An efficient new method of ytterbium(III) triflate catalysis approach to the synthesis of substituted pyrroles: DFT, ADMET, and molecular docking investigations.

In this study, the one-pot synthetic methodology for the preparation of substituted pyrroles with diethyl acetylene-dicarboxylate is reported for the various pyrrole derivatives via the Trifimow synthesis process from oximes. This method also offers the literature as a cyclization pathway using a ytterbium triflate catalyst. Another importance of this study is the use of pyrrole derivatives in pharmaceuticals, biological processes, and agrochemicals. From this point of view, the development of a new catalyst in synthetic organic chemistry and the difference in the method is also important. The syntheses of the target substituted pyrroles are accomplished in high yields. Also, all synthesized structures were confirmed by 1H NMR, 13C NMR, and IR spectra. The DFT computations were leveraged for structural and spectroscopic validation of the compounds. Then, FMO and NBO analyses were subsequently employed to elucidate the reactivity characteristics and intramolecular interactions within these compounds. Also, ADMET indices were ascertained to assess potential pharmacokinetic properties, drug-like qualities, and possible adverse effects of these compounds. Last, optimized molecules were analyzed by molecular docking methods against crystal structures of Bovine Serum Albumin and Leukemia Inhibitory Factor, and their binding affinities, interaction details, and inhibition constants were determined.

Molecular modeling study on the water-electrode surface interaction in hydrovoltaic energy.

The global energy problem caused by the decrease in fossil fuel sources, which have negative effects on human health and the environment, has made it necessary to research alternative energy sources. Renewable energy sources are more advantageous than fossil fuels because they are unlimited in quantity, do not cause great harm to the environment, are safe, and create economic value by reducing foreign dependency because they are obtained from natural resources. With nanotechnology, which enables the development of different technologies to meet energy needs, low-cost and environmentally friendly systems with high energy conversion efficiency are developed. Renewable energy production studies have focused on the development of hydrovoltaic technologies, in which electrical energy is produced by making use of the evaporation of natural water, which is the most abundant in the world. By using nanomaterials such as graphene, carbon nanoparticles, carbon nanotubes, and conductive polymers, hydrovoltaic technology provides systems with high energy conversion performance and low cost, which can directly convert the thermal energy resulting from the evaporation of water into electrical energy. The effect of the presence of water on the generation of energy via the interactions between the ion(s) and the liquid-solid surface can be enlightened by the mechanism of the hydovoltaic effect. Here, we simply try to get some tricky information underlying the hydrovoltaic effect by using DFT/B3LYP/6-311G(d, p) computations. Namely, the physicochemical and electronic properties of the graphene surface with a water molecule were investigated, and how/how much these quantities (or parameters) changed in case of the water molecule contained an equal number of charges were analyzed. In these computations, an excess of both positive charge and negative charge, and also a neutral environment was considered by using the Na+, Cl-, and NaCl salt, respectively.

Physicochemical properties, drug likeness, ADMET, DFT studies, and in vitro antioxidant activity of oxindole derivatives.

Poor pharmacokinetic and safety profiles create significant hurdles in the drug development process. This work focuses on a detailed understanding of drug discovery interplay among physicochemical, pharmacokinetic, toxicity endpoints, and antioxidant properties of oxindole derivatives. DFT compiutations were also performed at B3LYP/6-311G** level to evaluate the physicochemical properties, global reactivity features, and intramolecular interactions. The BOILED-Egg pharmacokinetic model envisaged gastrointestinal absorption, blood-brain barrier penetration, and no interaction with p-glycoprotein for compounds C1 and C2. The physicochemical evaluation revealed that C1 possesses superior drug-like properties fit for oral absorption. Both derivatives were predicted to have high plasma protein binding, efficient distribution, and inhibiting CYP 450 major isoforms but serve as substrates only for a few of them. Both molecules have mild to moderate clearance rates. Out of ten toxicity parameters, only hepatotoxicity was predicted. DFT results implied that the meta position of the -OH group made the possibility of charge transfer greater than -para positioned -OH, due to the ΔNmax (eV) values of molecules C1 and C2 being calculated at 2.596 and 2.477, respectively. Both C1 and C2 exhibited a concentration dependant DPPH and ABTS radical scavenging activity. The chemical structure-physicochemical-pharmacokinetic relationship identified the meta position as the favorite for the electron-withdrawing hydroxyl group. This provides useful insight to medicinal chemists to design 6-chlorooxindole derivatives with an acceptable drug-like and pharmacokinetic property.

