 1420
23 d(N1H) 1n(N1C) 1647 1536 1520 1506 1498 18 1518 1472 ms 1480 s 1461 s 1531 4 1494 1506
24 n(CvC) 1847 1712 1704 1690 1670 12 1701 1644 m 1632 vs 1641 s 1670 5 1673 1665
25 n(C4vO) 1995 1826 1830 1808 1757 100 1826 1741 vs 1688 vs 1753 100 1756 1729
26 n(C2vO) 2012 1868 1868 1845 1791 92 1864 1757.5 vs 1734 vs 1756 vs 1767 28 1763 1792
27 n(C6H) 3394 3263 3234 3221 3200 1 3231 3076 w 3200 0 3201 3200
28 n(C5H) 3429 3304 3281 3264 3242 0 3278 3084
k
3101 w 3124 m 3242 0 3241 3244
29 n(N3H) 3863 3612 3643 3620 3592 11 3642 3434.5 s 3427 w 3436 s 3592 8 3405 3388
30 n(N1H) 3902 3656 3682 3658 3636 17 3681 3484.3 s 3450 w 3484 s 3422 46 3637 3634
M
.
A
.
P
a
l
a
f
o
x
e
t
a
l
.
/
J
o
u
r
n
a
l
o
f
M
o
l
e
c
u
l
a
r
S
t
r
u
c
t
u
r
e
(
T
h
e
o
c
h
e
m
)
5
8
5
(
2
0
0
2
)
6
9

9
2
7
7
Table 2 (continued)
No. Uracil 13H
2
O
b
Raman
B3LYP
l
B3PW91
l
HF
l
Solid Solid
1H
2
O
Solution
m
Freq. I Freq. I Freq. I A
n
Dep.
o
1 62.9
p
1 66
p
0 56 0 1 0.75
2 171.3 0 172 0 176 1 0 0.75
3 423.2 4 421 4 449 3 1 0.70 401
4 426.8
q
1 435
q
1 445 2 2 0.75 426.0 426.0
5 544.1
r
14 541
r
8 575 2 3 0.54 526.6 526.6
6 563.2 2 564 2 606 1 3 0.31 534.0 534.0 536
7 579.3 1 582 1 622 2 0 0.72 552.5 554.3 553
8 799.1 15 817 15 718 8 0 0.40 574.6 574.6 573
9 953.2 12 989 11 934 20 0 0.68
10 717.9 0 722 1 811 4 0 0.70
11 772.3 0 777 0 859 0 0 0.68
12 785.2 1 792 0 835 0 15 0.04 786.9 786.9 782
13 823.7 1 827
s
0 901 0 1 0.75
14 1002.6 1 1016 0 1073 1 3 0.44
15 980.4 0 980 0 1108 0 4 0.75 982.3, 989 982.3, 993 966
16 998.7 3 1000 3 1079 2 1 0.03 1005.1 1006.8 1001
17 1106.5 0 1111 0 1185 0 6 0.31 1097.3 1099.0 1095
18 1230.3 4 1248 7 1353 4 22 0.32
19 1245.7 7 1253 1 1320 10 8 0.32 1234.4 1232.7 1232
20 1503.1
t
9 1511
t
8 1610 5 6 0.42 1393.6 1393.6
21 1443.9
u
10 1455
u
9 1571 16 0 0.27 1416.9 1416.9 1387
22 1404.4
v
6 1407
v
3 1529 3 17 0.18 1458.4 1457.5
23 1536.0 7 1544 6 1665 8 16 0.40 1503.0 1503.0
24 1668.0
r
13 1678
r
4 1819 8 34 0.02 1643.2 1644.6 1631
25 1725.4
r
67 1741
r
62 1907 100 45 0.23
26 1766.5 72 1783 65 1935 62 15 0.09 1712.3 1712.2 1708
27 3200.0 0 3207 0 3364 0 69 0.43 3079.7 3079.7 3079
28 3242.3 0 3253 0 3402 0 87 0.21 3095.7 3094.4 3094
29 3176.8 100 3112 100 3648 48 89 0.24
30 3417.2 51 3397 47 3785 32 100 0.19
a
With the 6-31G
pp
basis set.
b
With the 6-3111G(2d,p) basis set.
c
With the 6-31G
p
basis set.
d
Refs. [3542].
e
Refs. [35,42].
f
Ref. [43].
g
I, relative infrared intensities in %.
h
Complex A.
i
Complex B.
j
Complex C.
k
Raman, Ref. [35].
l
Complex D.
m
Ref. [44, 45].
n
Relative Raman intensities.
o
Raman depolarization ratios.
p
1gH
2
O13; H
2
O16:
q
1gH
2
O:
r
1dH
2
O:
s
1gN1H:
t
As dN3H:
u
As nCN 1dCH; NH:
v
As dCH 1nCN:
3.3.1. Non-hydrated form
Although frequency calculations on uracil have
been reported with PM3 [46,47], STO-3G [37], HF
[43,48,49,51,52], MP2 [53], B3LYP [44,45], and
several DFT methods [50], the present work repre-
sents an improvement because a full comparison of
the values obtained with more methods and better
basis sets has been carried out.
On the experimental side, unfortunately few studies
undertake the gas-phase vibrational spectrum of
uracil. Apart from an early work by Nowak et al.
[54], studying the n
NH
and n
CH
stretching region,
and the work of Bardi et al. [55], there are the
works of Nunziante-Cesaro (cited as Ref. [17] by
Harsanyi et al. [35]) and the Colarusso et al. [43],
Table 2. We select that of Colarusso et al. for
comments, since the assignments given there corre-
spond most closely to our own. The comparison of our
theoretical values was also performed on the gas
phase data [35,42], and in few cases from spectra in
argon matrices [3542,44,49]. When several bands
have been observed corresponding to a mode, only
the central band or the most intense appears in
Table 2.
The discussion of the assignments for the vibra-
tional modes of the uracil molecule is as follows:
NH modes: The NH stretching bands were
reported in gas phase by Harsanyi et al. [35] (cited
in Ref. [17]) with weak intensity, while by Colarusso
et al. in gas phase [43], by Ivanov et al. in Ar matrix
[42], and by our theoretical calculations they appear
with strong intensity. Another discrepancy with
Harsanyi et al. [35] is in the value of their frequencies,
especially with the N1H stretch reported at
3450 cm
21
while in Refs. [35,42] and in our scaled
values it appears at ca. 3480 cm
21
.
