Journal of Theoretical Chemistry

Volume 2014 (2014), Article ID 680987, 13 pages

http://dx.doi.org/10.1155/2014/680987

Research Article

Isolation, Identification, Molecular and Electronic Structure, Vibrational Spectroscopic Investigation, and Anti-HIV-1 Activity of Karanjin Using Density Functional Theory

Anoop kumar Pandey,¹ Abhishek Kumar Bajpai,² Ashok Kumar,³ Mahesh Pal,⁴ Vikas Baboo,³ and Apoorva Dwivedi²

¹Department of Physics, Government Danteshwari P.G.College, Dantewada 494449, India

²Department of Physics, Government Kakatiya Post Graduate College, Jagdalpur, Bastar, Chhattisgarh 494001, India

³Department of Chemistry, Lucknow University, Lucknow 226007, India

⁴National Botanical Research Institute, Lucknow 226007, India

Received 17 January 2014; Revised 9 April 2014; Accepted 9 April 2014; Published 7 May 2014

Academic Editor: Hugo Verli

Copyright © 2014 Anoop kumar Pandey et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract.

“Karanjin” (3-methoxy furano-2,3,7,8-flavone) is an anti-HIV drug, and it is particularly effective in the treatment of gastric problems. The method of isolation of “Karanjin” followed the Principles of Green Chemistry (eco-friendly and effortless method). The optimized geometry of the “Karanjin” molecule has been determined by the method of density functional theory (DFT). Using this optimized structure, we have calculated the infrared wavenumbers and compared them with the experimental data. The calculated wavenumbers are in an excellent agreement with the experimental values. On the basis of fully optimized ground-state structure, TDDFT//B3LYP/LANL2DZ calculations have been used to determine the low-lying excited states of Karanjin. Based on these results, we have discussed the correlation between the vibrational modes and the crystalline structure of “Karanjin.” A complete assignment is provided for the observed FTIR spectra. This is the first report of the isolation, molecular and electronic structure using vibrational spectroscopic investigation, density functional theory, and anti-HIV-1 activity of “Karanjin.”

1. Introduction

Pongamia pinnata is a medium sized glabrous tree, found throughout Indian forests [1]. Different parts of this plant have been used as a source of traditional medicine. P. pinnata seeds contain oil which is mainly used in tanning industry for dressing of leather and to some extent it is used in soap industry. Oil is employed in scabies, herpes, and leucoderma, and sometimes as stomachic and cholagogue in dyspepsia and sluggish liver [2]. “Karanjin” is an active principle responsible for the curative effects of the oil in skin disease [1]. Seed extract inhibits growth of herpes simplex virus and also possesses hypoglycemic, antioxidative, antiulcerogenic, anti-inflammatory, and analgesic properties [3]. During the course of exploration of new compounds from P. pinnata seed oil, several workers [4–6] have identified some new compounds of its seed oil apart from “Karanjin.” “Karanjin” possess pesticidal [7], insecticidal [8], and anti-inflammatory activity [9].

Considering the role of “Karanjin” in different areas, in the present communication, we have carried out isolation and identification of “Karanjin” by ecofriendly method and tested for its anti-HIV activity. The molecular structure of the well-known natural product “Karanjin” has been studied using the density functional theory. The equilibrium geometry, harmonic vibrational frequencies, and HOMO-LUMO gap have been calculated by the density functional B3LYP method employing 6-311 G (d, p) as the basis set. The detailed interpretation of the vibrational spectra of Karanjin in terms of the normal mode analysis has been reported. The main objective of the present study is to investigate in detail the vibrational spectra of the important biological molecule (Karanjin) by DFT [10] method, which can presumably help in understanding its dynamical behavior. To the best of our knowledge, no detailed DFT calculations and anti-HIV activity have been performed on “Karanjin” so far in the literature.

2. Experimental Methods (Structure and Spectra)

The molecular structure of the title compound “Karanjin” is made by molecular modeling. The model molecular structure of the compound is given in Figure 1. Fourier transform infrared spectrum was recorded with FTIR Perkin Elmer spectrometer in KBr dispersion in the range of 500 to 4000 cm⁻¹ for the title molecule. The comparison of the calculated and experimental FTIR and UV visible spectra of “Karanjin” is given in Figures 2 and 3, respectively.

Figure 1: Model molecular structure of Karanjin.

Figure 2: Comparison of calculated and experimental FTIR spectra of Karanjin.

Figure 3: Comparison of calculated and experimental UV visible spectra of Karanjin.

3. Computational Methods

The initial geometry was generated from the standard geometrical parameters and was minimized without any constraint in the potential energy surface. The gradient corrected density functional theory (DFT) with the three-parameter hybrid functional (B3) [11] for the exchange part and the Lee-Yang-Parr (LYP) correlation function [12] has been employed for the computation of molecular structure, vibrational frequencies, HOMO-LUMO, and energies of the optimized structures, using Gaussian 09 [13]. The calculated vibrational frequencies have also been scaled by a factor of 0.963 [14]. By combining the results of the GaussView program [15] with symmetry considerations, vibrational frequency assignments were made with a high degree of accuracy. We used this approach for the prediction of IR frequencies of title compound and found it to be very straightforward. Density functional theory calculations are reported to provide excellent vibrational frequencies of organic compound if the calculated frequencies are scaled to compensate for the approximate treatment of electron correlation, for basis set deficiencies and for anharmonicity. A number of studies have been carried out regarding calculations of vibrational spectra by using B3LYP methods with 6-311 G (d, p) basis set. The scaling factor was applied successfully for B3LYP method and was found to be easily transferable in a number of molecules. Thus, vibrational frequencies calculated by using the B3LYP functional with 6-311G (d, p) as basis set can be utilized to eliminate the uncertainties in the fundamental assignment in the IR spectra.

