In this work, The structural characteristics and vibrational spectroscopic analysis were carried out by quantum chemical methods with the hybrid exchange-correlation functional B3LYP using 6-31G (d, p) and 6-311++G (d, p) basis sets in order to investigate the fundamental modes of vibrational analysis and electronic properties of phenyl substituted compound N-((1-(phenylsulfonyl)-1H-indol-3-yl)methyl)acetamide. Density Functional Theory (DFT) method, using B3LYP functional, with 6-31G (d, p) and 6-311++G (d, p) basis sets, which in turn creates a platform to study the structure of the chosen compound. The experimentally obtained FTIR and FT Raman spectrum supports the results of theoretically observed ones. Detailed interpretations of the experimental spectra of the molecule along with the theoretical ones are reported based on Potential Energy Distribution (PED).
The total dipole moment, static total and anisotropy of polarisability and static first hyperpolarisability values were calculated. The FMOs, molecular electrostatic potential, global reactivity descriptors were also calculated and discussed. Molecular electrostatic potential and frontier molecular orbitals were constructed to understand the electronic properties. The intramolecular contacts are interpreted using Natural Bond Orbital (NBO) analysis to ascertain the charge distribution. The thermodynamic properties at different temperatures were calculated revealing the correlations between standard heat capacities, entropy and enthalpy changes with temperatures.
Keywords: N1PS3MA; NBO/NLMO; MEP; PED
N-((1-(phenylsulfonyl)-1H-indol-3-yl)methyl)acetamide is basically an indole derivative, otherwise called [N1PS3MA] having molecular formula C16H16N2O3S. The phenyl sulfonyl ring makes 66.5(7) dihedral angle with the indole unit. Some of the indole alkaloids extracted from plants possess interesting cytotoxic, antitumour or antiparasitic properties [1,2]. Pyrido[1,2-a] indole derivatives have been identified as potent inhibitors of human immunodeficiency virus type-1 , and 5-chloro-3-(phenylsulfonyl) indole-2-carboxamide is reported to be a highly potent non-nucleoside inhibitor of HIV-1 reverse transcriptase . The interaction of phenylsulfonylindole with calf thymus DNA has also been studied by spectroscopic methods . The Compound was synthesized one and the molecular parametric details are obtained from the similar compound synthesized by A. Thenmozhi et al.  and no further studies have been carried out for the title compound yet. Literature survey reveals that so far no spectroscopic and computational work was carried out on the title compound. Therefore in our present investigation, the spectroscopic properties of N-((1-(phenylsulfonyl)-1H-indol-3-yl)methyl)acetamide were studied by vibrational spectroscopy (FT-IR, FT-Raman) and additionally the structure, vibrational frequencies and other thermodynamical parameters of the title molecule were calculated by the DFT method. The redistribution of electron density (ED) in various bonding and antibonding orbitals and E(2) energies have been calculated by Natural Bond Orbital (NBO/NLMO) analysis using DFT method to give clear evidence of stabilization originating from the hyperconjugation of various intramolecular interactions. The HOMO and LUMO analysis have been used to elucidate the information regarding charge transfer occurs within the molecule. Moreover, the Mulliken population analyses of the title compound have been calculated and the calculated results have been reported.
The compound N-((1-(phenylsulfonyl)-1H-indol-3-yl)methyl) acetamide [N1PS3MA] was a synthesized one and reported in Literature  and used as such without further purification to record FTIR and FT Raman spectra. The FTIR spectrum of the compounds is recorded in the region 4000- 400 cm−1 in evacuation mode on Bruker IFS 66V spectrophotometer using KBr pellet technique (solid phase) with 4.0 cm−1 resolutions. The FT-Raman spectra of these compounds are also recorded in the same instrument with FRA 106 Raman module equipped with Nd: YAG laser source operating at 1.064 μm line widths with 200 mW powers. The spectra are recorded in the range of 3500– 100 cm−1 with scanning speed of 30 cm−1 min−1 of spectral width 2 cm−1. The frequencies of all sharp bands are accurate to ± 1 cm−1. The spectral measurements were carried out at Sophisticated Analytical Instrumentation Facility, IIT, Chennai, Tamil Nadu, India.
