Microsolvation and 13C-Li NMR coupling

The empirical expression (1)J(CLi) = L[n(a + d)](-1) is proposed; it claims a reciprocal dependence of the NMR coupling constant (1)J((13)C, Li) in a C-Li compound on two factors: (i) the number n of lithium nuclei in bonding contact with the observed carbanion center and (ii) the sum (a + d) of the numbers a of anions and d of donor ligands coordinated at the Li nucleus that generates the observed (1)J(CLi) value. The expression was derived from integrations of separate NMR resonances of coordinated and free monodentate donor ligands (t-BuOMe, Et2O, or THF) in toluene solutions of dimeric and monomeric 2-(alpha-aryl-alpha-lithiomethylidene)-1,1,3,3-tetramethylindan at moderately low temperatures. This unusually slow ligand interchange is ascribed to steric congestion in these compounds, which is further characterized by measurements of nuclear Overhauser correlations and by solid-state structures of the dimers bearing only one donor per lithium atom (d = 1). Increasing microsolvation numbers d are also accompanied by typical changes of the NMR chemical shifts delta (positive for the carbanionic (13)C(alpha), negative for C(para) and p-H). The aforementioned empirical expression for (1)J(CLi) appears to be applicable to other cases of solvated monomeric, dimeric, or tetrameric C-Li compounds (alkyl, alkenyl, alkynyl, and aryl) and even to unsolvated (d approximately 0) trimeric, tetrameric, or hexameric organolithium aggregates, indicating that (1)J(CLi) might serve as a tool for assessing unknown microsolvation numbers. The importance of obtaining evidence about the (13)C NMR C-Li multiplet splitting of both the nonfluxional and fluxional aggregates is emphasized.     

Synthesis and Conformational Analysis of Pentapeptides Containing Enantiomerically Pure 2,2‐Disubstituted Glycines

The synthesis and conformational analysis of model pentapeptides with the sequence Z‐Leu‐Aib‐Xaa‐Gln‐Valol is described. These peptides contain two 2,2‐disubstituted glycines (α,α‐disubstituted α‐amino acids), i.e., Aib (aminoisobutyric acid), and a series of unsymmetrically substituted, enantiomerically pure amino acids Xaa. These disubstituted amino acids were incorporated into the model peptides via the ‘azirine/oxazolone method’. Conformational analysis was performed in solution by means of NMR techniques and, in the solid state, by X‐ray crystallography. Both methods show that the backbones of these model peptides adopt helical conformations, as expected for 2,2‐disubstitued glycine‐containing peptides.     

Functionalisation of Graphene Sensor Surfaces for the Specific Detection of Biomarkers

We report on a controllable and specific functionalisation route for graphene field-effect transistors (GFETs) for the recognition of small physiologically active molecules. Key element is the noncovalent functionalisation of the graphene surface with perylene bisimide (PBI) molecules directly on the growth substrate. This Functional Layer Transfer enables the homogeneous self-assembly of PBI molecules on graphene, onto which antibodies are subsequently immobilised. The sensor surface was characterised by atomic force microscopy, Raman spectroscopy and electrical measurements, showing superior performance over conventional functionalisation after transfer. Specific sensing of small molecules was realised by monitoring the electrical property changes of functionalised GFET devices upon the application of methamphetamine and cortisol. The concentration dependent electrical response of our sensors was determined down to a concentration of 300 ng ml⁻¹ for methamphetamine.     

Genetic Encoding of bicyclononynes and trans-cyclooctenes for site-specific protein labeling in vitro and in live mammalian cells via rapid fluorogenic Diels-Alder reactions

Rapid, site-specific labeling of proteins with diverse probes remains an outstanding challenge for chemical biologists. Enzyme-mediated labeling approaches may be rapid but use protein or peptide fusions that introduce perturbations into the protein under study and may limit the sites that can be labeled, while many "bioorthogonal" reactions for which a component can be genetically encoded are too slow to effect quantitative site-specific labeling of proteins on a time scale that is useful for studying many biological processes. We report a fluorogenic reaction between bicyclo[6.1.0]non-4-yn-9-ylmethanol (BCN) and tetrazines that is 3-7 orders of magnitude faster than many bioorthogonal reactions. Unlike the reactions of strained alkenes, including trans-cyclooctenes and norbornenes, with tetrazines, the BCN-tetrazine reaction gives a single product of defined stereochemistry. We have discovered aminoacyl-tRNA synthetase/tRNA pairs for the efficient site-specific incorporation of a BCN-containing amino acid, 1, and a trans-cyclooctene-containing amino acid 2 (which also reacts extremely rapidly with tetrazines) into proteins expressed in Escherichia coli and mammalian cells. We demonstrate the rapid fluorogenic labeling of proteins containing 1 and 2 in vitro, in E. coli , and in live mammalian cells. These approaches may be extended to site-specific protein labeling in animals, and we anticipate that they will have a broad impact on labeling and imaging studies.     

Chemoselective transfer hydrogenation to nitroarenes mediated by cubane-type Mo3S4 cluster catalysts

Chemoselective cubes: Cubane-type [Mo(3)S(4)X(3)(dmpe)(3)](+) clusters (dmpe = 1,2-(bis)dimethylphosphinoethane), in combination with an azeotropic 5:2 mixture of HCOOH and NEt(3) as the reducing agent, act as selective cluster catalysts (X = H) or precatalysts (X = Cl) for the transfer hydrogenation of functionalized nitroarenes, without the formation of hazardous hydroxylamines.