Normal Mode Analysis, Electronic Parameters and molecular docking study of 3, 5, 4’-Trihydroxy-6, 7-Dimethoxy-Flavone (Eupalitin) using First Principle

 

Tanveer Hasan1*, Raza Murad Ghalib2, Sayed Hasan Mehdi3, P. K. Singh4, S. S. R. Baqri5

1Deptt. of Physics, Shia P.G. College, Lucknow, India.

2Deptt. of Chemistry, Faculty of Sciences & Arts, Khulais, University of Jeddah, Jeddah, KSA

3Deptt. of Chemistry, Shia P G College, Lucknow, India

4Deptt. of Applied Physics, SMS Institute, Lucknow, India.

5Deptt. of Zoology, Shia P G College, Lucknow, India

*Corresponding Author E-mail: tanveerhasan09@gmail.com

 

ABSTRACT:

The quest for novel molecules with therapeutic activity is a happening field and drives a lot of research in the area of chemical synthesis. In this connection, this paper describes the results of detailed spectroscopic investigations along with quantum chemical studies carried out on 3,5,4’-Trihydroxy-6,7-Dimethoxy-Flavone (Eupalitin), a compound which has earlier been shown to possess significant cytotoxicity against colorectal cancer HCT 116 cell line. The density functional method at B3LYP/6-311++G(d,p) level is used to obtain the equilibrium geometries of the title compound. Further, we have performed vibrational analysis of the title compound at its equilibrium geometries and have established complete assignments of the significant vibrational modes. The calculated vibrational frequencies are shown to be in perfect agreement with the experimentally observed FTIR spectra of the molecule under study. The electronic properties of the molecule are discussed with the help of the descriptors like HOMO-LUMO and MEP surface and several electronic parameters are calculated which are closely related to their chemical reactivity and reaction paths. In addition, molecular docking study has also been carried out to get a better insight into such interactions of the molecule that may explain its biological role.

 

KEYWORDS: 3,5,4’-Trihydroxy-6,7-Dimethoxy-Flavone (Eupalitin); Normal Mode analysis; DFT; NLO; Molecular Docking.

 


INTRODUCTION:

The field of chemical synthesis is always abuzz with activity and the pharmaceutical industry is one of the major contributors to the exponential rise of drugs being synthesized in the lab and used abundantly in clinical trials.

 

The title compound 3,5,4’-Trihydroxy-6,7-Dimethoxy-Flavone (Eupalitin), which has been taken from the work of Ghalib et al. represents such a synthetic molecule of therapeutic interest as it has been reported to possess significant cytotoxicity against colorectal cancer HCT 116 cell line1. Given the said medicinal properties, it is tempting enough a prospect to explore the various physical and chemical properties of this novel compound which may be of immense help in explaining its biological role and tapping its therapeutic potential. Keeping this in view, the present work was undertaken which deals with a comprehensive investigation of its geometric and electronic structure in ground as well as first excited state. Vibrational spectral features of this molecule have been explained and calculated spectrum has been compared with experimentally recorded FT-IR spectrum by DFT/B3LYP method using 6-311++G(d,p) as basis set. In this regard, VEDA 4 program has been used to carry out the potential energy distribution (PED) analysis2. This work also includes the analysis of HOMO, LUMO and 3-D Molecular Electrostatic Potential (MEP) surface analysis along with calculation of electric moments to predict the NLO properties of the molecule. The molecular docking study of the title compound which is an important prerequisite for predicting its molecular interactions in the living systems was also carried out using Glutathione s-Transferase 1AQW protein as a possible target. The bacterial origin of the target protein chosen for docking correlates well with the reported antimicrobial activity of the title compound.

 

2. EXPERIMENTAL:

2.1 Structure:

The crystal structure of the title compound Eupalitin is taken from the work of Ghalib et al whereas the molecular structure of the title compound as modelled by Gaussview package 5.0.8 showing number scheme is shown in Figure I3.

 

2.2 Spectroscopic measurements:

The FT-IR spectrum of the title compound is available online4.

 

3. RESULT AND DISCUSSION:

All quantum chemical calculations of the title compound Eupalitin are carried out on an AMD dual core/2.71 GHz personal computer using Gaussian 09 program package, invoking gradient geometry optimization and employing  the B3LYP/6-311++G (d,p) levels of theory to predict the molecular structure and vibrational wave numbers 5,6. The optimized structural parameters were used to calculate the vibrational wave numbers  and  the  stability  of  optimized  geometry  was  confirmed  by  the absence of any negative vibrational wave numbers. The vibrational frequency assignments have been carried out by combining the results of the Gaussview 5.0.8 program, symmetry considerations and the VEDA 4 program.

 

Fig. 1. Molecular structure of eupalitin as seen by gaussview

 

 

3.1 Optimized Molecular Geometry:

The optimized geometry of molecule with labeled atoms is shown in figure I. The optimized structural parameters (bond length, bond angle, dihedral angle etc.) calculated by B3LYP at 6-311++ (d, p) basis set are provided in table I and are compared with the experimental data. The calculated geometrical parameters show a good agreement with the experimental data and they are the basis for calculating vibrational frequencies and electronic properties.

 

The presence of hetero atom H10 in the molecular structure of the title compound Eupalitin has led to the possibility of intermolecular non-covalent interactions. The hydrogen atom H10 of one molecule is interacting with hydrogen atom of another molecule with bifurcated H-bond distances 0.836 Ĺ, which corresponds with bifurcated H-bond angle 108°.

