Open Access

Synthesis, spectroscopic, dielectric, molecular docking and DFT studies of (3E)-3-(4-methylbenzylidene)-3,4-dihydro-2H-chromen-2-one: an anticancer agent

  • T. Beena1,
  • L. Sudha1,
  • A. Nataraj1,
  • V. Balachandran2,
  • D. Kannan3 and
  • M. N. Ponnuswamy4Email author
Chemistry Central Journal201711:6

DOI: 10.1186/s13065-016-0230-8

Received: 9 May 2016

Accepted: 7 December 2016

Published: 10 January 2017

Abstract

Background

Coumarin (2H-chromen-2-one) and its derivatives have a wide range of biological and pharmaceutical activities. They possess antitumor, anti-HIV, anticoagulant, antimicrobial, antioxidant, and anti-inflammatory activities. Synthesis and isolation of coumarins from different species have attracted the attention of medicinal chemists. Herein, we report the synthesis, molecular structure, dielectric, anticancer activity and docking studies with the potential target protein tankyrase.

Results

Molecular structure of (3E)-3-(4-methylbenzylidene)-3,4-dihydro-2H-chromen-2-one (MBDC) is derived from quantum chemical calculations and compared with the experimental results. Intramolecular interactions, stabilization energies, and charge delocalization are calculated by NBO analysis. NLO property and dielectric quantities have also been determined. It indicates the formation of a hydrogen bonding between –OH group of alcohol and C=O of coumarin. The relaxation time increases with the increase of bond length confirming the degree of cooperation and depends upon the shape and size of the molecules. The molecule under study has shown good anticancer activity against MCF-7 and HT-29 cell lines. Molecular docking studies indicate that the MBDC binds with protein.

Conclusions

In this study, the compound (3E)-3-(4-methylbenzylidene)-3,4-dihydro-2H-chromen-2-one was synthesized and characterized by spectroscopic studies. The computed and experimental results of NMR study are tabulated. The dielectric relaxation studies show the existence of molecular interactions between MBDC and alcohol. Theoretical results of MBDC molecules provide the way to predict various binding sites through molecular modeling and these results also support that the chromen substitution is more active in the entire molecule. Molecular docking study shows that MBDC binds well in the active site of tankyrase and interact with the amino acid residues. These results are compared with the anti cancer drug molecule warfarin derivative. The results suggest that both molecules have comparable interactions and better docking scores. The results of the antiproliferative activity of MBDC and Warfarin derivative against MCF-7 breast cancer and HT-29 colon cancer cell lines at different concentrations exhibited significant cytotoxicity. The estimated half maximal inhibitory concentration (IC 50) value for MBDC and Warfarin derivative was 15.6 and 31.2 μg/ml, respectively. This enhanced cytotoxicity of MBDC in MCF-7 breast cancer and HT-29 colon cancer cell lines may be due to their efficient targeted binding and eventual uptake by the cells. Hence the compound MBDC may be considered as a drug molecule for cancer.

Keywords

Chromen DFT Dielectric studies Molecular docking Anti-cancer activity

Background

Coumarin (2H-chromen-2-one) is one of the important secondary metabolic derivatives which occurs naturally in several plant families. Coumarins are used as a fragrance in food and cosmetic products. Coumarins are widely distributed in the plant kingdom and are present in notable amounts in several species, such as Umbelliferae, Rutaceae and Compositae.

Coumarin and its derivatives have a wide range of biological and pharmaceutical activities. They possess antitumor [1], anti-HIV [2], anticoagulant [3], antimicrobial [4], antioxidant [5] and anti-inflammatory [6] activities. The antitumor activities of coumarin compounds have been extensively examined [7]. Synthesis and isolation of coumarins and its derivatives from different species have attracted the attention of medicinal chemists. The spectroscopic studies led to the beneficial effects on human health and their vibrational characteristics [8, 9].

Herein, we report the synthesis, the computed electronic structure and their properties in comparison with experimental FT-IR, FT Raman, UV and NMR spectra. Further, intra and inter molecular interactions, HOMO–LUMO energies, dipole moment and NLO property have been determined. The dielectric studies confirm the molecular interactions and the strength of hydrogen bonding between the molecule and the solvent ethanol. In addition, anti-cancer activity against MCF-7 and HT-29 cell lines and molecular docking studies have also been performed.

Experimental

Preparation of MBDC

MBDC was synthesised from the mixture of methyl 2-[hydroxy(4-methylphenyl)methyl]prop-2-enoate (0.206 g, 1 mmol) and phenol (0.094 g, 1 mmol) in CH2Cl2 solvent and allowed to cool at 0 °C. To this solution, concentrated H2SO4 (0.098 g, 1 mmol) was added and stirred well at room temperature (Scheme 1). After completion of the reaction as indicated by TLC, the reaction mixture was neutralized with 1 M NaHCO3 and then extracted with CH2Cl2. The combined organic layers were washed with brine (2 × 10 ml) and dried over anhydrous sodium sulfate. The organic layer was evaporated and the residue was purified by column chromatography on silica gel (100–200) mesh, using ethyl acetate and hexane (1:9) as solvents. The pure form of the title compound was obtained as a colorless solid (0.162 g). Yield: 65%, melting point: 132–134 °C.
Scheme 1

Reaction scheme showing the synthesis of the compound (MBDC)

Instrumentation

FTIR, FT-Raman, UV–Vis and NMR spectra were recorded using Bruker IFS 66 V spectrometer, FRA 106 Raman module equipped with Nd:YAG laser source, Beckman DU640 UV/Vis spectrophotometer and Bruker Bio Spin NMR spectrometer with CDCl3 as solvent, respectively. The dielectric constant (ε′) and dielectric loss (ε″) at microwave frequency were determined by X-Band microwave bench and the dielectric constant (ε) at optical frequency was determined by Abbe’s refractometer equipped by M/s. Vidyut Yantra, India. The static dielectric constant (ε0) was measured by LCR meter supplied by M/s. Wissenschaijftlich Technische, Werkstatter, Germany. Anticancer activity for two cell lines was obtained from National Centre for Cell Sciences, Pune (NCCS).

Cell line and culture

MCF-7 and HT-29 cell lines were obtained from National Centre for Cell Sciences, Pune (NCCS). The cells were maintained in Minimal Essential Medium supplemented with 10% FBS, penicillin (100 U/ml), and streptomycin (100 μg/ml) in a humidified atmosphere of 50 μg/ml CO2 at 37 °C.

