Synthesis, crystal structures and density functional theory study of dimeric copper(II) complexes of a tridentate Schiff-base ligand

Oxalate- or 4,4′-bipyridine-bridged dimeric copper(II) complexes, [Cu₂L₂(μ-ox)] (1) and [Cu₂L₂(μ-bipy)](BF₄)₂ (2) [where ox = oxalate, bipy = 4,4′-bipyridine, HL = N-(1H-pyrrol-2-ylmethylene)-2-pyridineethanamine, L⁻ = HL−H⁺], have been synthesised and characterised by elemental analysis, IR, UV-Vis and single crystal X-ray diffraction. Crystal structure determinations carried out on 1 and 2 reveal that 1 is an oxalate-bridged centrosymmetrical square pyramidal dimeric copper(II) complex while 2 is a 4,4′-bipyridine-bridged non-centrosymmetric square planar dinuclear copper(II) complex. Comparison of the optimised geometries with the corresponding crystal structures suggests that the B3LYP/LANL2DZ level can reproduce the structures of 1 and 2 on the whole. The electronic spectra of 1 and 2 predicted by B3LYP/LANL2DZ method show some blue shifts compared with their experimental data. Thermal analysis carried out on 1 shows that there is only one exothermal peak at about 260 °C and the residue is presumably Cu₂O₄N₆.     

Density functional theory studies of oxygen and carbonate binding to a dicopper patellamide complex

In this work we present results of density functional theory (DFT) calculations on dicopper patellamides and their affinity for molecular oxygen and carbonate. Patellamides are cyclic octapeptides that are produced by a cyanobacterium, and may show promise as therapeutics. Thus, carbonate binding to a dicopper patellamide center gives a stable cyclic octapeptide with a twist of almost 90°. The system exists in close-lying open-shell singlet and triplet spin states with two unpaired electrons in orthogonal σ^∗ orbitals on each metal center. Subsequently, we replaced carbonate with dioxygen and found a stable Cu₂(μ-O)₂ diamond shaped patellamide core. In this structure the original dioxygen bond is significantly weakened to essentially a single bond, which should enable the system to transfer these oxygen atoms to substrates. We predicted the IR and Raman spectra of the Cu₂(μ-O)₂ diamond shaped patellamide structure using density functional theory and found a considerable isotope effect on the O-O stretch vibration for ¹⁶O₂ versus ¹⁸O₂ bound structures. Our studies reveal that carbonate forms an extremely stable complex with dicopper patellamide, but that additional molecular oxygen to this system does not give a potential oxidant. Therefore, it is more likely that carbonate prepares the system for dioxygen binding by folding it into the correct configuration followed in the proposed catalytic cycle by a protonation event preceding dioxygen binding to enable the system to reorganize to form a stable Cu₂(μ-O)₂-patellamide cluster. Alternatively, carbonate may act as an inhibitor that blocks the catalytic activity of the system. It is anticipated that the Cu₂(μ-O)₂-patellamide structure is a potential active oxidant of the dicopper patellamide complex.     

Density functional theory studies of model complexes for molybdenum-dependent nitrate reductase active sites

