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Asian Journal of Spectroscopy, 14, 1-2, 2010, 57-61

Vibrational Properties of 2-chloro-10-(3-[4-(2-hydroxyethyl)-piperazin-1-yl)


propyl phenothiazine - 'Perphenazine' : An Anti AIDS Drug

Y.P.Singha*, Arvind Singh Tomarb and S.K.Vijayc


a
Department of Physics, Govt. Polytechnic College, Sagar (MP), INDIA
470001.E-mail: Y_P_S_2k@Yahoo.com
b
Department of Physics, S.V. Polytechnic College, Bhopal (MP), INDIA,
c
Department of Physics, Govt. Geetanjali Girls P.G. College, Bhopal (MP), INDIA

Abstract

Perphenazine has shown great promise in inhibiting the human immuno deficiency virus
and in reducing mortality among AIDS patients. Fourier transform infra red spectrum
was recorded and analyzed. Making use of the recorded data, the vibrational
assignments are made and analysis of the observed fundamental bands of molecule is
carried out. The experimental determinations of vibrational frequencies are compared
with those obtained theoretically from Semi empirical, ab initio and DFT quantum
mechanical calculations using semi emperical/PM3, ab-initio/6-311++G* , and
B3LYP/6-311++G* methods. The spectra exhibit distinct features originating from low
frequency vibrational modes caused by intra-molecular motion. The normal modes of
vibrations obtained from ab initio and DFT (B3LYP) calculations are in good agreement
with the experimentally observed data. Comparison of the simulated spectra provides
important information about the ability of the computational method (B3LYP) to describe
the vibrational modes.

Introduction which they work is unknown, they have potent


effects on the central nervous system and other
organs2. It has been reported that some
phenothiazines inhibit intracellular replication of
Acquired immune deficiency viruses including HIV3-5.
syndrome (AIDS) is a disease of the Spectroscopic studies of anti-AIDS
human immune system caused by the human drug have made a significant contribution of this
immunodeficiency virus (HIV) has caused a noble endeavor of striving to eliminate the fear
worldwide concern for fighting this disease of this dreadful disease. The calculation of
effectively1. vibrational frequencies by computational
Perphenazine {2-chloro-10-(3-[4-(2- methods is becoming increasingly important in
hydroxyethyl)-piperazin-1-yl) propyl many areas6. Infra red of molecules in their
phenothiazine} is used to treat AIDS, severe ground electronic states were predicted by
nausea and vomiting. It is also used to treat the molecular orbital theory7.
symptoms of psychosis. Perphenazine belongs to Thus the present study has been
a class of psychoactive drugs called undertaken with a view to understand the
phenothiazines. Although the mechanism by
spectroscopy of this drug and experimental Results and Discussions
results are compared with calculated frequencies
using semi empirical, ab initio and DFT Vibrational Assignments: The theoretical
(B3LYP) methods. Probably, this is the first time prediction of vibrational spectra is of practical
when we are reporting experimental frequencies importance for the identification of known and
with above cited calculated frequencies because unknown compounds, and has become an
we had surveyed lot of literature but we found important part of spectrochemical and quantum
nothing. Experimental and theoretical IR spectra chemical investigations13. According to
have been compared. theoretical calculations, Perphenazine has a
planar structure of Cs point group symmetry.
The title molecule consists of 53 atoms, which
undergoes 153 normal modes of vibrations. Of
the 153 normal modes of vibrations, 103 modes
of vibrations are in-plane and remaining 50 are
out-of plane. The bands that are in the plane of
Perphenazine the molecule is represented as A' and out-of-
Empirical plane as A". It has 52 bend stretching vibrations
C21H26ClN3OS and 101 angle bending vibrations. Thus the 153
Formula
normal modes of vibrations are distributed as
Molecular ΓVib = 103 A' + 50 A"
403.97
Weight
Fig 1 Structure and Formula of Perphenazine The vibrational assignments are given in Table 2.
The comparative experimental and theoretical
Computational and Theoretical Details spectra of experimental and calculated are
given in Figs. 2 and 3.
The PM3 semi empirical approaches
were performed as implemented in MOPAC Normal Modes: We can get information from
program 9 and the PRECISE keywords were used. computational vibrational spectra only when we
DFT and Ab-initio calculations were performed compare it with experimental spectra. As the
using HYPER CHEM program 10 at the B3LYP table 1 is self-explanatory and experimental
11
levels of theory with 6-311++G* basis set 12 . values and corresponding calculated values are
The vibrational IR spectra were calculated at the shown in table 1, we shall discuss here only
B3LYP/ 6-311++G* levels of theory. some important points.
Vibrational frequencies calculated at 6-311++G* The experimental bands are shown in
basis level were scaled by 0.95 and those figure 2 and theoretical bands are shown in
calculated at ab initio level were scaled by 0.81. figure 3. The OH stretch of the title molecule is
In order to obtain the most stable conformation, identified at 3600 cm-1. In the title molecule, the
a combination of molecular mechanics and band have been assigned at 2925 cm−1 to C–H
quantum chemical calculations at the semi- ring stretching vibrations. These assignments are
empirical level was used. Structure of the in line with the literature14. The (C=C) stretching
molecule (Fig. 1) was built by HyperChem modes are normally observed between 1400 and
Release 8 for Windows using a molecular 1650cm−1. Only two C=C stretching vibrations
mechanics procedure under MM+ . The have been found at 1600 cm−1 and 1520 cm−1.
geometry was optimized to an rms gradient of The C–C stretching peak is at 1630 cm-1. The
0.001 in vacuo . Then a molecular dynamics C–N stretching vibrations are always mixed with
program was run for 1 ps, with 0.001 ps steps other bands and normally occur in the region
and a relaxation time of 0.1 ps, at a simulation 1266–1382cm−1. A band is observed at 1360cm−1,
temperature of 300 K. This was followed by which is in close agreement with the literature
MM+ geometry optimization to an rms value15 and this vibration is combined with C–C
gradient of 0.2. The molecular dynamics run stretching vibration. The CCC bending bands
was repeated and a further MM+ protocol was always occur below 600cm−1 as reported in
carried out to a gradient of an rms 0.004 on the literature16. In the present work band at 570 cm-1
selected drug.. is assigned to CCC in plane bending and 490 to
out of plane bending. In experimental spectrum
we got number of peaks in between 2500 cm-1 -
1200 cm-1. In calculated IR spectrum we got less
number of peaks because our calculations are of fundamental vibrational modes of
based on a frozen molecule at 0K in a vacuum Perphenazine were examined and some
and do not take into account that the structure is assignments were proposed. Comparison of the
vibrating at all. In experimental IR spectrum experimental and calculated spectra showed that
there is influence of the medium in which DFT-B3LYP method is in good agreement with
chemical species are found. experimental data. The results confirm the ability
of the methodology (DFT) applied for
interpretation of vibrational spectra of the title
Conclusions molecule. The correlation between the computed
Based on the semi-empirical at PM3, ab IR frequencies for semi-empirical and ab-initio
initio at 6-311++G* and DFT with B3LYP/6- and the experimental is less satisfactory, but this
311++G* levels, complete vibrational properties is not the case with DFT method. The graph is
of Perphenazine have been investigated by FTIR linear which shows that theoretical and
spectroscopy. On the basis of agreement between experimental results are in good agreement.
the calculated and observed results, assignments

