Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 112 (2013) 351–363

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Spectrochimica Acta Part A: Molecular andBiomolecular Spectroscopy

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Vibrational analysis, electronic structure and nonlinear optical propertiesof Levofloxacin by density functional theory

Sethu Gunasekaran a, K. Rajalakshmi b,⇑, Subramanian Kumaresan c

a PG & Research Department of Physics, Pachaiyappa’s College, Chennai 600 030, Indiab Department of Physics, Sri Chandrasekharendra Saraswathi Viswa MahaVidhyalaya, Enathur, Kanchipuram 631 561, Indiac PG & Research Department of Physics, Arignar Anna Government Arts College, Cheyyar 604 407, India

h i g h l i g h t s

� The vibrational assignments havebeen carried for four ring structuredmolecule.� Stability of the molecule and charge

delocalization analyzed using NBOanalysis.� The most stable geometry of the

compound is determined from PES.� Density plots of HOMO–LUMO energy

surface plotted to identify donor andacceptor.� ESP surface plotted to get

electrophilic and nucleophilic sites ofthe molecule.

1386-1425/$ - see front matter � 2013 Elsevier B.V. Ahttp://dx.doi.org/10.1016/j.saa.2013.04.074

⇑ Corresponding author. Tel.: +91 9444132026.E-mail address: k_rajalakshmi123@yahoo.com (K.

g r a p h i c a l a b s t r a c t

In this work, complete vibrational assignments, NLO and NBO properties were performed by DFT with 6-31 G(d, p) basis sets. Electronic transitions within molecule and HOMO and LUMO energy of Levofloxacinwere studied. MESP map shows that the negative potential sites (red and yellow) are electronegative oxy-gen atoms, while the positive potential sites (blue) are around the hydrogen atoms. Thermodynamicproperties of the title compound were also calculated.

a r t i c l e i n f o

Article history:Received 6 February 2013Received in revised form 11 April 2013Accepted 16 April 2013Available online 25 April 2013

Keywords:DFTLevofloxacinFT-IRHyperpolarizabilityMESPHOMO–LUMO

a b s t r a c t

The Fourier transform (FT-IR) spectrum of Levofloxacin was recorded in the region 4000–400 cm�1 and acomplete vibrational assignment of fundamental vibrational modes of the molecule was carried out usingdensity functional method. The observed fundamental modes have been compared with the harmonicvibrational frequencies computed using DFT (B3LYP) method by employing 6-31 G (d, p) basis sets.The most stable geometry of the molecule under investigation has been determined from the potentialenergy scan. The first-order hyperpolarizability (bo) and other related properties (l, ao) of Levofloxacinare calculated using density functional theory (DFT) on a finite field approach. UV–vis spectrum of themolecule was recorded and the electronic properties, such as HOMO and LUMO energies were performedby DFT using 6-31 G (d, p) basis sets. Stability of the molecule arising from hyperconjugative interactions,charge delocalization have been analyzed using natural bond orbital analysis (NBO). The calculatedHOMO and LUMO energies show that, the charge transfer occurs within the molecule. The other molec-ular properties like molecular electrostatic potential (MESP), Mulliken population analysis and thermo-dynamic properties of the title molecule have been calculated.

� 2013 Elsevier B.V. All rights reserved.

ll rights reserved.

Rajalakshmi).

352 S. Gunasekaran et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 112 (2013) 351–363

Introduction

Levofloxacin C18H20FN3O4 ((S)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methylpiperazin-1-yl)-7-oxo-7H-pyrido[1,2,3-de]-1,4-ben-zoxazine-6-carboxylic acid) is an oral broad spectrum antibiotic ofthe fluoroquinolone drug widely used in the treatment of certainbacterial infections including pneumonia, urinary tract infectionsand abdominal infections [1–4]. Levofloxacin is active againstGram positive and Gram negative bacteria. It acts by inhibitingDNA gyrase, a type II topoisomerase which is an enzyme necessaryto separate replicated DNA, thereby inhibiting cell division [5].Levofloxacin is the L-isomer of the acemate ofloxacin, a quinoloneantimicrobial agent. In chemical terms, Levofloxacin, a chiral fluo-rinated carboxyquinolone, is the pure enantiomer of the racemicdrug substance ofloxacin. Levofloxacin is globally used for thetreatment of bacterial infections caused by susceptible strains likeHemophilus influenzae, Klebsiella pneumoniae, Legionella pneumo-phila, Moraxella catarrhalis, Streptococcus pneumoniae, Chlamydiapneumoniae, and Mycoplasma pneumoniae. Levofloxacin is valued forthis broad spectrum of activity, excellent tissue penetration, and fortheir availability in both oral and intravenous formulations [6].

The aim of the work is to investigate the molecular structure,vibrational study of the molecule due to its biological and pharma-ceutical importance been analyzed by density functional theoryusing 6-31 G (d, p) basis sets. In order to obtain the descriptionof the molecular vibrations of the title molecule, complete vibra-tional analysis have been carried out and it provides the detailedinformation about the intramolecular vibrations in entire mid-infrared region and especially in the fingerprint region. In orderto understand the activity of the molecule, the electronic energy,HOMO–LUMO energy, polarizability, first state hyperpolarizabilityalong with the electrostatic potentials have been calculated and re-ported. To the best of our knowledge, no work on vibrationalassignments, molecular structure, and stability have been reportedso far. This study may reveal the molecule is not only finding itsapplications in biological and pharmaceutical importance but alsofinds its importance in NLO applications.

Experimental: structure and spectra

The sample was obtained from M/s. Sigma–Aldrich Co., with astated purity of 99% and was used as such without further purifica-tion. The Fourier transform infrared spectrum was recorded usingPerkin–Elmer spectrometer in KBr dispersion in the range of4000–400 cm�1. The optical properties of the Levofloxacin wereexamined using UV–vis spectrum recorded at room temperaturein the range of 190–800 nm with Perkin–Elmer-Lambda950-UV–vis spectrometer. The optimized molecular structure of

Fig. 1. Molecular structure and num

Levofloxacin along with numbering scheme has been given inFig. 1. The experimental and calculated FT-IR spectra are given inFig. 2.

Computational details

In the present work, the density functional method (DFT) [7]has been employed using Becke’s three parameter hybrid exchangefunctional [8] with the Lee–Yang–Parr correlation functional [9,10]to optimize the structure of the molecule and also to calculate theelectronic structure of the title molecule. The entire calculationswere performed at ab initio Hartree Fock (HF) and DFT methodusing B3LYP levels at 6-31 G(d,p) basis sets on a PentiumV/1.6 GHz personal computer by using Gaussian 03 W programpackage [11,12] and applied geometry optimization [13]. Initialgeometry generated, was minimized at the Hartree Fock levelusing 6-31 G(d,p) basis set and also optimized at DFT/B3LYP levelsat 6-31G (d,p) basis set. The vibrational modes are assigned usingGauss-View molecular visualization program package [14]. Theoptimized structural parameters were used in the vibrational fre-quency calculations at the DFT levels to characterize all stationarypoints as minima. The vibrational frequencies were calculated andscaled down by the appropriate scaling factor and thereby thevibrational assignments are compared with observed values.

