Experimental, anticancer activity and density functional theory study on the vibrational spectra of 2-(4-fluorobenzylideneamino) propanoic acid

Article abstract of DOI:10.1016/j.saa.2008.07.006

2-(4-Fluorobenzylideneamino) propanoic acid was synthesized through the reaction of 4-fluorobenzaldehyde and α-alanine in refluxing EtOH. Its structure was verified by ¹H NMR, FTIR and Raman spectroscopy. The ground-state geometries were optimi

Full text of DOI:10.1016/j.saa.2008.07.006

Spectrochimica Acta Part A 72 (2009) 26–31
Contents lists available at ScienceDirect
Spectrochimica Acta Part A: Molecular and
Biomolecular Spectroscopy
journal homepage: www.elsevier.com/locate/saa
Experimental, anticancer activity and density functional theory study on the
vibrational spectra of 2-(4-fluorobenzylideneamino) propanoic acid
Min Ruana,b,∗, Yong Yea, Yuanzhi Songc, Qiongyao Zhanga, Yueping Zhaoa
a Key Laboratory for the Synthesis and Application of Organic Functional Molecules, Ministry of Education, Hubei University, Wuhan 430062, People’s Republic of China
b School of Chemical and Material Engineering, Huangshi Institute of Technology, Huangshi 435003, People’s Republic of China
c Key Laboratory for Chemistry of Low-Dimensional Materials, Jiangsu Province, Chemistry Department, Huaiyin Teachers College, Huaian 223300, People’s Republic of China
a r t i c l e i n f o
a b s t r a c t
Article history:
2-(4-Fluorobenzylideneamino) propanoic acid was synthesized through the reaction of 4-
fluorobenzaldehyde and ␣-alanine in refluxing EtOH. Its structure was verified by 1H NMR, FTIR
and Raman spectroscopy. The ground-state geometries were optimized at B3LYP/6-31G*, B3LYP/6-
31 + G** and B3LYP/6-31G** level without symmetry constrains. The vibrational wavenumbers of 4-FA
were calculated at same level. The scaled theoretical spectra using B3LYP methods are in a good
agreement with the experimental ones. The title compound was tested for anticancer activity of the Hela
cell line (using an MTT viability assay) with an IC50 166.6 ␮g/mL.
Received 19 December 2007
Received in revised form 18 June 2008
Accepted 8 July 2008
Keywords:
Schiff base
IR
Published by Elsevier B.V.
Raman
DFT calculations
Hela cell
MTT method
1. Introduction
(Fig. 1) [7]. In addition, we wish to report a theoretical study of
the vibrational properties of 4-FA. Many study results have indi-
Malignant tumor, i.e., cancer is a dreadful menace to human
beings [1]. So the development of potential and effective anticancer
drugs has become one of the most intensely persuaded goals of
contemporary medicinal chemistry. The role of schiff bases as inter-
mediate products in biologically important reactions is well known
and documented [2]. Derivatives of amino acids and pyridoxal or
salicylaldehyde have been widely studied [3,4]. In addition, flu-
oroaromatic compounds have become increasingly important in
view of their application as agrochemicals, drugs, textile chem-
icals, etc. [5] and the carbon–fluorine bonds enhances certain
molecular properties (e.g., lipid solubility, bioactivity, reduced
toxicity and oxidative stability). As this kind of fluoroaromatic, P-
fluorobenzaldehyde is very important due to its extensive use as
intermediate for pharmaceutical [6]. This gave a great impetus to
the search for potential pharmacologically active 4-fluorobenzidine
␣-alanine Schiff base (4-FA) derived from 4-fluorobenzaldehyde
and ␣-alanine. On the basis of its 1H NMR spectra and element
analyses the Schiff base structure immediately could be confirmed
cated that density-functional theory (DFT) is a powerful method
for predicting the geometry and harmonic vibration of organic com-
pounds [8–13]. DFT is a useful method for the investigation of large
molecules [11].
In our present work, the ground-state geometries of 4-FA were
optimized at B3LYP/6-31G**, B3LYP/6-31G* and B3LYP/6-31 + G**
levels, respectively. Analytical vibrational frequencies were calcu-
lated at the same level.