In the stretching and out-of-plane bending of the
N1 2H and N3 2H bonds, small but signicant
differences appear between our calculated frequencies
by B3LYP, and the data from Ref. [44,45]. Thus, the
n(N1H), n(N3H), g(N3H), and g(N1H) modes
are calculated [44,45] at 3654, 3613, 682 and
555 cm
21
, respectively, instead of the values of
Table 2.
The description of mode 22 is complex as can be
seen from Fig. 1. Mainly, we have characterized it as
d(C6H) 1d(NH), with some contribution of n(C
N), in agreement with the assignment by Harsanyi et
al. [35] and Colarusso et al. [43] as n(CN) 1b(N
H). However, these authors have not included the
d(C6H) bending as we have clearly observed and
corroborated with recent assignments [44,52].
Although mode 21 has some contribution of d(C6
H) and d (C5H), as reported by Colarusso et al. [43]
and Les et al. [49], we have characterized it as n(C
N) 1d(N3H) in agreement with Harsanyi et al. [35].
Mode 20 is characterized as d(N3H) with a high
contribution of d(C6H,C5H), differing from the
b(CH) assignment reported by Harsanyi et al. [35]
and Csaszar et al. [56]. We have not observed signi-
cant contribution of n(N3C4) in the mode 19 as
indicated by Refs. [35,43,57], and it was characterized
as d(C5H) 1d(NH). Due to its weak IR intensity,
it has not been detected in gas phase [43], although
Harsanyi et al. [35] reported a band with medium
intensity at 1228 cm
21
. Mode 18 was calculated
with strong IR intensity and scaled at ca.
1170 cm
21
, which was related to the strong IR band
[43] at 1172 cm
21
, differing from the band detected
[35] and assigned to this mode at 1089 cm
21
. Our
assignment is also in agreement with the very strong
band at 1388 cm
21
established by Szczepaniak et al.
[44].
The NH out-of-plane bends are predicted with
strong and medium intensity, N3H and N1H,
respectively, in agreement with the strong and
medium bands observed in Ar matrix [41] at 662.1
and 551.2 cm
21
and to that obtained by other calcula-
tions [50,56]. In gas phase the N1H mode is clearly
related to the band at 556 cm
21
[35] or at 545 cm
21
[43]. The N3H mode can be made to correspond to
the gas phase band at 659.5 cm
21
[43] (although it
appears with weak intensity), or to the band at
633 cm
21
[35] (although the frequency is slightly
low), while in Argon matrix this mode is detected
[42] with strong intensity at 662.1 cm
21
. These
experimental frequencies were assigned to the
g(N3H) mode in contrast to the characterization
reported [53] by MP2/6-31G
p
and 6-31G
pp
basis, but
in relative good agreement with other characteriza-
tions [49,50,56].
The band at 556 cm
21
in gas [35,42] phase is
assigned to the g(N1H) mode, in disagreement
with Aamouche et al. [53], who related this band to
the two calculated frequencies, corresponding to
d(C2yO) and g(N1H) modes.
M.A. Palafox et al. / Journal of Molecular Structure (Theochem) 585 (2002) 6992 78
The band corresponding to mode 6 was observed
only in Ar matrix at 536.4 cm
21
. The strong intensity
predicted by PM3 is a clear failure of this method.
Notwithstanding, the mode 6 is characterized at
527 cm
21
by Peticolas and Rush [52] from ab initio
(HF 1CI)/6-31G
p
calculus, and at 529 cm
21
by
Estrin et al. [50] from local density approximation
(LDA)-DFT/6-31G
pp
calculus.
CH modes: The weak intensity reported by
Harsanyi et al. [35] for the CH stretch bands is in
accordance to the almost null value predicted theore-
tically, although the frequency observed by Colarusso
et al. [43] for the n(C5H) mode at 3124 cm
21
is
more in accordance with our scaled results.
The mode n(C5H) was scaled [56] at 3081 cm
21
and related to the Raman band at 3084 cm
21
and to the
IR band in gas phase [43] at 3124 cm
21
, in agreement
with our calculations. Similarly, the n(C6H) mode is
calculated [56] at 3034 cm
21
, predicting an experi-
mental band at similar frequency, 3034 cm
21
, but
far from the experimental IR bands observed by
other authors at 3076 and 3080 cm
21
in Ar matrix
[35] and KBr pellet [58], respectively.
The band at 1228 cm
21
in gas phase [35] was
related to the band at 1217.4 cm
21
in Argon matrix,
instead of to the band at 1184 cm
21
[53], and it was
assigned to d(C5H) instead of to n(CN) [53].
Our characterization of modes 1416 is in agree-
ment with Harsanyi et al. [35] and Szczepaniak et al.
[44]. Although the gas phase band at 974 cm
21
,
assigned [35] simultaneously to the D(ring) and
g(C6H) modes, should correspond only to g(C6
H), and the mode D(ring) should be related to the
gas phase band at 999 cm
21
. According to Colarusso
et al. [43], however, the modes 16 and 15 appear inter-
changed; i.e. the gas phase IR band at 990 cm
21
is
assigned [43] to g(C6H) instead of d(NCC), Table
1ac, and by contrast, the band at 972 cm
21
is
assigned [43] to G(ring) instead of g(C6H). Analo-
gously, Aamouche et al. [53] related the band in gas
phase at 974 cm
21
to the Argon matrix band at
958 cm
21
, instead of at 963 cm
21
, and it has been
assigned [53] as n(ring) 1D(ring), instead of
g(C6H).
CyO modes: It should be noted that the CyO
stretching region is strongly inuenced by Fermi
interactions, and thus many bands appears in this
region, although only two fundamental bands are
expected. In our calculations, the C2yO and C4yO
stretches are the strongest IR bands. They are
predicted with similar intensity by DFT methods,
but by HF and MP2 the C4yO mode appears with a
remarkably higher intensity than the C2yO in contrast
to the experimental. In the spectrum reported by
Colarusso et al. [43] the shoulder at 1703 cm
21
is
assigned to the n(C4yO) and n(C2yO) modes; but
compared to our calculations this frequency is too
low and the intensity too weak; it seems to us that
the frequency of both modes is very close and
included in the broad band (unresolved) around
1750 cm
21
, and in accordance with the Ar matrix
results [3642,44]. The frequencies reported by
Harsanyi et al. [35] are too low and should not be
considered.
Our description of mode 13 as g(C5H) 1
g(C4yO) is in agreement with Colarusso et al. [43]
and other authors [44,49,56], although Harsanyi et al.
