def2-TZVP Basis Set Research Articles

Fragmentation Method for Computing Quantum Mechanics and Molecular Mechanics Gradients for Force Matching: Validation with Hydration Free Energy Predictions Using Adaptive Force Matching.

A fragmentation approach referred to as a simple overlapping region method for force matching (SORForM) is presented. SORForM is designed to enable efficient computation of quantum mechanical (QM) forces for large molecules and is validated in the framework of adaptive force matching (AFM) to develop solute models in water. The SORForM method divides a molecule into overlapping QM regions with each region containing a gradient zone and a buffer zone. The buffer zone ensures that the atoms in the gradient zone have their surroundings unchanged with fragmentation. The performance of the method is validated with mefenamic acid and linalyl acetate by comparing the hydration free energies of AFM models developed with and without SORForM. The AFM hydration free energies are also compared with that of the experiments. The models developed with B3LYP-D3(BJ) and def2-TZVP are in excellent agreement with experiments. Our work shows that PBE-D3(BJ) provides less satisfactory results when compared to B3LYP-D3(BJ). The def2-TZVP basis set is found to greatly improve the agreement with experiments when compared to a double-zeta quality basis set.

Exploring the water hydrogen-bonding effects on the ground and low-lying excited states of serotonin

In this work, we examined the ground and low-lying excited states of the serotonin (SERO) molecule and of four of its water hydrogen-bonded complexes (SERO-(H2O)n, with n = 1 and 2). Density functional theory (DFT) and its time-dependent variant (TD-DFT) were used for determining, respectively, ground state properties (such as equilibrium structures and relative energetics, when applicable) and excited state parameters (vertical excitation energies, generalized oscillator strengths (GOS), and structures). The CAM-B3LYP exchange–correlation functional with the def2-TZVP basis set was used and all the computations were performed in the gas-phase and in water (through the use of the integral equation formalism polarizable continuum model, IEF-PCM). In terms of ground-state, the existence of the H⋯O–H⋯N interaction in one of the SERO-H2O conformations contributed to the stabilization of the system when compared to its corresponding counterpart, with solvation decreasing (from 3.43 kcal/mol in the gas-phase to 1.75 kcal/mol in water) the differences regarding their relative energies. While no major differences regarding the excitation energies associated to an accessible state are suggested from the comparison between the results obtained for a given system through the consideration of solvation and those corresponding determined in the gas-phase, the hydrogen-bond interactions (originating from the explicit water molecules) combined with the implicit (water) solvation may be responsible for providing synergic effects in terms of increasing both the GOS related to a given open state as well as the number of excited states accessible, suggesting an enhancement in the photoabsorption. Taking one of the SERO-(H2O)2 conformations as instance, all the five lowest-lying excited singlets of the system were determined as being accessible (having GOS from 0.1036 to 0.5664) in water while only a single excited state (with GOS = 0.1150) is expected to be open in the gas-phase environment.

Theoretical studies, Hirshfeld surface analysis, and crystal structure determination of a newly synthesized benzothiazole copper(II) complex

A mononuclear copper(II) complex [Cu(LBTZ)2] was synthesized from the Schiff base HLBTZ (2-(benzo[d]thiazol-2-yl)-6-ethoxyphenol). The structural validation of the compounds was carried out with the help of different studies viz., elemental (C, H, and N), FT-IR, NMR (1H and 13C), and for [Cu(LBTZ)2], by X-ray crystal diffraction method. The complex was crystallized out in the orthorhombic Pbcn space group and exhibits a highly distorted tetrahedral geometry. Hirshfeld surface (HS) analysis using 2D fingerprint plots of the [Cu(LBTZ)2] was conducted to elaborate on different kinds of non-covalent, inter, and intramolecular interactions that existed in the solid crystalline scaffolds, which accounted for the strengthening of the crystal lattice. The molecular structures of the HLBTZ and [Cu(LBTZ)2] were further investigated by optimizing them with the help of DFT using the B3LYP hybrid method, and the Def2-TZVP basis set. The optimized geometries of the compounds and their related molecular parameters like frontier orbital energy gap, dipole moment, molecular electrostatic potential map, and natural bond orbitals calculation have also been used to understand the properties.

