An ab initio and DFT study of structure and vibrational spectra of γ form of Oleic acid: Comparison to experimental data

Oleic acid (cis-9-octadecenoic acid) is the most abundant cis-unsaturated fatty acid in nature; it is distributed in almost all organisms. In this work, we present a detailed vibrational spectroscopy investigation of Oleic acid by using infrared and Raman spectroscopies. These data are supported by quantum mechanical calculations, which allow us to characterize completely the vibrational spectra of this compound. The equilibrium geometry, harmonic vibrational frequencies, infrared intensities and activities of Raman scattering were calculated by ab initio Hartree-Fock (HF) and density functional theory (DFT) employing B3LYP with complete relaxation in the potential energy surface using 6-311G(d, p) basis set. After a proper scaling the calculated wavenumbers show a very good agreement with the observed values. A complete vibrational assignment is provided for the observed Raman and infrared spectra of Oleic acid. In this work, we also investigate the deviation of vibrational wavenumbers computed with two quantum chemical methods (HF and B3LYP).     

Kinetic study on the β-glucosidase-catalysed reaction of Trichoderma viride cellulase

A kinetic study of the -glucosidase-catalysed reaction of a commercial cellulase preparation from Trichoderma viride is described. The K _m and V _max values of the -glucosidase system were: (a) 0.5 mm and 6.6 mol/min, respectively, using p-nitrophenyl -d-glucopyranoside (pNPG) as substrate; and (b) 2.5 mm and 8.1 mol/min, respectively, using cellobiose as subtrate. The glucose effect on initial reaction velocity agrees with a mixed-inhibition pattern. The inhibition constant (K _i) values were, 0.53 and 0.39 mm with nNPG and cellobiose as substrates, respectively. The temperature and pH optima were determined. Correspondence to: A. Romeu     

DFT study on the effects of β-cyclodextrin in synthesis of 2-phenylbenzimidazole via benzaldehyde and o-phenylenediamine

The conversion of 2-phenylbenzimidazole using o-phenylenediamine and benzaldehyde can be improved significantly under β-cyclodextrin (β-CD). The density functional theory (DFT) method was applied to study the whole process. According to energy parameters (binding energy, deformation energy) and structural deformation, entry models and the reaction process can be pinpointed, with o-phenylenediamine embedding β-CD from a wide rim, and then benzaldehyde passing into the inclusion from the narrow rim. Subsequently, natural bonding orbital (NBO), Mulliken charge, frontier orbital, FuKui function and nuclear magnetic resonance (NMR) methods were employed to reveal the mechanism of electron transfer. The results illustrate that β-CD plays a catalytic role in synthesis reaction mechanism on the secondary side, improving the reactivity and selectivity of the process.

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Graphical Abstract Density functional theory study of the effects of β-cyclodextrin in synthesis of 2-phenylbenzimidazole via benzaldehyde and o-phenylenediamine

     

Synthetic analogues of the histidine–chlorophyll complex: a NMR study to mimic structural features of the photosynthetic reaction center and the light-harvesting complex

Mg(II)–porphyrin–ligand and (bacterio)chlorophyl–ligand coordination interactions have been studied by solution and solid-state MAS NMR spectroscopy. ¹H, ¹³C and ¹⁵N coordination shifts due to ring currents, electronic perturbations and structural effects are resolved for imidazole (Im) and 1-methylimidazole (1-MeIm) coordinated axially to Mg(II)-OEP and (B)Chl a. As a consequence of a single axial coordination of Im or 1-MeIm to the Mg(II) ion, 0.9–5.2 ppm ¹H, 0.2–5.5 ppm ¹³C and 2.1–27.2 ppm ¹⁵N coordination shifts were measured for selectively labeled [1,3-¹⁵N]-Im, [1,3-¹⁵N,2-¹³C]-Im and [1,3-¹⁵N,1,2-¹³C]-1-MeIm. The coordination shifts depend on the distance of the nuclei to the porphyrin plane and the perturbation of the electronic structure. The signal intensities in the ¹H NMR spectrum reveal a five-coordinated complex, and the isotropic chemical shift analysis shows a close analogy with the electronic structure of the BChl a–histidine in natural light harvesting 2 complexes. The line broadening of the ligand responses support the complementary IR data and provide evidence for a dynamic coordination bond in the complex.Abbreviations (B)Chl a (bacterio)chlorophyll a - HMBC heteronuclear multiple bond correlation - Im imidazole - LH light-harvesting - 1-MeIm 1-methylimidazole - Mg(II)-Por Mg(II)-porphyrin macrocycle - OEP 2,3,7,8,12,13,17,18-octaethylporphyrin     

