Experimental NMR Chemical Shifts Research Articles

1H, 13C, 15N NMR, and DFT Studies on Complex Formation of Zinc(II) Ion with Ethylenediamine in Ionic Liquid [C2mIm][TFSA

In bis(trifluoromethylsulfonyl)amide (TFSA-)-based ionic liquid (IL), 1-ethyl-3-methylimidazolium TFSA- ([C2mIm][TFSA]), the complex formation equilibria of zinc(II) ion (Zn2+) with ethylenediamine (EN) have been investigated. An EN molecule may coordinate with Zn2+ as a bidentate ligand. First, the formation of Zn2+-EN complexes in [C2mIm][TFSA] was confirmed from the difference of 1H and 13C NMR chemical shift values of EN molecules between [C2mIm][TFSA]-EN binary solvents and the 0.1 mol dm-3 Zn(TFSA)2/[C2mIm][TFSA]-EN solutions as a function of EN mole fraction xEN. Second, the stability constants of Zn2+-EN complexes formed in the IL were determined from the concentration ratio [EN]/[Zn2+] dependence of 15N NMR chemical shift values of the TFSA- N atom in the Zn2+/IL-EN solutions. In the IL, mono-, bis-, and tris-EN complexes are successively formed by 1:1 replacement of TFSA- anions coordinated with Zn2+ by EN molecules with increasing EN content. Third, 1H and 13C NMR measurements with the help of density functional theory (DFT) calculations were made on [C2mIm][TFSA]-EN binary solvents as a function of xEN to clarify key interactions to the mechanism of the complex formation. Fourth, the stability constants of Zn2+-EN complexes in the IL were compared with those in aqueous solutions. It was suggested that the hydrogen bonding of the EN molecule with the imidazolium ring H atoms and the TFSA- O atoms reduces the stability of the mono-EN complex in the IL. In contrast, the intracomplex hydrogen bonds between EN and TFSA- in the first coordination shell contribute to the higher stability of the bis-EN complex in the IL than that in aqueous solutions. The difference in the stability constants between the tris-EN complexes and hexaacetonitrile complexes, where acetonitrile (AN) molecules act as monodentate ligands, was interpreted in terms of the higher electron donicity of EN. Finally, to verify the present evaluation, the experimental 13C NMR chemical shift values of EN molecules in the solutions were compared with the theoretical values calculated by DFT using the stability constants determined.

Synthesis, QTAIM, anticancer activity analysis of pyrrole-imidazole/benzimidazole derivatives and investigation of their reactivity properties using DFT calculations and molecular docking

As part of our ongoing investigation into pyrrole derivatives, we here present the synthesis, spectroscopic characterization, QTAIM, reactivity, anticancer activity, and comparative experimental and computational analysis of pyrrole-imidazole ((3l), (3p)) and benzimidazole derivatives ((3h), (3i), (3j), (3k), (3m), (3n), (3o)). All synthesized compounds (3h-3p) have been well characterized by spectroscopic techniques (FT-IR, 1H and 13C NMR, Mass spectrometry). The experimental 1H and 13C NMR chemical shift values of synthesized pyrrole-imidazole (3l, 3p) and benzimidazole (3h-3o) derivatives have been well corroborated with computed chemical shifts. The vibrational analysis for four derivatives of pyrrole-benzimidazole (3m), (3n), (3o), and pyrrole-imidazole (3p) has the suitability for dimer formation in solid state by intermolecular heteronuclear hydrogen bonding (N–H···O) and the interaction energy of dimers are calculated to be 10.88, 11.70, 9.89 and 10.72 kcal/mol, using DFT. After basis-set superposition error (BSSE) correction, the interaction energies of dimers were found to be 11.12, 12.11, 10.13, and 11.52 kcal/mol. Estimated intermolecular H-bond in (3m-3n) compounds were found to be -13.38, -12.86, -11.02, and -11.28 kJ/mol using QTAIM. All the synthetic pyrrole-imidazole (3l, 3p) and benzimidazole (3h-3o) derivatives exhibit strong antileukemia activity in vitro against the proliferative cell line L1210 leukemia cells. A dataset of investigated compounds was subjected for molecular modelling simulation against three distinct proteins (SYK, PI3K, and BTK), which was found to be highly implicated in the favourable interaction between the compounds and their target proteins in every instance. The synthesized pyrrole-imidazole (3l, 3p) and benzimidazole (3h-3o) derivatives shown favourable interactions with their target proteins, with high activity and binding free energy values falling between 15.22 and 13.43 and -7.4 and -9.8 kcal/mol, respectively. The structure of pyrrole-imidazole (3l, 3p) and benzimidazole (3h-3o) derivatives is thoroughly examined, and several parameters are proposed here to improve their anticancer activity.

