Accepted Manuscript Computation and interpretation of vibrational spectra on the structure of Losartan using ab initio and Density Functional methods B. Latha, S. Gunasekaran, S. Srinivasan, G.R. Ramkumaar PII: DOI: Reference:

S1386-1425(14)00788-4 http://dx.doi.org/10.1016/j.saa.2014.05.017 SAA 12179

To appear in:

Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy

Received Date: Revised Date: Accepted Date:

23 February 2014 4 May 2014 9 May 2014

Please cite this article as: B. Latha, S. Gunasekaran, S. Srinivasan, G.R. Ramkumaar, Computation and interpretation of vibrational spectra on the structure of Losartan using ab initio and Density Functional methods, Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy (2014), doi: http://dx.doi.org/10.1016/j.saa.2014.05.017

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Computation and interpretation of vibrational spectra on the structure of Losartan using ab initio and Density Functional methods B. Lathaa,e, S. Gunasekaranb, S. Srinivasanc, G.R.Ramkumaard* a

Department of Physics, Dr. M.G.R. Educational & Research Institute University, Chennai 600 095, India. b

Research and Development, St. Peter’s Institute of Higher Education and Research, St. Peter’s University, Avadi, Chennai – 600054, TN, India

c

PG and Research Department of Physics, Presidency College, Chennai 600005, TN, India

d

Department of Physics, C. Kandaswami Naidu College for Men in Anna Nagar East, Chennai 600102, TN, India e

Department of Physics, SCSVMV University, Enathur, Kanchipuram 631561, TN, India.

*Corresponding Author (email: [email protected]) Tel.: +91 9884351008

Abstract The solid phase FTIR and FT-Raman spectra of Losartan have been recorded in the region 400– 4000 cm-1. The spectra were interpreted in terms of fundamental modes, combination and overtone bands. The structure of the molecule was optimized and the structural characteristics were determined by Quantum chemical methods. The vibrational frequencies

yield good agreement

between observed and calculated values. The infrared and Raman spectra were also predicted from the calculated intensities. (1)H and (13)C NMR spectra were recorded and resonance chemical shifts of the molecule were calculated. UV-Visible spectrum of the compound was recorded in the region 200–600nm and the electronic properties HOMO and LUMO energies calculated by TD – HF approach. NBO atomic charges of the molecules and second order perturbation theory analysis of Fock matrix also calculated and interpreted. The geometrical parameters, energies, harmonic vibrational frequencies, IR intensities, Raman intensities, and absorption wavelengths were compared with experimental and theoretical data of the molecule.

Keywords Losartan, FT-IR, UV-Visible, hyperpolarizability, NBO 1. Introduction Vibrational spectroscopy has significant contribution towards the studies of structure and physio-chemical properties of molecular systems [1-3]. IR spectroscopy—among spectroscopic techniques that provided detailed information about molecular structure. This is the most appropriate tool to perform the vibrational assignment and to elucidate the structure and confirmation of the molecule. In the present study, Infrared, Raman and UV-Visible have been applied to obtain the maximum amount of informations from the spectra of the title compound. Losartan is an effective anti-hypertensive drug. Hypertension is one of the most important causes of premature death worldwide. The WHO identified hypertension as the leading cause of cardio vascular mortality and the momentum picks up every year the WHL is confident that almost all the estimated 1.5 billion people are affected by elevated blood pressure can be reached [4]. Different classes of anti-hypertensive drugs are used to control blood pressure. Losartan belongs to the class of Angiotensin II Receptor Blocker (ARB) and it is chemically known as 2-butyl-4chloro-1-({4-[2-(2H-1,2,3,4- tetrazol-5-yI) phenyl] phenyl} methyl)-1H-imidazol-5-yl) methanol. It is a white crystalline powder which is highly soluble in water. Its molecular formula is C22H23ClN6O whose molecular mass is 422.91g. Losartan is a selective competitive Angiotensin II Receptor Blocker type I (AT1) receptor antagonist, reducing the end organ responses to angiotensin II. Losartan administration results in decrease in total peripheral resistance (after load) and cardiac venous return (pre load). All of the physiological effects of angiotensin II, including stimulation of release of aldostrerone, are antagonized in the presence of Losartan. Losartan include the tetrazole group. Tetrazole are the classes of synthetic organic heterocyclic compounds, consisting of five-member ring of four nitrogen and carbon atom (plus hydrogen atom) [5]. 2.

Experimental Details The pure sample of Losartan was obtained from a reputed company in Pondicherry and used

as such for experimental purpose. The FTIR spectrum has been recorded in the region 4000–400 cm-1 in evacuation mode using KBr pellet technique with 4 cm-1 resolution on PERKIN ELMER

SYSTEM ONE FTIR/ATR spectrometer at SAIF, IIT Madras, India. FT-Raman has been recorded in the region of 4000–400 cm-1 using BRUKER RFS 66V spectrophotometer at SAIF, IIT Madras, India. UV-Visible spectrum has been recorded in the region 200–600 nm using JASCO V-650 at Department of Chemistry, IIT Madras, India. (1)H and (13)C NMR spectra have been recorded using BRUKER AVANCE III 500 MHZ NMR at SAIF, IIT Madras, India. 3. Computational method In the present work, quantum chemical methods like Hartree-Fock (HF) and Density Functional B3LYP method with the 6-31G(d,p) basis set are employed to study the complete vibrational spectra of the title compound and to identify the various normal modes with greater accuracy. Literature survey reveals that to the best of knowledge, no DFT/HF method calculations of Losartan have been reported so far. Hence the present investigation was undertaken to study the vibrational spectra of this molecule completely. These calculations have been performed to support our wave number assignments. The vibrational wave numbers have been calculated to improve the simulation of the theoretical spectra. The calculations are performed by Gauss view molecular visualization program and the Gaussian 03W program package on the personal computer. The optimized molecular structures, vibrational frequencies, thermodynamic properties, NBO analysis, hyperpolarizability, UV-Visible and NMR spectra of the entitled compound were performed using the Gaussian 03W package program which is the modern computational chemistry software packages with gauss view molecular visualization program on the PC at B3LYP / 6-31G (d,p) level [6,7]. 4

Prediction of Raman intensities The Raman activities (SRa) calculated with Gaussian 03W program converted to relative

Raman intensities (IRa) using RAINT program [8] by the expression: 1
 =   −    

 where  is the laser exciting [9] wavenumber in cm−1 (in this work, we have used the excitation wavenumber  = 9398.5 cm−1, which corresponds to the wavelength of 1064 nm of a Nd:YAG

laser),  the vibrational wavenumber of the ith normal mode (cm−1), while  is the Raman scattering activity of the normal mode  . f (is a constant equal to 10−12) is a suitably chosen common normalization factor for all peak intensities.

