Regiodivergent and Stereoselective Hydrosilylation of 1,3‐Disubstituted Allenes

Methods for the highly stereoselective and regiodivergent hydrosilylation of 1,3‐disubstituted allenes have been developed. The synthesis of E allylsilanes is accomplished with palladium NHC catalysts, and trisubstituted Z alkenylsilanes are accessed with nickel NHC catalysts. Unsymmetrically substituted allenes are well tolerated with nickel catalysis and afford Z alkenylsilanes. Evidence for a plausible mechanism was obtained through an isotopic double‐labeling crossover study.     

Facile Hydrolysis and Alcoholysis of Palladium Acetate

Palladium(II) acetate is readily converted into [Pd₃(μ²‐OH)(OAc)₅] ( 1 ) in the presence of water in a range of organic solvents and is also slowly converted in the solid state. Complex 1 can also be formed in nominally anhydrous solvents. Similarly, the analogous alkoxide complexes [Pd₃(μ²‐OR)(OAc)₅] ( 3 ) are easily formed in solutions of palladium(II) acetate containing a range of alcohols. An examination of a representative Wacker‐type oxidation shows that the Pd‐OH complex 1 and a related Pd‐oxo complex 4 can be excluded as potential catalytic intermediates in the absence of exogenous water.     

Rare earth elements determined in Antarctic ice by inductively coupled plasma--time of flight, quadrupole and sector field-mass spectrometry: An inter-comparison study

Inductively coupled plasma mass spectrometry (ICP-MS) is a suitable tool for multi-element analysis at low concentration levels. Rare earth element (REE) determinations in standard reference materials and small volumes of molten ice core samples from Antarctica have been performed with an ICP-time of flight-MS (ICP-TOF-MS) system. Recovery rates for REE in e.g. SPS-SW1 amounted to ∼103%, and the relative standard deviations were 3.4% for replicate analysis at REE concentrations in the lower ng L⁻¹ range. Analyses of REE concentrations in Antarctic ice core samples showed that the ICP-TOF-MS technique meets the demands of restricted sample mass. The data obtained are in good agreement with ICP-Quadrupole-MS (ICP-Q-MS) and ICP-Sector Field-MS (ICP-SF-MS) results. The ICP-TOF-MS system determines accurately and precisely REE concentrations exceeding 5 ng L⁻¹ while between 0.5 and 5 ng L⁻¹ accuracy and precision are element dependent.     

Spectroelectrochemical and computational studies on the mechanism of hypoxia selectivity of copper radiopharmaceuticals

Detailed chemical, spectroelectrochemical and computational studies have been used to investigate the mechanism of hypoxia selectivity of a range of copper radiopharmaceuticals. A revised mechanism involving a delicate balance between cellular uptake, intracellular reduction, reoxidation, protonation and ligand dissociation is proposed. This mechanism accounts for observed differences in the reported cellular uptake and washout of related copper bis(thiosemicarbazonato) complexes. Three copper and zinc complexes have been characterised by X-ray crystallography and the redox chemistry of a series of copper complexes has been investigated by using electronic absorption and EPR spectroelectrochemistry. Time-dependent density functional theory (TD-DFT) calculations have also been used to probe the electronic structures of intermediate species and assign the electronic absorption spectra. DFT calculations also show that one-electron oxidation is ligand-based, leading to the formation of cationic triplet species. In the absence of protons, metal-centred one-electron reduction gives the reduced anionic copper(I) species, [CuIATSM](-), and for the first time it is shown that molecular oxygen can reoxidise this anion to give the neutral, lipophilic parent complexes, which can wash out of cells. The electrochemistry is pH dependent and in the presence of stronger acids both chemical and electrochemical reduction leads to quantitative and rapid dissociation of copper(I) ions from the mono- or diprotonated complexes, [CuIATSMH] and [Cu(I)ATSMH2]+. In addition, a range of protonated intermediate species have been identified at lower acid concentrations. The one-electron reduction potential, rate of reoxidation of the copper(I) anionic species and ease of protonation are dependent on the structure of the ligand, which also governs their observed behaviour in vivo.     

Systematic comparison of delta34S measurements by multicollector inductively coupled plasma mass spectrometry and evaluation of full uncertainty budget using two different metrological approaches

A systematic comparison of delta34S measurements by multicollector inductively coupled plasma mass spectrometry (MCICPMS) using two different standardisation approaches and two different reference materials as working standards is reported for the first time. Full uncertainty budgets have been calculated using the Kragten approach. Internal standardisation by measuring Si ratios and external standardisation by bracketing samples with either NIST RM8553 or NIST RM8554 have been compared to correct for the effects of mass bias. The delta34S value and the associated uncertainty ( per thousand) were found to be slightly different when using different approaches. Corrected 34S:32S ratios for NIST RM8553 and NIST RM8554 differed from those previously reported by 0.1 to 0.5% when using external standardisation. 34S:32S ratios for NIST RM8553 and NIST RM8554 differed from those previously reported by 0.06 to 0.15% when using Si internal standardisation. This indicated that in order to minimise deviation from true ratio values, Si internal standardisation would be a more appropriate option when using a Neptune MCICPMS instrument. delta(34)S values were obtained for four different methionine samples and expanded uncertainties (k = 2) expressed in delta34S ( per thousand) ranged from 0.7 per thousand to 1.6 per thousand. Regardless of the approach used for the mass bias correction, three parameters provided the major contributions to the standard uncertainty of the delta34S(V-CDT) value. These were the measured 34S:32S in the sample, the measured 34S:32S for the working standard and the known delta34S(V-CDT) value of the working standard. Results using both approaches are compared and the Si internal standardisation approach is used to provide results for an inter-laboratory comparison.     

