Spectroscopic investigation (FT-IR, FT-Raman, UV, NMR ... study, we report a detailed spectroscopic

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  • Spectroscopic investigation (FT-IR, FT-Raman, UV,

    NMR), Computational analysis (DFT method) and

    Molecular docking studies on 2-[(acetyloxy) methyl]-

    4-(2-amino-9h-purin-9-yl)butyl acetate

    Fathima Rizwana B. 1 , Johanan Christian Prasana

    1 and S.Muthu


    1 Department of Physics, Madras Christian College, Chennai-59, Tamilnadu, India,

    2 Department of Physics, Arignar Anna Govt. Arts College, Cheyyar-604407,

    Tamilnadu, India.

    *E-mail: mutgee@gmail.com


    A systematic approach has been adopted for structural analysis of, 2-

    [(acetyloxy)methyl]-4-(2-amino-9H-purin-9-yl)butyl acetate by FT-IR, FT-Raman,

    UV and NMR spectroscopic techniques. The optimized molecular geometry, the

    vibrational assignments, the IR and the Raman scattering activities were calculated by

    using density functional theory (DFT) B3LYP method with 6-311++G(d,p) basis set.

    The calculated HOMO and LUMO energies show the charge transfer within the

    molecule. Stability of the molecule arising from hyperconjugative interactions, charge

    delocalization have been analyzed using natural bond orbital analysis (NBO).

    Molecular electrostatic potential (MEP) and Fukui functions calculation were also

    performed. The thermodynamic properties (heat capacity, entropy, and enthalpy) of

    the title compound at different temperatures have been calculated. Antiviral activity

    was examined based on molecular docking analysis and it has been identified that the

    title compound can act as a good inhibitor against Herpes Simplex Virus.

    Key words : DFT, FTIR, NMR, UV-Visible, Docking.

    Introduction :

    2-[(acetyloxy)methyl]-4-(2-amino-9H-purin-9-yl)butyl acetate is a guanine analogue

    antiviral drug used for the treatment of various herpesvirus infections, most

    commonly for chronic delta hepatitis [1] herpes zoster (VZV), herpes simplex virus

    types 1 (HSV-1) and 2 (HSV-2) [2]. Commonly, 2-[(acetyloxy)methyl]-4-(2-amino-

    9H-purin-9-yl)butyl acetate is known as Famciclovir (FCV) [3]. It is also indicated for

    treatment of recurrent episodes of herpes simplex in HIV patients. Famciclovir is the

    recently licensed oral formulation of the guanosine analogue penciclovir. It is

    International Journal of Materials Science ISSN 0973-4589 Volume 12, Number 2 (2017) © Research India Publications http://www.ripublication.com



  • available in markets under the brand name Famtrex. Famciclovir is absorbed well and

    converted efficiently to penciclovir, which is a potent inhibitor of viral DNA

    synthesis. Few spectroscopic studies have been reported on the title compound [4,5].

    Structural and bonding features reveal that this FCV molecule has several reactive

    groups which contribute in both intra and intermolecular hydrogen bonding

    interactions with biological targets. Literature survey reveals that so far there is no

    detailed experimental and theoretical study of the title compound. In this present

    study, we report a detailed spectroscopic investigation of 2-[(acetyloxy)methyl]-4-(2-

    amino-9H-purin-9-yl)butyl acetate (FCV) using B3LYP/6-311++G(d,p) level of the

    theory. The FT-IR and FT-Raman spectral analysis of FCV are performed using

    density functional theory. The redistribution of electron density(ED) in various

    bonding, antibonding orbitals and E(2) energies are calculated by the natural bond

    orbital(NBO) investigation. The local reactivity descriptors are obtained with the help

    of Fukui function calculation. Several properties like molecular geometry, Highest

    Occupied Molecular Orbital (HOMO) and Lowest Unoccupied Molecular Orbital

    (LUMO) energies, Nuclear Magnetic Resonance (NMR), UV-Visible, Molecular

    Electrostatic Potential (MEP) analysis of the FCV gives clear information about

    charge transfer within the molecule. Antiviral activity was analyzed using molecular

    docking method.

    Experimental details:

    The title compound was purchased from sigma Aldrich company with 99% purity,

    and was used as such without any further purification. The FTIR spectrum of the title

    compound was recorded in the region 4000-400 cm -1

    in the evacuation mode using a

    KBr pellet technique with 1.0 cm -1

    resolution on a PERKIN ELMER FT-IR

    spectrophotometer. The FT-Raman spectrum of the title molecule was recorded in the

    region 4000-100cm -1

    in a pure mode using Nd:YAG Laser of 100mW with 2cm -1

    resolution on a BRUCKER RFS 27 at IIT SAIF, Chennai, India. The UV–vis

    spectrum of the molecule was also recorded by the UV–Visible spectrophotometer in

    the wavelength region 200–500 nm using DMSO as a solvent. Carbon( 13

    C) NMR and

    Proton( 1 H) NMR spectra were recorded on a Bruker AVANCE III 500 MHz (AV

    500) multi nuclei solution NMR Spectrometer using DMSO as solvent at 400 MHz at

    CAS in IIT SAIF, Chennai, India.

