FTIR and FT-Raman spectra and density functional computations of the vibrational spectra, molecular...

JOURNAL OF RAMAN SPECTROSCOPYJ. Raman Spectrosc. 2007; 38: 1227–1241Published online 22 August 2007 in Wiley InterScience(www.interscience.wiley.com) DOI: 10.1002/jrs.1725

FTIR and FT-Raman spectra and density functionalcomputations of the vibrational spectra, moleculargeometry and atomic charges of the biomolecule:5-bromouracil

V. K. Rastogi,1∗ M. A. Palafox,2 L. Mittal,3 N. Peica,4 W. Kiefer,4 K. Lang5 and S. P. Ojha1

1 Department of Physics, CCS University, Meerut-250 004, India2 Departmento of Quimica-Fisica (Espectroscopia), Facultad de Ciencias Quimicas, Universidad Compultense, Madrid-28040, Spain3 Department of Physics, Inderprastha Engineering College, Ghaziabad-201010, India4 Institut fur Physikalische Chemie, Universitat Wurzburg, Am Hubland, D-97074 Wurzburg, Germany5 Department of Kinetics, Institute of Inorganic Chemistry, Academy of Sciences of Czech Republic

Received 12 October 2006; Accepted 4 January 2007

FTIR and FT-Raman spectra of 5-bromouracil in the powder form were recorded in the region400–4000 cm−1 and 50–4000 cm−1, respectively. The observed wavenumbers were analysed and assignedto different normal modes of vibration of the molecule. Quantum chemical calculations were performedto support the assignments of the observed wavenumbers. The performance of the B3LYP hybrid densityfunctional (DFT) method was compared with other methods. With the 6–31 G∗∗ and 6–311+G(2d,p) basissets, the calculated geometry, dipole moments and harmonic vibrations were determined. A comparisonwith the uracil molecule was made, and specific scale factors were deduced and employed in the predictedwavenumbers of 5-bromouracil. The total atomic charges and thermodynamic parameters were calculated,and are discussed briefly. Structure and harmonic vibrations of 5-bromouracil were also calculated in thepresence of water within a simple model with one molecule. It is observed that the bromine atom atposition 5 exhibits smaller inductive effects than the fluorine atom, producing a small distortion of theelectrostatic potential around the ring and a reduction of the molecular dipole moment. Copyright 2007John Wiley & Sons, Ltd.

KEYWORDS: FTIR and FT-Raman spectra; density functional computations; molecular geometry; atomic charges;biomolecule; 5-bromouracil

INTRODUCTION

The halogenated pyrimidines were synthesised in the 1950sas potential anti-tumour agents after the discovery thatcertain tumours preferentially incorporated uracil ratherthan thymine into the DNA.1 Among these compoundsthe 5-halogenated uracils deserve special attention. Trans-formation of uracil into 5-X uracil (X = halogen) significantlychanges its chemical and spectroscopic properties, as wellas its in vivo activity. They have been found to exert pro-found effects in a variety of microbiological and mammaliansystems. It has been suggested that 5-halogeno deriva-tives may adopt rare hydroxy forms more easily than thenon-substituted uracil and therefore can act as a stronger

ŁCorrespondence to: V. K. Rastogi, Department of Physics, CCSUniversity, Meerut-250 004, India.E-mail: v [email protected]

mutagenic agent. Extensive work, both theoretical and exper-imental, have been done on uracil and its derivatives.2 – 5

5-Chlorouracil and 5-bromouracil (5-BrU) have been studiedto treat inflammatory tissues.6,7 The 5- and 6-halouracils havealso been investigated as a possible class of radio-sensitisers,which are used to control damage to healthy tissues in radi-ation therapy.8 However, their vibrational spectra have notbeen completely and accurately interpreted. This task canbe satisfactorily carried out with the use of density func-tional theory (DFT). As a first step towards this study of5-halogenated pyrimidines, we have studied the vibrationalspectra of 5-fluorouracil: an anticancer drug.3 This com-pound is widely recognised today as an effective treatmentmodality, especially with tumours of the head, neck andbreast.1,4 DNA normally contains uncommon nucleotidesusually in very small amount. 5-Bromouracil is one of thewell-known uncommon nucleotide bases and has the ability

Copyright 2007 John Wiley & Sons, Ltd.

1228 V. K. Rastogi et al.

to co-ordinate metals or to bind to tissues via metals. Inorder to extend this study further, the present work has beenundertaken on 5-bromouracil, which also interfaces with thegrowth of cancer cells.

Substitution of thymine with 5-BrU in DNA is knownto change interaction between DNA and proteins (increasethe cross-linking efficiency and reduce the direct damage),thereby inducing various biological phenomena.9,10 TheseDNA-interacting sites have been identified.11,12 Severalstudies reveal its great medicinal importance.3,13 5-BrUforms complexes with MS2 RNA-protein.14 Incorporatedinto nuclear DNA, 5-BrU is a well-known mutagen,15 andrepairs the replication of damaged DNA in UV irradiatedbacteria.16 In contrast to DNA, the presence of 5-BrU inDNA-PNA (peptide nucleic acid) chimeras destabilised thetriple helix.17 Mixed-ligand complexes of Co(II), Ni(II),Cu(II), Zn(II) and Cd(II) with adenine as primary ligandand 5-BrU as secondary ligand have been reported.18 – 22

Oligonucleotides containing 5-BrU have been used to studythe radiation-induced electron migration (a mechanism thatrandomly can lead to a damage along DNA) in nucleicacids.23 – 25

From spectroscopy point of view, 5-BrU in the gasphase has been studied by several experimental techniques,such as dissociative electron attachment (DEA),26 electronicabsorption and fluorescence emission spectra,27,28 NMR29,30

and ESR.31 Its vibrational spectra have been also studiedwithout any theoretical support: the Raman spectra byRai,32 and the FTIR in an Ar-matrix by Graindourzeet al.,33,34 Gusakova et al.,35 Srivastava et al.36 and Sanyalet al.37 However, there are doubts in the assignment ofseveral bands because the compound is highly fluorescent innature.38,39 In our previous work, IR and Raman studies onthis molecule have also been reported, but again withouttheoretical support.40 During the process of preparationof the present paper, a good report on the Ar-matrix IRspectra of 5-halouracils has also been published.41 However,the present work on 5-BrU remarkably improves upon theearlier results, identifying all the bands for the first timeand reviewing the assignments of several bands. Hartree-Fock (HF) and density functional ab initio calculations wereperformed to support our wavenumber assignments. To thebest of our knowledge, such studies have not been reportedearlier on 5-BrU.

The specific interactions between the purine and pyrim-idine bases are one of the corner stones of molecularbiology. These interactions, which underlie the transmis-sion of genetic information, are governed in large part by theNHÐ Ð ÐO or NHÐ Ð ÐN hydrogen bonds, and they are expectedto depend not only on the proton acceptor ability of the Oor N atoms but also on the intrinsic acidity of the NH bondsinvolved in the interaction. As first step in this study andto shed more light on the accurate prediction of geometryand spectroscopic characteristics of the molecule in questionin the gas phase and in water, detailed MO calculations can

be compared with the earlier reported data of uracil.42 Thehydration of 5-halo derivatives have been reported only in5-FU.43,44

EXPERIMENTAL

5-Bromouracil (solid state) of spectral grade was purchasedfrom M/s Aldrich Chemical Co (Milwankee, WI, USA) andused as such without any further purification.

The FT-Raman spectrum of 5-BrU was recorded at roomtemperature in the powder form in the region 50–4000 cm�1

on a Bruker IFS66 optical bench with an FRA 106 Ramanmodule attachment. The sample was mounted on the sampleilluminator using an optical mount and no sample pre-treatment was undertaken. The NIR output (1064 nm) ofan Nd : YAG laser was used to excite (the probe) thespectrum. The instrument was equipped with a liquid-nitrogen-cooled Ge detector. The laser power was set at100 mW and the spectrum was recorded over 1000 scans at afixed temperature. The spectral resolution was 6.0 cm�1 afterapodisation.

The mid-infrared spectrum of the compound from400–4000 cm�1 was recorded with a Perkin Elmer FTIRmodel 1760 X instrument, using the KBr technique with1 mg sample per 300 mg KBr. For the spectrum acquisition,four scans were collected at 4 cm�1 resolution.

COMPUTATIONAL METHODS

Ab initio calculations45 with wavefunction-based HF andMP2,46 and DFT47 were used. The DFT hybrid methods withthe Becke exchange functional (B)48 and the Becke’s three-parameter exchange functional (B3),49,50 and in combinationwith the correlational functional of Lee, Yang and Parr(LYP),51 Perdew 1986 (P86),52,53 Perdew and Wang’s 1991(PW91),54,55 and modified Perdew-Wang 91 (MPW1PW91)56

were used. These hybrid functionals were selected for theirbetter predicting ability of the molecular properties. The basissets used in this work are the two standard ones widely usedfor quantum chemical studies because of their reasonablequality and size: 6–31GŁŁ and 6–311CG(2d,p). Dunning’scorrelation-consistent basis sets double (cc-pVDZ) and triple-zeta (cc-pVTZ) have also been used.57 – 59 The presence ofboth polarization and diffuse functions in the basis setis necessary for a proper theoretical description of themolecular parameters. These procedures are implementedin the Gaussian 98 program package,60 which was utilized inthe Unix version with standard parameters.