Synthesis, crystal structure, spectral characterization, theoretical studies, and investigation of catalytic activity in selective oxidation of sulfides by oxo-peroxo tungsten(VI) Schiff base complex

A novel oxo–peroxo tungsten(VI) Schiff base complex, [WO(O2)L(CH3OH)], a homogeneous catalyst for sulfoxidation was synthesized by treating WO3 in the presence of H2O2 with a dibasic tridentate (ONO) Schiff base ligand. The complex was characterized by FT–IR, 1H NMR, and 13C NMR spectroscopy. Moreover, the structure of the crystalline tungsten(VI) complex was further investigated by single crystal X-ray diffraction analysis (SC-XRD). The crystal structure analysis revealed that the complex is hepta-coordinated, and metal ion is surrounded by ONO set of the coordinated doubly deprotonated ligand to adopt a distorted pentagonal–bipyramidal geometry. The theoratical calculations of the geometrical parameters, frontier molecular orbitals (FMOs), molecular electrostatic potential (MEP), and natural bond orbital (NBO) analysis of the synthesized compounds utilizing DFT at the B3LYP level of theory at the Def2-TZVP basis set revealed that the predicted data match the experimental results. The main purpose of the current study is to employ the synthesized W complex for its homogeneous catalytic effectiveness for the oxidation of aryl and alkyl sulfides in ethanol by using 30% aqueous H2O2.

Sequence Analysis, Structure Prediction of Receptor Proteins and In Silico Study of Potential Inhibitors for Management of Life Threatening COVID-19

Background:Treatment of the Covid-19 pandemic caused by the highly contagious and pathogenic SARS-CoV-2 is a global menace. Day by day, this pandemic is getting worse. Doctors, scientists and researchers across the world are urgently scrambling for a cure for novel corona virus and continuously working at break neck speed to develop vaccines or drugs. But to date, there are no specific drugs or vaccines available in the market to cope up with the virus.Objective:The present study helps us to elucidate 3D structures of SARS-CoV-2 proteins and also to identify natural compounds as potential inhibitors against COVID-19.Methods:The 3D structures of the proteins were constructed using Modeller 9.16 modeling tool. Modelled proteins were validated with PROCHECK by Ramachandran plot analysis. In this study, a small library of natural compounds (fifty compounds) was docked to the hACE2 binding site of the modelled surface glycoprotein of SARS-CoV-2 using AutoDock Vina to repurpose these inhibitors against SARS-CoV-2. Conceptual density functional theory calculations of the best eight compounds had been performed by Gaussian-09. Geometry optimizations for these molecules were done at M06-2X/ def2-TZVP level of theory. ADME parameters, pharmacokinetic properties and drug likeness of the compounds were analyzed using swissADME website.Results:In this study, we analysed the sequences of surface glycoprotein, nucleocapsid phosphoprotein and envelope protein obtained from different parts of the globe. We modelled all the different sequences of surface glycoprotein and envelop protein in order to derive 3D structure of a molecular target, which is essential for the development of therapeutics. Different electronic properties of the inhibitors have been calculated using DFT through M06-2X functional with def2-TZVP basis set. Docking result at the hACE2 binding site of all modelled surface glycoproteins of SARSCoV- 2 showed that all the eight inhibitors (actinomycin D, avellanin C, ichangin, kanglemycin A, obacunone, ursolic acid, ansamiotocin P-3 and isomitomycin A) studied here were many folds better compared to hydroxychloroquine which has been found to be effective to treat patients suffering from COVID-19. All the inhibitors meet most of the criteria of drug likeness assessment.Conclusion:We expect that eight compounds (actinomycin D, avellanin C, ichangin, kanglemycin A, obacunone, ursolic acid, ansamiotocin P-3 and isomitomycin A) can be used as potential inhibitors against SARS-CoV-2.