The MTT assay was used for the quantification of liv-
ing, metabolically active cells in initial experiments. Cellular
dehydrogenases metabolize MTT (3-(4,5-dimethylthiazol-2-yl)-
2,5-diphenyltetrazolium bromide) to
a purple formazan dye,
which is then solubilized in DMSO and measured photometri-
cally at 570 nm. After incubation of cells with fresh medium with
0.25 mg/mL MTT for 1 h, the medium was aspirated, cells were
washed once with PBS (+/+), and the formazan crystals were solubi-
lized in DMSO. Viability was calculated as percentage of formazan
formation in cells interacted with 4-FA compared to mock-treated
cells.
2. Experiment
∗
Corresponding author at: School of Chemical and Material Engineering, Huang-
shi Institute of Technology, Huangshi 435003, People’s Republic of China.
Tel.: +86 07 145206010.
All materials and solvents were obtained from commercial sup-
pliers and used without further purification. 4-Fluorobenzaldehyde
E-mail addresses: amin0241@sina.com (M. Ruan), yeyong@hubu.edu.cn (Y. Ye).
1386-1425/$ – see front matter. Published by Elsevier B.V.
doi:10.1016/j.saa.2008.07.006

M. Ruan et al. / Spectrochimica Acta Part A 72 (2009) 26–31
27
Fig. 1. The geometry and atom numbering of 4-FA.
was from Sigma. 1H NMR spectra were recorded on a AS 300 (VAR-
IAN) using TMS as an internal standard. Compound dissolved in
DMSO-d6. Element analyses were obtained on a PE 2400 CHN ana-
lyzer. Melting point was measured in WRS-1B digital melting point
instrument. Infrared spectra of the compound dispersed in KBr pel-
let in the range of 4000–400 cm−1 were recorded on an IR-Spectra
One (PE). The Raman spectra of powder sample were acquired on
with Renishaw RM1000 spectrometer using Nd:YAG laser as excita-
tion source (785 nm) with an output of about 200 mW. The spectral
3. Calculation
The DFT calculations were employed with the Becke–Lee–
Yang–Parr’s three-parameter hybrid functional (B3LYP) [17]
method in this study. The same basic sets (6-31G** and 6-31G*)
[18] were employed in the B3LYP calculations and the geometry
optimizations were performed without symmetry constrain. It is
known that ab initio and DFT potentials systematically overesti-
mate the vibrational wavenumbers [19]. These discrepancies can be
corrected either by computing an harmonic corrections explicitly
or by introducing a scaled field [20] or directly scaling the calculated
wavenumbers with proper factor [21]. Therefore, we have used the
scaling factor values of 0.9614, 0.9700 and 0.9670 for B3LYP/6-31G*,
B3LYP/6-31 + G** and B3LYP/6-31G** methods, respectively [21]. All
calculations were performed with the Gaussian 03W program suit
[22]. The assignment of the calculated wavenumbers is aided by the
animation option of Gauss View 3.0 graphical interface for Gaus-
sian programs, which gives a visual presentation of the shape of
the vibrational modes [23,24].
regions were 400–3500 cm−1
.
Synthesis of 4-FA: In a 1:1 molar ratio, ␣-alanine (0.7127 g,
8 × 10−3 mol) and potassium hydroxide (0.4489 g, 8 × 10−3 mol)
were added in 30 mL absolute EtOH The solution of ␣-alanine
potassium salt was filtered after the mixture was refluxed under
stirring for 1 h and left to stand at room temperature [14]. Under
stirring and nitrogen atmosphere, 4-fluorobenzaldehyde (1.00 mL,
10 × 10−3 mol) in 10 mL anhydrous EtOH was added. After 3 h, the
solvent was removed under reduced pressure and the remaining
solid residue was dissolved in EtOH (30 mL). Then we used concen-
trated H2SO4 to transform COOK to COOH [15]. After acidification of
the resulting solution, the precipitated crude product was filtered,
washed with petroleum ether, dried and recrystallized [16]. Yield:
91.5%. mp: 149–151 ◦C. Anal. Calc. for C10H10FNO2 (shown in Fig. 1):
C, 61.52; H, 5.16; N, 7.17. Found: C, 61.40; H, 5.12; N, 7.05. 1H NMR: ı
8.22(1H, bs, CH N), 7.74(2H, dd, H-2), 7.23(2H, t, H-3), 3.69(1H, m,
CH CH3), 1.25 (3H, d, CH CH3).