4. Results and Discussion

4.1. Eco-Friendly Method

Here it needs to be highlighted that so far “Karanjin” has been isolated through column chromatography (silica gel, 100–200 mesh) or by preparative HPLC [16–18], but in our study the method was eco-friendly and effortless and followed the Principles of Green Chemistry. Implementing these Green Chemical Principles requires a certain investment, since the current, very inexpensive chemical processes must be redesigned. A typical chemical process generates products and wastes from raw materials such as substrates, solvents, and reagents. If most of the reagents and the solvent can be recycled, the mass flow looks quite different.

4.2. Isolation of “Karanjin”

The shade dried Karanja seeds (Pongamia pinnata) of 3.5 kg were extracted with methanol (MeOH) (4.5 lit) at room temperature. The combined MeOH extract was concentrated under reduced pressure at 40°C to a dark viscous mass. It was concentrated to dryness and kept at 4°C for 24 hr; after adding ethanol, shake it properly and keep on for settling down of crystals for few hours. Colorless crystals (11.2 g) were obtained from crystallization with EtOH isolated with TLC in 98 : 2 chloroform and MeOH and a single spot was obtained.

4.3. Identification of “Karanjin”

Isolated compound identified as “Karanjin” (3-methoxy furano-(20,30 : 7,8)-flavone) by direct comparison of co-TLC and melting point of 162°C with that of authentic sample obtained from Sigma-Aldrich and was also confirmed by the ¹H NMR and ¹³C NMR reported in the literature [19].

4.4. Cytotoxicity and Anti-HIV-1 Activity of Compound

Compound “Karanjin” was tested for cytotoxicity against C8166 cells (CC50), and anti-HIV-1 activity was evaluated by the inhibition assay for the cytopathic effects of HIV-1(EC₅₀) < using AZT as a positive control; the compound exerted moderate cytotoxic activity against C8166 cells with CC₅₀ > 693.15 μM and showed anti-HIV-1 activity with EC₅₀ = 49.43 μM and selectivity index (CC₅₀/EC₅₀) more than 14.02. Cytotoxicity and anti-HIV-1 activity of compound is shown in Table 1.

Table 1

Compound
Cytotoxicity

CC₅₀ (μM)
Anti-HIV-1 activity,

EC₅₀ (μM)
Selectivity index,

CC₅₀/EC₅₀

KJ
693.15
49.43
>14.02

AZT
5746.1
0.0147
390406.06

4.5. Anti-HIV-1 Assay

Cytotoxicity against C8166 cells (CC₅₀) was assessed using the MTT method, and anti-HIV-1 activity was evaluated by the inhibition assay for the cytopathic effects of HIV-1(EC₅₀) [20].

4.6. Molecular Structure

The equilibrium geometry optimization of “Karanjin” has been achieved by energy minimization, using DFT at the B3LYP level, employing LANL2DZ as the basis set given in Table 2. The optimized geometry of the molecule under study is confirmed to be located at the local true minima on potential energy surface, as the calculated vibrational spectra contain no imaginary wavenumber. “Karanjin” is an unsymmetrical molecule having C₁ point group symmetry. The given molecule has four rings. Out of these, three are six membered hexagonal rings and one five membered pentagonal ring in which A and C are heterocyclic rings in which one carbon is replaced by oxygen. Due to the antibonding repulsion, these rings are slightly shifted towards the plane. The given structure of “Karanjin” is slightly shifted from the planar structure to minimize its surface energy. Due to this reason, ring D gets shifted from its plane. The optimized bond length of C–C in five membered ring A ranges between 1.353 Å and 1.438 Å, while, for another six membered ring B, this ranges between 1.379 Å and 1.415 Å. The optimized bond length of C–C in six membered ring C ranges between 1.367 Å and 1.471 Å, while, for another six membered ring D, this ranges between 1.389 Å and 1.405 Å. This difference in the C–C bond length is attributed to the difference in bond strength. The optimized C–O bond lengths in ring A are found to be 1.362 Å and 1.373 Å, while, in ring C, the optimized C–O bond lengths are found to be 1.357 Å and 1.371 Å. The optimized C–O bond length attached to ring C is found to be 1.363 Å. Bond length of carbonyl group C=O attached to the ring C is calculated to be 1.227 Å. Values of all the bond angles are given in Table 2 and all are in agreement with the previous experimental and theoretical studies on different biomolecules [21–23].

Table 2: Optimized geometrical parameters of Karanjin by B3LYP/6-311G (d, p) methods.