 

The title molecule Eupalitin contains three rings R1, R2 and R3 all are six member rings. The ring R1 contains one oxygen atom O1 and one molecule of the compound is attached with the other molecule with H10 of ring R3. The equilibrium geometry optimization of lowest energy has been achieved by energy minimization. The calculated vibration spectrum contains no imaginary wave number which indicates that the optimized geometry of the molecule Eupalitin represents the minima on potential energy surface. The optimized bond length of ν(C-C) in the ring R1, R2, and R3 ranges between 1.365-1.466 Ĺ. The optimized bond length of ν(C-O) varies between 1.357-1.439 Ĺ. As expected, the optimized bond length of ν(O3=C4) attached to R1 is calculated at 1.2168 Ĺ, which is lesser than the other ν(O-C) bond lengths suggesting a double bond structure. The bond lengths of ν(O2-H2), ν(O4-H4) and ν(O7-H3) are calculated as 0.843, 0.864 and 0.836 respectively. The optimized bond length of all ν(C-H) vibrational modes, are calculated as 0.95 Ĺ. The CH3 bond lengths such as ν(C17-H17A), ν(C17-H17B) and ν(C-17-H17C) etc. are calculated in the range 0.98 Ĺ which are in good agreement with the X-ray data.

 

 

Some of the characteristics bond angles like Ф(C6-O5-C17) , Ф(C7-O6-C18), Ф(O1-C2-C11), Ф(O7-C14-C15) and Ф(O7-C14-C15) are calculated as 118°,119°, 113°, 117° and 123° near the vicinity of ring R1 arise due to decrease in lateral distance between the carbon atoms C2 and C11.

 

The repulsive interaction between the electrons of the bonds increases thereby causing a decrease in bond angle.

 

 

 

The torsional angles of ring R1, R2 and R3 like τ(C9-O1-C2-C3), τ(C9-O1-C2-C11), τ(C2-O1-C9-C8), τ(C2-O1-C9-C10), τ(H4-O4-C5-C6), τ(H4-O5-O6-C7), τ(H7-O7-C14-C13) and τ(H7-C2-C14-C15) are calculated by DFT as 2.7°, 177.6°, 177°, 1.6°, 179°, 0.385°, 179.87°, and 0.142° respectively, which suggest that ring R1, R2 and R3 nearly lie on the same plane. Several values of torsional angles calculated by DFT method are also shown in table I which could not be found in X-ray method. All other optimized geometrical parameters in the title compound are reasonably matched with experimentally obtained X-ray data and are in accordance with the reported literature 7-10.


 

Table I Optimized ground state structural parameters of Eupalitin at B3LYP method

S .No

Parameter

Method

S. No

Parameter

Method

Stretching Ĺ

X-ray

DFT

Bending (deg)

X-ray

DFT

ν(O1-C2)

1.374

1.4026

45

Ф(C7-O6-C18)

118.3

119.01

2

ν(O1-C9)

1.372

1.3924

46

Ф(H7-O7-C14)

108

112.43

3

ν(O2-H2)

0.843

0.9916

47

Ф(O1-C2-C3)

120.1

118.36

4

ν(O2-C3)

1.357

1.3893

48

Ф(O1-C2-C11)

112.6

112.85

5

ν(O3-C4)

1.268

1.2974

49

Ф(C3-C2-C11)

127.3

128.79

6

ν(O4-H4)

0.864

1.0062

50

Ф(O2-C3-C2)

120.4

122.93

7

ν(O4-C5)

1.356

1.378

51

Ф(O2-C3-C4)

118

114.94

8

ν(O5-C6)

1.38

1.3891

52

Ф(C2-C3-C4)

121.6

122.14

9

ν(O5-C17)

1.439

1.4729

53

Ф(O3-C4-C3)

120.8

118.73

10

ν(O6-C7)

1.355

1.3801

54

Ф(O3-C4-C10)

122.5

123.76

11

ν(O6-C18)

1.436

1.4595

55

Ф(C3-C4-C10)

116.7

117.51

12

ν(O7-H7)

0.836

0.9792

56

Ф(O4-C5-C6)

118.9

119.71

13

ν(O7-C14)

1.364

1.3953

57

Ф(O4-C5-C10)

120.8

119.92

14

ν(C2-C3)

1.365

1.381

58

Ф(C6-C5-C10)

120.3

120.37

15

ν(C2-C11)

1.466

1.4642

59

Ф(O5-C6-C5)

119.4

123.28

16

ν(C3-C4)

1.428

1.4528

60

Ф(O5-C6-C7)

120.9

117.84

17

ν(C4-C10)

1.429

1.4402

61

Ф(C5-C6-C7)

119.7

118.73

18

ν(C5-C6)

1.37

1.4038

62

Ф(O6-C7-C6)

114.4

115.15

19

ν(C5-C10)

1.416

1.4301

63

Ф(O6-C7-C8)

124.2

123.29

20

ν(C6-C7)

1.412

1.4314

64

Ф(C6-C7-C8)

121.5

121.57

21

ν(C7-C8)

1.388

1.4105

65

Ф(C7-C8-H8)

121.3

122.36

22

ν(C8-H8)

0.95

1.0824

66

Ф(C7-C8-C9)

117.5

118.33

23

ν(C8-C9)

1.388

1.3962

67

Ф(H8-C8-C9)

121.3

119.31

24

ν(C9-C10)

1.393

1.4109

68

Ф(O1-C9-C8)

