Intramolecular Alkynylogous Mukaiyama Aldol Reaction Starting from Bicyclic Alkanones Tethered to Alkynyl Esters: Formal Total Synthesis of (±)‐Hamigeran B

Selecting the ring : tert‐Butyldimethylsilyltriflate (TBSOTf)/NEt₃ treatment of alkynyl esters tethered to bicycloalkanones leads to the formation of tricyclic allenoates with total diasteroselectivity at the ring junction. An intramolecular alkynylogous Mukaiyama aldol reaction promoted by a TBSOTf/NEt₃ dual activation is involved. This novel methodology was illustrated by a formal total synthesis of (±)‐hamigeran B.

     

Infrared characterization of hydroxyl groups on MgO: a periodic and cluster density functional theory study

The infrared OH stretching frequencies of the various types of hydroxyl groups on MgO surfaces have been calculated by periodic (VASP) and cluster (Gaussian) DFT simulations. Surface irregularities (mono and diatomic steps, corners, step divacancies, and kinks) have been considered to model the IR spectra of hydroxylated MgO powders. A good correspondence between calculated and experimental frequencies is obtained with the B3LYP functional. Hydrogen-bonding is the parameter which influences most the IR frequency of OH groups, followed by location of OH groups in concave or convex areas of the surface and then oxygen coordination. The evolution of experimental IR spectra upon evacuation at increasing temperature can be rationalized on the basis of calculated thermal stabilities of each kind of OH groups. A new model is finally proposed to help assign the experimental bands, in terms of hydrogen-bonding, local topology of the hydroxylated sites, and coordination of oxygen.     

Single electron transfer events and dynamical heterogeneity in the small protein azurin from Pseudomonas aeruginosa

Monitoring the fluorescence of single-dye-labeled azurin molecules, we observed the reaction of azurin with hexacyanoferrate under controlled redox potential yielding data on the timing of individual (forward and backward) electron transfer (ET) events. Change-point analysis of the time traces demonstrates significant fluctuations of ET rates and of mid-point potential E₀. These fluctuations are a signature of dynamical heterogeneity, here observed on a 14 kDa protein, the smallest to date. By correlating changes in forward and backward reaction rates we found that 6% of the observed change events could be explained by a change in midpoint potential, while for 25% a change of the donor–acceptor coupling could explain the data. The remaining 69% are driven by variations in complex association constants or structural changes that cause forward and back ET rates to vary independently. Thus, the observed spread in individual ET rates could be related in a unique way to variations in molecular parameters. The relevance for the understanding of metabolic processes is briefly discussed.

Observing electron transfer events in individual azurin molecules, we relate the spread in transfer rates in a unique way to variations in molecular parameters.     

Stochastic theory of size exclusion chromatography by the characteristic function approach

A general stochastic theory of size exclusion chromatography (SEC) able to account for size dependence on both pore ingress and egress processes, moving zone dispersion and pore size distribution, was developed. The relationship between stochastic-chromatographic and batch equilibrium conditions are discussed and the fundamental role of the 'ergodic' hypothesis in establishing a link between them is emphasized. SEC models are solved by means of the characteristic function method and chromatographic parameters like plate height, peak skewness and excess are derived. The peak shapes are obtained by numerical inversion of the characteristic function under the most general conditions of the exploited models. Separate size effects on pore ingress and pore egress processes are investigated and their effects on both retention selectivity and efficiency are clearly shown. The peak splitting phenomenon and peak tailing due to incomplete sample sorption near to the exclusion limit is discussed. An SEC model for columns with two types of pores is discussed and several effects on retention selectivity and efficiency coming from pore size differences and their relative abundance are singled out. The relevance of moving zone dispersion on separation is investigated. The present approach proves to be general and able to account for more complex SEC conditions such as continuous pore size distributions and mixed retention mechanism.     

Noninvasive assessment of hepatic fibrosis in patients with chronic hepatitis C using serum Fourier transform infrared spectroscopy