Reagents

MEM was purchased from Hi Media Laboratories, Fetal Bovine Serum (FBS) was purchased from Cistron laboratories trypsin, methylthiazolyl diphenyl-tetrazolium bromide (MTT) and dimethyl sulfoxide (DMSO) were purchased from (Sisco Research Laboratory Chemicals, Mumbai). All of other chemicals and reagents were obtained from Sigma Aldrich, Mumbai.

In vitro assay for anticancer activity (MTT assay)

Cells (1 × 105/well) were plated in 24-well plates and incubated at 37 °C with 5% CO2 condition. After the cell reaches the confluence, the various concentrations of the samples were added and incubated for 24 h. After incubation, the sample was removed from the well and washed with phosphate-buffered saline (pH 7.4) or MEM without serum. 100 µl/well (5 mg/ml) of 0.5% 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-tetrazolium bromide (MTT) was added and incubated for 4 h. After incubation, 1 ml of DMSO was added in all the wells. The absorbance at 570 nm was measured with UV-Spectrophotometer using DMSO as the blank. The %cell viability was calculated using the following formula:
$$\% {\text{cell viability }} = \frac{{\text{ A}}570{\text{ of treated cells }}}{{\text{ A}}570{\text{ of control cells }}} \times 100$$

Computational methods

Electronic structure and optimized geometrical parameters were calculated by density functional theory (DFT) using Gaussian 09W software package [10] with B3LYP/6-31 + G(d,p) basis set method and Gauss-View molecular visualization program package on a personal computer [11]. Vibrational normal mode wavenumbers of MBDC were derived with IR intensity and Raman intensity. The entire vibrational assignments were executed on the basis of the potential energy distribution (PED) of vibrational modes from VEDA 4 program and calculated with scaled quantum mechanical (SQM) method. The X-ray crystal structure of tankyrase (PDB ID: 4L2K) [12] was obtained from Protein Data Bank (PDB). All docking calculations were performed using induced-fit-docking module of Schrödinger suite [13].

Results and discussion

Molecular geometry

The optimized molecular structure of MBDC along with the numbering of atoms is shown in Fig. 1. The calculated and experimental bond lengths and bond angles are presented in Table 1. The molecular structure of the compound is obtained from Gaussian 09W and GAUSSVIEW program. The optimized structural parameters (bond lengths and bond angles) calculated by DFT/B3LYP with 6-31 + G(d,p) basis set are compared with experimentally available X-ray data for benzylidene [14] and coumarin [15].
Fig. 1

Optimized molecular structure and atomic numbering of MBDC

Table 1

Optimized geometrical parameters of (3E)-3-(4-methylbenzylidene)-3,4-dihydro-2H-chromen-2-one at B3LYP/6-31 + G(d,p) level of theory

Bond length

Value (Å)

Expt.a

Bond angle

Value (°)

Expt.a

C1–C2

1.411

1.407 (15)

C2–C1–C6

117.36

118.8 (14)

C1–C6

1.408

 

C6–C1–C7

124.68

124.0 (15)

C1–C7

1.464

1.456 (14)

C1–C2–H31

121.38

120.2 (15)

C2–C3

1.390

1.378 (14)

C3–C2–H18

119.56

119.0 (14)

C2–H18

1.086

0.950 (15)

C2–C3–C4

121.06

121.5 (15)

C3–C4

1.404

1.378 (14)

C3–C4–C5

117.74

117.3 (15)

C3–H19

1.087

0.990 (15)

C3–C4–C20

120.92

120.3 (15)

C4–C5

1.401

1.403 (15)

C5–C6–H25

118.79

119.8 (15)

C4–C20

1.509

1.499 (14)

C1–C7–C8

130.11

131.9 (14)

C5–C6

1.394

1.389 (14)

C8–C7–H26

114.99

 

C5–H24

1.087

0.990 (15)

C7–C8–C13

115.44

116.8 (14)

C6–H25

1.083

 

C7–C8–C9

126.11

125.5 (14)

C7–C8

1.355

 

C8–C9–C10

112.38

 

C7–H26

1.088

0.950 (15)

C8–C9–H28

109.63

 

C8–C9

1.511

 

C8–C9–H29

108.74

 

C8–C13

1.491

1.491 (14)

H28–C9–H29

106.06

107.2 (15)

C9–C10

1.509

 

C9–C10–C11

119.35

 

C9–H28

1.102

 

C9–C10–C14

122.68

 

C10–C11

1.394

 

C8–C13–O27

125.15

 

C10–C14

1.400

 

C10–C14–H30

118.76

 

C11–O12

1.387

 

O12–C11–C17

116.22

116.6 (15)

C11–C17

1.395

 

C9–C8–C13

118.44

118.96 (14)

O12–C13

1.376

 

C11–C10–C14

117.93

 

C13=O27

1.211

1.261 (15)

C1–C7–H26

114.86

 

C14–H30

1.087

 

C1–C6–C5

120.92

120.7 (14)

C15–C16

1.399

 

C1–C6–H25

120.23

 

C17–H33

1.084

 

C2–C3–H19

119.40

119.8 (15)

C10–C11–O12

121.79

120.8 (15)

aX-ray data from Refs. [14] and [15]

From the structural data, it is observed that the various C–C bond distances calculated between the rings 1 and 2 and C–H bond lengths are comparable with that of the experimental values of benzylidene and coumarins. The influence of substituent groups on C–C bond distances of ring carbon atoms seems to be negligibly small except that of C3–C4 (1.404 Å) bond length which is slightly longer than the normal value.

The calculated bond lengths of C8–C13 and C4–C20, are 1.491 and 1.509 Å in the present molecule and comparable with the experimental values of 1.491 and 1.499 Å. The experimental value for the bond C13–O7 (1.261 Å) is little longer than the calculated value 1.211 Å. The C–H bond length variations are due to the different substituent’s in the ring and other atoms [16]. The hyper-conjugative interaction effect leads to the deviation of bond angle for C10–C11–O12 (121.79°) from the standard value (120.8°).