The optimized molecular geometrical orientation and the vibrational frequency calculations are carried out for N1PS3MA, with the Gaussian 03W software package . Becke’s three parameter exchange functional (B3)  and combination with the correlation functional of Lee, Yang and Parr (LYP)  were adopted with standard 6-31G(d,p) and 6-311++G (d,p) basis sets. The optimized geometrical parameters namely, bond length and bond angles calculated by two basis sets are listed in Table 1 along with the experimental data on the geometric structure of the selected molecule. This molecule has fifteen C-H bond lengths, seventeen C-C bond lengths, four C-N bond lengths, two S-O bond lengths, one C-S and N-S bond length, and a C-O bond length. The C-C bond length value of the ring is found to be 1.337 Å at B3LYP/6-311++G (d,p) level. The C-O bond length value is found to be 1.208 Å. The C-H bond length value calculated at B3LYP/6-311++G (d,p) level vary from 1.096 to 1.101 Å and the N-H bond length value is 1.411 Å. Here the value of S-C bond length is found to be high compared to other bond length values. The calculated bond angles of C-C-H, C-C-C, O-C-H and H-C-H are found to be slightly on the higher side compared to experimental values of bond angle. The Cartesian representation of the theoretical force constants have been computed at the optimized geometry by assuming C1 point group symmetry. The vibrational wavenumbers are calculated with PED calculations at the optimized geometrical orientation. The atomic charges, electric dipole moment, polarizability, first hyperpolarizability, HOMO, LUMO and thermodynamic parameters are also calculated theoretically. The Natural Bonding Orbital (NBO) calculations are performed using NBO 3.1 program as implemented in the Gaussian 03W  package at DFT level in order to understand various second-order interactions between the filled orbital of subsystem and vacant of another subsystem, which is a measure of the intermolecular delocalization or hyperconjugation. Finally, the calculated normal mode of vibrational frequencies will provide the thermodynamic properties using the principle of statistical mechanics. The optimized structure of N1PS3MA is shown in Figure 1.
|Molecular parameters/Bond lengths||Experimental||B3LYP/6-31G(d,p)||B3LYP/6-311++G(d,p)|
|Bond angles (°)|
Table 1: Molecular geometrical parameters of N-((1-(phenylsulfonyl)-1H-indol- 3-yl)methyl)acetamide N1PS3MA.
The title molecule consists of 39 atoms, hence (3N-6) gives 111 normal modes of vibrations, and all are active in infrared and Raman spectra. The detailed vibrational assignments of fundamental modes along with the calculated IR, Raman intensities and normal mode description (characterized by PED) are reported in Table 2. For comparison, the observed and simulated Raman and IR spectra are presented in Figures 2 and 3.
