Theoretical 1H NMR Research Articles

Exploration of semi-carbazone derivatives as promising agents against cholera: Insights from spectroscopic analysis, reactivity studies (ELF, HOMO-LUMO, NBO), solvation effects, and molecular docking investigations

This study is aimed at evaluating the impact of solvation on the structural, spectroscopy (UV, NMR, FT-IR), reactivity, bonding interactions, and the drug potential of Pyridine 4-Carbaldehyde Semi-carbazone (PCS) against the disease (cholera) causing protein in the Gram-negative bacterium; Vibrio cholerae. Notably, the study was carried out using both experimental and theoretical calculations based on density functional theory (DFT) at the GD3B/B3LYP/6–311G++(2D,2P) level of theory along with molecular docking. Results from the UV- spectrum showed very fair absorption levels across the different solvents used, with theoretical peaks at 463 nm, 467 nm, 470 nm and 468 nm for PCS_DMSO, PCS_ETOH, PCS_H2O and PCS_MEOH, respectively. The study reveals discrepancies between experimental and theoretical 1H NMR shifts. However, theoretical 13C NMR shifts show minute differences. RDG analysis reveals steric repulsions in the pyridine ring. Whereas, the investigation of electronic properties reveal that the decreasing order of PCS_DMSO (3.668 eV) > PCS_H2O (3.206 eV) > PCS_MEOH (3.202 eV) > PCS_ETOH (0.312 eV). The results of docking showed that PCS had binding affinities of -5.0 Kcal/mol with protein 7P3R and -5.4 Kcal/mol with protein 1XTC which happen to be much lesser than -10.2 Kcal/mol formed between erythromycin and 7P3R. However, erythromycin formed a non-feasible bonding interactions with 1XTC with biding affinity of 18.0 Kcal/mol. Results of the MD simulation showed that PCS-MEOH had a higher energy value than PCS-DMSO, PCS-ETOH, and PCS-H2, indicating that it can interact with other substances more effectively, disperse more quickly. These results from the various studied objectives, however, suggest Pyridine 4-Carbaldehyde Semi-carbazone to be a lead compound for tackling the incidence, distribution and prevalence of cholera.

A theoretical protocol for the rational design of the bioinspired multifunctional hybrid material MIP@cercosporin.

Rational design of polymeric materials prepared with the molecular imprinting technology is gaining even more space, as it can provide the optimal conditions to direct the laboratory molecularly imprinting polymer (MIP) preparation, maximizing their efficiency while reducing costs and preparation time, when compared to try-and-error approaches. We perform a rational design of an MIP with specific cavities for cercosporin accommodation by means of computational tools. The main steps of an MIP preparation were simulated and it was found that the most appropriated functional monomer to be used in the MIP preparation for cercosporin is the acrylamide, while the most suitable crosslinking agent is found to be p-divinylbenzene. Also, the most suitable solvents to remove cercosporin from the cavity are those with low dielectric constant, such as chloroform. This kind of solvent can then be used in washing step, in the case of use the MIP for sensing destinations. On the other hand, solvents like water, which has high dielectric constants, can efficiently improve the interactions between cercosporin and the functional monomer acrylamide, being indicated when the objective is to attract or maintain the cercosporin inside the MIP cavity. Thus, a MIP@cercosporin hybrid material can be used in aqueous solutions more reliably, or even the cercosporin detection in this media can be favoured. In the selectivity analysis of the material prepared in this specific condition, the results point that this MIP can also detect elsinochrome A with high efficiency, and could be more selective for hypericin, altertoxin, hypocrelin A, and phleichrome mycotoxins. The main steps of a MIP synthesis were theoretically simulated trough density functional theory (DFT) calculations aiming to direct and optimize the synthesis and applications of the material before the bench tests. Initially, in order to choose the most suitable functional to be employed for cercosporin calculations, eight of the DFT functionals that had been previously used for cercosporin calculations in literature were tested, which were the LCWPBE, B3LYP, CAM-B3LYP, M062-X, mPW1PW91, PBE0, TPSSh, and ωb97Xd. The theoretical 1H NMR chemical shifts for cercosporin molecule were calculated and compared with experimental results to analyze the performance of the functionals. Of all these, the best results were obtained with the TPSSh functional, employing the 6-31G(d,p) basis set, and this level of theory was then used for all the following steps. All the simulations were performed by means of geometry optimizations and frequency calculations. Additionally, AIM calculations were employed for further analysis of the interactions between the chosen functional monomer and cercosporin template in step 1, which was functional monomer selection. In washing step, the calculations were done using implicit solvation model, and finally, in selectivity tests, the putative "solid" MIP was simulated by freezing the positions of the monomers after the template remotion, and then other structurally similar toxins were placed in its cavity for the geometry optimizations and frequency calculations.