The optimum geometry was determined, with thekeyword OPT, by minimising the energy with respectto all geometrial parameters without imposing molecularsymmetry constraints. Berny optimization under the tightconvergence criteria was used. Harmonic wavenumberswere calculated to characterise the stationary points and toevaluate the wavenumber shifts due to complex formation

Copyright 2007 John Wiley & Sons, Ltd. J. Raman Spectrosc. 2007; 38: 1227–1241DOI: 10.1002/jrs

FTIR and FT-Raman spectra of 5-bromouracil 1229

with water. The keyword Freq D Raman was used for thistask and at the same level of the respective optimisationprocess. The keyword Raman was employed to obtainRaman values. All the optimised structures showed positiveharmonic vibrations only (true energy minimum). For thecalculation of the zero-point vibrational energy (ZPE), thewavenumbers were retained unscaled.

RESULTS AND DISCUSSIONS

Geometry optimisationNon-hydrated formThe optimised bond lengths and angles for 5-BrU usingab initio and DFT methods are given in Table 1, while thelabelling of the atoms is plotted in Fig. 1. For comparisonpurposes, in the last three columns of Table 1 are collectedthe experimental data reported by X-ray and by electrondiffraction (ED) in the uracil molecule,61 – 63 together withtheir calculated values by B3LYP.

When the bromine atom is introduced in the position 5 ofthe uracil molecule, a small effect is observed in the molecularstructure, e.g. the calculated C C and C–C bond lengthsat B3LYP/6-31GŁŁ level in 5-BrU, 1.3513 A and 1.4699 A,respectively, appear very close to those determined in uracilmolecule, 1.3498 A and 1.4602 A, respectively. The otherbond lengths are observed to change insignificantly. Theangles C–C5 C and O C4 N3 in 5-BrU are found to be120.37° and 120.87°, respectively, which are fairly close tothe corresponding values of 119.94° and 120.38° in uracil.However, large errors were determined3 in 5-FU.

Figure 1. Labeling of the atoms in 5-BrU.

Except at the HF level, the calculated bond lengthsappear very close to the ED results of uracil, while theydiffer remarkably with the X-ray data.61 – 63 The calculatedC O bond lengths are sensitive to the inclusion of electroncorrelation. Its value is significantly underestimated by HF(1.19 vs 1.21 A reported experimentally in the gas phaseof uracil). As a result of H-bonding, the observed C Obond length obtained by X-ray diffraction is about 0.02 Alonger than in the gas phase of uracil. The lengths of theC–N and C–C single bonds are intermediate between thecorresponding aromatic and the saturated bonds, i.e. somearomatic character is on the ring structure.

With the increase of the basis set, the N–C, N–H,C C and C O bond lengths are slightly shortened, andthe C–C–Br angle is slightly opened. Among the methodsused, BLYP shows the longest calculated bond lengths. MP2computes N–C, C C, N–H, C O and C–Br bond lengthsremarkably longer than HF and much closer to B3LYP thanto HF. The results with the aug-cc-pVTZ basis set are similarto those obtained by using 6-311CCG(3df,pd) basis set.

The angles, in general, have not shown appreciabledifferences, at different levels, from those of the uracilmolecule. The molecule is completely planar, so the torsionalangles are 0 or 180°.

Hydrated formSpecial attention has been paid to the hydration because thebiological functions of nucleic acids are dependent on theirinteractions with the surrounding water. This interactiontakes place through both hydrophilic and hydrophobicsites forming two hydration shells, clearly described in thebibliography. To simulate theoretically the hydration effects,three procedures have been suggested64: (1) empirical scalingof the quantum mechanical force constants of the isolatedmolecule;65 (2) use of continuum model66 or (3) modellingof the solvated compound by a molecular complex withwater.67 The continuum model procedure has a solidtheoretical ground and is used mostly today, owing to mainlyits simplicity and the lower computation time required.However, from a strictly theoretical point of view, the thirdprocedure may be preferred, provided that the size of theconsidered complex is not too large. If this procedure is usedwith several water molecules, the first hydration shell canbe better reproduced than by using the continuum model.Therefore, for high accuracy this procedure is preferred inthe present work.

The presence of water is considered within a simplemodel with only one molecule, and in three positions,complexes A–C, which appear schematised at B3LYP levelin Table 2, making two simultaneous H-bonds to an aminohydrogen and to a carbonyl oxygen. A small difference inenergy appears among these conformations, the most stableone being the complex A. As in uracil molecule42 and itsderivatives44 the relation of stability is:

complexes A > complexes C > complexes B.



Tab

le1.

Geo

met

rical

par

amet

ers,

bon

dle

ngth

s(in

A)a

ndan

gles

(ind

egre

es)o

f5-B

rU

HF

B3L

YP

Ura

cila

Par

amet

ers

6–31

GŁŁ

6–31

CCG

ŁŁM

P2/

6–31

GŁŁ

BL

YP/

6–31

GŁŁ

B3P

86/

6–31

GŁŁ

6–31

GŁŁ

6–31

1C

G(2

d,p

)6–

311C

CG(3

df,p

d)

aug-

cc-

pVD

Zau

g-cc

-pV

TZ

B3P

W91

/6–

31G

ŁŁ

MPW

1P

W91

/6–

31G

ŁŁ

B3L

YP/

aug-

cc-

pVT

ZX

-ray

bE

lect

ron

diff

ract

ion

Bon

dle

ngth

sN

1–C

21.

3729

1.37

191.

3887

1.40

991.

3876

1.39

351.

3886

1.38

751.

3921

1.38

771.

3894

1.38

611.

3895

1.36

9(2)

c1.

395(

6)c

C2–

N3

1.37

021.

3693

1.38

691.

4008

1.38

111.

3865

1.38

191.

3806

1.38

561.

3808

1.38

241.

3793

1.37

941.

369(

2)c

1.39

1(6)

c

N3–

C4

1.38

891.

3887

1.40

431.

4273

1.40

191.

4087

1.40

601.

4051

1.40

971.

4050

1.40

421.

4006

1.40

801.

369(

2)c

1.41

5(6)

c

C4–

C5

1.47

041.

4704

1.46

611.

4766

1.46

411.

4699

1.46

481.

4652

1.47

001.

4651

1.46

601.

4639

1.45

461.

430(

3)1.

462(

8)C

5C

61.

3290

1.33

011.

3534

1.36

401.

3494

1.35

131.

3448

1.34

481.

3539

1.34

501.

3505

1.34

781.

3435

1.34

0(2)

1.34

3(24

)N

1–C

61.

3694

1.36

931.

3751

1.38

511.

3692

1.37

471.

3718

1.37

031.

3761

1.37

051.

3702

1.36

811.

3709

1.35

57e

1.39

6N

1–H

0.99

440.

9950

1.00

841.

0178

1.00

881.

0098

1.00

871.

0084

1.01

121.

0066

1.00

891.

0071

1.00

62–

1.00

2d

C2

O1.

1920

1.19

411.

2225

1.22

811.

2133

1.21

571.

2110

1.20

921.

2178

1.21

071.

2138

1.21

111.

2117

1.23

0(2)

c1.

212(

3)C

4O

1.18

891.

1907

1.22

371.

2288

1.21

321.

2156

1.21

021.

2081

1.21

631.

2098

1.21

361.

2107

1.21

431.

230(

2)c

1.21

1(3)

C–B

r1.

8758

1.86

701.

8802

1.90

731.

8680

1.88

471.

8912

1.88

561.

8923

1.88

661.

8728

1.86

84–

1.86

(2)f

–B

ond

angl

esN

–C2–

N11

3.52

113.

5811

2.30

112.

1711

2.69

112.

6311

2.90

112.

8411

2.96

112.

8411

2.62

112.

7111

3.06

114.

0(1)

114.

6(20

)C

–N3–

C12

8.33

128.

1812

9.47

129.

2712

9.01

128.

9512

8.56

128.

6812

8.67

128.

6712

9.08

129.

0112

7.97

126.

7(2)

126.

0(14

)N

–C4–

C11

3.08

113.

4311

2.27

112.

1711

2.59

112.

6011

2.90

112.

8011

2.78

112.

8111

2.52

112.

6011

3.61

115.

5(1)

115.

5(18

)C

–C5

C11

9.71

119.

2512

0.61

120.

9312

0.35

120.

3712

0.19

120.

1812

0.30

120.

1812

0.36

120.

2911

9.85

118.

9(2)

119.

