Asian Journal of Spectroscopy, 12, 1, 2008

Vibrational Properties of Dichloroacetate : An Anti Cancer Drug

Y.P.Singha, and R. A. Singhb

a Department of Physics, Govt. Women’s Polytechnic College, Sagar (MP), INDIA

470001.E-mail: Y_P_S_2k@Yahoo.com

b Department of Physics, Dr. H.S.Gour University, Sagar (MP), INDIA, 470001

Abstract

Dichloroacetate (DCA), appears to suppress the growth of cancer cells without

affecting normal cells, suggesting that it might not have the dramatic side
effects of standard chemotherapies. The vibrational absorption spectra of DCA
has been studied using AM1, PM3, DFT and Ab initio method. Assuming Cs point
symmetry, vibrational assignments for the observed frequencies have been proposed.
The spectra exhibit distinct features originating from low frequency vibrational
modes caused by intra-molecular motion. Normal modes have been calculated and an
assignment of the observed spectra has been proposed. Experimental frequencies are
compared with those obtained by AM1, PM3, DFT and Ab initio methods.

Introduction

Dichloroacetate (or DCA) is an analogue of acetic acid in which two of the

three hydrogen atoms of the methyl group have been replaced by chlorine atoms1.
DCA is an odorless, colourless, inexpensive, relatively non-toxic, small molecule
This drug, dichloroacetate (DCA), appears to suppress the growth of cancer
cells without affecting normal cells, suggesting that it might not have the
dramatic side effects of standard chemotherapies2.DCA is also a metabolite in the
biotransformation of several pharmaceuticals and has been administered orally and
parenterally for decades as an investigational drug for the treatment of numerous
cardiovascular and metabolic disorders3,4.
The calculation of vibrational frequencies by computational methods is
becoming increasingly important in many areas5. Infra red of molecules in their
ground electronic states were predicted by molecular orbital theory6.
Thus the present study has been undertaken with a view to understand the
spectroscopy of this drug and experimental results are compared with calculated
frequencies using AM1, PM3, DFT and Ab initio methods. Probably, this is the
first time when we are reporting experimental frequencies with above cited
calculated frequencies because we had surveyed lot of literature but we found
nothing. Experimental and theoretical IR spectra has been compared.

Dichloroacetate
Empirical Formula C2H2O2Cl2
Molecular Weight 267.24
Fig 1 Structure and Formula of Dichloroacetate

Computational and Theoretical Details

In noncomplex molecules, the G F Matrix 7 is given by:-

G tt’= Σ3Ni=1 (B ti B t’i’) 1/ mi where t, t’ = 1,2,3,……, 3N-
6
In which mi is the mass of the atom to which the subscript I refers
and Bti , Bt’i’ are constants determined by geometry of molecule.
Internal coordinate St are related with Cartesian displacement
coordinate ξi as :
St = Σ 3Ni=1 Bti ξi where t = 1,2,3….., 3N-6
On solving G.F. matrix for any atom α is obtained as:
G tt’= Σ3N α =1 μ α St α . St’ α
Where dot represents the scalar product of two vectors and μ α = 1/m α , the
reciprocal of the mass of atom α
The AM1 and PM3 semi empirical approaches were performed as implemented in
MOPAC program 8 and the PRECISE keywords were used. DFT and Ab-initio calculations
were performed using HYPER CHEM program 9 at the B3LYP 10 levels of theory with
6-31G* basis set 11 . The vibrational IR spectra were calculated at the B3LYP/ 6-
31G* levels of theory. We have transformed the harmonic force fields, determined
initially in the Cartesian coordinates, were transformed to the force fields in
the internal local coordinates. The force fields obtained were used to calculate
the potential energy distribution (PED)12. Contributions greater than 10% are
given.