Synthesis of 4-Amino-N-[2 (diethylamino)Ethyl]Benzamide Tetraphenylborate Ion-Associate Complex: Characterization, Antibacterial and Computational Study.

The 4-amino-N-[2 (diethylamino) ethyl] benzamide (procainamide)-tetraphenylborate complex was synthesized by reacting sodium tetraphenyl borate with 4-amino-N-[2 (diethylamino) ethyl] benzamide, chloride salt, and procainamide in deionized water at room temperature through an ion-associate reaction (green chemistry) at room temperature, and characterized by several physicochemical methods. The formation of ion-associate complex between bio-active molecules and/or organic molecules is crucial to comprehending the relationships between bioactive molecules and receptor interactions. The solid complex was characterized by infrared spectra, NMR, elemental analysis, and mass spectrometry, indicating the formation of ion-associate or ion-pair complex. The complex under study was examined for antibacterial activity. The ground state electronic characteristics of the S1 and S2 complex configurations were computed using the density functional theory (DFT) approach, using B3LYP level 6-311 G(d,p) basis sets. R2 = 0.9765 and 0.9556, respectively, indicate a strong correlation between the observed and theoretical 1H-NMR, and the relative error of vibrational frequencies for both configurations was acceptable, as well. HOMO and LUMO frontier molecular orbitals and molecular electrostatics using the optimized were used to obtain a potential map of the chemical. The n → π* UV absorption peak of the UV cutoff edge was detected for both configurations of the complex. Spectroscopic methods were structures used to characterize the structure (FT-IR and 1HNMR). In the ground state, DFT/B3LYP/6-311G(d,p) basis sets were used to determine the electrical and geometric properties of the S1 and S2 configurations of the title complex. Comparing the observed and calculated values for the S1 and S2 forms, the HOMO-LUMO energy gap of compounds was 3182 and 3231 eV, respectively. The small energy gap between HOMO and LUMO indicated that the compound was stable. In addition, the MEP reveals that positive potential sites were around the PR molecule, whereas negative potential sites were surrounding the TPB site of atoms. The UV absorption of both arrangements is comparable to the experimental UV spectrum.

A DFT Study on Diels-Alder Reaction of Dibenzazepine and 2,5-Dimethylfuran Using Different Solvents and Temperature Conditions

The Diels-Alder reaction involves cycloaddition of dienes and dienophiles to form a six-membered ring. The reaction involves the formation of adduct which can have two possible configurations, viz, endo and exo. For a vast majority of the Diels-Alder reactions, endo is the major adduct. This first ever study focuses on the Diels-Alder reaction between dibenzazepine and 2,5-dimethylfuran depicted by the computational method using Gaussian 16 software at different basis set levels. The formation of adduct is studied under different temperatures in the gas phase and aqueous medium. The kinetically favored endo adduct is preferred at low temperatures as compared to exo adduct. The adduct gets dehydrated further to give tribenzazepine as the final product. The applicability of the reaction is also proved experimentally in absence or presence of aqueous medium. The final product is characterized and its experimental and theoretical 1HNMR are compared.

A QUANTUM CHEMICAL STUDY OF SMALL MOLECULES USED AS ACTIVE LAYER COMPONENT OF ORGANIC SOLAR CELLS

Organic solar cells (OSCs) are one of the best alternatives in the photovoltaic area. These devices convert directly sunlight into electrical current with reasonable efficiencies. The most important component of an OSC is the photoconductive active layer which can be made of small organic molecules. In this theoretical study, a quantum chemical approach was applied to calculate the properties such as the energy of Highest Occupied Molecular Orbital (HOMO) and the Lowest Unoccupied Molecular Orbital (LUMO), LUMO-HOMO energy gap, and the theoretical 1H NMR chemical shifts (the latter only for one molecule) for four organic molecules that exist in the literature. The geometry optimization of the four small molecules and the corresponding calculations were performed using Gaussian 09 software by means of the Density Functional Theory (DFT) at the B3LYP/6-31G(d) theoretical level. All the reported experimental values given in the papers were compared with the obtained theoretical values via a linear regression analysis. Our computational study showed good agreement with the experimental data as the regression analysis showed a coefficient of determination greater than 0.99.

