Indole is a privileged s heterocyclic framework in view of its incorporation with proteins as amino acid tryptophan. Indole is a planar bicyclic compound with a benzene and pyrrole ring fused together. Since medicinal compounds have an indole center, they are a special heterocyclic structure with a wide variety of biological properties [1-4]. The astonishing biological properties of heterocyclic compounds containing indole nucleus are antimicrobial , antitubercular , anticonvulsant , anti-inflammatory , analgesic , anticancer , insecticidal activity , antioxidant , antiviral , antidepressant , and antihistaminic . Likewise, indanones appear to be a most promising lead for drug development [16-20].
Theoretical chemistry has advanced and DFT calculations are considered as valuable tool for predicting the structural, electronic, and spectral properties of the molecules [21-24]. Importantly, DFT computations offer a wealth of knowledge about the molecules' spectroscopic and quantum chemical parameters, allowing researchers to investigate their chemical behaviour [25-31]. DFT techniques have also been used to study UV-visible, NMR, and Raman spectroscopic examinations [32-34]. Theoretical calculations using DFT has been used to asses various structural, molecular and spectral properties 2,3-dihydrobenzofuran derivatives , 5,6-diaroylisoindoline-1,3-dione  , morphonium formate and acetate Ionic liquid salts  2,3-dihydrobenzofuran linked indanones , 2-(3-bromophenyl)-4-(4-bromophenyl)-2,3-dihydro-1H-1,5-benzodiazepine , (E)-3-(4-chlorophenyl)-1-(2-hydroxyphenyl)prop-2-en-1-one , ethyl 4-(4-isopropylphenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate , 5-(4-chlorophenyl)-3-(3,4-dimethoxyphenyl)-1-phenyl-4,5-dihydro-1H-pyrzole , (E)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-3-(3,4,5-trimethoxyphenyl)prop-2-en-1one , dihydropyrimidinones , (2E)-3-(2,6-dichlorophenyl)-1-(4-fluoro)-prop-2-en-1-one , and ethyl-4-(3,4-dimethoxyphenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate . The efficient synthesis methods were found to speed up the rate of reaction and thereby follow the principles of green chemistry [47-53].
The DFT method with the B3LYP functional is proved to be one of the best computational strategies to predict molecular properties [54-62]. Using the B3LYP functional with a 6-311G(d,p) basis set, the great deal of agreement between theoretical and experimental results can be obtained [21, 22]. In light of all of the above, I would like to present a DFT analysis on the structural, mechanical, and chemical reactivity of (E)-7-((1H-indol-3-yl)methylene)-1,2,6,7-tetrahydro-8H-indeno[5,4-b]furan-8-one in this paper. The usefulness of DFT on molecular structure, bond length, bond angle, and Mulliken atomic charges has been explored in the flow study. The DFT technique was used to analyse essential parameters such as total energy, HOMO-LUMO energies, charge distribution, thermodynamic properties, and so on. This is the first article on the synthesis and DFT investigation of the title compound.
The high-purity chemicals were purchased from the Sigma laboratory in Nashik. The chemicals were used exactly as they were obtained, with no further purification needed. The melting point was measured in an uncorrected open capillary system. A sophisticated multinuclear FT NMR Spectrometer model Advance-II (Bruker) was used to record 1H and 13C NMR spectra with a 1H frequency of 500 MHz and 13C frequency 126 MHz using DMSO-d6 as solvent. The reaction was monitored by thin-layer chromatography using aluminium sheets with silica gel 60 F254 (Merck).
Experimental Procedure for the Synthesis ITHF
A mixture of 1,2,6,7-tetrahydro-8H-indeno[5,4-b]furan-8-one (8 mmol) and 1H-indole-3-carbaldehyde (10 mmol) was mixed in 5 mL ethanol taken in a conical flask. To this mixture 2 mL 20 % NaOH was added. The resulting alkaline mixture was stirred on a magnetic stirrer at room temperature until the formation of the desired product (checked by TLC). The crude product was transferred into a beaker containing crushed ice, stirred, acidified by dilute HCl filtered, dried naturally, and recrystallized using hot ethanol to furnish pure yellow solid (Scheme 1).
Scheme 1. Synthesis of ITHF molecule
The Gaussian 03 W programme was used to perform all calculations . DFT method with B3LYP functional was used for the theoretical simulations . The title compound's geometry optimization and corresponding energy were determined using a 6-311G(d,p) base set and C1 point group symmetry. As a result, the optimum geometrical parameters, energy, atomic charges, dipole moment, were theoretically determined. In light of the optimised structure, the Mulliken atomic charges, molecular electrostatic potential surface, electronic properties such as HOMO–LUMO energies, and dipole moment were also investigated.
