Tetracyanoresorcin[4]arene selectively recognises trimethyllysine and inhibits its enzyme-catalysed demethylation

Abstract

Nε-methylation of lysine within proteins is a critical biological process that, among other roles, is involved in the control of gene expression. Compounds that recognise Nε-methylated lysine may therefore be useful probes for the study of the associated biological mechanisms and have therapeutic potential. Here, we show that tetracyanoresorcin[4]arene (1) selectively recognises Nε-trimethyllysine and binds to Nε-trimethyllysine within the context of a short peptide. Its binding properties compare favourably to a previously characterised Nε-trimethyllysine binder, p-sulfonatocalix[4]arene (2). We also show that both 1 and 2 inhibit the demethylation of Nε-trimethyllysine within a histone-derived peptide by the histone demethylase KDM4A.     

Towards an Understanding of Halide Interactions with the Carbonyl-Containing Molecule CH3CHO

The anion photoelectron spectra of Cl⁻⋅⋅⋅CD₃CDO, Cl⁻⋅⋅⋅(CD₃CDO)₂, Br⁻⋅⋅⋅CH₃CHO, and I⁻⋅⋅⋅CH₃CHO are presented with electron stabilisation energies of 0.55, 0.93, 0.48, and 0.40 eV, respectively. Optimised geometries of the singly solvated species featured the halide appended to the CH₃CHO molecule in-line with the electropositive portion of the C=O bond and having binding energies between 45 and 52 kJ mol⁻¹. The doubly solvated Cl⁻⋅⋅⋅(CH₃CHO)₂ species features asymmetric solvation upon the addition of a second CH₃CHO molecule. Theoretical detachment energies were found to be in excellent agreement with experiment, with comparisons drawn between other halide complexes with simple carbonyl molecules.     

Spectroscopic Investigation of Chalcogen Bonding: Halide–Carbon Disulfide Complexes

A combined experimental and theoretical approach has been used to study intermolecular chalcogen bonding. Specifically, the chalcogen bonding occurring between halide anions and CS₂ molecules has been investigated using both anion photoelectron spectroscopy and high-level CCSD(T) calculations. The relative strength of the chalcogen bond has been determined computationally using the complex dissociation energies as well as experimentally using the electron stabilisation energies. The anion complexes featured dissociation energies on the order of 47 kJ/mol to 37 kJ/mol, decreasing with increasing halide size. Additionally, the corresponding neutral complexes have been examined computationally, and show three loosely-bound structural motifs and a molecular radical.     

One-pot multicomponent synthesis of diversely substituted 2-aminopyrroles. A short general synthesis of rigidins A, B, C, and D

Privileged medicinal scaffolds based on the structures of tetra- and pentasubstituted 2-aminopyrroles were prepared via one-pot multicomponent reactions of structurally diverse aldehydes and N-(aryl-, hetaryl-, alkylsulfonamido)acetophenones with activated methylene compounds. This methodology was used in a four-step synthesis of alkaloids rigidins A, B, C, and D in overall yields of 61%, 58%, 60%, and 53%, respectively. Of these, rigidins B, C, and D were synthesized for the first time.     

Microwave-plasma interactions studied via mode diagnostics in ALPHA

The goal of the ALPHA experiment is the production, trapping and spectroscopy of antihydrogen. A direct comparison of the ground state hyperfine spectra in hydrogen and antihydrogen has the potential to be a high-precision test of CPT symmetry. We present a novel method for measuring the strength of a microwave field for hyperfine spectroscopy in a Penning trap. This method incorporates a non-destructive plasma diagnostic system based on electrostatic modes within an electron plasma. We also show how this technique can be used to measure the cyclotron resonance of the electron plasma, which can potentially serve as a non-destructive measurement of plasma temperature.     

Buffer Standards for the Physiological pH of the Zwitterionic Compound,DIPSO, from 5 to 55 °C

The values of the second dissociation constant, pK ₂, and related thermodynamic quantities of 3-[N,N-bis (2-hydroxyethyl)amino]-2-hydroxypropanesulfonic acid (DIPSO) have already been reported over the temperature range 5 to 55 °C including 37 °C. This paper reports the pH values of four NaCl-free buffer solutions and four buffer composition containing NaCl salt at I=0.16 mol⋅kg⁻¹. Conventional pa _H values are reported for all eight buffer solutions. The operational pH values have been calculated for four buffer solutions recommended as pH standards, at 25 and 37 °C after correcting the liquid junction potentials with the flowing junction cell.     

Buffer Standards for the Physiological pH of the Zwitterionic Compound, HEPPSO from 5 to 55 °C

The values of the thermodynamic second dissociation constant, pK ₂, and related thermodynamic quantities of N-(2-hydroxyethyl)piperazine-N′-2-hydroxypropanesulfonic acid (HEPPSO) have already been reported from 5 to 55?°C, including 37?°C, by the emf method. This paper reports the results for the pH of one chloride-free buffer solution containing the composition: (a) HEPPSO (0.08 mol?kg^?1)+NaHEPPSO (0.04 mol?kg^?1). The remaining seventeen buffer solutions contain a saline medium of ionic strength I=0.16 mol?kg^?1, matching closely that of physiological fluids. Conventional pH values, denoted as pa _H, for all eighteen buffer solutions from 5 to 55?°C have been calculated. The operational pH values, designated as pH, with residual liquid-junction corrections for five buffer solutions, one without NaCl, and four with buffer solutions in saline media of I=0.16 mol?kg^?1 are recommended as pH standards in the range of physiological application. These are based on the NBS/NIST standard scale for pH measurements.     

Mechanotropic Elastomers

Liquid crystal elastomers (LCEs) are anisotropic polymeric materials. When subjected to an applied stress, liquid crystalline (LC) mesogens within the elastomeric polymer network (re)orient to the loading direction. The (re)orientation during deformation results in nonlinear stress‐strain dependence (referred to as soft elasticity). Here, we uniquely explore mechanotropic phase transitions in elastomers with appreciable mesogenic content and compare these responses to LCEs in the polydomain orientation. The isotropic (amorphous) elastomers undergo significant directional orientation upon loading, evident in strong birefringence and x‐ray diffraction. Functionally, the mechanotropic displacement of the elastomers to load is also nonlinear. However, unlike the analogous polydomain LCE compositions examined here, the isotropic elastomers rapidly recover after deformation. The mechanotropic orientation of the mesogens in these materials increase the toughness of these thiol‐ene photopolymers by nearly 1300 % relative to a chemically similar elastomer prepared from wholly isotropic precursors.     

Compression of antiproton clouds for antihydrogen trapping

Control of the radial profile of trapped antiproton clouds is critical to trapping antihydrogen. We report the first detailed measurements of the radial manipulation of antiproton clouds, including areal density compressions by factors as large as ten, by manipulating spatially overlapped electron plasmas. We show detailed measurements of the near-axis antiproton radial profile and its relation to that of the electron plasma.