Density Functional B3LYP Method Research Articles

Synthesis, crystal structure, DFT, vibrational properties, Hirshfeld surface and antitumor activity studies of a new compound 2-(2-chloro-6-(m-tolyl)imidazo[1,2-a]pyridin-3-yl)-N,N-diethylacetamide

Imidazo[1,2-a]pyridine derivatives are a kind of fused heterocyclic substances, which play an important role in the chemical field and have been proved to be the core fragments of various drug molecules. In this study, a new title compound was finally synthesized by cyclization, substitution, Suzuki coupling, hydrolysis and condensation. And the crystal of the title compound was obtained by single crystal culture. The structure of 2-(2-chloro-6-(m-tolyl)imidazo[1,2-a]pyridin-3-yl)-N,N-diethylacetamide was confirmed by 1H NMR, 13C NMR, FT-IR and single crystal X-ray diffraction. In addition, the title compound was theoretically calculated at the level of 6–311+G (2d, p) based on density functional method B3LYP, and the molecular structure optimized by DFT was consistent with the results obtained by X-ray diffraction. By calculating the Hirschfield surfaces and 2D fingerprints of molecules, the interactions between molecules can be visually revealed based on the size and color of the spots near the atoms. In addition, according to the characteristic vibration absorption band, the vibration of the title compound is reliably attributed. Furthermore, MEP, RDG, and ELF analyses were conducted to characterize the reaction sites susceptible to electrophilic and nucleophilic attacks. FMOs was used to evaluate the stability of the molecular structure. Finally, the results of the determination of biological activity showed that the compound exhibited significant inhibitory activity against HCT116 cancer cell.

DFT study, and natural bond orbital (NBO) population analysis of 2-(2-Hydroxyphenyl)-1-azaazulene tautomers and their mercapto analouges

Theoretical research on the keto-enol tautomerization of 2-(2-Hydroxyphenyl)-1-aza azulene (2HPhAZ) and its thiol-thione (2MPhAZ) analouge has been performed using the density functional B3LYP method with the 6–311 + + G(2d,2p) basis set in gas and ethanol phases. The findings of the MO computation on the energy scale and the prediction of the frontier molecular orbital (FMO) energies demonstrate that the tautomeric structures exist in a static mixture in the ground state, with the enol and thiol structure being more stable than the keto and thione structures in gas phase. The ethanol solvent causes some reordering of the relative stability of 2HPhAZ and 2MPhAZ conformers. The geometries created at the B3LYP/6–311 + + G(2d,2p) level of theory were used for NBO analysis. In the tautomerization of 2HPhAZ and its mercapto analogue 2-(2-Mercaptophenyl)-1-azaazulene (2MPhAZ), it has been found that the O(S)-C sigma bond is weak due to nO(S)—> σ*C25-O26(S26) and nO(S)—> σ*C15-N16 delocalization. It is also noted that the resulting p character of the corresponding oxygen (sulfur) natural hybrid orbital (NHO) of σO(S)-C bond orbital is related to the decreased occupancy of the localized σO(S)-C orbital in the idealized Lewis structure or the increased occupancy of σ*O(S)-C of the non-Lewis orbital and their subsequent impact on molecular stability and geometry (bond lengths) in gas phase and ethanol. Additionally, the energy of charge transfer decreases as the potential rotamers' Hammett constants (R1–R3 for O(S) atoms) increase. The partial charge distribution on the skeleton atoms demonstrates that the intra- and intermolecular interactions can be significantly influenced by the electrostatic attraction or repulsion between atoms. Lastly, the currently applied NBO-based HB strength indicator enables a fair prediction of the frequency of the proton donor NH stretching mode, but this simple picture is hidden by abundant hype conjugative effects.

Density functional theory/time-dependent density functional theory investigations on the color-structure relationship of biopigment molecules

The study of molecular derivatives of biological dyes is of great importance for the green transformation of the printing, dyeing, and textile industries. In this study, B3LYP density functional methods are used to optimize the geometric configuration of the selected molecules and to explore the relationship between the structure and color of biological dye molecules and their color mechanism. This study focuses on the analysis of polyenes, quinones, indoles, and azide biological dyes in colors commonly used in the textile industry: blue, yellow, purple, red, green, and so on. Quantum chemical investigations show that the conjugate structure of a biological dye is directly related to its color and that the group or structure affecting the conjugate structure will in many cases cause a change in color. In addition, time-dependent density functional theory spectral calculations with the CAM-B3LYP functional for UV-Vis spectra show that in the visible band, the color of the remaining band after subtracting the absorption wavelengths was exactly the same as the color of the pigment. These results indicate that the color of the pigment is exactly complementary to the light absorption color of the material. Our study provides theoretical guidance for the design of molecular derivatives of biological dyes and is expected to promote the green transformation of the textile, printing, and dyeing industries to a certain extent.