|FTIR ν IR cm-1||FT Raman νR cm-1||B3LYP/6-31G(d,p)||B3LYP/6-311++G(d,p)||Assignments with PED % calculation|
|νcal cm-1||IR intensity||Raman activity||νcal cm-1||IR intensity||Raman activity|
|20||0.323||2.789||19||1.221||1.404||α ring scissoring (15)|
|25||2.441||1.833||24||1.008||9.701||τ ring (12)|
|32||0.707||10.770||32||0.586||5.473||β ring (16)+γSO2(wag) (28)|
|48||0.240||6.500||47||1.763||5.022||α ring (10)|
|147||145||4.598||1.900||144||2.960||0.754||α C N (27)+γCH (16)|
|226||222||2.027||3.754||221||1.600||0.857||β CN (27)+γCH (11)|
|248||1.811||1.348||249||2.244||0.816||α CH(16)+α CH3(14)|
|285||0.132||6.045||286||3.89||0.685||α CH(14)+α CH2(25)+ α CH3(13)|
|310||307||1.387||4.166||308||9.148||3.536||βCCC(37)+α NH(18)+α CH3(34)|
|365||363||3.240||0.589||363||0.054||0.487||γ ring 1 (12)|
|401||403||9.417||2.96||404||8.240||1.504||τCH3 (41)+α NH(10)|
|412||412||19.862||1.263||412||0.486||2.664||τring (19)+βCCC (24)|
|421||421||421||0.171||0.264||422||9.892||4.194||α SO2(20)+α CH3(32)|
|435||436||3.468||0.413||439||66.473||2.867||α CH(24)+α NH(14)+α CH2(36)|
|466||465||467||15.884||1.034||467||23.901||2.162||γCN (21)+βring (19)|
|489||487||485||4.964||5.145||486||83.144||13.301||γring 4 (53)+γCS (26)|
|537||536||1.237||3.037||536||89.263||1.692||τ ring (25)+γCH(19)|
|543||545||49.015||1.275||544||68.808||3.132||δNS (37), δring 4 (26)|
|577||576||81.884||2.600||574||61.412||87.798||α CH(12)+α SO2(36)+α CH3(18)|
|627||628||626||3.573||4.454||627||0.266||1.146||α CH(27)+α CH3(43)|
|866||865||1.460||3.625||866||90.347||4.019||α CH(26)+γCH (39)|
|998||998||997||0.156||0.171||998||39.504||1.876||α CH3(48)+α CH2(15)|
|1192||1191||0.237||5.448||1192||12.360||7.885||ν CN (79)|
|1211||1211||1210||29.888||8.555||1214||0.859||1.774||α CH2(27)+νCN (58)|
|1243||1243||1242||11.162||7.103||1245||35.552||8.144||ν CN (64)+δCH (53)+νsSO (67)|
|1260||1260||17.425||5.235||1261||6.130||12.543||α CH2(19)+α NH(38)+νSO2 (61)|
|1310||1307||7.081||20.766||1305||15.639||10.117||τCC (33)+νSO2 (58)|
|1410||1410||42.073||8.629||1409||31.733||5.515||νCC(62)+α CH3(18)+α CH2(52)|
Table 2: Vibrational assignments of N1PS3MA using B3LYP/6-31 G(d,p) and B3LYP/6-311++G(d,p).
CH2 and CH3 vibrations: There is one CH3 and a CH2 group in this compound. Earlier researchers [10,11] have reported infrared bands occurring in the range 3100-2900 cm−1 as due to C-H stretching in their study. The assignments of CH2 group frequency involve six fundamentals namely, CH2 symmetric stretch; CH2 asymmetric stretch; CH2 scissoring and CH2 rocking which belongs to in-plane vibration and out of plane vibration namely CH2 wagging and CH2 twisting modes. The fundamental CH2 vibrations due to scissoring, wagging, twisting and rocking appear in the region 1500–800 cm−1. The asymmetric CH2 stretching vibrations are generally observed in the region 3200 - 3050 cm−1, while the symmetric stretching will appear between 3050 and 2900 cm−1 [12-14]. In this compound the asymmetric stretching of CH2 vibration occurs at 3177 cm−1 in FTIR and 3175 cm−1 in FT Raman spectra. The symmetric stretching vibrations occur at 3059 cm−1 in FTIR and in FT Raman spectra. The results of symmetric and asymmetric CH2 vibrations agree well with the DFT method.
CH2 scissoring is assigned to 1492, 1410 cm−1 in experimental observation agrees the values at 1492, 1410 cm−1 in B3LYP method. CH2 wagging is attributed to 1392 cm−1, 1381 cm−1 in FTIR, and the corresponding values in FT-Raman are in good agreement B3LYP values. Emilio et al. have observed CH3 scissoring at 1513 cm−1 and based on this reference, in our compound the band at 1501 cm−1 is assigned to CH3 scissoring and CH2 wagging is assigned to the band at 1365 cm−1 in both FTIR and FT-Raman spectra .
The title compound has one CH3 group. The asymmetric CH3 is expected around 3187 cm−1 and CH3 symmetric stretching is expected at 3073 cm−1 [16,17]. In this study apart from CH2 and CH3 the other CH asymmetric and symmetric stretching vibrations are identified in their respective ranges and these results agree well with the values of DFT method.