Gauss View 4.1 program have been used to study HOMO (high-est occupied molecular orbital) and LUMO (lowest unoccupiedmolecular orbital) orbital energy distribution, HOMO and LUMOenergy gap, total density and molecular electrostatic potential sur-face (MESP) mapping. The thermodynamic properties and elec-tronic parameters like self-consistent field energy (SCF) (a.u.),Zero point vibrational energy (ZPVE) (kcal mol�1), rotational con-stants (GHz), specific heat (Cv) (cal mol�1 K�1), entropy(cal mol�1 K�1), dipole moment l (Debye), HOMO and LUMO ener-gies (eV), frontier orbital energy gaps (a.u.) and Mulliken atomiccharges (eV), polarizability (a), and the hyperpolarizability (b) ofthe title molecule were calculated by DFT method based on thefinite field approach.

Results and discussion

Analysis of conformers of Levofloxacin

The potential energy profile as a function of N21AC20AC18AF19

dihedral angle was obtained by employing DFT method and theplots of the potential energy surfaces (PESs) scan for this moleculeare shown in Fig. 3. During the calculations, all the geometricalparameters were simultaneously relaxed and the dihedral anglewas varied in steps of 15� from 180� and reduced up to zero

bering scheme of Levofloxacin.

Fig. 2. Comparison of normalized IR spectra: (a) experimental (FT IR) and (b) calculated IR spectra obtained using B3LYP /6-31 G(d,p) method.

Fig. 3. PES Scan for dihedral angle N21AC20AC18AF19 at DFT/B3LYP/6-31 G (d,p)method.

S. Gunasekaran et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 112 (2013) 351–363 353

[15]. The optimized structure was obtained at 120.721� for thedihedral angle N21AC20AC18AF19 and the corresponding minimumenergy was �1262.98 Hartree, which implies that the obtainedstructure was at global minimum.

Molecular geometry optimization

The equilibrium geometry optimization of lowest energy con-former has been achieved by energy minimization. The optimizedgeometry of the molecule was located at the global minima on

potential energy scan as the calculated vibrational spectrum con-tains no imaginary wavenumber. In the molecule, there are foursix membered rings R1, R2, R3 and R4 with the presence of bulkygroups in R4 and R2 attached at C20 and C10 respectively. The opti-mized bond length of CAC in R1 ranges between 1.375 Å and1.415 Å, while in R2 it ranges from 1.375 Å to 1.495 Å, for R3 thebond length of CAC ranges between 1.527 Å and 1.528 Å and inthe ring R4, it ranges between 1.527 Å and 1.529 Å where theCAC bond length in rings R3 and R4 are quite high when comparedto rings R1 and R2. The optimized CAN bond lengths in the ring R1

are found to be 1.406 Å and 1.423 Å and the bond lengths of CAN inring R4 is quite high and is calculated to be 1.454 Å and 1.470 Å be-cause CAN in ring R1 has just double bond character due to delocal-ization of lone pair electrons of nitrogen. N21AC20 bond lengthadjacent to ring R1 is found to be 1.423 Å, while the bond lengthof C9AN8 adjacent to ring R1 is found to be 1.350 Å which is smallcompared to the bond length of C2AN8 which is 1.483 Å due to thepresence of bulky groups. Also, adjacent to ring R1, the bond lengthof C25AN24 is high and is found to be 1.454 Å. The values of all thebond lengths are tabulated in Table 1, where the values are inaccordance with previous theoretical and experimental studies[1–3].

In the ring R4, torsion strain arises due to the fact that the lateraldistance between the bonds of two adjacent carbon atoms de-creases and the repulsive interaction between the electrons ofthe bonds increases, which results in the decrease of the bond an-gle. The unsaturated double bond has two electron pairs, one is ther bond and the other is the p bond. Repulsion between the twosingle electron pairs is smaller than the other bond pair which

Table 1Optimized geometrical parameters of Levofloxacin, bond length (A) and bond angle (�).

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

1 C1AH28 1.094 C2AC1AH29 108.742 C1AH30 1.092 H28AC1AH30 108.613 C2AH3 1.098 H29AC1AH28 108.334 C2AC4 1.527 H29AC1AH30 107.025 C2AC1 1.528 C1AC2AH30 112.566 C2AN8 1.483 H29AC2AH28 111.407 C4AO5 1.422 H3AC2AC4 107.718 C4AH31 1.092 C1AH3AC2 109.539 C4AH32 1.099 C2AH3AO5 111.81

10 O5AC6 1.366 C4AO5AH31 105.9211 C6AC7 1.415 C4AO5AH32 110.1212 C6AC20 1.402 H31AC4AH32 108.9113 C7AN8 1.406 C2AC4AH31 110.1314 C7AC16 1.407 C2AC4AH32 109.8515 N8AC9 1.350 C6AO5AC4 114.2716 C9AC10 1.375 O5A C6AC7 121.2517 C9AH33 1.082 O5AC6AC20 117.9718 C10AC11 1.482 C6AC7AC16 120.0019 C10AC14 1.465 C7AN8AC9 119.3120 C11AO12 1.346 C7AN8AC16 119.7421 C11AO13 1.223 C7AN8AC2 117.8922 O12AH34 0.972 N8AC9AH33 117.1423 C14AO15 1.228 H3AC9AC10 117.8524 C14AC16 1.495 N8AC9AC10 125.0125 C16AC17 1.400 C9AC10AC14 120.3826 C17AC18 1.378 C9AH10AC11 114.1327 C18AH35 1.083 C16AC10AC14 113.6328 C18AF19 1.352 C10AC11AC14 125.4929 C18AC20 1.408 O12AC11AC10 114.7330 C20AN21 1.423 O12AC11AO13 121.7231 N21AC22 1.470 O15AC14AC16 120.5132 C22AH36 1.095 C10AC14AO15 125.8633 C22AH37 1.101 C16AC17AH35 118.9534 C22AC23 1.527 C17AC18AH35 121.9635 C23AN24 1.461 C18AF19AC17 119.0636 C23AH38 1.108 F19AC18AC20 117.4737 C23AH39 1.096 C18AC20AC6 117.0038 N24AC25 1.454 C20AN21AC27 114.6939 C25AH40 1.095 N21AC22AC20 114.9440 C25AH42 1.107 C22AC23AH37 109.2341 C26AN24 1.461 C23AN24AC25 111.9542 C26AC27 1.527 N24AC25AC26 111.9543 C26AH43 1.108 N24AC26AH43 111.7144 C26AH44 1.096 C26AC27AN24 110.4845 C27AN21 1.470 C26AC27AH45 109.2546 C27AH45 1.101 C26AC27AH46 109.5247 C27AH46 1.095 C26AH45AH46 108.24

Fig. 4. UV–vis spectrum of Levofloxacin.

