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.
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 [
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.
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
Molecular structure and numbering scheme of gemifloxacin.
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.
UV-visible spectrum of gemifloxacin.
In the present communication the density functional theory (DFT) [
The comparative experimental and calculated FTIR spectrum plotted using the pure Lorentzian band shape is shown in Figure
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
PES scan for dihedral angle N9–O3–C28–H46 at B3LYP/6-31G(d,p).
PES scan for dihedral angle C18–C23–C27–O5 at B3LYP/6-31G(d,p).
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
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.
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
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 |
According to Buckingham’s definitions [
The
Table
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 |
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 [
3D and 2D plots of highest occupied molecular orbital.
3D and 2D plots of lowest unoccupied molecular orbital.
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
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
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 | |
2 | 3055 | 56.63 | 3578 | 3435 | 0.1998 | |
3 | 3491 | 3351 | 0.4316 | |||
4 | 3249 | 3119 | 10.0403 | |||
5 | 3233 | 3104 | 2.438 | |||
6 | 3229 | 3100 | 6.3866 | |||
7 | 3219 | 3090 | 1.1449 | |||
8 | 3165 | 3038 | 10.6528 | |||
9 | 3158 | 3032 | 4.3852 | |||
10 | 3151 | 3025 | 8.6429 | |||
11 | 3005 | 55.67 | 3147 | 3021 | 19.6229 | |
12 | 2936 | 54.31 | 3144 | 3018 | 3.2433 | |
13 | 3106 | 2982 | 38.7297 | |||
14 | 3101 | 2977 | 8.7738 | |||
15 | 3086 | 2963 | 33.0247 | |||
16 | 3069 | 2946 | 6.182 | |||
17 | 3039 | 2917 | 37.6489 | |||
18 | 3035 | 2914 | 92.4957 | |||
19 | 3022 | 2901 | 31.5689 | |||
20 | 3012 | 2892 | 42.9044 | |||
21 | 1875 | 1800 | 398.7119 | |||
22 | 1747 | 1677 | 10.4167 | |||
23 | 1716 | 47.92 | 1732 | 1663 | 266.1866 | |
24 | 1632 | 24.84 | 1674 | 1607 | 474.1293 | |
25 | 1667 | 1600 | 29.3607 | |||
26 | 1648 | 1582 | 6.6382 | |||
27 | 1565 | 54.16 | 1592 | 1528 | 96.152 | |
28 | 1548 | 53.99 | 1538 | 1476 | 29.2542 | |
29 | 1505 | 45.15 | 1532 | 1471 | 221.661 | |
30 | 1463 | 22.92 | 1523 | 1462 | 24.2871 | |
31 | 1521 | 1460 | 20.5083 | |||
32 | 1519 | 1458 | 14.6334 | |||
33 | 1514 | 1453 | 28.8567 | |||
34 | 1492 | 1432 | 1026.975 | |||
35 | 1489 | 1429 | 5.1036 | |||
36 | 1476 | 1417 | 5.8399 | |||
37 | 1401 | 53.42 | 1473 | 1414 | 38.2325 | |
38 | 1380 | 56.21 | 1425 | 1368 | 155.047 | |
39 | 1365 | 53.98 | 1422 | 1365 | 10.7429 | |
40 | 1411 | 1355 | 84.1162 | |||
41 | 1399 | 1343 | 32.1298 | |||
42 | 1333 | 55.02 | 1387 | 1332 | 113.0278 | |
43 | 1378 | 1323 | 37.0029 | |||
44 | 1360 | 1306 | 160.7416 | |||
45 | 1356 | 1302 | 5.7122 | |||
46 | 1348 | 1294 | 177.0604 | |||
47 | 1345 | 1291 | 20.6199 | |||
48 | 1277 | 64.25 | 1328 | 1275 | 7.0325 | |
49 | 1251 | 57.98 | 1286 | 1235 | 322.3537 | |
50 | 1200 | 32.68 | 1282 | 1231 | 5.9684 | |
51 | 1264 | 1213 | 72.3611 | |||
52 | 1259 | 1209 | 24.5975 | |||