4. Results and discussion
The schematic depiction of 4-FA and optimized structure are
shown in Fig. 1, and the optimized bond lengths, bond angles and
dihedral angles of 4-FA are shown in Table 1.
Biological testing: Cells were allowed to grow to 60–80% con-
fluence under conditions of 5% CO2 at 37 ◦C. A stock solution of
each compound was prepared in 1 mL of DMSO followed by dilu-
tion with fresh medium. A 96-well plate was set up for compound
with six in-plate replicates of the three concentrations on the
plate. Cell solution (200 ␮L, 5 × 104 cells/mL, 1 × 104 cells/well) was
plated and initially incubated for 24 h, after which the media were
removed and 100 ␮L of media containing 1% DMSO was added.
Plates were incubated at 5% CO2 at 37 ◦C for 3 days, after which
the cells were washed with 200 ␮L PBS, 200 ␮L of 0.5 mg/mL MTT
solution was added to each well, and the cells were incubated for 2 h
at 37 ◦C at 5% CO2. The MTT solution was then removed, the wells
were washed again with PBS, 200 ␮L DMSO solution was added
and the plates were incubated in the dark for 10 min. Absorbance
readings were taken at 570 nm using an Anthos III microplate spec-
trophotometer. The data were processed with the aid of Microsoft
The carboxylic group is practically planar with the asymmetrical
C(12) O(13) 1.212 and C(12) O(14) 1.353 Å distances, which are
consistent with the double and single C O bonds, respectively [25].
From Table 1, the bond lengths, bond angles and dihedral angles
calculated at B3LYP/6-31 + G** level are in agreement with those
calculated at B3LYP/6-31G* and B3LYP/6-31G** levels.
The values of zero-point vibrational energy, sum of electronic
and zero-point energy, EHOMO, ELUMO, thermal correction to energy
for 4-FA are listed in Table 2. The HOMO energy calculated by
B3LYP/6-31 + G** are 0.4 eV higher than by B3LYP/6-31G* and
B3LYP/6-31G**. The dipole moment calculated using B3LYP/6-
31 + G** level is 0.3 D higher than those using B3LYP/6-31G* and
B3LYP/6-31G** levels.
Figs. 2 and 3 show the observed FTIR and Raman spectra, respec-
tively. One can notice that many bands have shoulders or are quite
broad because of the overlapping of two or more unresolved com-
ponents. We have listed the strongest peaks and noted the presence
of appropriate shoulders.
Excel 2000 and the % growth at each compound concentration was
compound−blank
calculated as follows: % grown =
compound is the
control−blank
mean absorbance of the inhibitor and the cell culture, blank is the
absorbance of the media alone and control is the absorbance of
the media with cells. IC50 was defined as the compound concen-
tration, which caused 50% inhibition of the growth of the treated
cells compared to the control cells. The inhibition rates are 17.2,
19.5 and 24.0 for the 4-FA with the concentrations of 266.7, 133.4
and 66.7 ␮g/mL, respectively, and the IC50 is 166.6 ␮g/mL against
Hela cell.
The FTIR and Raman spectra of 4-FA were fully interpreted
on the basis of the IR and Raman spectra calculated at B3LYP/6-
31 + G**, B3LYP/6-31G** and B3LYP/6-31G* levels, respectively. The
calculated wavenumbers scaled by factor of 0.9700 at B3LYP/6-
31 + G**, 0.9670 at B3LYP/6-31G** and 0.9614 at B3LYP/6-31G*
levels, intensity and assignments are listed in Table 3, respectively.
The agreement between the experimental and scaled theoretical
frequencies is quite good in general.

28
M. Ruan et al. / Spectrochimica Acta Part A 72 (2009) 26–31
Table 1
Selected bond lengths, bond angles, dihedral angles of compound 4-FA.