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results in the deviation of the exact trigonal geometry. This trigo-nal geometry flattens as the distance between the two carbonbonds decreases due to steric hindrance. The double bond is sp3

hybridized and forms bonds with bond angles of less than or about120�. The same reason holds good for rings R1, R2, R3 and R4 whichshows lower bond angles than the values of regular planar trigonalgeometry.

Electronic spectra of Levofloxacin

All the molecular structure allows strong p–p⁄ transition in theUV–vis region with a high extinction coefficient. The lowest sin-glet ? singlet spin-allowed excited states were taken into accountto investigate the properties of electronic absorption. On the fullyoptimized structure at TDDFT/B3LYP/6-31 G (d, p) method todetermine the excited states of Levofloxacin. Fig. 4 presents the re-corded spectrum of Levofloxacin. The calculated results involvingthe vertical excitation energies, oscillator strength (f) and wave-length are tabulated in Table 2. The calculated excitation energiesof transition with the experimental values are compared and theresults are in good agreement with the calculated values [16].

As we can see in Table 2, the strong absorption peak is found tobe 323 nm and weak absorption peaks at 281 nm and 255 nm inUV–vis spectrum matches with the peaks at 323 nm, 311 nm and

Table 2Calculated parameters of Levofloxacin using TDDFT/B3LYP/6-31 G (d,p) levels.

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

Calculated Experimental

Excited state 193 ? 96 0.57167 323.43 323 0.0008 3.833493 ? 97 0.14953

Excited state 291 ? 96 0.46710 311.13 281 0.0018 3.984992 ? 96 0.4553895 ? 96 0.22208

Excited state 391 ? 96 �0.12167 307.84 255 0.0709 4.027692 ? 96 �0.1514595 ? 97 0.50446

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307 nm in TDDFT/B3LYP/6-31 G (d,p) method. The highest occu-pied molecular orbital (HOMO) and the lowest unoccupied molec-ular orbital (LUMO) are the main orbital’s that take part inchemical stability [17]. The HOMO is located over the ring R4 andthe HOMO ? LUMO transition implies an electron transfer fromRing R4 to Rings R1, R2, R3 and these orbital’s significantly overlapin their positions. The HOMO and HOMO-1 are characterized as ap-bonding molecular orbital and the LUMO and LUMO+1 exhibita p⁄ molecular orbital.

Dipole moment, polarizability and first static hyperpolarizability

NLO effects arise from the interactions of electromagneticfields in various media to produce new fields altered in phase,frequency, amplitude or other propagation characteristics fromthe incident fields [18]. NLO is at the forefront of current researchbecause of its importance in providing the key functions of fre-quency shifting, optical modulation, optical switching, optical lo-gic, and optical memory for the emerging technologies in areassuch as telecommunications, signal processing, and optical con-nectors [19,20].

The non-linear optical response of an isolated molecule in anelectric field Ei (x) can be represented as a Taylor series expansionof the total dipole moment, ltot, induced by the field:

ltotal ¼ l0 þ aijEj þ bijkEjk þ :::::

where a is the linear polarizability, l0 is the permanent dipole mo-ment and bijk are the first hyperpolarizability tensor components.The isotropic (or average) linear polarizability is defined as [21]:

atotal ¼axx þ ayy þ azz

3

First hyperpolarizability is a third rank tensor that can be describedby 3 � 3 � 3 matrix. The 27 components of 3D matrix can be re-duced to 10 components due to the Kleinman symmetry [22](bxyy = byxy = byyx = byyz = byzy = bzyy; . . . likewise other permutationsalso take same value). The output from Gaussian 03 provides10components of this matrix as bxxx, bxxy, bxyy, byyy, bxxz, bxyz, byyz, bxzz,byzz, bzzz, respectively. The components of the first hyperpolarizabil-ity can be calculated using the following equation [21]:

bi ¼ biii þ13

X

i–j

ðbijj þ bjij þ bajjiÞ

Using the x, y and z components of b, the magnitude of the firsthyperpolarizability tensor can be calculated by:

btotal ¼ ðb2x þ b2

y þ b2z Þ

1=2

The complete equation for calculating the magnitude of b fromGaussian 03W output is given a follows:

btotal ¼ ½ðbxxx þ bxyy þ bxzzÞ2 þ ðbyyy þ byzz þ bxxyÞ

2 þ ðbzzz þ bxxz

þ byyzÞ2�1=2

The calculations of the total molecular dipole moment (l), linearpolarizability (a) and first-order hyperpolarizability (b) from theGaussian output and DFT has been extensively used as an effectivemethod to investigate the organic NLO materials. In addition,the polar properties of the title molecule were calculated at theDFT/6-31G (d,p) levels.

In the present study of the title molecule, the calculated thedipole moment (l), polarizability (a) and the first static hyperpo-larizability (b) are correlated and discussed. The total intrinsichyperpolarizability btotal and a component of the first hyperpolar-izability along the direction of the dipole moment are representedby b.

Since the value of the polarizability a and the hyperpolarizabil-ity b components of the Gaussian output are reported in atomicunits, the calculated values have been converted into electrostaticunits (esu) (a: where 1 a.u. = 0.1482 � 10�24 esu: b: where1 a.u. = 8.3693 � 10�33 esu). Table 3 clearly shows that moleculehas major component of polarizability along axial direction; how-ever, perpendicular components of polarizability have negligiblecontribution. Thus the polarization ellipsoid nearly planar isstretched along X axis and contracted along Z axis. Thus dipole isformed along XYZ axis and less stretched along perpendiculardirection. The plane containing XX and YY are having major partof hyperpolarizability. It means ellipsoid is flattered along thisplane. This means that this molecule is optically reactive in Xdirection.

Domination of particular component indicates on a substantialdelocalization of charges in that direction. It is noticed that the big-gest values of hyperpolarizability is along bxxx direction and subse-quently delocalization of electron cloud is more in that direction.The maximum b value indicates the movement of p electron cloudfrom donor to acceptor [22,23].