7(21

)C

2–N

1–H

115.

7011

5.87

115.

1511

4.99

115.

1011

5.12

115.

4111

5.41

115.

4011

5.41

115.

1211

5.12

115.

18–

115.

7d

N3–

C2

O12

3.62

123.

5612

4.28

124.

7812

4.33

124.

3812

4.15

124.

1812

4.12

124.

1912

4.38

124.

3112

4.22

122.

3e12

1.6e

C4–

N3–

H11

6.02

116.

0911

5.39

115.

3811

5.62

115.

5911

5.77

115.

6911

5.72

115.

7011

5.55

115.

5911

6.32

––

N3–

C4

O12

0.89

120.

6212

1.25

120.

8012

0.98

120.

8712

0.58

120.

6412

0.57

120.

6312

0.95

120.

9812

0.23

119.

1e12

0.2

C4–

C5–

Br

118.

4611

8.85

117.

9511

7.89

117.

8211

7.97

118.

2811

8.30

118.

3111

8.30

117.

9211

7.91

118.

23–

118.

1d

C5

C6–

H12

2.25

122.

1512

2.49

122.

6312

2.24

121.

6612

2.37

122.

3612

2.47

122.

3712

2.31

122.

2612

2.65

–12

2.8d

aFr

omR

ef.4

1.b

From

Ref

.42.

cM

ean

valu

e.d

Fixe

dpa

ram

eter

.e

Det

erm

ined

wit

hth

ed

ata

repo

rted

inR

efs

41,4

2.fIn

brom

oben

zene

[52,

53].



Tab

le2.

Eq

uilib

rium

geom

etrie

sat

the

B3L

YP

/6–

311

CG

(2d

,p)l

evel

ofhy

dra

ted

5-B

rUw

ithon

ew

ater

mol

ecul

e.B

ond

leng

ths

are

inA

,and

bon

dan

gles

ind

egre

es

Bon

dle

ngth

sC

ompl

exA

Com

plex

BC

ompl

exC

Bon

dan

gles

Com

plex

AC

ompl

exB

Com

plex

CIn

tera

tom

ican

gles

Com

plex

AIn

tera

tom

ican

gles

Com

plex

BIn

tera

tom

ican

gles

Com

plex

C

N1–

C2

1.37

891.

3831

1.39

22N

–C2–

N11

3.90

114.

0011

3.19

N1–

HÐÐ

Ð O13

144.

98N

3–H

ÐÐÐ O

1314

3.85

N3–

HÐÐ

Ð O13

144.

99C

2–N

31.

3761

1.37

281.

3811

C2–

N3–

C4

128.

1712

7.76

127.

77C

2O

ÐÐÐ H

1510

8.75

C2

OÐÐ

Ð H15

109.

17C

4O

ÐÐÐ H

1511

1.27

N3–

C4

1.40

901.

4058

1.39

58N

3–C

4–C

511

2.67

113.

1411

3.92

H7Ð

ÐÐ O–H

1413

5.06

H9Ð

ÐÐ O–H

1413

1.45

H9Ð

ÐÐ O–H

1413

1.93

C4–

C5

1.46

191.

4673

1.46

04C

4–C

C12

0.18

120.

2811

9.91

H7Ð

ÐÐ O–H

1585

.14

H9Ð

ÐÐ O–H

1585

.77

H9Ð

ÐÐ O–H

1584

.64

CC

1.34

651.

3436

1.34

59C

2–N

1–C

612

3.05

123.

4312

3.75

O8Ð

ÐÐ H15

–O14

2.64

O8Ð

ÐÐ H15

–O14

1.37

O10

ÐÐÐ H

15–O

142.

34N

1–C

61.

3690

1.37

351.

3683

N3–

C2

O12

2.99

124.

2812

4.37

C2–

N1–

H7Ð

ÐÐ O�6

.17

C2–

N3–

HÐÐ

Ð O�5

.45

C4–

N3–

HÐÐ

Ð O�5

.55

C2

O1.

2230

1.22

241.

2103

C4–

N3–

H11

5.83

117.

1611

5.45

N1–

HÐÐ

Ð O–H

1411

6.89

N3–

HÐÐ

Ð O–H

1411

7.70

N3–

HÐÐ

Ð O–H

1411

6.32

C4

O1.

2102

1.20

941.

2210

N3–

C4

O12

0.40

120.

7912

0.92

N1–

HÐÐ

Ð O–H

157.

76N

3–H

ÐÐÐ O

–H15

8.79

N3–

HÐÐ

Ð O–H

158.

31C

5–B

r1.

8919

1.89

141.

8919

C4–

C5–

Br

118.

2511

8.30

118.

61N

1–C

2O

ÐÐÐ H

151.

88N

3–C

2O

ÐÐÐ H

151.

63N

3–C

4O

ÐÐÐ H

151.

54R

Ca

:A19

1521

2813

65µ

(Deb

ye)

4.01

84.

783

3.45

5C

2O

ÐÐÐ H

15–O

1.91

C2

OÐÐ

Ð H15

–O5.

10C

4O

ÐÐÐ H

15–O

4.28

B44

644

655

7bT

otal

Enb

.962

310

.959

050

.959

799

O8Ð

ÐÐ H15

–O–H

14�1

39.8

6O

8ÐÐÐ H

15–O

–H14

�138

.96

O10

ÐÐÐ H

15–O

–H14

�138

.29

C36

236

939

6Z

PEc

63.7

1063

.522

63.5

63H

7ÐÐÐ O

–H15

ÐÐÐ O

8�4

.08

O8Ð

ÐÐ H15

–OÐÐ

Ð H9

�6.7

9H

9ÐÐÐ O

–H15

ÐÐÐ O

10�5

.99

aC

alcu

late

dro

tati

onal

cons

tant

sin

MH

z.b

�306

4.(A

U).

cZ

ero-

poin

tvib

rati

onal

ener

gyin

Kca

l/m

ol.



This fact has been attributed to the larger acidity of theN1–H bond than that of the N3–H bond and the largerbasicity of the O8 atom than that of the O10 atom.44 From thevalues of the total atomic charges (Table 6) it can be notedthat the negative charge on O8 is slightly higher than that onO10, while on N1 it is lower than on N3. The positive chargeon H9 is very close to that of H7 or slightly larger. Thesefeatures lead to remarkably shorter O8Ð Ð ÐH15 and H7Ð Ð ÐO13intermolecular bonds in complex A (i.e. the most stable) thanthose in complex C, which in turn are shorter than those incomplex B.

The water molecule slightly changes the geometry andcharge distribution. The main effect observed on hydrationis lengthening of the N–H and C O bonds involved in theintermolecular H-bonds by 0.01 A. By contrast, the neigh-bours N–C bonds (or N–C and C–C, complex C) shrank by0.005 A. This resembles in behaviour of a typical amide bondin water (enhanced amide resonance due to solute–solventinteraction68). As expected, the C–H bonds are not sensitiveto the presence of water, and the C–Br bond has a very smalllengthening, 0.0007 A. Under hydration, the carbonyl oxy-gen and the amino nitrogen involved in the H-bonds showmore negative charge, by 0.04 and 0.06 respectively, whilethe hydrogen amino is more positive, by 0.08.

The data presented in Table 2 indicate that the inter-molecular distances depend on the nature of the substituentsimplanted on the uracil ring. In uracil42 the OHwaterÐ Ð ÐOdistances vary within the limits of 1.92–1.96 A and theNHÐ Ð ÐOwater distance between 1.94 and 2.00 A, while in5-FU44 the values are 1.96–1.99 A and 1.92–1.97 A, respec-tively. This fact has been discussed in terms of the protonaffinities and deprotonation enthalpies of the bonds or atomsinvolved in the interaction with water.

The O13Ð Ð ÐH7 intermolecular bond in the complex A,1.9165 A, is slightly shorter than that corresponding tohydrated uracil,42 1.9400 A, while the O8Ð Ð ÐH15 (1.9623 A) islarger than in uracil, 1.9424 A. Thus the H7Ð Ð ÐO–H15 angleis opened (85.14 vs 83.69° in uracil) and the O8Ð Ð ÐH15–O13is closed (142.64 vs 144.47° in uracil). The H2O molecule incomplexes B and C is slightly rotated with a C4 OÐ Ð ÐH15–Oangle of approximately 5°, while in complex A by approxi-mately 2°. The values are analogous to uracil.42

Other hydration forms can also be formed with a waterdimer instead of the water monomer, or complexes withdifferent amounts of water, to reproduce the first hydrationshell.42 Another possibility could be through the bromineatom, with two simultaneous H-bonds to Br atom and tocarbonyl oxygen. This possibility, pointed out by Del Bene43

with low ab initio calculations for 5-FU, was not real in 5-BrU.Calculations performed at B3LYP/6-311Cg(2d,p) level giverises to the form shown in Fig. 2, with the H2O moleculeplaced symmetrically on the bromine atom, and with anintermolecular distance of 3.10 A, far for the consideration ofan intermolecular H-bond.

