Spectroscopy: An International Journal

Volume 27 (2012), Issue 3, Pages 185-206

doi:10.1155/2012/614710

Electronic Structure, Nonlinear Optical Properties, and Vibrational Analysis of Gemifloxacin by Density Functional Theory

Shamoon Ahmad Siddiqui,¹ Tabish Rasheed,² Mohd Faisal,¹ Anoop Kumar Pandey,³ and Sher Bahadar Khan⁴

¹Centre for Advanced Materials and Nanoengineering, Najran University, P.O. Box 1988, Najran 11001, Saudi Arabia

²Department of Applied Sciences, School of Engineering and Technology, Sharda University, Plot No. 32–34, Knowledge Park III, Greater Noida 201306, India

³Department of Physics, University of Lucknow, Lucknow 226001, India

⁴Center of Excellence for Advanced Materials Research and Chemistry Department, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia

Copyright © 2012 Shamoon Ahmad Siddiqui 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.

The non-linear optical properties of gemifloxacin (C₁₈H₂₀FN₅O₄) have been examined using density functional theory (DFT). The molecular HOMO, LUMO composition, their respective energy gaps, MESP contours/surfaces have also been drawn to explain the activity of gemifloxacin. The equilibrium geometries and harmonic frequencies of title molecule was determined and analyzed at DFT/B3LYP level employing the 6-31G(d,p) basis set. The skeleton of both the optimized molecules is non-planar. In general, a good agreement between experimental and calculated normal modes of vibrations has been observed.

1. Introduction

Gemifloxacin (7-[(4E)-3-(aminomethyl)-4-methoxyiminopyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,8-naphthyridine-3-carboxylic acid) is an oral broad-spectrum quinolone antibacterial agent widely used in the treatment of acute bacterial exacerbation of chronic bronchitis and mild-to-moderate pneumonia [1–3]. Gemifloxacin acts by inhibiting DNA synthesis through the inhibition of both DNA gyrase and topoisomerase IV enzymes, which are essential for bacterial growth. Notably this drug has about 100 times higher affinity for bacterial DNA gyrase than for mammalian ones. Gemifloxacin is a broad-spectrum antibiotic that is highly active against both Gram-positive and Gram-negative bacteria [4, 5]. Gemifloxacin is globally used for the treatment of bacterial infection caused by susceptible strains like S. pneumoniae, H. influenzae, H. parainfluenzae, or M. catarrhalis, S. pneumoniae (including multi-drug-resistant strains (MDRSP)), M. pneumoniae, C. pneumonia; K. pneumoniae. Gemifloxacin rapidly absorbed from the gastrointestinal tract and the absolute bioavailability averages approximately 71%. Gemifloxacin is metabolized to a certain extent by the liver. All metabolites formed are minor (<10% of the administered oral dose); the principal ones are N-acetyl gemifloxacin, the E-isomer of gemifloxacin and the carbamyl glucuronide of gemifloxacin [6, 7].

The aim of the present communication is to investigate the molecular structure, vibrational spectra, and energetic data analysis of the molecule under study, in gas phase, due to biological and pharmaceutical importance of the title molecule. The structure and the ground-state energy of the drug under investigation have been analyzed employing density functional theory with B3LYP method. In order to obtain a more complete description of molecular vibration, vibrational frequency calculation has been carried out. The vibrational analysis also provides the detailed information about the intramolecular vibrations in the fingerprint region. The reported optimized geometries, molecular properties such as equilibrium energy, HOMO-LUMO gap, dipole moment, polarizability as well as first static hyperpolarizability components along with the electrostatic potential contours and surfaces have also been used to understand the activity of the molecules.

2. Experimental: Structure and Spectra

The fourier transform infrared spectrum was recorded with FT-IR Perkin Elmer spectrometer in KBr dispersion in the range of 400 to 4000 cm⁻¹. The optical properties of the gemifloxacin were examined using UV-visible spectrophotometer at room temperature. UV-visible spectrum was recorded in the range of 190–800 nm with Perkin Elmer-Lambda 950-UV-visible spectrometer. To measure the UV-visible absorption, the gemifloxacin particles were dispersed in distilled DI water and measured. The model molecular structure of gemifloxacin has been given in Figure 1. The experimental and calculated FT-IR spectra is given in Figure 2, and the experimental UV-visible spectrum is given in Figure 3.