[35] only indicates g(CyO) and they assign the very
weak IR band at a lower frequency as 672 cm
21
to
g(C5H) 1g(C4yO) mode. Likewise, the weak
intensity of the band [43] at 802 cm
21
is in contra-
diction with the strong intensity calculated theoreti-
cally and with the strong bands at 804 (Ar matrix [36
41]) and 810 cm
21
(gas phase [35]). The medium
intensity band reported in gas phase at 841 cm
21
by
Harsanyi et al. [35] has no correspondence with any
band in the spectrum reported by Colarusso et al. [43],
nor with the Ar matrix [3642,49], nor with our theo-
retical predictions. Only Barnes et al. [41] detected a
very weak band at 842 cm
21
which has been consid-
ered and related by Harsanyi et al. [35] and Csaszar et
al. [56] to their scaled frequencies at HF/4-21G level.
The very weak gas phase band at 672 cm
21
[35],
and possibly detected at 692 cm
21
[43], cannot be
related to mode 10 due to its low frequency, in
disagreement with Harsanyi et al. [35], and should
be related to the g(N3H) mode. However, the band
reported in gas phase at 717.4 cm
21
[43], and in
Argon matrix at 707.4 and 719 cm
21
by Ivanov et
al. [42] and Szczepaniak et al. [44], respectively, is
in accordance with our calculations, although
Aamouche et al. [53] assigned this band to the
g(C2yO) 1g(C4yO) mode. Another discrepancy is
in the band at 769 cm
21
in gas [35,42] assigned by
Aamouche et al. [53] to ring breathing, instead of
g(C2yO).
M.A. Palafox et al. / Journal of Molecular Structure (Theochem) 585 (2002) 6992 79
CyC and ring modes: The null IR intensity
predicted for mode 12 is in accordance with the lack
of bands in the gas phase IR spectra, although the
shoulder in Ar matrix at 759.2 cm
21
has been assigned
[42] to this mode in agreement with other authors
[41,49]. The strong Raman activity calculated for
this mode is in accordance with the very strong lines
detected at 786 and 789 cm
21
[53].
The frequency predicted for mode 17 is in agree-
ment with the IR band at 1082 cm
21
[43], but in
contrast to the band reported at 999 cm
21
[35] and
assigned to this mode. Our characterization of mode
17 as n(ring) involves a high contribution of the N1
C6 stretch in accordance to a recent assignment [44]
of the IR band at 1075 cm
21
in Ar matrix.
The ring deformation, mode 7, is predicted with
weak intensity and was related to the band in Ar
matrix at 559 cm
21
[42,49] (588 cm
21
in gas phase
[35]). The out-of-plane bending of the ring, mode 4,
has a strong contribution of the CyCH moiety.
3.3.2. Hydrated form
The calculated frequencies of the uracil normal
modes obtained with one water molecule in three
positions, complexes AC, and with three water
molecules, complexes DF are collected in Table 2.
For comparative purposes, the infrared intensities
listed were normalized to the intensity of the strongest
normal uracil mode and therefore the most intense
water bands were not considered.
The vibrational modes which are highly affected by
the presence of the surrounding water molecules are
the n(NH), n(CyO), and g(NH). It is noted that the
NH bond-stretching undergo strong wavenumber
downshifts of about 500 cm
21
in going from isolated
uracil to hydrated (13H
2
O) form, while the n(CH)
modes are less affected by H-bonding. The g(NH)
vibrations are considerably shifted to higher wave-
numbers, ,260 cm
21
, with the hydration.
The experimental Raman spectra of polycrystalline
uracil with different water contents are shown in
Fig. 2. The major effect with the hydration is a general
increase of the intensity of all the bands with the rst
amounts of water, then a decrease of this intensity,
and after that an increase with further additions of
water. The increases in intensity are specially high
for the bands at 786.9 and 1234.4 cm
21
, assigned to
n(ring) and d(C5H) 1d(NH), respectively. By
contrast, it is noted a slight shift to higher frequencies
in the bands at 552.5, 989.0, 1005.1, 1097.3 and
1643.2, and to lower frequencies in the bands at
1234.4, 1458.4 and 3095.7 cm
21
. These features
were conrmed with the spectra of other samples
with similar amounts of water.
Due to the amount of water added is very small, (1
4 mg H
2
O)/8 mg uracil, and that it is not observed
liquid water bands in the Raman spectra, it can be
deduced that the rst and second hydration shells of
uracil are formed.
It is noticeable that in the Raman spectra, the
n(CyO) mode is not shifted upon hydration and it
remains quite invariable. However, the bands at
1234.4 and 1458.4 cm
21
assigned to the bendings
d(C5H) 1d(NH) and d(C6H) 1d(NH),
respectively, shift to lower frequencies (12 cm
21
)
indicating stacking association of C5H and C6H
groups. Also the bands at 1643.2 and 1097.3 cm
21
assigned to the stretch n(CyC) and n(ring) 1d(C5
H), respectively, shift to higher frequencies indicating
stacking association. By contrast, the band at
3095.7 cm
21
assigned to n(C5H) shifts to lower
frequency indicating H-bonding of C5H group.
The relative Raman intensity of this band n(C5H)
increases slightly compared to the band n(C6H) at
3079.7 cm
21
indicating different association for C5
H and C6H groups.
In this analysis seems that the addition of water
increases the association in the solid state around
the C5yC6 moiety and that the water preferentially
H-bonds to C5H than C6H group. Contrarily to
that expected, the hydrophilic groups appear in the
Raman spectrum little affected with the hydration,
while the hydrophobic groups show larger changes.
This feature is in accordance to the analysis of crystal-
lographic data on hydration of bases reported [59]
from single crystals of oligonucleotides (DNA), in
which demonstrates that hydrophilic and hydrophobic
atoms in the major and the minor grooves are hydrated
and that the hydration of oligonucleotides can be
described only as a dynamic phenomenon even in
the crystalline phase.
The existence of CH O interactions has been
well established as weak H-bonds. However, recently
[60] this type of interaction has been included as an
`improper H-bonding' with spectral shifts opposite to
those of standard H-bonding. Thus, instead of a
M.A. Palafox et al. / Journal of Molecular Structure (Theochem) 585 (2002) 6992 80
M.A. Palafox et al. / Journal of Molecular Structure (Theochem) 585 (2002) 6992 81
Fig. 2. Raman spectra of 8 mg polycrystalline uracil: (a) dry, and (bd) with different water contents.
lengthening of the XH bond together a frequency
decrease of the CH stretching, the improper H-
bond leads to a shortening of the CH bond and a
frequency increase. The CH p improper H-bond-
ing has been theoretically predicted and experimen-
tally detected by double resonance ion-depletion
infrared spectroscopy. Analysis of the electron density
suggests that the specic features of the improper H-
bonds are originated from a redistribution of the elec-
tron density in the CH bond induced upon complexa-
tion. The electron density at the CH bond critical
point (bcp) increases if an improper H-bond is formed
while it decreases if a standard H-bond is formed [61].