116.9

117.63

25

ν(C11-C12)

1.403

1.422

69

Ф(O1-C9-C10)

120.3

120.31

26

ν(C11-C16)

1.4

1.4192

70

Ф(C8-C9-C10)

122.8

112.06

27

ν(C12-H12)

0.95

1.0839

71

Ф(C4-C10-C5)

121.7

121.71

28

ν(C12-C13)

1.384

1.3969

72

Ф(C4-C10-C9)

120.1

119.36

29

ν(C13-H13)

0.95

1.0853

73

Ф(C5-C10-C9)

118.1

118.93

30

ν(C13-C14)

1.384

1.4089

74

Ф(C2-C11-C12)

120.6

120

31

ν(C14-C15)

1.39

1.4092

75

Ф(C2-C11-C16)

121.4

121.57

32

ν(C15-H15)

0.95

1.089

76

Ф(C12-C11-C16)

117.9

118.42

33

ν(C15-C16)

1.38

1.4015

77

Ф(C11-C12-H12)

119.7

119.25

34

ν(C16-H16)

0.95

1.0823

78

Ф(C11-C12-C13)

120.6

121.12

35

ν(C17-H17A)

0.98

1.0921

79

Ф(H12-C12-C13)

119.7

119.63

36

ν(C17-H17B)

0.98

1.0987

80

Ф(C12-C13-H13)

119.7

121.49

37

ν(C17-H17C)

0.98

1.0931

81

Ф(C12-C13-C14)

120.6

119.61

38

ν(C18-H18A)

0.98

1.091

82

Ф(H13-C13-C14)

119.7

118.9

39

ν(C18-H18B)

0.98

1.0981

83

Ф(O7-C14-C13)

118.3

116.82

40

ν(C18-H18C)

0.98

1.0984

84

Ф(O7-C14-C15)

122.2

122.91

Bending (deg)

85

Ф(C13-C14-C15)

119.4

120.28

41

Ф(C2-O1-C9)

121.3

122.32

86

Ф(C14-C15-H15)

119.9

120.35

42

Ф(H2-O2-C3)

111

106.87

87

Ф(C14-C15-C16)

120.2

119.98

43

Ф(H4-O4-C5)

106

109.42

88

Ф(H15-C15-C16)

119.9

119.67

44

Ф(C6-O5-C17)

114.6

117.95

89

Ф(C11-C16-C15)

121.2

120.59

90

Ф(C11-C16-H16)

119.4

119.54

139

τ(C3-C4-C10-C9)

1.9

0.7674

91

Ф(C15-C16-H16)

119.4

119.87

140

τ(O4-C5-C6-O5)

5.9

3.6437

92

Ф(O5-C17-H17A)

109.5

104.83

141

τ(O4-C5-C6-C7)

177.6

179.0848

93

Ф(O5-C17-H17B)

109.5

110.16

142

τ(C10-C5-C6-O5)

172.7

176

94

Ф(O5-C17-H17C)

109.5

110.56

143

τ(C10-C5-C6-C7)

3.7

0.5637

95

Ф(H17A-C17-H17B)

109.5

109.91

144

τ(O4-C5-C10-C4)

2.4

0.0312

96

Ф(H17A-C17-H17C)

109.5

110.79

145

τ(O4-C5-C10-C9)

179

178.6354

97

Ф(H17B-C17-H17C)

109.5

110.46

146

τ(C6-C5-C10-C4)

176.1

179.62

98

Ф(O6-C18-H18A)

109.5

104.96

147

τ(C6-C5-C10-C9)

2.4

1.0124

99

Ф(O6-C18-H18B)

109.5

111.02

148

τ(O5-C6-C7-O6)

4.69

100

Ф(O6-C18-H18C)

109.5

111.13

149

τ(O5-C6-C7-C8)

174.6

175.42

101

Ф(H18A-C18-H18B)

109.5

109.83

150

τ(C5-C6-C7-O6)

178.5

179.62

102

Ф(H18A-C18-H18C)

109.5

109.82

151

τ(C5-C6-C7-C8)

0.27

103

Ф(H18B-C18-H18C)

109.5

109.97

152

τ(O6-C7-C8-H8)

0.3308

Torsion(deg)

153

τ(O6-C7-C8-C9)

178.2

179.25

104

τ(C9-O1-C2-C3)

2.7

0.0027

154

τ(C6-C7-C8-H8)

179.79

105

τ(C9-O1-C2-C11)

177.6

179.99

155

τ(C6-C7-C8-C9)

0.6356

106

τ(C2-O1-C9-C8)

177.1

179.66

156

τ(C7-C8-C9-O1)

175.9

179.77

107

τ(C2-O1-C9-C10)

1.6

0.398

157

τ(C7-C8-C9-C10)

2.8

0.1676

108

τ(H2-O2-C3-C2)

178.9

179.65

158

τ(H8-C8-C9-O1)

0.1745

109

τ(H2-O2-C3-C4)

0.2192

159

τ(H8-C8-C9-C10)

179.76

110

τ(H4-O4-C5-C6)

179.26

160

τ(O1-C9-C10-C4)

0.7861

111

τ(H4-O4-C5-C10)

0.3852

161

τ(O1-C9-C10-C5)

177.7

179.42

112

τ(C17-O5-C6-C5)

57.31

162

τ(C8-C9-C10-C4)

179.4

179.28

113

τ(C17-O5-C6-C7)

127.21

163

τ(C8-C9-C10-C5)

1

0.645

114

τ(C6-O5-C17-H17A)