Figure 1: Molecular structure and numbering scheme of gemifloxacin.

(a)

(b)

Figure 2: Comparison of normalized IR spectra: (a) experimental (FTIR) and (b) scaled simulated spectrum obtained by using DFT (scaling factor × 0.96) harmonic calculations for gemifloxacin.

Figure 3: UV-visible spectrum of gemifloxacin.

3. Computational Details

In the present communication the density functional theory (DFT) [8] has been employed using Becke’s three-parameter hybrid exchange functionals [9] with the Lee-Yang-Parr correlation functionals [10, 11] to optimize the molecular structure and to calculate the electronic structure properties of the drug molecule. The Gaussian 03W program [12] was used to calculate the vibrational spectra, dipole moment (μ), polarizability (α), and the first static hyperpolarizability (β) of the title molecule, based on the finite field approach. The vibrational frequencies are calculated and scaled down by the appropriate factor [13, 14]. The vibrational wavenumber assignments and PED calculation have been carried out by combining the result of the GaussView 4.1 and the VEDA program [15, 16] with symmetry considerations.

The comparative experimental and calculated FTIR spectrum plotted using the pure Lorentzian band shape is shown in Figure 2.

4. Result and Discussion

4.1. Analysis of Conformers of Gemifloxacin

Theoretical calculations for conformers of gemifloxacin were carried out using the B3LYP/6-31G(d,p) method. The plots of the potential energy surface (PES) scans for this molecule are shown in Figures 4 and 5. The dihedral angles N₉–O₃–C₂₈–H₄₆ and C₁₈–C₂₃–C₂₇–O₅ are the relevant coordinates for conformational calculations within the molecule. In these calculations, all the geometrical parameters were simultaneously relaxed during the calculations while the dihedral angles were varied in steps of . The global minimum energy structure was obtained at −179.821° and −132.892° for the dihedral angles N₉–O₃–C₂₈–H₄₆ and C₁₈–C₂₃–C₂₇–O₅, respectively. The corresponding minimum energy for both PES scans was −1372.3884 Hartree, which implies that the obtained structure was a global minimum. This structure is shown in Figure 1 and was used for performing frequency calculations.

Figure 4: PES scan for dihedral angle N₉–O₃–C₂₈–H₄₆ at B3LYP/6-31G(d,p).

Figure 5: PES scan for dihedral angle C₁₈–C₂₃–C₂₇–O₅ at B3LYP/6-31G(d,p).

4.2. Molecular Geometry Optimization

The equilibrium geometry optimization of lowest energy conformer has been achieved by energy minimization. The optimized geometry of the molecule under study is confirmed to be located at the global minima on PES, as the calculated vibrational spectrum contains no imaginary wavenumber. The given molecule has three rings. Out of these two are six membered and one five membered. Ring R1 and R2 are in a plane while ring R3 deviates from the given plane due to two bulky groups, one attached at 6N of ring R1 and the other attached at 19C. The optimized bond length of C–C in six-membered pyridine ring R1 ranges between 1.367 Å and 1.475 Å, while, for another pyridine ring R2, this ranges between 1.366 Å and 1.401 Å. For five-membered pyrrole ring R3, C–C bond lengths are quite high and range between 1.510 Å and 1.536 Å. The optimized value of C23–C27 bond length adjacent to pyridine ring R1 is found to be 1.496 Å, which is also high in comparison to the C–C bond length in R1. The optimized value of C15–C22 bond length adjacent to pyrrole ring R3 is found to be 1.546 Å, which is also high in comparison to the C–C bond length in R3. Another important C–C bond length in cyclopropane attached to pyridine ring R1 is found in the range 1.501 Å–1.508 Å. The optimized C–N bond lengths in pyridine ring R1 are found to be 1.367 Å and 1.401 Å, while, in pyridine ring R2, the optimized C–N bond lengths are found to be 1.337 Å and 1.341 Å. On the other hand the optimized C–N bond lengths in pyrrole ring R3 are calculated as 1.473 Å and 1.469 Å, which is quite high in comparison to C–N bond length in both pyridine ring R1 and R2 because C–N bond in R2 is double bond while C–N bond in ring R1 has just double bond character due to delocalization of lone pair electrons of nitrogen in R1. C11–N6 bond length adjacent to ring R1 is found to be 1.451 Å, while C20–N7 bond length between ring R2 and R3 is calculated as 1.365 Å, which is quite small in comparison to C11–N6 bond length. The length of C19=N9 bond adjacent to ring R3 is found to be 1.276 Å, while C22–N10 bond length is found to be 1.465 Å. The length of C28–O3 bond adjacent to pyrrole ring R3 is found to be 1.425 Å. Values of all the bond angles are given in Table 1, and all are in accordance with previous experimental and theoretical studies on different biomolecules [17–19].