For the CH O improper H-bond in uorofor-
m ethylene oxide has been reported [62] a shorten-
ing of 0.001 A

in the CH bond and an increase in the

frequency (,30 cm
21
) of the CH stretching mode
together a lowering in the intensity of this vibration.
These three characteristics are the same that those
observed for stacking interaction of nucleobases in
aqueous solution [63]. In the present study, the
observed intensity and frequency changes upon the
uracil hydration could be interpreted in terms of stan-
dard H-bonds with water molecules, and improper H-
bonds or stacking interactions.
The Raman frequencies were compared to the theo-
retical calculations. It is noted large differences in the
frequencies of the NH groups due to the isolated
molecule forms strong H-bonds with water in the
theoretical model, while the stacked structure of the
solid state impedes a strong interaction of the NH
groups to water when it is added in small amount.
However, a remarkable increase of the intensity is
observed in the band at 1393.6 cm
21
described as a
bending d(N3H) 1d(CH), indicating that the
hydration increases the polarizability of the N3H
bond.
With the assignments proposed in Table 2 and the
correspondence established with the experimental
data, remarkable differences are observed between
the calculated and experimental frequencies in the
ring modes of the uracil molecule, which are shown
in Table 3. The experimental values selected in the
second column of Table 3, were those reported in gas
phase by Colarusso et al. [43], and several in Ar
matrix. The rst column refers to the number of the
modes of Fig. 1. The bottom of the table shows the
root-mean square (rms) error obtained for the calcu-
lated frequencies with several of the methods used.
The largest errors are marked in bold type.
By HF and MP2 the vibrational frequencies are
usually calculated using the simple harmonic oscilla-
tor model, and therefore, they are typically larger than
the fundamentals observed experimentally. With DFT
methods the frequencies are signicantly close to the
experimental, although the results do not adequately
reproduce all the experimental pattern of frequencies
and intensities. The use of scale factors may solve this
problem.
Although the limitations of the DFT theory for
weak interactions have been reported [64], the effects
on the calculated frequencies is very small, a few
cm
21
for the modes involved in the interactions and
almost null for the other vibrations. Thus the benets
of the B3LYP method can be used, specially with the
scaling, leading to low errors, Table 4. When the
hydration is reproduced with only one or two water
molecules, the use of a continuous solvent gives to
better calculated frequencies [65]. However, when
three or more molecules are used to reproduce the
rst hydration shell, leads to the best results.
3.4. Scaling the frequencies
In this section, it is described how the calculated
frequencies can be directly scaled with three proce-
dures: using an overall scale factor, a scaling equation,
or specic scale factors for each mode.
3.4.1. With a single overall scale factor for each
calculation level
The calculated frequencies of a molecule at a speci-
c level of theory are scaled with a unique scale factor
which is common for all the molecules with the same
level of calculation.
Several scale factors have been reported at different
levels, but we considered to be more satisfactory those
reported by Scott et al. [7]. These authors recom-
mended using two scale factors, one for high frequen-
cies, and another for low frequencies.
The rms errors and the largest positive and negative
errors are shown in Table 4. In parenthesis is indicated
the number of the mode, according to Fig. 1, with the
largest error. With ab initio methods, the error is
remarkably reduced using this procedure, especially
in HF with more than eight times. However in several
M.A. Palafox et al. / Journal of Molecular Structure (Theochem) 585 (2002) 6992 82
M
.
A
.
P
a
l
a
f
o
x
e
t
a
l
.
/
J
o
u
r
n
a
l
o
f
M
o
l
e
c
u
l
a
r
S
t
r
u
c
t
u
r
e
(
T
h
e
o
c
h
e
m
)
5
8
5
(
2
0
0
2
)
6
9

9
2
8
3
Table 3
Values of the absolute error (v
cal.
2n
exp.
) in cm
21
, obtained in the calculated frequencies of uracil, and scaled frequencies
No. Non-hydrated uracil Uracil Uracil 13H
2
O
a
Scaled freq.
a
1H
2
O
a
Uracil Uracil 13H
2
O
f
Exp. freq. HF
c
MP2
d
B3P86
c
B3LYP
c
B3LYP
a
B3PW91
c
B3LYP
b
HF B3LYP B3PW91 B3LYP
e
B3LYP
e
B3LYP
g
1 171.1 90.9
2 185 26 224 214 215 220 214 188.2 193.9 191.7
3 391 35 28 26 26 24 26 3 48 22 20 400.0 434.3 427.4
4 395 34 216 2 1 0 1 214 19 1 9 407.6 438.1 427.0
5 512 49 6 7 7 11 6 1 48 17 14 529.7 549.7 532.6
6 536.4 57 5 7 5 7 6 15 72 29 30 548.8 567.8 555.7
7 559 50 1 1 21 1 0 20 68 25 28 565.0 583.1 591.7
8 545 43 21 26 18 2 25 222 143 224 242 552.6 715.6 698.8
9 659.5 70 38 33 27 17 32 676.6 767.1 752.6
10 717.4 86 65 15 12 11 14 725.2 779.5 773.1
11 756.5 105 235 3 25 8 2 760.5 792.9 790.6
12 759.2 47 244 21 210 213 23 212 48 22 5 764.3 816.7 837.9
13 802 103 23 12 11 17 12 812.0 939.8 933.2
14 952 101 38 23 13 10 18 948.4 965.5 969.8
15 972 138 242 21 22 0 1 23 126 22 22 957.9 983.6 999.0
16 990 86 9 4 0 4 3 29 72 28 27 978.9 987.5 999.0
17 1073 102 40 25 18 13 24 23 86 7 12 1066.7 1085.7 1092.7
18 1172 134 64 38 26 19 37 1166.8 1204.0 1210.3
19 1217.4 160 86 53 44 40 50 11 87 13 20 1201.2 1219.2 1205.4
20 1356 174 57 32 26 26 31 26 216 109 117 1349.0 1369.9 1377.6
21 1387 167 49 30 20 19 28 20 154 27 38 1371.9 1408.1 1424.5
22 1400 157 49 28 22 23 26 242 71 253 250 1388.1 1464.4 1478.6
23 1461 186 75 59 45 37 57 28 162 33 41 1459.6 1495.8 1498.1
24 1641 206 71 63 49 29 60 25 174 23 33 1623.7 1621.7 1639.0
25 1741 254 85 89 67 16 85 1706.7 1676.1 1709.3
26 1756 256 112 112 89 35 108 55 223 54 71 1739.1 1715.2 1731.6
27 3076 318 187 158 145 124 155 120 284 120 127 3083.0 3061.0 3053.7
28 3124 305 180 157 140 118 154 148 308 148 159 3123.1 3083.0 3083.5
29 3436 427 176 207 184 156 206 3456.9 3123.0 3101.3
30 3484 418 172 198 174 152 197 3498.9 3289.9 3274.2
rms
h
184 82 77 66 54 75 70 151 76 82
a
With the 6-3111G(2d,p) basis set.