Predicted and Experimental NMR Chemical Shifts at Variable Temperatures: The Effect of Protein Conformational Dynamics.

NMR chemical shifts provide a sensitive probe of protein structure and dynamics but remain challenging to predict and interpret. We examine the effect of protein conformational distributions on 15N chemical shifts for dihydrofolate reductase (DHFR), comparing QM/MM predicted shifts with experimental shifts in solution as well as frozen distributions. Representative snapshots from MD trajectories exhibit variation in predicted 15N chemical shifts of up to 25 ppm. The average over the fluctuations is in significantly better agreement with room temperature solution experimental values than the prediction for any single optimal conformations. Meanwhile, solid-state NMR (SSNMR) measurements of frozen solutions at 105 K exhibit broad lines whose widths agree well with the widths of distributions of predicted shifts for samples from the trajectory. The backbone torsion angle ψi-1 varies over 60° on the picosecond time scale, compensated by φi. These fluctuations can explain much of the shift variation.

The Scope of the Applicability of Non-relativistic DFT Calculations of NMR Chemical Shifts in Pyridine-Metal Complexes for Applied Applications.

Heavy metals are toxic, but it is impossible to stop using them. Considering the variety of molecular systems in which they can be present, the multicomponent nature and disorder of the structure of such systems, one of the most effective methods for studying them is NMR spectroscopy. This determines the need to calculate NMR chemical shifts for expected model systems. For elements beyond the third row of the periodic table, corrections for relativistic effects are necessary when calculating NMR parameters. Such corrections may be necessary even for light atoms due to the shielding effect of a neighboring heavy atom. This work examines the extent to which non-relativistic DFT calculations are able to reproduce experimental 15N and 113Cd NMR chemical shift tensors in pyridine-metal coordination complexes. It is shown that while for the calculation of 15N NMR chemical shift tensors there is no real need to consider relativistic corrections, for 113Cd, on the contrary, none of the tested calculation methods could reproduce the experimentally obtained tensor to any extent correctly.

Stereochemical and NMR computational study of some natural dimeric bisindole alkaloids

AbstractThe initial conformational search followed by the optimization of geometric parameters and high‐level calculation of 1H and 13C NMR chemical shifts were carried out for 12 bisindole alkaloids of the Corynanthe‐Strychnos series. Configurational assignments of all compounds from this series were performed based on the correlation of calculated and experimental NMR chemical shifts. For some alkaloids, the reassignment of the individual resonances together with spectral assignment of experimentally unresolved signals were suggested.

Computation of 31P NMR chemical shifts in Keggin-based lacunary polyoxotungstates.