Molybdenum and tungsten complexes as models for the active sites of assimilatory or dissimilatory nitrate reductases (NR) were computed at the CPCM-B98/SDDp//B3LYP/Lanl2DZp* plus zero point energy level of density functional theory. The ligands were chosen on the basis of available experimental protein or small chemical model structures. A water molecule is found to bind to assimilatory NR models [(Me₂C₂S₂)MO(YMe)]⁻ (−11.5 kcal mol⁻¹ for M is Mo, Y is S) and may be replaced by nitrate (−4.5 kcal mol⁻¹) (but a hydroxy group may not). Nature’s choice of M is Mo and Y is S for NR has the largest activation energy for protein-free models (13.3 kcal mol⁻¹) and the least exothermic reaction energy for the nitrate reduction (−14.9 kcal mol⁻¹) compared with M is W and Y is O or Se alternatives. Water binding to dissimilatory NR model complexes [(Me₂C₂S₂)₂M(YR)]⁻ is considerably endothermic (10.3 kcal mol⁻¹); nitrate binding is only slightly so (1.5 kcal mol⁻¹ for RY⁻ is MeS⁻). The exchange of an oxo ligand (assimilatory NR) for a dithiolato ligand (dissimilatory NR model) reduces the exothermicity (−8.6 kcal mol⁻¹ relative to the fivefold-coordinate reduced complex) and raises the barrier for oxygen atom transfer (OAT) in the nitrate complex (19.2 kcal mol⁻¹). Not for the mono but only for the bisdithiolato complexes hydrogen bonding involving the coordinated substrate may significantly lower the OAT barrier as shown by explicitly adding water molecules. Substitution of tungsten for molybdenum generally lowers OAT activation energies and makes nitrate reduction reaction energies more negative. Bidentate carboxylato binding identified in Escherichia coli NarGHI is the preferred binding mode also for an acetato model. However, one dithiolato ligand folds when the Mo^VI center is bare of a good π-donor ligand, e.g., an oxo group. Computations on [(mnt)₂Mo^IV(YR)(PPh₃)]⁻ [mnt is (CN)₂C₂S₂ ²⁻] gave a smaller nitrate reduction activation energy for RY⁻ is Cl⁻, compared with RY⁻ is PhS⁻, although experimentally only the phenyl thiolato complex and not the chloro complex was found to be a functional NR model. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Density functional theory molecular modelling,DNA interactions,antioxidant, antimicrobial,anticancer and biothermodynamic studies of bioactive water soluble mixed ligand complexes

A novel series of bioactive water soluble mixed ligand complexes (1–5) [M^II(L)(phen)AcO]. nH₂O {where M?=?Cu (1) n?=?2; Co (2), Mn (3), Ni (4), n?=?4 and Zn (5) n?=?2} were synthesized from 2-(2-Morpholinoethylimino) methyl)phenol Schiff base ligand (LH), 1, 10-phenanthroline and metal(II) acetate salt in a 1:1:1 stoichiometric ratio and characterized by several spectral techniques. The obtained analytical and spectral data suggest the octahedral geometry around the central metal ion. Density functional theory calculations have been further supportive to explore the optimized structure and chemical reactivity of these complexes from their frontier molecular orbitals. Gel electrophoresis result indicates that complex (1) manifested an excellent DNA cleavage property than others. The observed binding constants with free energy changes by electronic absorption technique and DNA binding affinity values by viscosity measurements for all compounds were found in the following order (1)?>?(2)?>?(4)?>?(5)?>?(3) > (LH). The binding results and thermodynamic parameters are described the intercalation mode. In vitro antioxidant properties disclose that complex (1) divulges high scavenging activity against DPPH^?, ^?OH, O₂^?? NO^?, and Fe³⁺. The antimicrobial reports illustrate that the complexes (1–5) were exhibited well defined inhibitory effect than ligand (LH) against the selected different pathogenic species. The observed percentage growth inhibition against A549, HepG2, MCF-7, and NHDF cell lines suggest that complex (1) has exhibited superior anticancer potency than others. Thus, the complex (1) may contribute as potential anticancer agent due to its unique interaction mode with DNA.GRAPHICAL ABSTRACT

Communicated by Ramaswamy H. Sarma     

Conformational preferences of 1,4,7-trithiacyclononane: a molecular mechanics and density functional theory study

Conformational preferences of 1,4,7-trithiacyclononane were studied using a highly efficient sampling technique based on local nonstochastic deformations and the MM2(91) force field. The results show that conformers that the molecule adopts in the crystal state were found to be low-energy conformers (LECs) within 5 kcal mol(-1) of the global minimum. A conformation with C1 symmetry was the global minimum and the C3 and C2 conformations were calculated to be 0.03 and 1.78 kcal mol(-1) higher in energy, respectively. The structures were further minimized using Density Functional Theory (DFT) calculations with two different functionals. The C2 and the C1 conformations were found to be LECs with the C3 conformation more than 4.0 kcal mol(-1) above the global minimum. The relative energies and structural ordering obtained using the BP86 functional are in agreement with the previously reported relative energies calculated using second-order Moller-Plesset (MP2) ab initio calculations. With the energy ordering being dependent on the molecular mechanics force field used, the approach of MM-->DFT (searching exhaustively the available conformational space at the MM level followed by generating the energy ordering through DFT calculations) appears to be appropriate for thiacrown ethers.     