S. number
Bond lengths
Calculated
Exp.
Bond angles
Calculated
Exp.

1
(1, 2)
1.3795
1.363
(2, 1, 6)
116.5065
116.5

2
(1, 6)
1.3975
1.399
(2, 1, 28)
122.364
—

3
(1, 28)
1.0821
—
(6, 1, 28)
121.1293
—

4
(2, 3)
1.4157
1.403
(1, 2, 3)
121.6696
121.6

5
(2, 27)
1.0826
—
(1, 2, 27)
121.4181
—

6
(3, 4)
1.3939
1.384
(3, 2, 27)
116.9123
—

7
(3, 7)
1.4717
1.466
(2, 3, 4)
120.0707
120.9

8
(4, 5)
1.4039
1.411
(2, 3, 7)
120.5299
121.4

9
(4, 10)
1.3573
1.352
(4, 3, 7)
119.3901
117.8

10
(5, 6)
1.3991
1.374
(3, 4, 5)
119.8451
118.8

11
(5, 24)
1.4389
1.431
(3, 4, 10)
122.4041
124.0

12
(6, 26)
1.3621
1.355
(5, 4, 10)
117.7498
117.2

13
(7, 9)
1.4724
1.443
(4, 5, 6)
117.6428
117.9

14
(7, 11)
1.2273
1.238
(4, 5, 24)
136.2417
135.7

15
(8, 9)
1.3672
1.353
(6, 5, 24)
106.1152
106.3

16
(8, 10)
1.3712
1.366
(1, 6, 5)
124.264
124.4

17
(8, 13)
1.4743
1.474
(1, 6, 26)
125.9683
125.1

18
(9, 12)
1.3632
1.365
(5, 6, 26)
109.7673
110.5

19
(12, 31)
1.4406
1.454
(3, 7, 9)
114.5711
115.3

20
(13, 14)
1.4043
1.395
(3, 7, 11)
122.8728
122.5

21
(13, 18)
1.4055
1.389
(9, 7, 11)
122.5555
122.1

22
(14, 15)
1.391
1.388
(9, 8, 10)
120.8623
120.9

23
(14, 19)
1.0793
—
(9, 8, 13)
127.8731
127.8

24
(15, 16)
1.3929
1.390
(10, 8, 13)
111.2639
111.3

25
(15, 20)
1.0841
—
(7, 9, 8)
121.7683
122.4

26
(16, 17)
1.3936
1.367
(7, 9, 12)
119.0806
117.7

27
(16, 21)
1.0841
—
(8, 9, 12)
119.0731
119.8

28
(17, 18)
1.3894
1.388
(4, 10, 8)
120.97
119.6

29
(17, 22)
1.0842
—
(9, 12, 31)
116.681
113.6

30
(18, 23)
1.0818
—
(8, 13, 14)
122.193
121.2

31
(24, 25)
1.3531
1.335
(8, 13, 18)
119.157
120.1

32
(24, 29)
1.0773
—
(14, 13, 18)
118.6442
118.7

33
(25, 26)
1.3737
1.377
(13, 14, 15)
120.2939
121.0

34
(25, 30)
1.0771
—
(13, 14, 19)
119.5231
—

35
(31, 32)
1.0891
—
(15, 14, 19)
120.1826
—

36
(31, 33)
1.0884
—
(14, 15, 16)
120.6002
119.1

37
(31, 34)
1.0949
—
(14, 15, 20)
119.3481
—

38
—
—
—
(16, 15, 20)
120.051
—

39
—
—
—
(15, 16, 17)
119.5338
120.1

40
—
—
—
(15, 16, 21)
120.2524
—

41
—
—
—
(17, 16, 21)
120.2136
—

42
—
—
—
(16, 17, 18)
120.2358
120.9

43
—
—
—
(16, 17, 22)
120.136
—

44
—
—
—
(18, 17, 22)
119.6282
—

45
—
—
—
(13, 18, 17)
120.6874
120.0

46
—
—
—
(13, 18, 23)
119.4489
—

47
—
—
—
(17, 18, 23)
119.8616
—

48
—
—
—
(5, 24, 25)
105.5988
105.5

49
—
—
—
(5, 24, 29)
127.7368
—

50
—
—
—
(25, 24, 29)
126.6633
—

51
—
—
—
(24, 25, 26)
112.0571
112.3

52
—
—
—
(24, 25, 30)
132.815
—

53
—
—
—
(26, 25, 30)
115.1279
—

54
—
—
—
(6, 26, 25)
106.4614
105.4

55
—
—
—
(12, 31, 32)
105.499
—

56
—
—
—
(12, 31, 33)
110.6157
—

57
—
—
—
(12, 31, 34)
110.2584
—

58
—
—
—
(32, 31, 33)
110.4607
—

59
—
—
—
(32, 31, 34)
109.3804
—

60
—
—
—
(33, 31, 34)
110.5095
—

4.7. Vibrational Assignments

The molecule “Karanjin” contains 34 atoms and therefore has 96 normal modes of vibration. All the 96 fundamental vibrations are IR active. The harmonic vibrational frequencies calculated for Karanjin at DFT (B3LYP) level using LANL2DZ as the basis set and the experimental frequencies (FTIR) have been compared in Table 3 along with their vibrational assignments of the normal modes. Vibrational assignments are based on the observation of the animated modes in GaussView.