Figure 2. Optimum form computed by B3LYP/6-311CCG(2d,p)for the interaction of bromine atom with one H2O molecule.

Rotational constants, dipole moments, energy and har-monic ZPE for each system are also included at the bottomof Table 2. As in the uracil molecule,42 a significantly higherdipole moment is predicted for the complex B (the less stable)than for the complex A (the most stable). Complex C has thelowest dipole moment but it is only slightly more stable thancomplex B.

Vibrational wavenumbersThe present molecule belongs to the Cs point group withthe normal mode distribution 21a0 C 9a00. According to theselection rules, both a0 and a00 vibrations are allowed inRaman and IR spectra; a0 vibrations are totally symmetricand give rise to polarized Raman lines, whereas a00 vibrationsare antisymmetric and give rise to depolarized Raman lines.

The vibrational bands computed with our theoreticalmethods are shown in Table 3. The first and second columnslist their calculated wavenumbers at the HF/6-31GŁŁ andHF/6-31CCGŁŁ levels with their relative infrared intensities(the third column), their Raman activities (the fourth column)and the depolarization ratios (the fifth column). The relative



intensities (and activities) were obtained by normalisingthe computed value to the intensity of the strongest line.The 6–19th columns collect the calculated values with theMPW1PW91, B3P86, B3LYP and B3PW91 methods. In the lastcolumn appears the percentage contribution of the differentmodes to a computed wavenumber. Contributions lowerthan 10% were not considered. The correspondence with theuracil ring modes36 appears in the previous column. It isobserved that most of the vibrational wavenumbers arise onaccount of mixing of different normal modes.

The observed IR and FT-Raman lines of 5-BrU along withtheir relative intensities are collected in Table 4. The IR datahave been reported in Ar-matrix by Graindourze et al.,33,34

Szczesniak et al.69 and Nowak et al.,70 columns 15–16th, andRaman lines by Rai,32 column 19. Our results in the solidstate, columns 17–18, complete these data specially in thelow-wavenumber region. For simplicity, the last column withthe assignments include only the contributions of the pre-dominant modes. Figures 3 and 4 show respectively, the FTIRand FT-Raman spectra of 5-BrU recorded in the solid state.

For comparison with our theoretical calculations, withexperimental only those wavenumbers were selected thatwere reported in Ar-matrix,69,70 but complemented with thevalues of Graindourze et al.33,34 and our Raman data. Onemay note that the computed wavenumbers correspond toAr-matrix or to solid state. Remarkable differences appearamong these data. The intermolecular forces present in thesolid state play a dominant role in modifying the magnitudesand intensities of the wavenumbers. However, in Ar-matrixthese forces are very low and therefore their wavenumberswere selected for the comparison, and thus a satisfactoryone-to-one correspondence can be established in Table 4. Theintensity of a band is another factor for its selection. Thus theexperimental band37 at 3058 cm�1 was chosen instead of theweak band33,34 at 3040 cm�1. This selection was in accordancewith our theoretical calculations. Table 4 also shows therevised assignment of several infrared bands, e.g. the bandat 906 cm�1 was reassigned as �(C6–H) instead of ring.33,34

The assignments for several modes are obvious andrequire no further discussion and therefore only a briefanalysis is given here. A general analysis of the differentmodes is as follows:

N–H modesThree fundamental modes are expected to appear above3000 cm�1, namely (C–H), (N1–H) and (N3–H) stretchingmodes. The C–H stretching appears in the 3030–3080 cm�1

range, while the N–H stretches are in 3420–3490 cm�1

range. These modes are essentially pure group modes, andare comparable to uracil or its other derivatives42,71; thesubstitution only induces shifts of about 1% or less. TheN–H stretching modes were calculated with medium IRintensity in accordance with the experimental results. Also,these modes were determined as the strongest Raman bandsin contrast to their non-detection in the Raman spectrum,

and may be due to fluorescence. In 5-FU the strongestRaman intensity corresponds to the C6–H stretching. Thepredicted values for the (N–H) stretching modes agreewell with the Ar-matrix data.33,34 Considerable loweringof the wavenumber of these modes is observed in the solidstate, indicating the presence of strong intermolecular forcesin 5-BrU. The lower magnitude of the stretching (N3–H)vibrational mode is due to the involvement of the H-atom atthe N3 position in the hydrogen bonding (with the O atomat the C4 position) of the type C OÐ Ð ÐH-N.

The N-H in-plane bendings are highly coupled to theother group or ring modes.

C O modesThe typical pattern of the absorption bands due to the C Ostretching vibrations of uracil and its derivatives is alwaysvery complex, and appears as very broad and strong IRbands. The C2 O vibrational mode was calculated by theDFT methods with the strongest IR intensity, which agreeswith the experimental value and higher than that of C4 Ovibrational mode. By contrast, by using HF the mode, C4 Oappears at a higher intensity than C2 O. In the uracilmolecule,71 mode C4 O appears by HF and DFT methodswith higher IR intensity than that of C2 O mode, althoughby DFT methods the difference in IR intensity is very smallwhile by HF it is very high (approximately 3 times). Asmall coupling is determined among the C2 O, C4 O andN–H modes. Under substitution, the mode remains almostunchanged, and thus the calculated wavenumbers of theC O modes in 5-BrU is observed close to uracil, only fewcm�1 higher, and they shift towards lower wavenumbersunder hydration.

The oxygen atom at the C4 position is involved inhydrogen bonding and therefore, the C2 O stretching modeis expected to appear at a higher wavenumber than theC4 O mode. The lower wavenumber of this mode in thesolid state and its broad intensity are due to different andstrong intermolecular forces through this group.

The planar bending modes due to C2 O and C4 Obonds are assigned at lower wavenumbers than the corre-sponding non-planar bending modes.

C–Br modesThe predicted C–Br stretching vibration at approximately620 cm�1 is in range reported in the literature,72 545 š75 cm�1. The in-plane C–Br deformation predicted at approx-imately 290 cm�1 is also in accordance with the literaturevalues, 300 š 60 cm�1, and it was assigned to the banddetected at 300 cm�1. However, the out-of-plane (C–Br)deformation is predicted at approximately 100 cm�1, far fromthe 230 š 65 cm�1 range reported for this mode as such theRaman band at 101 cm�1 has been assigned to this mode.72

C C and ring modesThe wavenumber of the (C C) stretch is slightly loweredwith the 5-X substitution of uracil, with the exception of 5-FU.



Tab

le3.

Vib

ratio

nalw

aven

umb

ers

(incm

�1)o

bta

ined

in5-

BrU

atd

iffer

ent

theo

retic

alle

vels

HFb

MPW

1PW

91B

3P86

B3L

YPf

B3P

W91

Ura

cil

wav

.aw

av.

IcA

dD

ep.e

wav

.aIc

wav

.aw

av.j

wav

.aw

av.

IcA

dD

ep.a,

eD

ep.e

Red

.gfo

rc.h

wav

.aIc

sym

.m

ode

Cha

ract

eris

atio

ni

3896

3888

1310

0.1

937

0219

3679

3628

.336

5336

32.7

1710

0.2

3.1

91.

088.

3936

7718

a030

100%

,v(N

1–H

)38

5838

479

69.2

336

6313

3639

3585

.036

1635

89.5

1176

.28

.23

1.08

8.18

3638

12a0

2910

0%,v

(N3–

H)

3410

3405

067

.33

3267

032

4832

25.4

3237

3213

.70

62.3

4.3

11.

096.

6632

470

a027

100%

,v(C

6–H

)20

1719

8753

35.1

218

8510

018

7017

94.7

1847

1793

.310

014

.21

.18

7.99

15.1

418

6710

0a0

2678

%,v

(C2

O)C

11%

,v(

C4

O)C

10%

,υ(N

–H)

2001

1971

100

24.5

618

4867

1831

1761

.618

0817

59.1

6524

.33

.38

9.20

16.7

718

2865

a025

76%

,v(C

4O

)C11

%,

v(C

2O

)C10

%,υ

(N3–

H)

1846

1839

1566

.14

1708

1116

9516

65.5

1679

1662

.011

36.1

7.1

45.

518.

9616

9211

a024

70%

,v(C

5C

6)C

20%

,v(r

ing)

1641

1638

1012

.59

1519

1615

0714

84.4

1493

1486

.112

10.5

9.4

92.

443.

1815

0515

a023

60%

,υ(N

1–H

)C38

%,v

(rin

g)15

4715

476

4.3

614

3714

1425

1404

.014

1114

08.8

132

.54

.61

2.11

2.47

1423

14a0

2265

%,v

(rin

g)C

30%

,υ(N

1–H

)15

6015

5911

1.6

914

122

1400

1392

.413

9613

99.8

51

.71

.75

2.50

2.89

1400

2a0

2175

%,υ

(N3–

H)C

14%

,υ(N

1–H

)C

10%

,υ(r

ing)

1482

1482

142

.28

1369

113

5913

42.7

1353

1346

.62

22.3

3.2

61.