5. Results and discussions In this study, we have tried to determine the molecular geometry, vibrational frequencies, (including IR, Raman and Electronic spectra)

13

C and 1H chemical shifts, thermodynamic

properties, NBO analysis, hyperpolarizability, second order perturbation for the characterization of entitled compound. 5.1 Molecular geometry It is the 3 dimensional arrangement of the atoms that constitute a molecule. It can be specified in terms of bond length and bond angles whereas bond length is the average distance between the centers of two atoms bonded together in any given molecule and bond angle is formed between three atoms across at least two bonds. Molecular geometry is determined by the quantum mechanical behavior of the electrons. Using the valence bond approximation this can be understood by the type of bonds between the atoms that make up the molecule. The geometry can also be understood by molecular orbital theory where the electrons are delocalized. As a whole, molecular geometry is equal to general shape of molecule as determined by the relative positions of the atomic nuclei. The shape of a molecule plays a role in determining its properties such as smell, taste and proper targeting of drugs. Apart from that, it gives properties of substance like polarity, colour, reactivity, phase of matter and biological activity. The atomic numbering scheme of the compound is given in Fig. 1 and optimized geometrical parameters are presented in Table 1. The bond lengths are compared with the literature values [10]. From the structural data given in the Table 1, it is observed that the various bond length, bond angles are found to be almost same at HF and DFT methods. It can be inferred that the bond to be stronger, the overlap should be greater, which in turn would shorten the distance between the nuclei (i.e.,) bond length. Therefore a stronger bond has shorter bond length [11]. For Losartan, the strongest bonds are formed between O2-H33 = 0.9553A° (DFT method)

and 0.9571A°(HF method) which have very small bond distance value compared to others. The next strongest bond is formed between N21-H44 = 0.993 (DFT method) and 0.992 (HF method). Weakest bond is formed between C5-Cl26 = 1.7245A° (DFT method) and that of 1.7244A° (HF method), which have high bond distance value. The C-X (X:Cl, Br) bond length indicates a considerable increase when substituted in the place of C-H, in other words, bond length increases from C-Cl to C-Br. For C-Cl, the bond length is 1.719A°. The calculated value of C-Cl is in good agreement with standard value (Table 1). The C-C bond length of benzene ring (R2) are observed in the range from 1.3821A°-1.4011A° by DFT method and from 1.3820A°-1.4011A° by HF method. Likewise, in ring (R1) the C-C bond length varies from 1.3331A°-1.5007A° by DFT method and from 1.3323A°-1.5012A° by HF method which are in good agreement with standard values. The other deviations are due to intermolecular interactions in the crystalline state of the molecule. The bond angles obtained by both methods (DFT, HF) correlate well with the standard values. There are some variations in bond angle which depends on the electronegativity of the central atom, the presence of lone pair of electrons and the conjugation of double bonds. If the electronegativity of the central atom decreases, the bond angle also decreases. Furthermore, the other deviations are due to the theoretical calculations belong to isolated molecules in gaseous phase and experimental results belong to molecules in solid state. In spite of the differences, the calculated geometries represent a good approximation and they are the bases for calculating vibrational frequencies and thermodynamical properties. 5.2 Vibrational analysis The compound chosen has 53 atoms and it belongs to C1 point group symmetry having only identity operation symmetry element. It is known that a molecule containing N number of atoms provide 3N internal modes due to three Cartesian displacements. 6 – mode of them is for translation and rotational modes [12,13]. Hence, 153(3N-6) vibrational modes are observed in the molecule. In this part, the spectroscopic signature of the entitled compound was interpreted by means of frequency calculation analysis. Table 2 presents the detailed vibrational assignments of fundamental modes along with the calculated IR intensities. For visual comparison, the observed

and calculated (simulated) FTIR and FT- Raman spectra of the title compound were presented in Figs. 2 and 3 which help to understand the observed spectral features. O-H vibrations Generally, the hydroxyl group of alcohols absorb strongly in the region 3670 – 3580 cm-1. The frequency of O-H stretching band depends on concentration, nature of solvent and temperature because these factors affect the hydrogen bonding which affect the absorption frequency [14]. The stretching vibration of O-H group in the title compound was obtained at 3206 cm-1 (DFT method) and 3372 cm-1 (HF method). The highest IR intensity is observed at 1235 at 3206 cm-1 (DFT method). This can be due to the fact that the intensity of an absorption in the IR spectrum depends on the change in dipole moment that occurs during the vibration. Consequently, the vibrations that produce a large change in dipole (O-H), result in a more intense absorption [15]. N-H vibrations The N-H stretching vibrations occur in the region 3500 cm-1- 3400 cm-1 [16]. Usually frequency of this vibration is decreased in the presence of hydrogen bond. In the present work, for the compound bands observed at 3743 cm-1 (FTIR), 3663 cm-1 (DFT method) and 3927 cm-1 (HF method) have been assigned to N-H vibrations. This absorption is absent in Raman spectrum. The bands are deviated trivially from the expected range. This is because, the position of absorption in this region depends upon the degree of hydrogen bonding and physical state of the sample. C-H vibrations The aromatic structure shows the presence of C-H stretching vibration in the region 3250 cm-1 – 2950 cm-1 which is the characteristic region for the ready identification of C-H vibrations [17]. In the present work, FTIR bands observed at 2930 cm-1, 2869 cm-1 and bands observed at 2934 cm-1, 2871 cm-1 (FT-Raman) have been assigned to C-H stretching vibrations. In general aromatic C-H stretching vibrations are in good agreement with the experimentally reported values. C-Cl vibrations

The C-Cl stretching vibrations give generally strong bands in the region 760–505

cm-1 .