Frontier molecule orbitals and molecular electrostatic potential(MESP)

The frontier orbital gap helps to characterize the chemical reac-tivity of the molecule. HOMO and LUMOs determine the way inwhich it interacts with other species. A molecule which have moreorbital gap is less polarized and less chemically reactive [24]. In thepresent DFT calculations, the frontier orbital gap in the given mol-ecule is 6.02 eV. The HOMO and LUMO plots and electrostatic po-tential for the molecule are shown in Figs. 5–7. HOMO is locatedon Ring R4 and it is shown in 3D plot. If you see the 2D plot, a neg-ative equipotential concentric line appear around N atom in ring R4

and F atom in Ring R1. However, a surface of positive line is closely

Table 3Calculated values of polarizability and hyperpolarizability for Levofloxacin by DFT method using B3LYP/6–31 G (d,p) basis sets.

Polarizability parameters Value (esu) Hyperpolarizability parameters Value (esu)

lx �3.2732 bxxx 24687.3426ly 8.08185 bxxy �1885.0174lz �0.0650 bxyy �3995.5875l 9.4066 byyy 639.7178axx 60.6582 bxxz 1216.1790axy �1.2389 bxyz �356.0300ayy 48.8469 byyz 245.7226axz 0.0059 bxzz �859.5271ayz 0.6046 byzz 552.2064azz 26.1454 bzzz �333.2655atotal 45.2168 btotal 6.2854

Fig. 5. (a) 3D and (b) 2D plots of highest occupied molecular orbital.

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concentrated around O atom of ring R3 and R2 which clearly indi-cates that delocalized electrons are confined to negative region ofgiven molecule, however, shifted from positive part. This type ofdelocalized electron takes part in reaction and behaves as activepart for binding to the receptor.

LUMOs are located (Fig. 7) on the rings R1, R2, R3 and in the caseof given molecule, the electronegative region (red) is1 towards the

1 For interpretation of color in Fig. 7, the reader is referred to the web version ofthis article.

outer part and near the oxygen which is adjacent to rings R1 and R2

and moderate positive region (green) is located nearly over wholemolecule.

The importance of MESP lies in the fact that it simultaneouslydisplays size as well as shape and with the help of color grading(shown in Fig. 6) defined positive, negative, and neutral electro-static potential regions, which are very useful in investigation ofmolecular structure with its physiochemical property [25,26].From 2D molecular electrostatic potential plot (Fig. 7), negativeequipotential surface lines are passing near to O atom which is

Fig. 6. (a) 3D and (b) 2D plots of lowest occupied molecular orbital.

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adjacent to ring R2, and other negative potential regions are foundnear to N atom of ring R4 (where negative lines closely form a con-centric circle). Negative potential surface line near to O atom ispassing through F atom. This indicates that it is suitable place forelectrophilic substitution reaction. The energy equal to the shieldPES is required for any substitution reaction near the oxygen. Theelectronegative lines (between �0.08 a.u. and �0.04 a.u.) form aclosed contour which clearly indicates that the total flux passingin between these curves is not equal to zero. It generates a negativeelectric field region near the oxygen atom which opposes the elec-trophilic substitution. The molecule acts as a dipole in which thearea near the oxygen atom acts as the negative pole (better sitefor positive radicals in human bodies); however, the remainingpart of the molecule is suitable for electrophilic substitution reac-tion. Out of these, all regions are surrounded by the positive poten-tial surface line over the whole molecule.

Vibrational assignments

The molecule Levofloxacin contains 46 atoms, and it has 132normal modes of vibration. According to group theory the pointgroup symmetry for the molecule is C1 symmetry and all the 138fundamental modes of vibrations are IR active. The harmonic-vibrational frequencies calculated for Levofloxacin have been com-pared with the experimental frequencies and is given in Table 4.

The calculated vibrational wavenumbers are usually higher thanthe corresponding experimental quantities because of the combi-nation of electron correlation effects and basis sets deficiencies.Therefore, it is customary to scale down the calculated harmonicwavenumber in order to improve the agreement with the experi-mental values. After applying a uniform scaling factor, the theoret-ical calculation reproduces the experimental data well. Vibrationalassignments are based on the observations of the animated modesin Gauss View and assignments reported in the literature.

In particular, the vibration associated with the carboxylic acidgroups are affected by the intermolecular interactions. In aromaticcompounds, the CAH stretching wavenumbers appear in the range3000–3100 cm�1 and the CAH in plane and out-of-plane bendingvibrations are in the range 1000–1300 cm�1 and 750–1000 cm�1

respectively [27–29]. In the present study, the aromatic CAHstretching bands appear at 2934 cm�1 for B3LYP and 2935 cm�1

in IR spectrum. The CAH peaks were observed in the range3095–2885 cm�1 by Natraj et al. [30].

The carboxylic acid OAH stretching bands are characterized bya very broad band appearing near about 3400 cm�1 [25,26]. In thepresent study the OAH stretching band was observed at 3420 cm�1

from DFT/B3LYP and a very sharp band at 3421 cm�1 in FT-IR spec-trum is assigned to OAH stretching mode. In Levofloxacin, theOAH in-plane bending and out of plane bending vibrations are as-signed to 1393 cm�1 and 1380 cm�1 respectively from DFT/B3LYP

Fig. 7. (a) 3D and (b) 2D plots of molecular electrostatic potential.

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calculations and in IR spectrum a band observed at 1396 is as-signed to OAH bending mode. The OAH in-plane and out-of-planebending vibrations are increased in value because of the hydrogenbonding through the carbonyl groups.

The CAN stretching wavenumber is rather a difficult task sincethere are problems in identifying these wavenumbers from othervibrations. Sundaraganesan et al. [25,26] assigned CAN stretchingabsorptions in the region 1391 cm�1 for 2-amino-5-iodopyridine.In the present work, the band observed at 1208 cm�1 in FT-IRhas been assigned to CAN stretching vibrations and theoreticallycomputed value at 1208 cm�1 is in good agreement.

The ring stretching vibrations are very important in the spec-trum of pyridine and its derivatives are highly characteristic ofthe aromatic rings. The aromatic ring carbon–carbon stretchingvibrations occur in the region 1430–1625 cm�1. In the presentwork, the CAC aromatic stretch is observed in the region 1723–1593 cm�1 in the DFT/B3LYP calculations and in FT-IR spectrum,it is observed in the region 1724–1595 cm�1. These vibrationsare in good agreement with the calculated values. The CAC in-plane and out-of-plane vibrations are in good agreement withthe literature values [31].

Methyl group vibrationsMethyl group vibrations are generally referred to as electron

donating substituent in the aromatic rings system the asymmetric

CAH stretching mode of CH3 is expected around 2870 cm�1 andCH3 symmetric stretching is expected around at 2870 cm�1 [32].The CAH stretching mode is observed in the region 2934–2917 cm�1 from DFT/B3LYP method and a medium band in FT-IRspectrum observed at 2935 cm�1 is assigned to CH stretching modeand is in good agreement. The asymmetric stretching of CH2 is ob-served as weak band in IR Spectrum as 2848 cm�1 and in DFTmethod it is observed at 2835 cm�1. The intensity enhancementand blue shifting of the methyl stretching wavenumbers are dueto the influence of electronic effect resulting from the hyperconju-gation and induction of methyl group in the aromatic ring [33].Hyperconjugation causes the interaction of the orbital of themethyl group with p orbital of an aromatic ring system. Hypercon-jugation occurs with the release of electronic charge from CAHbond to CAC bond in the phenyl ring and CAN bond in the pirazinering, which is evident from the shortening of bond length C2AC1-

and C25AN24 from its normal value [34].