831.

9613

571

a020

65%

,υ(C

6–H

)C20

%,v

(rin

g)C

13%

,υ(N

1–H

)13

2813

306

2.4

712

236

1211

1193

.811

9611

91.6

121

.52

.58

1.89

1.58

1208

8a0

1960

%,υ

(N1–

H,C

6–H

)C38

%,

v(ri

ng)

1255

1255

91

.14

1195

911

8711

62.7

1170

1156

.13

2.7

4.6

64.

373.

4411

857

a018

52%

,v(N

1–C

6)C

46%

,v(r

ing)

1147

1154

63

.25

1073

810

6310

49.7

1053

1055

.28

1.2

8.2

97.

074.

6410

628

a017

100%

,v(r

ing)

1062

1063

15

.56

989

198

197

0.4

971

970.

82

2.6

6.6

43.

001.

6697

92

a014

32%

,υ�N

3–H

�C

28%

,υ�C

6–H

�C

15%

,v(C

–N)C

18%

,υ(r

ing)



1074

1124

12

.75

937

292

792

1.8

928

926.

02

2.7

5.7

51.

39.7

092

62

a0015

97%

,�(C

6–H

)84

083

91

12.0

579

00

784

772.

177

777

8.5

019

.11

.74

9.23

3.30

783

0a0

1210

0%,v

(rin

g)87

290

03

2.7

578

85

782

772.

577

677

3.5

41

.75

.07

9.00

3.17

781

5a00

1060

%,�

(C4

O)C

40%

,�

(N3–

H)

852

849

70

.75

763

875

575

5.5

748

757.

88

0.7

5.7

510

.62

3.59

754

8a00

1153

%,�

(C2

O)C

34%

,�

(C4

O)C

13%

,�(r

ing)

726

738

81

.75

689

1168

569

1.0

681

667.

512

3.7

5.7

51.

150.

3068

411

a009

68%

,�(C

–N3–

H)C

32%

,�

(rin

g)68

068

34

2.1

863

56

630

625.

762

662

9.2

61

.56

.34

7.20

1.68

630

6a0

–75

%,υ

(rin

g)C

20%

,v(C

–Br)

650

648

06

.25

604

060

059

3.6

598

597.

60

5.3

7.2

86.

611.

3960

00

a07

60%

,υ(r

ing)

C40

%,υ

(CO

)59

159

56

0.7

557

610

574

585.

756

755

1.3

92

.75

.75

1.11

0.20

573

10a00

898

%,�

(N1–

H)

587

588

14

.20

542

153

853

5.8

536

539.

52

3.3

2.2

28.

231.

4153

71

a06

100%

,υ(r

ing)

437

436

32

.55

400

339

739

3.5

395

397.

03

2.5

7.4

812

.29

1.14

396

3a0

353

%,υ

(CO

)C35

%,υ

(rin

g)42

948

83

1.7

539

63

393

393.

839

238

8.1

32

.75

.75

2.91

0.26

393

3a00

468

%,�

(C–H

)C32

%,�

(rin

g)30

630

90

5.2

729

10

289

283.

328

528

3.9

03

.32

.26

18.2

60.

8728

80

a0–

70%

,υ(C

–Br)

C30

%,υ

(rin

g)30

435

21

0.7

528

60

284

274.

428

126

8.2

00

.75

.75

11.2

90.

4828

40

a00–

75%

,�(N

CC

)C25

%,�

(C–H

)20

119

80

1.7

218

70

185

183.

318

618

3.2

01

.73

.72

13.0

00.

2618

50

a0–

80%

,υ(C

–Br)

C20

%,υ

(rin

g)16

817

00

0.7

515

50

155

154.

215

314

8.7

00

.75

.75

8.75

0.11

154

0a00

167

%,�

(CO

)C18

%,�

(rin

g)96

970

0.7

592

091

89.8

9187

.20

1.7

5.7

510

.84

0.05

920

a00–

37%

,�(C

O)C

29%

,�(C

–Br)

C22

%,�

(N1–

H)C

12%

,�(r

ing)

aW

ith

the

6–31

GŁŁ

basi

sse

t.b

Wit

hth

e6–

31CC

GŁŁ

basi

sse

t.c

I,re

lati

vein

frar

edin

tens

itie

sin

%.

dA

,rel

ativ

eR

aman

inte

nsit

ies

in%

.e

Ram

and

epol

ariz

atio

nra

tios

.fW

ith

the

6–31

1C

G(2

d,p

)bas

isse

t.g

Red

uced

mas

s(a

mu)

.h

Forc

eco

nsta

nts

(md

yneA

�1).

iB

yB

3LY

P/6–

311

CG

(2d

,p).

j Wit

hth

eau

g-cc

-pV

DZ

basi

sse

t.



Tab

le4.

Sca

led

wav

enum

ber

s(in

cm�1

)by

seve

ralp

roce

dur

esin

5-B

rUw

ithth

e6

–31

GŁŁ

bas

isse

t

Wit

han

over

all

scal

efa

ctor

aW

ith

one

scal

ing

equa

tion

bW

ith

two

scal

ing

equa

tion

sfW

ith

spec

ific

scal

efa

ctor

sbE

xper

imen

talg

HF

B3L

YP

HF

B3L

YP

B3L

YPc

B3L

YPd

MP

W1

PW91

eB

3LY

PcM

PW

1PW

91H

FB

3P86

B3L

YP

B3L

YPc

MP

W1

PW91

IRh

IRi

IRj

Ram

anj

Ram

ank

Ura

cil

mod

eA

ssig

nmen

t

3503

3513

3484

3486

3496

3491

3488

3478

3475

3479

3481

3479

3481

3481

3459

3471

m–

––

30�(

N1–

H)

3469

3476

3450

3451

3454

3450

3452

3438

3441

3432

3432

3432

3434

3433

3413

3425

m33

46w

?–

–29

�(N

3–H

)30

6631

1130

5030

9330

9631

0730

8230

9330

9230

9030

8930

9130

8930

9030

58l,

m–

3055

vs30

52.0

3058

27�(

C6–

H)

2904

vs28

95.6

w23

44s

1814

1776

1806

1779

1741

1741

1792

1760

1796

1760

1758

1758

1758

1760

1761

m–

1682

br16

75.3

vs17

7026

v(C

2O

)17

9917

3817

9217

4317

0917

1017

5817

2717

6117

4617

4217

4117

4317

4317

29m

1675

25v(

C4

O)

1660

1614

1654

1621

1616

1618

1627

1632

1630

1640

1632

1630

1633

1633

m16

35m

––

1618

.1s

–24

v(C

5C

6)14

95.0

m14

96–

–14

7614

3514

7114

4514

4814

4514

5114

6114

5314

5614

4914

4814

4914

4914

6314

58m

1440

s14

50.2

w14

4723

υ(N

1–H

)Cv(

ring

)13

9113

5713

8713

6813

7513

6813

7413

8513

7613

9113

9713

8913

8613

9714

0013

90m

–14

05.6

m14

2722

v(ri

ng)C

υ(N

1–H

)14

0313

4213

9813

5313

6613

5713

5113

7713

5313

9213

7013

7613

8113

7313

9713

77m

21υ(

N3–

H)

1333

1301

1329

1313

1315

1310

1311

1325

1312

1313

1328

1328

1321

1326

1327

m–

1342

s13

40.7

vs13

5020

υ(C

6–H

)Cv(

ring

)n

1194

1150

1191

1164

1167

1168

1174

1174

1175

1170

1159

1153

1153

1162

1192

1189

m12

29vs

1181

.1w

1255

19υ(

N1–

H,C

6–H

)Cv(

ring

)n

1128

1124

1126

1140

1133

1138

1148

1139

1149

1126

1150

1145

1138

1149

–11

54m

18v(

N1–

C6)

Cv(

ring

)10

3110

0710

3010

2910

3710

3010

3410

4110

3510

4710

3910

3610

4310

4110

5510

48m

1060

s10

53w

1060

17v(

ring

)95

593

495

495

295

795

595

695

895

696

095

895

896

196

096

2?m

–10

04m

1014

w10

0814

υ(N

3–H

,C6–

H)Cv

(C–N

)n

966

892

965

911

914

908

907

915

907

941

928

930

926

927

906?

m–

943m

945.

4w–

15�

(C6–

H)

870b

r–

872

––

763

777

756

769

773

765

770

771

770

792

785

787

792

786

––

–74

7.5w

–12

v(ri

ng)

793

777

784

768

769

766

768

766

768

779

766

763

762

766

760m

–77

8s–

873

10�

(C4

O)C

�(N

3–H

)n

774

749

766

741

754

750

745

751

744

748

752

753

750

752

753?

m–

755s

785.