Spectroscopic, crystal structure and DFT-assisted studies of some nickel(II) chelates of a heterocyclic-based NNO donor aroylhydrazone: in vitro DNA binding and docking studies.

Five new nickel(II) complexes have been synthesised with an NNO donor tridentate aroylhydrazone (HFPB) employing the chloride, nitrate, acetate and perchlorate salts, and all the complexes are physiochemically characterized. Elemental analyses suggested stoichiometries as Ni(FPB)(NO3)]·2H2O (1), [Ni(HFPB)(FPB)]Cl (2), [Ni(FPB)(OAc)(DMF)] (3), [Ni(FPB)(ClO4)]·DMF (4), [Ni(FPB)2] (5). Aroylhydrazone is found coordinating in deprotonated iminolate form in four of the complexes (1, 3, 4, 5) however in one case (complex 2), two aroylhydrazone moieties are binding to the metal centre in the neutral and anionic forms. The structure of the bisligated complex 5, found using single crystal X ray diffraction studies confirmed that the metal has a distorted octahedral N4O2 coordination environment, with each of the two deprotonated ligands coordinating through the pyridine nitrogen, imino-hydrazone nitrogen and the enolate oxygen of the hydrazone moiety. To compare and study, the electronic interactions and stabilities of the metal complexes, various quantum chemical parameters were calculated. Moreover, Hirshfeld surface analysis was carried out for complex 5 to determine the intermolecular interactions. The biophysical attributes of the ligand and complex 5 have been investigated with CT-DNA and experimental outcomes show that the Ni(II) complex exhibited higher binding propensity towards DNA as compared to ligand. Furthermore, to specifically understand the type of interactions of the metal complexes with DNA, molecular docking studies were effectuated. In addition, the electronic and related reactivity behaviors of the ligand and five Ni(II) complexes were studied using B3LYP/6-31 + + G**/LANL2DZ level. As expected, the obtained results from Natural Bond Orbital (NBO) computations displayed that the resonance interactions (n → π* and π → π*) play a determinant role in evaluating the chemical attributes of the reported compounds.

Substituted naphthoxy-phthalonitrile derivatives: Synthesis, substituent effects, DFT, TD-DFT Calculations, antimicrobial properties and DNA interaction studies.

Herein, substituted-naphthol derivatives 4a-e were synthesized in two steps, namely the Diels Alder cycloaddition and Cu-catalyzed aromatization reactions, respectively. Then, pththalonitrile derivatives 7-12 have been prepared by a nucleophilic displacement reaction of 3-nitrophthalonitrile with the naphthol derivatives 4a-e, 5 and, obtained in excellent yields. Structural characterization of the compounds was identified by different spectroscopic techniques. Antimicrobial properties of the synthesized compounds were determined by the microdilution procedure against Gram-positive, Gram-negative bacteria, and yeast. Furthermore, the DNA interaction of the compounds were determined by gel electrophoresis. One of the most prominent findings is that compounds 9 and 10 have more inhibitory effects on Gram-positive bacteria than Gram-negative bacteria. These compounds especially exhibited the highest antibacterial potency against S. aureus (625 µg/mL) among Gram-positive bacteria. According to the plasmid DNA interaction results, the synthesized compounds caused changes in the structure and mobility of the plasmid DNA. Then, geometry optimizations and frequency calculations were conducted at B3LYP/6-311 G(d,p) level of DFT, and optimized structures were used for further analyses. The NBO results revealed that the π→π * and n→π * interactions were greatly contributed to lowering the stabilization energy of all compounds (7-12). FMO energy analyses showed that compound 9 has the biggest electrodonating power.

Strychnos alkaloids: total synthesis, characterization, DFT investigations, and molecular docking with AChE, BuChE, and HSA.