Exploration of 4-Chloro-3-nitrocoumarin: Spectroscopic Analysis, DFT Insights, Molecular Docking, Assessments of Antibacterial and In Vitro Anticancer Activities as a Potent Bioactive Agent

The detailed theoretical and experimental (FT-IR, FT-Raman, UV-visible) spectroscopy analyses of the 4-Chloro-3-nitrocoumarin (CNC) molecule were carried out. The CNC compound's pharmacological properties were also investigated utilizing antibacterial and anticancer activity investigations. Initially, the CNC molecule was optimized by the density functional theory B3LYP method with a cc-pVTZ basis set using the Gaussian 09W program. The optimized molecular structure provides the harmonic vibrational frequencies of the CNC molecule. The observed and computed vibrational wavenumbers were assigned and found to be well correlated. UV-Vis absorption spectrum analysis indicates that the molecule contains π→π* electronic transition. Frontier molecular orbitals (FMOs) analysis indicates that the LUMO of CNC molecule is mainly located over the nitro group, it indicates that the nitro group is particularly prone to accepting electrons from other molecules and participate in chemical reactions where acts as an electrophile. Mulliken atomic charge distribution analysis further confirms the FMOs results. The antibacterial test results validate that the CNC molecule exhibits a stronger inhibitory effect on Staphylococcus aureus compared to the other tested bacteria. In vitro anticancer cytotoxicity analysis clearly evidences that the CNC compound inhibits the growth of HeLa cervical cancer cell lines more than A549 lung cancer cell lines. In silico molecular docking study further validates that the CNC molecule inhibits the function of the p38a Mitogen-activated protein kinase 14, which has been associated with cervical cancer. As a result, the present study paves the way for the development of new drugs to treat cervical cancer.
 Keywords: 4-Chloro-3-nitrocoumarin; DFT; FT-IR; FT-Raman; Anticancer; Molecular docking; Cervical cancer drug.

Spectroscopic Characterization, Quantum Chemical, Molecular Docking, Antibacterial and Anticancer Studies on Ethyl Coumarin-3-Carboxylate: an Antibacterial and Lung Cancer Agent

The detailed theoretical and experimental (FT-IR, FT-Raman, UV-visible) spectroscopy analyses of the Ethyl Coumarin-3-Carboxylate (ECC) molecule were carried out. The ECC compound’s pharmacological properties were also investigated, utilizing antibacterial and anticancer activity investigations. Initially, the ECC molecule was optimized by the density functional theory B3LYP method with a 6-311 G++ (d,p) basis set using the Gaussian 09 W program. The optimized molecular structure provides the harmonic vibrational frequencies of the ECC molecule. The observed and computed vibrational wavenumbers were assigned and found to be well correlated. UV-Vis absorption spectrum analysis indicates that the molecule contains π →π* and n → π* electronic transitions. The Frontier molecular orbital analysis confirmed the molecular reactivity and bioactivity of ECC, while the Mulliken atomic charge distribution analysis pinpointed the molecule’s reactive sites. Antibacterial testing demonstrated the ECC compound’s inhibitory effect on various bacterial strains, with a particular impact on Klebsiella pneumonia. In vitro, anticancer assessments showcased ECC's stronger inhibitory effects on A549 lung cancer cell lines compared to HeLa cervical cancer cell lines. Additionally, in silico molecular docking investigations provided further validation that the ECC compound can inhibit the function of the epidermal growth factor receptor, a factor associated with lung cancer. As a result, this study lays the foundation for the development of novel drugs for lung cancer treatment.

Novel Thiazolactone Derivatives: Synthesis and Quantum Chemical Study

In this research, 15 novel derivatives of the thiazolactone skeleton were synthesized using the Erlenmeyer–Plöchl reaction procedure. Glycine, alanine and leucine amino acids were used to make dithiocarbamate precursor by reacting amino acids with carbon disulfide and benzyl chloride. Obtained benzyl dithiocarbamate underwent thiazolactone formation in the presence of acetic anhydride and then condensed with arylglyoxals as condensing carbonyl group source. Products were characterized using their spectroscopic IR, 1H NMR, and 13C NMR data. In continuation, computational chemistry methods were used to get some information about the products such as structural characteristics, charge distribution, 1H NMR and UV-visible spectra. Results showed that the calculated chemical shifts are in good agreement with experimentally recorded ones. The B3LYP density functional method in conjunction with the 6-311++G(d,p) basis set was used for all calculations.

