The identification of 1,3-oxazolidine-2-thiones and 1,3-thiazolidine-2-thiones from the reaction of glucose with benzyl isothiocyanate

The structure of interaction products resulting from the reaction of unmodified glucose with benzyl isothiocyanate is reported. Prior to their identification, the main products of this reaction were isolated using solid-phase extraction (SPE) as well as preparative HPLC. They were then identified by NMR and MS as 3-benzyl-4-hydroxy-5-(D-arabino-1,2,3,4-tetrahydroxybutyl)-1,3-oxazolidine-2-thione, 3-benzyl-4-hydroxy-4-hydroxymethyl-5-(D-erythro-1,2,3-trihydroxypropyl)-1,3-oxazolidine-2-thione, N-benzyl-(D-gluco-4,5-dihydroxy-6-hydroxymethyl-tetrahydropyrano)[2,3-b]oxazolidine-2-thione and 3-benzyl-4-(N-benzyl amino)-5-(D-arabino-1,2,3,4-tetrahydroxybutyl)-1,3-thiazolidine-2-thione. The identity of the last compound was secured by X-ray crystal structure data.     

A theoretical DFT investigation of the lysozyme mechanism: computational evidence for a covalent intermediate pathway

To test the occurrence of local particularities during the unfolding of Ca2+-loaded goat alpha-lactalbumin (GLA) we replaced Trp60 and -118, either one or both, by Phe. In contrast with alternative studies, our recombinant alpha-lactalbumins are expressed in Pichia pastoris and do not contain the extra N-terminal methionine. The substitution of Trp60 leads to a reduction of the global stability. The effect of the Trp118Phe substitution on the conformation and stability of the mutant, however, is negligible. Comparison of the fluorescence spectra of these mutants makes clear that Trp60 and -118 are strongly quenched in the native state. They both contribute to the quenching of Trp26 and -104 emission. By the interplay of these quenching effects, the fluorescence intensity changes upon thermal unfolding of the mutants behave very differently. This is the reason for a discrepancy of the apparent transition temperatures derived from the shift of the emission maxima (Tm,Fl lambda) and those derived from DSC (Tm,DSC). However, the transition temperatures derived from fluorescence intensity (Tm,Fl int) and from DSC (Tm,DSC), respectively, are quite similar, and thus, no local rearrangements are observed upon heat-induced unfolding. At room temperature, the occurrence of specific local rearrangements upon GdnHCl-induced denaturation of the different mutants is deduced from the apparent free energies of their transition state obtained from stopped-flow fluorescence measurements. By phi-value analysis it appears that, while the surroundings of Trp118 are exposed in the kinetic transition state, the surroundings of Trp60 remain native.     

The effective molarity (EM) - A computational approach

The effective molarity (EM) for 12 intramolecular S_N2 processes involving the formation of substituted aziridines and substituted epoxides were computed using ab initio and DFT calculation methods. Strong correlation was found between the calculated effective molarity and the experimentally determined values. This result could open a door for obtaining EM values for intramolecular processes that are difficult to be experimentally provided. Furthermore, the calculation results reveal that the driving forces for ring-closing reactions in the two different systems are proximity orientation of the nucleophile to the electrophile and the ground strain energies of the products and the reactants.     

A computational approach to the synthesis of dirithromycin

Dirithromycin is a macrolide antibiotic derived from erythromycin A. Dirithromycin is synthesized by the condensation of 9(S)-erythromycylamine with 2-(2-methoxyethoxy)-acetaldehyde. To gain insight into the synthesis, the condensation mechanism has been analyzed computationally by the AM1 method in the gas phase. First, the formation of the Schiff bases of dirithromycin and epidirithromycin from 9(S)-erythromycylamine and 2-(2-methoxyethoxy)-acetaldehyde were modeled. Then, the tautomerization of the Schiff bases to dirithromycin and epidirithromycin were considered. Finally, the epimerization of the Schiff base of epidirithromycin to the Schiff base of dirithromycin was investigated. Our results show that, even though carbinolamine forms faster for epidirithromycin than the corresponding structure for dirithromycin, dirithromycin is the major product of the synthesis. Figure Synthesis of dirithromycin     

The role of weakly polar and H-bonding interactions in the stabilization of the conformers of FGG, WGG, and YGG: an aqueous phase computational study

The energetics of intramolecular interactions on the conformational potential energy surface of the terminally protected N-Ac-Phe-Gly-Gly-NHMe (FGG), N-Ac-Trp-Gly-Gly-NHMe (WGG), and N-Ac-Tyr-Gly-Gly-NHMe (YGG) tripeptides was investigated. To identify the representative conformations, simulated annealing molecular dynamics (MD) and density functional theory (DFT) methods were used. The interaction energies were calculated at the BHandHLYP/aug-cc-pVTZ level of theory. In the global minima, 10%, 31%, and 10% of the stabilization energy come from weakly polar interactions, respectively, in FGG, WGG, and YGG. In the prominent cases 46%, 62%, and 46% of the stabilization energy is from the weakly polar interactions, respectively, in FGG, WGG, and YGG. On average, weakly polar interactions account for 15%, 34%, and 9% of the stabilization energies of the FGG, WGG, and YGG conformers, respectively. Thus, weakly polar interactions can make an important energetic contribution to protein structure and function. (c) 2008 Wiley Periodicals, Inc. Biopolymers 89: 1002-1011, 2008.This article was originally published online as an accepted preprint. The "Published Online" date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com.     