Density Functional Theory (DFT) calculations were employed to systematically study the accuracy of various exchange-correlation functionals in reproducing experimental 31P NMR chemical shifts, δExp(31P) for Keggin, [PW12O40]3- and corresponding lacunary clusters: [PW11O39]7-, [A-PW9O34]9-, and [B-PW9O34]9-. Initially, computed chemical shifts, δCalc(31P) were obtained with without neutralising their charge in which associated error, δError(31P), decreased as a function of Hartree-Fock (HF) exchange, attributed to constriction of the P-O tetrahedron. By comparison, δCalc(31P) performed with explicitly located counterions to render the system charge neutral, reduced discrepancies, δError(31P) by 1-2 ppm. However, uncertainties in δCalc(31P) remain, particularly for [B-PW9O34]9- anions attributed to direct electrostatic interactions between the counterions and the central tetrahedron. Optimal results were achieved using the PBE/TZP//PBE0/TZP method, achieving a mean absolute error (MAE) and a mean squared error (MSE) of 4.03 ppm. Our results emphasize that understanding the nature of the electrolyte and solvent environment is essential to obtaining reasonable agreement between theoretical and experimental results.

Synthesis, characterization, DFT, vibrational analysis (FT-IR and FT-Raman), topology and molecular docking studies of 3,3′-((1E,1′E)-((sulfonylbis(4,1-phenylene)) bis (azaneylylidene)) bis (methaneylylidene)) diphenol

The 3,3′-((1E,1′E)-((sulfonylbis(4,1-phenylene)) bis (azaneylylidene)) bis (methaneylylidene)) diphenol (D3H) was characterized by experimental and theoretical approaches. Titled compound FT-IR, FT-Raman, NMR (1H), UV–vis and fluorescence spectral analysis were developed in experimentally. After that, theoretical computations at the DFT/WB97XD/cc-pVDZ basis set level were carried out. The experimental geometrical parameters and the theoretical geometrical parameters were compared and well matched. The frequencies calculated using FT-Raman and FT-IR matched those obtained from experiments. The potential energy distributions analysis was calculated. Comparisons were made between the theoretical and experimental NMR chemical shifts. Absorption wavelengths in the UV–Vis spectrum were measured experimentally and compared to those predicted by TD-DFT. It is optical material, because its showed good fluorescence spectrum. The frontier molecular orbital, natural bond orbital analysis, molecular electrostatic potential, electron localized function, reduced density gradient and localized orbital locator, were carried out and thoroughly explained. According on the results of docking tests, the greatest possible binding energy score is -7.52 kcal/mol.

Quantum-Chemical Simulation of 13C NMR Chemical Shifts of Fullerene C60 Exo-Derivatives

The 13C NMR chemical shifts of fullerene C60 exo-derivatives were calculated using quantum chemical hybrid functionals combined with Pople, Dunning correlation-consistent, and def2-TZVP split valence basis sets taking into account the solvent effect (polarizable continuum model). A relationship between theoretical and experimental 13C NMR chemical shifts (CSs) is assessed quantitatively to select a functional/basis set combination. It is found that the CAM-B3LYP/6-31G and M06L/6-31G combinations have the best convergence with experimental data in modeling the 13С NMR CSs of sp3 fullerene carbon atoms in С60 derivatives, whereas X3LYP/6-31G and CAM-B3LYP/6-31G(d) in modeling the 13С NMR CSs of their sp2 fullerene carbon atoms.

Assessment of the Commercially Available Chemical Space for Using in the 19F NMR FAXS Method: a Enamine Ltd. Case

Aim. To analyze commercially available fluorine containing compounds for the possibility of their use in the 19F NMR FAXS method.Materials and methods. The selection of fluorine-containing fragments for the study was performed using 3.9 million instock screening compounds and 248,000 in-stock building-blocks from Enamine Ltd library. The selection and classification of the compounds was carried out using the DataWarrior and KNIME software. The Fluorinated Fragments library of Enamine Ltd. containing 6377 compounds, was also analyzed. To analyze the abovementioned sets of substances, the multistep workflows specially designed were used.Results and discussion. As a result of applying the workflow developed to the compound sets (both screening compounds and building blocks), 13 800 compounds were selected and further classified according to the presence of one out of 12 fluorine-containing groups. The Fluorinated Fragments library was also subjected to a similar workflow. For the latter, 8 out of 12 fluorine-containing groups were identified. Additionally, experimental 19F NMR chemical shift values for Fluorinated Fragments library compounds spectra were analyzed. It has been found that some structural classes have areas of chemical shifts intersection. On the other hand, the ranges from –40 to –60 ppm and beyond –160 ppm are free from any group of compounds from the library analyzed.Conclusions. The analysis has shown that commercially available fluorine-containing fragments do not satisfy the needs of the 19F NMR FAXS method, and further expansion of the chemical space of fluorine-containing compounds by increasing their diversity is required.