1vs

750

11�

(C2

O)C

�(C

4O

)n

660

681

654

678

667

688

676

663

675

656

652

654

651

653

656m

–64

6vs

633.

9–

9�

(C–N

3–H

)C�

(rin

g)n

618

624

613

626

631

626

625

625

624

626m

–61

5w60

9.8s

––

υ(ri

ng)C

v(C

–Br)

n

591

599

586

600

601

595

596

595

595

597

599

599

597

599

594m

––

547.

9s58

07

υ(ri

ng)C

υ(C

O)



756

753

357

055

758

857

054

956

954

854

854

954

954

754

8m–

546v

s–

560

8�

(N1–

H)

534

537

530

541

545

540

539

538

537

531

531

531

533

532

532m

545

6υ(

ring

)44

2s39

739

639

640

840

940

440

639

940

440

140

340

140

140

339

0m–

419w

423.

8m42

53

υ(C

O)C

υ(ri

ng)n

390

392

389

405

401

404

402

390

400

395

391

391

388

391

390

4�

(C–H

)C�

(rin

g)n

278

283

279

304

302

299

304

289

302

–30

0.4m

––

υ(C

–Br)

Cυ(

ring

)0n

276

279

277

300

287

290

300

273

297

�(C

H)C

�(r

ing)

n

183

184

185

210

206

204

207

191

204

201.

0m–

–υ(

ring

)Cυ(

CB

r)13

8.5v

s15

315

315

617

917

317

617

715

717

412

5.6v

s–

1�

(CO

)C�

(rin

g)n

8790

9112

111

411

411

997

115

101.

1vs

––

�(C

O,C

–Br)C

�(N

1–H

)n

79.7

m–

aW

ith

0.89

92(H

F)an

d0.

9614

(B3L

YP

),an

dfo

rlo

w-w

aven

umbe

rvi

brat

ions

(<80

0cm

�1),

0.90

89(H

F)an

d1.

0013

(B3L

YP

),R

ef.4

9,50

.b

From

Ref

s27

,48.

cW

ith

the

6–31

1C

G(2

d,p

)bas

isse

t.d

Wit

hth

eau

g-cc

-pV

DZ

basi

sse

t;th

esc

alin

geq

uati

onus

edw

as:v

scal

.D

28.6

C0.

9543

vcal..

eW

ith

the

equa

tion

:vsc

al.D

32.7

C0.

9334

vcal..

fW

ith

the

scal

ing

equa

tion

s:vsc

al.

D12

.0C

0.97

49vca

l.�v

cal.

<20

00cm

�1�

and

vscal

.D

141.

4C

0.91

84vca

l.�v

cal.

>20

00cm

�1�

for

B3L

YP

/6–

311

CG

(2d

,p);

and

wit

hvsc

al.D

28.9

C0.

9375

vcal.

�vca

l.<

2000

cm�1

�an

dvsc

al.D

218.

8C

0.87

96vca

l.�v

cal.

>20

00cm

�1�

for

MPW

1PW

91.

gN

ote:

vs,v

ery

stro

ng;s

,str

ong;

m,m

ediu

m;w

,wea

k;br

,bro

ad.

hIn

Ar-

mat

rix,

Ref

.22.

iR

ef.5

1.j Pr

esen

twor

k.k

Ref

.21.

lFr

omR

ef.2

5.m

Val

uese

lect

edfo

rth

eth

eore

tica

lcom

pari

son.

nL

owco

ntri

buti

onof

this

mod

e.



Figure 3. Infrared spectrum of 5-BrU in solid state.

The null IR intensity predicted for mode 12 is inaccordance with the lack of bands in the IR spectra, but itwas computed with medium Raman intensity and thereforeit was observed at 747.5 cm�1.

Several combination and overtone lines were alsoobserved, and are included in Table 4.

ScalingTable 5 shows the rms (root-mean-square) errors obtainedwith the different methods and basis sets used in the presentwork. The second column shows the error in the calculatedwavenumbers. It is noted that a remarkably large erroris obtained by HF, while BLYP gives the lowest errors.The HF calculated results are usually more overestimatedthan the corresponding DFT ones, but even with these DFTmethods the error is too large for an accurate comparisonof our calculated wavenumbers with the experimental ones.Therefore, scaling is required.

It is well known that the calculated HF and DFT harmonicwavenumbers could significantly overestimate experimentalvalues because of a lack of electron correlation, insufficientbasis sets or anharmonicity. Much effort has been madeto reproduce accurately the experimental wavenumbers intheoretical calculations. Both uniform and individual scaling

Table 5. Errors (rms)Ł obtained in the calculated and scaledwavenumbers of 5-BrU by the different procedures, methodsand levels

Method (a) (b) (c) (d) (e)

HF/6–31GŁŁ 181 26.6 23.5 21.9 17.0HF/6–31CCGŁŁ 179 – 28.6 27.9 26.9BLYP/6–31GŁŁ 40 38.5 27.0 19.6 19.5B3P86/6–31GŁŁ 76 25.4 19.5 18.3 14.2B3LYP/6–31GŁŁ 67 25.9 18.7 16.6 15.2B3LYP/6–311 C G(2d,p) 55 – 18.6 15.0 15.6B3LYP/aug-cc-pVDZ – – – 14.4 14.2B3PW91/6–31GŁŁ 75 26.2 19.6 18.4 14.2MPW1PW91/6–31GŁŁ 86 – 19.0 18.3 13.9

rmsŁ, defined as (�ωcal � vexp�2/n�1/2, where the sum is over allthe modes, n, and vexp is from the second column: (a) calculatedwavenumbers; (b) scaled wavenumbers with an overall factor;(c) scaled with one scaling equation; (d) scaled with two scalingequations; (e) scaled wavenumbers with specific scale factors foreach mode.

of force constants and/or wavenumbers have been thesubject of substantial discussion in the literature.42,71,73 Thesescaling procedures are based on the transferability of theforce constants and/or the wavenumbers among similarmolecules and characteristic groups.

To improve the computed wavenumbers, in Table 4appears the scaled wavenumbers obtained by four pro-cedures.71 With the first one, all the computed wavenumbersat a specific level of theory were multiplied by a uniformscale factor.74 Another scale factor is required to be usedfor wavenumbers lower than 800 cm�1. Scale factors havebeen reported only for a few basis sets,74 and thereforethis procedure was not applied to several levels used inthe present work. The results obtained by HF and B3LYPmethods by applying this scaling are shown in the 1st and 2ndcolumns of Table 4. With this procedure error is remarkablyreduced, and the values obtained with the different methodsused are shown in the 3rd column of Table 5. With HF, thereduction is so large that the scaled wavenumbers are of

Figure 4. Raman spectrum of 5-BrU in solid state.



accuracy comparable to B3-methods. In B-based proceduresa significant improvement with the scaling is not observedand they have the largest errors. However, with B3-basedprocedures, the errors are remarkably reduced and they areclose to HF; but in both cases the errors are larger than therequired accuracy. A noticeable improvement is obtainedwith the use of a scaling equation.

The second scaling procedure uses specific scaling equa-tions obtained previously from the uracil molecule.71 Theresults obtained with HF, B3LYP, B3PW91 and MPW1PW91methods are listed in the 3rd to 7th columns of Table 4, whilethe rms errors are shown in the 4th column of Table 5. Animprovement of approximately 20% is achieved over theoverall scale factor procedure.

With the use of the scaling equation approach, thelow-wavenumber vibrations are usually predicted fairlyaccurately, while stretching wavenumbers appear overes-timated. By dividing the wavenumber range into two parts,and using one scaling equation for the 0–2000 cm�1 rangeand another one for the 2000–4000 cm�1 range, the error inthe stretching region is remarkably reduced.68 These equa-tions were obtained by linear fittings of the values for theuracil molecule. Thus the main purpose of this third proce-dure is to improve the scaled stretching wavenumbers. Thescaled values for B3LYP and MPW1PW91 are shown in the8th–9th columns of Table 4, while the rms errors obtainedappear in the 5th column of Table 5. A significant improve-ment is reached in 5-BrU, and notoriously in the uracilmolecule with a reduction of 33% error over one scalingequation (rms of 9.1 vs 13.7).

Again a new improvement can be carried out on thecomputed wavenumbers if specific scale factor proceduresare used. The scaled values obtained using this fourth scalingprocedure are listed in the 10th–14th columns of Table 4 andthe rms errors in the last column of Table 5. This scalingleads to the lowest errors. Individual scaling is however

more complex and time consuming, and thus this approachis less recommended to be used, except for special cases.

An overall conclusion is that the increase of the basisset has a small effect and the calculations with B3-basedmethods and with the 6-31GŁŁ basis set appear in generalto be useful with the best cost effective relationships, whenthey are combined with an adequate scaling procedure.

OTHER MOLECULAR PROPERTIES

The values of the Mulliken charge obtained with thetheoretical methods used are listed in Table 6. Close valuesare obtained between HF and MP2 ab initio methods, butthey differ considerably with the DFT results. Appreciabledifferences in values are also noted among the BLYP, B3P86and B3LYP methods.