Table 1: Optimized geometrical parameters of gemifloxacin, bond length (Å), and bond angle (°).

S. no.
Optimized parameters
Bond length
Optimized parameters
Bond angle

1
F1–C25
1.3568
N9–O3–C28
108.7776

2
O2=C24
1.2292
C27–O4–H45
108.8845

3
O3–N9
1.4063
C11–N6–C14
119.7248

4
O3–C28
1.425
C11–N6–C18
120.7158

5
O4–C27
1.3734
C14–N6–C18
119.1417

6
O4–H45
0.9675
C16–N7–C17
112.2795

7
O5=C27
1.2025
C16–N7–C20
120.2429

8
N6–C11
1.4508
C17–N7–C20
125.3726

9
N6–C14
1.4014
C14–N8–C20
119.5509

10
N6–C18
1.3673
O3–N9–C19
111.185

11
N7–C16
1.4734
C22–N10–H43
109.9774

12
N7–C17
1.4695
C22–N10–H44
109.7683

13
N7–C20
1.3647
H43–N10–H44
106.2508

14
N8–C14
1.3369
N6–C11–C12
119.8908

15
N8–C20
1.3412
N6–C11–C13
119.6133

16
N9–C19
1.2761
N6–C11–H29
113.1169

17
N10–C22
1.4655
C12–C11–H29
116.832

18
N10–H43
1.0166
C13–C11–H29
117.5714

19
N10–H44
1.018
C11–C12–H30
117.0507

20
C11–C12
1.5012
C11–C12–H31
117.4329

21
C11–C13
1.5077
C13–C12–H30
117.2739

22
C11–H29
1.0867
C13–C12–H31
119.4588

23
C12–C13
1.5081
H30–C12–H31
114.7379

24
C12–H30
1.0845
C11–C13–H32
118.7106

25
C12–H31
1.0847
C11–C13–H33
117.2653

26
C13–H32
1.0853
C12–C13–H32
117.1928

27
C13–H33
1.0851
C12–C13–H33
119.3677

28
C14–C21
1.4051
H32–C13–H33
114.1386

29
C15–C16
1.5356
N6–C14–N8
116.6219

30
C15–C19
1.5101
N6–C14–C21
119.0267

31
C15–C22
1.546
N8–C14–C21
124.3514

32
C15–H34
1.095
C16–C15–C19
103.1176

33
C16–H35
1.0901
C16–C15–C22
112.5205

34
C16–H36
1.0988
C16–C15–H34
111.7457

35
C17–C19
1.5139
C19–C15–C22
111.514

36
C17–H37
1.093
C19–C15–H34
109.6012

37
C17–H38
1.0974
C22–C15–H34
108.2916

38
C18–C23
1.3673
N7–C16–C15
104.2976

39
C18–H39
1.084
N7–C16–H35
110.6862

40
C20–C25
1.428
N7–C16–H36
110.474

41
C21–C24
1.4753
C15–C16–H35
111.9643

42
C21–C26
1.4077
C15–C16–H36
111.7943

43
C22–H40
1.0995
H35–C16–H36
107.6519

44
C22–H41
1.0964
N7–C17–C19
102.8584

45
C23–C24
1.4728
N7–C17–H37
111.4483

46
C23–C27
1.4958
N7–C17–H38
112.38

47
C25–C26
1.3663
C19–C17–H37
111.6618

48
C26–H42
1.0846
C19–C17–H38
111.1651

49
C28–H46
1.0921
H37–C17–H38
107.3873

50
C28–H47
1.0954
N6–C18–C23
124.8211

51
C28–H48
1.0953
N6–C18–H39
114.179

In five-membered ring, torsional strain also arises from the fact that, as the lateral distance between the bonds on two adjacent carbon atoms decreases, the repulsive interaction between the electrons of the bonds increases which cause decrease in bond angle. The double bond is sp² hybridized and forms bonds with bond angles of about 120°. In such cases the unsaturated double bond has two electron pairs, one of the sigma bond and the other of the pi bond. Repulsion by these two electron pairs, the other bond pair is greater than that between two single bond pairs. This leads to deviations from exact trigonal geometry. The same is the reason for R1 and R2 which shows lower bond angles as compared to true trigonal geometry.