Parameters
B3LYP/6-31 + G** B3LYP/6-31G* B3LYP/6-31G**
Bond length (Å)
C(6)–F(7)
C(1)–C(2)
C(2)–C(3)
C(3)–C(4)
C(4)–C(5)
C(5)–C(6)
C(6)–C(1)
C(3)–C(8)
1.358
1.396
1.403
1.407
1.391
1.393
1.389
1.474
1.275
1.460
1.531
1.541
1.212
1.353
1.095
0.972
1.094
1.348
1.394
1.403
1.406
1.390
1.394
1.390
1.472
1.274
1.459
1.532
1.540
1.210
1.354
1.096
0.976
1.095
1.348
1.394
1.402
1.406
1.389
1.394
1.390
1.472
1.275
1.459
1.532
1.540
1.210
1.353
1.095
0.972
1.094
C(8)–N(9)
N(9)–C(10)
C(10)–C(12)
C(10)–C(11)
C(12)–C(13)
C(12)–O(14)
C(10)–H(20)
O(14)–H(24)
C(11)–H(21)
Fig. 2. The FTIR spectra of 4-FA.
Bond angle (◦)
C(1)–C(2)–C(3)
121.1
121.0
121.0
C(2)–C(3)–C(8)
C(4)–C(3)–C(8)
C(3)–C(8)–H(19)
C(3)–C(8)–N(9)
C(8)–N(9)–C(10)
N(9)–C(10)–C(11)
N(9)–C(10)–C(12)
N(9)–C(10)–H(20)
C(11)–C(10)–H(20)
C(12)–C(10)–H(20)
C(10)–C(12)–O(13)
C(14)–C(12)–O(13)
C(12)–O(14)–H(24)
119.3
121.6
114.8
122.4
121.1
118.8
108.6
106.3
108.7
104.1
124.8
122.8
107.1
119.6
121.4
114.7
122.2
120.9
118.7
108.7
106.5
108.6
104.3
125.0
122.9
106.0
119.6
121.4
114.8
122.1
120.9
118.9
108.6
106.6
108. 7
104.2
125.0
123.0
106.0
Dihedral angle (◦)
C(4)–C(3)–C(8)–N(9)
C(3)–C(8)–N(9)–C(10)
C(8)–N(9)–C(10)–C(12)
C(8)–N(9)–C(10)–C(11)
C(8)–N(9)–C(10)–H(20)
N(9)–C(10)–C(12)–O(13)
C(10)–C(12)–O(14)–H(24)
−0.6
−179.6
−126.3
−0.6
−0.8
180.0
−122.9
2.3
125.2
−130.0
178.4
−0.8
180.0
−123.1
2.1
125.2
−129.3
178.5
122.2
−128.4
178.8
Fig. 3. The Raman spectra of 4-FA.
Figs. 4 and 5 show the unscaled calculated IR and Raman spectra
of 4-FA at B3LYP/6-31 + G** (a), B3LYP/6-31G** (b) and B3LYP/6-
31G* (c) levels, respectively.
tion. The C H aromatic stretches is very weak, which is observed at
3040 cm−1 in FTIR and 3044 cm−1 in Raman spectra, respectively
[27]. The band observed at 2936 cm−1 in FTIR and 2939 cm−1 in
Raman spectra are assigned to the symmetric stretching vibration
of CH3 mixed with the stretching vibration of C8–H19. The medium
intense band at 1455 cm−1 in FTIR and 1456 cm−1 in Raman spectra
are assigned to the asymmetric deformation of CH3. The medium
band at 1379 cm−1, the strong peak at 1362 cm−1 in FTIR and the
medium band at 1383 cm−1, the very weak band at 1365 cm−1 in
Raman spectra are assigned to the symmetric deformation of CH3
mixed with in-plane wagging of C8–H19.
The calculations show that the strong band at 3643 cm−1 in
FTIR is associated with the stretching vibration of O H of carboxyl,
which is observed at 3498 cm−1. The bands near 3100 cm−1 can
be attributed to the aromatic C H stretching [26]. The band of
C
H stretching vibrational mode for benzene appears at 3080 cm−1
in FTIR and 3083 cm−1 in Raman spectra. The very weak intense
peak at 2974 cm−1 in FTIR and weak intense peak at 2976 cm−1
in Raman spectra are attributed to the C10–H20 stretching vibra-
Table 2
Thermodynamic parameter for 4-FA.