An efficient five steps, the protection-deprotection synthetic a novel synthetic routes to(±) noruleine (±)-uleine, are reported starting from tetrahydrocarbazole fused monoalkyl nitrile at C-2 position that is prepared on multigram scale from 2-(3-ethyl-1-oxo-2,3,4,9-tetrahydro-1H-carbazol-2-yl)acetonitrile (1) as well as the key azocino[4,3-b]indole skeleton is constructed via the tetrafluoro-1,4-benzoquinone (TFB)-mediated cyclization of a tetrahydrocarbazole derivative possessing direct amide synthesis from nitrile. As a result, Total synthesis of noruleine and uleine has been developed, which is accomplished in 4 and 5- steps synthesis of the ABCD tetracyclic of the strychnos alkaloids with an overall yield of 44% and 39%, respectively. The DFT computations were performed with B3LYP/6-311g(d,p) level to determine inter and intramolecular interactions and reactivity features of the compound 3-6. Also, TD-DFT computations were performed to characterize the electronic absorption spectra of all compounds. Last, the interactions of compounds 3-6 with selected targets AChE, BuChE, and HSA were evaluated in light of the molecular dockings. The bioactivity and drug-likeness scores revealed that compound 6 3-6 can be proper candidate for future drug-design studies more than the other compounds.

Novel Ag(I)-NHC complex: synthesis, in vitro cytotoxic activity, molecular docking, and quantum chemical studies.

The importance of organometallic complexes in cancer biology has attracted attention in recent years. In this paper, we look for the in vitro cytotoxic capability of novel benzimidazole-based N-heterocyclic carbene (NHC) precursor (1) and its Ag(I)-NHC complex (2). For this purpose, these novel Ag(I)-NHC complex (2) was characterized by spectroscopic techniques (1H, 13C{1H} nuclear magnetic resonance (NMR), and Fourier-transform infrared spectroscopy (FT-IR)). Then, in vitro cytotoxic activities of NHC precursor (1) and Ag(I)-NHC complex (2) were investigated against MCF-7, MDA-MB-231 human breast, DU-145 prostate cancer cells, and L-929 healthy cells using MTT assay for 24, 48, and 72 h incubation times. Ag(I)-NHC complex (2) showed promising in vitro cytotoxic activity against all cell lines for three incubation times, with IC50 values lower than 5 µM. It was also determined that (NHC) precursor (1) were lower in vitro cytotoxic activity than Ag(I)-NHC complex (2) against all cell lines. Selectivity indexes (SIs) of Ag(I)-NHC complex (2) against cancer cells were found higher than 2 for 24 and 48 h incubation time. Besides, the electronic structure and spectroscopic data of the newly synthesized precursor and its Ag-complex have been supported by density functional theory (DFT) calculations and molecular docking analysis. After, the anticancer activity of these compounds has been discussed considering the results of the frontier molecular orbital analysis. We hope that the obtained results from the experiments and computational tools will bring a new perspective to cancer research in terms of supported by quantum chemical calculations.

DFT computational study of trihalogenated aniline derivative's adsorption onto graphene/fullerene/fullerene-like nanocages, X12Y12 (X = Al, B, and Y = N, P).

Adsorption of 2,4,6-tribromoaniline (BA), 2,4,6-trifluoroaniline (FA) and 2,4,6-trichloroaniline (CA) onto the surface of coronene/fullerene/fullerene-like nanocages was investigated by theoretical calculations. Due to the adsorption of BA/FA/CA, there are significant changes in chemical descriptors and nonlinear optical properties. Energy gap values of all nanoclusters are lowered, giving an increase in conductivity of complexes except for fullerene. All complex's ultraviolet visible wavenumber is blue-shifted and especially for fullerene complex, the values are very high. The enhancement of Raman intensities shows that it is possible to design a nanocage sensor for detecting these compounds by surface-enhanced Raman scattering (SERS).Communicated by Ramaswamy H. Sarma.

Zeolite/Cellulose Acetate (ZCA) in Blend Fiber for Adsorption of Erythromycin Residue From Pharmaceutical Wastewater: Experimental and Theoretical Study.

The expanding amount of remaining drug substances in wastewater adversely affects both the climate and human well-being. In the current investigation, we developed new cellulose acetic acid derivation/zeolite fiber as an effective technique to eliminate erythromycin (ERY) from wastewater. The number of interchangeable sites in the adsorbent structures and the ratio of ERY to the three adsorbents were identified as the main reasons for the reduction in adsorption as the initial ERY concentrations increased. Additionally, for all adsorbents, the pseudo-second-order modeling showed better fitting for the adsorption than the pseudo-first-order modeling. However, the findings obtained in the pseudo-first-order model were still enough for explaining the sorption kinetics of ERY, showing that the surface displayed all chemisorption and physi-sorption adsorption processes by both adsorbents. The R 2 for the second order was very close to 1 for the three adsorbents in the case of pseudo-second-order. The adsorption capacity reached 17.76 mg/g. The three adsorbents showed negative values of ΔH, and these values were -6,200, -8,500, and -9600 kJ/mol for zeolite, CA, and ZCA, respectively, and this shows that the adsorption is exothermic. The desorption analysis shows no substantial loss of adsorption site after three trials, indicating higher stability and resilience of the three adsorbents, indicating a strong repeatability of their possible use in adsorption without contaminating the environment. In addition, the chemical attitude and possible donor-acceptor interactions of ERY were assessed by the quantum chemical parameters (QCPs) and NBO analysis performed, at the HF/6-311G** calculations.