Table 3: Vibrational assignments of Karanjin with B3LYP/6-311G (d, p).

B3LYP (calculate)
IR (int.)
Exp.
Vibrational assignments

41
0.4616
—
Ring D twist from rest of the molecule

47
0.0408
—
Slight bending in whole molecule

58
1.4783
—
Slight bending in whole molecule

71
1.2198
—
Rock CH₃

86
1.3868
—
Slight bending in whole molecule

99
1.2684
—
Twist CH₃

139
1.8339
—
Twist CH₃

165
0.5168
—
Twist CH₃

182
1.3627
—
Bending in whole molecule

216
3.8318
—
Floating of whole molecule

231
1.4454
—
Bending in whole molecule

257
4.7668
—
(C–C–C) in whole molecule

265
0.8668
—
Whole molecule stretching

299
1.2843
—
γ(C–C–C) in whole molecule

314
3.3777
—
Twist (C–O–CH₃)

324
4.4912
—
τ(C–C–C=O)

362
1.0152
—
τ(C–C–O–CH₃)

398
0.2783
—
γ(C–C–C) Ring D

412
16.6519
422
Ring A bends from joint to ring B

441
1.5627
—
γ(C–C–C) ring D

477
10.432
—
τ(C–C–C–C) in whole molecule

486
4.307
490
τ(C–C–O–CH₃)

525
0.5385
—
γ(C–C–H) rings A and B

549
1.0232
—
τ(C–C–C–C) ring B

580
5.7233
589
γ(C–C–H) ring A

607
1.0343
—
τ(C–C–C–C) ring D

615
5.088
—
τ(C–C–C–C) ring D

622
5.8291
—
τ(C–C–C–C) ring D

629
7.1766
632
γ(C–C–C) ring D + γ(C–C–H) ring D

639
2.7418
—
τ(C–C–C–O) + τ(C–C–C–C)

673
15.257
—
β(C–C–C) ring B

681
35.221
693
γ(C–C–H) ring D

714
5.4099
—
γ(C–C–H) ring A

739
70.1363
730
γ(C–C–H) ring A

743
19.7507
—
Bending in whole molecule

757
18.7847
757
γ(C–C–H) ring D + γ(C–C–C) ring D

773
7.1237
—
γ(C–C–H) in whole molecule

809
11.2216
—
γ(C–C–H) ring B

819
9.2691
—
β(C–C–C) ring B + β(C–O–C) ring A

825
1.1522
—
γ(C–C–H) ring D

839
0.8883
833
γ(C–C–H) ring A

870
12.1445
886
β(C–C–O) ring A + β(C–C–C) ring A

907
1.2768
—
γ(C–C–H) ring D

922
9.1487
—
β(C–C–C) rings C and D

935
16.2356
—
β(C–C–H) ring A + β(C–C–C) ring B

945
0.0615
—
γ(C–C–H) ring B

951
1.3957
954
(C–C–H) ring D

968
0.4403
—
(C–C–H) ring D

976
0.873
—
β(C–C–C) ring D

1002
24.0341
—
(O–H)

1006
14.4736
—
β(C–C–H) rings A and B + β(C–C–C) ring B

1014
24.7318
—
β(C–C–H) ring D

1034
37.6874
1032
β(C–C–O) ring A + β(C–C–H) ring A

1065
37.523
1078
β(C–C–H) ring D

1108
32.1303
—
β(C–C–H) rings A and B

1112
3.026
—
β(C–C–H) rings A and B

1120
14.9274
—
Twist CH₃

1138
3.8577
—
β(C–C–H) ring D

1140
195.8791
1132
β(C–C–H) in whole molecule + β(C–C–C) ring B

1151
51.793

Twist CH3 + β(C–C–H) in whole molecule

1164
11.6598
1163
β(C–C–H) ring D

1187
103.9113
—
β(C–C–H) in whole molecule

1195
103.0799
—
β(C–C–H) ring B + twist CH₃

1214
5.214
—
β(C–C–H) rings A and B

1250
100.8387
1225
Breathing in ring B

1273
8.6432
—
Ring D deformation

1304
6.3433
—
β(C–C–H) ring D

1310
19.154
—
β(C–C–H) in whole molecule

1330
153.5339
1339
β(C–C–C) rings B and C + β(C–C–H) ring D

1369
121.7396
1369
Ring A deformation

1408
52.4486
1405
Butterfly in CH₃

1417
8.0248
—
β(C–C–H) in whole molecule

1418
17.7601
—
β(C–C–H) in whole molecule

1424
2.3616
—
(H–C–H) in CH₃

1434
72.9917
—
β(C–C–H) ring B + (C–C) ring A

1456
17.1709
—
(H–C–H) in CH₃

1465
14.0125
1460
β(C–C–H) ring D

1504
14.0743
—
(C–C) ring A

1539
26.0649
1526
(C–C) rings C and D

1554
6.2017
—
(C–C) in whole molecule

1566
74.9616
—
(C–C) in whole molecule

1578
1.1856
—
(C–C) ring D

1592
64.7197
—
Ring A deformation

1632
379.2331
1624
(C=O)

2902
62.4466
2929
(C–H) in (O–CH₃)

2989
35.857
2972
(C–H) in (O–CH₃)

3024
7.4574
—
(C–H) in (O–CH₃)

3038
0.0903
—
(C–H) ring D

3048
14.3705
—
(C–H) ring D

3060
29.321
3052
(C–H) ring D

3072
1.1549
—
(C–H) ring B

3078
5.8476
—
(C–H) ring D

3084
4.8586
—
(C–H) ring B

3106
2.4619
—
(C–H) ring D

3127
1.4105
3131
(C–H) ring A

3149
0.1629
3153
(C–H) ring A

: stretching; : in plane bending; : out of plane bending; : torsion.