Comprehensive understanding of Methyl 2-Naphthyl Ether Molecule by Ab Initio Calculation method

The development of the geometrical structure and vibrational wave numbers of Methyl 2-Naphthyl Ether molecule (M2NE) are done with the help of ab initio HF- and Density functional method (DFT/B3LYP) of 6-31G(d, p) basis set. HF and DFT calculations optimize the geometric structure of the selected molecule. The B3LYP density functional method, with a base of 6-31G (d, p), is the best level of theory to repeat the expected wave numbers. Density functional theory was used to calculate the first hyperpolarization (β), electrical dipole moment (μ) of the examined molecule. The results of the calculations also show that a natural bond orbital (NBO) analysis of the M2NE could be performed. The FT-IR and FT-Raman spectrum were theoretically constructed for the title compound. There was a detailed understanding of FTIR and FT-Raman spectrum from experimental analysis. The considered HOMO and LUMO energies demonstrate that charge transfer takes place inside the molecule.

Experimental spectroscopy, eco-friendly solvents effect on transitions, reactive sites and biological research on methyl gallate – MTT assay (cytotoxicity)

In this research, a Phytochemical Compound Methyl gallate was characterized experimentally and theoretically using spectroscopy profiling. Density functional theory B3LYP method with 6–311++G (d, p) basis set was used to depict the most stable molecular geometry of the title compound. The calculated vibrational wavenumbers were equated to the measured frequency, revealing measured and computed frequencies agree with each other well. Electronic properties of various environmentally friendly solvents water, DMSO, acetone, ethanol were evaluated using TD-DFT from UV–visible spectrum. According to the computed HOMO-LUMO band gap energy, charge transfer takes place inside the molecule. From MEP map electrophilic and nucleophilic regions of Methyl gallate was found. Stability of the molecule was investigated using natural bond orbital analysis. To find the bonding zones and weakest interactions in Methyl gallate, topological research ELF, LOL, and RDG studies, were carried out using Multiwfn 3.7. Non-linear optical behavior was also analyzed and compared with standard prototype substance urea. NMR spectroscopy 13C and 1H of the title compound was also computed. In addition, to examine biological activity of Methyl gallate, drug likeness, Ramachandran plot, molecular docking was done. Molecular docking of Methyl gallate with 5gks (Systemic Lupus Erythematosus) and 2bxk (anti-inflammatory) proteins was performed and lowest binding energy was obtained. Since it has low binding affinity with both proteins it may be potentially used in treating Systemic Lupus Erythematosus and anti-inflammatory diseases. In-vitro assays such as cytotoxicity and anti-inflammatory were carried out, and the results are highly biocompatible.

Synthesis and experimental/theoretical evaluation of an efficient Calix[4]arene based sensor for selective detection of Pt2+ ion

In this study, a novel derivative of functionalised Calix[4]arene chem-sensor (4-amino thiazole 2-thiol-Calix[4]arene (R-Sensor)) was investigated, using the FT-IR spectroscopic method. Fluorescent properties and the ability to detect the sensor toward different cation ions in acetonitrile aqueous solution were investigated using the UV–Vis method, fluorescence titration, and Job’s plot method. The results showed that among the studied cations, the presence of Pt(II) has a greater effect on the intensity and wavelength of the emission. In addition, the optimised structure and electronic properties of this R-sensor was studied, using the density functional theory (DFT), B3LYP and M062X methods, at the LANL2DZ (6-311 + G/CPCM and 6-311++G/CPCM) basis set, and quantum theory of atoms in molecules (QTAIM). The results of these theoretical-computational studies showed that the selectivity of this sensor is related to its molecular structure, electronic properties, and surface electrostatic properties. Theoretical studies have shown that electronic properties such as energy gap, sensitivity, and charge/energy transfer change dramatically in the presence of Pt(II) cations. In addition, the molecular competitive tests showed that this R-sensor could be a good candidate for monitoring/measuring Pt(II) in physiological samples/ environments.