N-H vibrations: Normally the vibrational bands due to the N-H stretching are sharp by virtue of which they can be easily identified. Tsuboi  reported the N-H stretching frequency at 3481 cm−1 in aniline. In our study the band appear at 3460 and 3461 cm−1 in the FTIR and FT Raman spectrum is assigned to N-H stretching vibrations. The theoretically calculated value by DFT method at 3459 cm−1 shows agreement with experimentally observed value. Though the identification of bands is difficult, with the help of the animation option of chemcraft graphical interface for Gaussian programs, the N-H vibration is identified.
C-N vibrations: The identification of C-N vibrations is a very difficult task, since mixing of several bands are possible in this region. The conjugated C-N linkage in amine group gives rise to medium to weak bands near 1350-1150 cm−1 because of C-N stretching vibration. Silverstein have assigned C-N stretching absorption in the region 1300- 800 cm−1. Gnanasambandan et al. have identified in m-nitromethyl benzoate 1290, 1400 and 1420 cm−1 as C-N stretching vibrations. C–N stretching absorption in the region 1382-1266 cm−1 for aromatic amines. In our present work 1408, 1294, 1243, 1211 cm−1 in FT-IR and 1408, 1293, 1243 and 1211 cm−1 in FT-Raman are assigned to C-N stretching. The B3LYP values 1242, 1210, 1191 cm−1 corresponds to C-N stretching vibration. Our assignment is in good agreement with the literature [19-24].
C=O vibrations: The carbonyl group shows a strong absorption band due to C=0 stretching vibrations and is observed in the region 1850-1550 cm−1. Because of its high intensity and relatively interference free region in which it occurs, this band is reasonably easy to recognize [25-29]. In the present work the bands observed at 1610 cm−1 in FTIR and FT Raman spectrum is assigned to C=O stretching mode of vibration, and it well agrees with the values of DFT method.
C-S vibrations: In general the assignment of the band due to C-S stretching vibration in a compound is difficult. Since it is of variable intensity and may be found over the wide region 1035–245 cm−1 both in aliphatic and aromatic sulfides have a weak to medium band due to C-S stretching vibration in the region 710–570 cm−1 . In the present work the band observed at 764cm−1 in FTIR and 762 cm−1 in FT Raman are assigned to C-S stretching vibration. Theoretically computed values are found to be in good agreement with the experimental results.
SO2 vibrations: Seshadri et al.  have reported SO vibrations in 1338 cm−1, 1226 cm−1, and 1217 cm−1 in FTIR spectrum. The wavenumbers at 1310 cm−1 and 1293 cm−1 in FTIR spectrum is assigned to SO2 asymmetric stretching vibration. The corresponding B3LYP values are 1307 and 1293 cm−1. B3LYP values are in good agreement with the experimental values. The symmetric and asymmetric SO2 stretching vibrations occur in the region 1125–1260 cm−1 and 1260– 1330 cm−1 respectively. In the title molecule, SO2 symmetric stretching is observed at 1260 cm−1 in FTIR and in FT-Raman. The calculated B3LYP values are 1260 cm−1. The values are in good agreement with the literature.
NBO (natural bond orbital) analysis provides an efficient method for studying intra- and intermolecular bonding and interaction among bonds. It also provides a convenient basis for the investigation of charge transfer or conjugative interactions in molecular system . Another useful aspect of NBO method is that it gives information about interactions in both filled and virtual orbital spaces that could enhance the analysis of intra and intermolecular interactions. The second order Fock matrix was carried out to evaluate the donor–acceptor interactions in the NBO analysis. For each donor NBO (i) and acceptor NBO (j), the stabilization energy associated with ij delocalization can be estimated as:
Where qi is the donor orbital occupancy, are εi and εj diagonal elements and F (i, j) is the off diagonal NBO Fock matrix element.