Several thermodynamic parameters were also calculatedand collected in Tables 7 and 8. For an accurate predictionin determining the ZPVE (zero-point vibrational energies),the enthaply Hvib.�T�, and the entropy Svib.�T�, scale factorshas been reported74 for the 6-31GŁ basis set. Dipole momentshave been reported75 only for different excited states of5-BrU.

A replacement of the H11 atom by fluorine in 5-FU3

produces a slightly higher change of the local charge dis-tribution than the replacement by bromine atom. However,the calculated dipole moment by HF and MP2 in 5-FU3 islower than in 5-BrU, while by B3P86 and B3LYP it is slightlyhigher. Compared to uracil, the dipole moment in 5-BrU isvery much lower, e.g. at the B3LYP/6-311CG(2d,p) level is4.518 D in uracil and 4.028 D in 5-BrU. It is noted that with the6-31G** basis set, the value is overestimated by MP2 (4.57 D)and slightly underestimated by DFT methods. The increaseof the basis set remarkably improves the calculated values,which are more in accordance with the experimental ones,76

Table 6. Total atomic charges on the atoms

HF B3LYP

Atoms 6–31GŁŁ 6–31CCGŁŁMP2/

6–31GŁŁB3P86/6–31GŁŁ 6–31GŁŁ

6–311 C G(2d,p)

6–311CCG(3df,pd)

aug-cc-pVTZ

B3PW91/6–31GŁŁ

MPW1PW91/6–31GŁŁ

N1 �0.785 �0.628 �0.786 �0.613 �0.568 �0.409 �0.981 0.015 �0.615 �0.628C2 1.025 0.913 1.038 0.781 0.750 0.659 1.391 0.147 0.787 0.804N3 �0.836 �0.738 �0.843 �0.654 �0.606 �0.492 �0.964 0.186 �0.658 �0.672C4 0.853 0.281 0.862 0.639 0.611 0.268 1.045 0.391 0.646 0.662C5 �0.245 0.264 �0.242 �0.105 �0.061 0.482 0.004 0.146 �0.118 �0.134C6 0.257 �0.104 0.260 0.144 0.152 �0.329 0.369 �0.373 0.149 0.157H7 0.349 0.401 0.355 0.321 0.296 0.282 0.304 0.044 0.320 0.322O8 �0.589 �0.598 �0.605 �0.495 �0.487 �0.482 �0.783 �0.634 �0.495 �0.501H9 0.354 0.418 0.360 0.323 0.298 0.285 0.314 0.080 0.322 0.325O10 �0.554 �0.518 �0.578 �0.476 �0.471 �0.444 �0.766 �0.633 �0.475 �0.480Br11 �0.046 0.101 �0.043 �0.052 �0.068 0.036 �0.088 0.072 �0.049 �0.046H12 0.217 0.208 0.224 0.187 0.155 0.144 0.155 0.561 0.187 0.192



Table 7. Theoretical computed total energies (A.U.),zero-point vibrational energies (Kcal mol�1) and dipolemoments (Debyes) in 5-BrU

MethodsTotal energy

(RH)Zero-point

energyDipole

moments

HF/6–31GŁŁ �2981.77893 52.698 4.278HF/6–31CCGŁŁ �2981.81314 52.862 4.436MP2/6–31GŁŁ �2981.77257 – 4.574B3P86/6–31GŁŁ �2987.75006 48.836 3.907B3LYP/6–31GŁŁ �2985.92184 48.468 3.868B3LYP/6–311 CG(2d,p)

�2988.48631 48.095 4.028

B3LYP/6–311CCG(3df,pd)

�2988.51390 – 3.987

B3LYP/aug-cc-pVDZ �2988.43186 48.158 4.035B3LYP/aug-cc-pVTZ �2988.60290 – 3.978B3PW91/6–31GŁŁ �2985.75074 48.789 3.896MPW1PW91/6–31GŁŁ �2985.98067 49.204 3.917

4.1 š 0.01 D. The addition of diffuse functions increases thevalue of the dipole moment.

SUMMARY AND CONCLUSIONS

The calculated structure for 5-BrU appears coherent incomparison with the experimental values reported for uracil,with all the values well within the uncertainties of themethods used. The geometries and values of the propertiespresented here appear to be the most accurate to date.

The structural and characteristics of the first hydrationshell were analyzed through realistic molecular models. Thethree stable complexes determined with one water moleculeare the ones in which the oxygen atom of water accepts theacidic NH proton while donating a proton to the carbonyloxygen. The presence of water molecule increases harmonicvibration intensities of 5-BrU, and both C O and N–Hstretching wavenumbers appear at lower values.

The accuracy of different ab initio methods in predictingthe spectra was compared. To improve the calculatedwavenumbers, three procedures were used. The scalingequation procedure gives rise to a slight improvement inthe predicted wavenumbers, when a single overall scalefactor is used. With the use of two scaling equations asignificantly better accuracy is obtained for the predictedstretching wavenumbers. Use of scale factors transferredfrom uracil molecule permits us to make an a priori predictionof the IR and Raman bands of 5-BrU of sufficient quality toconfirm many of the previously assigned fundamental modesand to suggest several alterations. After proper scaling thecomputed wavenumbers were in good agreement with theobserved wavenumbers, except in a few cases. However,the computed intensities show marked deviations form theobserved values.

B3-based DFT procedures with 6-31GŁŁ basis set pro-vide a very cost-effective means of determining harmonicwavenumbers. They show better results than HF-and MP2-based procedures.

The bromine atom at position 5 exhibit smaller inductiveeffect than the fluorine atom, producing a small distortion ofthe electrostatic potential around the ring and a reduction ofthe molecular dipole moment.

REFERENCES

1. Morris SM. Mutat. Res. 1993; 297: 39.2. Dobrosz-Teperek K, Zwierzchowska Z, Lewandowski W, Baj-

dor K, Dobrowolski JCZ, Mazurek AP. J. Mol. Struct. 1998; 471:115.

3. Rastogi VK, Jain V, Yadav RA, Singh C, Alcolea Palafox M. J.Raman Spectrosc. 2000; 31: 595.

4. Schmittgen TD, Danenberg KD, Horikoshi T, Lenz HJ, Danen-berg PV. J. Biol. Chem. 1994; 269: 16269.

5. Rastogi VK, Singh C, Jain V, Alcolea Palafox M. J. RamanSpectrosc. 2000; 31: 1005.

6. Henderson JP, Byun J, Takeshita J, Heinecke JW. J. Biol. Chem.2003; 278: 32834.

7. Jiang Q, Bloun BC, Ames BN. J. Biol. Chem. 2003; 278: 32834.8. Denfil S, Ptasinsxa S, Gstir B, Scheier P, Mark TD. Int. J. Mass

Spectrom. 2004; 232: 99.

Table 8. Calculated values of rotational constants (GHz) and entropies (cal mol�1 K�1)

ParametersHF/

6–31CCGŁŁMP2/

6–31GŁŁB3LYP/

6–311CCG(3df,pd)B3LYP/

aug-cc-pVTZB3PW91/6–31GŁŁ

MPW1PW91/6–31GŁŁ

Rotational constants 3.036 2.963 2.986 2.985 2.979 2.993– 0.655 0.645 0.646 0.645 0.648 0.651– 0.538 0.529 0.531 0.530 0.532 0.535

Entropy: Total 86.53 – 89.07a 88.85b 88.64 88.46Translational 41.63 – 41.63a 41.63b 41.63 41.63Rotational 30.09 – 30.14a 30.16b 30.13 30.11Vibrational 14.81 – 17.30a 17.06b 16.89 16.71

a With the 6–31 C G(2d,p) basis set.b With the aug-cc-pVDZ basis.



9. Ogino H, Fujii M, Satou W, Suzuki T, Michishita E, Ayusawa D.DNA Res. 2002; 9: 25.

10. Katouzian-Safadi M, Charlier M. Biochimie 1994; 76: 129.11. Seki K, Ohkura K. Radioisotopes 1996; 45: 227.12. Katouzian-Safadi M, laine B, Charlier F, Cremet JY, Belaiche D,

Sautiere P, Charlier M. Nucleic Acids Res. 1991; 19: 4937.13. Chattapadhyay MK, Sengupta D, Sengupta S. Med. Sci. Res. 1995;

775: 775.14. Grahn E, Moss T, Helgstrand C, Fridborg K, Sundaram M,

Tars K, Lago H, Stonehouse NJ, Davis DR, Stockely PG, Liljas L.RNA Pubi, RNA Soc. 2001; 7: 1616.