NON-LINEAR OPTICAL PROPERTIES STUDY OF TWO HETEROCYCLIC COMPOUNDS

In an attempt towards understanding the relation between molecular structure-nonlinear optic activity (NLO) among heterocycles, with special reference to the identity, number and position of the heteroatom, semiempirical calculations were carried out. This paper reports the Non-linear optical properties of two heterocyclic compounds namely 3-[2-Oxo-2-(2-oxo-2H-chromen-3-yl)-ethylidene]-1,3-dihydro-indol-2-one (3OCEDI) and Quinolin-8-ol (QL). To understand the Non-Linear Optical properties of coumarin dyes we computed dipole moment (μ), electronic polarizability (α), and the mean was first hyperpolarizability (βo) using B3LYP density functional theory method in conjunction with 6-31G(d, p) basis set.All the calculations were carried out in gas phase and in acetonitrile medium. The optimized geometry of both compounds shows a 3D helical structure. The results indicate that given the same number and type of atoms and double bonds in a molecule, linear conjugation excels over cyclic or crossed conjugation in enhancing hyperpolarizabilities and it seems to be far more critical than a chiral centre.

Predicting Reaction Mechanisms for the Threonine-Residue Stereoinversion Catalyzed by a Dihydrogen Phosphate Ion.

The stereoinversion of amino acid residues in proteins is considered to trigger various age-related diseases. Serine (Ser) residues are relatively prone to stereoinversion. It is assumed that threonine (Thr) residues also undergo stereoinversion, which results in the formation of the d-allo-Thr residue, by the same mechanisms as those for Ser-residue stereoinversion; however, d-allo-Thr residues have not been detected in vivo. To date, although Ser-residue stereoinversion has been suggested to progress via enolization, plausible reaction mechanisms for Thr-residue stereoinversion have not been proposed. In this study, we investigated the pathway of Thr-residue enolization and successfully identified the three types of plausible reaction pathways of Thr-residue stereoinversion catalyzed by a dihydrogen phosphate ion. The geometries of reactant complexes, transition states, and enolized product complexes were optimized using B3LYP density functional methods, and single-point calculations were performed for all optimized geometries using Møller–Plesset perturbation theory to obtain reliable energies. As a result, the calculated activation energies of Thr-residue stereoinversion were 105–106 kJ mol–1, which were comparable with those of Ser-residue stereoinversion reported previously. The infrequency of Thr-residue stereoinversion may be due to other factors, such as the hydrophobicity and/or the steric hindrance of the γ-methyl group, rather than the high activation energies.

Quantum Density Functional Theory Studies on Additive Hydration of Tuftsin Tetrapeptide

Density functional B3LYP method has been used to study the molecular properties of the tuftsin tetrapeptide (threonine-lysine-proline-arginine) and its retro form (arginine-proline-lysine-threonine). The influence of single water molecule on the conformations and relative stabilities of solvated tuftsin complexes has been studied by placing the water molecule at the individual amino acid residues of both the tuftsin complexes. The contribution of four water molecules to the system energetics of tuftsin complexes has also been analyzed. The conformational changes occurred in the solvated tuftsin complexes have been explored through their dihedral angles. The tuftsin is found to be sensitive to structural changes, and our results indicate that water-tuftsin hydrogen bonds (H-bonds), in addition to intramolecular H-bonds, stabilize the β-turn structure with H-bonds between threonine and arginine residues of tuftsin. Difference in the stability of the hydrated complexes is confined to the amino acid residues at which the water molecule is attached to tuftsin. The interaction energy calculations have been used to investigate the strength of the intermolecular H-bond interactions. The AIM theory and NBO analysis were employed to survey the H-bonding patterns in hydrated tuftsin complexes. The maximum ellipticity value (0.129) is noted for the Cα-H (Arg)…O (W) interaction in Tuftsin…4W complex which indicates the higher chance of structural deformation under external perturbations. The interactions between oxygen lone pairs in water and C-H antibond orbitals of tuftsin and retro tuftsin complexes exist withE2in the range of 4.03-5.7 and 3.59-4.14 kcal/mol, respectively.