Carbonyl group vibrationThe characteristic infrared absorption frequencies of carbonyl

group has been investigated earlier and the C@O stretching vibra-tion are expected in the region 1715–1680 cm�1 [35,36]. In Levo-floxacin, the C@O stretching vibration is calculated at 1685 cm�1

and is observed a strong band in IR spectrum at 1620 cm�1. ThecarbonAoxygen bond is formed by ppApp� between carbon and

Table 4Vibrational assignments of Levofloxacin.

Mode no. Experimental frequency FTIR (cm�1) Calculated Frequency using DFT/B3LYP/6-31 G(d,p) Vibrational assignments

Scaled Intensity (kcal/mol) Scaled Intensity (kcal/mol)

1 3421 44.89 3420 71.96 t(OH)2 2935 86.97 2934 2.85 tsym(CH)3 2917 7.08 tsym(CH)4 2848 87.87 2835 10.36 tasy(CH2)5 2826 35.79 tasy(CH2)6 2820 1.13 tasy(CH2)7 2804 2806 30.98 tasy(CH2)8 2785 19.39 tasy(CH)9 2783 29.93 tasy(CH)

10 2767 86.86 tasy(CH)11 2764 46.58 tsym(CH)12 2763 3.69 tsym(CH2)13 2759 11.31 tsym(CH3)14 2738 29.19 tsym(CH2ACH)15 2723 24.13 tsym(CH2ACH2)16 2706 50.67 tsym(CH2ACH)17 2692 92.56 2701 30.84 tsym(CH2)18 2637 107.95 tsym(CH) tsym(CH3)19 2633 25.47 t(CH) tsym(CH2ACH3)20 2631 31.07 t(CAH)21 1724 70.38 1723 366.67 tasy(R2) t(C@O) c(CAC) c(OAH) t(CAO)22 1685 299.28 t(R2) t(C@O) c(CAC) b(CAO) b(OAH)23 1620 33.09 1606 93.32 t(R1 R2 R3) t(C@C) t(C@O) c(OAH)24 1595 69.54 1593 149.57 t(R1 R2 R3) t(CAC) c(OAH)25 1541 67.41 1543 176.82 b(CAH) t(R1 R2) x(CH2)26 1473 52.47 1474 24.21 t(R1 R2 R3) f(CH2) b(CAH)27 1472 11.26 s(CH3) f(CH2)28 1471 7.77 s(CH3) f(CH2)29 1470 3.13 q(CH3) f(CH2)30 1463 31.97 s(CH3) f(CH2)31 1455 10.40 s(CH3) q(CH2)32 1454 15.54 s(CH3) qi(CH2)33 1454 61.83 1454 0.16 s(CH3) qi(CH2)34 1448 7.08 s(CH3) qo(CH2)35 1446 300.10 t(R1) x(CH2) s(CH3) t(CAF) c(CAH)36 1444 1.09 s(CH3) qi(CH2) b(OAH)37 1421 0.58 s(CH3) f(CH2)38 1396 55.21 1393 12.43 s(CH3) qi(CH2) b (OAH)39 1385 24.94 b(OAH) x(CH2) q(CH3)40 1382 8.8677 b(OAH) x(CH2) q(CH3)41 1380 131.12 das(R2) s(CH3) x(CH2) b(CO) t(CACAO) c(OAH)42 1369 47.30 x(CH2) s(CH3) t(CAF)43 1365 55.12 x(CH2) b(CAH)44 1354 8.08 das(R4) x(CH2)45 1342 71.48 1345 4.32 x(CH2) b(CAF) s(CH3) c(CAH) t(R1 R2)46 1336 103.49 c(CAH) s(CH2)47 1323 105.45 c(CAH) x(CH2) t(R1 R2)48 1320 0.50 x(CH2)49 1307 22.60 s(CH2) b(CAH)50 1292 71.78 1293 11.05 das(R1) s(CH2) c(CAH) c(CAF) b(OAH)51 1284 26.82 s(CH2) b(CAH)52 1282 66.65 x(CH2) c(CAH) b(CAF) ds(R1)53 1271 56.28 1278 36.06 q(CAH) b(CAN) s(CH3) ds(R4)54 1256 50.10 s(CH2) b(CAH) t(CAN) tas(R2)55 1237 18.03 b (OAH) s(CH2) c(CAH) d(R1 R2 R3 R4)56 1217 2.0905 b(CAN) q(CH2) s(CH3) d(R4)57 1208 1208 123.91 s(CH2) b(OAH) b(CAH) t(CAN) t(CAO) t(R1)58 1187 0.45 s(CH2) d(R4)59 1168 95.22 b(C@OACAOH) c(CAH) d(R1 R2 R3 R4)60 1134 81.67 1133 324.01 t(CAO) c(OAH) b(CAC) q0(CH3) b(C@O)61 1125 6.19 b (OAH) c(CAN) c(CAH)62 1119 15.69 b(CAN) s(CH2) q(CH3)63 1112 35.15 b(CAN) tas(R4) b(OAH) qi(CH3) s(CH2)64 1109 53.87 b(CAOAH) q(CH3) tsy(R3) t(CAO) c(CAH)65 1098 75.98 1102 49.95 c(OAH) qi(CH3) tasy(R3 R1 R2 R3)66 1080 95.56 d(R1 R2 R3) c(OAH b(CAH) q(CH3)67 1075 98.48 t(CAO) q(CH2) t(R3)68 1068 22.71 d(R1 R2 R3) b(CAH) s(CH2) q(CH3)69 1056 1.27 d(R4) b(CAH) s(CH2) q(CH3)70 1047 81.26 1044 7.31 d(R4) s(CH2) q(CH3)71 1031 4.51 d(R4) s(CH2)72 1004 5.91 c(CAH) d(R1 R2 R3)73 979 68.35 979 62.81 d(R4) c(CAH) t(CAN) x(CH2)

(continued on next page)

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Table 4 (continued)

Mode no. Experimental frequency FTIR (cm�1) Calculated Frequency using DFT/B3LYP/6-31 G(d,p) Vibrational assignments

Scaled Intensity (kcal/mol) Scaled Intensity (kcal/mol)