Vibrational spectra

The title compound possesses C s point group symmetry and the available 93 normal modes of vibrations are distributed into two types, namely A′ (in-plane) and A″ (out-plane). The irreducible representation for the Cs symmetry is given by ГVib = 63 A′ + 30 A″. All the vibrations are active in both IR and Raman spectra. Vibrational assignments have been carried out from FT-IR (Fig. 2) and FT-Raman (Fig. 3) spectra. The theoretically predicted wavenumbers along with their PED values are presented in Table 2. The fundamental vibrational modes are also characterized by their PED. The calculated wavenumbers are in good agreement with experimental wavenumbers.
Fig. 2

a Experimental and b predicted FT-IR spectra of MBDC

Fig. 3

a Experimental and b predicted FT-Raman spectra of MBDC

Table 2

The observed FT-IR, FT-Raman and calculated frequencies (in cm−1) using B3LYP/6-31 + G (d,p) along with their relative intensities, probable assignments, reduced mass and force constants of (3E)-3-(4-methylbenzylidene)-3,4-dihydro-2H-chromen-2-one

Mode nos

Observed frequencies (cm−1)

Calculated frequencies (cm−1)

Reduced mass (amu)

Force constant (mdyn/Å)

IR intensity (km/mol)

Raman intensity (Å4 amu−1)

Vibrational assignments (PED%)

FTIR

FT Raman

Unscaled

Scaled

1

  

23

20

4.139

0.001

0.140

98.862

τ Ring (56), τ CH3 (20)

2

 

30

36

29

1.041

0.001

0.259

2.839

τ Ring (56), τ CH3 (20)

3

 

43

48

42

4.317

0.006

0.138

4.698

τ Ring (55), τ CH3 (18)

4

 

60

61

60

4.037

0.009

0.126

4.758

τ Ring (56), τ CH3 (20)

5

  

81

78

6.433

0.025

1.029

1.382

τ Ring (55), τ CH3 (22)

6

  

101

96

4.785

0.029

0.456

0.906

γ C=O (58), τ CH3 (21)

7

  

156

143

4.419

0.064

1.546

0.321

τ CH3 (56)

8

  

189

181

3.393

0.072

0.402

1.098

τ CH2 (56), γ CH3 (18)

9

 

200

225

202

6.604

0.197

2.382

0.235

γ C–CH3 (54), γ CH (18), γ CH3 (12)

10

  

252

237

4.366

0.164

1.529

0.314

γ CC (62), γ CH (20), γ CH2 (10)

11

  

274

255

4.050

0.179

1.403

0.314

γ CCC (60), γ CH (22), γ CH3 (11)

12

  

314

286

4.114

0.240

0.632

0.065

γ CCC (59), γ CH (18), γ CH3 (10)

13

  

327

309

5.288

0.335

1.339

0.029

γ CCC (58), γ CH (18), γ CH3 (11)

14

 

350

368

354

3.122

0.249

0.038

0.119

γ CCC (60), γ CH (22), γ CH3 (12)

15

 

400

409

400

3.550

0.350

1.104

0.482

γ CCC (62), γ CH (18), γ CH3 (10)

16

  

421

413

2.977

0.310

1.829

0.326

γ CCC (62), γ CH (20), γ CH3 (10)

17

  

444

437

4.136

0.482

3.120

0.773

γ CCC (62), γ CH (20), γ CH3 (11)

18

 

450

457

453

4.033

0.496

3.817

0.144

γ CCC (63), γ CH (18), γ CH3 (12)

19

  

490

479

5.515

0.783

24.603

0.378

βC=O (58), βCC (22), βCO (10)

20

 

500

524

506

2.790

0.452

12.486

0.794

γ C–O (64), γ CH3 (23), γ CO (10)

21

  

540

527

5.569

0.786

5.539

0.239

γ CH (58), γ CH3 (22), γ CC (10)

22

 

540

545

540

3.662

0.642

4.599

0.033

γ CH (58), γ CC (21), γ CH2 (11)

23

 

575

582

572

6.588

1.319

2.309

0.138

γ CH (58), γ CH3 (20), γ CC (11)

24

 

600

639

601

6.329

1.526

7.519

0.104

γ CH (56), γ CC (20), γ CH3 (10)

25

  

650

633

6.834

1.703

0.662

0.176

γ CH (58), γ CC (18), γ CH2 (11)

26

  

693

669

5.112

1.447

4.947

0.007

γ CH (56), γ CH3 (18), γ CC (12)

27

  

711

689

3.832

1.142

0.262

0.116

γ CH (56), γ CC (16)

28

  

727

716

3.876

1.208

9.921

0.085

γ CH (56), γ CC (18)

29

 

725

737

723

5.549

1.776

11.299

0.128

γ CH (58), γ CC (18)

30

  

740

735

4.346

1.404

0.599

0.184

βC–CH3 (60), βCH (23)

31

750

 

768

748

1.335

0.465

62.541

0.034

βC–O (62), βCC (22)

32

  

778

760

4.144

1.481

7.458

0.587

βCC (58), βCH (21), βCH3 (10)

33

810

 

829

811

1.610

0.653

37.872

0.230

βCCC (63), βCH (21), βCH3 (12)

34

  

851

824

1.26

0.540

0.813

0.119

βCCC (63), βCH (18), βCH3 (11)

35

  

858

830

3.739

1.625

14.149

0.099

βCCC (62), βCH3 (20), βCH (10)

36

  

862

838

2.202

0.964

0.532

0.221

βCCC (62), βCH3 (21), βCH (12)

37

 

850

876

850

1.962

0.888

3.587

0.199

βCCC (56), βCH (18), βCH3 (10)

38

  

919

861

6.652

3.314

11.953

0.057

βCCC (58), βCH3 (18), βCH (12)

39

  

947

869

1.572

0.831

5.009

0.061

βCCC (56), βCH (16), βCH3 (11)

40

 

875

954

872

1.399

0.751

11.534

1.087

βCCC (61), βCH (20), βCH3 (10)

41

  

970

889

1.579

0.877

5.474

0.037

βCH (78), ν CC (18)

42

 

900

981

903

1.476

0.837

5.323

0.410

βCH (76), ν CC (16)

43

  

984

923

1.377

0.786

2.738

0.150

βCH (78), ν CC (13)

44

  

988

951

1.282

0.738

0.051

0.002

βCH (66), ν CC (16)

45

  

1010

968

1.409

0.848

2.809

0.020

βCH (66), ν CC (20)

46

 

990

1033

992

2.848

1.794

2.530

0.024

βCH (70), ν CC (18)

47

  

1056

1011

2.122

1.396

3.275

0.289

βCH (76), ν CC (18)

48

  

1060

1029

1.545

1.024

11.399

0.009

βCH (78), ν CC (17)

49

  

1088

1042

4.259

2.975

171.99

0.044

βCH (78), ν CC (17)

50

 

1000

1133

1053

1.775

1.344

19.980

0.028

βCH2ipr (67), βCH (20)

51

  