53 | 1242 | 1192 | 39.123 | |||
54 | 1230 | 1181 | 53.4191 | |||
55 | 1214 | 1165 | 30.0027 | |||
56 | 1211 | 1163 | 31.2091 | |||
57 | 1208 | 1160 | 33.2809 | |||
58 | 1199 | 1151 | 1.5623 | |||
59 | 1190 | 1142 | 7.6781 | |||
60 | 1179 | 1132 | 0.683 | |||
61 | 1173 | 1126 | 5.1076 | |||
62 | 1167 | 1120 | 5.5937 | |||
63 | 1154 | 1108 | 1.5315 | |||
64 | 1075 | 55.26 | 1126 | 1081 | 1.49 | |
65 | 1048 | 35.07 | 1101 | 1057 | 193.4065 | |
66 | 1093 | 1049 | 91.3698 | |||
67 | 1090 | 1046 | 5.5213 | |||
68 | 1087 | 1044 | 53.7568 | |||
69 | 1084 | 1041 | 73.8575 | |||
70 | 1070 | 1027 | 15.8765 | |||
71 | 1045 | 1003 | 41.2686 | |||
72 | 1044 | 1002 | 7.029 | |||
73 | 1005 | 965 | 14.8417 | |||
74 | 995 | 62.23 | 996 | 956 | 7.3192 | |
75 | 966 | 65.78 | 975 | 936 | 3.9291 | |
76 | 949 | 911 | 16.5036 | |||
77 | 948 | 910 | 1.6637 | |||
78 | 944 | 906 | 18.9177 | |||
79 | 936 | 899 | 79.4214 | |||
80 | 914 | 877 | 21.479 | |||
81 | 899 | 63.39 | 899 | 863 | 9.4454 | |
82 | 846 | 69.37 | 883 | 848 | 18.0586 | |
83 | 808 | 61.76 | 851 | 817 | 45.6951 | |
84 | 790 | 67.54 | 837 | 804 | 5.8479 | |
85 | 780 | 67.77 | 826 | 793 | 37.0415 | |
86 | 819 | 786 | 74.1025 | |||
87 | 805 | 773 | 29.7494 | |||
88 | 744 | 71.20 | 784 | 753 | 5.5338 | |
89 | 730 | 69.94 | 774 | 743 | 2.3155 | |
90 | 649 | 70.04 | 770 | 739 | 11.5353 | |
91 | 633 | 69.26 | 733 | 704 | 4.0076 | |
92 | 565 | 65.32 | 724 | 695 | 7.5578 | |
93 | 709 | 681 | 15.554 | |||
94 | 687 | 660 | 8.2598 | |||
95 | 678 | 651 | 1.8987 | |||
96 | 644 | 618 | 11.4498 | |||
97 | 632 | 607 | 47.2942 | |||
98 | 556 | 64.01 | 583 | 560 | 0.9083 | |
99 | 537 | 65.90 | 563 | 540 | 8.1788 | |
100 | 546 | 524 | 2.0577 | |||
101 | 532 | 511 | 10.7569 | |||
102 | 524 | 503 | 38.0854 | |||
103 | 491 | 70.38 | 510 | 490 | 36.598 | |
104 | 488 | 468 | 18.4656 | |||
105 | 462 | 444 | 0.6491 | |||
106 | 456 | 438 | 0.4181 | |||
107 | 411 | 75.35 | 442 | 424 | 9.799 | |
108 | 378 | 363 | 3.8598 | |||
109 | 374 | 359 | 2.5382 | |||
110 | 364 | 349 | 3.7118 | |||
111 | 357 | 343 | 10.0529 | |||
112 | 332 | 319 | 4.4483 | |||
113 | 318 | 305 | 2.6928 | |||
114 | 307 | 295 | 4.629 | |||
115 | 282 | 271 | 6.6786 | |||
116 | 270 | 259 | 5.1601 | |||
117 | 266 | 255 | 4.2444 | |||
118 | 257 | 247 | 36.9303 | |||
119 | 212 | 204 | 3.3546 | |||
120 | 206 | 198 | 1.8688 | |||
121 | 199 | 191 | 0.1723 | |||
122 | 178 | 171 | 4.4266 | |||
123 | 170 | 163 | 4.0924 | |||
124 | 160 | 154 | 1.2498 | |||
125 | 147 | 141 | 14.9009 | |||
126 | 136 | 131 | 5.0938 | |||
127 | 129 | 124 | 1.5802 | |||
128 | 111 | 107 | 3.1136 | |||
129 | 87 | 84 | 2.5982 | |||
130 | 85 | 82 | 2.211 | |||
131 | 69 | 66 | 0.8606 | |||
132 | 63 | 60 | 2.5986 | |||
133 | 61 | 59 | 0.327 | |||
134 | 56 | 54 | 1.5885 | |||
135 | 50 | 48 | 0.9022 | |||
136 | 44 | 42 | 0.4721 | |||
137 | 25 | 24 | 0.8119 | |||
138 | 15 | 14 | 0.0919 |
aAbbreviations:
In gemifloxacin, the C–H functional group is present at a number of positions. The stretching vibration,
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
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
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
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.
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.