4.3. Electronic Spectra of Gemifloxacin

On the basis of fully optimized ground-state structure, TDDFT/B3LYP/6-31G(d,p) calculations have been used to determine the low-lying excited states of gemifloxacin. The calculated results involving the vertical excitation energies, oscillator strength , and wavelength are carried out using the Gaussian 03W program and compared with measured experimental wavelength. Electronic transitions determined from excited-state calculations are listed in Table 2 for the three lowest energy transitions of the molecule. TD-DFT calculation predicts two intense electronic transition at 3.8040 eV (325.93 nm) and 4.1959 eV (295.49) with oscillator strengths of 0.3149 and 0.0394, respectively, in good agreement with the measured experimental data (exp = 270 nm and 342 nm) as shown in Figure 3.

Table 2: Calculated parameters using TDDFT/B3LYP/6-31G(d,p) for gemifloxacin.

Excitation
CI expansion coefficient
Wavelength (nm)
Oscillator strength
Energy (eV)

Calculated
Experimental

Excited state 1

325.93
342
0.3149
3.8040

102 → 103
0.63798

102 → 104
0.14530

Excited state 2

309.18

0.0090
4.0101

99 → 103
0.65753

100 → 103
−0.12556

Excited state 3

295.49
270
0.0394
4.1959

100 → 103
−0.29490

101 → 103
0.31447

102 → 104
0.50647

4.4. Dipole Moment, Polarizability, and First Static Hyperpolarizability

According to Buckingham’s definitions [20], DFT has also been used to calculate the dipole moment (μ), polarizability (α), and the first static hyperpolarizability (β). The total intrinsic hyperpolarizability [21] and a component of the first hyperpolarizability along the direction of the dipole moment are represented by β [21, 22].

The β components of the Gaussian output are reported in atomic units, where 1 a.u. = 8.3693 * 10⁻³³ e.s.u..

Table 3 clearly shows that molecule has major component of polarizability along axial direction; however, perpendicular components of polarizability have negligible contribution. Thus the polarization ellipsoid nearly planar is stretched along axis and contracted along axis. Thus dipole formed along axis and less stretched along perpendicular direction. The plane contains and having major part of hyperpolarizability. It means ellipsoids flattered along this plane. This means that this molecule is optically reactive in direction.

Table 3: Calculated values of polarizability and hyperpolarizability using DFT/6-31G(d,p) for gemifloxacin.

S. no
Polarizability parameters
Value (e.s.u)
Hyperpolarizability parameters
Value (e.s.u)

1

155.517

588.2079

2

7.2473627,

157.9636

3

239.2203429

38.9723

4

−13.711457

26.2387

5

140.0071631

0.8472

6

−4.3056718

−1.4496

7

122.9957

24.0212

8

7.9028

9

9.3606

10

8.7427

11

94.3118

4.5. Electronic Properties

HOMOs and LUMOs determine the way the molecule interacts with other species. The frontier orbital gap helps characterize the chemical reactivity of molecule. A molecule which have more orbital gap is more less polarized and less chemically reactive [23]. According to the present DFT calculations, the frontier orbital gap in case of given molecule is 4.30 eV. The 3D and 2D plots of the HOMO, LUMO, and electrostatic potential for the molecule are shown in Figures (6–8). HOMO is located at ring R1 and R2, however, half R3 and F atom part of pentagon ring. If we see 2D plot of HOMO (Figure 6) a negative equipotential concentric line appears around N atom (ring R1) and F atom (adjacent to ring R2). However, a surface of positive line is closely concentrated around O atom adjacent to ring R1. It clearly indicates that delocalized electrons are confined at negative region of given molecule, however, shifted from positive part. This type of delocalized electron takes part in reaction and behaves as active part for binding to the receptor. LUMOs are located (Figure 7) at same place as HOMOs, except to those two carbon which are adjoint to ring R1 and R2. In the case of given molecule, the electronegative region (red) is towards the outer part and near the oxygen which is adjacent to ring R1, and moderate positive region (green) is located nearly over whole molecule.