Experimentally Established 15N NMR Absolute Shielding Scale for Theoretical Calculations.

The nitrogen atom of 2,6-di-tert-butyl-N,N-diethylpyridin-4-amine (DEAP) is not available for non-covalent interactions. This molecule has been used to define the reference 15N NMR absolute chemical shielding (σref) required to convert between the chemical shift scale used in experiments and the absolute shielding scale used in theoretical calculations. The accuracy of the obtained σref was tested for solid samples of acetanilide-15N, the protonated homodimer of pyridine-15N, and poly(4-vinylpyridine-15N). Experimental 15N NMR chemical shift tensors were compared to 15N NMR shielding tensors calculated using the TPSSh, B3LYP, and ωB97XD functionals and the polarizable continuum model approximation. General recommendations are given for the smallest reliable basis set size. The reported structure of DEAP can be used to calculate σref for any other calculation method.

DELTA50: A Highly Accurate Database of Experimental 1H and 13C NMR Chemical Shifts Applied to DFT Benchmarking

Density functional theory (DFT) benchmark studies of 1H and 13C NMR chemical shifts often yield differing conclusions, likely due to non-optimal test molecules and non-standardized data acquisition. To address this issue, we carefully selected and measured 1H and 13C NMR chemical shifts for 50 structurally diverse small organic molecules containing atoms from only the first two rows of the periodic table. Our NMR dataset, DELTA50, was used to calculate linear scaling factors and to evaluate the accuracy of 73 density functionals, 40 basis sets, 3 solvent models, and 3 gauge-referencing schemes. The best performing DFT methodologies for 1H and 13C NMR chemical shift predictions were WP04/6-311++G(2d,p) and ωB97X-D/def2-SVP, respectively, when combined with the polarizable continuum solvent model (PCM) and gauge-independent atomic orbital (GIAO) method. Geometries should be optimized at the B3LYP-D3/6-311G(d,p) level including the PCM solvent model for the best accuracy. Predictions of 20 organic compounds and natural products from a separate probe set had root-mean-square deviations (RMSD) of 0.07 to 0.19 for 1H and 0.5 to 2.9 for 13C. Maximum deviations were less than 0.5 and 6.5 ppm for 1H and 13C, respectively.

Evaluation of the CHARMM36m force field combined with the OPC water model for protein simulations.

The accuracy of atomistic molecular dynamics (MD) simulations depends on the accuracy of the used force field. For proteins many force fields have been developed so far, each in combination with a particular water model. Typically, combining a protein force field with a water model for which is has not been developed is not expected to yield reliable results. However, recently the combination of the CHARMM36m force field with the OPC water model was shown to accurately estimate the compactness and secondary structure content of intrinsically disordered proteins. Whether CHARMM36m+OPC yields similar accuracy for globular proteins as well has, however, not yet been evaluated systematically. Here, we benchmark this combination on a set of six different globular proteins. To this end, we performed 50 x 1 μs MD simulations per protein using CHARMM36m+OPC and, for comparison, the same simulations using the well-established Amber99SB-ILDN+TIP4P force field. We compared the generated ensembles by means of RMSD, radius of gyration and secondary structure content and also compared the conformational dynamics. We found that CHARMM36m+OPC generates less compact ensembles and shows higher barriers for conformational transitions. Furthermore, we compare ensembles of both force fields to experimental crystal structures, B-factors, and NMR chemical shifts. Here, we found that both force fields compare equally well to experimental data, with CHARMM36m+OPC ensembles agreeing with chemical shifts slightly better, whereas Amber99SB-ILDN+TIP4P ensembles better agree with crystal structures. Our results show that CHARMM36m+OPC and Amber99SB-ILDN+TIP4P yield similar accuracy for globular proteins. Combined with earlier results for disordered proteins, these findings suggest that CHARMM36m+OPC should provide good accuracy for a broad range of disordered and folded proteins as well.