Fully bio-based furyl-functionalized bisphenols and bio-based cross-linking poly(aryl ether ketone)s with high biomass content, thermo-reversibility, excellent processing and mechanical properties

Poly(aryl ether ketone)s (PAEKs) exhibit excellent thermal and mechanical properties, but their poor processability limit further application. In this regard, a bio-based cross-linking high-performance PAEK was prepared through the Diels-Alder (DA) reaction between furyl-functionalized PAEK and N,N'-4,4′-diphenylmethylene-bismaleimide (BMI). First, two novel fully bio-based furyl-functionalized bisphenols, BPF-M and BPF-AM, were prepared by simple one-step aromatic substitution of two bio-based o‑methoxy-phenols and furfural. Orbital interaction of the DA reactions between the two bisphenols and BMI was investigated with B3LYP density functional method, and the quantitative study was performed with DSC and 1H NMR. Next, a series of PAEKs (LINKERs) with high biomass content of 58.7–72.8% were prepared with BPF-M, 2,5-bis(4-flurobenzoly)furan (BFBF) and 6-(4hydroxy-3-methoxyphenyl)pyridazin-3(2H)-one (GSPZ). LINKERs had excellent thermal properties (Tg = 182–212 °C, Td10% = 415–452 °C), processing properties (lowest rheology viscosities = 178–3217 Pa·s) and solution processability. Finally, PAEK themo-reversible gel and cross-linking film were prepared through the DA reaction between LINKER-73 and BMI. The film had solvent resistance and high tensile strength, which increased from 75 MPa to 101 MPa compared to the uncrosslinked one. Besides, LINKERs gained the ability of reprocessing and recycled via DA and r-DA reactions. We expect to provide important theoretical and practical references on bio-based furyl-functionalized bisphenols and high-performance PAEKs.

Benchmark Study of Redox Potential Calculations for Iron-Sulfur Clusters in Proteins.

Redox potentials have been calculated for 12 different iron–sulfur sites of 6 different types with 1–4 iron ions. Structures were optimized with combined quantum mechanical and molecular mechanical (QM/MM) methods, and the redox potentials were calculated using the QM/MM energies, single-point QM methods in a continuum solvent or by QM/MM thermodynamic cycle perturbations. We show that the best results are obtained with a large QM system (∼300 atoms, but a smaller QM system, ∼150 atoms, can be used for the QM/MM geometry optimization) and a large value of the dielectric constant (80). For absolute redox potentials, the B3LYP density functional method gives better results than TPSS, and the results are improved with a larger basis set. However, for relative redox potentials, the opposite is true. The results are insensitive to the force field (charges of the surroundings) used for the QM/MM calculations or whether the protein and solvent outside the QM system are relaxed or kept fixed at the crystal structure. With the best approach for relative potentials, mean absolute and maximum deviations of 0.17 and 0.44 V, respectively, are obtained after removing a systematic error of −0.55 V. Such an approach can be used to identify the correct oxidation states involved in a certain redox reaction.

Investigation of the Molecular Structures, Electronic Properties and Vibrational Spectrum of Trifluoroacetophenone Using Density Functional Theory

Trifluroacetophenone is considered a highly efficient, inexpensive, and green organocatalyst that is used in organic synthesis. Geometry optimization, electronic properties, and frequency calculations of 2,2,2-trifluoroacetophenone are performed using the B3LYP density functional theory method and the 6-311++G(d, p) basis set. The geometrical parameters, frontier molecular orbitals, molecular electrostatic potential surface, and simulated infrared spectrum are reported. The structural parameters are compared with available X-ray diffraction experimental values, and the calculated electronic properties are compared with those of its structural analogue, acetophenone.

Design of new visible light Pt photocatalyst based on the TDDFT study of properties of transition metal complexes

AbstractVisible light photocatalysis has been paid a lot of attention because of its green and lower energy consuming. To trigger a reaction via energy transfer, a potential visible light photocatalyst not only has absorption under visible light but also needs a high triplet excitation energy. In this scene, the density functional theory B3LYP methods were used to investigate the properties of transition metal complex photocatalysts and design new potential visible light photocatalysts. The calculation result shows that the studied Ir complexes have a relatively high ET values (energy gap between the triplet excited state and ground state). The introduction of electron‐donating groups to Ir complexes causes a slight redshift in the absorption spectrum. Moreover, the electronic structure and atomic radius of the central metal atom have a great influence on the properties of those complexes of “fac‐M(ppy)3” (transition metal complexes with facial structure and three ppy ligands, M = Pt, Ni, Rh, Ru, Fe). Based on the study of transition metal complexes, new visible light Pt complex photocatalysts that have both good absorption under visible light and high ET value have been designed here. The designed new Pt complexes are expected to be potential candidates as visible light photocatalysts.