Synthesis, identification, density functional and Hirshfeld surface studies of 2,2'-disulfanediylbis(tetrahydro-4H-cyclopenta[d][1,3,2]dioxaphosphole-2-sulfide).

The new compound 2,2'-disulfanediylbis (tetrahydro-4H-cyclo penta[d][1,3,2]dioxaphosphole 2-sulfide), the dimeric form of 2-mercaptotetrahydro-4H-cyclopenta[d] [1,3,2] dioxaphosphole 2-sulfide, has been synthesized and characterized by elemental analysis, molecular weight determination and spectral data (1 H-NMR, 13 C-NMR, 31 P-NMR, FTIR). The molecular geometry was confirmed by single X-Ray crystallography. The ground state property was examined by PBE0 and B3LYP density functionals using aug-cc-pV(Q+d)Z basis set in the gas phase and in DMSO solution. The preference of PBE0 functional was statistically established. Thermodynamic parameters and standard heat of dissociation reaction ( Δ H R 298 K o ) have been established. The calculated equilibrium constants at different temperatures reflect the stability of the dimer over the monomers at low temperatures and vice versa. Valency and Fukui indices calculations showed that the monomer is more reactive than the dimer. 2D-fingerprint revealed that, while the H…X; [X = H, O and S] nonbonding intermolecular interactions and reciprocals play a crucial role in strengthening of molecules packing in the crystal unit cell while the S…S ones contribute negatively on it.

The composite microbeads of alginate, carrageenan, gelatin, and poly(lactic-co-glycolic acid): Synthesis, characterization and Density Functional Theory calculations.

Binary (AC, AG), ternary (ACG, ACP, AGP), quaternary (ACGP) composite beads of alginate (A), carrageenan (C), gelatin (G), and poly (lactic-co-glycolic acid) (P) were prepared. The dried beads had a 700 µm average diameter. The microspheres with and without P were characterized by FT-IR, TGA/DTA, SEM, and PZC analysis. The results proved that the features of the composites were completely different from their bare components. Density Functional Theory (DFT) calculations were performed at the B3LYP/6-311++G** level to enlighten the elementary physical and chemical properties of A, C, P, and G compounds. The vibrational modes obtained by calculations were compared with those observed in the FT-IR spectra. The Frontier Molecular Orbital (FMO) analyses showed that the component G was the softer and had smaller energy gap than the other components and vice versa for component P. NBO (Natural Bond Orbital) analyses implied that the n → П* (resonance) interactions for components A, G, and P contributed to the lowering of the molecular stabilization, whereas that the n → σ* (anomeric) interactions were responsible for decreasing of the stabilization of the component. From the obtained results, these kinds of components can be hoped the promising materials for usage in the many scientific fields, especially in medicine and in drug design.

Adsorption of adipic acid in Al/B-N/P nanocages: DFT investigations.

Drug delivery clusters based on nanocages recently have been the most capable to study. Adipic acid (ADPA) interaction mechanism over nanocages of X(Al/B)12Y(N/P)12 was investigated. We analyzed various electronic, chemical, and spectroscopic properties with nanocages of the adsorbed ADPA molecule. Adsorption energies were calculated to study the adsorption of ADPA with nanocages. Raman enhanced surface scattering is used to track the drug as an effective approach to vibrational spectroscopy. Detection of the drug has been investigated using the SERS properties of nanocages. Title drug acts as a donor of electrons and adsorbs at the electrophilic site of nanocages. Variations in chemical descriptors to recognize the sensing property of ADPA-nanocages are also noted. Analysis of various properties explains enhancement which makes it possible to detect the drug in other products. • Interaction of adipic acid with fullerene-like metal nanocages • Enhancement of spectral properties • Changes in charge transfer values in nanocage-drug system • Docking studies identify the drug delivery property.