b
Complex A.
c
With the 6-31G
pp
basis set.
d
With the 6-31G
p
basis set.
e
With the scaling eqns.
f
Complex D.
g
With specic scale factors.
h
Rms, dened as (S(v
cal.
2n
exp.
)
2
/n)
1/2
, where the sum is over all the modes, n, and n
exp.
is from the second column.
modes the error is still very large, and far from the
desired accuracy, e.g. the vibrations nos. 25 and 26
with an error of ca. 50 cm
21
at HF level. MP2 remark-
ably fails for particular cases, e.g. modes nos. 11, 12
and 15 with an absolute error of ca. 80 cm
21
.
In B-based procedures is not observed a signicant
improvement with the scaling. However, with B3-
based procedures, the errors are remarkably reduced
and they are close to HF; but in both cases the errors
are larger than the wished accurate. A noticeable
improvement is reached with the use of a scaling
equation.
3.4.2. With a scaling equation
This procedure uses a scaling equation to correct
the computed frequencies of a molecule at a specic
level of theory. This scaling equation is determined in
an analogous, but simpler molecule. Thus for the
study of uracil derivatives, the scaling equation is
calculated in the uracil molecule.
Due to the differences in the gas phase data between
Harsanyi et al. [35] and Colarusso et al. [43], two sets
of scaling equations were determined. In Table 5, only
those with Colarusso et al. [43] are listed, because
with them a better correlation coefcient (r), and a
lower error in the scaled frequencies are obtained.
The resume with the rms errors obtained with this
procedure of scaling and the largest positive and
M.A. Palafox et al. / Journal of Molecular Structure (Theochem) 585 (2002) 6992 84
Table 4
Errors obtained in the calculated and scaled frequencies of the uracil modes by the different procedures and methods
Method Calculated frequencies Scaled frequencies with an overall
factor
Scaled frequencies with the
scaling equations
rms Largest error rms Largest error rms Largest error
Positive Negative Positive Negative Positive Negative
Non-hydrated uracil
HF/6-31G
pp
184 427 (29) 6 (2) 23 53 (25,26) 37 (12) 22.6 46 (26) 57 (28)
HF/6-3111G
pp
177 418 (29) 11 (2) 16.7 27 (19) 50 (28)
MP2/6-31G
p
82 187 (27) 44 (12) 37 53 (9) 95 (15) 25.4 50 (10) 66 (15)
BP86/6-31G
pp
35 86 (29) 44 (11) 33 56 (29) 50 (11) 18.1 34 (9) 32 (21)
BLYP/6-31G
pp
34 73 (29) 49 (11,15) 34 54 (29) 54 (15) 19.6 34 (9) 36 (21)
B3P86/6-31G
pp
77 207 (29) 14 (2) 24 46 (29) 44 (15) 15.0 32 (26) 26 (15)
B3LYP/6-31G
pp
66 184 (29) 15 (2) 21 44 (29) 40 (12) 13.8 24 (9) 23 (21)
B3LYP/6-3111G(2d,p) 54 156 (29) 20 (2) 13.7 21 (29) 34 (25)
B3PW91/6-31G
pp
75 206 (29) 14 (2) 25 50 (29) 41 (15) 14.9 30 (26) 26 (22)
Uracil 1H
2
O
a
B3LYP/6-3111G(2d,p) 49 148 (28) 242 (22) 26.2 39 (20) 77 (22)
Uracil 13H
2
O
b
HF/6-3111G(2d,p) 151 308 (28)
B3LYP/6-3111G(2d,p) 57 148 (28) 53 (22) 32.7 70 (20) 87 (22)
B3PW91/6-3111G(2d,p) 62 159 (28) 50 (22)
a
Complex A, without mode 8.
b
Complex B, without mode 8.
Table 5
Scaling equations n
scaled
a 1bv
calculated
obtained in uracil
molecule
Methods a b Correlation
coefent, r
HF/6-31G
pp
5.7 0.8928 0.9997
HF/6-3111G
pp
10.5 0.8938 0.9998
MP2/6-31G
p
34.5 0.9372 0.9996
BP86/6-31G
pp
46.0 0.9678 0.9998
BLYP/6-31G
pp
46.4 0.9718 0.9998
B3P86/6-31G
pp
34.1 0.9389 0.9999
B3LYP/6-31G
p
30.8 0.9468 0.9999
B3LYP/6-31G
pp
34.6 0.9447 0.9999
B3LYP/6-3111G(2d,p) 30.8 0.9538 0.9999
B3PW91/6-31G
p
30.1 0.9421 0.9999
B3PW91/6-31G
pp
34.9 0.9393 0.9999
negative errors are listed in Table 4. An analysis of
this table gives rise to the following conclusions: in
HF methods, the use of a scaling equation leads to an
error similar to that of an overall scale factor. MP2
calculations, although they require considerably more
computer time and memory than HF, show a higher
degree of error, and this method is not recommended.
It is noted that the DFT methods show a more reli-
able prediction for the calculated frequencies than
with the more expensive HF and MP2 methods. In
DFT methods, the use of the scaling equations reduces
the errors more than a 40% of those found with an
overall scale factor, showing that the errors in the
calculated frequencies with DFT methods are
systematic and partially associated with the kind of
molecules studied; and therefore they can be reduced
employing scaling equations determined in related
molecules.
The most cost-effective procedures found for
predicting vibrational frequencies are the B3-based
DFT procedures. The B-based DFT procedures,
while not performing quite as well as the correspond-
ing B3-based procedures, have the advantage of stan-
dard frequency scale factors close to unity, meaning
that they can often be used without scaling.
3.4.3. With a specic scale factor for each mode
It is well known that in organic molecules many of
the vibrational modes are localized and that many
functional groups have characteristic frequencies
that do not vary much between different molecules.