177.53

164

τ(C2-C11-C12-H12)

0.0294

115

τ(C6-O5-C17-H17B)

59.34

165

τ(C2-C11-C12-C13)

179.8

179.95

116

τ(C6-O5-C17-H17C)

63.03

166

τ(C16-C11-C12-H12)

 

179.98

117

τ(C6-O6-C7-C6)

177.91

167

τ(C16-C11-C12-C13)

0.8

0.004

118

τ(C18-O6-C7-C8)

2.2

168

τ(C2-C11-C16-C15)

179.9

179.9493

119

τ(C16-O6-C18-H18A)

 

178.95

169

τ(C2-C11-C16-H16)

0.0265

120

τ(C16-O6-C18-H18B)

60.34

170

τ(C12-C11-C16-C15)

0.9

0.0014

121

τ(C16-O6-C18-H18C)

62.4

171

τ(C12-C11-C16-H16)

 

179.98

122

τ(H7-O7-C14-C13)

179.87

172

τ(C11-C12-C13-H13)

 

179.984

123

τ(H7-O7-C14-C15)

0.142

173

τ(C11-C12-C13-C14)

0.4

0.0033

124

τ(O1-C2-C3-O2)

177.9

179.86

174

τ(H12-C12-C13-H13)

 

0.0072

125

τ(O1-C2-C3-C4)

0.0005

175

τ(H12-C12-C13-C14)

 

179.97

126

τ(C11-C2-C3-O2)

1.7

0.1481

176

τ(C12-C13-C14-O7)

179.5

179.99

127

τ(C11-C2-C3-C4)

178.9

179.99

177

τ(H13-C13-C14-O7)

0.0132

128

τ(O1-C2-C11-C12)

0.0709

178

τ(H13-C13-C14-C15)

 

0.0174

129

τ(O1-C2-C11-C16)

179.98

179

τ(H15-C14-C13-O7)

179.99

130

τ(C3-C2-C11-C12)

179.94

180

τ(H15-C15-C14-O7)

0.0091

131

τ(C3-C2-C11-C16)

18.7

0.0116

181

τ(C16-C15-C14-O7)

179.4

179.99

132

τ(O2-C3-C4-O3)

0.232

182

τ(C13-C14-C15-H15)

 

179.99

133

τ(O2-C3-C4-C10)

179.74

183

τ(C13-C14-C15-C16)

0.3

0.0158

134

τ(C2-C3-C4-O3)

179.64

184

τ(C14-C15-C16-C11)

0.7

0.0084

135

τ(C2-C3-C4-C10)

0.8

0.386

185

τ(C14-C15-C16-H16)

 

179.97

136

τ(O3-C4-C10-C5)

3

0.6605

186

τ(H15-C15-C16-C11)

 

179.99

137

τ(O3-C4-C10-C9)

178.5

179.26

187

τ(H15-C15-C16-H16)

 

0.0204

138

τ(C3-C4-C10-C5)

176.5

179.37

 

 


3.2 Vibrational Analysis:

3.2.1 (O-H) Stretch:

In the vibrational spectra, the strength of hydrogen bond decides the position of O-H band. In general the O-H stretching appears in 3600-3400 cm-1 11,12. In the present study the title molecule exhibits a weak absorption peak in the FTIR spectra at 3520 cm-1 and two calculated vibrational modes are assigned at 3549 and 3365 cm-1 with 100 and 99% PED’s respectively.

 

3.2.2 (C-H) stretch:

The hetero aromatic structure of ring R1 of the title compound shows the presence of (C-H) stretching vibration in the region 3133-3056 cm-1, which is the characteristic region for ready identification of C-H stretching vibration and is assigned a strong peak at 3270 cm-1 in the FTIR spectra 13. There is a discrepancy in the calculated and observed peaks due to the position of substitution of other moieties. The (C-H) in-plane bending vibrations appear in the range 1500-1000 cm-1 and are very useful for the purpose of characterization. The (C-H) in-plane bending vibrations appearing as strong band in the FTIR spectra at 1470, 1410 and 1360 cm-1 and are well assigned at 1474, 1402 and 1359 cm-1 respectively. These are well supported by literature 14.

 

3.2.3 Methyl (CH3) Vibrations:

The asymmetric CH3 stretching vibrations are calculated at 3062, 3022, 2994, 2919 and 2909 cm-1 and are assigned to two observed weak absorption peaks at 3220 and 3200 cm-1 respectively in FTIR spectra. These assignments are also supported by literature 15.

 

3.2.4 (C-C)-Vibrations:

The ν(C-C) aromatic stretching vibrational modes also known as semicircle stretching were calculated at 1666, 1639, 1627, 1594, 1580, 1557, 1522, 1402, 1391, 1370, 1333 and 1324 cm-1 and are assigned to vibrational modes in-plane bending ф(C-C-C) and torsional τ(H-C-C-C) mixed with stretching modes. The corresponding absorption peaks are 1680, 1640, 1630, 1610, 1550, 1410 and 1380 cm-1 respectively in the FTIR spectra. Therefore theoretically calculated values are in good agreement with experimental FTIR spectra. The absorption peak at 1410 cm-1 in the FTIR spectra appears to be one of the characteristics peaks of the title molecule.


 

 

Table I: Frequency assignments for Eupalitin at B3LYP/6-311G (d,p) in cm–1, with PED % in Square Brackets

S.

No.