DFT Study of the Molecular and Electronic Structure of Metal-Free Tetrabenzoporphyrin and Its Metal Complexes with Zn, Cd, Al, Ga, In.

The electronic and molecular structures of metal-free tetrabenzoporphyrin (H2TBP) and its complexes with zinc, cadmium, aluminum, gallium and indium were investigated by density functional theory (DFT) calculations with a def2-TZVP basis set. A geometrical structure of ZnTBP and CdTBP was found to possess D4h symmetry; AlClTBP, GaClTBP and InClTBP were non-planar complexes with C4v symmetry. The molecular structure of H2TBP belonged to the point symmetry group of D2h. According to the results of the natural bond orbital (NBO) analysis, the M-N bonds had a substantial ionic character in the cases of the Zn(II) and Cd(II) complexes, with a noticeably increased covalent contribution for Al(III), Ga(III) and In(III) complexes with an axial –Cl ligand. The lowest excited states were computed with the use of time-dependent density functional theory (TDDFT) calculations. The model electronic absorption spectra indicated a weak influence of the nature of the metal on the Q-band position.

Interaction of halomethane CH3Z (Z = F, Cl, Br) with X12Y12 (X = B, Al, Ga & Y = N, P, As) nanocages

The feasibility of detecting halomethanes containing CH3F, CH3Cl, and CH3Br onto the exterior surface of inorganic-based nanocages X12Y12 (X = B, Al, Ga, and Y = N, P, As) was investigated using a density functional theory (DFT). All of the configurations, including the pristine halomethanes or nanocages and the gas/nanocage systems, were optimized by B3LYP functional and DEF2-TZVP basis sets. Comparative single point energy calculations were performed using different functional containing B3LYP, M06-2X, ωB97XD, and CAM-B3LYP, together with DEF2-TZVP and DEF2-QZVP. Al12N12, Al12P12, Al12As12 have relatively higher adsorption energies compared with other studied here. Cages with Boron viz. B12N12, B12P12, B12As12 found to have very weak interaction with halomethanes. HOMO-LUMO gap and total density of states (TDOS) plots were analyzed to confirm the kind of interaction nanocages having with halomethanes. The nature of intermolecular interactions was considered by implementing the quantum theory of atoms in molecules (QTAIM). The adsorption of halomethanes onto nanocages was found to be exothermic and hence energetically favorable.

Atom accurate structure determination of alprazolam/cyclodextrin inclusion complexes by ROESY and computational approaches

A lot of interest has been seen in computational methods that provide reliable atom accurate structures of different molecular systems. In this article, we describe the complexation of alprazolam (ALP) with three cyclodextrins, i.e., α-, β- and γ-CD. ROESY spectra showed that no complex was formed between ALP and α-CD however, ring A of ALP formed ICs with β- and γ-CD. Therefore, structures of ALP/β-CD and ALP/γ-CD were obtained by a combination of NMR (2D-ROESY) and computational methods by a quantitative ROESY approach. Here we determined the structures of CD ICs by a method recently used in our laboratory and then the structures were obtained independently by DFT (B3LYP functional and def2-TZVP basis set). The structures obtained by both methods were compared with each other. Results demonstrated that our method provides reasonable structures comparable to DFT, and can be used to obtain highly atom accurate structures of CD inclusion complexes. Quantitative ROESY analysis of MM and MD structures consume less time and are cheap as compared to DFT, which is highly CPU demanding and time taking. Negative values of binding energy showed that the process of inclusion was spontaneous and complexes formed were stable. The large negative value of binding energy for ALP/β-CD as compared to ALP/γ-CD showed a higher binding affinity of ALP towards β-CD. FMO studies also revealed the higher HOMO-LOUMO gap for inclusion complexes as compared to pure ALP. Intermolecular H-bonds formed in both the complexes are also one of the forces responsible for inclusion complex formation.