Density functional study of the catalytic cycle of nickel–iron [NiFe] hydrogenases and the involvement of high-spin nickel(II)

In light of recent experiments suggesting high-spin (HS) Ni(II) species in the catalytic cycle of [NiFe] hydrogenase, a series of models of the Ni(II) forms Ni-SI(I,II), SI-CO and Ni-R(I,II,III) were examined in their high-spin states via density functional calculations. Because of its importance in the catalytic cycle, the Ni-C form was also included in this study. Unlike the Ni(II) forms in previous studies, in which a low-spin (LS) state was assumed and a square-planar structure found, the optimized geometries of these HS Ni(II) forms resemble those observed in the crystal structures: a distorted tetrahedral to distorted pyramidal coordination for the NiS4. This resemblance is particularly significant because the LS state is 20-30 kcal/mol less stable than the HS state for the geometry of the crystal structure. If these Ni(II) forms in the enzyme are not high spin, a large change in geometry at the active site is required during the catalytic cycle. Furthermore, only the HS state for the CO-inhibited form SI-CO has CO stretching frequencies that match the experimental results. As in the previous work, these new results show that the heterolytic cleavage reaction of dihydrogen (where H2 is cleaved with the metal acting as a hydride acceptor and a cysteine as the proton acceptor) has a lower energy barrier and is more exothermic when the active site is oxidized to Ni(III). The enzyme models described here are supported by a calibrated correlation of the calculated and measured CO stretching frequencies of the forms of the enzyme. The correlation coefficient for the final set of models of the forms of [NiFe] hydrogenase is 0.8.     

Influence of cytosolic conditions on the reaction equilibrium and the reaction enthalpy of the enolase reaction accessed by calorimetry and van ‘t HOFF

BackgroundThermodynamic methods are finding more and more applications in systems biology, which attempts to understand cell functions mechanistically. Unfortunately, the state variables used (reaction enthalpy and Gibbs energy) do not take sufficient account of the conditions inside of cells, especially the crowding with macromolecules.MethodsFor this reason, the influence of crowding agents and various other parameters such as salt concentrations, pH and temperature on equilibrium position and reaction enthalpy of the glycolytic example reaction 9 (2-Phospoglycerate - > Phosphoenolpyruvate + H₂O) was investigated. The conditions were chosen to be as close as possible to the cytosolic conditions. Poly(ethylene glycol) MW = 20,000 g mol⁻¹ (PEG 20,000) was used to analyze the influence of crowding with macromolecules. The equation of state electrolyte Perturbed-Chain Statistical Associating Fluid Theory (ePC-SAFT) was applied to consider the influence of crowding agents on the reaction equilibria.Results and conclusionsFor the reaction enthalpies and for the equilibria, it was found that the influence of salts and temperature is not pronounced while that of pH and PEG 20,000 concentration is considerable. Furthermore, it could be shown that under identical measurement conditions there are no differences between the van ‘t Hoff and the calorimetrically determined reaction enthalpy.General significanceThe results show how important it is to consider the special cytosolic conditions when applying thermodynamic data in systems biology.     