(a)

(b)

Figure 6: 3D and 2D plots of highest occupied molecular orbital.

(a)

(b)

Figure 7: 3D and 2D plots of lowest unoccupied molecular orbital.

(a)

(b)

Figure 8: 3D and 2D plots of molecular electrostatic potential.

The importance of MESP lies in the fact that it simultaneously displays size as well as shape and with the help of colour grading (shown in Figure 8) defined positive, negative, and neutral electrostatic potential regions, which are very useful in investigation of molecular structure with its physiochemical property relationship [24–28]. As we see from 2D molecular electrostatic potential plot (Figure 8), negative equipotential surface lines are passing near to O atom which is adjacent to ring R1, and other negative potential regions are found near to N atom of ring R2 (where negative lines closely form a concentric circle). Negative potential surface line near to O atom is passing through F atom. This indicates that it is suitable place for nucleophilic substitution reaction. The energy equal to the shielded PES is required for any substitution reaction near the oxygen. The electronegative lines (between −0.08.u. and −0.04.u.) form a closed contour which clearly indicates that the total flux passing in between these curves is not equal to zero. It generates a negative electric field region near the oxygen atom which opposes the electrophilic substitution. The molecule acts as a dipole in which the area near the oxygen atom acts as the negative pole (better site for positive radicals in human bodies), however, the remaining part of the molecule is suitable for electrophilic substitution reaction. Out of these, all regions are surrounded by the positive potential surface line over whole molecule.

4.6. Vibrational Assignments

The molecule gemifloxacin contains 48 atoms, and it has 138 normal modes of vibration. All the 138 fundamental vibrations are IR active. The harmonic-vibrational frequencies calculated for gemifloxacin and experimental frequencies (FTIR) have been compared in Table 4. Vibrational assignments are based on the observation of the animated modes in GaussView and assignments reported in the literature.

Table 4: Vibrational assignments for gemifloxacin.

Mode no.
Experimental frequencies
Calculated frequencies and intensities
Vibrational assignmenta

and intensities
using DFT/6-31G(d,p)

FTIR (cm⁻¹)
Intensity profile (% transmittance)
Unscaled (cm⁻¹)
Scaled (cm⁻¹)
Intensity (km/mol)

1
3439
48.64
3804
3652
16.9813
(O₃₉–H) (100)

2
3055
56.63
3578
3435
0.1998
(NH₂) (98)

3

3491
3351
0.4316
(NH₂) (98)

4

3249
3119
10.0403
(H₂C–CH₂) (98)

5

3233
3104
2.438
(H₂C–CH₂) (97)

6

3229
3100
6.3866
ν(C–H) (100)

7

3219
3090
1.1449
ν(C–H) (97)

8

3165
3038
10.6528
ν(C–H) (91), (H₂C–CH₂)

9

3158
3032
4.3852
(CH₂) (89)

10

3151
3025
8.6429
(CH₂) (94)

11
3005
55.67
3147
3021
19.6229
(CH₃) (92)

12
2936
54.31
3144
3018
3.2433
(CH₂) (97)

13

3106
2982
38.7297
(CH₃) (100)

14

3101
2977
8.7738
(CH₂) (91)

15

3086
2963
33.0247
ν(C–H) (91)

16

3069
2946
6.182
ν(C–H) (89), (CH₂)

17

3039
2917
37.6489
(CH₂) (90)

18

3035
2914
92.4957
(CH₃) (91)

19

3022
2901
31.5689
(CH₂) (95)

20

3012
2892
42.9044
(CH₂) (87)

21

1875
1800
398.7119
ν(C=O) (86), β(O–H)

22

1747
1677
10.4167
ν(C=N) (84)

23
1716
47.92
1732
1663
266.1866
ν(C=O) (83)

24
1632
24.84
1674
1607
474.1293
ν(C–H) (40),β(C–H) (10), ν(R1), ν(R2)

25

1667
1600
29.3607
ζ(NH₂) (86)

26

1648
1582
6.6382
β(C–H) (66)

27
1565
54.16
1592
1528
96.152
ν(R2) (57), β(C–H)

28
1548
53.99
1538
1476
29.2542
ζ(CH₂) (52)

29
1505
45.15
1532
1471
221.661
ζ(CH₂) (21), ν(C–C) (10), ν(C–N) (13)

30
1463
22.92
1523
1462
24.2871
ζ(CH₂) (81)