    Computational method:

    Quantum chemical density functional computations were carried out at the Becke3-

    Lee-Yang-parr (B3LYP)[6] level with 6-311++G(d,p) basis set using Gaussian [7]

    program package to get a clear knowledge of optimized parameters. The optimized

    molecular structure is used for the computation of vibrational frequencies, Raman

    activities and IR intensities with the Gaussian software system molecular visualization

    program at the same level of theory and basis set. The theoretical vibrational

    assignments of the title molecule using percentage potential energy distribution (PED)

    International Journal of Materials Science ISSN 0973-4589 Volume 12, Number 2 (2017) © Research India Publications http://www.ripublication.com


  • were done with the VEDA [8] program. Raman scattering activities of the

    fundamental modes were suitably converted into the relative Raman intensities [9,10].

    The electronic properties such as HOMO and LUMO energies were determined. In

    order to understand the electronic properties, the theoretical UV-Vis spectra have

    been investigated by TD-DFT method with 6-311++G(d,p) basis set for the gas phase.

    The 1 H and

    13 C NMR chemical shift were calculated with gauge-including atomic

    orbital (GIAO) approach [11] by applying B3LYP/6-311++G(d,p) method of the title

    molecule and compared with the experimental NMR spectra. The NBO analysis and

    MEP calculations were performed on the title molecule. NBO analysis gives a clear

    evidence of stabilization originating from hyperconjugation of various intramolecular

    interactions. The Mulliken population analysis and condensed Fukui functions were

    reported. Molecular docking (ligandprotein) simulations have been performed by

    using AutoDock 4.2.6[12] free software package.

    Results and discussion:

    Molecular geometry:

    The bond parameters (bond length and bond angles) of the title molecules are

    obtained using DFT/B3LYP method with 6-311++G(d,p) basis set and are listed in

    Table 1. The optimized molecular structure of title compound is shown in Fig. 1. The

    theoretical calculations were carried out isolated molecule in the gas phase. The

    homonuclear bonds (C6-C7, C6-C19, C5-C6, C1-C2) have higher bond lengths as

    1.541Å, 1.533Å, 1.531Å, 1.513Å respectively and heteronuclear bonds (N18-H36,

    N18-H37, C5-H27, C10-H34, C23-H42) have less bond lengths as 1.007Å, 1.007Å,

    1.094Å, 1.081Å, 1.091Å respectively.

    Fig. 1. Optimized geometric structure with atoms numbering of FCV molecule

    Table 1. Geometrical parameters optimized in 2-[(acetyloxy)methyl]-4-(2-amino-9H-purin-9-yl)butyl acetate bond

    length (Å) and bond angle (o) with 6-311++G(d,P) basis set.

    International Journal of Materials Science ISSN 0973-4589 Volume 12, Number 2 (2017) © Research India Publications http://www.ripublication.com


  • Vibrational Assignments:

    The maximum number of potentially active observable fundamentals of the non-linear

    molecule, which contains N atoms, is equal to (3N-6) apart from three translational

    Bond Length(Å) B3LYP/6-311++G(d,p) Bond Angle(o) B3LYP/6-311++G(d,p)

    C1-C2 1.513 C2-C1-O3 123.9

    C1-O3 1.201 C2-C1-O4 117.8

    C1-O4 1.364 C1-C2-H24 111

    C2-H24 1.093 C1-C2-H25 108.2

    C2-H25 1.087 C1-C2-H26 111.5

    C2-H26 1.093 O3-C1-O4 118.3

    O4-C5 1.44 C1-O4-C5 122.1

    C5-C6 1.531 H24-C2-H25 109.2

    C5-H27 1.094 H24-C2-H26 107.4

    C5-H28 1.092 H25-C2-H26 109.5

    C6-C7 1.541 O4-C5-C6 106.7

    C6-C19 1.533 O4-H5-C27 110

    C6-H29 1.099 O4-C5-H28 110.3

    C7-C8 1.534 C6-C5-C27 111

    C7-H30 1.092 C6-C5-H28 110.3

    C7-H31 1.094 C5-C6-C7 111.7

    C8-N11 1.459 C5-C6-C19 111.4

    C8-H32 1.091 C5-C6-H29 105.9

    C8-H33 1.094 H27-C5-H28 108.5

    N9-C10 1.304 C7-C6-C19 113.2

    N9-C17 1.387 C7-C6-H29 108.8

    C10-N11 1.39 C6-C7-C8 112.9

    C10-H34 1.081 C6-C7-H30 108.8

    N11-C12 1.374 C6-C7-H31 109.7

    C12-N13 1.327 C19-C6-H29 105.4

    C12-C17 1.409 C6-C19-O20 112.5

    N13-C14 1.344 C6-C19-H3