In the present work, bands observed at 501 cm-1(FTIR), 505 cm-1(DFT method) 553 cm-1(HF method) are assigned to C-Cl stretching vibrations. This absorption is absent in Raman spectrum. The compound entitled has a chlorine substitution. The heavier mass of chlorine obviously makes C-Cl stretching mode to appear in longer wavelength region. This assignment is well within the expected range suggested by Varsanyi [18]. Methylene group vibrations The stretching vibrations of methylene group (CH2) usually occur in the region near 2926 cm-1. The frequency of methylene stretching is increased when the methylene group is part of a strained ring [19]. For the title compound, it was observed at 3064 cm-1(FTIR) and in FT- Raman spectrum it was observed at 3061 cm-1 and 2990 cm-1.The bending vibrations of the C-H bonds in the methylene group are expressed as scissoring, rocking, wagging and twisting. The scissoring band (CH2) in the spectra of hydrocarbons occurs in the region near 1465 cm-1 [20]. For the title compound, the bands identified at 1531 cm-1, 1496 cm-1, 1443 cm-1 in FTIR and those at 1522 cm1

, 1499 cm-1 in FT-Raman have been assigned to CH2 bending (scissoring). Absorption of hydrocarbons because of methylene twisting and wagging vibrations, is

observed in 1350 cm-1- 1150 cm-1 region. These bands are generally appreciably weaker than those resulting from methylene scissoring. In this case, the bands are identified at 1310 cm-1, 1301 cm-1 in IR and similar vibration is identified at 1296 cm-1 in Raman spectrum. The calculated wave numbers by DFT method approximately coincide with the experimental results. 5.3 Thermodynamic parameters The thermodynamical parameters like rotational constants, dipole moments, rotational temperature, specific heat capacity at constant volume and Entropy were performed using DFT, HF methods and presented in the Table 3. The parametric value correlates well when compared with both methods. The highest value (ZPVCE) zero Point Vibrational Energy of Losartan is 285.47 kcal./mol obtained at HF method and whereas the lowest value is 265.04 kcal./mol obtained at DFT method. The dipole moment of the molecule was also calculated by DFT and HF methods. Dipole moment

of the molecule reflects the molecular charge distribution. Dipole moments are strictly determined for neutral molecules.

For charged systems, its value depends on the choice of origin and

molecular orientation. As a result of our calculations, the highest dipole moments were obtained for DFT method whereas the smallest one was observed for HF method in Losartan.

5.4 UV- Visible Spectral analysis Electronic transitions are classified according to the orbitals engaged. The common types of transitions in organic compounds are π → π*, n → π*. In order to explain the electronic transitions of Losartan, theoretical calculations on electronic absorption spectrum capable of describing the special features of the molecule were performed by Gaussian03W using B3LYP/631G(d,p) level. The experimental UV-Visible spectrum of entitled compound was given in Fig. 4. The calculated excitation energies, singlet A, oscillator strength and λmax are reported in the Table 4. As seen from the table, only one absorption maxima λmax has been obtained from experimental part where as three λmax from theoretical part. The band observed at 226 nm is due to π → π* transition those at 297 nm is due to n → π* and 510 nm due to π → π*. 5.5 HOMO and LUMO analyses Highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) are very important parameters for quantum chemistry. We can determine the way the molecule interacts with other species; hence, they are called the frontier orbitals. HOMO, which can be thought the outermost orbital containing electrons, tends to give these electrons such as an electron donor. On the other hand; LUMO can be thought the innermost orbital containing free places to accept electrons [21]. Owing to the interaction between HOMO and LUMO orbital of a structure, transition state transition of π → π* type is observed with regard to the molecular orbital theory [22, 23]. Therefore, while the energy of the HOMO is directly related to the ionization potential, LUMO energy is directly related to the electron affinity. Energy difference between HOMO and LUMO orbital is called as energy gap that is an important stability for structures [24].

3D plots of highest occupied molecular orbitals (HOMO) and lowest unoccupied molecular orbitals (LUMO) with the energy values presented in the Fig. 5. According to TD-HF/6-31G (d,p) level of theory, the energy band gap |(E)| (value of the energy separation between HOMO and LUMO) of the titled molecule is 0.3244 a.u at TD-HF/631G(d,p) level. For Losartan, the HOMO lying at -0.2432 a.u is localized at the ring Ring1, whereas the rings Ring2, Ring3 and Ring4 are delocalized (π orbital). The LUMO lying at 0.0812 a.u is delocalized π* orbital at the ring Ring1 whereas Ring2 is partially localized. The Ring3 and Ring4 are completely localized. 5.6 Hyperpolarizability calculation NLO is at the future of current research because it provides the key functions of frequency shifting, optical modulation, optical switching, optical logic, and optical memory for the emerging technologies in areas such as telecommunications, signal processing, and optical interconnections [25, 26]. In discussing NLO properties, the polarization of the molecule by an external radiation field is often approximated as the creation of an induced dipole moment by an external electric field, and this change can be calculated as =  0 +  + 12 :  + ⋯ … … …  0 → dipole moment in the absence of an electric field  → second rank tensor called the polarizability tensor  → first in an infinite series of dipole hyperpolarizabilities The first hyperpolarizability ( ) of this molecular system is calculated using B3LYP/6-31G (d,p) method. The complete equations for calculating the magnitude of the mean first polarizability  , using the x, y, z components from Gaussian 03W outputs are as follows /

 =   + ! + " #

 =  + !! + ""  = !!! + ! + !""  = """ + " + !!"

The calculated hyperpolarizability values of Losartan are given in Table 5. Urea is one of the most important prototypical molecules used in the study of the NLO properties of the molecular systems and frequently used is a threshold value for comparative purposes. The computed first hyperpolarizability of Losartan molecule is 32.67 x 10-31 esu in B3LYP method which is ten times more than urea [27]. Thus we conclude that the title compound is like a honey pot for future studies of Non Linear Optical properties. 5.7 NBO analysis Natural bond orbital (NBO) analysis provides an efficient method for studying intra and intermolecular bonding and interaction among bonds, and also provides a convenient basis for investigating charge transfer or conjugative interaction in molecular systems [28]. NBO theory also allows the assignment of the hybridization of atomic lone pairs and of the atoms involved in bond orbitals. Some electron donor orbital, acceptor orbital and the interacting stabilization energy resulted from the second-order micro-disturbance theory are reported [29,30]. The second-order Fock matrix was carried out to evaluate the donor–acceptor interactions in NBO analysis [31]. The result of interactions is the loss of occupancy from the localized NBO of the idealized Lewis structure into an empty non-Lewis orbital. For each donor (i) and acceptor (j), the stabilization energy E(2) associated with the delocalization i→j is estimated as  = ∆& = ' ()* )/ (+& − +& Where, qi is the donor orbital occupancy, ej and ei are the diagonal elements and F(ij) is the off diagonal NBO Fock matrix element. The second order perturbation theory analysis of Fock matrix in NBO shows strong intra molecular hyperconjugative interactions, which are presented in Table 6. The larger the E(2) value, the more intensive is the interaction between electron donors and electron acceptors, i.e. the more donating tendency from electron donors to electron acceptors and the greater the extent of conjugation of the whole system [32]. Delocalization of electron density between occupied Lewis-type (bond or lone pair) NBO orbitals and formally unoccupied (antibond or Rydberg) non-Lewis NBO orbitals correspond to a stabilizing donor–acceptor interaction. NBO analysis has been performed on the title molecule at the B3LYP/6-31G(d,p) level in order to elucidate the delocalization of electron density within the molecule. The string

