Emerging Methods and Design Principles for Cell‐Penetrant Peptides

Biomolecules such as antibodies, proteins, and peptides are important tools for chemical biology and leads for drug development. They have been used to inhibit a variety of extracellular proteins, but accessing intracellular proteins has been much more challenging. In this review, we discuss diverse chemical approaches that have yielded cell‐penetrant peptides and identify three distinct strategies: masking backbone amides, guanidinium group patterning, and amphipathic patterning. We summarize a growing number of large data sets, which are starting to reveal more specific design guidelines for each strategy. We also discuss advantages and disadvantages of current methods for quantifying cell penetration. Finally, we provide an overview of best‐odds approaches for applying these new methods and design principles to optimize cytosolic penetration for a given bioactive peptide.     

Vapour–liquid equilibrium data for the 1,1,1,2 tetrafluoroethane (R134a) + dimethyl ether (DME) system at temperatures from 293.18 to 358.15 K and pressures up to about 3 MPa

Isothermal vapour–liquid equilibrium data have been measured for the binary system R134a + DME at five temperatures between 293.18 and 358.15 K, and pressures between 0.4899 and 2.9442 MPa. The peculiarity of this system is the existence of an azeotrope with a minimum pressure, which disappears at 358.15 K. The experimental method used in this work is of the static-analytic type, taking advantage of two pneumatic capillary samplers (Rolsi™, Armines’ patent) developed in the CENERG/TEP Laboratory. The data were obtained with uncertainties within ±0.02 K, ±0.0001 MPa and ±1% for molar compositions.

The isothermal P, x, y data are well represented with the Redlich and Kwong equation of state using the Mathias–Copeman alpha function and the Huron–Vidal mixing rules involving the NRTL model.     

Novel sulfate ion-selective polymeric membrane electrode based on a derivative of pyrilium perchlorate

A sulfate ion-selective PVC membrane sensor based on 4-(4-bromophenyl)-2,6-diphenylpyrilium perchlorate (BDPP) as a novel sensing material is successfully developed. The electrode shows a good selectivity for sulfate ion with respect to common organic and inorganic anions. The sensor exhibits a good linear response with slope of -28.9+/-0.5 mV per decade over the concentration range of 1.0x10(-6)-1.0x10(-2) M, and a detection limit of 8.0x10(-7) M of SO(4)(2-) ions. The electrode response is independent of pH in the range of 4.0-9.0. The proposed sensor was applied as an indicator electrode in potentiometric titration of sulfate and barium ions, and to the determination of zinc in zinc sulfate tablets.     

Formation of third generation poly(pyrazolyl)borate ligands from alkyne coupling reactions of Fe[(p-IC6H4)B(3-Rpz)3]2 (R = H, Me; pz = pyrazolyl): pathways toward controlling an iron(II) electronic spin-state crossover

Sonogashira coupling reactions of terminal alkynes with Fe[(p-IC6H4)B(3-Mepz)3]2 (pz = pyrazolyl ring) yield Fe[(p-PhC2C6H4)B(3-Mepz)3]2 (2), Fe[(p-Me3SiC2C6H4)B(3-Rpz)3]2 (R = H, 3a, R = Me, 3b), and Fe[(p-HC2C6H4)B(3-Mepz)3]2 (R = H, 4a, R = Me, 4b), a series of new complexes containing "third generation" poly(pyrazolyl)borate ligands. Complex 2 undergoes a fairly gradual iron(II) electronic spin-state crossover with a 30 K hysteresis, whereas complex 3b is an unusual example of a complex with equivalent iron(II) sites in the high-spin form that shows an abrupt 50% spin crossover. For complex 4b, 50% of the iron(II) sites undergo a gradual spin-state transition between 185 and 350 K with an activation energy of 1590 +/- 30 cm(-1) and a T(1/2) = 280 K and, for the remaining iron(II) sites, an abrupt cooperative spin-state crossover between 106 and 114 K. The crystal structures of 4b obtained for each of the three distinct electronic spin states reveal two crystallographically different iron(II) sites, and analysis of the molecular/supramolecular structures indicates that the difference in the degree of pyrazolyl ring tilting in the ligands between the two sites, rather than the strength of the intermolecular forces, play a prominent role in determining the temperature of the spin-state crossover.     