Theoretical studies on the reaction mechanism of PP1 and the effects of different oxidation states of the Mn–Mn center on the mechanism

Protein phosphatase 1 (PP1) is a dinuclear metalloenzyme that catalyzes the dephosphorylation of serine and threonine residues. In this work, the catalytic reaction mechanism of PP1 was theoretically investigated by hybrid density functional theory. Firstly, an initial model of the Mn(II)–Mn(II) active site of PP1 was constructed on the basis of the high-resolution crystal structure, and stationary points along the reaction pathway were optimized and analyzed. The calculations provide strong support for the mechanism of the dephosphorylation by PP1 and suggest that His125 plays the role of donating a proton to the leaving group. Furthermore, reaction models with the Mn–Mn centers at different oxidation states [Mn(III)–Mn(II) and Mn(III)–Mn(III) centers] were designed. Our calculations show that increasing the oxidation state of one or both Mn(II) can shorten the bond lengths between the metal ions and the ligands, and increase the energy barrier of the related reactions. We found it interesting that artificially adding a negatively charged hydroxy ligand into the Mn(III)–Mn(II) center can recover the shortened coordination bonds and lower the increased energy barrier. Our investigation suggests that the definite oxidation states of the metal centers should be significantly correlated to the negative charges of the ligands not only in phosphoprotein phosphatases, but also in purple acid phosphatases and Escherichia coli 5′-nucleotidase. This means that all the members of phosphoprotein phosphatases adopt homodivalent centers, and suggests the heterovalent active sites of purple acid phosphatases have evolved from homodivalent ones.     

An ab initio study of di- and trifluorobenzene–benzene complexes as relevant to carbonic anhydrase II–drug interactions

Ab initio calculations at the MP2/6-31G* level have shown that variously substituted di- and trifluorobenzenes form non-covalent complexes with benzene that adopt either aromatic–aromatic or H---F binding, the choice being determined by the pattern of fluorination. The binding energies of these structures are from 3.4 to 4.5 kcal mol^–1. This range is large enough to account for observed variations in the binding affinity of a library of fluoroaromatic inhibitors of carbonic anhydrase. This enzyme has an aromatic amino acid at a central position in the active site. The diverse modes of binding of the dimers also suggest that aggregates of fluorobenzenes might adopt specified 3-dimensional shapes in the solid state. Figure Observed structure for 1,2-difluorobenzene     

Synthesis and physicochemical characterization of the lanthionine analog of somatostatin[1–14]

Summary The synthesis of the lanthionine analog of somatostatin[1–14] on a Kaiser-oxime resin is described. The 12-residue peptide segment [3–14] was assembled and cyclized on the resin by using the method of peptide cyclization on an oxime resin (PCOR); the product was obtained with good yield (41%) and purity (94%). The Fmoc protecting group on the N-terminus was cleaved with DBU, followed by a 2+12 segment condensation in solution. The chromatographic (HPLC, CZE) and spectral (UV, NMR) properties of the lanthionine and the natural somatostatins have been studied and compared. Preliminary biological tests show that the lanthionine and the natural somatostatins exhibit similar binding affinities to somatostatin receptor SSTR2.Abbreviations Ala_L one end of a lanthionine unit - Boc tert-butyloxycarbonyl - BOP benzotriazol-l-yl-oxy-tris-(dimethylamino)-phosphonium hexafluorophosphate - Bzl benzyl - Cbz benzyloxycarbonyl - DQF-COSY double-quantum-filtered correlated NMR spectroscopy - CZE capillary zone electrophoresis - DBU 1,8-diazabicyclo[5.4.0]undec-7-ene - DCC N,N-dicyclohexylcarbodiimide - DCM dichloromethane - DIEA N,N-diisopropylethylamine - DMF N,N-dimethylformamide - DMSO-d₆ hexadeuterated dimethylsulfoxide - EDC 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide - Fmoc 9-florenylmethoxycarbonyl - For formyl - HMPA hexamethylphosphoramide - HOBt N-hydroxybenzotriazole - HOHAHA homonuclear Hartmann-Hahn experiment - HPLC high-performance liquid chromatography - ROESY rotating frame nuclear Overhauser enhancement spectroscopy - TFA trifluoroacetic acid - PCOR peptide cyclization on an oxime resin - Tmac₂O trimethylacetic or pivalic anhydride - Tos p-toluenesulfonyl     