intra molecular hyper conjugative interaction of the S and P electrons of C-C bond of the ring leads to the stabilization of some part of the ring as evident from Table 6. The intramolecular hyper conjugative interactions of σ(C1–H31) to σ*(C6-N7) leads to stabilization of 7.1 kcal./mol. The interactions of π(N24–C25) to π*(N22-N23) leads to stabilization of 24.66 kcal./mol. The π(C3 –N4) bond interacts with π*(C5-C6) with the energy of 22.04 kcal./mol, whereas the same interacts with σ*(C27-H45) with the energy of 2.15 kcal./mol. The maximum energy transfer from LP(1) N21 to anti-bonding N24-C25 is 50.63 kcal./mol. The interaction between LP(1) C13 and σ*(O2-H33) resulting in the stabilization of 37.64 kcal./mol. From the NBO analysis, the interaction LP(1) N21→N24-C25 observed in Losartan shows a large amount of Stabilization energy about 50.63 kcal./mol. 5.8 Atomic charges The atomic charges of titled compound is calculated by NBO method at the B3LYP/631G(d,p) level of theory are given in the Table 7. As seen from the table, the magnitudes of nitrogen atomic charges found to be negative were noted to change from

-0.503 to -0.051.

The charge magnitude of N4 was found to be more negative than the other nitrogen atoms. The magnitudes of hydrogen atomic charges found to be positive and the values ranging from 0.186 to 0.480. The charge magnitude of H33 was found to be more positive which is connected to electronegative oxygen atom, whereas minimum charge was obtained for H32.The magnitude of chlorine atomic charge was obtained as positive value. This is due to the presence of carbon atom. The chlorine atom attracts positive charge from carbon atoms. The atomic charge magnitude for the oxygen atom was obtained to be negative. The charge magnitude of carbon atom varies from -0.683 to 0.406. The atomic charge of C30 atom is found to be more negative than other carbon atoms due to the presence of electron accepting substitution at that position in Losartan. The result suggests that almost all the hydrogen atoms are electron acceptors. Thus computations of atomic charges support the results of molecular interactions. 5.9 NMR spectra analysis

In this study, 13C and 1H NMR chemical shifts of Losartan were calculated and depicted in Table 8. These calculations obtained at B3LYP/6-31G(d,p) levels for the optimized geometry were observed to be in good agreement with experimental results. The 1H isotropic chemical shift values were observed from 0.43 to 7.6 parts per million (ppm) while these values were calculated from 2.50 to 12.42 ppm. As seen from table, all computations are in good agreement with experimental data. The proton (H38), observed to be about 7.6 ppm was found to be 7.62 ppm at B3LYP/631G(d,p) calculation level of theory. In addition, 13C isotropic chemical shifts with regard to TMS calculated at the same basis set is given in the same table. 13C chemical shift values were obtained from 31.31 to 259.39 ppm where as these values were experimentally observed from 28.80 to 161.84 ppm. The chemical shift of C6 connected with nitrogen N7 was observed to be 130.74 ppm where as it was noted to be 130.06 ppm at B3LYP/6-31G(d,p) level of theory. The carbon atom C13 appearing at very higher chemical shift value (259.3 ppm) than the other carbon atoms and hence the shielding is very small (Table 8). The more electron rich atoms are C1, C27, C28, C29, C30. These are highly shielded atoms and hence appear at downfield (lower chemical Shift). The carbon atom C13 in the benzene is deshielded than other carbon atoms so that they have higher chemical shift values. For visual comparison, the observed and calculated

13

C and 1H NMR

spectra of the titled compound were presented in Figs. 6 and 7. Apart from that deviations are due to the theoretical calculations belong to isolated molecules in gaseous phase and experimental results belong to molecules in solid state. 6

Conclusion

The molecular geometry of Losartan was optimized by both DFT-B3LYP and HF methods using 6-31G(d,p) as basis set. B3LYP methods treat the electronic energy as a function of the electron density of all electrons simultaneously and thus includes electron correlation effect. The complete molecular structural parameters and thermodynamic properties of the compound have been obtained. The vibrational frequencies are compared both experimentally as well as theoretically. The energies of MOs, absorption wavelength (λmax), oscillator strength excitation energies of the compound were determined and compared with experimental values. This study also predicted the 13

C and 1H NMR chemical shifts using B3LYP/6-31G (d, P) level.

The dipole moment,

polarizability and the hyperpolarizability of the compound studied that have been calculated by B3LYP method with 6-31G(d,p) basis set. Homo–Lumo energy explains the eventual charge transfer interactions taking place within the molecule. NBO population analysis is suitable for the estimation of atomic charges.

Thus, the present investigation provides complete vibrational

assignments, structural informations and electronic properties of the title compound which may be useful to upgrade the knowledge on Losartan.

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[30]

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[31]

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[32]

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Fig. 1. Atomic numbering scheme of Losartan

Fig. 2. Experimental and Theoretical FTIR spectra of Losartan

Fig. 3. Experimental and Theoretical FT-Raman spectra of Losartan

Fig. 4. Experimental UV-Visible Spectrum of Losartan

Fig. 5. 3D plots of Homo and Lumo of Losartan

Fig. 6. Experimental and Theoretical spectra of carbon NMR.

Fig. 7. Experimental and Theoretical spectra of hydrogen NMR.

Table 1 Literature values and theoretical optimized geometric parameters of Losartan by DFT-B3LYP/6-31G(d,p) and HF/6-31G(d,p) methods Bond Literature

B3LYP/6-

HF/6-

Values

31G(d,p)

31G(d,p)

C1-C6

1.50

1.50

1.50

C1-H31

1.11

1.08

1.08

C1-H32

1.11

1.09

1.09

O2-H33

0.94

0.96

0.96

C1-O2

1.40

1.39

1.39

C3-N4

1.37

1.29

1.29

C3-N7

1.31

1.36

1.36

C3-C27

1.50

1.50

1.50

N4-C5

1.37

1.36

1.36

C5-C6

1.37

1.35

1.35

C5-Cl26

1.72

1.72

1.72

length (A˚ )