Ion mobility spectrometry of <i>N</i>-methylimidazole and possibilities of its determination

Objectives. To determine the ion mobility of N-methylimidazole, establish the structure of ions corresponding to characteristic signals, and determine the detection limit of N-methylimidazole on the ion-drift detector Kerber.Methods. Ion mobility spectrometry was used to study the ionization processes. The enthalpies of the reactions of monomer and dimer ions were calculated in the ORCA 4.1.1 software by the B3LYP density functional method with a set of basic functions 6-31G (d, p).Results. The drift time and ion mobility values of N-methylimidazole were determined. A method for mathematical processing of spectra and a program for its implementation was developed. The changing peculiarities of the ion mobility spectrum during measurement at a given time were studied. According to the interpretation of the spectrum signals, the structure of the generated ions was proposed, and the enthalpies of ion formation were determined.Conclusions. The characteristic signal of the N-methylimidazole ion protonated at the nitrogen atom of the pyridine type was revealed. It was found that two signals in the ion mobility spectra of N-methylimidazole correspond to the presence of the monomer and dimer ions. The detection limit of N-methylimidazole on the ion-drift detector Kerber was determined, amounting to 3 pg.

M(BO)k+1- Anions: Novel Superhalogens Based on Boronyl Ligands.

Superhalogens have been a subject of continuous attraction in the last four decades due to their unusual structures and interesting applications. In the quest for new superhalogens based on boronyl (BO) ligands, we investigate M(BO)k+1- anions using a high-level ab initio CCSD(T) and B3LYP density functional method for M = Li, Na, K, Be, Mg, Ca, B, and Al. Their structures are linear for M = Li, Na, K; trigonal planar for M = Be, Mg, Ca; and tetrahedral for M = B, Al. These anions are energetically and thermodynamically stable against various fragmentations. Their superhalogen property has been established due to their higher vertical detachment energy (VDE) than halogen, being in the range 4.44-7.81 eV. For a given k, the stability and VDE of M(BO)k+1- anions decrease with an increase in the size of M, which is due to the decrease in charge delocalization on BO moieties. There exists a linear correlation between frontier orbitals energy gap and VDE with coefficient R2 = 0.93888. It was also noticed that the BO ligand, due to the lower dimerization energy, can be preferably used as an inorganic analogue of CN. However, the structural relaxation in BO-based neutral species significantly affect the VDE and, hence, their superhalogen nature. We believe that these findings should be interesting for researchers working in superatomic chemistry as well as in boron chemistry.

Application of Polarisable Continuum Modelling to assess Minoxidil solubility in mixed solvents

ABSTRACT Experimental solubility of minoxidil was obtained in binary aqueous mixtures of ethanol, methanol and acetonitrile at 298.2 K. The effects of pH and micellisation were investigated on the solubility of the drug. Experimental solubility data was correlated by three co-solvency models, i.e. Yalkowsky, CNIBS/R-K, and the modified Wilson model. Density functional theory and hybrid functional B3LYP method was used with Polarisable Continuum Model (PCM) to correlate the experimental solubility data in various mass fractions of the binary solvent mixtures. We report the results of solute–solvent interaction energy as free energy of solvation (∆G sol ) of minoxidil in various mass fractions of ethanol + water mixtures. Total electrostatic energy, dipole moment, total Gibbs free energy and dielectric constant (ε) of minoxidil were also investigated.

Conformational analysis, molecular structure, spectroscopic, NBO, reactivity descriptors, wavefunction and molecular docking investigations of 5,6-dimethoxy-1-indanone: A potential anti Alzheimer's agent

The objective of the present study is focused to elucidate the structure of potential anti-Alzheimer's compound 5,6-Dimethoxy-1-indanone (5,6-DMI) and study its binding interaction towards the active site by molecular docking studies. The structural and various spectroscopic tools are used to understand the various interaction behaviors of the title compound. The theoretical calculation of 5,6-DMI molecule is computed by Gaussian 09W software with Density functional B3LYP and CAM-B3LYP method utilizing 6-311G(d,p) as basis set. The Natural Bond Orbital (NBO) analysis has been performed to find all possible transition was correlate with electronic transition. The Non covalent interaction of 5,6-DMI molecule was examined by adopt Reduced Density Gradient (RDG) analysis and colour filled ELF diagram. Molecular docking results suggest that 5,6-DMI may exhibit inhibitory activity against apoE protein and may act as potential against Alzheimer's disease.