1148

1061

1.367

1.063

20.088

0.106

γ CH2opr (66), βCH (21)

52

 

1075

1180

1072

1.113

0.914

4.889

0.005

βCH3ipr (65), βCC (30)

53

 

1100

1190

1104

2.389

1.994

564.050

3.029

γ CH3opr (71), βCC (23)

54

 

1150

1215

1153

1.274

1.109

16.185

0.942

ν CO (58), βCH (18), ν CC (11)

55

1189

 

1218

1190

1.580

1.381

27.443

0.044

ν CO (58), βCH (18), ν CC (12)

56

  

1227

1197

2.167

1.924

37.004

1.290

ν C=C (82), βCH3 (14)

57

  

1238

1209

2.485

2.247

7.534

0.045

ν CC (71), βCH (16), ν CH3 (12)

58

  

1255

1217

2.115

1.964

33.951

0.281

ν C–CH3 (50), βCH (20), βCO (12)

59

1215

 

1258

1231

3.099

2.893

219.799

0.644

βCH2sb (66), βCC (22), βCH (11)

60

  

1288

1243

1.825

1.785

19.982

0.588

βCH2asb (70), βCC (20), βCH (10)

61

 

1250

1340

1250

5.462

5.782

49.937

0.759

βCH3sb (71), βCC (23), βCH (11)

62

1261

 

1342

1260

1.625

1.727

2.543

0.527

βCH3asb (66), βCH (17), ν CC (10)

63

  

1349

1287

2.373

2.544

13.033

0.436

βCH3asb (60), βCH (18), ν CC (10)

64

  

1369

1306

2.450

2.709

31.517

0.047

ν CC (68), βCH (18)

65

  

1407

1330

1.776

2.074

9.480

0.143

ν CC (66), βCH (19)

66

  

1420

1343

1.248

1.483

0.324

0.393

ν CC (66), βCH (18)

67

  

1440

1362

2.310

2.850

7.463

0.084

ν CC (68), βCH (19)

68

  

1476

1387

1.277

1.449

12.963

0.069

ν CC (68), βCH (19)

69

  

1491

1395

1.072

1.450

11.786

0.102

ν CC (70), βCH (18)

70

  

1492

1404

2.295

3.013

30.676

0.013

ν CC (70), βCH (17)

71

1432

 

1496

1430

1.114

1.469

9.704

0.119

ν CC (68), βCH (17)

72

  

1529

1487

2.593

3.574

57.049

0.019

ν CC (66), βCH (18)

73

1500

 

1548

1502

2.482

3.505

23.043

0.262

ν CC (65), βCH (18)

74

 

1540

1603

1543

5.415

8.200

5.106

0.867

ν CC (66), βCH (19)

75

  

1636

1587

6.310

9.958

21.097

0.660

ν CC (65), βCH (18)

76

  

1654

1592

6.049

9.754

145.323

3.229

ν CC (66), βCH (18)

77

  

1659

1604

6.840

11.109

9.718

0.093

ν CC (68), βCH (18)

78

 

1600

1668

1615

7.222

11.846

91.204

0.131

ν CC (70), βCH (16)

79

1616

1690

1793

1692

12.541

23.775

370.738

0.460

ν C=O (72), ν CC (14)

80

  

2980

2801

1.072

5.615

14.012

0.299

ν ssCH2 (80)

81

 

2800

3034

2809

1.039

5.641

33.955

0.722

ν assCH2 (82)

82

  

3080

2863

1.088

6.085

4.273

0.081

ν ssCH3 (72), ν CH (23)

83

  

3092

2889

1.097

6.182

17.402

0.180

ν assCH3 (80), ν CH (16)

84

  

3122

2911

1.102

6.330

15.019

0.127

ν assCH3 (88), ν CH (11)

85

  

3172

2936

1.088

6.451

3.815

0.088

ν CH (96)

86

  

3175

2945

1.088

6.464

5.999

0.065

ν CH (96)

87

  

3177

2962

1.088

6.464

7012

0.109

ν CH (96)

88

  

3179

2989

1.089

6.488

17.412

0.127

ν CH (98)

89

  

3192

2993

1.089

6.536

7.580

0.129

ν CH (98)

90

  

3193

2999

1.094

6.574

14.859

0.219

ν CH (96)

91

  

3206

3007

1.094

6.629

18.471

0.243

ν CH (98)

92

 

3020

3218

3018

1.096

6.687

5.949

0.335

ν CH (98)

93

 

3100

3225

3101

1.091

6.690

6.782

0.076

ν CH (98)

ν, stretching; β, in plane bending; γ, out of plane bending; ω, wagging; τ, torsion; ρ, rocking; δ, scissoring; ss, symmetric stretching; ass, antisymmetric stretching; sb, symmetric bending; asb, antisymmetric bending; ipr, in-plane-rocking; opr, out-of-plane rocking

Carbon–hydrogen vibrations

The C–H stretching vibrations are expected to appear at 3100−2900 cm−1 [17] with multiple weak bands. The four hydrogen atoms left around each benzene ring give rise to a couple of C–H stretching, C–H in-plane bending and C–H out-of-plane bending vibrations. In MBDC, the calculated wavenumbers at 2936, 2945, 2962, 2989, 2993, 2999, 3007, 3018 and 3101 cm−1 are assigned to C–H stretching modes which show good agreement with the literature values [18]. The C–H in-plane bending vibrations occur in the region of 1390–990 cm−1. The vibrational assignments at 900, 990 and 1000 cm−1 (Fig. 3) occur due to the effect of C–H in-plane bending vibrations. The calculated wavenumbers at 889, 903, 923, 951, 968, 992, 1011, 1029 and 1042 cm−1 are due to C–H in-plane bending vibrations which show good agreement with recorded spectral values.

The out-of-plane bending of ring C–H bonds occur below 900 cm−1 [19]. In MBDC, the C–H out-of-plane bending vibrations are observed at 540, 575, 600 and 725 cm−1 which are compared with the computed values at 527, 540, 572, 601, 633, 669, 689, 716 and 723 cm−1.