Accurate and Cost-Effective NMR Chemical Shift Predictions for Nucleic Acids Using a Molecules-in-Molecules Fragmentation-Based Method.

We have developed, implemented, and assessed an efficient protocol for the prediction of NMR chemical shifts of large nucleic acids using our molecules-in-molecules (MIM) fragment-based quantum chemical approach. To assess the performance of our approach, MIM-NMR calculations are calibrated on a test set of three nucleic acids, where the structure is derived from solution-phase NMR studies. For DNA systems with multiple conformers, the one-layer MIM method with trimer fragments (MIM1trimer) is benchmarked to get the lowest energy structure, with an average error of only 0.80 kcal/mol with respect to unfragmented full molecule calculations. The MIMI-NMRdimer calibration with respect to unfragmented full molecule calculations shows a mean absolute deviation (MAD) of 0.06 and 0.11 ppm, respectively, for 1H and 13C nuclei, but the performance with respect to experimental NMR chemical shifts is comparable to the more expensive MIM1-NMR and MIM2-NMR methods with trimer subsystems. To compare with the experimental chemical shifts, a standard protocol is derived using DNA systems with Protein Data Bank (PDB) IDs 1SY8, 1K2K, and 1KR8. The effect of structural minimizations is employed using a hybrid mechanics/semiempirical approach and used for computations in solution with implicit and explicit-implicit solvation models in our MIM1-NMRdimer methodology. To demonstrate the applicability of our protocol, we tested it on seven nucleic acids, including structures with nonstandard residues, heteroatom substitutions (F and B atoms), and side chain mutations with a size ranging from ∼300 to 1100 atoms. The major improvement for predicted MIM1-NMRdimer calculations is obtained from structural minimizations and implicit solvation effects. A significant improvement with the explicit-implicit solvation model is observed only for two smaller nucleic acid systems (1KR8 and 7NBK), where the expensive first solvation shell is replaced by the microsolvation model, in which a single water molecule is added for each solvent-exposed amino and imino protons, along with the implicit solvation. Overall, our target accuracy of ∼0.2-0.3 ppm for 1H and ∼2-3 ppm for 13C has been achieved for large nucleic acids. The proposed MIM-NMR approach is accurate and cost-effective (linear scaling with system size), and it can aid in the structural assignments of a wide range of complex biomolecules.

Disentangling global and local ring currents.

Magnetic field-induced ring currents in aromatic and antiaromatic molecules cause characteristic shielding and deshielding effects in the molecules' NMR spectra. However, it is difficult to analyze (anti)aromaticity directly from experimental NMR data if a molecule has multiple ring current pathways. Here we present a method for using the Biot-Savart law to deconvolute the contributions of different ring currents to the experimental NMR spectra of polycyclic compounds. This method accurately quantifies local and global ring current susceptibilities in porphyrin nanorings, as well as in a bicyclic dithienothiophene-bridged [34]octaphyrin. There is excellent agreement between ring current susceptibilities derived from both experimental and computationally-predicted chemical shifts, and with ring currents calculated by the GIMIC method. Our method can be applied to any polycyclic system, with any number of ring currents, provided that appropriate NMR data are available.

Anomalous 1 H NMR chemical shift behavior of substituted benzoic acid esters.