Therefore, considering groups of similar molecules,
scaling factors can be calculated, bringing the
computed frequencies in line with the available
experimental data. That is, the procedure is based on
the assumption that the ratios between experimental
and computed frequencies are fairly constant for each
type of characteristic frequency, such as CH stretch,
CCl stretch, NH
2
torsion, etc. It is then possible to
derive for known experimental spectra a correction
factor for each characteristic frequency by taking
the average of the ratios between the experimental
and computed frequencies, and to use them for
predicting or assigning unknown spectra.
The introduction of different scale factors for
distinct types of vibrational modes, instead of using
a uniform correction factor for all the modes, removes
the error which is systematic and associated with the
same mode in related molecules, improving the scaled
frequencies.
It should be noted that certain types of vibrational
modes are much more readily identied than others,
e.g. the stretches. On the other hand, many of the
torsion and out-of-plane modes are delocalized
throughout a wide range at low frequency, and it is
difcult to identify these modes or to differentiate
among them. Thus, the scale factors obtained for
these modes are not so transferable, and should be
considered with caution.
Previously, this procedure of scaling was applied to
several organic molecules with biological and phar-
macological applications, with errors lower than 3%
in the majority of the cases [6672]. For uracil deri-
vatives, Table 6 collects the specic scale factors
determined in the uracil molecule at several levels.
As examples of the adequacy of these procedures of
scaling, the present work shows the prediction of the
spectra of eight molecules: 5-uorouracil (5-FU),
5-bromouracil (5-BrU), 5-methyluracil (5-MeU),
5-nitrouracil (5-NU), 1-methyluracil (1-MeU),
2-thiouracil (2-TU), 3-methyluracil (3-MeU), and
1,3-dimethyluracil (1,3-DMeU), several of them
with great medical importance [7380]. The analysis
of their vibrational bands is collected in Table 7. It
appears that most of the uracil fundamentals absorb in
relatively narrow frequency ranges.
As experimental values, those reported mainly in
Argon matrix were used. We have changed the assign-
ments of several bands according to our scaled values.
For example, we have inverted the contribution of the
g(C4yO) and g(C5H) modes in the calculated
bands at 810 and 720 cm
21
of 1-MeU, and thus the
experimental bands at 802 and 712 cm
21
were
reassigned.
The rms errors obtained in the calculated and in the
scaled frequencies by the three procedures of scaling
are shown in Table 8. The large rms errors in the
calculated frequencies contradict to Rush et al. [91],
for whom a good agreement appeared for U, 1-MU, 5-
MU, between the calculated and experimental spectra,
even without scaling.
It is noted in these compounds that the NH
stretching modes are essentially pure group modes
and substitution only induces shifts of about 1% or
less. The NH in-plane bends are highly coupled
to other groups or ring modes and the inuence of
M.A. Palafox et al. / Journal of Molecular Structure (Theochem) 585 (2002) 6992 85
substitution is not straightforward. Methylation on
one of the N atoms slightly decreases the frequency
of the other NH mode. Methylation on N1 lowers
d(N3H) and methylation on N3 decreases d(N1H)
by about 3050 cm
21
.
The carbonyl stretching motion couples signi-
cantly with the N1H and N3H bending motions.
Replacement of a CyO group by the CyS group has
the largest effect on the NH stretching frequencies.
It also strongly increases the bending of the vicinal
NH, while substitution at C5 has a limited effect.
As far as the CyO fundamentals are concerned, the
out-of-plane modes are almost insensitive to substitu-
tion with the exception of the frequency decrease
(4050 cm
21
) of g(C4yO) in 5-substituted uracils.
The fact that these out-of-plane CyO modes remain
approximately (,1%) constant might be taken as
evidence for almost pure CyO group modes (C2yO)
or similar coupling (C4yO 1C5H) that uracil mole-
cule.
The frequency of the CyC stretching mode slightly
increases with methylation on N1 or N3 (the effect in
1,3-diMeU is additive), while a CyS or a C5X
substitution lowers this frequency, with the exception
of 5-FU. The CH modes are found at surprisingly
constant frequencies: d(C6H) 12101160 cm
21
,
d(C5H) 14001320 cm
21
, g(C6H) 1000
950 cm
21
, g(C5H) 730660 cm
21
.
M.A. Palafox et al. / Journal of Molecular Structure (Theochem) 585 (2002) 6992 86
Table 6
Calculated specic scale factors, n
exp.
/v
cal.
, for each normal mode of uracil molecule and at some of the levels considered
No. HF
a
MP2
b
BP86
a
BLYP
a
B3P86
a
B3LYP
b
B3LYP
a
B3LYP
c
B3PW91
a
2 1.0335 1.1491 1.1280 1.1212 1.0819 1.0882 1.0882 1.1212 1.0819
3 0.9178 1.0209 1.0625 1.0625 1.0156 1.0156 1.0156 1.0103 1.0156
4 0.9207 1.0422 1.0422 1.0395 0.9950 1.0000 0.9975 1.0000 0.9975
5 0.9127 0.9884 1.0260 1.0220 0.9865 0.9865 0.9865 0.9790 0.9884
6 0.9039 0.9908 1.0328 1.0328 0.9871 0.9889 0.9908 0.9871 0.9889
7 0.9179 0.9982 1.0429 1.0429 0.9982 1.0000 1.0018 0.9982 1.0000
8 0.9269 0.9629 0.9945 1.0037 0.9545 0.9715 0.9680 0.9963 0.9561
9 0.9041 0.9456 0.9851 0.9910 0.9524 0.9579 0.9607 0.9749 0.9538
10 0.8929 0.9169 1.0214 1.0228 0.9795 0.9822 0.9835 0.9849 0.9808
11 0.8782 1.0485 1.0617 1.0692 0.9960 1.0066 1.0066 0.9895 0.9974
12 0.9433 1.0596 1.0454 1.0553 1.0013 1.0116 1.0129 1.0169 1.0038
13 0.8862 1.0037 1.0308 1.0256 0.9853 0.9865 0.9865 0.9792 0.9853
14 0.9041 0.9616 1.0370 1.0337 0.9764 0.9835 0.9865 0.9896 0.9814
15 0.8757 1.0452 1.0463 1.0531 1.0010 1.0031 1.0021 1.0000 0.9990
16 0.9201 0.9910 1.0345 1.0366 0.9960 0.9980 1.0000 0.9960 0.9970
17 0.9132 0.9641 1.0151 1.0229 0.9772 0.9799 0.9835 0.9880 0.9781
18 0.8974 0.9482 1.0200 1.0362 0.9686 0.9742 0.9783 0.9840 0.9694
19 0.8812 0.9324 0.9958 0.9950 0.9573 0.9588 0.9643 0.9674 0.9596
20 0.8863 0.9597 1.0226 1.0249 0.9769 0.9755 0.9812 0.9812 0.9776
21 0.8925 0.9659 1.0259 1.0335 0.9788 0.9809 0.9858 0.9865 0.9802
22 0.8992 0.9662 1.0211 1.0189 0.9804 0.9790 0.9845 0.9838 0.9818
23 0.8871 0.9512 1.0041 1.0111 0.9612 0.9663 0.9701 0.9753 0.9624
24 0.8885 0.9585 1.0061 1.0130 0.9630 0.9699 0.9710 0.9826 0.9647
25 0.8727 0.9534 0.9977 1.0104 0.9514 0.9624 0.9629 0.9909 0.9534
26 0.8728 0.9400 0.9826 0.9949 0.9400 0.9512 0.9518 0.9805 0.9421
27 0.9063 0.9427 0.9805 0.9812 0.9511 0.9529 0.9550 0.9612 0.9520
28 0.9110 0.9455 0.9802 0.9836 0.9521 0.9556 0.9571 0.9636 0.9530
29 0.8895 0.9513 0.9756 0.9792 0.9432 0.9536 0.9492 0.9566 0.9434
30 0.8929 0.9529 0.9781 0.9822 0.9462 0.9571 0.9524 0.9582 0.9465
a
With the 6-31G
pp
basis set.
