A Cucurbit[8]uril 2:2 Complex with a Negative pKa Shift

A viologen derivative carrying a benzimidazole group ( V-P-I ²⁺; viologen–phenylene–imidazole V-P-I ) can be dimerized in water using cucurbit[8]uril (CB[8]) in the form of a 2:2 complex resulting in a negative shift of the guest pK_a, by more than 1 pH unit, contrasting with the positive pK_a shift usually observed for CB-based complexes. Whereas 2:2 complex protonation is unclear by NMR, silver cations have been used for probing the accessibility of the imidazole groups of the 2:2 complexes. The protonation capacity of the buried imidazole groups is reduced, suggesting that CB[8] could trigger proton release upon 2:2 complex formation. The addition of CB[8] to a solution containing V-P- I ³⁺ indeed released protons as monitored by pH-metry and visualized by a coloured indicator. This property was used to induce a host/guest swapping, accompanied by a proton transfer, between V-P-I ³⁺ ⋅ CB[7] and a CB[8] complex of 1-methyl-4-(4-pyridyl)pyridinium. The origin of this negative pK_a shift is proposed to stand in an ideal charge state, and in the position of the two pH-responsive fragments inside the two CB[8] which, alike residues engulfed in proteins, favour the deprotonated form of the guest molecules. Such proton release triggered by a recognition event is reminiscent of several biological processes and may open new avenues toward bioinspired enzyme mimics catalyzing proton transfer or chemical reactions.     

Divergent Synthesis of Bioactive Dithiodiketopiperazine Natural Products Based on a Double C(sp3)−H Activation Strategy

This article provides a detailed report of our efforts to synthesize the dithiodiketopiperazine (DTP) natural products (−)-epicoccin G and (−)-rostratin A using a double C(sp³)−H activation strategy. The strategy's viability was first established on a model system lacking the C8/C8’ alcohols. Then, an efficient stereoselective route including an organocatalytic epoxidation was secured to access a key bis-triflate substrate. This bis-triflate served as the functional handles for the key transformation of the synthesis: a double C(sp³)−H activation. The successful double activation opened access to a common intermediate for both natural products in high overall yield and on a multigram scale. After several unsuccessful attempts, this intermediate was efficiently converted to (−)-epicoccin G and to the more challenging (−)-rostratin A via suitable oxidation/reduction and protecting group sequences, and via a final sulfuration that occurred in good yield and high diastereoselectivity. These efforts culminated in the synthesis of (−)-epicoccin G and (−)-rostratin A in high overall yields (19.6 % over 14 steps and 12.7 % over 17 steps, respectively), with the latter being obtained on a 500 mg scale. Toxicity assessments of these natural products and several analogues (including the newly synthesized epicoccin K) in the leukemia cell line K562 confirmed the importance of the disulfide bridge for activity and identified dianhydrorostratin A as a 20x more potent analogue.     

Bi-Sobolev solutions to the prescribed Jacobian inequality in the plane with Lp data and applications to nonlinear elasticity

We construct planar bi-Sobolev mappings whose local volume distortion is bounded from below by a given function $f\in L^p$ with $p>1$. More precisely, for any $1<q<(p+1)/2$ we construct $W^{1,q}$-bi-Sobolev maps with identity boundary conditions; for $f\in L^{\infty }$, we provide bi-Lipschitz maps. The basic building block of our construction are bi-Lipschitz maps which stretch a given compact subset of the unit square by a given factor while preserving the boundary. The construction of these stretching maps relies on a slight strengthening of the celebrated covering result of Alberti, Csörnyei, and Preiss for measurable planar sets in the case of compact sets. We apply our result to a model functional in nonlinear elasticity, the integrand of which features fast blowup as the Jacobian determinant of the deformation becomes small. For such functionals, the derivation of the equilibrium equations for minimizers requires an additional regularization of test functions, which our maps provide.     

Access to New Endoperoxide Derivatives by Electrochemical Oxidation of Substituted 3‐Azabicyclo[4.1.0]hept‐4‐enes

A series of substituted 3‐azabicyclo[4.1.0]hept‐4‐ene derivatives were prepared and analysed by cyclic voltammetry. Preparative aerobic electrochemical oxidation reactions were then carried out. Three original endoperoxides were isolated, characterised and subjected to antimalarial and cytotoxicity activity assays.     

Experimental and numerical study of shock wave propagation in water generated by pulsed arc electrohydraulic discharges

The objective of this study is to simulate the propagation of the shock wave in water due to an explosion. The study is part of a global research program on the development of an alternative stimulation technique to conventional hydraulic fracturing in tight gas reservoirs aimed at inducing a distributed state of microcracking of rocks instead of localized fracture. We consider the possibility of increasing the permeability of rocks with dynamic blasts. The blast is a shock wave generated in water by pulsed arc electrohydraulic discharges. The amplitude of these shock waves is prescribed by the electrohydraulic discharges which generate high pressures of several kilobars within microseconds. A simplified method has been used to simulate the injected electrical energy as augmentation of enthalpy in water locally. The finite element code EUROPLEXUS is used to perform fluid fast dynamic computation. The predicted pressure is consistent with the experimental results. In addition, shock wave propagation characteristics predicted with simulation can be valuable reference for design of underwater structural elements and engineering of underwater explosion.