In “Karanjin,” the C–H functional group is present at a number of positions. The stretching vibration, ν(C–H), is expected to occur in the region 2900–3200 cm⁻¹. The calculated values of the ν(C–H) vibration lie within this spectral range. For C–H stretching vibrations, intense bands are calculated at 2902, 2989, and 3060 cm⁻¹ which matches well the experimental frequencies observed at 2929, 2972, and 3052 cm⁻¹.

The other important stretching vibrations correspond to the C=O moieties at the C₇ position. The region 1600–1750 cm⁻¹ is generally considered as the double bond stretching region for C=O, C=C, and C=N bonds [24–27]. The C=O stretching vibration, ν(C=O), appears as a prominent mode in the FTIR spectra at 1624 cm⁻¹ which matches well the calculated one, that is, 1632 cm⁻¹. For C–C stretching vibration an intense band is calculated at 1539 cm⁻¹ which is found to be in good agreement with the experimental one, that is, 1526 cm⁻¹. Due to the deformation of ring A vibration, an intense band is calculated at 1369 cm⁻¹ which is in very good agreement with the experimental one, that is, 1369 cm⁻¹. Due to breathing mode in ring B vibration, intense band is calculated at 1250 cm⁻¹ which nearly matches the experimental one, that is, 1225 cm⁻¹. Due to out of plane (C–C–H) vibration, intense band appears at 739 cm⁻¹. The –CH₃ functional group is an important constituent of “Karanjin” and vibrations corresponding to this group are present in a number of modes. The stretching vibrations of these groups appear in a number of modes. An intense band due to butterfly motion in CH₃ appears in the experimental spectrum at 1405 cm⁻¹ which matches well the peak at 1408 cm⁻¹, in the calculated spectrum.

In “Karanjin,” a very important vibration corresponds to the modes involving the vibrations of the ring atoms. For the purpose of simplifying the analysis, we have classified the structure of “Karanjin” into four rings A, B, C, and D as shown in Figure 1. The ring stretching vibrations, ν (ring), are complicated combinations of the stretching of C–O and C–C bonds. The most important ring stretching vibrations are the ring breathing, ring deformation, and so forth. Other ring vibration modes present a mixed profile.

There are some frequencies in the lower region due to the torsion and mixed bending modes having appreciable IR intensity in calculated FTIR spectrum. Furthermore, the study of low frequency vibrations is of great significance, because it gives information on weak intermolecular interactions, which takes place in enzyme reactions [28]. Knowledge of low frequency mode is also essential for the interpretation of the effect of electromagnetic radiation on biological systems [29].

The calculated (scaled) and experimental frequencies show some deviation which can be due to the combination of electron correlation effects, insufficiency of basis set, and the unevenness of the potential energy surface and also may be explained by the presence of external medium taken during experimental FTIR analysis. The theoretical calculations have been done on gas-phase molecule.

4.8. Electronic Spectra and Electronic Properties of Karanjin

On the basis of fully optimized ground-state structure, TDDFT//B3LYP/LANL2DZ calculations have been used to determine the low-lying excited states of “Karanjin.” The parameters calculated involve the vertical excitation energies, oscillator strength (), and wavelength by using the Gaussian 09W code. Experimental wavelengths are not available so these calculated data can presumably help the experimentalists. Electronic transitions determined from excited state calculations are listed in Table 4 for the three lowest energy transitions of the molecule. TD-DFT calculation predicts three intense electronic transitions at 4.2188 eV (293.89 nm), 5.9317 eV (209.02), and 6.7948 eV (182.47) with an oscillator strengths of 0.2818, 0.3189, and 0.2131, respectively, which are compared with the measured experimental data (Exp. = 310 nm and 274 nm).

Table 4: Calculated parameters using TDDFT//B3LYP/LANL2DZ for Karanjin.

Excitation
CI coefficient
Expansion wave length (nm) calculated (Exp.)
Oscillator strength
Energy (eV)

Excited state 1

    74 → 77
0.29364
                    293.89 (310)
0.2818
4.2188

    75 → 77
0.59270

Excited state 2

    73 → 78
0.38454
                    209.02 (274)
0.3189
5.9317

    75 → 79
0.28540

    76 → 81
0.35123

Excited state 3

    69 → 78
0.29225
                    182.47
0.2131
6.7948

    70 → 79
0.37746

    72 → 80
0.37599

The electronic structure of the “Karanjin” in the gas phase has been calculated with DFT using the B3LYP /6-311 G (d, p) as the basis set. HOMO and LUMO are the basic electronic parameters associated with the orbital in a molecule and the difference between them, resulting in energy gap. Not only energy gap (frontier orbital gap) helps to describe the chemical reactivity and kinetic stability of the molecule but also these orbitals find out the way the molecule interacts with other species. The HOMO-LUMO energy gap is an important measure for stability index. It establishes correlations in various chemical and biochemical systems [30, 31].