31

1521
1460
20.5083
(CH₃) (89)

32

1519
1458
14.6334
ζ(H₂C–CH₂) (80)

33

1514
1453
28.8567
ζ(CH₂) (83)

34

1492
1432
1026.975
β(R2) (55)

35

1489
1429
5.1036
ζ(CH₃) (79)

36

1476
1417
5.8399
ζ(H₂C–CH₂) (93)

37
1401
53.42
1473
1414
38.2325
(CH₃)–Umbrella (84)

38
1380
56.21
1425
1368
155.047
β(C–H) (54)

39
1365
53.98
1422
1365
10.7429
ω(CH₂) (76)

40

1411
1355
84.1162
β(C–H) (20)

41

1399
1343
32.1298
β(C–H) (33)

42
1333
55.02
1387
1332
113.0278
ω(CH₂) (15), β(C–H)

43

1378
1323
37.0029
ω(CH₂) (49), τ(CH₂), β(C–H)

44

1360
1306
160.7416
ω(CH₂) (33), τ(CH₂) (15), β(C–H), β(O–H)

45

1356
1302
5.7122
ω(CH₂) (42), τ(CH₂)

46

1348
1294
177.0604
β(C–H) (23)

47

1345
1291
20.6199
τ(NH₂) (64), τ(CH₂), β(C–H)

48
1277
64.25
1328
1275
7.0325
ω(CH₂) (40), β(C–H)

49
1251
57.98
1286
1235
322.3537
β(O–H) (35), β(C–H)

50
1200
32.68
1282
1231
5.9684
ω(CH₂) (22), β(C–H)

51

1264
1213
72.3611
β(C–H) (24)

52

1259
1209
24.5975
β(O–H) (45), β(C–H), τ(CH₂), ω(CH₂)

53

1242
1192
39.123
τ(CH₂) (36)

54

1230
1181
53.4191
β(O–H) (43), ζ(H₂C–CH₂)

55

1214
1165
30.0027
τ(CH₂) (45), (CH₃)

56

1211
1163
31.2091
τ(CH₂) (13), β(C–H), β(O–H)

57

1208
1160
33.2809
(CH₃) (62), τ(CH₂)

58

1199
1151
1.5623
τ(H₂C–CH₂) (56)

59

1190
1142
7.6781
β(C–H) (30), τ(NH₂)

60

1179
1132
0.683
(CH₃) (21)

61

1173
1126
5.1076
τ(CH₂) (53), τ(NH₂)

62

1167
1120
5.5937
β(C–H) (20), β(O–H)

63

1154
1108
1.5315
β(C–H) (36)

64
1075
55.26
1126
1081
1.49
γ(C–H) (51)

65
1048
35.07
1101
1057
193.4065
β(C–H) (13)

66

1093
1049
91.3698
β(C–H) (61), ω(NH₂)

67

1090
1046
5.5213
ω(H₂C–CH₂) (88)

68

1087
1044
53.7568
ν(C–N) (65)

69

1084
1041
73.8575
β(C–H), β(O–H)

70

1070
1027
15.8765
δ(H₂C–CH₂)-Umbrella (65)

71

1045
1003
41.2686
δ(H₂C–CH₂) (11), β(C–H)

72

1044
1002
7.029
ρ(CH₂), τ(NH₂)

73

1005
965
14.8417
ρ(CH₂) (60)

74
995
62.23
996
956
7.3192
β(C–H), ω(CH₂)

75
966
65.78
975
936
3.9291
δ(H₂C–CH₂)

76

949
911
16.5036
ρ(CH₂), ρ(NH₂)

77

948
910
1.6637
γ(C–H)

78

944
906
18.9177
γ(C–H)

79

936
899
79.4214
ω(CH₂), ν(O–N)

80

914
877
21.479
β(C–H), δ(H₂C–CH₂)

81
899
63.39
899
863
9.4454
τ(CH₂), β(C–H)

82
846
69.37
883
848
18.0586
ω(NH₂), ρ(CH₂)

83
808
61.76
851
817
45.6951
δ(H₂C–CH₂)

84
790
67.54
837
804
5.8479
γ(C–H), δ(H₂C–CH₂)

85
780
67.77
826
793
37.0415
ω(NH₂), ρ(H₂C–CH₂)

86

819
786
74.1025
ω(NH₂), ρ(CH₂)