Application of 1-aminocyclohexane carboxylic acid to protein nanostructure computer design

Conformationally restricted amino acids are promising candidates to serve as basic pieces in redesigned protein motifs which constitute the basic modules in synthetic nanoconstructs. Here we study the ability of constrained cyclic amino acid 1-aminocyclohexane-1-carboxylic acid (Ac6c) to stabilize highly regular beta-helical motifs excised from naturally occurring proteins. Calculations indicate that the conformational flexibility observed in both the ring and the main chain is significantly higher than that detected for other 1-aminocycloalkane-1-carboxylic acids (Acnc, where n refers to the size of the ring) with smaller cycles. Incorporation of Ac6c into the flexible loops of beta-helical motifs indicates that the stability of such excised building blocks as well as the nanoassemblies derived from them is significantly enhanced. Thus, the intrinsic Ac6c tendency to adopt folded conformations combined with the low structural strain of the cyclohexane ring confers the ability to both self-adapt to the beta-helix motif and to stabilize the overall structure by absorbing part of its conformational fluctuations. Comparison with other Acnc residues indicates that the ability to adapt to the targeted position improves considerably with the ring size, i.e., when the rigidity introduced by the strain of the ring decreases.     

Photo-induced electron emission from 17beta-estradiol and progesterone and possible biological consequences

It was established for the first time, that the sexual hormones 17beta-estradiol (17betaE2) and progesterone (PRG) are able to emit electrons from their excited single state in water-ethanol mixtures. The yield of the "solvated electrons" (e(s)(-)) depends on the substrate concentration, the ratio of water-alcohol-mixtures and the temperature. The e(s)(-) yield obtained from 17betaE2 is by two orders of magnitude higher than this of PRG. The possible relationship of the resulting hormone transients from 17betaE2 leading via specific metabolites to breast cancer is discussed.     

Proton-sponge coated quantum dots for siRNA delivery and intracellular imaging

We report the rational design of multifunctional nanoparticles for short-interfering RNA (siRNA) delivery and imaging based on the use of semiconductor quantum dots (QDs) and proton-absorbing polymeric coatings (proton sponges). With a balanced composition of tertiary amine and carboxylic acid groups, these nanoparticles are specifically designed to address longstanding barriers in siRNA delivery such as cellular penetration, endosomal release, carrier unpacking, and intracellular transport. The results demonstrate dramatic improvement in gene silencing efficiency by 10-20-fold and simultaneous reduction in cellular toxicity by 5-6-fold, when compared directly with existing transfection agents for MDA-MB-231 cells. The QD-siRNA nanoparticles are also dual-modality optical and electron-microscopy probes, allowing real-time tracking and ultrastructural localization of QDs during delivery and transfection. These new insights and capabilities represent a major step toward nanoparticle engineering for imaging and therapeutic applications.     

Simple route to new oxadiazaboroles and oxadiazoles via amidoximes

Abstract

The novel push–pull alkene, the 2-(nitro-nitrosomethylene)-pyrrolidine with numerous aliphatic or aromatic amines as nucleophiles afforded amidoximes. Various substituted oxadiazaborole and oxadiazole derivatives were prepared starting from these amidoximes, widening the synthetic applicability of the push–pull alkenes. Acylation of the amidoximes was also examined. The mechanism of the amidoxime formation was investigated by computational methods.     

Active Intermediates in Copper Nitrite Reductase Reactions Probed by a Cryotrapping‐Electron Paramagnetic Resonance Approach

Redox active metalloenzymes catalyse a range of biochemical processes essential for life. However, due to their complex reaction mechanisms, and often, their poor optical signals, detailed mechanistic understandings of them are limited. Here, we develop a cryoreduction approach coupled to electron paramagnetic resonance measurements to study electron transfer between the copper centers in the copper nitrite reductase (CuNiR) family of enzymes. Unlike alternative methods used to study electron transfer reactions, the cryoreduction approach presented here allows observation of the redox state of both metal centers, a direct read‐out of electron transfer, determines the presence of the substrate/product in the active site and shows the importance of protein motion in inter‐copper electron transfer catalyzed by CuNiRs. Cryoreduction‐EPR is broadly applicable for the study of electron transfer in other redox enzymes and paves the way to explore transient states in multiple redox‐center containing proteins (homo and hetero metal ions).