Experimental and Theoretical Studies of Novel Azo Benzene Functionalized Conjugated Polymers: In-vitro Antileishmanial Activity and Bioimaging

To study the effect of insertion of azobenzene moiety on the spectral, morphological and fluorescence properties of conventional conducting polymers, the present work reports ultrasound-assisted polymerization of azobenzene with aniline, 1-naphthylamine, luminol and o-phenylenediamine. The chemical structure and polymerization was established via Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (1H-NMR) spectroscopy, while the electronic properties were explored via ultraviolet-visible (UV-vis) spectroscopy. Theoretical IR and UV spectra were computed using DFT/B3LYP method with 6–311G basis set while theoretical 1H-NMR spectra was obtained by gauge independent atomic orbital (GIAO) method. The theoretically computed spectra were found to be in close agreement with the experimental findings confirming the chemical as well as electronic structure of the synthesized polymers. Morphology was investigated by X-ray diffraction and transmission electron microscopy studies. Fluorescence studies revealed emission ranging between 530–570 nm. The polymers also revealed high singlet oxygen (1O2) generation characteristics. In-vitro antileishmanial efficacy as well as live cell imaging investigations reflected the potential application of these polymers in the treatment of leishmaniasis and its diagnosis.

Structural Determination of Antioxidant and Anticancer Flavonoid Rutin in Solution through DFT Calculations of 1H NMR Chemical Shifts

As the knowledge of the predominant molecular structure of antioxidant and anticancer flavonoid rutin in solution is very important for understanding the mechanism of action, a quantum chemical investigation of plausible rutin structures including solvent effects is of relevance. In this work, DFT calculations were performed to find possible minimum energy structures for the rutin molecule. 1H NMR chemical shift DFT calculations were carried out in DMSO solution using the polarizable continuum model (PCM) to simulate the solvent effect. Analysis of the experimental and theoretical 1H NMR chemical shift profiles offers a powerful fingerprint criterion to determine the predominant molecular structure in solution. Therefore, our aim is to find the best match between experimental (in DMSO‐d) and theoretical (PCM–DMSO) 1H NMR spectrum profiles. Among 34 optimized structures located on the potential energy surface, we found that structure 32, with a B‐ring deviated 30° from a planar configuration (geometry usually assumed for polyphenols), showed an almost perfect agreement with experimental the 1H NMR pattern when compared to the corresponding fully optimized planar geometry. This structure is also predicted as the global minimum based on room‐temperature Gibbs free energy calculations in solution and, therefore, should be experimentally observed. This is new and valuable structural information regarding structure–activity relationship studies, and such information is hard to obtain by experimentalists without the aid of the X‐ray diffraction technique.

Microwave synthesis of some N-phenylhydrazine-1-carbothioamide Schiff bases

We have synthesized and characterized a series of carbothioamide derivatived molecules, obtained by reaction of aromatic aldehyde (Anisaldehyde, 9-anthraldehyde, cinnamaldehyde, indole-3-carboxaldehyde, 1-naphthaldehyde and o-vanillin) with an equimolar amount of 4-phenylthiosemicarbazide with microwave irradiation. The synthesized compounds have been characterized by FT-IR, 1H NMR and 13C NMR spectroscopy. Quantum calculations of the physical properties, based on density functional theory method at B3LYP/6-31+G(d,p) level of theory, were performed, by means of the Gaussian 09W set of programs. The theoretical 1H NMR chemical shift results of the studied compounds have been calculated at B3LYP method and standard 6-31+G(d,p) basis set using the standard Gauge-Independent Atomic Orbital approach. The calculated values are also compared with the experimental data available for these molecules. A good linear relationship between the experimental and calculated data has been obtained.

Density Functional Theory Study on the Complexation of NOTA as a Bifunctional Chelator with Radiometal Ions.