Density functional and docking studies of retinoids for cancer treatment

The retinoic acid receptor (RAR) and retinoid X receptor (RXR) are members of the nuclear receptor superfamily. The ligand-binding domain contains the ligand-dependent activation function. The isotypes RAR, and are distinct pharmacological targets for retinoids involved in the treatment of various cancers and skin diseases. There is thus considerable interest in synthetic retinoids with isotype selectivity and reduced side effects. In this work we have focused on the retinoid acid receptor and three of its panagonists. We have carried out density functional geometry optimizations at the B3LYP/6-31G* level, computed two types of atomic charges and also electrostatic potentials. A docking program was used to investigate the interactions between the receptor and the three ligands. A theoretically more potent inhibitor, which was obtained by modifying one of the retinoic acids investigated, is proposed. Figure Superposition of the crystal structure (Å) of the 1FCX ligand with the proposed new inhibitor     

Effect of microsolvation on zwitterionic glycine: an ab initio and density functional theory study

The effect of microsolvation on zwitterionic glycine, considering both (-NH3(+)) as proton donor and (-COO(-)) as proton acceptor at correlated ab initio (MP2) level and density functional methods (B3LYP, PW91, MPW1PW91 and PBE) using 6-311++G** basis set has been reported. DFT methods have been employed so as to compare the performance/quality of different gradient-corrected correlation functionals (PW91, PBE), hybrid functionals (B3LYP, MPW1PW91) and to predict the near quantitative structural and vibrational properties, at reduced computational cost. B3LYP method outperforms among the different DFT methods for the computed hydrogen bond distances and found closer to the value obtained by correlated MP2 level, whereas MPW1PW91 and PBE methods shows very similar values but approximately 0.03 A less, compared to B3LYP method. MP2 calculation and single point CCSD(T)//MP2 calculation have been considered to decompose the interaction energy, including corrections for basis set superposition error (BSSE). Moreover, charge distribution analysis has also been carried out to understand the long raised questions, how and why the two body energies have significant contribution to the total binding energy.     

Quantum chemical modeling of enzymatic reactions: the case of 4-oxalocrotonate tautomerase

The reaction mechanism of 4-oxalocrotonate tautomerase (4-OT) is studied using the density functional theory method B3LYP. This enzyme catalyzes the isomerisation of unconjugated alpha-keto acids to their conjugated isomers. Two different quantum chemical models of the active site are devised and the potential energy curves for the reaction are computed. The calculations support the proposed reaction mechanism in which Pro-1 acts as a base to shuttle a proton from the C3 to the C5 position of the substrate. The first step (proton transfer from C3 to proline) is shown to be the rate-limiting step. The energy of the charge-separated intermediate (protonated proline-deprotonated substrate) is calculated to be quite low, in accordance with measured pKa values. The results of the two models are used to evaluate the methodology employed in modeling enzyme active sites using quantum chemical cluster models.     

Density functional study of isoguanine tetrad and pentad sandwich complexes with alkali metal ions

