Synthesis of a Helical Bilayer Nanographene

A rigid, inherently chiral bilayer nanographene has been synthesized as both the racemate and enantioenriched M isomer (with 93 % ee) in three steps from established helicenes. This folded nanographene is composed of two hexa‐peri‐hexabenzocoronene layers fused to a [10]helicene, with an interlayer distance of 3.6 Å as determined by X‐ray crystallography. The rigidity of the helicene linker forces the layers to adopt a nearly aligned AA‐stacked conformation, rarely observed in few‐layer graphene. By combining the advantages of nanographenes and helicenes, we have constructed a bilayer system of 30 fused benzene rings that is also chiral, rigid, and remains soluble in common organic solvents. We present this as a molecular model system of bilayer graphene, with properties of interest in a variety of potential applications.     

MTD-ADJ: A multiconformational minimal topologic difference for determining bioactive conformers using adjusted biological activities

The active conformation is part of a conformational mixture with experimental activity Yexp, and is used in QSAR studies to extract more information regarding the ligand-receptor interaction. To reflect the relative amount () of the active conformation, we adjust Yexp : Yadj = Yexp - log . We establish a quantitative structure-activity relationship (QSAR) between Yadj and 3D conformational characteristics for the acetylcholinesterase (AChE) hydrolysis rates of 25 acetic esters. The 3D-QSAR model was obtained using the adjusted multiconformational minimal steric/topologic difference (MTD-ADJ) method, optimizing the receptor map based on Yadj for each conformer. Yadj was updated during each step of the optimization process. and Yadj are based on the Boltzmann distribution calculated using AM1 (MOPAC 6.0) relative energies of the COSMIC 90 derived conformers. The MTD-ADJ results are: (i) the 3D-QSAR models obtained by this procedure have significant statistical parameters and are similar to the unadjusted (MTD-MC, using Yexp) models; (ii) the selected bioactive conformations are extended, occupy cavity vertices and, for the same structures, have the same MTD value; and (iii) the optimized conformational map of the neutral ligands obtained from the MTD-ADJ model fits well in the active site of the crystallographic structure of AChE (from Torpedo californica). We propose a neutral ligands binding site model for AchE. Our results show that MTD-ADJ, which can be implemented in any 3D-QSAR method, is capable of providing additional information regarding the active conformations, and can be used to gain further insight into the ligand-receptor models for which no structural data are available.     

Alcohol uncaging with fluorescence reporting: evaluation of o-acetoxyphenyl methyloxazolone precursors

This paper evaluates a series of photolabile protecting groups with built-in fluorescence reporting. They rely on readily available o-acetoxyphenyl methyloxazolones as activated precursors. Alcohol substrates are easily caged. The resulting photoactivable esters exhibit large one- and two-photon uncaging cross sections. The alcohol substrates are quantitatively released in a 1:1 molar ratio with a strongly fluorescent coumarin coproduct that serves as a reporter to quantify substrate delivery.     

Screening of pi-basic naphthalene and anthracene amplifiers for pi-acidic synthetic pore sensors

Synthetic ion channels and pores attract current attention as multicomponent sensors in complex matrixes. This application requires the availability of reactive signal amplifiers that covalently capture analytes and drag them into the pore. pi-Basic 1,5-dialkoxynaphthalenes (1,5-DAN) are attractive amplifiers because aromatic electron donor-acceptor (AEDA) interactions account for their recognition within pi-acidic naphthalenediimide (NDI) rich synthetic pores. Focusing on amplifier design, we report here the synthesis of a complete collection of DAN and dialkoxyanthracene amplifiers, determine their oxidation potentials by cyclic voltammetry, and calculate their quadrupole moments. Blockage experiments reveal that subtle structural changes in regioisomeric DAN amplifiers can be registered within NDI pores. Frontier orbital overlap in AEDA complexes, oxidation potentials, and, to a lesser extent, quadrupole moments are shown to contribute to isomer recognition by synthetic pores. Particularly important with regard to practical applications of synthetic pores as multianalyte sensors, we further demonstrate that application of the lessons learned with DAN regioisomers to the expansion to dialkoxyanthracenes provides access to privileged amplifiers with submicromolar activity.     

Concomitant Carboxylate and Oxalate Formation From the Activation of CO2 by a Thorium(III) Complex

Improving our comprehension of diverse CO₂ activation pathways is of vital importance for the widespread future utilization of this abundant greenhouse gas. CO₂ activation by uranium(III) complexes is now relatively well understood, with oxo/carbonate formation predominating as CO₂ is readily reduced to CO, but isolated thorium(III) CO₂ activation is unprecedented. We show that the thorium(III) complex, [Th(Cp′′)₃] ( 1 , Cp′′={C₅H₃(SiMe₃)₂‐1,3}), reacts with CO₂ to give the mixed oxalate‐carboxylate thorium(IV) complex [{Th(Cp′′)₂[κ²‐O₂C{C₅H₃‐3,3′‐(SiMe₃)₂}]}₂(μ‐κ²:κ²‐C₂O₄)] ( 3 ). The concomitant formation of oxalate and carboxylate is unique for CO₂ activation, as in previous examples either reduction or insertion is favored to yield a single product. Therefore, thorium(III) CO₂ activation can differ from better understood uranium(III) chemistry.     

The weakness of being cohesive,thin or free in reverse mathematics

Informally, a mathematical statement is robust if its strength is left unchanged under variations of the statement. In this paper, we investigate the lack of robustness of Ramsey’s theorem and its consequence under the frameworks of reverse mathematics and computable reducibility. To this end, we study the degrees of unsolvability of cohesive sets for different uniformly computable sequence of sets and identify different layers of unsolvability. This analysis enables us to answer some questions of Wang about how typical sets help computing cohesive sets.     

Sard theorems for Lipschitz functions and applications in optimization

We establish a “preparatory Sard theorem” for smooth functions with a partially affine structure. By means of this result, we improve a previous result of Rifford [17, 19] concerning the generalized (Clarke) critical values of Lipschitz functions defined as minima of smooth functions. We also establish a nonsmooth Sard theorem for the class of Lipschitz functions from R^d to R^p that can be expressed as finite selections of C^k functions (more generally, continuous selections over a compact countable set). This recovers readily the classical Sard theorem and extends a previous result of Barbet–Daniilidis–Dambrine [1] to the case p > 1. Applications in semi-infinite and Pareto optimization are given.     

Chemiluminescent probe for the in vitro detection of protease activity

A strategy involving the use of a self-immolative linker has been investigated for the chemiluminescent sensing of proteases. The reactive linker enabled the release of a 1,2-dioxetane light precursor. As a proof of principle, caspase-3, a key peptidase involved in apoptosis has been targeted. An in vitro assay has been carried out and proved the decomposition of the linker and the selectivity for caspase-3.