The plots of the HOMO, LUMO, and electrostatic potential for both the molecules in 2D and 3D are shown in Figures 4, 5, and 6. The HOMO is found to be concentrated over the whole atoms, but the LUMO lies mainly over the whole molecule but less over ring A. The calculated value of the frontier orbital energy gap is 4.25 eV (Table 5). The low frontier orbital gap is also associated with a high chemical reactivity and low kinetic stability [32]. The molecular electrostatic potential (MESP) is an important factor by which we can confirm the electrostatic potential region distribution of size and shape of molecules as well as the total physiology of the molecules. We have plotted 2D and 3D MESP structures of the title compound as shown in Figure 6. The electronegative region is outside the molecule near the oxygen atoms. The energy equal to the shielded potential energy surface is required for any substitution reaction near oxygen. The electronegative lines (in between −0.08 a.u. and −0.02 a.u.) form a closed contour which clearly indicates that total flux passing in between these curves is not equal to zero. For any nucleophilic substitution reaction near oxygen (closed contour area), an amount of energy equal to shielded potential energy surface is required; however, remaining part of molecule is suitable for electrophilic substitution reaction. Thus, it can be asserted that MESP values have been shown to be well related to biological properties [33–35].

Table 5: Lowest energy, HOMO-LUMO gap (frontier orbital energy gap), and dipole moment of Karanjin by B3LYP/6-311G (d, p) methods.

Parameters
Karanjin

Energy (in au)
−994.2536

HOMO (in eV)
−6.17377

LUMO (in eV)
−1.92332

Frontier orbital energy gap (in eV)
4.25045

Dipole moment (in Debye)
3.86

Figure 4: 3D and 2D plots of the highest occupied molecular orbital for Karanjin.

Figure 5: 3D and 2D plots of lowest unoccupied molecular orbital for Karanjin.

Figure 6: 3D and 2D plots of molecular electrostatic potential.

4.9. Global Reactivity Descriptors

The energies of frontier molecular orbitals , energy band gap , electronegativity (), chemical potential (), global hardness (), global softness (), and global electrophilicity index () [36–39] of “Karanjin” have been listed in Table 6. On the basis of and , these parameters are calculated using (1) as given below

Table 6: Calculated , , energy band gap (), chemical potential (), electronegativity (), global hardness (), global softness (), and global electrophilicity index () for Karanjin at B3LYP/6-311G (d, p) level.

Karanjin

A
−6.17377
−1.92332
4.25045
4.04854
−4.04854
2.12523
0.23527
3.85622

4.10. Local Reactivity Descriptors

The Fukui function (FF) of a molecule provides information on the reactivity. The FF successfully predicts relative site reactivities for most chemical systems and as such it provides a method for understanding and categorizing chemical reactions. The atom with the highest FF value is highly reactive when compared to the other atoms in the molecule. These values represent the qualitative descriptors of reactivity of different atoms in the molecule. Ayers and Parr [40] have elucidated that molecules tend to react where the FF is the largest when attacked by soft reagents and in places where the FF is found to be smaller when attacked by hard reagents. The use of the Fukui functions for the site selectivity of the Karanjin molecule for nucleophilic and electrophilic attacks has been made with special emphasis to the dependence of the Fukui values on the basis of B3LYP/6-311G(d, p) level of theory. Using the Mulliken atomic charges of neutral, cation, and anion, state of Karanjin, the Fukui functions , local softness , and local electrophilicity indices [37, 38], the Fukui functions are calculated using the following (2):

Local softness and electrophilicity indices are calculated using (3)

where +, −, and 0 signs show nucleophilic, electrophilic, and radical attack, respectively.

The Fukui functions, local softnesses, and local electrophilicity indices for selected atomic sites in “Karanjin” have been listed in Table 7. The maximum values of all the three local electrophilic reactivity descriptors at C7 and C2 indicate that this site is prone to nucleophilic attack, while, for electrophilic attack, C31 and C24 are found to be the most active sites.

Table 7: (a) Fukui functions (, ), local softnesses (, ), and local electrophilicity indices (, ) for selected atomic sites of Karanjin, using the Mulliken population analysis at B3LYP/6-311G (d, p) level. (b) (All atomic sites.)