C6-N7

1.37

1.39

1.39

N7-C8

1.47

1.45

1.45

C8-C12

1.50

1.52

1.52

C8-H35

1.11

1.08

1.08

C8-H36

1.10

1.08

1.08

C9-C10

1.39

1.33

1.33

C9-C14

1.39

1.50

1.50

C9-C15

1.34

1.49

1.50

C10-C11

1.39

1.45

1.44

C10-H37

1.10

1.07

1.07

C11-C12

1.39

1.36

1.36

C11-H38

1.10

1.08

1.08

C12-C13

1.39

1.43

1.43

C13-C14

1.39

1.48

1.49

C14-H34

1.10

1.10

1.11

C14-H39

1.10

1.09

1.09

C15-C16

1.39

1.40

1.40

C15-C20

1.39

1.39

1.39

C16-C17

1.39

1.39

1.39

C16-C25

1.34

1.48

1.48

C17-C18

1.39

1.38

1.38

C17-H40

1.10

1.08

1.08

C18-C19

1.39

1.38

1.38

C18-H41

1.10

1.07

1.07

C19-C20

1.39

1.38

1.38

C19-H42

1.10

1.08

1.07

C20-H43

1.10

1.07

1.07

N21-N22

1.38

1.33

1.33

N21-C25

1.31

1.34

1.34

N21-H44

1.05

0.99

0.99

N22-N23

1.33

1.25

1.25

N23-N24

1.34

1.34

1.34

N24-C25

1.36

1.30

1.30

C27-C28

1.52

1.53

1.53

C27-H45

1.11

1.09

1.09

C27-H46

1.11

1.09

1.09

C28-C29

1.52

1.53

1.53

C28-H47

1.11

1.09

1.09

C28-H48

1.11

1.08

1.08

C29-C30

1.52

1.53

1.53

C29-H49

1.11

1.09

1.09

C29-H50

1.11

1.09

1.09

C30-H51

1.11

1.09

1.09

C30-H52

1.11

1.09

1.09

C30-H53

1.11

1.09

1.09

114.58

113.91

Bond angle (degree ) O2-C1-C6

109.50

O2-C1-H31

114.84

107.15

107.85

O2-C1-H32

114.84

111.19

111.19

C6-C1-H31

109.44

107.40

107.48

C6-C1-H32

109.46

109.51

109.55

H31-C1-H32

109.52

106.61

106.51

C1-O2-H33

114.00

109.76

110.71

N4-C3-N7

111.48

111.84

111.84

N4-C3-C27

124.26

124.67

124.57

N7-C3-C27

124.26

123.49

123.58

C3-N4-C5

107.48

105.15

105.17

N4-C5-C6

105.02

112.42

112.37

N4-C5-Cl26

127.49

120.61

120.59

C6-C5-Cl26

127.49

126.97

127.03

C1-C6-C5

124.64

130.86

131.00

C1-C6-N7

124.64

125.46

125.20

C5-C6-N7

110.72

103.66

103.78

C3-N7-C6

105.31

106.93

106.84

C3-N7-C8

127.35

126.16

126.12

C6-N7-C8

127.35

126.90

127.04

N7-C8-C12

109.50

113.95

114.85

N7-C8-H35

109.46

107.49

107.53

N7-C8-H36

108.40

108.42

108.01

C12-C8-H35

109.46

109.30

109.17

C12-C8-H36

109.41

110.62

110.31

H35-C8-H36

109.00

106.78

106.63

C10-C9-C14

120.00

118.83

119.19

C10-C9-C15

120.00

121.70

121.75

C14-C9-C15

120.00

119.39

119.00

C9-C10-C11

120.00

119.75

119.53

C9-C10-H37

120.00

121.58

121.64

C11-C10-H37

120.00

118.64

118.82

C10-C11-C12

120.00

123.97

123.94

C10-C11-H38

120.00

116.49

116.41

C12-C11-H38

120.00

119.54

119.63

C8-C12-C11

120.00

121.00

119.86

C8-C12-C13

120.00

117.94

118.89

C11-C12-C13

120.00

120.92

121.23

C12-C13-C14

120.00

115.33

115.42

C9-C14-C13

120.00

120.54

120.33

C9-C14-H34

109.41

108.62

106.88

C9-C14-H39

120.00

110.91

111.50

C13-C14-H34

109.41

101.35

101.89

C13-C14-H39

120.00

110.07

110.51

H34-C14-H39

109.00

103.60

103.91

C9-C15-C16

120.00

123.92

124.10

C9-C15-C20

120.00

117.74

117.48

C16-C15-C20

120.00

118.31

118.39

C15-C16-C17

120.00

119.74

119.60

C15-C16-C25

120.00

122.15

122.25

C17-C16-C25

120.00

118.08

118.12

C16-C17-C18

120.00

121.14

121.22

C16-C17-H40

120.00

119.60

119.68

C18-C17-H40

120.00

119.23

119.07

C17-C18-C19

120.00

119.37

119.37

C17-C18-H41

120.00

120.01

119.99

C19-C18-H41

120.00

120.62

120.63

C18-C19-C20

120.00

119.92

119.87

C18-C19-H42

120.00

120.33

120.36

C20-C19-H42

120.00

119.75

119.77

C15-C20-C19

120.00

121.52

121.54

C15-C20-H43

120.00

118.82

118.81

C19-C20-H43

120.00

119.66

119.65

N22-N21-C25

105.76

108.49

108.44

N22-N21-H44

127.12

120.67

120.59

C25-N21-H44

127.12

130.73

130.87

N21-N22-N23

110.96

106.64

106.72

N22-N23-N24

105.02

111.32

111.26

N23-N24-C25

109.84

106.38

106.43

C16-C25-N21

125.79

124.81

124.84

C16-C25-N24

125.79

128.00

127.99

N21-C25-N24

108.42

107.17

107.15

C3-C27-C28

109.50

113.04

112.88

C3-C27-H45

109.44

109.04

109.21

C3-C27-H46

109.46

109.20

109.17

C28-C27-H45

109.44

109.53

109.33

C28-C27-H46

109.46

109.43

109.52

H45-C27-H46

109.52

106.38

106.53

C27-C28-C29

109.50

112.20

112.25

C27-C28-H47

109.44

109.23

109.24

C27-C28-H48

109.46

109.09

109.04

C29-C28-H47

109.44

110.01

109.99

C29-C28-H48

109.46

109.97

110.01

H47-C28-H48

109.52

106.14

106.11

C28-C29-C30

109.50

112.67

112.69

C28-C29-H49

109.44

109.54

109.57

C28-C29-H50

109.46

109.61

109.58

C30-C29-H49

109.44

109.24

109.22

C30-C29-H50

109.46

109.25

109.25

H49-C29-H50

109.52

106.33

106.33

C29-C30-H51

109.50

111.24

111.26

C29-C30-H52

109.44

111.11

111.10

C29-C30-H53

109.46

111.05

111.05

H51-C30-H52

109.44

107.81

107.80

H51-C30-H53

109.46

107.81

107.82

H52-C30-H53

109.52

107.67

107.66

Table 2 Comparison of the Experimental (FT-IR and FT-Raman) wave numbers (cm-1) and Computed wave numbers (cm-1) of Losartan Experimental Wavenumber FTIR FT-Raman

Computed Wavenumber B3LYP/6-31G(d,p)