Calc Freq Unscaled

Scaled

Exp freq FTIR

Assignment Modes[PED]

1

3705

3549

3715(m)

ν(O9-H10)[100]

2

3513

3365

3520(m)

ν(O2-H3)[99]

3

3270

3133

3270(s)

ν(C29-H30)[97]

4

3262

3125

ν(C17-H18)[99]

5

3256

3119

ν(C22-H23)[76]+ν(C24-H25)[22]

6

3231

3095

3220(wsh)

ν(C24-H25)[77] + ν(C22-H23)[23]

7

3196

3062

ν(C31-H32)[55] + ν(C31-H34)[32]+ ν(C35-H34)[11]

8

3195

3061

3200(w)

ν(O5-H6)[87]

9

3190

3056

ν(C27-H28)[98]

10

3155

3022

ν(C31-H32)[22]+ν(C31-H33)[33]+ν(C31-H34)[44]

11

3125

2994

2870(m)

ν(C35-H37)[52]+ν(C35-H38)[48]

12

3047

2919

ν(C31-H33)[66]+ν(C31-H34)[19]+ν(C31-H32)[15]

13

3037

2909

ν(C35-H38)[47]+ν(C35-H37)[42]+ν(C35-H36)[11]

14

1695

1624

1680(m)

ν(C1=C12)a[13]+ν(C17=C19)a[10]+ν(C14=C15)[19]

15

1667

1639

1640(s)

ν(C22=C24)[22]+ν(C1=C12)[13]+ν(C29=C27)[22]+ν(C11=C12)[12]

16

1655

1627

1630(m)

ν(C11=C12)[29]

17

1622

1594

1610(m)

ν(C21=C29[11]a + ν(C26=C27)[32]

18

1607

1580

ν(C16=C17)[22]+ν(C19=C20)[24]+φ(C15-C14-C20)[13]

19

1584

1557

1550(s)

ν(C17-C19)[14]+ν(O4-C13)[15]+φ(H6-O5-C14)[17]

20

1548

1522

ν(C21-C29)[10] + φ(H30-C29-C27)[16]+ φ(H28-C27-C29)[16]

21

1528

1502

1510(s)

φ(H33-C31-H34)[53]+ φ(H33-C31-H34)[28]+ τ(H34-C31-O7-C15)[12]

22

1518

1492

φ(H36-C35-H38)[51]+ φ(H36-C35-H37)[10]+ φ(H38-C35-H37)[16]+ τ(H36-C35-O7-C16)[10]

23

1517

1491

1500(m)

φ(H37-C35-H36)[46]+ φ(H38-C35-H37)[23]+τ(H37-C35-O8-C16)[11]

24

1511

1485

φ(H38-C35-H37)[46]+ν(C13-C20)[18]

25

1503

1477

φ(H32-C31-H33)[57]+ φ(H33-C31-H34)[16]+ φ(H32-C31-H34)[15]

26

1499

1474

1470(s)

φ(H36-C35-H38)[11]+ φ(H32-C31-H34)[13]+ φ(H37-C35-H36)[10]

27

1482

1457

φ(H38-C35-H37)[12]+ φ(H34-C31-H33)[13]+ φ(H32-C31-H34)[20]

28

1468

1443

ν(C22-C24)[14]+ν(C27-C29)[10]+ν(O4-C13)[10]

29

1465

1440

ν(O4-C13)[12]

30

1426

1402

1410(vs)

ν(C14-C20)[10]+φ(H6-O5-C14)[19]

31

1415

1391

1380(s)

ν(C16-C17)[19]+ν(C14-C15)[14]+ν(C17-C19)[12]

32

1394

1370

ν(C24-C26)[16] + ν(C27-C29)[15]+ν(C21-C29)[19]+φ(H10-O9-C26)[11]

33

1382

1359

1360(s)

φ(H30-C29-C27)[12]+φ(H6-O5-C14)[17]

34

1356

1333

ν(C21-C29)[15]+φ(H30-C29-C27)[13]

35

1347

1324

ν(C11-C21)[22]+φ(H3-O2-C12)[33]

36

1345

1322

ν(O8-C16)[11]+ν(C17-C19)[13]

37

1296

1274

ν(O9-C26)[11]+ν(O7-C15)[13]+φ(H3-O2-C12)[16]

38

1288

1266

1250(m)

ν(O9-C26)[30]+φ(H23-C22-C24)[11]

39

1242

1221

ν(O7-C15)[16]+φ(H18-C17-C19)[15]

40

1227

1206

1215(m)

φ(H28-C27-C29)[25]+φ(H18-C17-C19)[17]

41

1217

1196

ν(O8-C16)[26]+φ(H18-C17-C19)[17]

42

1206

1185

1190(vs)

ν(O1-C11)[26]+ν(O8-C16)[20]+τ(H37-C35-O8-C16)[17]+

τ(H38-C35-O8-C16)[16]

43

1193

1173

φ(H32-C31-H33)[25]+φ(H32-C31-H34)[12]+τ(H33-C31-O7-C15)[29]+

 τ(H34-C31-O7-C15)[26]

44

1177

1157

1165(w)

φ(H10-O31-C26)[16]+φ(H25-C24-C22)[17]

45

1172

1152

1150(w)

R3-brth[33]

46

1151

1131

φ(H36-C35-H38)[13]+φ(H36-C35-H37)[14]+τ(H36-C35-O8-C16)[39]+

τ(H37-C35-O8-C12)[18]