Isoguanine tetraplexes and pentaplexes contain two or more stacked polyads with intercalating metal ions. We report here the results of a density functional study of sandwiched isoguanine tetrad and pentad complexes consisting of two polyads with Na⁺, K⁺ and Rb⁺ ions at the B3LYP level. In comparison to single polyad metal ion complexes, there is a trend towards increased non-planarity of the polyads in the sandwich complexes. In general, the pentad sandwiches have relatively planar polyad structures, whereas the tetrad complexes contain highly non-planar polyad building blocks. As in other sandwich complexes and in metal ion complexes with single polyads, the metal ion-base interaction energy plays an essential role. In iG sandwich structures, this interaction energy is slightly larger than in the corresponding guanine sandwich complexes. Because the base–base interaction energy is even more increased in passing from guanine to isoguanine, the isoguanine sandwiches are thus far the only examples where the base–base interaction energy is larger than the base–metal ion interaction energy. Stacking interactions have been studied in smaller models consisting of two bases, retaining the geometry from the complete complex structures. From the data obtained at the B3LYP and BH&;H levels and with Møller-Plesset perturbation theory, one can conclude that the B3LYP method overestimates the repulsion in stacked base dimers. For the complexes studied in this work, this is only of minor importance because the direct inter-tetrad or inter-pentad interaction is supplemented by a strong metal ion-base interaction. Using a microsolvation model, the metal ion preference K⁺≈Rb⁺?>?Na⁺ is found for tetrad complexes. On the other hand, for pentads the ordering is Rb⁺?>?K⁺?>?Na⁺. In the latter case experimental data are available that agree with this prediction.

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Figure Structures of isoguanine pentad complexes with Rb⁺ at different symmetries.

     

Density Functional Theory Calculations of Molecular Hyperpolarizabilities

Recent density functional theory calculations of molecular hyperpolarizabilities are reviewed in order to try to assess the accuracy and reliability of DFT in the specified field by comparison with experiment and with ab initio HF and post-HF methods. In a table [1] (p. 157) containing results from the paper defining the compound electronic structure method Gaussian 2 [2], Foresman presents the relative accuracies of various 'model chemistries' for calculating thermochemical quantities. The Mean Absolute Deviation (MAD) from experiment, its Standard Deviation, and the largest positive and negative errors in the computed values, are the statistical means that allow the various models to be arranged in order of increasing MAD, and thus decreasing overall accuracy. These same statistical quantities, on a percent basis for size consistency and dimensionlessness, are used in this communication for quantifying the accuracies of various combinations of DFT functionals/basis sets/quantum chemical techniques/applied field strengths, in calculations of molecular mean dipole polarizabilities <>, first-order hyperpolarizabilities and second-order hyperpolarizabilities . The relative accuracies of DFT model chemistries are thus surveyed in three tables (including authors/references arranged in chronological order, compounds studied, and program codes employed), and can serve as guidelines for selecting optimal computational methodologies.     

Interaction energies in non-covalently bound intermolecular complexes derived using the subsystem formulation of density functional theory

Interaction energies for a representative sample of 39 intermolecular complexes are calculated using two computational approaches based on the subsystem formulation of density functional theory introduced by Cortona (Phys. Rev. B 44:8454, 1991), adopted for studies of intermolecular complexes (Wesolowski and Weber in Chem. Phys. Lett. 248:71, 1996). The energy components (exchange-correlation and non-additive kinetic) expressed as explicit density functionals are approximated by means of gradient-free- (local density approximation) of gradient-dependent- (generalized gradient approximation) approximations. The sample of the considered intermolecular complexes was used previously by Zhao and Truhlar to compare the interaction energies derived using various methods based on the Kohn-Sham equations with high-level quantum chemistry results considered as the reference. It stretches from rare gas dimers up to strong hydrogen bonds. Our results indicate that the subsystem-based methods provide an interesting alternative to that based on the Kohn-Sham equations. Local density approximation, which is the simplest approximation for the relevant density functionals and which does not rely on any empirical data, leads to a computational approach comparing favorably with more than twenty methods based on the Kohn-Sham equations including the ones, which use extensively empirical parameterizations. For various types of non-bonding interactions, the strengths and weaknesses of gradient-free and gradient-dependent approximations to exchange-correlation and non-additive kinetic energy density functionals are discussed in detail.     