Benzoic acid esters represent key building blocks for many drug discovery and development programs and have been advanced as potent PDE4 inhibitors for inhaled administration for treatment of respiratory diseases. This class of compounds has also been employed in myriad industrial processes and as common food preservatives. Recent work directed toward the synthesis of intermediates for a proprietary medicinal chemistry program led us to observe that the 1 H NMR chemical shifts of substituents ortho to the benzoic acid ester moiety defied conventional iterative chemical shift prediction protocols. To explore these unexpected results, we initiated a detailed computational study employing density functional theory (DFT) calculations to better understand the unexpectedly large variance in expected versus experimental NMR chemical shifts.

Structural studies of human fission protein FIS1 reveal a dynamic region important for GTPase DRP1 recruitment and mitochondrial fission

Fission protein 1 (FIS1) and dynamin-related protein 1 (DRP1) were initially described as being evolutionarily conserved for mitochondrial fission, yet in humans the role of FIS1 in this process is unclear and disputed by many. In budding yeast where Fis1p helps to recruit the DRP1 ortholog from the cytoplasm to mitochondria for fission, an N-terminal "arm" of Fis1p is required for function. The yeast Fis1p arm interacts intramolecularly with a conserved tetratricopeptide repeat core and governs invitro interactions with yeast DRP1. In human FIS1, NMR and X-ray structures show different arm conformations, but its importance for human DRP1 recruitment is unknown. Here, we use molecular dynamics simulations and comparisons to experimental NMR chemical shifts to show the human FIS1 arm can adopt an intramolecular conformation akin to that observed with yeast Fis1p. This finding is further supported through intrinsic tryptophan fluorescence and NMR experiments on human FIS1 with and without the arm. Using NMR, we observed the human FIS1 arm is also sensitive to environmental changes. We reveal the importance of these findings in cellular studies where removal of the FIS1 arm reduces DRP1 recruitment and mitochondrial fission similar to the yeast system. Moreover, we determined that expression of mitophagy adapter TBC1D15 can partially rescue arm-less FIS1 in a manner reminiscent of expression of the adapter Mdv1p in yeast. These findings point to conserved features of FIS1 important for its activity in mitochondrial morphology. More generally, other tetratricopeptide repeat-containing proteins are flanked by disordered arms/tails, suggesting possible common regulatory mechanisms.

AlCl3-Catalyzed Cascade Reactions of 1,2,3-Trimethoxybenzene and Adipoyl Chloride: Spectroscopic Investigations and Density Functional Theory Studies.

The reaction of 1,2,3-trimethoxybenzene with adipoyl chloride in the presence of AlCl3 gave two isomeric cyclopentene derivatives, 1,6-bis(2,3,4-trimethoxyphenyl)hexane-1,6-dione, and two demethylation products of aryl methyl ethers. The cyclopentene derivatives including unconjugated or conjugated enones are products formed in a cascade reaction resulting from first the Friedel-Crafts acylation reaction and then aldol condensation. All compounds were optimized by density functional theory calculated using two functional levels, B3LYP and M06-2X, with the 6-311+G(d,p) basis set. The structural properties were established, natural bond orbital analysis of donor-acceptor interactions was carried out, and charges on the atoms and quantum chemical reactivity identifiers were determined to compare the strength of the intramolecular hydrogen bonds formed and their stabilities. To compare the experimental 1H and 13C NMR chemical shifts with the calculated values, NMR chemical shift calculations were carried out using the gauge-invariant atomic orbital method.

Structural insights, spectral, flourescence, Z-scan, C-H…O/N-H…O hydrogen bonding and AIM, RDG, ELF, LOL, FUKUI analysis, NLO activity of N-2(Methoxy phenyl) acetamide