B3LYP/6-31 + G**
B3LYP/6-31G*
B3LYP/6-31G**
Thermodynamic parametera
Zero-point vibrational energy (kJ mol−1
)
486.0
519.9
486.8
488.5
522.2
485.5
487.6
521.4
485.7
Thermal correction to energy (kJ mol−1
)
Entropy (J mol−1 K−1
)
CV (J mol−1 K−1
EHOMO (eV.)
ELUMO (eV)
)
200.8
199.6
200.1
−6.905
−1.767
3.026
−692.0
−6.514
−1.325
2.691
−691.9
−6.519
−1.335
2.717
−692.0
Dipole moment (D)
Sum of electronic and zero-point energy (kJ mol−1
)
a
Unscaled for 298 K and 1 atm.

Table 3
The observed fundamentals and calculated wavenumbers (cm−1), FTIR and Raman intensity and assignments for 4-FA.
Descriptions
Calculated
Observed
B3LYP/6-31 + G**
B3LYP/6-31 + G**a
B3LYP/6-31G*
B3LYP/6-31G*a
B3LYP/6-31G**
B3LYP/6-31G**a
IR intensityb
Raman intensity
IR exp
Raman exp
ꢀs(O–H)
ꢀ(C–H)benz
ꢀ(C–H)benz
ꢀ(C10–H20)
ꢀ(CH3) + ꢀ (C8–H19)
ꢀs(C O)
ꢀs(C N)
ꢀ(C C)benz
ꢀ(C C)benz
ꢀ(C C)benz
ıas(CH3)
ꢀ(C C)benz
ıs(CH3) + ꢁ(C8–H19)
ıs(CH3) + ꢁ(C8–H19)
ꢀ(C C)benz
ꢁ(C–H)benz
ꢁ(C–H)benz
3756
3182
3131
3073
3044
1816
1726
1650
1635
1544
1504
1452
1419
1404
1346
1321
1315
1259
1196
1175
1125
1113
1097
1029
1005
989
3643
3087
3037
2980
2952
1761
1674
1601
1586
1498
1459
1408
1376
1362
1306
1281
1276
1221
1160
1140
1091
1080
1064
998
3685
3184
3138
3078
3050
1850
1735
1666
1642
1561
1526
1465
1434
1422
1354
1329
1324
1288
1213
1185
1133
1122
1105
1034
1014
983
3543
3063
3017
2959
2932
1779
1668
1602
1579
1501
1467
1408
1379
1367
1302
1278
1273
1238
1166
1139
1089
1079
1062
997
3753
3183
3136
3073
3043
1848
1733
1663
1640
1556
1509
1459
1425
1409
1351
1320
1315
1286
1205
1177
1127
1116
1101
1033
1012
985
3629
3078
3033
2972
2943
1787
1676
1608
1586
1505
1459
1411
1378
1363
1306
1276
1272
1244
1165
1138
1090
1079
1065
999
52.8
10
18.8
9.8
149.8
53.3
64
148.9
27.2
5.8
476.6
331.6
30.9
35
18.3
10.8
4.3
3498(s)
3080(vw)
3040(vw)
2974(vw)
2936(vw)
1683(s)
3083(w)
3044(vw)
2976(w)
2939(w)
1655(s)
1642(vs)
1606(vs)
1596(s)
1511(w)
1456(m)
1420(m)
1383(vw)
1365(vw)
1313(vw)
1299(m)
1279(w)
1229(s)
1158(s)
1133(w)
1100(w)
1081(w)
1048(w)
1014(vw)
978(w)
969(w)
937(vw)
890(s)
21
380
86.2
111.3
17.9
71.8
7
6.8
19.3
4.7
1650(s)
1603(vs)
1583(vs)
1508(s)
1455(m)
1404(s)
1379(m)
1362(s)
6.7
3.5
2.1
7.8
1309(m)
1294(m)
1276(m)
1230(vs)
1155(vs)
1129(m)
1095(m)
23.2
22.9
39.8
5
20.8
7.8
9.8
5.6
4.5
5.7
0.3
1
7.4
22.8
1.9
16.5
146.9
149.5
35.9
16.7
9
35.4
61.9
11.2
0
0.2
9.9
16.6
44.9
7