青蒿素及其类似物抗疟构效关系的DFT研究

为了从原子水平上揭示青蒿素及其类似物的结构与抗疟活性之间的关系,运用密度泛函理论DFT方法,在B3LYP/6-31G*水平上对青蒿素及其类似物二氢青蒿素、蒿甲醚和青蒿琥酯的结构和性质进行了理论计算。从分子的平衡构型、Wiberg键级、溶剂化能、偶极矩和静电势等方面分析了青蒿素及其类似物的抗疟构效关系。结果表明,青蒿素及其类似物结构中七元环上的过氧桥键、醚氧键以及六元环上的内酯结构是其抗疟作用的关键活性位,过氧桥键处负的静电势越多,青蒿素与血红素的相互作用越强,分子的抗疟活性越强。理论预测四个药物分子的抗疟活性顺序为:青蒿素<二氢青蒿素<蒿甲醚<青蒿琥酯,与实验活性结果一致。     

The electronic structure of Ti(BH4)3: Photoelectron spectra and calculation of vertical ionization energies

He I and He II PE spectra of Ti(BH₄)₃ are reported and assigned by reference to density functional calculations on the molecule and cation. The performance of different functionals in predicting the first vertical ionization energy is assessed. Calculations based on hybrid functionals are found to give ionisation energies closer to the experimental value than those using pure density functionals. The accuracy of the ΔSCF method and time dependent density functional theory in calculating higher vertical ionization energies is also examined.     

Density functional studies of closed-shell attractions of S(AuPH3)2 and HS(AuPH3)2 + and their dimers

With the help of quantum chemical calculations, S(AuPH₃)₂, [HS(AuPH₃)₂]⁺ and their dimers have been examined by using scalar-relativistic theory. In agreement with experimental data, [HS(AuPH₃)₂ ⁺]₂ is a C_2h structure. However, [S(AuPH₃)₂]₂ is predicted to favor a D_2d structure. Experimental structure parameters of the title compounds were reproduced at the Xα level. The electronic structure and HOMO–LUMO gaps were investigated. When two monomers formed a dimer, the electronic structure of the dimer changed only slightly, but the chemical stability decreased. The intermolecular aurophilic interaction energy is decomposed and analyzed.     

Effect of covalent links on the structure, spectra, and redox properties of myeloperoxidase--a density functional study

The enzyme myeloperoxidase shows several unusual properties compared to other peroxidases, e.g. a red-shifted absorption spectrum and a peroxidase activity towards chloride. It has been suggested that this is caused by the unusual covalent links between the heme group and the surrounding protein, but whether it is caused by the two ester links to Glu-242 and Asp-94 or the sulfonium ion linkage to Met-243 is unclear. To investigate these suggestions, we have used density functional theory to study the structure, spectra, and reduction potential of 25 models of myeloperoxidase in the reduced (Fe^II) and oxidized (Fe^III) states, as well as in the compound I (formally Fe^VO) and II (Fe^IVO or Fe^IVOH) states, using appropriate models of the linkages to the Asp, Glu, and Met residues (including the back-bone connection between Glu-242 and Met-243) in varying combinations. The calculated spectral shifts indicate that both the ester and sulfonium linkages play a role in the spectral shift. On the other hand, the sulfonium linkage seems to be mainly responsible for the high positive reduction potential for the both ferric/ferrous and compound I/II couples of myeloperoxidase.     

Characterization of the active site of catalytically inactive forms of [NiFe] hydrogenases by density functional theory

The inactive forms, unready (Ni-A, Ni-SU) and ready (Ni-B), of NiFe hydrogenases are modeled by examining the possibility of hydroxo, oxo, hydroperoxo, peroxo, and sulfenate groups in active-site models and comparing predicted IR frequencies and g tensors with those of the enzyme. The best models for Ni-A and Ni-SU have hydroxo (μ-OH) bridges between Fe and Ni and a terminal sulfenate [Ni–S(=O)Cys] group, although a hydroperoxo model for Ni-A is also quite viable, whereas the best model for Ni-B has only a μ-OH bridge. In addition, a mechanism for the activation of unready hydrogenase is proposed on the basis of the relative stabilities of sulfenate models versus peroxide models.     