Computational study of the electronic structure and magnetic properties of the Ni–C state in [NiFe] hydrogenases including the second coordination sphere

[NiFe] hydrogenases catalyze the reversible formation of H₂. The [NiFe] heterobimetallic active site is rich in redox states. Here, we investigate the key catalytic state Ni?CC of Desulfovibrio vulgaris Miyazaki F hydrogenase using a cluster model that includes the truncated amino acids of the entire second coordination sphere of the enzyme. The optimized geometries, computed g?tensors, hyperfine coupling constants, and IR stretching frequencies all agree well with experimental values. For the hydride in the bridging position, only a single minimum on the potential energy surface is found, indicating that the hydride bridges and binds to both nickel and iron. The influence of the second coordination sphere on the electronic structure is investigated by comparing results from the large cluster models with truncated models. The largest interactions of the second coordination sphere with the active site concern the hydrogen bonds with the cyanide ligands, which modulate the bond between iron and these ligands. Secondly, the electronic structure of the active site is found to be sensitive to the protonation state of His88. This residue forms a hydrogen bond with the spin-carrying sulfur atom of Cys549, which in turn tunes the spin density at the nickel and coordinating sulfur atoms. In addition, the unequal distribution of spin density over the equatorial cysteine residues results from different orientations of the cysteine side chains, which are kept in their particular orientation by the secondary structure of the protein.     

Ab initio modelling of the structure and redox behaviour of copper(I) bound to a His–His model peptide: relevance to the β-amyloid peptide of Alzheimer’s disease

A contributing factor to the pathology of Alzheimer's disease is the generation of reactive oxygen species, most probably a consequence of the beta-amyloid (Abeta) peptide coordinating copper ions. Experimental and theoretical results indicate that His13 and His14 are the two most firmly established ligands in the coordination sphere of Cu(II) bound to Abeta. Abeta1-42 is known to reduce Cu(II) to Cu(I). The Abeta-Cu(II) complex has been shown to catalytically generate H(2)O(2) from reducing agents and O(2). Cu(II) in the presence of Abeta has been reported to have a formal reduction potential of +0.72-0.77 V (vs. the standard hydrogen electrode). Quantum chemical calculations using the B3LYP hybrid density functional method with the 6-31G(d) basis set were performed to model the reduction of previously studied Cu(II) complexes representing the His13-His14 portion of Abeta (Raffa et al. in J. Biol. Inorg. Chem. 10:887-902, 2005). The effects of solvation were accommodated using the CPCM method. The most stable complex between Cu(I) and the model compound, 3-(5-imidazolyl)propionylhistamine (1) involves tricoordinated Cu(I) in a distorted-T geometry, with the Npi of both imidazoles as well as the oxygen of the backbone carbonyl bound to copper. This model would be the most likely representation of a Cu(I) binding site for a His-His peptide in aqueous solution. A variety of possible redox processes are discussed.     