Def of benz ring(ip) + ꢀ(C–F)
ꢁ(O–H)
ı(C–H)benz
ı(C–H)benz
ꢀ(C9–C10) + ı (C–H)benz
ꢀ(C10–C11) + ı(C–H)benz
Def of benz ring (ip)
Breath of benz ring
Breath of benz ring
Breath of benz ring
ꢀ(N9–C10–C11)
ꢀske of benz ring
ꢂ(C–H)benz
1047(s)
1012(m)
975(m)
966(w)
920(w)
888(m)
975
959
926
881
856
830
806
975
945
910
878
851
820
800
979
952
917
881
858
824
804
955
908
882
856
947
913
888
853
948
911
887
852
859(s)
838(w)
822(w)
838(vs)
ꢂ(C–H)benz
831
832
831
5
Def of benz ring (ip)
Def of benz ring (op)
Def of benz ring (ip)
ω(O–H)
Def of benz ring (op)
Def of benz ring (op)
Def of benz ring (op)
ı(C10–C11–C12)
ꢃ(C10–C11)
812
719
650
612
525
516
428
330
788
697
631
594
509
501
415
320
817
718
654
624
532
518
430
328
785
690
629
600
511
497
413
315
816
718
653
621
531
518
431
329
789
694
631
601
513
501
417
318
2.9
0.3
7.4
65.3
21
20
0.6
1.8
3.2
4.5
0.9
1.2
4.8
0.6
0.9
0.2
2.6
790(m)
712(w)
643(m)
795(s)
641(w)
610(w)
508(s)
483(m)
511(vw)
487(vw)
433(vw)
315(vw)
292(vw)
232(m)
222(vs)
297
235
226
288
228
219
302
237
226
290
228
218
301
236
226
291
228
219
1.3
1.6
1.7
ı(C3–C4–C8)
ω(N9–C10–C11)
1.5
1.3
Abbreviation: as, asymmetric; s, symmetric; benz, benzene; ꢄ, stretching vibration; def, deformation; ꢃ, torsion; ω, wagging out-of-plane; ꢁ, wagging in-plane; op, out-of-plane mode; ip, in-plane mode; ı, scissors vibration;
ıas, asymmetric deformation; ıs, symmetric deformation; ˇ, bending in-plane; ꢂ, bending out-of-plane; ske, skeleton; s, strong; w, weak; m, medium; vs, very strong; vw, very weak.
a
Scaling factor: B3LYP/6-31 + G**, 0.97; B3LYP/6-31G**, 0.967; B3LYP/6-31G*, 0.9614.
The absolute IR intensity in KM(mol)-1; Raman scattering activity in Å 4 (amu)-1 from B3LYP/6-31G* calculation.
b

30
M. Ruan et al. / Spectrochimica Acta Part A 72 (2009) 26–31
and 1606 cm−1 in Raman spectra are all very strong absorptions.
The bands at 1508, 1404 cm−1 in FTIR and 1596 cm−1 in Raman
spectra are strong, and the one at 1420 cm−1 in Raman spectra is
medium. The strongest band is observed at 1603 cm−1 in FTIR, how-
ever, the most intense one appears at 1683 cm−1 in the calculated
IR spectra.
The very strong absorption band at 1230 cm−1 in FTIR and
strong band at 1229 cm−1 in Raman are due to the stretching vibra-
tion of C F. The bands are in good agreement with the literature
value (1230 cm−1) obtained for 2-fluoro-4, 6-dinitrophenol [30].