87

805
773
29.7494
ρ(CH₂), γ(C=O), γ(C–H)

88
744
71.20
784
753
5.5338
ρ(H₂C–CH₂)

89
730
69.94
774
743
2.3155
ρ(H₂C–CH₂)

90
649
70.04
770
739
11.5353
ν(Ring)-breathing (39), ρ(H₂C–CH₂)

91
633
69.26
733
704
4.0076
γ(Ring), τ(H₂C–CH₂)

92
565
65.32
724
695
7.5578
δ(R3), ρ(CH₂)

93

709
681
15.554
τ(CH₂), δ(H₂C–CH₂)

94

687
660
8.2598
β(C–H), δ(H₂C–CH₂), δ(R2)

95

678
651
1.8987
β(O–H), γ(R2), β(C–H)

96

644
618
11.4498
β(O–H), β(C–H)

97

632
607
47.2942
ω(CH₂), β(O–H), δ(R2)

98
556
64.01
583
560
0.9083
τ(CH₂), γ(R3)

99
537
65.90
563
540
8.1788
γ(O–H)

100

546
524
2.0577
γ(O–H), δ(H₂C–CH₂)

101

532
511
10.7569
γ(O–H), ω(CH₂)

102

524
503
38.0854
γ(O–H)

103
491
70.38
510
490
36.598
γ(O–H), γ(C–H)

104

488
468
18.4656
δ(H₂C–CH₂), γ(O–H), γ(C–H)

105

462
444
0.6491
γ(C–H), γ(O–H)

106

456
438
0.4181
γ(C–H), γ(O–H)

107
411
75.35
442
424
9.799
β(C=O), β(O–H), ρ(CH₂)

108

378
363
3.8598
δ(H₂C–CH₂), ν(C–F)

109

374
359
2.5382
γ(C–H), γ(O–H)

110

364
349
3.7118
β(O–CH₃)

111

357
343
10.0529
β(O–H), ν(C–N), (CH₃)

112

332
319
4.4483
β(C–F), δ(CH₂), δ(NH₂)

113

318
305
2.6928
ρ(CH₂), ν(C–COOH)

114

307
295
4.629
ρ(CH₂), (CH₃)

115

282
271
6.6786
ρ(CH₂) )

116

270
259
5.1601
β(C–F), β(C=O), ρ(H₂C–CH₂), ρ(CH₂), ρ(NH₂)

117

266
255
4.2444
ρ(CH₂), δ(H₂C–CH₂)

118

257
247
36.9303
ρ(NH₂)

119

212
204
3.3546
δ(H₂C–CH₂), β(C=O), β(O–H), ω(CH₂)

120

206
198
1.8688
ρ(NH₂), ρ(CH₂)

121

199
191
0.1723
β(R1), β(R3), δ(H₂C–CH₂)

122

178
171
4.4266
ρ(CH₂), ω(CH₂), γ(R1), γ(R2)

123

170
163
4.0924
(CH₃)

124

160
154
1.2498
(CH₃), ρ(CH₂)

125

147
141
14.9009
ρ(CH₂), τ(NH₂), (CH₃), δ(H₂C–CH₂)

126

136
131
5.0938
ρ(CH₂), β(O–CH₃), δ(H₂C–CH₂)

127

129
124
1.5802
β(C–COOH), ρ(H₂C–CH₂)

128

111
107
3.1136
β(O–CH₃), ρ(CH₂)

129

87
84
2.5982
(CH₃)

130

85
82
2.211
(CH₃), ω(NH₂), δ(H₂C–CH₂), γ(C=O)

131

69
66
0.8606
ρ(H₂C–CH₂), γ(C–H), β(O–CH₃)

132

63
60
2.5986
τ(COOH), ρ(H₂C–CH₂), γ(C–H), ρ(CH₂), γ(C–F)

133

61
59
0.327
δ(H₂C–CH₂), γ(C–H), ρ(NH₂)

134

56
54
1.5885
τ(COOH), ρ(NH₂), γ(C–F)

135

50
48
0.9022
γ(O–CH₃), β(C–NH₂), ρ(CH₂), β(C–(H₂C–CH₂))

136

44
42
0.4721
ρ(CH₂), β(O–CH₃), β(C–NH₂), β(C–OH)

137

25
24
0.8119
β(C–(H₂C–NH₂)), β(C–H), β(C–(H₂C–CH₂))

138

15
14
0.0919
β(O–CH₃), β(C–NH₂)

aAbbreviations: ν, stretching; , symmetric stretching; , asymmetric stretching; β, in-plane bending; γ, out-of-plane bending; , symmetrical deformation; , asymmetrical deformation; ζ, scissoring; ρ, rocking; , in-plane rocking; , out-of-plane rocking; ω, wagging; τ, twisting.