b
With the 6-31G
p
basis.
c
With the 6-3111G(2d,p) basis set.
M
.
A
.
P
a
l
a
f
o
x
e
t
a
l
.
/
J
o
u
r
n
a
l
o
f
M
o
l
e
c
u
l
a
r
S
t
r
u
c
t
u
r
e
(
T
h
e
o
c
h
e
m
)
5
8
5
(
2
0
0
2
)
6
9

9
2
8
7
Table 7
Vibrational wavenumbers at B3LYP/6-31G
pp
level and experimental ones in cm
21
and error obtained in the scaled values with the three procedures of scaling
Ring
mode
5-Fluorouracil 5-Bromouracil 5-Methyluracil
Frequencies Absolute error
a
Frequencies Absolute error
a
Frequencies Absolute error
a
No. Cal. Exp.
b
(1) (2) (3) Cal. Exp.
c
(1) (2) (3) Cal. Exp.
d
(1) (2) (3)
1 153 167 214 12 153 154 152 2 28
2 117 109 8 36 18 111 100 11 39 21
3 388 414 225 213 220 395 390 6 18 11 387 394 26 6 21
4 377 365 12 26 11 391 397 391 7 19 5
5 536 460? 462 21 7 28
6 300? 536 532 5 9 21 606? 617 210 210 217
7 628? 633 24 25 24 598 594 5 6 5 545 540 6 9 6
8 545 545 1 4 217 566 548? 19 21 0 563 541 23 25 4
9 674 638 37 33 10 680 656 25 21 23 686 689 22 26 230
10 741? 735 7 0 26 767 767 1 28 213
11 746 757
c
210 218 26 753 749 755 25 213 21
12 748 768 219 227 210 737 761 223 230 214
13
e
347 331 16 31 11 776 760 17 8 6 300? 321 221 23 225
14 969? 949 217 1 7 971 962? 228 210 24 966 963 234 216 210
15 888 895 241 222 25 928 906? 214 5 24 910 885 210 9 27
16
f
455 464 28 0 29 278? 280 22 17 22
17 817? 809 9 23 25 1047 1048
g
241 224 218 805 804 230 29 212
18 1160 1169 1154
g
230 225 210 1158 1078?
19 1187 1182
c
241 226 237 1196 1189
g
239 225 236 1201 1154 1 15 4
20 1355 1349 246 234 219 1353 1327 226 214 1 1379 1357 231 220 24
21 1398 1386
c
242 231 28 1396 1377
g
235 224 21 1400 1395 249 238 215
22 1431? 1424 248 238 215 1411 1390
g
233 222 21 1426 1409 238 227 25
23 1507 1477
c
228 219 215 1493 1458
g
223 213 210 1499 1472 231 221 218
24 1732 1685
c
220 214 23 1679 1635 221 214 25 1714 1668 220 214 24
25 1813 1742
c
1 5 4 1808 1729 9 14 12 1792 1725 22 3 1
26 1846 1754
c
21 25 3 1847 1761 15 18 23 1843 1772 0 4 218
27 3243 3067 51 31 30 3236 3058 53 34 32 3213 3076 13 26 28
28
h
1285 1224 11 25 6 1236 1178 10 24 5
29 3617 3416
c
61 36 17 3616 3425
g
51 25 7 3619 3437 42 16 22
30 3662 3468
c
53 26 20 3654 3471
g
42 16 9 3659 3484 34 7 1
M
.
A
.
P
a
l
a
f
o
x
e
t
a
l
.
/
J
o
u
r
n
a
l
o
f
M
o
l
e
c
u
l
a
r
S
t
r
u
c
t
u
r
e
(
T
h
e
o
c
h
e
m
)
5
8
5
(
2
0
0
2
)
6
9

9
2
8
8
Table 7 (continued)
Ring
mode
5-Nitrouracil 1-Methyluracil 2-Thiouracil
Frequencies Absolute error
a
Frequencies Absolute error
a
Frequencies Absolute error
a
No. Cal. Exp.
g
(1) (2) (3) Cal. Exp.
g
(1) (2) (3) Cal. Exp.
i
(1) (2) (3)
1 141 160 178
j
218 8 123
p
2 264 233 266
k
233 211 212 168
3 384 387 389 21 11 4 270 269 1 21 5
4 403 422
l
218 27 220 406 402 5 16 3 402
5 542 534 9 13 1 467 462 6 14 21 537 530 8 12 0
6 628 626 3 2 24 543 538 6 10 0 493 491 3 9 23
7 641 625 619 7 6 7
8 618 112?