74 960 2.12 t(R2 R3) c(CAH) b(C@O) q(CH3) b(CAN)75 956 9.53 c(CAH) c(CAO) d(R1 R3) t(CAF) b(CAH) b(OAH)76 931 27.79 c(CAH) q(CH2)77 928 7.70 c(CAH)78 914 12.81 b(CAH) q(CH2) t(R3) t(CACAO)79 904 3.66 q(CH2) x(CH2) d(R4) b(CAN)80 873 87.64 870 13.98 d(R3) q(CH2) s(CH3)81 860 10.57 c(CAH)82 831 0.01 q(CH2)83 819 76.99 806 1.77 RING BREATHING84 802 79.14 801 16.19 d(R1 R2 R3) b(C@O) b(CACAOAH) x(CH2)85 772 40.18 t(R2) b(C@OAOAH) b(CAC)86 742 89.45 758 11.63 t(R4) q(CH2) c(CAH) t(CAN)87 724 22.23 t(R4) t(C@O) b(C@OAOAH) b(CAH)88 723 12.81 d(R4) q(CH2) b(C@OAOAH)89 698 3.01 t(R1) x(CH2)90 690 8.98 q(CH2) b(OAH)91 651 90.54 650 22.39 d(R1 R2 R3 R4) x(CH2) b(C@OAOH)92 638 16.99 b(C@O) b(CAC) d(R1 R2 R3) c(OAH) b(CAH)93 622 60.315 d(R1 R2) c(OAH) b(C@O)94 599 64.57 c(OAH)95 593 15.01 x(CH2) d(R2)96 559 91.29 549 4.53 d(R3) b(CAH) b(OAH) q(CH2)97 531 0.35 d(R1 R2 R3) x(CH2)98 534 9.16 d(R1 R2 R3) q(CH2) b(C@OAOAH)99 516 23.00 tsym(R3) b(CAO) q(CH2) t(CAF)

100 495 94.18 485 0.58 b(CANACACH3) x(CH2) d(R1 R2 R3)101 480 3.51 b(CAH) x(CH2) d(R4)102 459 94.10 478 4.15 x(CH2) d(R4)103 415 3.89 b(C@OAOH) b(CAF) d(R4)104 412 0.89 s(CH2) d(R4) c(CAN)105 403 0.29 d(R4) b(CANACH3) q(CH2)106 398 3.34 b(CANACH3) x(CH2)107 370 9.63 t(R1 R2 R3) c(CAF) b(CH3) d(CH2) b(CAN)108 360 1.75 c(C@O) b(CAF) b(CH3) d(CH2) b(CAN)109 344 1.95 b(CH3) d(CH2) b(CAN) b(CAF)110 343 9.67 q(CH2)111 334 1.11 q(CH2) b(C@O) x(CH3) c(CACOOH)112 316 0.41 b(C@O) b(CAF) q(CH2ACH2)113 287 4.22 d(CH2ACH2) q(CH2) b(C@O) b(CAF)114 262 0.31 d(CH2ACH2) b(CH3) b(CAF)115 260 0.25 d(CH2ACH2) q(CH3AN)116 258 2.54 x(CH2) qi(CH3) b(CAF)117 239 1.26 t(R1) q(CH3)118 222 0.41 q(CH3) s(CH2)119 219 0.47 x(CH2) s(CH3)120 216 4.78 s(CH3) q(CH2)121 185 2.06 t(R1) t(R4) t(R3)122 177 0.66 b(CAF) b(R1)123 150 0.21 qi(CH3) d(R4)124 146 3.24 d(R4)125 126 1.29 b(CAN CH2) b(CACACACH3)126 109 0.49 b(CAN CH2)127 63 1.61 s(CH3) q(CH2)128 51 0.81 b(CACACH3) b(CAF) d(R4)129 47 2.23 c(C@OAOAH)130 39 0.05 b(CAN CH3) b(CAOH) d(R4)131 23 0.00 b(CAN) b(C@OAOAH)132 19 0.20 d(R4)

Abbreviations: m – stretching; tsym – symmetric stretching; tasy – asymmetric stretching; b – in-plane bending; c – out-of-plane bending; ds – symmetrical deformation; das –asymmetrical deformation; f – scissoring; q – rocking; qi – in-plane rocking; qo – out-of-plane rocking; x – wagging; s – twisting.

360 S. Gunasekaran et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 112 (2013) 351–363

oxygen and the lone pair of electron on oxygen also determines thenature of carbonyl group. The higher degree of conjugation is dueto the maximum overlap of p-orbital, occurring because of the pla-narity of the group (ACH@C@(C@O)AC@CHA). The conjugation in-creases the single bond character of C@O bond [37] andconsequently lowers the wave number of the carbonyl absorption.The calculated values always overestimate the observed values dueto anharmonicity in the real system.

Methylpiperazin ring vibrationsAmong the CH3 and CH2 groups that are present in the mole-

cule, the spectral behavior of CH3 and CH2 groups in the Methylpi-perazin ring is different from the other CH3 and CH2 groups whichis due to the steric interaction with the phenyl and methylpipera-zin rings. The distinction is clearly understood from the downshif-ting of CH2 stretching wave number. The asymmetric CH2

stretching vibration of C4H(31,32) is observed at 2826 cm�1 in R3

S. Gunasekaran et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 112 (2013) 351–363 361

and the asymmetric CH2 stretching vibration of C27H(45,46) is ob-served at 2785 cm�1 in ring R4. The observed bands at 2848 cm�1

in IR spectrum is assigned to asymmetric CH2 stretching vibration.The symmetric CH2 stretching vibration of C4H(31,32) is observed at2723 cm�1 in R3 and the symmetric CH2 stretching vibration ofC27H(45,46) is observed at 2706 cm�1 in ring R4. The observed bandsat 2848 cm�1 in IR spectrum is assigned to asymmetric CH2

stretching vibration. The CH2 wagging is observed at 1320 cm�1

in DFT method and it is observed a band at 1316 cm�1 in FT-IRspectrum. The CH2 scissoring is observed at 1473 cm�1 in FT-IRspectrum and the calculated band for CH2 scissoring is at1474 cm�1. The CH2 rocking vibrations are observed at1278 cm�1 from DFT/B3LYP methods and 1271 cm�1 in FT-IR spec-trum. The twisting mode of CH3 vibrations are observed at 1278from DFT/B3LYP method and from FT-IR spectrum it was foundto be 1292 cm�1. The ring stretching vibrations m (Ring) are compli-cated combinations of stretching of CAN, C@C, and CAC bonds. Themost important ring stretching vibration is the ring breathingvibration at mode 83. In this mode, all bonds of the rings appearto stretch and contract in-phase with each other [20]. In the exper-imental infrared spectrum of Levofloxacin, this mode appears at819 cm�1.