Redox-Neutral Syntheses and Electrochemical Studies of 10-Bromo-Substituted Light-Stable Antivitamin B12 Candidates

This publication describes the straightforward and redox-neutral synthesis of 10-bromophenylethynylcobalamin and its facile conversion to 10-bromoaquacobalamin. In this approach, the phenylethynyl ligand acts as convenient light-stable protecting group that is removed in quantitative yield under acidic conditions. The proteolytic cleavage at pH 2.0 was studied under pseudo-first-order conditions and is 1.5 times slower than that of phenylethynylcobalamin with a hydrogen instead of a bromine at C(10). Preliminary electrochemical studies of organometallic ethynyl-Cbls (Cbl=cobalamin) are reported for the first time. A reduction potential of −0.94 V vs. Ag/AgCl was determined for the Co^III/Co^I reduction of 10-bromophenylethynylcobalamin. The positive potential shift of 180 mV compared to phenylethynylcobalamin is in agreement with earlier electrochemical studies of related cyanocobalamins.     

Octadecyl silica membrane disks modified with a new Schiff's base for the preconcentration of lead and copper before their determination in water samples

A simple and fast method for the extraction and determination of ppt level of Pb2+ and Cu2+ ions using octadecyl-bonded silica membrane disks modified by a new tetradentates Schiffs base [Bis(2,4-dimethoxy benzaldehyde) ethylen diimine](TDSB) and inductively coupled plasma atomic emission spectrometry is described. Extraction efficiency, and influence of flow rate, pH, type and the least amount of acid for stripping of Cu2+ and Pb2+ from the modified disks and break through volume were evaluated. The maximum capacity of the membrane disks modified by 5 mg of TDSB used was found to be 347 +/- 7 and 470 +/- 6 microg of copper and lead, respectively. The concentration factor is 500 (for 2500 mL water sample and flow rate of 20 mL min(-1)) and detection limit of the proposed method is 12.5 and 150.5 pg/ml for Cu2+ and Pb2+, respectively. The method was applied to the determination of Cu2+ and Pb2+ ions from various water, wastewater, black tea, and hot pepper samples.     

Epoxidation of alkenes with molecular oxygen and isobutyraldehyde catalyzed by immobilized vitamin B12 within Al-MCM-41

Vit-B₁₂/ Al-MCM-41 catalyzed successfully the epoxidation either of cis or trans — stilbene with O₂ as oxidant and isobutyraldehyde as co-reductant with 86–98% reactivity and 97–100% selectivity. Other olefins such as norbornene and styrene undergo epoxidation reaction under similar conditions with good to fair selectivity. Details of the reactions will be presented in this article.     

The Behavior of Phosphorus Reagents Towards Substituted Diazine and Hydrazine Derivatives

Summary. The reaction of dibenzoyldiazine with phosphorus ylides afforded the new 2-[(benzoylhydrazono)phenylalkyl]but-2-enedioic acid dialkylesters. Moreover, ethyl-2(triphenylphosphoranylidene)propionate reacts with dibenzoyldiazine to give the olefinic compound and triphenylphosphine oxide. On the other hand, oxovinylidene-triphenylphosphorane reacts with dibenzoyldiazine to give a new phosphorane adduct. Trialkyl phosphites react with dibenzoyldiazine to yield the dialkyl phosphonate products. The reaction of dibenzoylhydrazide with Wittig reagents gave rise to the new 3,7-diphenylpyrazolo[1,2-α]pyrazole-1,5-diones. Possible reaction mechanisms are considered, and the structural assignments are based on analytical and spectroscopic results.     

Modeling of the nonlinear vibrations of a stiffened moderately thick plate

We consider a multi-structure consisting of a plate reinforced by a thin stiffener on a portion of its boundary. The model we consider for this structure (viewed as a heterogeneous plate) is nonlinear and takes into account the transverse shear effects. Our aim is to model this junction and reproduce the effect of the thin stiffener by means of approximate boundary conditions on the junction region.