m
153
j
620 604 17 16 24
9 685 661 25 21 23 683 659 25 21 23 716 694 23 17 26
10 720 712 9 3 24 745 710 36 28 23
11 750 753 22 210 2 756 761 23 211 1 653
n
12 778 775 4 25 13 758 749 10 2 19 719 727 27 213 1
13 810 802 223 22 23 806
14 966 971 963 229 211 25 911 907 231 212 28
15 988 956 26 12 34 966 987
o
? 258 240 219 972
16 1044? 1003 986 222 24 17
17 1106 1170? 1150 225 210 1 1085 1060 217 0 7
18 1183 1180 243 228 223 1202? 1177? 221 27 21 1212 1191 226 211 25
19 1224 1194 217 23 214 1351? 1320 221 29 217 1238 1223 233 219 229
20 1341? 1311 222 210 5 1390 1358 222 210 6 1389 1363 228 216 0
21 1393? 1377 238 226 24 1415 1386 226 215 9 1407 1376 223 212 11
22 1416 1393 232 221 1 1464 1418
k
211 0 23 1460 1430 226 216 7
23 1516 1475 218 28 24 800?
q
790 11 0 214 1576 1534 219 211 25
24 1679 1640 226 219 210 1686 1638 217 211 21 1681 1634 218 211 22
25 1833 1752 10 14 13 1807 1705? 32 37 35 1816 1738 8 12 11
26 1859 1773 14 18 24 1818 1738 10 14 28 1162
r
27 3249 3215 3024
o
? 67 48 46 3224 3068 32 12 11
28 3262 3091 45 25 31 3265 3108 31 11 17
29 3612 3419 54 28 10 3619 3430 49 23 5 3609 3415 55 29 11
30 3639 3456 43 16 10 1233
s
1188 23 11 214 3643 3457 45 19 13
M
.
A
.
P
a
l
a
f
o
x
e
t
a
l
.
/
J
o
u
r
n
a
l
o
f
M
o
l
e
c
u
l
a
r
S
t
r
u
c
t
u
r
e
(
T
h
e
o
c
h
e
m
)
5
8
5
(
2
0
0
2
)
6
9

9
2
8
9
Table 7 (continued)
Ring
mode
3-Methyluracil 1,3-Dimethyluracil
Frequencies Absolute error
a
Frequencies Absolute error
a
No. Cal. Exp.
c
(1) (2) (3) Cal.
t
Exp.
u
(1) (2) (3)
1 121 207?
2 166 258?
3 344 356
4 419 400 20 30 18 427
5 405? 513 512
v
2 7 26
6 543 540 4 8 22 632 613
v
20 19 13
7 589 583 7 8 7 480? 477
v
4 11 4
8 569 104?
m
9 225
m
129?
m
10 727 721 7 0 26 715 712?
11 751 760 28 216 24 753 763 29 217 25
12 706 815
13 810 810 1 210 211 808 803 226 25 26
14 868 946 921
v
212 7 12
15 966 974 245 227 26 962 989 264 246 225
16 1090? 1070 222 26 20 1190?
17 1130? 1081
18 1232 1212 227 214 27 1155 1140 230 214 210
19 1292 1274 232 219 228 1370? 1339 222 210 218
20 504
q
502 3 9 27 400?
q
404
c
23 8 212
21 1401 1400 1375 229 218 5
22 1414 1398 239 228 26 1488 1446 215 26 19
23 1507 1471 222 213 29 684
q
664 21 17 0
24 1696 1648 217 211 21 1693 1656
c
228 222 212
25 1773 1697 8 13 10 1800 1724 7 11 9
26 1824 1744 10 14 28 1764 1686 10 15 27
27 3221 3070
c
27 7 6 3213 3070
c
19 0 22
28 3264 3262
29 1180
s
1288
s
1242? 24 9 219
30 3657 3480 36 9 3 1257
s
a
D(n
scaled
2n
exp.
) where n
scaled
is: (1) with an overall scale factor; (2) with a scaling equation; (3) with specic scale factors for each mode.
b
Ref. [81].
c
In Ar matrix Ref. [82,83].
d
Ref. [43].
e
g(C5-X) mode.
f
d(C5X) mode.
g
Ref. [85,86].
h
n(C5X) mode.
i
In Ar and N matrix Ref. [87].
j
Ref. [89].
k
Raman in the crystal Ref. [90].
l
Ref. [84].
m
g(NX) mode.
n
g(C2yX) mode.
o
Ref. [82,83].
p
g(N2C2yX).
q
d(NX) mode.
r
n(C2yX) mode.
s
n(NX) mode.
t
Ref. [65].
u
In gas phase Ref. [88].
v
Ref. [46,47].
The strong coupling of the group modes in the
uracil spectrum remains highly constant for their deri-
vatives or its variation is directly related to the elec-
tron donating or withdrawing effects of substituents.
4. Resume and conclusions
The normal modes of uracil structure were charac-
terized and described by the different semiempirical,
ab initio and DFT methods with a higher basis sets
than those reported. The structural and vibrational
characteristics of the rst hydration shell were
analyzed through realistic molecular models. The
frequency and intensity changes on Raman bands on
hydration are shown to be sufcient to discuss hydra-
tion of uracil in terms of normal modes affected by
water interactions. This information may be important
to understand the structure of the hydration shells.
The accuracy of these quantum chemical methods
in predicting the spectra was compared. To improve
the calculated frequency values, three procedures
were proposed, two of them new. A list with scaling
equations and specic scale factors for each mode is
collected to be used in uracil derivatives. The scaling
equation procedure gives rise to a slight improvement
in the predicted frequencies, that when a single overall
scale factor is used.
B3-based DFT procedures provide a very cost-
effective means of determining harmonic vibrational
frequencies. They show better results than HF- and
MP2-based procedures.
Use of scale factors transferred from uracil mole-
cule permits us to make an a priori prediction of the IR
bands of uracil derivatives of sufcient quality to
conrm many of the previously assigned fundamental
modes and to suggest several alterations.
The selected scaling procedure depends on the size
of the organic molecule and the accuracy required for
the predicted frequencies. With large organic mole-
cules, but less than 30 atoms, HF, MP2 and DFT
methods and large basis sets can be used to calculate
frequencies. If the accuracy required is not very high,
then the use of one or two scale factors, one for higher
and another for lower frequencies is the simplest and
easiest procedure. In this case, among the HF, MP2
and DFT methods, the most cost-effective are the HF
and the B3-based. If the accuracy required is high,
then specic scale factors for each mode should be
used.
With molecules larger than 30 atoms, semiempiri-
cal methods, and HF and DFT methods with small
basis set, can be used to calculate frequencies.
However, because the cost-effective ratio with HF
and DFT methods is very high versus semiempirical
methods, their use is less recommended. In contrast
the AM1 and SAM1 semiempirical methods, when a
specic scale factor for each mode is used, give good
predicted frequencies, with error lower than 5%. In
general, both the use of an adequate level of computa-
tion and the application of a suitable scaling proce-
dure are required to obtain the desired accuracy in the
frequencies.
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