Substitution of chloride by nitrosyl ligand in a scorpionate ruthenium(III) compound: A theoretical study

A theoretical study of the ruthenium(III) complex [RuCl₂(pz₂CHSO₃)(en)] and of its nitrosyl-substituted product [Ru(NO)Cl(pz₂CHSO₃)(en)]⁺ is presented, based on density functional calculations. Several isomers of each compound differing in the position of the anionic tail of a bis(3,4-dimethyl-1-yl)methanesulfonate scorpionate ligand, pz₂CHSO₃⁻, relative to the monodentate ligands have been optimized. A two-step mechanism is proposed for the ligand substitution reaction that is consistent with the computational results and the weak coordination of the sulfonate group.     

A heterogeneity-aware approach to load balancing of computational tasks: a theoretical and simulation study

One of the distinct characteristics of computing platforms shared by multiple users such as a cluster and a computational grid is heterogeneity on each computer and/or among computers. Temporal heterogeneity refers to variation, along the time dimension, of computing power available for a task on a computer, and spatial heterogeneity represents the variation among computers. In minimizing the average parallel execution time of a target task on a spatially heterogeneous computing system, it is not optimal to distribute the target task linearly proportional to the average computing powers available on computers. In this paper, effects of the temporal and spatial heterogeneity on performance of a target task have been analyzed in terms of the mean and standard deviation of parallel execution time. Based on the analysis results, an approach to load balancing for minimizing the average parallel execution time of a target task is described. The proposed approach whose validity has been verified through simulation considers temporal and spatial heterogeneities in addition to the average computing power on each computer.

Characterization and DNA interaction of the Pt(II)(pq)(bdt) complex: A theoretical and experimental research

A mononuclear complex Pt(pq)(bdt) (1) (where pq = 2-(2′pyridyl)quinoxaline and bdt = benzene-1,2-dithiolate) has been prepared and characterized by NMR spectroscopy, ES mass spectroscopy and elemental analysis. Furthermore, its molecular and electronic structure has been fully elucidated by means of the density functional theory (DFT) and time-dependent density functional theory (TDDFT). The former reveals an extensive distortion of the planarity of complex 1, while the latter an intense mixed metal ligand to ligand charge transfer (MM′LLCT) transition in the visible region of the spectrum. Interactions of complex 1, the free ligands pq and bdt with double stranded calf thymus DNA before and after illumination were studied by UV-spectrophotometric (melting curves) and circular dichroism (CD) measurements, indicating that complex 1 is able to form adducts with DNA and to distort the double helix by changing the base stacking. Under our experimental conditions, it is unclear that complex 1 can photocleave DNA. Viscosity changes of calf thymus DNA (CT-DNA) in the presence of an incremental amount of complex 1 demonstrate that in very low ratios, [1]/[DNA]  0.02, this complex binds intercalatively to the DNA, while in higher ratios a partial or a non-classical interacalation should occur due to the tetrahedral distortion of the molecule and the existence of the dithiolato-ligand.     

Characterization of the Valence and Conduction Band Levels of n = 1 2D Perovskites: A Combined Experimental and Theoretical Investigation

This study presents a combined experimental and theoretical study of the electronic structure of two 2D metal halide perovskite films. Ultraviolet and inverse photoemission spectroscopies are performed on solution‐processed thin films of the n = 1 layered perovskite butylammonium lead iodide and bromide, BA₂PbI₄ and BA₂PbBr₄, characterized by optical absorption and X‐ray diffraction, to determine their valence and conduction band densities of states, transport gaps, and exciton binding energies. The electron spectroscopy results are compared with the densities of states determined by density functional theory calculations. The remarkable agreement between experiment and calculation enables a detailed identification and analysis of the organic and inorganic contributions to the valence and conduction bands of these two hybrid perovskites. The electron affinity and ionization energies are found to be 3.1 and 5.8 eV for BA₂PbI₄, and 3.1 and 6.5 eV for BA₂PbBr₄. The exciton binding energies are estimated to be 260 and 300 meV for the two materials, respectively. The 2D lead iodide and bromide perovskites exhibit significantly less band dispersion and a larger density of states at the band edges than the 3D analogs. The effects of using various organic ligands are also discussed.     