Carbon–carbon vibrations

The ring C=C and C–C stretching vibrations, known as semicircle stretching modes, usually occur in the region of 1625–1400 cm−1 [20]. Generally, these bands are of variable intensity and observed at 1625–1590 cm−1, 1590–1575 cm−1, 1540–1470 cm−1, 1465–1430 cm−1 and 1380–1280 cm−1 [21]. In MBDC, the aromatic C–C stretching vibrations are observed at 1209 cm−1 (Fig. 2). The C–C stretching vibrations are assigned at 1432 and 1500 cm−1 in FT-IR and at 1540 and 1600 cm−1 in FT-Raman spectrum. These values perfectly match with the calculated wavenumbers, 1306–1615 cm−1 (mode no. 64–78). The C–C–C in-plane bending vibrations are observed at 810 cm−1 in FT-IR spectrum and at 850 and 875 cm−1 in FT-Raman spectrum. The calculated values are 811–872 cm−1 (mode no: 33–40). The C–C–C out-of-plane bending vibrations appeared at 350 and 400 cm−1 in FT-Raman spectrum and the corresponding calculated wavenumbers at 255–453 cm−1 (mode no: 11–18) show good agreement with the literature values [16]. These observed wavenumbers show that the substitutions in the benzene ring affect the ring modes of vibrations to a certain extent.

C–O vibrations

The C–O stretching vibrations are observed at 1300–1200 cm−1 [22]. In the present molecule, the C–O stretching is observed at 1189 cm−1 in FT-IR spectrum and the calculated vibration is at 1153 and 1190 cm−1. The C–O in-plane bending vibration is observed at 750 cm−1 in FT-IR matches with the theoretical value of 748 cm−1. In this molecule, the peak observed at 500 cm−1 in FT-Raman and 506 cm−1 in FT-IR are attributed to C–O out-of-plane bending vibrations. The C=O stretching vibration is generally observed at 1800–1600 cm−1 [23]. In MBDC, the C=O stretching is observed at 1616 cm−1 in FT-IR and at 1690 cm−1 in FT-Raman spectrum. This peak matches with the calculated value (1692 cm−1).

CH2 vibrations

The asymmetric CH2 stretching vibrations are generally observed between 3000 and 2800 cm−1, while the symmetric stretch appears between 2900 and 2800 cm−1 [24]. In MBDC, the CH2 asymmetric and symmetric stretching vibrations are calculated at 2809 and 2801 cm−1 respectively. The asymmetric bending is calculated at 1243 cm−1. In FT-IR spectrum the symmetric bending vibration is observed at 1215 cm−1 and calculated at 1231 cm−1. The in-plane CH2 bending vibration is observed at 1000 cm−1 in FT-Raman spectrum and the calculated vibration is at 1053 cm−1. The out-of-plane CH2 bending vibration is calculated at 1061 cm−1. The above results suggest that the observed frequencies are in good agreement with calculated in-plane and out-of-plane modes.

CH3 vibrations

There are nine fundamental modes associated with each CH3 group. In aromatic compounds, the CH3 asymmetric and symmetric stretching vibrations are expected in the range of 2925–3000 cm−1 and 2905–2940 cm−1, respectively [25]. In CH3 antisymmetric stretching mode, two C–H bonds are expanding while the third one is contracting. In symmetric stretching, all the three C–H bonds are expanding and contracting in-phase. In MBDC, the assigned vibrations at 2911, 2889 and 2863 cm−1 represent asymmetric and symmetric CH3 stretching vibrations [26]. The CH3 symmetric bending vibrations are observed at 1250 cm−1 in FT-Raman spectrum and calculated at 1250 cm−1 which are in good agreement with experimental and theoretical vibrations. The CH3 asymmetric bending vibrations are observed at 1261 cm−1 and calculated at 1260 and 1287 cm−1 match with the experimental values. The in-plane CH3 bending vibration is assigned at 1075 cm−1 in FT-Raman and calculated at 1072 cm−1 in B3LYP and out-of-plane CH3 bending vibration is observed at 1100 cm−1 in FT-Raman and calculated at 1104 cm−1. Predicted wavenumbers derived from B3LYP/6-31 + G(d,p) method synchronise well with those of the experimental observations.

HOMO–LUMO analysis

The most important orbitals in the molecule is the frontier molecular orbitals, called highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO). These orbitals determine the way the molecule interacts with other species. The HOMO–LUMO energy gap of MBDC is shown in Fig. 4. The HOMO (−51.0539 kcal/mol) is located over the coumarin group and LUMO (−49.0962 kcal/mol) is located over the ring; the HOMO→LUMO transition implies the electron density transfer to ring benzylidene. The calculated self-consistent field (SCF) energy of MBDC is −506,239.7545 kcal/mol. The frontier orbital gap is found to be E = −101.9576 kcal/mol and this negative energy gap confirms the intramolecular charge transfer. This proves the non-linear optical (NLO) activity of the material [27]. A molecule with a small frontier molecular orbital is more polarizable and generally associated with high chemical reactivity, low kinetic stability termed as soft molecule [28]. The low value of frontier molecular orbital in MBDC makes it more reactive and less stable.
Fig. 4

The calculated frontiers energies of MBDC

NBO analysis

Natural bond orbital (NBO) of the molecule explains the molecular wave function in terms of Lewis structures, charge, bond order, bond type, hybridization, resonance, donor–acceptor interactions, etc. NBO analysis has been performed on MBDC to elucidate the intramolecular, rehybridization and also the interaction which will weaken the bond associated with the anti-bonding orbital. Conversely, an interaction with a bonding pair will strengthen the bond.

The corresponding results are presented in Tables 3 and 4. The intramolecular interaction between lone pair of O27 with antibonding C13–O12 results in a stabilized energy of 35.64 kcal/mol. The most important interaction in MBDC is between the LP(2)O12 and the antibonding C13–O27. This results in a stabilization energy 41.74 kcal/mol and denotes larger delocalization. The valence hybrid analysis of NBO shows that the region of electron density distribution mainly influences the polarity of the compound. The maximum electron density on the oxygen atom is responsible for the polarity of the molecule. The p-character of oxygen lone pair orbital LP(2) O27 and LP(2) O12 are 99.66 and 99.88, respectively. Thus, a very close pure p-type lone pair orbital participates in the electron donation in the compound.
Table 3

Second-order perturbation energy [E(2), kcal/mol] between donor and acceptor orbitals of MBDC calculated at B3LYP/6-31 + G(d,p) level of DFT theory

Donor (i)

Acceptor (j)

E(2)

ED (i) (e)

ED (j)(e)

E(j) − E(i) (a.u.)

F(i,j) (a.u.)