1,4,7-Triazacyclononane-1,4,7-triacetic acid (NOTA) is a key bifunctional chelator utilized for the complexation of metal ions in radiopharmaceutical applications; the ability of these chelators depends on the strength of their binding with ions. The focus of the present work is to evaluate the complexation of Cu2+, Ga3+, Sc3+, and In3+ radiometal ions with NOTA using density functional theory (B3LYP functional) and 6-311+G(2d,2p)/DGDZVP basis sets. The significant role of ion-water interactions in the chelation interaction energies in solution reflects the competition between ion-water and NOTA-ion interaction in the chelation process. There is reasonable agreement between experimental and theoretical binding constants, geometries, and 1H NMR chemical shifts. Chelation interaction energies, Gibbs free energies, and entropies in solution show that the NOTA-Ga3+ and NOTA-Cu2+ are the most and least stable complexes, respectively. The natural atomic charges and second order perturbation analysis reveal charge transfer between NOTA and radiometal ions. The theoretical 1H NMR chemical shifts of NOTA are in good agreement with experiment; these values are influenced by the presence of the ions, which have a deshielding effect on the protons of NOTA. Global scalar properties such as EHOMO/ELUMO, ΔELUMO-HOMO, and chemical hardness/softness confirm that the NOTA-Cu2+ complex, which has a singly occupied molecular orbital, has the lowest ΔELUMO-HOMO value, the least chemical hardness, and the highest chemical softness. The significant variation of the hardness and ΔELUMO-HOMO values of the complexes can be attributed to the different positions of the metal ions on the periodic table. This study affirms that, among the radiometal ions, Ga3+ can be used to effectively radiolabel NOTA chelator for radiopharmaceutical usage as it binds most stably with NOTA.

Palladium(II) complexes bearing di-(2-picolyl)amine functionalized chrysin fragments. An experimental and theoretical study

A new series of chrysin derivatives containing the di-(2-picolyl)amine (2a–d) moiety have been designed, synthesized, and treated with PdCl2·2CH3CN allowing the preparation of new cationic Palladium(II) complexes (3a–d). Solution-phase studies by 1H NMR spectroscopy of 3a–d revealed that the protons of the methylene groups of the di(2-picolyl)amine fragment are diasterotopic. GIAO/DFT studies were performed to predict the molecular structures of 3a–d by comparing the experimental and theoretical 1H-NMR chemical shifts. The molecular structure of 3c was determined by X-ray crystallographic analysis revealing that di-(2-picolyl)amine fragment is coordinated to the palladium center in a κ3-N,N,N-tridentate fashion in an overall square-planar geometry completed with a chloride atom.

Structural analysis of flavonoids in solution through DFT 1H NMR chemical shift calculations: Epigallocatechin, Kaempferol and Quercetin

In this work, we showed that comparison between experimental and theoretical 1H NMR chemical shift patterns, calculated using Density Functional Theory (DFT), can be used for the prediction of molecular structure of flavonoids in solution, what is experimentally accessible for gas phase (electron diffraction methods) and solid samples (X-ray diffraction). The best match between B3LYP/6-31G(d,p)-PCM 1H NMR calculations for B ring rotated structures and experimental spectra can provide information on the conformation adopted by polyphenols in solution (usually DMSO-d6, acetone-d6 as solvents), which may differ from solid state and gas phase observed structures, and also DFT optimized geometry in the vacuum.

Computational investigation on the host-guest inclusion process of norfloxacin into β-cyclodextrin.

A theoretical (1)H NMR spectroscopy and thermodynamic analysis of the host-guest inclusion process involving the norfloxacin (NFX) into β-cyclodextrin (β-CD) was carried out. DFT structure and stabilization energies were obtained in both gas and aqueous phases. We could establish that the complex formation is enthalpy driven, and the hydrogen bonds established between NFX and β-CD play a major role in the complex stabilization. Besides, a theoretical (1)H NMR analysis has shown to be a supplementary proceeding to predict appropriately the inclusion mode of norfloxacin molecule into the β-CD. In this work, a theoretical study of the NFX@β-CD complex is reported for the first time, seeking a deep understanding of topology and thermodynamics of the inclusion complex formation. Graphical Abstract Topology, thermodynamic and (1)H NMR analysis of NFX@β-CD host-guest complexes.