DFT study on the radical scavenging activity of β,β-dimethylacrylalkannin derivatives

The radical scavenging activity of β,β-dimethylacrylalkannin derivatives has been studied by using density functional theory. The hydrogen bond property of the studied structures was investigated using the atoms in molecules theory. It turned out that the hydrogen bond is important for good radical scavenging activity. The hydrogen atom transfer for β,β-dimethylacrylalkannin derivatives is difficult to occur compared with the zero compound phenol. However, β,β-dimethylacrylalkannin derivatives appear to be good candidates for the one-electron transfer, particularly for β,β-dimethylacrylalkannin derivatives with electron-donating groups. Their naphthoquinone planar conformation and the extended electronic delocalisation between adjacent substituent groups determine low adiabatic ionisation potential (IP_a) values. The IP_a values of β,β-dimethylacrylalkannin derivatives with –NHPh, –N(CH₃)Ph, –N(CH₂CH₂)O and –N(CH₃)₂ groups are lower than that of the parent compound β,β-dimethylacrylalkannin, suggesting that these derivatives are expected to be the promising candidates for radical scavenging activity compounds. Taking this system as an example, we present an efficient method for the investigation of radical scavenging activity from theoretical point of view.     

The adenosine diphosphate–adenosine triphosphate-exchange reaction of cerebral microsomes and its relation to the sodium ion-stimulated adenosine-triphosphatase reaction

Microsomes from guinea-pig cerebral cortex contain a system capable of exchanging ADP with ATP at rates of about 20mumoles/mg. of protein/hr. The ADP-ATP-exchange reaction requires Mg(2+) for activity. The reaction is not stimulated by Na(+) or K(+) and is not inhibited by ouabain, in contrast with the Na(+)-plus-K(+)-stimulated adenosine triphosphatase. The pH optimum also differs from that of the adenosine triphosphatase. The ADP-ATP-exchange reaction is stimulated two- to three-fold by non-ionic, anionic and cationic detergents, even when these agents are inhibiting the adenosine-triphosphatase reaction. This reaction may represent a component of the Na(+)-plus-K(+)-stimulated adenosine-triphosphatase reaction but is more likely to be due to other enzyme systems present in microsomal subfractions.     

Ab initio model studies of copper binding to peptides containing a His–His sequence: relevance to the β-amyloid peptide of Alzheimer’s disease

Two of the defining hallmarks of Alzheimer’s disease (AD) are deposits of the β-amyloid peptide, Aβ, and the generation of reactive oxygen species, both of which may be due to the Aβ peptide coordinating metal ions. The Cu²⁺ concentrations in cores of senile plaques are significantly elevated in AD patients. Experimental results indicate that Aβ1–42 in particular has a very high affinity for Cu²⁺, and that His13 and His14 are the two most firmly established ligands in the coordination sphere of the copper ion. Quantum chemical calculations using the unrestricted B3LYP hybrid density functional method with the 6–31G(d) basis set were performed for geometries, zero point energies and thermochemistry. The effects of solvation were accommodated using the CPCM method. The enthalpies were calculated with the 6–311+G(2df,2p) basis set. Calculations show that when Cu(H₂O)₄²⁺ combines with the model compound 1 (3-(1H-imidazol-5-yl)-N-[2-(1H-imidazol-5-yl)ethyl] propanamide) in the aqueous phase, the most stable binding site involves the Nπ atoms of His13 and His14 as well as the carbonyl of the intervening backbone amide group. These structures are fairly rigid and the implications for conformational changes to the Aβ backbone are discussed. In solution at pH=7, Cu²⁺ promotes the deprotonation and involvement in the binding of the backbone amide nitrogen in a β-sheet like structure. This geometry does not induce strain in the peptide backbone, making it the most likely representation of that portion of the Cu²⁺–Aβ complex monomer in aqueous solution.     

A DFT study of the structure–property relationships of bistetrazole-based high-nitrogen energetic metal complexes