Vibrational Assignment

3927

IR Intensity 16.7 NH stretching

0.6

3913

100.0

CH3 stretching

3209

0.8

3383

2.2

CH2 stretching

-

3206

100.0

3372

1.7

OH stretching

-

-

3201

7.4

3370

1.6

CH stretching

-

-

3197

0.9

3359

0.6

CH3 stretching

-

-

3189

0.6

3350

0.5

CH2 stretching

-

-

3147

2.1

3322

3.7

CH stretching

-

-

3116

0.5

3289

1.4

CH2 stretching

-

-

3112

4.9

3278

4.9

CH2 stretching

-

-

3112

3.5

3260

10.1

CH2 stretching

-

-

3101

0.5

3245

5.8

CH3 stretching

-

-

3090

8.3

3243

4.2

CH stretching

-

-

3082

1.1

3237

4.4

CH stretching

3743

-

3663

3224

-

3219

-

-

-

IR Intensity 7.4

HF/6-31G(d,p)

3064

3061

3068

2.1

3213

3.1

CH2 stretching

-

-

3061

1.7

3208

0.6

CH2 stretching

-

-

3043

1.6

3202

2.5

CH2 stretching

-

-

3040

2.6

3188

2.2

CH3 stretching

-

-

3021

-

-

3014

2.7

3166

7.5

CH2 stretching

-

2990

2995

1.5

3158

0.7

CH2 stretching

2930

2934

2922

8.9

3148

9.7

CH stretching

2869

2871

2863

6.2

3130

0.5

CH stretching

-

2832

1652

0.7

1840

5.9

C=C stretching + CCC bending

1643

-

1643

1.9

1812

4.1

C=C stretching

1604

1611

1617

0.8

1780

7.7

C=C stretching

-

-

1598

3.6

1773

5.2

C=C stretching

1574

1573

1586

2.4

1766

0.7

NC stretching + C=C stretching

1564

-

1562

2.8

1715

14.7

C-C stretching

-

-

1544

1.0

1710

7.7

C-C stretching

-

-

1540

5.2

1662

8.7

C-C stretching

2.0

3178

4.3

CH2 stretching

1531

-

1526

0.2

1654

0.5

CH2 bending

-

1522

1521

3.6

1640

0.5

CC stretching +HCC bending

-

-

1515

0.7

1633

5.3

CH2 bending

-

-

1514

0.4

1627

0.6

HCH bending + HCCC torsion

-

-

1512

-

-

1500

0.1

1618

0.2

HCH bending

1496

1499

1496

0.7

1618

1.6

HCH bending

-

-

1487

0.8

1613

0.5

HCH bending

1472

-

1479

1.0

1611

10.2

HCC bending

1461

1460

1455

7.0

1598

9.5

NC stretching+ HCCN torsion

1443

-

1428

0.0

1591

4.3

HCH bending

1428

1428

1422

6.9

1573

0.7

CCN bending + HCCC torsion

-

-

1412

0.6

1553

0.6

HCCC torsion

1409

-

1410

1.1

1544

0.5

NC stretching + (HNN + NNC) bending

-

-

1404

7.4

1539

6.1

HCCN torsion

-

-

1393

0.4

1531

18.6

HCCN torsion

-

1381

1381

0.2

1511

0.2

(NN + CC) stretching + HNN bending

0.0

1624

0.7

HCH bending

1378

-

1376

0.2

1509

0.9

HCC bending

-

-

1374

0.3

1488

2.3

CC stretching + HCC bending

1361

-

1360

1.1

1481

6.6

HCCC Torsion

-

-

1348

2.1

1473

3.4

HCH bending + HCCC torsion

-

-

1334

1324

1325

1327

1.7

1446

0.1

CC stretching

-

-

1320

0.1

1443

0.5

HCC bending

1310

-

1309

0.1

1432

0.1

HCH bending

1301

1296

1300

0.7

1414

0.4

(HCC + HCH) bending

-

-

1290

4.5

1400

2.2

NC stretching + HCCC Torsion

-

-

1277

9.1

1391

24.3

NC stretching + NCN bending

-

-

1273

0.2

1374

1.1

(NN + CC) stretching + HCC bending

-

-

1271

1.6

1372

2.1

NN stretching + HNN bending

1260

1262

1270

1.2

1350

0.0

NC stretching + HCO bending + HCCN torsion

1245

1248

1244

0.1

1342

3.2

HCC bending

-

-

1241

4.2

1329

1.5

CC stretching + HCC bending

-

-

1227

0.8

1316

3.6

HCC bending

0.0

1463

0.6

HCC bending

1209

1210

1208

1.1

1298

2.6

(NC + CC) stretching

1199

0.0

1292

1.0

HCC bending

1186

1187

1180

0.0

1267

3.3

(NC + CC) stretching + HCC bending

1161

1162

1163

1.1

1236

0.0

CC stretching + HCC bending

1147

-

1137

-

-

1134

0.0

1219

2.3

HCC bending + (HCCC + HCCN) torsion

1127

1126

1128

0.1

1215

1.5

CC stretching + HCCC torsion

1106

1106

1103

0.1

1212

1.5

CC stretching

1098

-

1092

5.7

1208

10.4

OC stretching

-

-

1090

0.7

1201

0.4

(CC + NN) stretching

-

1078

1081

0.5

1190

4.3

NN stretching + (NNN + NCN + NNC) bending

1073

-

1073

1.8

1171

1.5

(OC + CC) stretching

-

-

1064

3.5

1159

1.8

(NC + NN) stretching + (NNN + HNN) bending

-

1054

1061

2.3

1136

5.9

(OC + CC) stretching + CNC bending

1026

-

1034

0.6

1135

0.1

CC stretching

1013

1012

1021

0.2

1132

0.0

NC stretching + NNC bending