A DFT investigation on the host/guest inclusion process of prilocaine into β-cyclodextrin

A theoretical analysis of the host/guest inclusion process involving the prilocaine into the β-cyclodextrin was performed. Structure and stabilization energies were calculated, in both gas and aqueous phases, using Density Functional Theory level of theory. As results, a qualitative structure property relationship could be established with structural features being relevant for inclusion complex stabilization: (i) the hydrogen bonds established between guest and host molecules and (ii) the dispersion effect in the formation of the complexes. Besides, a theoretical 1H NMR analysis has shown to be an adequate procedure to predict correctly the inclusion mode of guest molecule into the host.

HOMO–LUMO energy interactions between endocrine disrupting chemicals and ionic liquids using the density functional theory: Evaluation and comparison

Extraction of endocrine disrupting chemicals such as pentachlorophenol [PCP] and pthalic acid [PA] using ionic liquids (IL's) as solvents has been found to be effective for wastewater treatment. New insights are required to explain the interaction between IL's and organic compounds by quantum chemical descriptors. In this work, the parameters like global hardness and softness, chemical potential, electronegativity and electrophilicity index, HOMO/LUMO energy, and HOMO–LUMO energy gap were predicted for systems such as: [PCP]+[C4DMIM][PF6] and [PA]+[C4DMIM][PF6] and individual species. Initially geometry optimization was carried out using the DFT based B3LYP/6-31G* method for individual molecules of [PCP], [PA], cations, anions and [PCP]\\[PA]+IL complexes. Thereafter, the quantum chemical descriptors were predicted and analyzed. In addition, the experimental and theoretical 1H NMR chemical shifts of [PCP]+[C4DMIM][PF6] and [PA]+[C4DMIM][PF6] were also carried out to benchmark the predictions. The highest and lowest HOMO–LUMO energy gap was obtained for [PCP]+[C4DMIM][PF6] (0.146eV) and [PA]+[C4DMIM][PF6] (0.0597eV) respectively. Charge distribution using the CHELPG (CHarges from Electrostatic Potentials using a Grid based method) analysis was also studied in detail.

Preparation, spectral studies, theoretical, electrochemical and antibacterial investigation of a new Schiff base and its some metal complexes

A new Schiff base ligand, 1,6-Bis(2-(5-bromo-2-hydroxybenzylideneamino)-4-chlorophenoxy)hexane was synthesized. Some Schiff metal complexes of the new Schiff base were prepared by the reaction of some metal salts and the Schiff base. The complexes are non-electrolytes as shown by their molar conductivities (ΛM). The structures of metal complexes are proposed from elemental analysis, FT-IR, UV–vis, magnetic susceptibility measurements, molar conductivity measurements, mass spectra and thermal gravimetric analysis. In addition theoretical 1H NMR, HOMO–LUMO studies of the ligand; antimicrobial and cyclic voltammetric studies of the compounds were also carried out. In this study antioxidant and antibacterial activities of the compounds were examined via in vitro methods.

Synthesis, characterization and experimental, theoretical, electrochemical, antioxidant and antibacterial study of a new Schiff base and its complexes

A new Schiff base ligand was synthesized by reaction of salicylaldehyde with 1,6-bis(4-chloro-2-aminophenoxy)hexane. Then the Schiff base complexes were synthesized by metal salts and the Schiff base. The metal to ligand ratio of metal complexes was found to be 1:1. The Cu(II) complex is proposed to be square planar and the Co(II), Ni(II), Mn(II) and Zn(II) complexes are proposed to be tetrahedral geometry. The Ti(III) and V(III) complexes are proposed to be a capped octahedron in which a seventh ligand has been added to triangular face. The complexes are non-electrolytes as shown by their molar conductivities (ΛM). The structure of metal complexes is proposed from elemental analysis, FT-IR, UV–vis, magnetic susceptibility measurements, molar conductivity measurements, Mass Spectra and thermal gravimetric analysis. In addition antimicrobial and antioxidant studies, cyclic voltammetry of the complexes, theoretical 1H NMR and HOMO–LUMO energy calculations of the new di-functional ligand were done.