A problem in the mechanism of carbodiimide-mediated synthesis of peptides in aqueous medium

Leucylleucine was synthesized in aqueous solution using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide as the condensing agent. The yield was strongly dependent on acid concentration and was maximal at about 0.1 M HCl. The nature of this dependence suggests that the mechanism established for aprotic systems may not apply at all acid concentrations to aqueous peptide syntheses.     

Hydrogen-bond assisted stabilization of the less favored conformation of a tridentate Schiff base ligand in dinuclear nickel(II) complex: An experimental and theoretical study

The Schiff base ligand, HL (2-[1-(3-methylamino-propylimino)-ethyl]-phenol), the 1:1 condensation product of 2-hydroxy acetophenone and N-methyl-1,3-diaminopropane, has been synthesized and characterized by X-ray crystallography as the perchlorate salt [H₂L]ClO₄ (1). The structure consists of discrete [H₂L]⁺ cations and perchlorate anions. Two dinuclear Ni^II complexes, [Ni₂L₂(NO₂)₂] (2), [Ni₂L₂(NO₃)₂] (3) have been synthesized using this ligand and characterized by single crystal X-ray analyses. Complexes 2 and 3 are centrosymmetric dimers in which the Ni^II ions are in distorted fac- and mer-octahedral environments, respectively, bridged by two μ₂-phenolate ions of deprotonated ligand, L. The plane of the phenyl rings and the Ni₂O₂ basal plane are nearly coplanar in 2 but almost perpendicular in 3. We have studied and explained this different behavior using high level DFT calculations (RI-BP86/def2-TZVP level of theory). The conformation observed in 3, which is energetically less favorable, is stabilized via intermolecular non-covalent interactions. Under the excitation of ultraviolet light, characteristic fluorescence of compound 1 was observed; by comparison fluorescence intensity decreases in case of compound 3 and completely quenched in compound 2.     

Piperazine: An excellent catalyst for the synthesis of 2-amino-3-cyano-4H-pyrans derivatives in aqueous medium

An improved, forthright, and highly efficient one-pot synthesis of a wide range of pharmaceutically exciting diverse kind of functionalized 2-amino-3-cyano-4H-pyrans and especially bis-pyrans compounds is developed using piperazine as a low-cost and environmentally benign commercially available basic catalyst in aqueous media. The attractive features of this process are simple procedure, short reaction times, high yields, no column chromatographic separation and commercial availability and recyclability of the catalyst. Also, piperazine can catalyze the synthesis of the target compounds on a larger scale. Furthermore, rational mechanism was suggested via GC-Mass analysis of the trapped intermediates.     

Green synthesis of naphthyl derivative as an optical sensor for the detection of l-carnitine in food samples

An economical and green approach to the synthesis of naphthyl derivative for detection of l -carnitine (3-hydroxy-4-N-trimethyl-aminobutyrate) is practically important. We developed a naphthyl derivative as a probe showing ‘turn-on’ response towards l -carnitine selectively at pH 7.2 through ICT mechanism with a good limit of detection (LOD) of 0.126 μM. Using Job's plot for determining the binding stoichiometry, it was found that probe could form a more stable complex (1:1) with carnitine. The binding constant (K) between probe and carnitine was calculated as 8 × 10⁷ M⁻¹ using the Benesi–Hildebrand plot. The binding interaction of the probe with l -carnitine was confirmed by nuclear magnetic resonance titrations, Fourier-transform infrared spectroscopy, photo physical studies and density functional theory calculations. Meanwhile, the probe can be used to quantitatively detect carnitine in food samples.     

Inhibition of the D-fructose transporter protein GLUT5 by fused-ring glyco-1,3-oxazolidin-2-thiones and -oxazolidin-2-ones

The glucose transporter 5 (GLUT5)-a specific D-fructose transporter-belongs to a family of facilitating sugar transporters recently enlarged by the human genome sequencing. Prompted by the need to develop specific photolabels of these isoforms, we have studied the interaction of conformationally locked D-fructose and L-sorbose derived 1,3-oxazolidin-2-thiones and 1,3-oxazolidin-2-ones to provide a rational basis for an interaction model. The inhibition properties of the D-fructose transporter GLUT5 by glyco-1,3-oxazolidin-2-thiones and glyco-1,3-oxazolidin-2-ones is now reported. In vitro, the fused-rings systems tested showed an efficient inhibition of GLUT5, thus bringing new insights on the interaction of D-fructose with GLUT5.     