CAH. . .O hydrogen bondingAlthough the CAH. . .O interactions are considered weak they

form 20–25% of the total number of hydrogen bonds constitutingthe second most important group. These interactions are shownto be important to elucidate the structural activity relationship inbiological systems. The CAH. . .O interactions has been identifiedfrom ab initio calculations in which the CAH donor group isstrengthened, shortened and blue shifted in the stretching vibra-tional wavenumber [34]. The intramolecular distance H. . .O dis-tances of H33AO13 and H35AO15 are found to be 2.32 and 2.45 Årespectively. These distances are shorter than the vander Waalsseparation between the O atom and H atom (2.72 Å) [34] whichindicate the existence of the CAH. . .O in Levofloxacin. The calcu-lated CAH. . .O angle is nearly equal to 85.7� for both interactionand is well within the angle limit, as the interaction path is not lin-ear and several CAH. . .O hydrogen bonding has a bend structure.The DFT calculation predicts the shortening of C14AH35 andC11AH33 bonds, while C@O is elongated as mentioned earlier.

NBO analysis

NBO analysis provides the most accurate possible ‘natural Lewisstructure’ picture of w, because all the orbital details are mathe-matically chosen to include the highest possible percentage ofthe electron density. A useful aspect of the NBO method is that itgives information about interactions in both filled and virtual orbi-tal spaces that could enhance the analysis of intra- and inter-molecular interactions. The second-order Fock matrix was carriedout to evaluate the donor–acceptor interactions in NBO analysis[36]. The interactions result is the loss of occupancy from the local-ized NBO of the idealized Lewis structure into an empty non-Lewisorbital. For each donor (i) and acceptor (j), the stabilization energyE(2) associated with the delocalization i ? j is estimated as:

Eð2Þ ¼ DEy ¼ qi

F2ðijÞ

ej � ei

where qi is the donor orbital occupancy. ej and ei are diagonal ele-ments and F(i, j) is the off diagonal NBO Fock matrix element. Someelectron donor orbital, acceptor orbital and the interacting stabiliza-tion energy resulting from the second-order micro-disturbance the-ory are reported [37,38]. The larger the E(2) value, the moreintensive is the interaction between electron donors and electron

acceptors, i.e., the more donating tendency from electron donorsto electron acceptors and the greater the extent of conjugation ofthe whole system. Delocalization of electron density between occu-pied Lewis-type (bond or lone pair) NBO orbitals and formally unoc-cupied (antibond or Rydgberg) non-Lewis NBO orbitals correspondto a stabilizing donor–acceptor interaction. NBO analysis has beenperformed on the molecule at the B3LYP/6-31G (d, p) level in orderto elucidate the intra-molecular, rehybridization and delocalizationof electron density within the molecule. The intramolecular interac-tion is formed by the orbital overlap between r(CC) and r⁄(CC)bond orbital which results intra-molecular charge transfer (ICT)causing stabilization of the system. These interactions are observedas increase in electron density (ED) in CAC antibonding orbital thatweakens the respective bonds.

In order to investigate the various second-order interactions be-tween the filled orbitals of one subsystem and vacant orbitals ofanother subsystem the DFT/B3LYP level has been used and it pre-dicts the delocalization or hyperconjugation [39].

The interaction between the oxygen lone-pair LP2O5 and theanti-bonding orbitals r⁄(C17AH35) and r⁄(C10AC14) has been cal-culated using NBO analysis and the results are tabulated in Table 5.The energetic contribution of (C17AH35) is found to be 0.52 kcal/mol and the hyperconjugative interaction is weak, these E(2)values are chemically significant and can be used as a measure ofthe intramolecular delocalization. The strengthening and contrac-tion of CAH bond is due to rehybridization [40] which revealsthe low value of electron density (�0.52503) in the r⁄(C17AH35)orbital. This indicates the presence of CAH. . .O hydrogen bondinginteraction in Levofloxacin.

The nature and strength of the intermolecular hydrogen bond-ing can be explained by studying the changes in electron densityin the vicinity of CAO bondings. The NBO analysis of Levofloxacinclearly explains the evidences of the formations of strong interac-tion between LP(O) and r⁄CAO anti-bonding orbitals. The stabil-ization energy E(2) associated with hyperconjugative interactionLPO12 ? r⁄C11AO13, LPO13 ? r⁄C25AO12 are calculated to be50.12 and 30.94 kJ mol�1 extend of intermolecular CAO bonding.The differences in E(2) energies are due to the fact that the accrualof the electron density in the CAO bond is not only drawn from theLP (O) but also from the whole molecule.

The intramolecular hyperconjugative interaction of therC7AC16 distribute to r⁄C6AC20 leading to enormous stabilizationof 20.64 kJ mol�1 which lead to strong delocalization. The mostinteraction energy related to the resonance in the molecule is elec-tron donated from LPN8 and LPN24 to the anti-bonding acceptorr⁄C7AC16 and r⁄C25AH42 leading to the stabilization energy of35.64 and 8.05 kJ mol�1 as shown in Table 6.

The NBO analysis also describes the bonding in terms of the nat-ural hybrid orbital r⁄O12AH34 which occupy a higher energy orbi-tal (1.98542 a.u.) with considerable p-character (79.02%) and lowoccupation number (�0.73459 a.u.) and the other group is r⁄C4-

AH31 which occupy a higher energy orbital (1.97944 a.u.) withconsiderable p-character (74.21%) and it has low occupation num-ber (�0.52632 a.u.). The lower energy orbitals occupy LPF19, LPO13

and LPO5 (�1.03262, �0.69397 and �0.53631 a.u.) with p charac-ter (30.77%, 41.19% and 60.89%) and high occupation number(1.98794 a.u., 1.97599 a.u. and 1.96176 a.u.). Thus, a very close topure p-type lone pair orbital participates in the electron donationto ? r⁄OAH and r⁄CAH orbitals for LPF19 ? C18AC20, LPO5 ? r⁄-

C4AH31 and LPO13 ? r⁄O12AH34 interaction in the compoundand are shown in Table 7.

Mulliken population analysis

The Mulliken population analysis in Levofloxacin was calcu-lated using DFT/B3LYP/6-31G (d, p) level. The charge distribution

Table 5Second-order perturbation theory analysis of Fock matrix in NBO basis corresponding to the intramolecular CAHAO hydrogen bonds of Levofloxacin.

Donor NBO(i) Acceptor NBO (j) E(2) (kcal/mol) E(j)-E(i) (a.u.) F(i,j) (a.u.) ED/Energy (a.u.)