In Table 3, the perturbation energies of significant donor–acceptor interactions are presented. The larger the E(2) value, the intensive is the interaction between electron donors and electron acceptors. In N1PS3MA, the interactions between the anti bonding orbitals C18− C23→C21−C22 and C18−C23→C19C20 have the highest E(2) value around 200.25 and 186.87 kcal/mol. The other significant interactions gives stronger stabilization energy values of 171.92 kcal/mol to the structure are the interaction between anti bonding orbital of C7– C8→C9−C14.
|Donor||Acceptor||E(2) kJ/mol||% from parent NBO||Hybrid atoms|
|LP(1)N6||π*(C9-C14)||50.68||81.47||C7, C8, C9, C14, S15|
|LP(1)O17||σ*(N6-S15)||28.09||89.96||S15, O16, C18|
Table 3: Occupancy, percentage of p character of significant natural atomic hybrid of the natural bond orbital, Significant of NLMO’s and second Perturbation theory analysis of N1PS3MA calculated at B3LYP/6-311++G(d,p).
The natural localized molecular orbital (NLMO) analysis has been carried out since they show how bonding in a molecule is composed from orbitals localized on different atoms. The derivation of NLMOs from NBOs give direct insight into the nature of the localized molecular orbital’s ‘‘delocalization tails’’ [33,34]. Table 3 shows significant NLMO’s percentage from parent NBO and atomic hybrid contributions of N1PS3MA calculated at B3LYP level using 6-311++G (d,p) basis set. The NLMO of first lone pair of nitrogen atom N6 is the most delocalized NLMO and has only 82% contribution from the localized LP(1) N6 parent NBO, and the delocalization tail (∼16%) consists of the hybrids of C14 and C9.
Molecular Electrostatic Potential (ESP) at a point in the space around a molecule gives an indication of the net electrostatic effect produced at that point by the total charge distribution (electron+nuclei) of the molecule and correlates with dipole moments, electronegativity, partial charges and chemical reactivity of the molecules. It provides a visual method to understand the relative polarity of the molecules. An electron density isosurface mapped with electrostatic potential surface depicts the size, shape, charge density and site of chemical reactivity of the molecules. The different values of the electrostatic potential represented by different colors; red represents the regions of the most negative electrostatic potential, blue represents the regions of the most positive electrostatic potential and green represents the region of zero potential. Potential increases in the order red < orange < yellow < green < blue. Such mapped electrostatic potential surfaces have been plotted for title molecules in 6-311++G(d,p) basis set using the computer software Gauss view. Projections of these surfaces along the molecular plane and a perpendicular plane are given in Figure 4 for N1PS3MA. The Figure 4 provides a visual representation of the chemically active sites and comparative reactivity of atoms.
It may see that, in the molecules, a region of zero potential envelopes the p-system of the aromatic rings, leaving a more electrophilic region in the plane of hydrogen atoms. The shapes of the electrostatic potential at sites close to the polar group in the two molecules. The nitrogen group in the molecules is influenced by the stereo structure and the charge density distribution. These sites show regions of most negative electrostatic potential and high activity of the nitrogen groups. In contrast, regions close to the other polar atomoxygen of the aromatic ring show regions of mildly negative and zero potential, respectively .
The atomic charges at all the exocyclic atoms are in accordance with their electro-negativity whereas the charges at all the C atoms of the ring are in accordance with the net flow of p electrons(delocalization of electron density) . The Mulliken atomic charges at each atomic site of N1PS3MA is collected in Table 4 and displayed in Figure 5 along with atom numbering.
Table 4: Population analysis of N1PS3MA calculated by B3LYP/6-311++G(d,p) basis set.
According to our calculation the negative charge in an investigated molecule is delocalized between nitrogen and oxygen atoms. The charges calculated for nitrogen atoms are different but the oxygen atoms (O(16) and O(17)) are having same charges (−0.533respectively). The charge on the O16 and O17 atom are found to be equal as they experience the same environment. This depreciation of the negative charges on the oxygen atom may be due to delocalization through the p−electron system of the pyrazole. The positive charges are localized on the hydrogen atoms. The charges on hydrogen’s H24, H25and H26 are found to be 0.108, 0.145 and 0.147 respectively and the differences in calculated charges are relatively small. For better visualization, the charge and atom graph is plotted for each charged atom and is displayed in the Figure 6.