Predicting CO2 adsorption and reactivity on transition metal surfaces using popular density functional theory methods

ABSTRACT

In this work, with Ni (110) as a model catalyst surface and CO₂ as an adsorbate, a performance study of Density Functional Theory methods (functionals) is performed. CO being a possible intermediate in CO₂ conversion reactions, binding energies of both, CO₂ and CO, are calculated on the Ni surface and are compared with experimental data. OptPBE-vdW functional correctly predicts CO₂ binding energy on Ni (?62?kJ/mol), whereas CO binding energy is correctly predicted by the rPBE-vdW functional (?138?kJ/mol). The difference in computed adsorption energies by different functionals is attributed to the calculation of gas phase CO₂. Three alternate reaction systems based on a different number of C=O double bonds present in the gas phase molecule are considered to replace CO₂. The error in computed adsorption energy is directly proportional to the number of C=O double bonds present in the gas phase molecule. Additionally, both functionals predict similar carbon–oxygen activation barrier (40?kJ/mol) and equivalent C1s shifts for probe species (?2.6?eV for CCH₃ and +1.5?eV CO₃^?), with respect to adsorbed CO₂. Thus, by including a correction factor of 28?kJ/mol for the computed CO₂ gas phase energy, we suggest using rPBE-vdW functional to investigate CO₂ conversion reactions on different metals.     

Adsorption and dimerisation of thiol molecules on Au(111) using a Z-matrix approach in density functional theory

The adsorption energetics of methanethiolate and benzenethiolate on Au(111) have been calculated using periodic density functional theory (DFT), based on the SIESTA methodology, with an internal coordinates implementation for geometry input and structure optimisation. Both molecules are covalently bound with interaction energies of 1.85 and 1.43 eV for methanethiolate and benzenethiolate, respectively. The preferred binding site is slightly offset from the bridge site in both cases towards the fcc-hollow. The potential energy surfaces (PES) have depths of 0.36 and 0.22 eV, the hollow sites are local maxima in both cases, and there is no barrier to diffusion of the molecule at the bridge site. The corresponding dimers are weakly bound for methanethiolate and benzenethiolate, with binding energies of 0.38 and 0.16 eV, respectively, and the preferred binding geometry is with the two sulphur atoms close to adjacent atop sites. The barrier to dissociation of the dimer dimethyl disulphide is estimated to lie between 0.3 and 0.35 eV.     

An attempt to determine the absolute configuration of two ascolactone stereoisomers with time-dependent density functional theory

Two stereoisomers of ascolactone (A, B), natural products with two asymmetric carbon atoms, are isolated from the marine-derived fungus Ascochyta salicorniae. Although these compounds show virtually opposite CD spectra and [alpha]D, 1H- and 13C-NMR data exclude the presence of enantiomers and suggest ascolactone A and B to be epimeric lactones. By comparing the experimental CD spectra with those calculated employing time-dependent density functional theory (TDDFT), we elucidate the configuration at one of the asymmetric carbon atoms.     

Insight into the copper coordination environment in the prion protein through density functional theory calculations of EPR parameters

Density functional theory (DFT) calculations of Cu(II) electron paramagnetic resonance (EPR) parameters for the octarepeat unit of the prion protein were conducted. Model complexes were constructed and optimized using the crystal structure of the octarepeat unit of the prion protein. Copper g and A tensors and nitrogen hyperfine and quadrupole coupling constants were calculated using DFT. Solvent effects were incorporated using the conductor-like screening model as well as through the inclusion of explicit water molecules. Calculations using the model with an additional axial water molecule added to the coordination sphere of the Cu(II) metal center give the best qualitative agreement for the copper g and A tensors. The S-band experimental EPR spectra were interpreted in light of the DFT calculations of the directly coordinated nitrogen hyperfine coupling constants which indicate that the three directly coordinated nitrogen atoms in the octarepeat unit are not equivalent. These results demonstrate that DFT calculations of EPR parameters can provide important insight with respect to the structural interpretation of experimental EPR data. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.