Size matters--strong binding of the terephthalate dianion by thiourea functionalised fused [n]polynorbornane hosts

Remarkably strong binding of the new [5]polynorbornane based host to the terephthalate dianion is based on size complementarity of the preorganised binding cleft with the rigid dicarboxylate guest.     

A screening test for heroin based on sequential injection analysis with dual-reagent chemiluminescence detection

A sequential injection analysis procedure with dual-reagent chemiluminescence detection was applied to the screening of street drug seizure samples for the presence of heroin. The chemiluminescence reagents (acidic potassium permanganate and tris(2,2'-bipyridine)ruthenium(III)) were aspirated from either side of a sample aliquot that was sufficiently large to prevent interdispersion of the reagent zones, and therefore two different chemical reactions could be performed simultaneously at either end of the sample zone. The presence of heroin in seizure samples was indicated by a strong response with the tris(2,2'-bipyridine)ruthenium(III) reagent and confirmed by a significant increase in the response with the permanganate reagent when the sample was treated with sodium hydroxide to hydrolyse the heroin to morphine. Nicomorphine (a morphine-derived pharmaceutical) was synthesised and tested under the same conditions. The responses with the permanganate reagent were similar to those for heroin, which supports the proposed chemical basis for the test. However, the responses with tris(2,2'-bipyridine)ruthenium(III) were far lower for nicomorphine than heroin (approximately 5-fold for the samples that had not been hydrolysed).     

Dynamic kinetic resolution of racemic beta-haloalcohols: direct access to enantioenriched epoxides

The direct chemo-enzymatic DKR of racemic beta-haloalcohols is reported, yielding the corresponding optically active epoxides in a single step. The mutant haloalcohol dehalogenase HheC Cys153Ser Trp249Phe is used for the asymmetric ring closure, whereas racemization of the remaining enantiomer of the haloalcohol is achieved using the new iridacycle 3, one of the most effective racemization catalysts to date for beta-haloalcohols.     

Mass spectrometry‐based proteomics of oxidative stress: Identification of 4‐hydroxy‐2‐nonenal (HNE) adducts of amino acids using lysozyme and bovine serum albumin as model proteins

Modification of proteins by 4‐hydroxy‐2‐nonenal (HNE), a reactive by‐product of ω6 polyunsaturated fatty acid oxidation, on specific amino acid residues is considered a biomarker for oxidative stress, as occurs in many metabolic, hereditary, and age‐related diseases. HNE modification of amino acids can occur either via Michael addition or by formation of Schiff‐base adducts. These modifications typically occur on cysteine (Cys), histidine (His), and/or lysine (Lys) residues, resulting in an increase of 156 Da (Michael addition) or 138 Da (Schiff‐base adducts), respectively, in the mass of the residue. Here, we employed biochemical and mass spectrometry (MS) approaches to determine the MS “signatures” of HNE‐modified amino acids, using lysozyme and BSA as model proteins. Using direct infusion of unmodified and HNE‐modified lysozyme into an electrospray quadrupole time‐of‐flight mass spectrometer, we were able to detect up to seven HNE modifications per molecule of lysozyme. Using nanoLC‐MS/MS, we found that, in addition to N‐terminal amino acids, Cys, His, and Lys residues, HNE modification of arginine (Arg), threonine (Thr), tryptophan (Trp), and histidine (His) residues can also occur. These sensitive and specific methods can be applied to the study of oxidative stress to evaluate HNE modification of proteins in complex mixtures from cells and tissues under diseased versus normal conditions.     

Indole as a scaffold for anion recognition

Indole has an acidic N-H that can be used to form hydrogen bonds to anions and in this paper the synthesis of three new suitably functionalised indole based anion receptors is presented along with their evaluation using (1)H NMR titration techniques.     

Microwave-accelerated 1,3-dipolar cycloaddition for the formation of fused [n]polynorbornanes

Microwave irradiation induces the 1,3-dipolar cycloaddition of cyclobutane epoxides with norbornenes to afford [n]polynorbornane scaffolds. Greatly enhanced reaction rates and significantly reduced levels of decomposition were observed.     

Synthesis of planar chiral iridacycles by cationic metal π-coordination: facial selectivity, and conformational and stereochemical consequences

Facial selectivity during the π-coordination of pseudo-tetrahedral iridacycles by neutral (Cr(CO)(3)), monocationic (Cp*Ru(+)), and biscationic (Cp*Ir(2+)) metal centers was directly influenced by the coulombic imbalance in the coordination sphere of the chelated Ir center. We also showed by using theoretical calculations that the feasibility of the related metallacycles that displayed metallocenic planar chirality was dependent to the presence of an electron-donating group, such as NMe(2), which contributed to the overall stability of the complexes. When the π-bonded moiety was the strongly electron-withdrawing Cp*Ir(2+) group, the electron donation from NMe(2) resulted in major conformational changes, with a barrier to rotation of about 17?kcal mol(-1) for this group that became spectroscopically diastereotopic (high-field (1)H?NMR spectroscopy). This peculiar property is proposed as a means to introduce a new type of constitutional chirality at the nitrogen center: planar chirality at tertiary aromatic amines.     

Redox self-sufficient biocatalyst network for the amination of primary alcohols

Driving the machinery: A biocatalytic redox-neutral cascade for the preparation of terminal primary amines from primary alcohols at the expense of ammonia has been established in a one-pot one-step method. Applying this artificial biocatalyst network, long-chain 1,ω-alkanediols were converted into diamines, which are building blocks for polymers, in up to 99?% conversion.     

Asymmetric induction in domino Heck-aza-Michael reactions

Domino Heck-aza-Michael reactions are an efficient method for the rapid synthesis of functionalised N-heterocycles. An asymmetric version of this domino process has been developed to access chiral 1,3-disubstituted N-heterocycles from amino acid precursors in excellent yields (68–81%) with moderate to high diastereoselectivity (up to 92% de).