15. Henderson JP, Byun J, William MV, Mueller DM, McCormick ML, Heinecke JW. J. Biol. Chem. 2001; 276: 7867.

16. Hanawalt PC. Mutat. Res. DNA Repair 2001; 485: 1.17. Ferrer E, Shevchenko A, Eritja R. Bioorg. Med. Chem. 2000; 8: 291.18. Singh UP, Ghose R, Ghose AK, Si RK, Geeta B, Sodhi A. Indian

J. Cancer Chemother. 1991; 33.19. Rastogi VK, Singh A, Chawla SC, Gupta SL. In proceeding 5th

International conference on the spectroscopy of biological molecules.Theophanides T, Anastasspoulou J, Fotopoulos N (eds). KluwerAcademis publisher: The Netherlands.

20. Rastogi VK, Lal B, Sharma YC, Jain CL. In Metal Ions in Biology,Proceedings International Symposium, 2nd, 1992; 184.

21. Singh R, Tyagi S, Singh S, Singh SM, Singh UP. Synth. React.Inorg. Met.-Org. Chem. 2002; 32: 853.

22. Singh S, Singh R, Babbar P, Singh UP. Trans. Met. Chem. 2000; 25:9.

23. Fuciarelli AF, Sisk EC, Zimbrick JD. Int. J. Radiat. Biol. 1994; 65:409.

24. Fuciarelli AF, Sisk EC, Miller JH, Zimbrick JD. Int. J. Radiat. Biol.1994; 66: 505.

25. Beach C, Fuciarelli AF, Zimbrick JD. Radiat. Res. 1994; 137: 385.26. Abdoul H-Carime, Huels MA, Bruning F, Illenberger E,

Sanche L. J. Chem. Phys. 2000; 113: 2517.27. Parkanyi C, Boniface C, Aaron JJ, Gaye MD, von Szentpaly L,

Ghosh R, RaghuVeer KS. Struct. Chem. 1992; 3(4): 277.28. Waghorne E, Duggan E, Will G, Fitzmaurice D, Mukherjee S.

Indian J. Phys. 1999; 73B: 671.29. Nagasaka B, Takeda S, Nakamura N. Chem. Phys. Lett. 1996; 222:

486.30. Rabbani SR, Edmonds DT, Gosling P. J. Magn. Reson. 1987; 72:

422.31. Sevilla MD, Swarts S, Riederer H, Huttermann J. J. Phys. Chem.

1984; 88: 1601.32. Rai JN. Proc. Ind. Acad. Sci. Chem. Sci. 1990; 102: 68.33. Graindourze M, Grootaers T, Smets J, Zeegers-Huyskens Th,

Maes G. J. Mol. Struct. 1990; 237: 389.34. Graindourze M, Grootaers T, Smets J, Zeegers-Huyskens Th,

Maes G. J. Mol. Struct. 1991; 243: 37.35. Gusakova GV, Kul’bida AI, Plekhova GN, Smolyanskii AL.

J. Appl. Spectrosc. 1987; 46: 381.36. Srivastava SL, Prasad Rohitashava M, Pandey VS. Spectrochim.

Acta 1984; 40A: 675.37. Sanyal NK, Srivastava SL, Goel RK. Indian J. Phys. 1977; 52 B:

108.38. Zwierzchowska Z, Dobrosz-Teperek K, Lewandowski W,

Kolos R, Bajdor K, Dobrowolski JCz, Mazurek AP. J. Mol. Struct.1997; 410–411: 415.

39. Dobrosz-Teperek K, Zwierzchowska Z, Lewandowski W, Baj-dor K, Dobrowolski JCZ, Mazurek AP. J. Mol. Struct. 1998; 471:115.

40. Rastogi VK, Arora S, Gupta SL, Sharma DK. Spec. Publ. Roy. Soc.Chem. 1991; 94: 401, (Spectrosc Biol Mol).

41. Dobrowolski Jan CZ, Rode JE, Kolos R, Jamroz MH, Bajdor K,Mazurek AP. J. Phys. Chem. 2005; 109: 216.

42. Alcolea Palafox M, Iza N, Gil M. J. Mol. Struct. (THEOCHEM)2002; 585: 69.

43. Del Bene JE. J. Phys. Chem. 1982; 86: 1341.44. Chandra AK, Uchimaru T, Zeegers-Huyskens T. J. Mol. Struct.

2002; 605: 213.45. Hehre WJ, Radom L, Schleyer PVR, Pople JA. Ab Initio Molecular

Orbital Theory. John Wiley and Son: New York, 1986.46. Pople JA, Krishnan R, Schlegel HB, Binkley JS. Int. J. Quantum

Chem. Quantum Chem. Symp. 1979; 13: 225.47. Seminario JM, Politzer P (eds). Modern Density Functional Theory;

A Tool for Chemistry, vol 2. Elsevier: Amsterdam, 1995.48. Becke AD. Phys. Rev. 1988; A 38: 3098.49. Becke AD J. Chem. Phys. 1992; 97: 9173.50. Becke AD J. Chem. Phys. 1993; 98: 5648.51. Lee C, Yang W, Parr RG. Phys. Rev. 1988; B 37: 785.52. Perdew JP. Phys. Rev. 1986; B 33: 8822.53. Perdew JP. Phys. Rev. 1986; B 34: 7406.54. Perdew JP, Wang Y. Phys. Rev. 1992; B 45: 13244.55. Perdew JP, Chevary JA, Vosko SH, Jackson KA, Pederson MR,

Singh DJ, Fiolhais C. Phys. Rev. 1992; B46: 6671.56. Adamo C, Barone V. J. Chem. Phys. 1998; 108: 664.57. Woon DE, Dunning TH Jr. J. Chem. Phys. 1993; 98: 1358.58. Peterson KA, Woon DE, Dunning TH Jr. J. Chem. Phys. 1994; 100:

7410.59. Wilson A, Van Mourik T, Dunning TH Jr. J. Mol. Struct.

(THEOCHEM) 1997; 388: 339.60. Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA,

Cheeseman JR, Zakrzewski VG, Montgomery JA Jr, Strat-mann RE, Burant JC, Dapprich S, Millam JM, Daniels AD,Kudin KN, Strain MC, Farkas O, Tomasi J, Barone V, Cossi M,Cammi R, Mennucci B, Pomelli C, Adamo C, Clifford S, Ochter-ski J, Petersoon GA, Ayala PY, Cui Q, Morokuma K, Malick DK,Rabuck AD, Raghavachari K, Foresman JB, Cioslowski J,Ortiz JV, Baboul AG, Stefanov BB, Liu G, Liashenko A,Piskorz P, Komaromi I, Gomperts R, Martin RL, Fox DJ, Keith T,Al-Laham MA, Peng CY, Nanayakkara A, Challacombe M,Gill PMW, Johnson B, Chen W, Wong MW, Andres JL, Gon-zalez C, Head-Gordon M, Replogle ES, Pople JA. Gaussian 98,Revision A 9. Gaussian, Inc: Pittsburgh, PA, 1998.

61. Ferenczy G, Harsanyi L, Rozsondai B, Hargittai I. J. Mol. Struct.1986; 140: 71.

62. Harsanyi L, Csaszar A, Csaszar P. J. Mol. Struct. (THEOCHEM)1986; 137: 207.

63. Stewart RF, Jensen LH. Acta Crystallogr. 1967; 13: 1102.64. Aamouche A, Berthier G, Cadioli B, Gallinella E, Ghomi M.

J. Mol. Struct. (THEOCHEM) 1998; 426: 307.65. Williamns RW, Lowrey AH. J. Comput. Chem. 1991; 12: 861.66. Towasi J, Persico M. Chem. Rev. 1994; 94: 2027.67. Williams RW, Cheh JL, Lowrey AH, Weif AF. J. Phys. Chem. 1995;

99: 5299.68. Blicharska B, Kupka T. J. Mol. Struct. 2002; 613: 153.69. Szczesniak M, Nowak MJ, Szzczepaniak K, Chin S, Scott I,

Person WB. Spectrochim. Acta 1985; 41A: 233.70. Nowak MJ, Lapinski L, Bienko DC, Michalska D. Spectrochim.

Acta 1997; 53A: 855.71. Alcolea Palafox M, Rastogi VK. Spectrochim. Acta 2002; 58A: 411.72. Roeges NPG. A Guide to the Complete Interpretation of Infrared

Spectra of Organic Structures. John Wiley and Sons: New York,1994.

73. Alcolea Palafox M. Recent. Res. Dev. Phys. Chem. 1998; 2.74. Scott AP, Radom L. J. Phys. Chem. 1996; 100: 16502.75. Monshi M, Al-Fahan K, Al-Resayes S, Ghaith A, Hasanein AA.

Spectrochim. Acta. 1997; 53: 2669.76. Kulakowska I, Geller M, Lesyng B, Wierzchowski KL. Biochim.

Biophys. Acta 1947; 361: 119.


FTIR and FT-Raman spectra and density functional computations of the vibrational spectra, molecular...

Documents

Transcript of FTIR and FT-Raman spectra and density functional computations of the vibrational spectra, molecular...