The agar diffusion method was used to access the antimicrobial activities . Chloramphenicol was used as a standard for antibacterial evaluation and Amphotericin-B for antifungal screening. The antibacterial screening was performed against Escherichia coli, Proteus vulgaris, Staphylococcus aureus and Bacillus subtilis while the antifungal screening was performed against Aspergillus niger, and Candida albicans.
Results and Discussion
Spectral Analysis of ITHF
The 1H NMRspectrumpredicts the types and total number of hydrogen atoms in the molecule. There are total of ten types of protons in the title molecule and therefore has furnished ten signals in the 1H NMRspectrum. The NH group signal is located at 12.05 δ as broad singlet. The two proton present in benzene ring are ortho coupled with J = 7.1 Hz. All other signals are correctly matched with the structure of the ITHF molecule. The 13C NMRspectrumpredicts types of carbons atoms in the molecule and therefore one can anticipate the skeleton of the molecule. There are total of 20 types of carbons that have displayed 20 signals in the 13C NMRspectrum affirming the structure. The signal at 193.23 δ is due to the carbonyl carbon of ketone group.
Spectral Data of the ITHF
1H NMR (500 MHz, DMSO) δ 12.05 (s, 1H), 7.97 (m, 1H), 7.87 (d, J = 7.7 Hz, 1H), 7.84 (d, J = 2.1 Hz, 1H), 7.51 – 7.48 (m, 1H), 7.36 (d, J = 8.1 Hz, 1H), 7.24 – 7.20 (m, 1H), 7.08 (d, J = 8.1 Hz, 1H), 4.63 (t, J = 8.8 Hz, 2H), 3.91 – 3.87 (m, 2H), 3.46 (t, J = 8.8 Hz, 2H). 13C NMR (126 MHz, DMSO) δ 193.23, 160.35, 141.10, 136.58, 135.59, 130.95, 129.35, 127.95, 125.73, 124.92, 124.31, 123.07, 121.14, 118.63, 114.98, 112.67, 112.10, 72.34, 32.72, 28.42.
Molecular Structure Study
Figure 1 shows the optimised molecular structure of the title molecule. Figure 2 illustrates the geometrical viewpoints around various dimensions (A, B, and C Cartesian axes). The optimised molecular geometry reveals a lot about the spatial orientation of different atoms in a molecule. From optimized molecular structures, it tends to be handily observed that the ITHF molecule possesses C1 point group symmetry due to the overall asymmetry of the molecule. Moreover, it is additionally apparent that it contains a non-planar dihydrofuran ring.
Figure 1. Optimized molecular structure of ITHF molecule
Figure 2. Molecular structures of ITHF molecule along Cartesian axes
The non-planarity of dihydrofuran can be ascribed to the CH2 group (adjacent to an oxygen atom) which is either above or beneath the plane. It can likewise be seen that the remaining skeleton is in immaculate planar position and hence can have broadened conjugation. This data is a lot of value for the assurance of different spectroscopic elements. The optimized geometrical parameters bond lengths and bond angles are presented in Table 1 and Table 2respectively. The longest and the shortest aromatic (benzene ring) double bonds are C33-C37 (1.4072 Å) and C29-C37 (1.3869 Å) respectively. The C16-O20 bond length is 1.2207 Å and the C21-C22 is 1.3489 Å. The N35-H36 is 1.0064 Å C24-C28 is 1.452 Å, C24-C25 is 1.3864 Å, and C27-C28 is 1.4155 Å. Other bond length data are also having great agreement with the structure of the title compound.The bond angle of C2-C1-C6 is 118.5673°, N35-C27-C37 is 167.6792°, C25-N35-H36 is 124.8482°, C27-N35-H36 is 125.3017°, C27-C37-C29 is 61.6042°, and C27-C37-C33 is 59.6078°. Similar to bond lengths, bond angles are also in great agreement.
Table 1. Optimized bond length data of ITHF molecule by DFT/ B3LYP with 6-311G(d,p) basis set
Table 2.Optimized bond angle data of ITHF molecule by DFT/ B3LYP with 6-311G(d,p) basis set
Mulliken Charge Study
Mulliken nuclear charges are computed employing electron density. The charge distribution on molecules plays a crucial role in quantum mechanical computations for molecular structures. Figure 3 displays a pictorial representation of the ITHF molecule's Mulliken atomic charges as calculated by the DFT/B3LYP strategy with a 6-311G(d,p) base collection, which are tabulated in Table 3.According to Mulliken atomic charges, all hydrogen atoms have a net positive charge, but the H36 hydrogen atom, with an atomic charge of 0.231206, is extremely electropositive. This can be explained by the presence of a nitrogen atom. Of all carbon atoms, the C6 atom has the largest net positive charge (0.238011), while the C21 atom has the highest net negative charge (-0.223465).