LP(1)O27

σ*C8–C13

3.01

1.97789

0.07355

1.11

0.052

LP(1)O27

σ*C13–O12

0.08

1.97789

0.10629

1.03

0.026

LP(2)O27

π*C8–C13

18.58

1.83804

0.07355

0.67

0.102

LP(2)O27

π*C13–O12

35.64

1.83804

0.10629

0.60

0.132

LP(2)O27

π*C7–H26

0.70

1.83804

0.01944

0.73

0.021

LP(1)O12

σ*C8–C13

6.30

1.95794

0.07355

0.96

0.070

LP(1)O12

σ*C10–C11

6.54

1.95794

0.03331

1.11

0.076

LP(1)O12

σ*C11–C17

0.77

1.95794

0.02024

1.10

0.026

LP(1)O12

σ*C13–O27

2.06

1.95794

0.01348

1.16

0.044

LP(2)O12

σ*C10–C11

25.17

1.95794

0.38783

0.36

0.088

LP(2)O12

σ*C13–O27

41.74

1.76210

0.24560

0.34

0.106

σC8–C9

σ*C8–C7

3.21

1.9767

0.01864

1.29

0.057

σC8–C13

σ*C7–C1

4.13

1.97727

0.02282

1.14

0.061

πC9–H28

π*C8–C7

3.36

1.96228

0.06368

0.55

0.038

πC9–H29

π*C10–C11

3.31

1.96216

0.38783

0.53

0.041

σC10–C14

σ*C11–O12

4.82

1.97139

0.03516

1.03

0.063

σC11–C17

σ*C10–C11

4.15

1.97581

0.03331

1.28

0.065

σH30–C14

σ*C10–C11

4.18

1.98112

0.03331

1.10

0.061

σC17–C16

σ*C11–O12

4.34

1.97651

0.03516

1.03

0.060

σC17–H33

σ*C10–C11

4.56

1.97906

0.03331

1.09

0.063

σC7–H26

σ*C8–C9

7.24

1.96715

0.02414

0.94

0.074

σC2–H18

σ*C1–C6

4.35

1.98162

0.02521

1.08

0.061

σC6–H25

σ*C1–C2

4.31

1.98170

0.02470

1.09

0.061

σC5–H24

σ*C6–C4

4.24

1.98119

0.02266

1.00

0.029

πC20–H21

π*C5–C4

4.04

1.98750

0.34063

0.53

0.045

Table 4

NBO results showing the formation of Lewis and non Lewis orbitals of MBDC molecule by B3LYP/6-31G + (d,p) method

Bond (A–B)

ED/energy (a.u.)

EDA %

EDB %

NBO

s %

p %

σ C8–C9

1.97667

50.31

49.69

0.7093 (sp2.03)

0.7049 (sp2.71)

32.95

26.97

67.02

72.98

−0.65200

σ C8–C13

1.97727

51.86

48.14

0.7201 (sp2.48)

0.6938 (sp1.52)

28.69

39.66

71.27

60.28

−0.68595

σ C9–H28

1.96228

63.78

36.22

0.7986 (sp3.34)

0.6019 (sp0.00)

23.04

99.95

76.91

00.05

−0.51190

σ C10–C14

1.97139

51.60

48.40

0.7184 (sp1.82)

0.6957 (sp1.91)

35.47

34.37

64.50

65.59

−0.70409

σ C11–C17

1.97581

51.16

48.84

0.7153 (sp1.62)

0.6989 (sp2.00)

38.17

33.31

61.80

66.64

−0.71570

σ H30–C14

1.98112

37.66

62.34

0.6137 (sp0.00)

0.7896 (sp2.37)

99.95

29.65

00.05

70.31

−0.53074

σ C17–C16

1.97651

50.46

49.54

0.7103 (sp1.79)

0.7039 (sp1.88)

35.85

34.75

64.11

65.20

−0.25929

σ C17–H33

1.97906

63.18

36.782

0.7948 (sp2.24)

0.6068 (sp0.00)

30.81

99.95

69.15

00.04

−0.52986

σ C7–H26

1.96715

63.87

36.13

0.7992 (sp2.36)

0.6011 (sp0.00)

29.74

99.95

70.22

00.05

−0.52611

σ C2–H18

1.98162

62.58

37.42

0.7911 (sp2.34)

0.6117 (sp0.00)

29.94

99.95

70.02

00.05

−0.52927

σ C6–H25

1.98170

62.53

37.47

0.7908 (sp2.34)

0.6121 (sp0.00)

29.93

99.95

70.03

00.05

−0.53031

σ C5–H24

1.98119

62.30

37.70

0.7893 (sp2.37)

0.6140 (sp0.00)

29.62

99.95

70.34

00.05

−0.52761

σ C20–H21

1.98750

62.42

37.58

0.7901 (sp3.12)

0.6130 (sp0.00)

24.25

99.95

75.70

00.05

−0.51049

LP(1) O27

1.97789

  

sp0.70

58.63

41.30

−0.69724

LP(2) O27

1.83804

  

sp99.99

00.05

99.66

−0.26311

LP(1) O12

1.95794

  

sp1.89

34.56

65.38

−0.54749

LP(2) O12

1.76210

  

sp1.00

00.00

99.88

−0.33734

Mulliken charges

The Mulliken atomic charges of MBDC were calculated by B3LYP/6–31 + G (d,p) level theory (Table 5). It is important to mention that the atoms C1, C2, C4, C7, C10, H18, H19, O27 of MBDC exhibit positive charges, whereas the atoms C3, C5, C6, C11, O12 exhibit negative charges. The maximum negative and positive charge values are −0.95788 for C11 and 0.90500 for C10 in the molecule, respectively.
Table 5

The charge distribution calculated by the Mulliken method

Atoms

Mulliken charge

NBO

C1

0.35122

−0.09783

C2

0.07866

−0.22079

C3

−0.25976

−0.23196

C4

0.28427

−0.03843

C5

−0.54829

−0.23334

C6

−0.26856

−0.22441

C7

0.10817

−0.12331

C8

0.48781

−0.15456

C9

−0.49756

−0.50908

C10

0.90500

−0.08766

C11

−0.95788

0.29617

O12

−0.39388

−0.51439

C13

0.33449

0.80701

C14

−0.31967

−0.21966

C15

0.13614

−0.25219

C16

−0.08232

−0.23483

C17

−0.15764

−0.26075

H18

0.13200

0.24986

H19

0.12586

0.24422

C20

−0.60604

−0.70947

H21

0.17095

0.24897

H22

0.16101

0.24929

H23

0.15358

0.25629

H24

0.12235

0.24404

H25

0.12453

0.24877

H26

0.15765

0.27521

O27

−0.44633

−0.56839

H28

0.18552

0.27671

H29

0.16406

0.27813

H30

0.12443

0.24480

H31

0.12660

0.24891

H32

0.13021

0.25025

H33

0.14289

0.26243

UV–Visible analysis

Theoretical UV–Visible spectrum (Table 6) of MBDC was derived by employing polarizable continuum model (PCM) and TD-DFT method with B3LYP/6-31 + G(d,p) basis set and compared with experimentally obtained UV–Visible spectrum (Fig. 5). The spectrum shows the peaks at 215 and 283 nm whereas the calculated absorption maxima values are noted at 223, 265 and 296 nm in the solvent of ethanol. These bands correspond to one electron excitation from HOMO–LUMO. The band at 223 and 265 nm are assigned to the dipole-allowed σ → σ* and π → π* transitions, respectively. The strong transitions are observed at 2.414 eV (215 nm) with f = 0.0036 and at 2.268 eV (283 nm) with f = 0.002.
Table 6