-

-

1015

0.4

1127

0.5

NCN bending + (HCCC + CCCC) torsion

0.8

1223

1.6

HCC bending + (HCCC + HCCN) torsion

-

-

1014

1.9

1124

3.1

NCN bending + (HCCC + CCCC) torsion

1008

-

1007

0.8

1106

0.6

(CCC + NCN) bending

-

-

1002

0.0

1103

0.9

HCCC Torsion

-

-

1001

0.4

1089

0.2

CCCC Torison

993

994

992

-

973

973

4.1

1057

0.1

CCC bending + HCCC torsion

953

954

965

0.2

1052

1.1

HCCC torsion

-

-

943

0.1

1018

0.2

HCC bending + HCCC torsion

933

-

934

0.2

1011

1.2

HCC bending + HCCC torsion

-

-

916

0.5

1004

0.2

CC stretching + HCCC torsion

901

902

902

0.3

980

0.5

HCCC torsion

879

881

890

0.5

978

2.7

HCCC torsion

850

-

840

0.2

903

0.4

(CC + NC) stretching

831

832

827

3.9

879

4.1

HOCC torsion

-

-

811

0.6

875

0.6

CC stretching

-

808

809

0.1

873

0.0

HCCC torsion

787

784

787

2.1

855

2.7

(HCCC + NCNN) torsion + CNNC out of plane

0.2

1082

1.1

CCC bending

-

-

775

2.7

850

3.6

CC stretching + (CCN + OCC) bending

762

-

768

0.9

840

1.5

(HCCC + CCCC) torsion

751

755

753

0.9

822

1.1

CCC bending

-

-

742

0.5

806

0.4

(NCNN + CCCC) torsion

740

735

741

-

-

730

0.2

796

0.2

CCNC torsion

-

-

727

0.6

790

0.5

(HNNN + NCNN + NNNC) torsion

715

714

713

0.7

757

0.6

HCC bending + (HOCC + CCCC) torsion

690

691

685

0.3

735

9.3

(CCNC + CNCN) torsion

669

669

676

0.3

726

0.2

CCC bending

643

637

637

0.1

691

0.1

CC stretching + (CCNC + CNCN) torsion

619

-

626

1.0

661

5.9

CCC bending

611

612

617

0.4

652

7.0

CC stretching + CCC bending

-

-

597

6.0

646

2.5

(HNNN + NNNC) torsion

561

562

562

0.4

607

0.7

CC stretching + (HOC + CNC + HCC) bending

540

541

552

0.3

604

1.4

CCCC torsion

521

525

527

0.6

570

1.6

(CCC + CCN) bending + CCCC out of plane

0.2

805

1.0

HCC bending + HCCC torsion

501

-

505

0.3

1.4

553

CCl stretching

Table 3 Thermodynamic parameters of Losartan calculated by DFT-B3LYP and HF methods. Parameter

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

Zero point vibrational energy (Kcal\Mol ) 265.05

285.48

Rotational constants (GHz) X

0.19

0.19

Y

0.07

0.08

Z

0.07

0.07

Dipole moment(μ)

15.05

14.46

Rotational Temp, Kelvin X

0.009

0.009

Y

0.003

0.004

Z

0.003

0.003

Total energy (thermal) (kcal./mol)

282.32

301.92

Specific heat, Cv (cal mol-Kelvin)

103.43

96.39

Entropy, S (cal mol-1 K-1)

191.28

186.10

Table 4 Experimental and calculated absorption wavelength(λmax), excitation energies(E), singlet A, oscillator strength(f), Assignment and Transition of Losartan by TD-HF method Excitation

Singlet A

E(eV)

Wave length(nm) Exp

Excited state-1 111 ->112 111 ->114 111 ->115 111 ->117

0.60951 0.19103 0.16482 0.10845

Excited state-2 109 ->112 110 ->112 110 ->114 111 ->117 111 ->118 111 ->119 111 ->122

0.30052 0.54768 0.11831 -0.13327 -0.12057 0.13657 -0.12091

Excited state-3 107 ->113 108 ->112 108 ->115 110 ->112 111 ->112 111 ->114

0.18815 -0.21662 0.13833 0.13651 -0.22893 0.10904

2.431

4.171

5.466

-

-

205

Oscillator Strength(f)

Assignment

Transition

Calc

510

297

226

0.0286

0.1342

0.4048

π→π *

n→π *

π→π *

Homo↔Lumo Homo↔Lumo+2 Homo↔Lumo+3 Homo↔Lumo+5

Homo-2↔Lumo Homo-1↔Lumo Homo-1↔Lumo+2 Homo↔Lumo+5 Homo↔Lumo+6 Homo↔Lumo+7 Homo↔Lumo+10

Homo-4↔Lumo+1 Homo-3↔Lumo Homo-3↔Lumo+3 Homo-1↔Lumo Homo↔Lumo Homo↔Lumo+2

111 ->115 111 ->116 111 ->117 111 ->118 111 ->119 111 ->122

0.2215 0.14307 0.23263 0.2172 -0.21211 0.14588

Homo↔Lumo+3 Homo↔Lumo+4 Homo↔Lumo+5 Homo↔Lumo+6 Homo↔Lumo+7 Homo↔Lumo+10

Table 5 The first hyperpolarizability (X 10 -33 esu) of Losartan using DFT-B3LYP method with 6-31(d,p) basis set. Parameters

B3LYP

βxxx

951.253

βxxy

-260.963

βxyy

59.9335

βyyy

-188.658

βxxz

-117.059

βxyz

62.8111

βyyz

-22.4455

βxzz

63.4731

βyzz

-42.8423

βzzz

-127.239

Table 6 Second order perturbation theory analysis of Fock matrix in NBO analysis of Losartan using DFT-B3LYP method with 6-31(d,p) basis set

Donor

Type

Acceptor

E(2)

E(j)-E(i)

F(i,j)

Kcal./mol

a.u.

a.u.