Figure 3. Mulliken atomic charges of ITHF molecule
Table 3. Mulliken atomic charges of ITHF molecule
Molecular Electrostatic Surface Potential (MESP) Study
The MESP plot of ITHF is shown in Figure 4. The MESP guide can be used to relate any molecule's properties such as dipole moment, electronegativity, partial charges, and chemical reactivity. The molecular electrostatic potential is the total charge distribution of a molecule space. Different coloured areas reflect positive, negative, and neutral potentials. It can be shown that negative electrostatic potential occurs over oxygen atoms in this situation. The positive electrostatic potential, on the other hand, is located over two aromatic rings' hydrogen atoms. The zones with varying electrostatic potential are likely to provide important knowledge about multiple types of intermolecular interactions, allowing one to predict the molecule's chemical behaviour.
Figure 4. Molecular electrostatic surface potential of ITHF molecule
Frontier Molecular Orbital Study
The HOMO-LUMO analysis is often used to forecast the most receptive condition in -electron frameworks and to describe a few forms of conjugated mechanism responses [66-71]. A smaller HOMO-LUMO energy difference indicates a weaker molecule, while a large gap indicates a harder molecule. The knowledge about charge transfer within the molecule can be envisioned using the frontier molecular orbital (FMO) investigation. Figure 5 depicts the ITHF molecule's maximum inhabited molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO). The bioactive property of the molecule is based on the charge transfer phenomenon. The FMO thesis elucidates the molecule's reactivity, and the active site can be determined by the distribution of frontier orbitals. The HOMO and LUMO parameters are important in the analysis of quantum chemical parameters. The HOMO-LUMO analysis is often used to forecast the most receptive condition in electron frameworks and to describe a few forms of conjugated mechanism responses. A smaller HOMO-LUMO energy difference indicates a weaker molecule, while a large gap indicates a harder molecule. In ITHF, the HOMO-LUMO energy difference is 3.67 eV.
Figure 5. HOMO-LUMO pictures of ITHF molecule
Antimicrobial Screening Study
The antibacterial activity of the synthesised compound ITHF was examined on two Gram positive and two Gram negative bacteria, while the antifungal activity was tested on two fungal species. Table 4 summarises the findings of the antimicrobial evaluation. According to the observations, the ITHF is a mild antimicrobial agent against the strains examined. The findings have showed that ITHF is a more antibacterial than antifungal agent, with stronger antibacterial activity than antifungal activity. The ITHF has not been found to be successful against Staphylococcus aureus Gram strain among the strains examined. The ITHF compound has been identified to be a more effective antibacterial agent than an antifungal agent. The antimicrobial information provided here may indeed be a good approach for further antimicrobial agent research.
Table 4. Zone of inhibition shown by ITHF against four bacterial and two fungal agents
In summary, the present investigation covers the synthesis, antibacterial, antifungal, and computational aspects of (E)-7-((1H-indol-3-yl)methylene)-1,2,6,7-tetrahydro-8H-indeno[5,4-b]furan-8-one. The 1H NMR and 13C NMR spectral techniques were used to affirm the structure of the titled compound. The DFT examination used the Becke-3-Lee-Yang-Parr functional (B3LYP) level of theory at the 6-311G(d,p) basis set. The ITHF molecule has C1 point group symmetry. The optimized geometrical parameters bond lengths and bond angles are also described. All hydrogen atoms have a net positive charge, the C6 atom has the highest net positive charge and the C21 atom has the highest net negative charge in the titled compound. It can be seen from MESP that, negative electrostatic potential exists over oxygen atoms. The HOMO-LUMO energy gap in ITHF is 3.67 eV. The antimicrobial screening against bacterial and fungal strains revealed here that the ITHF compound is a more effective antibacterial agent than an antifungal agent.
The author acknowledges the central instrumentation facility (CIF), Savitribai Phule Pune University, Pune for the spectral analysis. The author is very much thankful to Prin. Dr. B.S. Jagdale for providing necessary research facilities. The author is grateful to Professor Dr. A. B. Sawant and Professor Dr. T.B. Pawar for the Gaussian study. Dr. Aapoorva P. Hiray Coordinator, M. G. Vidyamandir institute is gratefully acknowledged for the Gaussian package.
No potential conflict of interest was reported by the author.