UV-Vis excitation energy and electronic absorption spectra of MBDC using TD-B3LYP/631G + (d,p) method

Exp. (nm)

Wavelength (nm)

Energy (eV)

Oscillator strength (f)

Assignments

283

296

2.2007

0.0134

π → π*

283

265

2.2684

0.002

π → π*

215

223

2.4147

0.0036

σ − σ*

Fig. 5

Experimental UV spectrum of MBDC. Inset figure predicated MEP map of MBDC

Molecular electrostatic potential

Molecular electrostatic potential at the surface are represented by different colours (inset in Fig. 5). Red colour indicates electronegative character responsible for electrophilic attack, blue colour indicates positive region representing nucleophilic attack and green colour represents the zero potential. The electrostatic potential increases in the order red < orange < yellow < green < blue [29]. The mapped electrostatic potential surface of the molecule shows that atoms O27 and O12 of chromen possess negative potential and all H atoms have positive potential. The same regions are identified in the Mulliken charges also.

Hyper polarizability

On the basis of the finite-field approach, using B3LYP/6–31 + G (d,p) basis set, the first hyperpolarizability (β), dipole moment (μ) and polarizability (α) for MBDC are calculated and compared with urea (Table 7) [30]. The dipole moment of MBDC is 1.6941 times greater than the magnitude of urea (μ tot of urea is 3.2705 D) and the first hyperpolarizability is 1.51 times greater than the magnitude of urea (β tot of urea is 3.7472 × 10−31 esu). Urea is the standard NLO crystal reported earlier [31] so that a direct comparison was made.
Table 7

The calculated electric dipole moment (μtot D) the average polarizability (αtot × 10−24 esu) and the first hyperpolarizability (βtot × 10−31 esu)

Parameters

Values

μx

2.9237

μy

−4.6995

μz

−0.2541

μtot (D)

5.5406

αxx

−93.6767

αxy

6.1433

αyy

−119.8535

αxz

−0.1725

αyz

−4.4825

αzz

−111.9369

αtot (esu)

2.32632 × 10 24

βxxx

23.1945

βxxy

−28.7842

βxyy

20.1351

βyyy

−51.2342

βxxz

−32.9779

βxyz

−12.6553

βyyz

−7.0618

βxzz

5.9903

βyzz

8.6308

βzzz

6.4779

βtot (esu)

5.6583 × 10−31

Dielectric studies

The experimental data of ε0, ε′, ε and τ of MBDC in ethanol at various concentrations are presented in Table 8. The static and microwave dielectric constants decrease with increasing concentration of the compound. This shows a weak interaction exists between the molecule and the solvent at low frequencies. Optical dielectric constant increases with increasing solute concentration which leading to a strong interaction between MBDC and ethanol at high frequency. It indicates the formation of a hydrogen bonding between –OH group of alcohol and C=O of coumarin. The relaxation time increases with the increase of bond length confirming the degree of cooperation, shape and size of the molecule [32].
Table 8

Values of dielectric constant (ε0, ε′, ε) and relaxation time τ(ps) of MBDC in ethanol at 303 K

System

Mole conc.

Static dielectric constant (ε0)

Microwave dielectric constant (ε′)

Optical dielectric constant (ε)

Relaxation time τ (ps)

Ethanol + MBDC

0.025

24.10

22.45

1.848

125.45

0.040

21.14

20.33

1.945

132.61

0.055

19.36

18.39

2.570

148.44

0.070

15.89

16.59

2.832

153.89

NMR study

The characterization of MBDC was further enhanced by the study of 1H NMR method. The computed 13C NMR and 1H NMR chemical shifts and experimental 1H NMR are compiled in Table 9. The experimental 1H NMR spectrum in CDCl3 solution is shown in Fig. 6. The relevant difference of 1H NMR chemical shifts calculated by GIAO/B3LYP method is: 0.06(H31), 0.17(H26) and 0.19(H24). The maximum deviation from experimental value is responded to be 0.19 ppm for H24 atom [33]. Overall the calculated values agree with the experimental chemical shift values and the slight deviations may be due to the influence of proton exchange, hydrogen bond and solvent effect in complex real systems. The results of 13C NMR chemical shift of the MBDC compound is reliable for the interpretation of spectroscopic parameters. The C1 and C2 atoms of the compound are attached with the electron releasing group and hence they are more electron donating than C15. This causes more shielding at C1 and C2 positions and hence the chemical shift values are lesser.
Table 9

Experimental (in CDCl3), predicted (δpred) 13C and 1H chemical shifts (ppm) and calculated GIAO/B3LYP/6-31 + G(d,p) isotropic magnetic shielding tensors (σcalc) for (3E)-3-(4-methylbenzylidene)-3,4-dihydro-2H-chromen-2-one

1H

δexp (CDCl3)

CDCl3

Gas phase

13C

CDCl3

Gas phase

δpred

σcalc

δpred

σcalc

δpred

σcalc

δpred

σcalc

H18

7.36

7.42

23.9144

7.20

24.1513

C1

115.85

62.9668

116.66

62.1766

H19

7.36

7.46

23.8777

7.22

24.1263

C2

117.49

61.3681

117.18

61.6766

H21

2.42

2.66

28.8984

2.63

28.9317

C3

111.81

66.8779

111.47

67.2105

H22

2.42

2.39

29.1857

2.34

29.2393

C4

127.41

51.7495

125.56

53.5485

H23

2.42

2.21

29.3704

2.14

29.4509

C5

111.58

67.1015

111.27

67.4047

H24

7.21

7.40

23.9349

7.15

24.2029

C6

112.70

66.0193

112.14

66.5622

H25

7.39

7.41

23.9272

7.24

24.1070

C7

129.24

49.9746

127.65

51.5188

H26

7.96

8.13

23.1789

8.01

23.3020

C8

106.14

72.3815

106.55

71.98

H28

4.07

4.08

27.4169

3.92

27.5850

C9

15.45

160.332

16.03

159.7719

H29

4.07

4.02

27.4732

3.92

27.5830

C10

106.20

72.3198

104.77

73.708

H30

7.24

7.25

24.0981

6.95

24.4081

C11

134.84

44.5441

135.63

43.7844

H32

7.28

7.33

24.0134

7.10

24.2574

C13

149.18

30.6419

146.48

33.261

H33

7.10

7.10

24.2534

6.93

24.4260

C14

110.11

68.5299

109.42

69.2007

      

