Switching the Switch: Ligand Induced Disulfide Formation in HDAC8

Human histone deacetylase 8 is a well-recognized target for T-cell lymphoma and particularly childhood neuroblastoma. PD-404,182 was shown to be a selective covalent inhibitor of HDAC8 that forms mixed disulfides with several cysteine residues and is also able to transform thiol groups to thiocyanates. Moreover, HDAC8 was shown to be regulated by a redox switch based on the reversible formation of a disulfide bond between cysteines Cys₁₀₂ and Cys₁₅₃. This study on the distinct effects of PD-404,182 on HDAC8 reveals that this compound induces the dose-dependent formation of intramolecular disulfide bridges. Therefore, the inhibition mechanism of HDAC8 by PD-404,182 involves both, covalent modification of thiols as well as ligand mediated disulfide formation. Moreover, this study provides a deep molecular insight into the regulation mechanism of HDAC8 involving several cysteines with graduated capability to form reversible disulfide bridges.     

17O and 33S nuclear magnetic shielding of sulfur trioxides from the experimental measurements and theoretical calculations

In a recent ¹⁷O NMR spectra of liquid sulfur trioxide, several unexpected peaks appeared with the temperature‐dependent integrated peak ratio. In order to interpret NMR spectra and assign peaks to possible molecular structures, the theoretical quantum mechanical density functional theory and Møller–Plesset second‐order perturbation theory calculations were performed. It is suggested that in the liquid sulfur trioxide, apart from monomeric SO₃, a significant amount of (SO₃)₃ cyclic trimers should appear. No theoretical data support hypothesis on (SO₃)₂ dimers formation. Copyright © 2014 John Wiley & Sons, Ltd.     

C-Acylation of Electron-Excess Heterocycles by Isocyanatophosphoric Acid Dichlorides

Abstract

Isocyanatophosphoric acid dichlondes was used for introduction of phosphorus-containing groups at electron-excess heterocycles. Hetaryl containing dichlorophosphates, convenient starting material for synthesis for wide set of derivatives, were prepared by C-acylation with this reagent.     

A new type of cation‐exchange polymeric microspheres with pendant methylenethiol groups

Synthesis and characterization of the new styrene microspheres with pendant methylenethiol groups are presented. At the first stage, the polymeric matrices were obtained by the suspension–emulsion polymerization of monomers: styrene (St) with 2,3‐(2‐hydroxy‐3‐methacryloyloxypropoxy)naphthalene (NAF.DM) or (bis[4(2‐hydroxy‐3‐methacryloyloxypropoxy)phenyl]sulfide (BES.DM) or divinylbenzene (DVB). At the second stage, the modification of the sythesized matrices was performed as follows: the matrices were reacted with paraformaldehyde in the presence of hydrochloric acid forming chloromethyl derivatives. Next, by reaction with thiourea, a thiouronium salt was obtained, and then the hydrolysis with NaOH solution and acidification with HCl were carried out. Finally, microspheres with –CH₂SH groups on their surface were obtained. The –SH group content (elemental analysis), thermal properties (thermogravimetric analysis), Fourier transform infrared as well as the swelling characteristics of the functional microspheres were examined. The surface texture was also visualized by the atomic force microscopy (AFM) method. The obtained polymers were screened towards sorption of Cu(II) ions. It was found that a better correlation between the experimental Cu(II) uptake and the theoretical curves predicted by the Langmuir or Freundlich models is obtained in the case of the DVB–St–SH polymer. In the case of the BES.DM–St–SH and 2,3‐NAF–St–SH ones, the Freundlich model corresponded quite well to the experimental data. Copyright © 2013 John Wiley & Sons, Ltd.     

A superhydrophobic magnetic elastomer actuator for droplet motion control

For the fast droplet transportation on an open surface, a new magnetic elastomer with a superhydrophobic surface has been developed. Because the surface is superhydrophobic, the water droplet can easily roll off on the surface. The movement of the droplet was controlled by a deliberate local deformation of the surface of the elastomer induced by magnetic actuation. The direction and speed of the droplet motion was easily controlled by changing the surface topography using magnetic force. We also demonstrate the applicability of the devices as a new type of open‐surface digital microfluidics using a simple chemical reaction. Copyright © 2013 John Wiley & Sons, Ltd.     

The influence of oxidation number of sulfur on the polymerization and thermo-mechanical properties of dimethacrylate copolymers

Structure and characterization of the sulfur-containing monomers bis[4(2-hydroxy-3-methacryloyloxypropoxy)phenyl]sulfide (S·DM), bis[4(2-hydroxy-3-methacryloyloxypropoxy)phenyl]sulfinyl (SO·DM), bis[4(2-hydroxy-3-methacryloyloxypropoxy)phenyl]sulfonyl (SO₂·DM), and their photopolymerization with N-vinyl-2-pyrrolidone (NVP) are presented. The monomers were obtained in the reaction of derivatives of aromatic diols with 2-(chloromethyl)oxirane in the two-phase liquid/liquid system, including organic and aqueous phases. Next, esterification of the obtained diglycidyl ether was carried out with the use of methacrylic acid. Photopolymerization of the compositions (S·DM, SO·DM, SO₂·DM and NVP) and the initiator (Irgacure 651) was carried out. The influence of oxidation number of sulfur on the properties of the obtained copolymers was studied. The following properties were determined: density, glass transition temperature, Young’s modulus, hardness and tensile strength. Additionally, dynamic-mechanical and thermal properties were investigated. Thermal properties of copolymers under different conditions (in air, in nitrogen and in helium) were tested.     

Performance of density functional theory in computing nonresonant vibrational (hyper)polarizabilities

A set of exchange‐correlation functionals, including BLYP, PBE0, B3LYP, BHandHLYP, CAM‐B3LYP, LC‐BLYP, and HSE, has been used to determine static and dynamic nonresonant (nuclear relaxation) vibrational (hyper)polarizabilities for a series of all‐trans polymethineimine (PMI) oligomers containing up to eight monomer units. These functionals are assessed against reference values obtained using the Møller–Plesset second‐order perturbation theory (MP2) and CCSD methods. For the smallest oligomer, CCSD(T) calculations confirm the choice of MP2 and CCSD as appropriate for assessing the density functionals. By and large, CAM‐B3LYP is the most successful, because it is best for the nuclear relaxation contribution to the static linear polarizability, intensity‐dependent refractive index second hyperpolarizability, static second hyperpolarizability, and is close to the best for the electro‐optical Pockels effect first hyperpolarizability. However, none of the functionals perform satisfactorily for all the vibrational (hyper)polarizabilities studied. In fact, in the case of electric field‐induced second harmonic generation all of them, as well as the Hartree–Fock approximation, yield the wrong sign. We have also found that the Pople 6–31+G(d) basis set is unreliable for computing nuclear relaxation (hyper)polarizabilities of PMI oligomers due to the spurious prediction of a nonplanar equilibrium geometry. © 2013 Wiley Periodicals, Inc.