LP2O15 r⁄(C10AC14) 20.30 0.72 0.110 1.97211–0.67688LP2O15 r⁄(C14AC16) 20.30 0.69 0.107 1.97372–0.65108LP2O15 r⁄(C17AH35) 0.52 0.72 0.018 1.97424–0.52503LP2O15 r⁄(C10AC14) 2.28 1.11 0.045 1.97211–0.67688LP2O15 r⁄(C14AC16) 2.08 1.15 0.045 1.97372–0.65108

Table 6Second order perturbation theory analysis of Fock Matrix in NBO Basis of Levofloxacin.

Donor (i) ED/e Acceptor (j) ED/e E(2)a (kJ mol�1) E(j) � E(i)b (a.u.) F(i,j)c (a.u)

rC9AH33 1.9756 r⁄C10AC14 0.0633 4.88 1.03 0.064rC22AH23 1.9821 r⁄C20AN21 0.0245 2.75 1.02 0.047rC22AH36 1.9802 r⁄N21AC27 0.0249 3.47 0.85 0.049rC7AC16 1.6447 r⁄C6AC20 0.3813 20.64 0.29 0.069LPO5 1.9617 r⁄C2AC4 0.0314 2.56 0.91 0.043LPN8 1.5586 r⁄C7AC16 0.4523 35.64 0.29 0.091LPO12 1.9762 r⁄C11AO13 0.0202 50.12 0.33 0.1180LPO13 1.8512 r⁄C25AO12 0.0896 30.94 0.63 0.1260LPN24 1.8821 r⁄C25AH42 0.0296 8.05 0.71 0.0690

a E(2) means energy of hyperconjugative interaction (stabilization energy).b Energy difference between donor and acceptor I and j NBO orbitals.c F(i, k) is the Fock matrix element between i and j NBO orbitals.

Table 7NBO showing the formation of Lewis and non-Lewis orbitals.

Bond (AAB) Energy/ED (a.u.) EDA (%) EDB (%) NBO s (%) p (%)

rC1AC2 1.98099 48.05 51.95 0.6932(sp2.69) 27.12 72.84�0.62786 0.7208(sp2.48) 28.69 71.27

rC2AC4 1.98173 51.55 48.45 0.7180(sp2.79) 26.37 73.57�0.63685 0.7208(sp2.46) 28.38 71.07

rC9AC10 1.97400 49.82 50.18 0.7058(sp1.57) 38.90 61.07�0.01248 0.7084(sp1.92) 34.27 65.69

rO12AH34 1.98542 76.34 23.66 0.8737(sp3.78) 20.91 79.02�0.73459 0.4864(sp1.00) 19.76 0.24

rC14AO15 1.99498 35.02 64.98 0.5912(sp2.21) 31.13 68.77�1.05032 0.8061(sp1.35) 42.44 57.25

rC4AH31 1.97944 63.08 36.92 0.7942(sp2.88) 25.74 74.21�0.52632 0.6076(sp0.00) 99.95 0.05

rC10AC14 1.977530 52.38 47.62 0.7237(sp1.92) 34.26 65.71�0.67538 0.6901(sp1.82) 35.49 64.46

LPO5 1.96176 – – sp1.55 39.14 60.81�0.53631

LPO13 1.97599 – – sp0.70 58.77 41.19�0.69397

LPN21 1.89092 – – sp7.74 11.44 88.52LPO15 1.97825 – – sp0.74 57.46 42.50

�0.67236LPF19 1.98794 – – sp0.44 69.23 30.77

�1.03262

Fig. 8. The Mulliken charge distribution of Levofloxacin.

362 S. Gunasekaran et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 112 (2013) 351–363

Table 8Theoretically computed energies (a.u.), zero-point vibrational energies (kcal mol�1),rotational constants (GHz), entropies (cal mol�1 K�1) and dipole moment (D).

Thermodynamic parameters HF/6-31 G(d,p)

DFT/B3LYP/6-31 G(d,p)

SCF energy (a.u.) �1255.5421 �1262.9585Total energy (thermal) Etotal (kcal mol�1) 263.751 247.066Vibrational energy, Evib (kcal mol�1) 261.973 245.289Zero point vibrational energy (kcal mol�1) 250.4962 232.9180Specific heat, Cv (cal mol�1 K�1) 81.715 88.002Entropy, S (cal mol�1 K�1) 154.355 160.482Rotational constants (GHz)

X 0.4654883 0.4583948Y 0.1080715 0.1062926Z 0.0910473 0.0895255

Dipole moment l (Debye)lx �2.5340 �2.5342ly 6.6775 6.3898lz �0.1189 �0.0799

Total 7.1431 6.8745

S. Gunasekaran et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 112 (2013) 351–363 363

of Levofloxacin in Fig. 8 shows, that the double bond carbon atomsand the carbon atoms attached to nitrogen atom are negative,whereas all the hydrogen atoms have positive charges. The oxygen(O13) atom has more negative charges and this result suggest thatthe atoms bonded oxygen atoms are electron acceptor, and also itindicates that the charge transfer from H to O. The relationship be-tween the CAH wavenumber and the calculated Mulliken atomiccharges of C17 (0.1995e) and F19 (�0.2861e) also take part in theintramolecular hydrogen bonds. The influence of electronic effectresulting from the hyperconjugation and induction of methylgroup in the ring R3 causes a large negative charged value in thecarbon atoms C1 (0.3427e) and also in the carbon atom C25

(�0.1453e).

Other molecular properties

Entropy of the title molecule is presented in Table 8. Scale fac-tors have been recommended [41] for an accurate prediction indetermining the zero-point vibration energies (ZPVEs), and the en-tropy (S). The variation in the ZPVE’s seemed to be insignificant.The total energies and the changes in the total energy of Levoflox-acin at room temperature at different methods are also presented.Dipole moment is a measure of the symmetry in the molecularcharge distribution and is given as a vector in the three dimen-sions. The values of dipole moments and energies for Levofloxacinmolecule were calculated. According to HF and B3LYP calculations,the largest dipole moment were observed for HF and increase inthe energy were observed for DFT.

Conclusion

In the present work, the calculated geometric parameters,vibrational wavenumber, frontier molecular orbitals, molecularelectrostatic potential contours and surfaces and the nonlinearproperties of Levofloxacin using DFT/B3LYP method were dis-cussed. Vibrational spectral analysis of Levofloxacin showed a bet-ter agreement with the experimental spectral data. The higherfrontier orbital gap of 6.02 eV indicates that Levofloxacin is a hardmolecule and has high kinetic stability. The molecular electrostaticpotential shows that the molecule has several possible sites forelectrophilic attack and the negative regions are associated withN8, O5, and O15. The intensity enhancement and blue shifting ofmethyl stretching wavenumber is explained by hyperconjugation.

Nonlinear Optical behavior of the examined molecule was investi-gated and molecule is highly polar. An NBO result reflects thecharge transfer mainly due to CAH and OAH groups of the mole-cule. HOMO–LUMO transitions predicted as a p ? p⁄ transition.

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