Quantum chemical calculations of geometries and vibrational wavenumbers of N-2(methoxy phenyl)acetamide(N2MPA) in the ground state were carried out by using density functional theory (DFT/B3LYP) method with 6-31G (d,p) basis set. The scaled harmonic vibrational frequencies have been compared with experimental FT-IR spectra. Theoretical vibrational spectra of the title compound were interpreted by means of potential energy distributions (PEDs) using MOLVIB program. The experimental 1H and 13C NMR chemical shifts were investigated and then compared with computed NMR data using the gauge – invariant atomic orbital (GIAO) method. The optical nature of the grown crystal was evaluated by using the UV-Vis optical transmittance spectrum. The lower wavelength absorption range and various optical constant for instance, energy band gap, absorption and extinction coefficient, refractive index, susceptibility and Urbach energy values were evaluated. The colourless crystal of N2MPA was grown by slow-evaporation technique. The nonlinear optical (NLO) properties of N2MPA have been investigated using Z-scan technique. The emission behavior of N2MPA was analyzed by fluorescence spectral analysis. Thermal stability of N2MPA was studied by TG-DTA analysis. The HOMO and LUMO energy levels are constructed and the corresponding frontier energy gaps are determined to realize the charge transfer within the molecule. The molecular electrostatic potential(MESP), natural bond orbital(NBO) analysis and topological analysis such as electron localization function(ELF), reduced density gradient(RDG), localized orbital locator(LOL), atoms in molecule(AIM) and FUKUI function analysis have been used to evaluate the intermolecular interaction, especially the hydrogen bonds. Fingerprint plots of Hirshfeld surfaces were used to locate and analyze the percentage of hydrogen bonding interactions.

Catellatolactams A–C, Plant Growth-Promoting Ansamacrolactams from a Rare Actinomycete of the Genus Catellatospora

Catellatolactams A-C (1-3), three novel ansamacrolactams, were isolated from the culture extract of an underexplored rare actinomycete of the genus Catellatospora. Spectroscopic and spectrometric analyses by NMR and MS elucidated the structure of 1 to be a lactamized pentaketide presumably extended on a 3-amino-5-hydroxybenzoic acid starter unit. Compounds 2 and 3 further received epoxidation and intramolecular cross-linking to incorporate a 2-indolinone unit, with a 3-amino-5-hydroxybenzoic acid pendant on 3. The absolute configurations of 2 and 3 were unequivocally established to both be 2S,6R,7R by comparison of the experimental NMR chemical shifts and ECD spectra with those predicted by DFT-based quantum chemical calculation. While 1-3 showed no appreciable antimicrobial activity or cytotoxicity, root elongation of germinated lettuce seeds was promoted by 2 and 3 at 1-10 μM.

Structural, vibrational spectroscopy, molecular docking, DFT studies and antibacterial activity of (E)-N1-(3-chlorobenzylidene)benzene-1,4-diamine

In this work, (E)-N1-(3-chlorobenzylidene)benzene-1,4-diamine (CBD) compound was synthesized with good yield. The spectral studies were recorded by FT-IR, FT-Raman, NMR and UV-Vis to determine structural parameters. The geometrical parameters were optimized using DFT calculations at 6-311++G(d,p) basis set. The calculated structural parameters of the molecule were in line with the experimental data. The molecular orbitals of the compound were investigated through highest occupied molecular orbital (HOMO), lowest unoccupied molecular orbital (LUMO) analysis. The hyper conjugative interaction energy E(2) along with donor, acceptor electron densities (EDs) were determined by natural bond orbital (NBO) analysis. The molecular electrostatic potential (MEP), mulliken atomic charges, non-linear optical (NLO) properties and potential energy surface (PES) scan were also calculated. The 1H and 13C NMR chemical shifts calculated using Gauge invariant atomic orbital (GIAO) method were compared with the experimental NMR chemical shifts. Thermogravimetry (TG) and Differential Scanning Calorimetry (DSC) were carried out to characterise the thermal behaviour and stability of CBD molecule. In addition, PreADMET tool was also used to estimate ADME and Toxicity of CBD compound. The compound screened against four pathogens two gram positive and two gram negative had shown good anti-bacterial behaviour. The molecular docking studies executed against anti-bacterial target topoisomerase DNA gyrase enzyme (2XCT) emphasized good binding behaviour over the standard drug. Communicated by Ramaswamy H. Sarma