C15

107.00

71.5493

105.72

72.7857

      

C16

109.94

68.6951

109.65

68.9804

      

C17

99.92

78.414

100.35

77.9959

Fig. 6

Experimental 1H NMR spectrum of MBDC

Molecular docking studies

Glide docking was used to study the binding orientations and affinities of MBDC with tankyrase as target protein (Fig. 7). Tankyrases are ADP-ribosyltransferases that play key roles in various cellular pathways, including the regulation of cell proliferation, and thus they are promising drug targets for the treatment of cancer [12]. The keto atom in MBDC interacts with SER1068 and GLY1032 at distances of 3.17 and 2.91 Å, respectively (Table 10). This result suggests that the MBDC binds well in the active site pocket of tankyrase and interact with the amino acid residues. These results are compared with the anti cancer drug molecule warfarin derivative. This drug molecule fits in the active site and favourable interactions are observed with the same residues. The results obtained reveals that both the molecules have comparable interactions and better docking scores.
Fig. 7

a MBDC interacts with the amino acid in the active site of tankyrase, b anticancer drug Warfarin derivative interacts with the amino acid in the active site of tankyrase, c surface diagram showing MBDC fit into the active site of tankyrase

Table 10

Hydrogen bond interactions of title compound and co-crystal ligand with amino acids at the active site of tankyrases

Docking score

Glide energy (kcal/mol)

Hydrogen bonding interactions

Donor

Acceptor

Distance (Å)

MBDC

 −10.823

−49.845

N–H[GLY1032]

O

2.91

O–H[SER1068]

O

3.17

Warfarin

 −10.625

−55.759

NH[Tyr1060]

O

2.0

NH[Gly1032]

O

2.1

OH

O[Gly1032]

2.0

OH

N[His 1031]

3.7

N[His1031]

O

3.3

O[His1048]

O

3.5

Anticancer activity

The results of the antiproliferative activity of MBDC and Warfarin derivative against MCF-7 breast cancer and HT-29 colon cancer cell lines at different concentrations (7.8, 15.6, 31.2, 62.5, 125, 250, 500 and 1000 μg/ml) for 24 h, and cell proliferation was measured by a standard MTT assay. As shown in Figs. 8a, b and 9a, b, MCF-7 and HT-29 cells exposed to MBDC and Warfarin derivative exhibited significant cytotoxicity in the dose dependent manner after 24 h treatment. The estimated half maximal inhibitory concentration (IC 50) value for MBDC and Warfarin derivative was 15.6 and 31.2 μg/ml respectively. This enhanced cytotoxicity of MBDC in MCF-7 breast cancer and HT-29 colon cancer cell lines may be due to their efficient targeted binding and eventual uptake by the cells.
Fig. 8

Graphical representation of MBDC molecule on a MCF-7 cell line and b HT-29 cell line

Fig. 9

Graphical representation of Warfarin derivative on a MCF-7 cell line and b HT-29 cell line

Conclusion

The vibrational and molecular structure analysis have been performed based on the quantum mechanical approach using DFT calculations. The difference in the observed and scaled wavenumber values of most fundamentals is very small. Therefore, the assignments made using DFT theory with experimental values seem to be correct. The geometrical structure shows a little distortion due to the substitution of methyl benzylidene and chromen group in the benzene.

The chromen group substitution plays an important role with its characteristic peaks compared in both experimental and theoretical FTIR and FT-Raman spectra. The MEP map shows negative potential sites on O27 and O12 of chromen and positive potential sites on all H atoms which are responsible for electrophilic and nucleophilic attacks, respectively.

In addition, HOMO and LUMO orbitals are in agreement with MEP. The results indicate that the title compound is found to be useful to bond metallicity and inter molecular interaction. The NBO analysis explains the large delocalization of charge in the molecule. The predicted NLO properties are compared with that of urea and the title compound seems to be a good candidate of second-order NLO materials.

Molecular docking study shows that MBDC binds well in the active site of tankyrase and interact with the amino acid residues. These results are compared with the anti cancer drug molecule of warfarin derivative. The results suggest that both the molecules have comparable interactions and better docking scores. The results of the antiproliferative activity of MBDC and Warfarin derivative against MCF-7 breast cancer and HT-29 colon cancer cell lines at different concentrations exhibited significant cytotoxicity. The estimated half maximal inhibitory concentration (IC 50) value for MBDC and Warfarin derivative was 15.6 and 31.2 μg/ml, respectively. This enhanced cytotoxicity of MBDC in MCF-7 breast cancer and HT-29 colon cancer cell lines may be due to their efficient targeted binding and eventual uptake by the cells. Hence the compound MBDC may be considered as a drug molecule for cancer. The dielectric relaxation studies show the existence of molecular interactions between MBDC and alcohol. The NMR spectrum confirms the molecular structure of the compound.

Declarations

Authors’ contributions

TB proposed the work, carried out the DFT studies, dielectric, NMR and anticancer studies, arranged the results and drafted the manuscript under the guidance of LS. Spectroscopic studies carried out by AN under the guidance of VB. DK synthesized the title compound. Molecular docking, manuscript revision and final shape were done by MNP. All authors read and approved the final manuscript.

Acknowledgements

MNP thanks UGC, New Delhi for the financial support in the form of UGC-Emeritus Fellowship. We wish to thank (BIF) at CAS in Crystallography and Biophysics, University of Madras, Chennai-25.

Competing interests

This is the characterization study which provides the needed information to prove that the molecule MBDC competes with Warfarin derivative as an anti-cancer agent.

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Authors’ Affiliations

(1)
Department of Physics, SRM University
(2)
Research Department of Physics, A.A. Government Arts College
(3)
Department of Organic Chemistry, University of Madras
(4)
CAS in Crystallography & Biophysics, University of Madras

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