Quantum Mechanical Modeling of Fluoromethylated-pyrrol Derivatives a Study on their Reactivities, Structures and Vibrational Properties

In this work, the structural and vibrational properties of 1-5-(difluoromethyl-1H-pyrrol-2-yl-) ethanone (DFPE) were studied by using the hybrid B3LYP/6-31G* method. The properties were analyzed and compared with those obtained for 1-(1H-pyrrol-2-yl) ethanone (PE) and 1-(5-(trifluoromethyl)-1H-pyrrol-2-yl) ethanone (TFPE). The theoretical 1H-NMR, 13C-NMR and 19F-NMR chemical shifts for DFPE were predicted by using the B3LYP/6-311++G** approach with the GIAO and CGST methods showing the three spectra good concordances with the corresponding experimental ones. A complete assignment of the vibrational spectra was presented.

Erratum to: Theoretical and experimental study of the regioselectivity of phenylacetylene 1,3-dipolar cycloaddition to some arylazides

1,3-Dipolar cycloaddition of phenylacetylene to two arylazides afforded new 1,2,3-triazoles. The regioselectivity and reactivity of these reactions was investigated on the basis of density functional theory-based reactivity indexes and activation energy calculations. Theoretical 1H NMR chemical shifts of the cycloadducts obtained by use of the GIAO method were similar to observed values.

Experimental and quantum chemical studies of a novel synthetic prenylated chalcone

BackgroundChalcones are ubiquitous natural compounds with a wide variety of reported biological activities, including antitumoral, antiviral and antimicrobial effects. Furthermore, chalcones are being studied for its potential use in organic electroluminescent devices; therefore the description of their spectroscopic properties is important to elucidate the structure of these molecules. One of the main techniques available for structure elucidation is the use of Nuclear Magnetic Resonance Spectroscopy (NMR). Accordingly, the prediction of the NMR spectra in this kind of molecules is necessary to gather information about the influence of substituents on their spectra.ResultsA novel substituted chalcone has been synthetized. In order to identify the functional groups present in the new synthesized compound and confirm its chemical structure, experimental and theoretical 1H-NMR and 13C-NMR spectra were analyzed. The theoretical molecular structure and NMR spectra were calculated at both the Hartree-Fock and Density Functional (meta: TPSS; hybrid: B3LYP and PBE1PBE; hybrid meta GGA: M05-2X and M06-2X) levels of theory in combination with a 6-311++G(d,p) basis set. The structural parameters showed that the best method for geometry optimization was DFT:M06-2X/6-311++G(d,p), whereas the calculated bond angles and bond distances match experimental values of similar chalcone derivatives. The NMR calculations were carried out using the Gauge-Independent Atomic Orbital (GIAO) formalism in a DFT:M06-2X/6-311++G(d,p) optimized geometry.ConclusionConsidering all HF and DFT methods with GIAO calculations, TPSS and PBE1PBE were the most accurate methods used for calculation of 1H-NMR and 13C-NMR chemical shifts, which was almost similar to the B3LYP functional, followed in order by HF, M05-2X and M06-2X methods. All calculations were done using the Gaussian 09 software package. Theoretical calculations can be used to predict and confirm the structure of substituted chalcones with good correlation with the experimental data.

Experimental and theoretical NMR determination of isoniazid and sodium p-sulfonatocalix[n]arenes inclusion complexes

In this work the inclusion complex formation of isoniazid with sodium p-sulfonatocalix[n]arenes is reported aiming to improve the physicochemical and biopharmaceutical properties of isoniazid a first line antibuberculosis drug. The architectures of the complexes were proposed according to NMR data Job plot indicating details on the insertion of the isoniazid in the calix[n]arenes cavities. DFT theoretical NMR calculations were also performed for sodium p-sulfonatocalix[4]arene complex with isoniazid, with various modes of complexation being considered, to provide support for the experimental proposal. A comparison between experimental and theoretical 1H NMR chemical shifts profiles allowed for the inclusion complex characterization confirming the isoniazid inclusion mode which is preferentially through the hydrazide moiety. The remarkable agreement between experimental and theoretical NMR profiles adds support to their use in the structural characterization of inclusion compounds. Antibacterial activity was evaluated and the results indicated the inclusion complexes as a potential strategy for tuberculosis treatment.