The medium bands at 1294, 1276 cm−1 in FTIR and the bands at
1299, 1279 cm−1 in Raman spectra are assigned to the C H in-plane
wagging vibrations for benzene. The bands with medium intensi-
ties observed at 1129, 1095 and 1047 cm−1 in FTIR, and the bands
with weak intensities appear at 1133, 1100, 1081 and 1048 cm−1
in Raman spectra are assigned to the C H scissors vibrations for
phenyl. The peaks at 975, 966 and 920 cm−1 in FTIR and 978, 969
and 937 cm−1 in Raman spectra can be assigned to the breathing
vibrations of benzene ring. The intensity of the breath vibration of
benzene ring is weak, and the band at 975 cm−1 in FTIR is a medium
one and the band at 937 cm−1 in Raman spectra is a very weak
one. The strong intense peak observed at 859 cm−1 in Raman spec-
tra is attributed to the skeletal vibration of benzene. The medium
intensity band obtained at 888 cm−1 in FTIR and strong intensity
band obtained at 890 cm−1 in Raman spectra are assigned to the
stretching vibration of N9–C10–C11. The very strong intensity band
observed at 838 cm−1 in FTIR and weak intensity bands appear at
838 and 822 cm−1 in Raman spectra are assigned to the C H out-
plane bending for benzene ring. The bands at 790, 712, 643 cm−1 in
FTIR and 795, 641 cm−1 in Raman spectra can be assigned to the in-
plane deformation of benzene ring. The out-of-plane deformations
of benzene ring are observed at 508 and 483 cm−1 in FTIR and 511,
487, 433 cm−1 in Raman spectra. The band with very weak intensity
at 315 cm−1 in Raman spectra is assigned to the scissors vibration
of C10–C11–C12. The band of torsion for C10–C11 is observed at
292 cm−1 in Raman spectra with very weak intensity. The medium
peak at 232 cm−1 in Raman spectra is assigned to the out-plane
deformation of C3–C4–C8. The peak with very strong intensity at
222 cm−1 in Raman spectra is assigned to the out-of-plane wagging
of N9–C10–C11.
Fig. 4. The unscaled IR spectra of 4-FA at (a) B3LYP/6-31+G**, (b) B3LYP/6-31G* and
(c) B3LYP/6-31G** level.
The strong absorption bands of the C O stretching vibration are
observed at 1683 cm−1 in FTIR and 1655 cm−1 in Raman, which are
in accordance with the experimental values (1692 and 1640 cm−1
)
obtained for monoglycine dihydrogenphosphate [28] and dimmer
dibenzyl carbamic acid [29], respectively. The discrepancy between
simulation and experiment spectra is due to the intermolecular
interactions. The strong intense peaks appear at 1650 cm−1 in FTIR
and 1642 cm−1 in Raman spectra assigned as the stretching vibra-
tion of C N, which is in accordance with the experimental value
(1637 cm−1) obtained for Sal–ala–Mn compound [17]. The inten-
sity of the band observed at 1642 cm−1 in Raman spectra is the
strongest one, and the band is also the most intense one of the
calculated intensity in Raman spectra.
The bands of C C stretching vibrations for benzene ring appear
at 1603, 1583, 1508, 1404 cm−1 in FTIR and 1606, 1596, 1511,
1420 cm−1 in Raman spectra. The bands at 1603, 1583 cm−1 in FTIR
5. Conclusion
4-FA obtained in the reaction of 4-fluorobenzaldehyde with ␣-
alanine potassium salt in refluxing EtOH. Its structure was verified
by 1H NMR, FTIR and Raman. The mp = 149–151 ◦C. FTIR and Raman
spectra of 4-FA were carried out. The ground-state geometries
were optimized without symmetry constrains using the DFT-B3LYP
method with 6-31G*, 6-31 + G** and 6-31G** basis sets, respec-
tively. The vibrational wavenumbers of 4-FA were calculated on
optimized geometry by means of B3LYP/6-31G*, B3LYP/6-31 + G**
and B3LYP/6-31G**, respectively. After scaled with uniform scaling
factors, the predicted spectra are well consistent with experimental
spectra. The title compound was assayed for anticancer activ-
ity by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
bromide) method. The inhibition rates are 17.2, 19.5 and 24.0 for
the 4-FA with the concentrations of 266.7, 133.4 and 66.7 ␮g/mL,
respectively, and the IC50 is 166.6 ␮g/mL against Hela cell.
Acknowledgements
This work is supported by the National Science Foundation of
China (grants no. 20405011), the Natural Science Fund of Hubei
Province and opened Foundation of Key Laboratory for Chem-
Fig. 5. The unscaled Raman spectra of 4-FA at (a) B3LYP/6-31+G**, (b) B3LYP/6-31G*
and (c) B3LYP/6-31G** level.

M. Ruan et al. / Spectrochimica Acta Part A 72 (2009) 26–31
31
istry of Low-Dimensional Materials of Jiangsu Province (grants no.
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