Type

C1 - O2

Σ

C5 - C6

σ*

0.60

1.37

0.03

C1 - O2

Σ

C5 - C6

π*

1.48

0.81

0.03

C1 - C6

σ

N7

RY*2

0.94

2.40

0.04

C1 - C6

σ

C1 - H31

σ*

0.54

1.11

0.02

C1 - C6

σ

C3 - N7

σ*

2.03

1.10

0.04

C1 - H31

σ

C1 - C6

σ*

0.67

0.92

0.02

C1 - H31

σ

O2 - H33

σ*

2.24

0.96

0.04

C1 - H31

σ

C6 - N7

σ*

7.10

0.93

0.07

C3 - N4

π

C5 - C6

π*

22.04

0.33

0.08

C3 - N4

π

C27 - H45

σ*

2.15

0.72

0.04

C3 - N4

π

C27 - H46

σ*

2.09

0.71

0.04

C6 - N7

σ

C8

RY*1

0.87

1.86

0.04

C6 - N7

σ

C1 - C6

σ*

0.71

1.21

0.03

C6 - N7

σ

C3 - N4

σ*

0.53

1.34

0.02

C6 - N7

σ

C3 - N7

σ*

2.33

1.24

0.05

C6 - N7

σ

C3 - C27

σ*

4.10

1.20

0.06

C6 - N7

σ

C5 - C6

σ*

1.14

1.37

0.04

N7 - C8

σ

C12

RY*3

0.54

1.64

0.03

N7 - C8

σ

C3 - N4

σ*

1.45

1.33

0.04

C9 - C10

σ

C9 - C14

σ*

2.24

1.16

0.05

C9 - C10

σ

C9 - C15

σ*

2.69

1.19

0.05

C9 - C10

σ

C10 - C11

σ*

2.50

1.25

0.05

C11 - C12

σ

C8

RY*1

1.15

1.84

0.04

C11 - C12

σ

C10

RY*1

0.81

1.96

0.04

C11 - C12

σ

C10

RY*2

1.35

1.49

0.04

C11 - C12

σ

C13

RY*1

0.65

1.81

0.03

C11 - C12

σ

C13

RY*2

0.58

1.51

0.03

C16 - C17

σ

C9 - C15

σ*

3.43

1.17

0.06

C16 - C17

σ

C15 - C16

σ*

4.30

1.25

0.07

C16 - C17

σ

C16 - C25

σ*

2.20

1.17

0.05

C16 - C17

σ

C17 - C18

σ*

2.60

1.28

0.05

C16 - C17

σ

C17 - H40

σ*

1.02

1.16

0.03

C16 - C17

σ

C18 - H41

σ*

2.02

1.18

0.04

N21 - N22

σ

C25

RY*4

0.53

2.24

0.03

N21 - N22

σ

C16 - C25

σ*

4.33

1.33

0.07

N21 - N22

σ

N21 - C25

σ*

1.21

1.33

0.04

N21 - N22

σ

N24 - C25

σ*

0.83

1.40

0.03

N24 - C25

π

C14 - H34

σ*

0.86

0.71

0.02

N24 - C25

π

C15 - C16

σ*

0.57

0.86

0.02

N24 - C25

π

C16 - C17

σ*

0.61

0.87

0.02

N24 - C25

π

C16 - C17

π*

6.73

0.34

0.05

N24 - C25

π

N22 - N23

π*

24.66

0.29

0.08

C29 - H50

σ

C28 - H48

σ*

2.69

0.96

0.05

N7

LP1

C3 - N4

π*

49.91

0.28

0.11

N7

LP1

C5 - C6

π*

33.67

0.29

0.09

C29 - H50

σ

C30 - H53

σ*

2.76

0.94

0.05

C30 - H51

σ

C28 - C29

σ*

3.02

0.89

0.05

C30 - H52

σ

C29 - H49

σ*

2.64

0.94

0.05

C30 - H53

σ

C29 - H50

σ*

2.65

0.94

0.05

O2

LP1

C1 - C6

σ*

1.75

0.95

0.04

O2

LP1

C1 - H31

σ*

1.97

1.00

0.04

O2

LP1

C1 - H32

σ*

1.93

0.96

0.04

O2

LP2

C1 - C6

σ*

7.47

0.68

0.06

O2

LP2

C1 - H32

σ*

7.23

0.68

0.06

O2

LP2

C5 - C6

π*

0.94

0.29

0.02

N21

LP1

N24 - C25

π*

50.63

0.29

0.11

C13

LP1

O2 - H33

σ*

37.64

0.73

0.15

Cl26

LP1

C5 - C6

σ*

1.84

1.49

0.05

Cl26

LP2

N4 - C5

σ*

6.58

0.80

0.07

Cl26

LP2

C5 - C6

σ*

4.41

0.89

0.06

E(2) means energy of hyper conjugative interaction (stabilization energy) Energy difference between donar and acceptor i and j NBO orbitals F(i,j) is the Fock matrix element between i and j NBO orbitals. Table 7 NBO population analysis of Losartan using DFT-B3LYP method with 6-31(d,p) basis set Atom No

Charge

C1

-0.141

O2

-0.784

C3

0.407

N4

-0.504

C5

0.094

C6

0.072

N7

-0.382

C8

-0.268

C9

0.083

C10

-0.258

C11

-0.109

C12

-0.151

C13

-0.057

C14

-0.607

C15

-0.030

C16

-0.088

C17

-0.208

C18

-0.223

C19

-0.214

C20

-0.208

N21

-0.393

N22

-0.053

N23

-0.052

N24

-0.325

C25

0.346

Cl26

0.000

C27

-0.506

C28

-0.458

C29

-0.460

C30

-0.684

H31

0.244

H32

0.187

H33

0.481

H34

0.378

H35

0.265

H36

0.243

H37

0.254

H38

0.244

H39

0.290

H40

0.240

H41

0.253

H42

0.253

H43

0.253

H44

0.456

H45

0.241

H46

0.237

H47

0.247

H48

0.250

H49

0.226

H50

0.225

H51

0.233

H52

0.230

H53

0.231

Table 8 13C and 1H istotropic Chemical Shifts (with respect to TMS all values in ppm) of Losartan using DFT-B3LYP method with 6-31(d,p) basis set Atom

Absolute

Chemical Shifts

Experimental values

Number

Shielding

ppm

ppm

C1

161.50

38.47

28.80

C3

56.97

143.00

140.25

C5

43.23

156.75

149.20

C6

69.23

130.74

130.06

C8

122.03

77.95

51.17

C9

43.54

156.43

149.20

C10

84.89

115.09

124.85

C11

66.33

133.65

134.58

C12

15.28

184.70

161.84

C13

-59.41

259.39

-

C14

114.02

85.96

51.17

C15

55.61

144.36

140.44

C16

77.52

122.46

124.85

C17

66.65

133.32

130.36

C18

70.59

129.38

129.33

C19

64.62

135.36

134.58

C20

72.33

127.64

128.28

C25

43.07

156.90

161.84

C27

155.05

44.93

46.77

C28

141.84

58.14

51.17

C29

158.41

41.57

46.77

C30

168.67

31.31

28.80

H31

26.12

6.47

4.8

H32

29.01

3.58

3.15

H33

45.37

0.77

0.43

H34

20.73

11.86

7.6

H35

24.52

8.07

7.6

H36

24.03

8.56

7.6

H37

26.53

6.05

7.1

H38

24.97

7.62

7.6

H39

28.81

3.78

3.15

H40

24.58

8.01

7.6

H41

24.31

8.28

7.6

H42

24.11

8.48

7.6

H43

24.29

8.30

7.6

H44

20.17

12.42

7.6

H45

28.41

4.18

4.15

H46

28.21

4.38

4.15

H47

29.16

3.43

3.15

H48

26.28

6.31

4.8

H49

29.97

2.62

2.17

H50

29.96

2.63

2.17

H51

29.77

2.82

2.17

H52

30.02

2.57

2.17

H53

30.09

2.50

2.17

Graphical Abstract

HIGHLIGHTS ► FT-IR, FT-Raman and UV-vis spectra of Losartan in the solid phase were recorded and analyzed. ► Selected vibrational assignment and spectroscopic analysis have been carried out. ► Natural atomic analysis explained the intramolecular hydrogen bonding. ► The calculated HOMO and LUMO energies show that charge transfers occurs within molecule. ► The 13C and 1H NMR chemical shift data assignment for Losartan have also been reported.