In gemifloxacin, 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 3010–3120 cm⁻¹. The calculated values of the ν(C–H) vibration lie within this spectral range. The other important stretching vibration corresponds to the C=O moieties at the C₂₄ and C₂₇ positions. The region 1650–1750 cm⁻¹ is generally considered as the double bond stretching region for C=O, C=C, and C=N bonds [29–32]. The C=O stretching vibration, ν(C=O) appears as a prominent mode in the FTIR spectra at 1716 cm⁻¹. Another important stretching vibration in gemifloxacin is the O–H stretching vibration. The O–H group vibrations are likely to be most sensitive to the environment, so they show pronounced shifts in the spectra of the hydrogen-bonded species. In the subject molecule, the ν(O–H) vibration appears at 3439 cm⁻¹ in the FTIR spectrum. The calculated (scaled) and experimental frequencies are deviated by large amount, which may be explained by the presence of hydrogen bondings in the solid sample.

The –NH₂, and –CH₂, functional groups are important constituents of gemifloxacin and vibrations corresponding to these groups are present in a number of modes. The stretching vibrations of these groups appear in a number of modes. The wagging vibrations ω(CH₂) and ω(NH₂) are also present in a number of modes. Mode 39 shows a pure ω(CH₂) vibration, and there is excellent correspondence between calculated (scaled) and experimental FTIR wavenumber as can been seen in Table 4. The twisting (τ) and rocking (ρ) vibrations for both the functional groups are present mixed with other vibrations.

The other important functional group in gemifloxacin is the –CH₃ group. There are nine modes of vibration of methyl group, which are distributed as follows: one symmetric stretching , two anti-symmetric stretching , one symmetrical deformation , two asymmetrical deformation , one in-plane rocking , one out-of-plane rocking , and one twisting (τ) vibration modes [30]. The (CH₃) and (CH₃) vibrations, are present in higher frequency modes as pure vibrations, and the other vibrations are mixed with other vibrations. The H₂C–CH₂ functional group which is attached to the C₁₁ atom in gemifloxacin has unique vibrational fingerprints. It shows a number of vibrations, and these are distributed throughout the spectrum.

In gemifloxacin, a very important vibration corresponds to the modes involving the vibrations of the ring atoms. For the purpose of easing the analysis, we have classified the structure of gemifloxacin into three rings R1, R2, and R3 as shown in Figure 1. The ring stretching vibrations ν(Ring) are complicated combinations of stretchings of C–N, C=C, and C–C bonds. The most important ring stretching vibration is the ring breathing vibration at mode 90. In this mode, all bonds of the rings appear to stretch and contract in-phase with each other [33]. In the experimental infrared spectrum of gemifloxacin, this mode appears at 649 cm⁻¹. Other ring vibration modes present a mixed profile.

5. Conclusion

In the present work we have calculated the geometric parameters, vibrational frequencies, frontier molecular orbitals, molecular electrostatic potential contours, and surfaces and the nonlinear optical properties of gemifloxacin using DFT/B3LYP method. Optimized geometry clearly shows that the skeleton of the title molecule is nonplanar. The higher frontier orbital gap of 4.30 eV shows that gemifloxacin has high kinetic stability and can be termed as hard molecule. However, the higher value of dipole moment shows that gemifloxacin molecule is highly polar. Nonlinear optical behavior of title molecule was investigated by the determination of the dipole moment, the polarizability, and the first static hyperpolarizability using density functional B3LYP method. In general, a good agreement between experimental and calculated normal modes of vibrations has been observed. The molecular electrostatic potential contours and surfaces have also been drawn to explain the activity of gemifloxacin molecule. The present quantum chemical study may further play an important role in understanding of the structure, activity, and dynamics of the molecule.

Acknowledgment

One of the authors (Shamoon Ahmad Siddiqui) is thankful to the Deanship of Scientific Research for Grant no.: NU 16/11, Najran University, Najran, Kingdom of Saudi Arabia for financial support.

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