In this work, six series of new energetic metal complexes were designed. Each complex contained a large, high-energy, high-nitrogen, anionic chelating ligand (either the 5,5′-bistetrazolate anion, the 5,5′-azobistetrazolate anion, or the 5,5′-(hydrazine-1,2-diyl)bis-[1H-tetrazol-1-ide] anion—each of which has a different bridging group), Cu or Ni as the metal atom, and two small complexing agent ligands (NH₃ and/or NH₂NO₂). The molecular and electronic structures, heats of formation, densities, detonation properties, and impact sensitivities of the novel complexes were studied using density functional theory. Furthermore, the effects of varying the large chelating ligand (and thus the bridging group), the small complexing agents, and the metal atom on the structure and properties of the complex were investigated and analyzed in depth. The results show that the particular metal, bridging group, and complexing agents included in the energetic complex influence its structure and properties, but the effects of varying the constituents of the complex are complicated or unclear, and these effects are sometimes intertwined. In addition, the detonation pressures, detonation velocities, and impact sensitivities of the novel complexes ranged from 25.9 to 38.6 GPa, from 7.21 to 8.80 km s^?1, and from 17 to 48 cm, respectively. Five of the complexes (B3, C3, D3, E3, and F3) appear to possess comparable performance to the famous and widely used high explosive 1,3,5-trinitro-1,3,5-triazinane, making these new complexes attractive to energetic materials experimentalists.     

Combined DFT and NBO study on the electronic basis of Si···N-β-donor bond

Two groups of isoelectronic molecules with different SiXN (X=C, N, O ) units are analyzed by a combined DFT and NBO study to investigate the electronic basis of Si···N-β-donor bond. The influence of various energy components on the formation of Si···N-β-donor bond is explored. The importance of the electron delocalization from the lone pair of nitrogen atom into the acceptor-orbitals connected with Si atom is elicited by our calculations. The electron delocalization from the lone pair of nitrogen atom into the antibonding orbital of Si-X bond is quite different among the isoelectronic molecules with various types of SiXN units.     

Application of DFT methods to the study of the coordination environment of the VO2+ ion in V?proteins

Density functional theory (DFT) methods were used to simulate the environment of vanadium in several V proteins, such as vanadyl-substituted carboxypeptidase (sites A and B), vanadyl-substituted chloroplast F(1)-ATPase (CF(1); site 3), the reduced inactive form of vanadium bromoperoxidase (VBrPO; low- and high-pH sites), and vanadyl-substituted imidazole glycerol phosphate dehydratase (IGPD; sites α, β, and γ). Structural, electron paramagnetic resonance, and electron spin echo envelope modulation parameters were calculated and compared with the experimental values. All the simulations were performed in water within the framework of the polarizable continuum model. The angular dependence of [Formula: see text] and [Formula: see text] on the dihedral angle θ between the V=O and N-C bonds and on the angle φ between the V=O and V-N bonds, where N is the coordinated aromatic nitrogen atom, was also found. From the results it emerges that it is possible to model the active site of a vanadium protein through DFT methods and determine its structure through the comparison between the calculated and experimental spectroscopic parameters. The calculations confirm that the donor sets of sites B and A of vanadyl-substituted carboxypeptidase are [[Formula: see text], H(2)O, H(2)O, H(2)O] and [N(His)(||), N(His)(⊥), [Formula: see text], H(2)O], and that the donor set of site 3 of CF(1)-ATPase is [[Formula: see text], OH(Thr), H(2)O, H(2)O, [Formula: see text]]. For VBrPO, the coordination modes [N(His)(||), N(His)(∠), OH(Ser), H(2)O, H(2)O(ax)] for the low-pH site and [N(His)(||), N(His)(∠), OH(Ser), OH(-), H(2)O(ax)] or [N(His)(||), N(His)(∠), [Formula: see text], H(2)O] for the high-pH site, with an imidazole ring of histidine strongly displaced from the equatorial plane, can be proposed. Finally, for sites α, β, and γ of IGPD, the subsequent deprotonation of one, two, and three imidazole rings of histidine and the participation of a carboxylate group of a glutamate residue ([N(His)(||), [Formula: see text], H(2)O, H(2)O], [N(His)(||), N(His)(||), [Formula: see text], H(2)O], and [N(His)(||), N(His)(||), [Formula: see text], OH(-), [Formula: see text]], respectively) seems to be the most plausible hypothesis.