Accurate 57Fe Mössbauer Parameters from General Gaussian Basis Sets.

The prediction of isomer shifts in 57Fe Mossbauer spectra is typically achieved by building calibration lines using the values of the density at the nuclear position. Using Slater-type orbital basis or large and specific Gaussian-type orbital basis has been thus far mandatory to achieve accurate predictions with density functional theory methods. In this work, we show that replacing the value of the density at the nucleus by the density integrated in a sphere of radius 0.06 au centered on the Fe nuclei yields excellent calibration lines (r2 = 0.976) with a high predictive power (q2 = 0.975, MAE = 0.055 mm·s–1) while using the conventional def2-TZVP basis set and X-ray geometrical parameters. Our data set comprises 69 57Fe-containing compounds and 103 signals. We also find B3LYP performing significantly better than the PW91 functional.

Sonication-assisted synthesis of new Schiff bases derived from 3-ethoxysalicylaldehyde: Crystal structure determination, Hirshfeld surface analysis, theoretical calculations and spectroscopic studies

• A novel series of the Schiff bases have been synthesized by treating substituted aminopyridines with 3-ethoxysalicylaldehyde with the help of ultrasonic irradiations. • Single crystals of the two compounds were screened via X-ray diffraction analysis. • Hirshfeld surface (HS) analysis was conducted by using crystal explorer software. • Electronic and structural parameters of all prepared compounds were investigated by employing the B3LYP/Def2-TZVP method. A rapid and efficient preparation of a new series of the Schiff bases (Pn) by the reaction of 2-aminopyridine derivatives with 3-ethoxysalicylaldehyde under ultrasonic irradiation is reported. Sono-chemical synthesis is the safest and greener method for the preparation of Schiff bases in the shorter period of time with higher yield as compared to traditional methods. The synthesized compounds have been characterized by 1 H NMR spectroscopic technique and elemental analyses. Furthermore, the crystal structures of two compounds ( P0 and P6 ) were determined by single crystal X-ray diffraction studies. Hirshfeld surface analysis showed that H…H interatomic contact is the most significant contributor in crystal packing of both compounds with percentage contribution of 53.7% and 57.7% for P0 and P6 , respectively. Theoretical calculations of the synthesized compounds were carried out by DFT using B3LYP method with the help of Def2-TZVP basis set, indicating that the results of calculation are in accordance with the experimental findings. The synthesis, crystal structure, Hirshfeld surface analysis, theoretical calculation and spectroscopic studies of new Schiff bases derived from 3-ethoxysalicylaldehyde have been reported.

Synthesis, spectral characterization, crystal structure and catalytic activity of a novel dioxomolybdenum Schiff base complex containing 4-aminobenzhydrazone ligand: A combined experimental and theoretical study

A novel dioxomolybdenum Schiff base complex, [MoO2(L)(H2O)], was synthesized by the reaction of MoO2(acac)2 and an ONO donor Schiff base ligand (H2L:(E)-4-amino-N'-(3-ethoxy-2-hydroxybenzylidene)benzohydrazide) derived by the condensation of 4-aminobenzohydrazide and 3-ethoxysalicylaldehyde. The synthesized ligand and complex were characterized by various spectroscopic techniques like FT-IR, 1H NMR, 13C NMR, and elemental analysis (CHN). The structure of the complex was confirmed by single crystal X-ray diffraction analysis (SC-XRD). The geometry around the central metal ion in the complex was distorted octahedral as revealed by the data collected from diffraction studies. Theoretical calculations of the synthesized compounds, carried out by DFT using B3LYP and PBE0 levels of theory at the Def2-TZVP basis set, indicated that the calculated results are in agreement with the experimental findings. Moreover, the catalytic efficiency of the complex was investigated by oxidizing the aryl and alkyl sulfides in the presence of 30 % aqueous H2O2 in ethanol.