47

1149

1129

φ(H36-C35-H38)[13]+φ(H36-C35-H37)[14]+τ(H36-C35-O8-C16)[39]+

τ(H37-C35-O8-C12)[18]

48

1141

1122

1125(w)

ν(C22-C24)[10]+φ(H10-O9-C26)[26]+φ(H23-C22-C24)[11]

49

1117

1098

1190(vs)

ν(O8-C35)[10]+φ(O1-C11=C12)[16]+ν(O1-C11)[14]

50

1069

1051

1050(wsh)

ν(O2-C12)[11]+ ν(O8-C35)[17]+φ(C13-C20-C14)[12]

51

1058

1040

ν(O25-C14)[12]+φ(C20-C19-C17)[12]

52

1032

1014

1020(m)

R3-defrm[86]

53

1026

1009

1005(w)

τ(H23-C22-C24-C26)[25]+τ(H30-C29-C27-C26)[34]+τ(H25-C24-C26-C27)[19]

54

1016

999

984(wsh)

τ(H23-C22-C24-C26)[26]+τ(H30-C29-C27-C26)[31]+τ(H25-C24-C26-C27)[15]

55

978

961

950(m)

R2-brth[30]+ν(O7-C31)[52]

56

943

927

ν(O8-C35)[45]+φ(C16-O8-C35)[16]

57

893

878

R3-brth[11]+ φ(C19-O1-C11)[10]

58

882

867

870(m)

τ(H23-C22-C24-C26)[24]+τ(H28-C27-C29-C21)[10]+τ(H25-C24-C26-C27)[33]+

ω(O9-C24-C27-C26)[13]

59

872

857

τ(C20-C19-C17-H18)[50]+ ω(O8-C15-C17-C16)[18]+ω(C20-C17-O1-C19)[10]

60

856

841

τ(H28-C27-C29-C21)[53]+τ(H30-C29-C27-C26)[17]+τ(H25-C24-C26-C27)[12]

61

847

833

τ(H6-O5-C14-C15)[85]

62

821

807

R3-def[67]

63

809

795

τ(H18-C17-C16-C20)[17]+ω(O5-C15-C20-C14)[12]+ω(O7-C14-C16-C15)[12]

64

790

777

845(m)

τ(H18-C17-C16-C20)[18]+ω(O5-C15-C20-C14)[15]+ω(O7-C14-C16-C15)[12]

65

768

755

τ(C21-C29-C27-C26)[18]+ ω(O4-C20-C12-C13)[11]

66

758

745

775(wsh)

τ(C21-C29-C27-C26)[18]+ω(C20-C17-O1-C19)[10]

67

733

721

φ(O1-C17-C19)[11]+φ(O8-C16-C17)[13]

68

676

665

ω(O1-C17-C19-C20)[16]+τ(C1-O1-C19-C17)[18]

69

674

663

ω(O1-C17-C19-C20)[20]+τ(C1-O1-C19-C17)[14]

70

656

645

φ(C22-C24-C26)[18]+φ(C29-C27-C26)[27]+φ(C21-C29-C27)[19]

71

638

627

ω(C12-C21-O1-C11)[23]+ω(O4-C20-C12-C13)[11]+τ(H3-O2-C12-C13)[16]

72

625

614

639(m)

R1&R2-puck[20]

73

615

605

  612(wsh)

ω(O5-C15-C20-C14)[26]+τ(H3-O2-C12-C13)[15]+τ(H18-C17-C19-C20)[12]+

ω(O8-C15-C17-C16)[11]

74

606

596

τ(H3-O2-C12-C13)[62]+τ(H3-O2-C12-C11)[15]

75

600

590

φ(C19-O1-C11)[18]+φ(C12=C11-O1)[20]

76

562

552

520(wsh)

R1R2&R3 Puck[16]

77

519

510

ω(O9-C24-C27-C26)[33]+τ(C29-C27-C26-C24)[10]

78

498

490

φ(C15-C14-C20)[15]+φ(C31-O7-C15)[10]

79

479

471

φ(C31-O7-C15)[14]

80

438

431

430(s)

τ(C14-C15-C16-C17)[18]+τ(C21-C22-C24-C26)[12]

81

429

422

φ(O9-C26-C27)[28]+φ(C11-C21-C29)[11]

82

428

421

τ(C22-C24-C26-C27)[14]+τ(C29-C27-C24-C26)[13]

83

410

403

ω(O2-C13-C11-C12)[12]+φ(O9-C26-C27)[10]+φ(C35-O8-C16)[14]

84

397

390

ω(O2-C13-C11-C12)[25]

85

377

371

360(s)

τ(H10-O9-C26-C24)[57]+τ(H10-O9-C26-C27)[38]+φ(O5-C14-C20)[12]+ φ(O2-C12-C13)[10]

86

352

346

φ(O4=C13-C12)[25]+φ(O2=C12-C13)[14] +φ(O5-C14-C20)[15]

87

331

325

τ(C19-O1-C11-C21)[13]

88

321

316

τ(C19-O1-C11-C21)[12]

89

297

292

φ(O1-C11-C21)[13]+φ(O2-C12-C13)[25]

90

288

283

ω(C13-C14-C19-C20)[12]

91

279

274

ω(C13-C14-C19-C20)[14]

92

255

251

ω(C13-C14-C19-C20)[11] +ω(C20-C17-O1-C19)[12]+τ(H36-C35-O8-C16)[12]+ ω(O5-C15-C20-C14)[11]

93

238

234

ν(C11-C21)[12]+φ(O7-C15-C16)[12]