(a)

Atom number

C1
−0.0098
0.09366
−0.0023
0.02203
−0.0377
0.36116

C2
0.09201
−0.0089
0.02165
−0.0021
0.35482
−0.0344

C7
0.09812
−0.0179
0.02309
−0.0042
0.37838
−0.0692

C14
0.02752
0.02195
0.00648
0.00516
0.10614
0.08463

C15
0.00421
0.02187
0.00099
0.00515
0.01623
0.08434

C16
0.06111
0.02641
0.01438
0.00621
0.23566
0.10185

C17
0.00646
0.01716
0.00152
0.00404
0.02491
0.06616

C18
0.044
0.01018
0.01035
0.0024
0.16969
0.03926

C24
−0.0138
0.05979
−0.0032
0.01407
−0.053
0.23054

C25
0.05104
0.03085
0.01201
0.00726
0.19682
0.11898

C31
−0.1047
0.06052
−0.0246
0.01424
−0.4038
0.23338

(b)

Atom number

C1
−0.1023
−0.0925
−0.0086
−0.0098
0.09366
0.08389
−0.0023
0.02203
0.01974
−0.0377
0.36116
0.3235

C2
0.01541
−0.0766
0.00648
0.09201
−0.0089
0.08308
0.02165
−0.0021
0.01955
0.35482
−0.0344
0.32039

C3
−0.171
−0.1801
−0.1926
0.0091
−0.0217
−0.0126
0.00214
−0.0051
−0.003
0.03511
−0.0835
−0.0484

C4
0.29134
0.20787
0.22905
0.08347
−0.0623
0.02118
0.01964
−0.0147
0.00498
0.32189
−0.2402
0.08169

C5
−0.1988
−0.1379
−0.1236
−0.0609
0.07519
0.01429
−0.0143
0.01769
0.00336
−0.2348
0.28995
0.05512

C6
0.31443
0.18389
0.2206
0.13054
−0.0938
0.03671
0.03071
−0.0221
0.00864
0.5034
−0.3618
0.14157

C7
0.36424
0.26612
0.3463
0.09812
−0.0179
0.08019
0.02309
−0.0042
0.01887
0.37838
−0.0692
0.30921

C8
0.21434
0.15357
0.23516
0.06077
0.02083
0.0816
0.0143
0.0049
0.0192
0.23433
0.08032
0.31465

C9
0.01435
0.02251
0.13566
−0.0082
0.12131
0.11315
−0.0019
0.02854
0.02662
−0.0314
0.46778
0.43634

O10
−0.3576
−0.3513
−0.2938
−0.0063
0.06379
0.05753
−0.0015
0.01501
0.01354
−0.0242
0.246
0.22185

O11
−0.4282
−0.4309
−0.2719
0.00268
0.15627
0.15895
0.00063
0.03677
0.0374
0.01032
0.60263
0.61295

O12
−0.2842
−0.3904
−0.3292
0.10616
−0.045
0.06119
0.02498
−0.0106
0.0144
0.40939
−0.1734
0.23595

C13
−0.1414
−0.1257
−0.1241
−0.0157
0.01735
0.00163
−0.0037
0.00408
0.00038
−0.0606
0.06689
0.00628

C14
−0.039
−0.0665
−0.017
0.02752
0.02195
0.04947
0.00648
0.00516
0.01164
0.10614
0.08463
0.19077

C15
−0.1101
−0.1143
−0.0882
0.00421
0.02187
0.02608
0.00099
0.00515
0.00614
0.01623
0.08434
0.10057

C16
−0.0675
−0.1286
−0.0411
0.06111
0.02641
0.08752
0.01438
0.00621
0.02059
0.23566
0.10185
0.33751

C17
−0.1018
−0.1082
−0.0846
0.00646
0.01716
0.02362
0.00152
0.00404
0.00556
0.02491
0.06616
0.09107

C18
−0.0203
−0.0643
−0.0101
0.044
0.01018
0.05418
0.01035
0.0024
0.01275
0.16969
0.03926
0.20895

H19
0.17629
0.09163
0.14199
0.08465
−0.0343
0.05035
0.01992
−0.0081
0.01185
0.32644
−0.1323
0.19418

H20
0.0974
0.05258
0.13397
0.04482
0.03657
0.08139
0.01055
0.0086
0.01915
0.17285
0.14101
0.31386

H21
0.09873
0.04495
0.13962
0.05377
0.0409
0.09467
0.01265
0.00962
0.02227
0.20735
0.15772
0.36507

H22
0.09777
0.05104
0.13087
0.04674
0.0331
0.07984
0.011
0.00779
0.01878
0.18022
0.12764
0.30787

H23
0.10521
0.07289
0.12009
0.03232
0.01489
0.04721
0.0076
0.0035
0.01111
0.12464
0.0574
0.18204

C24
−0.109
−0.0952
−0.0492
−0.0138
0.05979
0.04603
−0.0032
0.01407
0.01083
−0.053
0.23054
0.1775

C25
0.08553
0.03449
0.11639
0.05104
0.03085
0.08189
0.01201
0.00726
0.01927
0.19682
0.11898
0.3158

O26
−0.3851
−0.2927
−0.2394
−0.0924
0.1457
0.05331
−0.0217
0.03428
0.01254
−0.3563
0.56187
0.20559

H27
0.12614
0.07306
0.15104
0.05309
0.0249
0.07799
0.01249
0.00586
0.01835
0.20471
0.09602
0.30074

H28
0.12425
0.06315
0.15403
0.06109
0.02978
0.09088
0.01437
0.00701
0.02138
0.23559
0.11485
0.35044

H29
0.12266
0.08408
0.13502
0.03858
0.01236
0.05093
0.00908
0.00291
0.01198
0.14876
0.04765
0.1964

H30
0.1577
0.07866
0.16266
0.07904
0.00496
0.084
0.0186
0.00117
0.01976
0.3048
0.01914
0.32394

C31
−0.202
−0.0973
−0.1414
−0.1047
0.06052
−0.0442
−0.0246
0.01424
−0.0104
−0.4038
0.23338
−0.1704

H32
0.07267
0.07634
0.15422
−0.0037
0.08155
0.07788
−0.0009
0.01919
0.01832
−0.0142
0.31449
0.30033

H33
0.18683
0.12381
0.17165
0.06302
−0.0152
0.04784
0.01483
−0.0036
0.01126
0.24303
−0.0585
0.18449

H34
0.05282
0.07183
0.1301
−0.019
0.07728
0.05826
−0.0045
0.01818
0.01371
−0.0733
0.29799
0.22467