Assessment of liver fibrosis is of paramount importance to guide the therapeutic strategy in patients with chronic hepatitis C (CHC). In this pilot study, we investigated the potential of serum Fourier transform infrared (FTIR) spectroscopy for differentiating CHC patients with extensive hepatic fibrosis from those without fibrosis. Twenty-three serum samples from CHC patients were selected according to the degree of hepatic fibrosis as evaluated by the FibroTest: 12 from patients with no hepatic fibrosis (F0) and 11 from patients with extensive fibrosis (F3–F4). The FTIR spectra (ten per sample) were acquired in the transmission mode and data homogeneity was tested by cluster analysis to exclude outliers. After selection of the most discriminant wavelengths using an ANOVA-based algorithm, the support vector machine (SVM) method was used as a supervised classification model to classify the spectra into two classes of hepatic fibrosis, F0 and F3–F4. Given the small number of samples, a leave-one-out cross-validation algorithm was used. When SVM was applied to all spectra (n = 230), the sensitivity and specificity of the classifier were 90.1% and 100%, respectively. When SVM was applied to the subset of 219 spectra, i.e., excluding the outliers, the sensitivity and specificity of the classifier were 95.2% and 100%, respectively. This pilot study strongly suggests that the serum from CHC patients exhibits infrared spectral characteristics, allowing patients with extensive fibrosis to be differentiated from those with no hepatic fibrosis.     

Synthesis of 3-methoxyazetidines via an aziridine to azetidine rearrangement and theoretical rationalization of the reaction mechanism

The synthetic utility of N-alkylidene-(2,3-dibromo-2-methylpropyl)amines and N-(2,3-dibromo-2-methylpropylidene)benzylamines was demonstrated by the unexpected synthesis of 3-methoxy-3-methylazetidines upon treatment with sodium borohydride in methanol under reflux through a rare aziridine to azetidine rearrangement. These findings stand in contrast to the known reactivity of the closely related N-alkylidene-(2,3-dibromopropyl)amines, which are easily converted into 2-(bromomethyl)aziridines under the same reaction conditions. A thorough insight into the reaction mechanism was provided by both experimental study and theoretical rationalization.     

Galactose oxidase models: solution chemistry, and phenoxyl radical generation mediated by the copper status

Galactose oxidase (GO) is an enzyme that catalyzes two-electron oxidations. Its active site contains a copper atom coordinated to a tyrosyl radical, the biogenesis of which requires copper and dioxygen. We have recently studied the properties of electrochemically generated mononuclear Cu(II)-phenoxyl radical systems as model compounds of GO. We present here the solution chemistry of these ligands under various copper and dioxygen statuses: N(3)O ligands first chelate Cu(II), leading, in the presence of base, to [Cu(II)(ligand)(CH(3)CN)](+) complexes (ortho-tert-butylated ligands) or [(Cu(II))(2)(ligand)(2)](2+) complexes (ortho-methoxylated ligands). Excess copper(II) then oxidizes the complex to the corresponding mononuclear Cu(II)-phenoxyl radical species. N(2)O(2) tripodal ligands, in the presence of copper(II), afford directly a copper(II)-phenoxyl radical species. Addition of more than two molar equivalents of copper(II) affords a Cu(II)-bis(phenoxyl) diradical species. The donor set of the ligand directs the reaction towards comproportionation for ligands possessing an N(3)O donor set, while disproportionation is observed for ligands possessing an N(2)O(2) donor set. These results are discussed in the light of recent results concerning the self-processing of GO. A path involving copper(II) disproportionation is proposed for oxidation of the cross-linked tyrosinate of GO, supporting the fact that both copper(I) and copper(II) activate the enzyme.     

Activation of bismuth(III) derivatives in ionic liquids: novel and recyclable catalytic systems for Friedel-Crafts acylation of aromatic compounds

The activity of four bismuth(III) derivatives when employed as Friedel-Crafts catalysts for the acylation of aromatics was found to increase dramatically when dissolved in ionic liquids. Solutions of bismuth oxide or triflate in [emim][NTf(2)] and [bmim][NTf(2)] are the most efficient catalytic systems, with catalyst loading as low as 1% leading to clean, high-yielding acylation of a variety of benzene derivatives. These improved Friedel-Crafts catalytic systems can also be efficiently recycled as opposed to traditional systems. [reaction: see text]     

One-pot synthesis of Cu1.94S-CdS and Cu1.94S-Zn(x)Cd(1-x)S nanodisk heterostructures

Nanodisk heterostructures consisting of monoclinic Cu(1.94)S and wurtzite CdS have been colloidally synthesized for the first time. Initially, hexagonal-shaped nanodisks of Cu(1.94)S were produced upon thermolysis of a copper complex in a solvent mixture of HDA and TOA at 250 °C. Rapid addition of Cd precursor to the reaction mixture resulted in the partial conversion of Cu(1.94)S into CdS, yielding Cu(1.94)S-CdS nanoheterostructures. The original morphology of the Cu(1.94)S nanodisks was conserved during the transformation. When Zn precursor was added together with the Cd precursor, Cu(1.94)S-Zn(x)Cd(1-x)S nanodisks were generated. These two-component nanostructures are potentially useful in the fabrication of heterojunction solar cells.