A combined molecular dynamic simulation, DFT calculations, and experimental study of the eriochrome black T dye adsorption onto chitosan in aqueous solutions.

This study aims to evaluate and understand the adsorption of eriochrome black T (EB) by chitosan extracted from local shrimp shells under different experimental conditions. Chitosan samples were characterized by XRD, SEM, and FTIR. Experimental results indicate that the process was pH-dependent with a high adsorption capacity in acidic medium. The adsorption was rapid and kinetic data were suitably correlated to the pseudo-second-order kinetic model. EB molecules were adsorbed on monolayer according to the Langmuir model with an adsorption capacity of 162.3 mg/g. On the other hand, it should be noted that calculated quantum chemical parameters support the experimentally obtained results. The interaction energies calculated for (molecule/chitosan) complexes were in the order of H2EB- > HEB2- (O38) > HEB2- (O48) > EB > H3EB > EB3-, which means that the best and possible adsorption process can take place with H2EB- form. The molecular dynamics (MD) approach was performed to illuminate the nature of the relationship between the EB and the chitosan (110) surface. It was found that the chitosan (110) surface adsorbs EB molecule in a nearby parallel orientation. The higher negative adsorption energy determined for the H2EB- implies that the adsorption mechanism is the typical chemisorption.

Conformational analysis and quantum descriptors of two new imidazole derivatives by experimental, DFT, AIM, molecular docking studies and adsorption activity on graphene.

1-[2-(2-hydroxy-3-methoxy-5-(4-methoxyphenylazo)benzaldeneamino)ethyl]-3-methyl-3H-imidazole (HMY) and 1-[2-(2-hydroxy-3-methoxy-5-(4-methylphenylazo)benzaldene amino)ethyl]-3-methyl-3H-imidazole (HMM) were synthesized and characterized using spectral analysis. Conformational analysis has been achieved using potential energy scan for different rotable bonds for obtaining the lowest energy conformer. Conformer with minimum energy is obtained along the dihedral angle N30-C31-C34-N37. QTAIM analysis gives nature and strength of hydrogen bonding interactions. UV-Vis, electrostatic potential and chemical descriptors are analyzed. Interaction of HMY and HMM with graphene is analyzed in terms of SERS activity. Chemical reactivity descriptors were investigated for graphene-drug systems. NLO activity of parent drugs and its graphene complexes show good activity. The wavenumber downshift of different modes is noted. Title molecules exhibit inhibitory activity against cytochrome C peroxidase. Interactions with graphene sheets are theoretically predicted for the title compounds.

New route for synthesis of 2-(2,2-dimethoxyethyl)-1,2,3,4,5,6-hexahydro-1,5-methanoazocino[4,3-b]indole and DFT investigation.

Development of efficient sequences for the synthesis of the title compound (2-(2,2-dimethoxyethyl)-1,2,3,4,5,6-hexahydro-1,5-methanoazocino[4,3-b]indole) (7) was described. The title compound was synthesized through several steps starting from phenylhydrazine hydrochloride and dimethyl (R)-2-(3-oxocyclohexyl)malonate. In this route, all synthesized compounds were observed by spectroscopic tools (FT-IR, NMR): Methyl-2-(2,3,4,9-1H-carbazol-2-yl)acetate (3), 2-(2,3,4,9-tetrahydro-1H-carbazol-2-yl)acetic acid (4), N-(2,2-dimethoxyethyl)-2-(2,3,4,9-tetrahydro-1H-carbazol-2-yl)acetamide (5), 2-(2,2-dimethoxyethyl)-1,2,4,5,6,7-hexahydro-3H-1,5-methanoazocino[4,3-b]indol-3-one (6), 2-(2,2-dimethoxyethyl)-2,3,4,5,6,7-hexahydro-1H-1,5-methanoazocino[4,3-b]indole (7). The central step in these syntheses is the dehydrogenative reaction, which constructs the tetracyclic ring system from a much simpler tetracyclic precursor. The six-stable conformers of the compound (7) were used for further calculations such as FT-IR, NMR, NLO, and FMO analyses, performed at the B3LYP/6-311++G(d,p) level. This work revealed that (7) can be a good material to use in the non-linear optical material because its ß tensor is greater ten times than that of the urea.