94

217

213

τ(H38-C35-O8-C16)[11]+ω(O8-C15-C17-C16)[12]+τ(H37-C35-O8-C16)[12]+ τ(C16-C17-C19-C20)[20]

95

205

202

φ(O7-C15-C16)[13]+φ(C31-O7-C15)[13]+τ(C15-C14-C20-C19)[11]

96

182

179

R1,R2&R3-rock[65]

97

156

153

τ(C31-H32-H33-H34)[42]

98

152

149

τ(C31-H32-H33-H34)[41]

99

130

128

ω(C20-C17-O1-C19)[10]+τ(C14-C20-C19-C17)[18]+τ(C19-O1-C11-C21)[10]+

τ(C35-O8-C16-C15)[10]

100

113

111

τ(C17-C19-O1-C11)[12]+τ(C35-O8-C16-C15)[45]

101

82

81

R1,R2 & R3-rock[49]

102

79

78

τ(C17-C19-O1-C11)[13]+τ(C5-C14-C20-C19)[12]

103

71

70

τ(C14-C20-C19-C17)[15]+τ(C35-O8-C16-C15)[27]

104

63

62

τ(C31-O7-C15-C14)[62]

105

42

41

τ(O1-C11-C21-C2)[81]

106

34

33

τ(C14-C20-C19-C17)[14]+τ(C19-O1-C11-C21)[35]+ω(C11-C22-C29-C21)[14]

Abbreviations:- ν: Stretching; s: symmetric stretching; as: asymmetric stretching; asi: asymmetric in plane, def: deformation;  φ: bending in-plane; ω: bending out-of-plane; τ: torsion/twisting; R: ring; puck: puckering; roc: in plane rocking; breth:breathing.


3.2.5 (C-O) Vibration:

In the present study the ν(C-O) stretching vibrational mode is calculated in the frequency range of 1322-1190 cm-1 which is in good coherence with the experimental FTIR values. The various bending and torsional modes assigned in this study are also supported by the literature12. The absorption peak at 1190 cm-1 in the FTIR spectra is very strong and seems to be one of the characteristics peaks of the present compound.

 

3.2.6 Low-Frequency Region Modes:

The lower frequency vibrational modes are of great importance as it provides the information about the weak intermolecular interactions, which occurs in enzyme reactions and it is also useful for interpretation of the effect of e-m radiation on biological systems 16,17. In the present study several out of plane modes namely torsional, wagging, ring deformation, ring puckering and ring-rocking modes are calculated in the range 875-33 cm-1 and are in coherence with the experimental FTIR spectra. Two peaks calculated at 431 and 371 cm-1 are assigned to 430 and 360 cm-1 to the experimental values are also the characteristics peaks of the title molecule. Some discrepancies are seen in the experimental and theoretical intensity in lower range of frequencies

 

Which, are possibly due to impurity of the sample used, the intermolecular interactions, an harmonicity and probable mixing of different modes of vibrations.

 

3.3 Electronic Properties:

The frontier molecular orbital not only take part in chemical reactions but also the energy gap between them tells about the quantitative chemical reactivity of the molecule 18. HOMO-LUMO energy gap is an important indicator of the stability of the compound. Small energy gap suggests that the molecule is more polarizable, is generally associated with high chemical reactivity and low kinetic stability, and is termed as soft molecule 19,20. In present DFT study, the plots of LUMO and HOMO are shown in figure II and III respectively, and their values are given in table III. From 2D plot of HOMO    (-5.95734 eV), it is clear that HOMO is distributed on all three rings R1, R2 and R3 except the atoms C16 and O8. The 2D plot of LUMO (-2.394688 eV) of the title molecule is spread on all three rings R1, R2 and R3 except again the C16 and O8 atoms. The frontier orbital energy band gap is calculated by the difference of LUMO and HOMO values and is found to be 3.56 eV.

 

The molecular electrostatic potential (MEP) surface plot mapped on to the iso electron density surface, shows the molecular shape, size and electrostatic potential values in terms of color coding and is an experimental tool in the identification of correlation between molecular structure and the physiochemical property relationship of molecules including bio molecules 21-26. The MEP map of the title molecule is shown in fig IV, with color coding ranging from -4.003 e-4 to 4.003 e-4. Various electronic parameters viz, ionization potential (I), electron affinity (A), absolute electro negativity (χ) and chemical hardness (η) etc. at B3LYP/6-311++ G(d,p) level are calculated as the negative energy eigen values of HOMO and LUMO respectively. These parameters are often used to describe the chemical reactivity of the molecules. All the parameters are presented in table III and it is evident that the value of electro negativity (χ) is high for the present molecule (4.176016 eV).

 

Fig. 2. Homo of Eupalitin as seen by gaussview 5.0

 

 

Fig. 3. Lumo of eupalitin as seen by gaussview 5.0

 

 

Fig. 4. 2D MEPS plot of Eupalitin as seen by Gaussview 5.0

 

Table III: Electronic Parameters and Thermo Chemistry of Eupalitin calculated at 6-311++(d,p)

S. No.

Parameter

DFT Values (eV)

1

eHOMO

5.957344

2

eLUMO

2.394688

3

Δ(eHOMO–eLUMO)

3.562656

4

µx

2.9542

5

µy

2.9542

6

µz

1.4829

7

µ

4.222

8

Ionization Potential(I)

5.957344

9

Electron Affinity(A)

2.394688

10

Electronegativity

4.176016

Index (χ)

11

Chemical Hardness(η)

1.781328

12

Global Hardness (S)

0.280689

13

Electrophilicity (ω)

62.129

 

 

Table IV: Polarizability and first static hyperpolarizability for Eupalitin calculated at B3LYP/6-311++G(d,p) level

Compo-nents

Polarizability

Compo-nents

Hyperpolarizability

a.u

a.u.