In pentagonal ring A, carbon is replaced by oxygen which has the most electronegative lone pair antibonding electron which extracts electrons from the neighboring carbon having the positive charge. To cancel this positive charge, it attracts the electron from C24 carbon. So C24 provides a better electrophilic site for the soft receptors. In hexagonal ring C, a carbon is replaced by oxygen having two lone pair antibonding electrons. Due to the repulsion of these antibonding electrons, the shape of the ring gets distorted. Ring C has two substituent groups at para and meta positions. At meta position, oxygen is attached to the ring C and at para position O–CH₃ group is attached. Oxygen is more electronegative than carbon which extracts electron from carbon. Due to this reason, C31 carbon atom of methyl group is a better center for electrophilic substitution. In hexagonal ring C, electron withdrawing group O–CH₃ extracts electron from C9 atom of the ring C to fulfill the deficiency; C9 atom extracts electron from C7 atom and hence because of the C7 atom being electron deficient it extracts electron from O11 so C7 atom becomes a potential site for a nucleophilic attack.

4.11. Dipole Moment, Polarizability, Hyperpolarizability, and Thermodynamic Properties

Dipole moment (), polarizability , and total first static hyperpolarizability [41, 42] are also calculated (in Tables 5 and 8) by using density functional theory. They can be expressed in terms of , , and components and are given by following (4):

The components of Gaussian output are reported in atomic units, where 1 a.u. = 8.3693 × 10⁻³³ e.s.u. For Karanjin, the calculated dipole moment value is 3.86 Debye. Having higher dipole moment than water (2.16 Debye), “Karanjin” can be used as better solvent. We see a greater contribution of in molecule which shows that the molecule is elongated more towards direction and is more contracted to direction. Perpendicular part contributes with a less part of polarizability of molecule. and contribute with a larger part of hyperpolarizability in the molecule. This shows that plane and -axis are more optically active in these directions. Standard thermodynamic functions such as free energy, constant volume heat capacity CV, and entropy have also been calculated for “Karanjin” and are given in Table 9. These functions can provide helpful information for further study of the title compounds.

Table 8: Polarizability and hyperpolarizability of Karanjin.

Polarizability
Values
Hyperpolarizability
Values

−109.2190

22.0796

3.9546

−8.6890

−121.6217

−2.3092

1.5294

−61.3104

−127.8736

−8.1237

0.5918

1.2207

119.5714

22.2892

—
—

1.4229

—
—

11.6211

—
—

0.2894

—
—

63.6404

Table 9: Calculated thermodynamic properties of Karanjin by B3LYP/6-311G (d, p) methods.

(thermal) (kcalmol⁻¹)
CV (cal K⁻¹mol⁻¹)
(cal K⁻¹mol⁻¹)

Total
171.700
67.244
133.534

Translational
0.889
2.981
42.913

Rotational
0.889
2.981
34.406

Vibrational
169.922
61.283
56.215

5. Conclusion

In this work, the compound “Karanjin” an anti-HIV drug was experimentally isolated and identified and its bioactivity along with detailed quantum chemical studies was carried out. The optimized geometry of the “Karanjin” molecule has been determined by the method of density functional theory (DFT). For both geometry and total energy, it has been combined with B3LYP functional having 6-311 g (d, p) as the basis set. Using this optimized structure, we have calculated the infrared wavenumbers and compared them with the experimental data. The calculated wavenumbers are in an excellent agreement with the experimental values. On the basis of fully optimized ground-state structure, TDDFT//B3LYP/LANL2DZ calculations have been used to determine the low-lying excited states of “Karanjin.” Reactivity reflects the susceptibility of a substance towards a specific chemical reaction and plays a key role in, for example, the design of new molecules and understanding biological systems and material science. Hyperpolarizability is mainly controlled by the planarity of the molecules, the donor and accepter strength, and bond length alteration. The values of hyperpolarizability indicate a possible use of these compounds in electrooptical applications. We have also discussed global and local reactivity descriptors sites for both molecules during electrophilic, nucleophilic, and radical attacks. These values represent the qualitative descriptors of reactivity of different atoms in the molecule. This compound shows anti-HIV activity so these theoretical and experimental aspects can provide a path for researchers in future.

Conflict of Interests

The authors of the paper have no conflict of interests in the present work.

Acknowledgment

The corresponding author Apoorva Dwivedi is grateful to Professor Neeraj Misra for providing valuable suggestions.

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