A comparison of three DFT exchange-correlation functionals and two basis sets for the prediction of the conformation distribution of hydrated polyglycine.

The performance of three density functional theory (DFT) exchange-correlation functionals, namely, Perdew-Burke-Ernzerhof (PBE), BP86, and B3LYP, in predicting conformational distributions of a hydrated glycine peptide is tested with two different basis sets in the framework of adaptive force matching (AFM). The conformational distributions yielded the free energy profiles of the DFT functional and basis set combinations. Unlike traditional validations of potential energy and structural parameters, our approach allows the free energy of DFT to be validated. When compared to experimental distributions, the def2-TZVP basis set provides better agreement than a slightly trimmed aug-cc-pVDZ basis set. B3LYP is shown to be better than BP86 and PBE. The glycine model fitted against B3LYP-D3(BJ) with the def2-TZVP basis set is the most accurate and named the AFM2021 model for glycine. The AFM2021 glycine model provides better agreement with experimental J-coupling constants than C36m and ff14SB, although the margin is very small when compared to C36m. Our previously published alanine model is also refitted with the slightly simplified AFM2021 energy expression. This work shows good promise of AFM for developing force fields for a range of proteinogenic peptides using only DFT as reference.

Mechanism and Selectivity of Cyclopropanation of 3-Alkenyl-oxindoles with Sulfoxonium Ylides Catalyzed by a Chiral N,N'-Dioxide-Mg(II) Complex.

The mechanism and stereoselectivity of an asymmetric cyclopropanation reaction between 3-alkenyl-oxindole and sulfoxonium ylide catalyzed by a chiral N,N'-dioxide-Mg(II) complex were explored using the B3LYP-D3(BJ) functional and the def2-TZVP basis set. The noncatalytic reaction occurred via a stepwise mechanism, with activation barriers of 21.6-23.5 kcal mol-1. The C2-Cα bond formed followed by the carbanion SN2 substitution, constructing a three-membered ring in spiro-cyclopropyl oxindoles, accompanied by the release of dimethylsulfoxide. The electron-withdrawing N-protecting t-butyloxy carbonyl (Boc) and acetyl (Ac) groups in isatin enhanced the local electrophilicity of the C2 atom and the repulsion between the two COPh groups in the reactants, contributing to high reactivity as well as good diastereoselectivity results. The N-Boc-3-phenacylideneoxindole coordinated to the chiral ligand (L-PiPr2) in a bidentate fashion, forming a hexacoordinate-Mg(II) complex as the reactive species. The origin of enantioselectivity was from the shielding effect of 2,6-diisopropylphenyl groups in the ligand toward the si-face of oxindole. The repulsion between the SO(CH3)2 and COPh groups in 3-alkenyl-oxindole and the neighboring ortho-iPr group in the ligand directed the re-face of ylide to attack the re-face of oxindole preferably, contributing to the high diastereoselectivity of the product. A metal-ion-ligand matching relationship was important for a good asymmetric induction effect of the chiral N,N'-dioxide-metal catalyst. A large chiral cavity in the Zn(II) catalyst weakened the shielding effect of 2,6-diisopropylphenyl groups in the ligand toward the prochiral face of oxindole, leading to inferior enantioselectivity observed in the experiment.

The SN2 reaction and its relationship with the Walden inversion, the Finkelstein and Menshutkin reactions together with theoretical calculations for the Finkelstein reaction

This communication gives an overview of the relationships between four reactions that although related were not always perceived as such: SN2, Walden, Finkelstein, and Menshutkin. Binary interactions (SN2 & Walden, SN2 & Menshutkin, SN2 & Finkelstein, Walden & Menshutkin, Walden & Finkelstein, Menshutkin & Finkelstein) were reported. Carbon, silicon, nitrogen, and phosphorus as central atoms and fluorides, chlorides, bromides, and iodides as lateral atoms were considered. Theoretical calculations provide Gibbs free energies that were analyzed with linear models to obtain the halide contributions. The M06-2x DFT computational method and the 6-311++G(d,p) basis set have been used for all atoms except for iodine where the effective core potential def2-TZVP basis set was used. Concerning the central atom pairs, carbon/silicon vs. nitrogen/phosphorus, we reported here for the first time that the effect of valence expansion was known for Si but not for P. Concerning the lateral halogen atoms, some empirical models including the interaction between F and I as entering and leaving groups explain the Gibbs free energies.