Electron density analysis
An analysis of the electron density of highest occupied molecular orbitals (HOMO) and lowest unoccupied molecular orbitals (LUMO) of N1PS3MA can give us some idea about the ground and excited state proton transfer processes. The energies corresponding to HOMO and LUMO levels of N1PS3MA are performed by density functional method. The HOMO–LUMO energy calculation reveals that, there are 86 occupied and 429 unoccupied molecular orbitals associated with N1PS3MA. The energies corresponding to the highest occupied and lowest unoccupied molecular orbitals of N1PS3MA are found to be -5.886 and -1.2547 eV respectively as shown in Table 5. The energy gap between occupied and unoccupied molecular orbitals of N1PS3MA calculated at B3LYP/6-311++G (d,p) level is given in Table 5 reflects the chemical reactivity of the molecule. LUMO as an electron acceptor represents the ability to obtain an electron. HOMO represents the ability to donate an electron.
|Molecular properties||B3LYP/6-311++G(d,p)||B3LYP/6-31G(d,p)||Molecular properties||B3LYP/6-311++G(d,p)||B3LYP/6-31G(d,p)|
|Ionization potential(I)||5.88668||6.32696||Electrophilicity index(ω)||6.37498||7.3218|
Table 5: Molecular properties of N1PS3MA.
HOMO orbital on the aromatic ring of N1PS3MA (Figure 7) is primarily of anti-bonding character type over C1, C7, C8 atoms, whereas C2, C5, C10 and N4, N6 show bonding character. Both the hydroxyl and carbonyl oxygen having bonding character type, with a larger electron density over hydroxyl oxygen [37-39]. By using the HOMO and LUMO energy values, the global chemical reactivity descriptors of molecules such as hardness (), chemical potential (μ), softness (S) and electrophilicity index (χ) are calculated using the standard formulas and are defined as follows.
The values obtained for those global reactivity descriptors are listed in Table 5. For visual comparison the HOMO and LUMO diagram of the compound is shown in Figure 7.
The temperature dependence of the thermodynamic properties such as heat capacity at constant pressure (Cp), entropy (S) and enthalpy change (ΔH0 →T)  for N1PS3MA were also determined by B3LYP/6-311++G(d,p) method and listed in Table 6. The Figure 7 depicts the correlation of heat capacity at constant pressure (Cp), entropy (S) and enthalpy change (ΔH0 →T) with temperature and the corresponding fitting equations are as follows
|T (K)||S (J/mol.K)||Cp (J/mol.K)||ddH (kJ/mol)|
Table 6: Thermodynamic parameters of N1PS3MA.
Sºm=240.03433+0.7328 T-1.79433 × 10-4 T2 (R2=0.9999)
Cºpm=15.26587+0.65639 T-2.82786 × 10-4 T2 (R2=0.9998)
Hºm=-7.65942+0.08696 T+1.73344 × 10-4 T2 (R2=0.9998)
The entropies, heat capacities, and enthalpy changes are increasing with temperature ranging from 100 to 1000 K due to the increase in vibrational intensities with temperature. For the title compound, all thermodynamic parameters have been increased steadily.
The vibrational FT-IR and FT-Raman spectra of N1PS3MA were recorded and computed vibrational wavenumbers and their PED were calculated. The molecular structural parameters like bond length, bond angles, thermodynamic properties and vibrational frequencies of the fundamental modes of the optimized geometry have been determined from DFT calculations using 6-31G (d,p) and 6-311++G(d,p) basis sets. NBO analysis was made it indicated the intra molecular charge transfer between the bonding and antibonding orbital’s. The calculated HOMO and LUMO energies were used to analyse the charge transfer within the molecule. With the help of HOMO, LUMO values, the global reactivity descriptors were calculated. The predicted MEP Figure 8 revealed the negative regions of the molecule was subjected to the electrophilic attack of this compound.