αxx

-126.9198

βXXX

172.879

αxy

-16.1837

βXXY

-83.5488

αyy

-127.5581

βXYY

-44.2854

αxz

-8.3936

βYYY

73.7869

αyz

-1.3139

βxxz

49.4112

αzz

-141.7956

βXYZ

4.2988

<α>

-132.091

βYYZ

-1.1632

βXZZ

-22.2741

βYZZ

-3.4601

βZZZ

0.3716

β1

11303.83608

β2

174.821284

β3

2363.865504

βtotal

117.6542514

 

3.4 Dipole Moment, Polarizability and First-Satic Hyperpolarizability:

The dipole moment, polarizability and hyperpolarizabilty are important non-linear optical (NLO) response properties for organic molecules. With the help of polarizabilty and hyperpolarizability one can estimate the stability of chemical bonds and characteristics of interactions27,28. The value of dipole moment is calculated as 4.22 Debye for the title molecule. The components αXX, αYY and αZZ of the mean polarizability <α> are calculated as -126.9198 as -127.5581 and -141.795 a.u. which suggest that title molecule is elongated maximum along Z-axis. The largest βXXX component (172.879 a.u) hyperpolarizability βtotal suggest that the charge delocalization occurs maximum along the X-axis and the molecule is more optically along the X-axis. The β components of the title molecule are shown in table IV in atomic units where 1 a.u.= 8.3693* 10-33 e.s.u. The calculated value of βtotal for Eupalitin was found to be 117.6543 a.u. (0.984* 10-30 esu) which is nearly five times to that of urea (0.1947* 10-30 esu).

 

3.5 Molecular Docking:

Molecular docking is a method to predict the manner in which two molecules, such as a drug (protein) and a receptor (ligand or molecule) fit together and dock to each other. Molecular docking is an important technique in structure based drug design and is often the starting point in our search for a drug against a given target molecule. In order to perform a theoretical study for inhibition of protein “Glutathione s-Transferase 1AQW” by the title ligand “Eupalitin”, we have carried out molecular docking studies using HEX program 8.0. The target protein has been obtained from the protein data bank (PDB) database with PDB ID =1AQW 29. The choice of target protein was made keeping in view the documented anti-microbial activity of the title compound which motivated us to perform random screening of bacterial proteins for binding with Eupalitin and eventually led to identification of the protein as 1AQW as the one giving the best binding score. Fig V shows the docked conformation of the protein 1AQW showing the interaction with the residues in the binding site of the target ligand Eupalitin.


 

Fig. 5. 2D  Docking of Eupalitin with IAQW Protein


The overall docking score can be obtained as function of the six degrees of freedom in a rigid body docking search just by writing expressions for the overlap of pairs of parametric functions. The docking score thus obtained can be approximated to an interaction energy “e-value” which is minimized successively. The higher the negative e-value, the better is the docking. In the present study the total e-value is calculated as -138.26 for 1AQW, which suggest that the title compound Eupalitin can inhibit the 1AQW protein.

 

CONCLUSIONS:

In the present work, we have carried out os comprehensive study on 3,5,4’-Trihydroxy-6,7-Dimethoxy-Flavone (Eupalitin), which has been a synthetic molecule of enough pharmacological interest ever since it was implicated in carcenogenic activity. The molecular geometry, vibrational wave numbers, and NLO behavior , of title molecule have been calculated using DFT (B3LYP) method adopting 6-311++(d,p) basis set. A good coherence between experimental and calculated normal modes of vibrations is achieved. The nonlinear optical (NLO) behviour of the title molecule has been investigated by the dipole moment, the polarizability and first hyperpolarizability measurements. The frontier orbital energy gap is calculated 3.56 eV. Dipole moment μ, molecular polarizability <α> and total first static hyperpolarizability βtotal are computed as 4.22 D, -132.091 a.u. and 117.654 respectively. Lower value of frontier orbital energy gap and a higher value of dipole moment suggest that the nature of the title compound is highly reactive. The value of βtotal is nearly five times to that of urea indicating that Euaplitin possesses nonlinear optical properties and is a potential candidate for nonlinear optical applications. The molecular orbitals and MEPS map may lead to the understanding of properties and activity of Eupalitin. The results of molecular docking studies speculate that this biologically active molecule might emerge as a potential candidate for the inhibition to protein “Glutathione s-Transferase 1AQW” thereby indicating its possible pharmacological importance. Thus, the present study provides a comprehensive vibrational analysis, structural information and electronic properties of the title compound. Although the molecular docking studies have led to the identification of a target protein of bacterial origin which may satisfactorily explain the molecular basis of antimicrobial activity of the title compound, yet it furnishes no clue as to how the same compound might exert an anticancer effect. Besides, the sequence of molecular events triggered by the binding of Eupalitin with the target protein 1AQW that results in cytotoxicity action remains to be explored and is likely to form the basis of future studies about the therapeutic potential of the title compound.

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Received on 25.08.2017         Modified on 19.09.2017

Accepted on 28.10.2017         © AJRC All right reserved

Asian J. Research Chem. 2017; 10(6):789-797.

DOI:   10.5958/0974-4150.2017.00132.8