Adsorption of alkali and alkaline earth ions on nanocages using density functional theory

The adsorption of alkali and alkaline earth ions onto the exterior surface of inorganic nanocages X12Y12 (X = B, Al, Ga and Y = N, P, As) was investigated by using the density functional theory (DFT). All of the configurations, including the pristine ions or nanocages, as well as the ion adsorbed nanocage systems, were optimized using B3LYP-D3 functional and DEF2-TZVP basis sets. Comparative single point energy calculations were performed using different functionals viz. B3LYP-D3, M06-2X, ωB97XD and CAM-B3LYP, together with DEF2-TZVP and DEF2-QZVP basis sets. The results of natural bond orbital (NBO), quantum theory of atoms in molecules (QTAIM), and non-covalent interaction (NCI) analyses were compatible with the results of electronic properties. Total density of states (TDOSs), the natural charge, Wiberg bond index (WBI), natural electron configuration, donor–acceptor NBO interactions and second-order perturbation energies are obtained. Strong interaction between the ions and the nanocages is observed and the tendency of the ions to adsorb onto the surfaces of the mentioned X12Y12 nanocages is in the order Be++ > Mg++ > Ca++ > Li+ > Na+ > K+. These nanocages may be potential sensors for these alkali and alkaline earth ions.

Facile Charge Transfer between Barbituric Acid and Chloranilic Acid over g-C3N4: Synthesis, Characterization and DFT Study

The molecular complexes between barbituric acid (BU) and chloranilic acid (ChA) over graphitic nitride (g-C3N4) are investigated. The molecular complexes and the nanocomposite were investigated both in solid state and in methanol. The solid complexes and the corresponding nanocomposite were investigated using FTIR, TGA, and UV-Vis spectroscopy. The structures were explored using DFT calculations using wB97XD/ and def2-TZVP basis set. The DFT calculations revealed the formation of hydrogen-bonded complexes, which initiate the proton transfer from ChA to BU. Immobilization of the BUChA complex over the g-C3N4 sheet was stabilized by weak non-covalent interactions, such as π–π interactions. g-C3N4 facilitated the charge transfer process, which is beneficial for different applications.

Novel oxovanadium and dioxomolybdenum complexes of tridentate ONO-donor Schiff base ligand: Synthesis, characterization, crystal structures, Hirshfeld surface analysis, DFT computational studies and catalytic activity for the selective oxidation of benzylic alcohols

Two new oxovanadium and dioxomolybdenum Schiff base complexes, [VvO(L)(OCH3)(CH3OH)] and [MoVIO2(L)(CH2CH3OH)], were synthesized by treating an ONO-donor type Schiff base ligand (H2L) derived by condensation of 5-nitrosalicylaldehyde and nicotinic hydrazide with oxo and dioxo acetylacetonate salts of vanadium and molybdenum, [VO(acac)2 and MoO2(acac)2], respectively. The synthesized ligand and complexes were characterized by various spectroscopic techniques like FT-IR, multinuclear (1H, 13C) NMR, elemental analysis and the most authentic single crystal X-ray diffraction analysis. In both complexes the geometry around the central metal ions was distorted octahedral as revealed by the data collected from diffraction studies. Theoretical calculation of the synthesized compounds were carried out by DFT as well as TD-DFT using B3LYP method by employing the Def2-TZVP basis set. The findings of theoretical data indicated that the calculated results are in accordance with the experimental findings. Moreover, the catalytic efficiencies of both complexes were investigated by oxidizing the benzylic alcohols in the presence of urea hydrogen peroxide (UHP) in acetonitrile.