Protonation and deprotonation enthalpies of alloxan and implications for the structure and energy of its complexes with water: a computational study

The optimized geometries, harmonic vibrational frequencies, and energies of the structures of monohydrated alloxan were computed at the DFT/ωB97X-D and B3LYP/6–311++G** level of theory. Results confirm that the monohydrate exists as a dipolar alloxan–water complex which represents a global minimum on the potential energy surface (PES). Trajectory dynamics simulations show that attempt to reorient this monohydrate, to a more favorable orientation for H-bonding, is opposed by an energy barrier of 25.07?kJ/mol. Alloxan seems to prefer acting as proton donor than proton acceptor. A marked stabilization due to the formation of N–H–OH₂ bond is observed. The concerted proton donor–acceptor interaction of alloxan with one H₂O molecule does not increase the stability of the alloxan–water complex. The proton affinity of the O and N atoms and the deprotonation enthalpy of the NH bond of alloxan are computed at the same level of theory. Results are compared with recent data on uracil, thymine, and cytosine. The intrinsic acidities and basicities of the four pyrimidines were discussed. Results of the present study reveal that alloxan is capable of forming stronger H-bonds and more stable cyclic complex with water; yet it is of much lower basicity than other pyrimidines.     

Electrochemically Modifying the Electronic Structure of IrO2 Nanoparticles for Overall Electrochemical Water Splitting with Extensive Adaptability

Designing the electrocatalysts that are stable and active for extensively adaptable water splitting is highly desirable for developing hydrogen based energy. IrO₂ is a promising and widely used catalyst for the oxygen evolution reaction in commercial applications, but is rarely used for the hydrogen evolution reaction (HER), due to the high Gibbs free energy for hydrogen adsorption (ΔG_H*). Herein, an approach to modify the electronic structure of IrO₂ via cyclic voltammetry is proposed. In this process, Ir(+4) is partially reduced and trace Pt is simultaneously deposited on IrO₂, which greatly lowers the ΔG_H* and thus accelerates the reaction kinetics. The as‐prepared Pt–IrO₂/CC with low noble metal loading (36.6 µg cm^?2_(Ir+Pt)) exhibits excellent HER activity with overpotentials of 5, 22, and 26 mV at 10 mA cm^?2 in 0.5 m H₂SO₄, 1 m KOH, and 1 m phosphate buffer solution, respectively, making it possible to organize an all‐IrO₂ based water electrolyzer. The Pt–IrO₂/CC||IrO₂/CC couple exhibits a promising activity and stability in pH‐universal conditions as well as natural seawater for H₂ production. Density function theory calculations reveal that the optimized electronic structure of IrO₂ balances the ΔG_H*, resulting in a much enhanced HER performance.     

A computational approach to explore the functional missense mutations in the spindle check point protein Mad1

In this work, the most detrimental missense mutations of Madl protein that cause various types of cancer were identified computationally and the substrate binding efficiencies of those missense mutations were analyzed. Out of 13 missense mutations, I Mutant 2.0, SIFT and PolyPhen programs identified 3 variants that were less stable, deleterious and damaging respectively. Subsequently, modeling of these 3 variants was performed to understand the change in their conformations with respect to the native Madl by computing their root mean squared deviation （RMSD）. Furthermore, the native protein and the 3 mutants were docked with the binding partner Mad2 to explain the substrate binding efficiencies of those detrimental missense mutations. The docking studies identified that all the 3 mutants caused lower binding affinity for Mad2 than the native protein. Finally, normal mode analysis determined that the loss of binding affinity of these 3 mutants was caused by altered flexibility in the amino acids that bind to Mad2 compared with the native protein. Thus, the present study showed that majority of the substrate binding amino acids in those 3 mutants displayed loss of flexibility, which could be the theoretical explanation of decreased binding affinity between the mutant Madl and Mad2.     

A Systematic Approach to the Design Optimization of Light‐Absorbing Indenofluorene Polymers for Organic Photovoltaics

The synthesis and optimization of new photovoltaic donor polymers is a time‐consuming process. Computer‐based molecular simulations can narrow the scope of materials choice to the most promising ones, by identifying materials with desirable energy levels and absorption energies. In this paper, such a retrospective analysis is presented of a series of fused aromatic push–pull copolymers. It is demonstrated that molecular calculations do indeed provide good estimates of the absorption energies measured by UV–vis spectroscopy and of the ionization potentials measured by photoelectron spectroscopy in air. Comparing measured photovoltaic performance of the polymer series to the trend in efficiencies predicted by computation confirms the validity of this approach.     

A new approach for the asymmetric total synthesis of umbelactone

The asymmetric total syntheses of (R)-(+)- and (S)-(-)-umbelactone were achieved by using the Sharpless asymmetric epoxidation reaction to generate the stereogenic center and a ring-closing metathesis (RCM) for the formation of the lactone structure. Starting from 3-methyl-2-buten-1-ol, the asymmetric total synthesis was achieved in an efficient 6-step protocol with an overall yield of 16%.