Results and Discussions

The theoretical prediction of vibrational spectra is of practical importance

for the identification of known and unknown compounds, and has become an important
part of spectrochemical and quantum chemical investigations13.
We can get information from computational vibrational spectra only when we
compare it with experimental spectrum. The vibrational infrared frequencies are
shown in table 1. DCA contains 8 atoms so that it has 18 normal modes. The
calculated normal modes are distributed among 13 a΄ and 5 a΄΄ species of Cs
symmetry group. The table 1 also shows that PED contributions for 18 normal modes.
These assignments are partly based on the calculated frequencies. As the table 1
is self-explanatory, we shall discuss here only some important points.
The experimental bands are shown in figure 2 and theoretical bands are shown
in figure 3. In experimental IR spectrum strongest peak is at 1743 cm-1 for C=O
stretch but in calculated (DFT) IR spectrum strongest peak is at 3680.6 cm-1. For
OH stretch, peak for experimental OH stretch is medium and peak for calculated
(DFT) C=O stretch is also medium. In calculated (DFT) IR spectrum we got number of
peaks in between 1000 cm-1 – 500 cm-1 . In experimental spectrum we got number of
peaks in between 1500 cm-1 - 1000 cm-1. In calculated IR spectrum we got less
number of peaks because our calculations are based on a frozen molecule at 0K in a
vacuum and do not take into account that the structure is vibrating at all. In
experimental IR spectrum there is influence of the medium in which chemical
species are found.
For fundamentals band, the experimental values very roughly agree with PM3
and MMFF94 values as listed in table 1. Out of the total 18 calculated bands, 17
are assigned and 1 left unassigned. The C-O stretch is strongly coupled with OH
bend and the corresponding experimental bands are at 1419 cm-1 and 1239 cm-1,
the calculated frequencies (DFT) are at 1417.4 cm-1 and 1228.0 cm-1 respectively.
The agreement between the experimental and calculated (DFT Method) wave
numbers is good. The plot between these two is linear with a unit slope

Conclusions

Theoretical semi-empirical quantum mechanical PM3, DFT, Ab-initio and GF

matrix calculations of the geometry and vibrational frequencies of the DCA drug
are presented in this paper and compared with experimental infrared spectra. The
calculated geometries and frequencies, except for PM3, agree well with the
experimental ones, but there are some differences between frequencies mainly due
to intermolecular interactions, anharmonicity and computational basis set. The
correlation between the computed IR frequencies for PM3 and MMFF94 and the
experimental is less satisfactory, but this is not the case with DFT and Ab-initio
methods.

ACKNOWLEDGEMENTS

The authors are grateful to Director, Directorate of Technical Education-

Madhya Pradesh, Bhopal and Head, Department of Physics and Department of Chemistry
, Dr. H.S.Gour University, Sagar (MP), India and National Institute of Advanced
Industrial Science and Technology, Japan for IR spectra

Fig 2: IR Spectrum (Experimental) of DCA

Fig 3: IR Spectrum (Theoretical) of DCA

Table 1 Experimental and Calculated Frequencies and Potential Distribution in
C2H2O2Cl2

Assignment Experimental Frequencies

(in cm )
G F Matrix Frequencies
(in cm )

Frequencies
(in cm )
PED and Mode PM3 MMFF94 DFT/
B3LYP
(6-31G*) Ab-initio

Species a'
1 3616 3702.6 OH str 3757.7 3632.6 3680.6 3611.3
2 2913 3000.2 CH str 3276.0 2953.3 2949.3 3006.4
3 1743 1815.3 C=O str 1523.8 1790.4 1754.7 1759.5
4 1419 1431.5 OH bend + C-O str 1430.0 1386.5 1417.4 1423.8
5 1404.9 OH i.p. def 1398.5 1351.8 1375.7 1362.8
6 1279 1311.3 CH bend 1326.7 1303.8 1297.3 1300.3
7 1239 1299.8 OH bend + C-O str 1302.4 1266.6 1228.0 1250.9
8 827 905.3 C-Cl str 842.5 812.2 837.5 831.2
9 807 821.6 CC str 818.3 800.7 807.4 810.1
10 660.5 C=O o.p.bend 635.8 643.5 715.8 711.5
11 607 616.4 C-Cl str 621.7 618.8 621.5 628.1
12 395.7 OCO bend 388.4 399.3 408.7 402.9
13 287.3 CCO bend 259.3 293.9 290.0 301.7

Assignment Experimental Frequencies

(in cm )
G F Matrix Frequencies
(in cm )

Frequencies
(in cm )
PED and Mode PM3 MMFF94 DFT/
B3LYP
(6-31G*) Ab-initio
Species a''
1 913 973.5 OH o.p.def 1068.7 926.4 918.8 921.6
2 459 483.5 C-O torsion 491.3 436.7 446.3 439.8
3 268.7 CH rocking 270.1 266.0 242.7 250.3
4 220.2 wagging 226.2 231.5 207.2 229.7
5 24.1 20.6 26.0 62.9 28.4

Fig 4: Correlation Diagram for Experimental Vs Calculated Frequencies (PM3 method)

Fig 5: Correlation Diagram for Experimental Vs Calculated Frequencies (DFT method)

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