Quantum Chemical Study of the Structures and Stability of Copper(II) Bis(diketonate) Dimers

The quantum-chemical study of the copper diketonate dimers ([Cu(Acac)2]2 and [Cu(Acac)Hfac)]2) is performed using various functionals (B3LYP, TPSSh, PBE0, and B2PLYP) and basis sets (6-311++G(d,p) and Def2-TZVP) and taking into account dispersion interactions (D3BJ). The calculations using the B3LYP and TPSSh functionals combined with the Def2-TZVP basis set give the best agreement with experiment. The Basis Set Superposition Errors introduce no substantial changes to the stabilization energies of the considered systems. The obtained results show that the quantum-chemical study of similar associates of transition metals should be performed without empirical D3BJ dispersion corrections.

A DFT investigation of anion-π interactions between halogen oxyanions (XO3 −, X = Cl, Br, I) and aromatic π-systems (benzene and coronene)

Anion-π interactions have proved to play a key role in many chemical and biochemical phenomena. In order to investigate the nature and the applications of these interactions, the anion-π interactions of the chlorate (ClO3 −), bromate (BrO3 −), and iodate (IO3 −) oxyanions with benzene and coronene have been studied using density functional theory (DFT). The structures, adsorption energies, and electronic properties of XO3 −(X = Cl, Br, I) adsorbed on benzene and coronene have been explored using dispersion corrected DFT hybrid functional, M06-2X-D3, with the def2-TZVP basis set. Benzene and coronene have been respectively used as a building block and a simple flake of graphene. The interaction of these anions with benzene is found to be unexpectedly favorable. Their binding strength is further increased when the anions are adsorbed on coronene. Moreover, energy decomposition analysis based on symmetry adapted perturbation theory (SAPT) has been performed and the nature of interaction is characterized using noncovalent interaction analysis (NCI) based on reduced density gradient (RDG) method. Generally, the favorable binding of these anions with benzene or coronene is mainly ascribed to dispersion interactions. These anion-π interactions with graphene flakes or with benzene can be utilized in the design of anions receptors and detectors.

An oxalate-bridged oxidovanadium(IV) binuclear complex that improves the in vitro cell uptake of a fluorescent glucose analog

The centrosymmetric oxidovanadium(IV) complex (Et3NH)2[{VO(OH2)(ox)}2(μ–ox)] (I), where ox2− = oxalate, was synthesized and characterized by X-ray diffraction (single-crystal and powder, PXRD), thermogravimetric (TGA), magnetic susceptibility (at room temperature) and spectroscopic analyses (infrared, Raman and electron paramagnetic resonance, EPR, spectroscopies). In the solid state, each vanadium center is coordinated by the oxygen atoms of a bis-bidentate oxalate bridging ligand, a terminal oxalate, an oxo group and one water molecule. The electronic structure of the binuclear complex was investigated by density functional theory (DFT) calculations, both in vacuum and in a simulated aqueous environment, employing the ωB97XD functional and the def2TZVP basis set. The cytotoxicity of I was evaluated in vitro in the human hepatocellular carcinoma cell line HepG2, giving an IC50 value of 15.67 µmol L−1 after incubation for 24 h. The EPR analysis of I in aqueous solution suggested the maintenance of the binuclear structure, while in the hyperglycemic medium DMEM the complex suffers dissociation to give a mononuclear oxidovanadium(IV) species. HepG2 cell treatment with 0.10 and 0.50 µmol L−1 of I in DMEM increased 2-NBDG (2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose) uptake significantly (up to 91% as compared to HepG2 in hyperglycemic condition, 59%). These results indicate a promising activity of I to be investigated further in additional antidiabetic studies.