Table 1 Principal Experimental and Calculated IR Signals (cm-1) and their Assignments in Perphenazine

Assign Experimental Assignments −1


Frequencies (in cm )
ment Frequencies
−1
(in cm ) semi-empirical DFT/ B3LYP Ab-initio
(PM3) (6-311++G*) 6-311++G*)
Species a'
1 3600 OH str 3195.75 3506.29 3201.45
2 2925 CH str 3169.24 2961.33 3005.71
3 1630 CC Str 1776.85 1656.05 1694.86
4 1600 C=C aromatic ring vibration 1526.81 1564.54 1578.25
5 1520 C=C aromatic ring vibration 1518.71 1517.79 1563.21
6 1390 C-O str 1363.37 1387.82 1362.37
7 1360 CN str 1225.66 1367.16 1351.61
8 1150 C=S str 1138.96 1151.45 1143.96
9 860 CH o.p. plane 879.17 879.17 870.49
10 750 C-Cl str 755.96 745.35 766.38
11 570 CCC i. p. bending 651.73 588.61 601.75
12 520 CN o. p. bending 589.36 613.42 628.67
13 490 CCC o. p. bending 503.72 474.58 491.39

Assign Experimental Assignments −1


Frequencies (in cm )
ment Frequencies
−1 Semi-empirical DFT/ B3LYP Ab-initio
(in cm )
(PM3) (6-311++G*) 6-311++G*)
Species a''
1 OH o.p.def 332.80 244.82 228.61
2 580 CH wagging 878.89 587.72 678.74
Figure 2: IR Spectrum (Experimental) of Perphenazine

Figure 3: IR Spectrum (Theoretical) of Perphenazine


Correlation Diagram

4000

3500
Calculated Wavenumbers

3000

2500

2000

1500

1000

500

0
0 500 1000 1500 2000 2500 3000 3500 4000

Experimental Wavenumbers
Exp Vs PM3
Exp Vs DFT
Exp Vs Ab-initio

Figure 4: Correlation Diagram for Experimental Vs Calculated Frequencies

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