Synthesis of Highly Enantioenriched Sulfonimidoyl Fluorides and Sulfonimidamides by Stereospecific Sulfur–Fluorine Exchange (SuFEx) Reaction

Sulfonimidamides present exciting opportunities as chiral isosteres of sulfonamides, with potential for additional directional interactions. Here, we present the first modular enantioselective synthesis of sulfonimidamides, including the first stereoselective synthesis of enantioenriched sulfonimidoyl fluorides, and studies on their reactivity. A new route to sulfonimidoyl fluorides is presented from solid bench-stable, N-Boc-sulfinamide (Boc=tert-butyloxycarbonyl) salt building blocks. Enantioenriched arylsulfonimidoyl fluorides are shown to be readily racemised by fluoride ions. Conditions are developed, which trap fluoride and enable the stereospecific reaction of sulfonimidoyl fluorides with primary and secondary amines (100 % es, es=enantiospecificity) generating sulfonimidamides with up to 99 % ee. Aryl and alkyl sulfonimidoyl fluoride reagents are suitable for mild late stage functionalisation reactions, exemplified by coupling with a selection of complex amines in marketed drugs.     

Shifting of gas chromatographic retention times due to solvent effects — a study using sulfur chemiluminescence detection

Gas chromatrography (GC) with sulfur chemiluminescence detection (SCD) is an outstanding combination for selectively determining trace concentrations of sulfur compounds in hydrocarbon samples. GC peaks can be identified by retention times when reproducible, automated injection techniques are used. However, as described in this work, analysts should be on the look out for retention shifting due to solvent effects from sample components. Three examples of retention shifting are presented: (1) thiophene by benzene; (2) methylthiophenes by toluene; and (3) dibenzothiophene by gas oil. Depending on samples and analysis conditions, retention shifts from a few hundredths to 1.5 min have been observed. Such retention shifts are likely to cause errors in peak identifications. Therefore, when using SCD, simultaneous FID monitoring is recommended as an aid in evaluating chromatograms for possible retention shifting due to solvent effects.     

Antibacterial Activity of Pharmaceutical-Grade Rose Bengal: An Application of a Synthetic Dye in Antibacterial Therapies

Rose bengal has been used in the diagnosis of ophthalmic disorders and liver function, and has been studied for the treatment of solid tumor cancers. To date, the antibacterial activity of rose bengal has been sporadically reported; however, these data have been generated with a commercial grade of rose bengal, which contains major uncontrolled impurities generated by the manufacturing process (80–95% dye content). A high-purity form of rose bengal formulation (HP-RBf, >99.5% dye content) kills a battery of Gram-positive bacteria, including drug-resistant strains at low concentrations (0.01–3.13 μg/mL) under fluorescent, LED, and natural light in a few minutes. Significantly, HP-RBf effectively eradicates Gram-positive bacterial biofilms. The frequency that Gram-positive bacteria spontaneously developed resistance to HP-RB is extremely low (less than 1 × 10⁻¹³). Toxicity data obtained through our research programs indicate that HP-RB is feasible as an anti-infective drug for the treatment of skin and soft tissue infections (SSTIs) involving multidrug-resistant (MDR) microbial invasion of the skin, and for eradicating biofilms. This article summarizes the antibacterial activity of pharmaceutical-grade rose bengal, HP-RB, against Gram-positive bacteria, its cytotoxicity against skin cells under illumination conditions, and mechanistic insights into rose bengal’s bactericidal activity under dark conditions.     

Propagation of Relativistic Quantum Particles in Spacetime in Quantum Field Theory

The paper deals with a recent systematic study of the propagation of relativistic quantum particles in spacetime. This study was a reaction to the overwhelming number of experiments dealing with the localization of not only massive but also of photons by detectors. The method of study is based on a configuration unitarity expansion of the vacuum-to-vacuum transition amplitudes as, massive and massless, particles propagate between emitters and detectors. Topics treated are the amplitudes of propagation from one time-space coordinate to another, limiting velocities of particles and their reconciliations with relativity, emergence of particles into cones in detection regions versus the direction of their moments, stimulated emissions by external sources in spacetime, scattering theory in quantum field theory in configuration space, and finally a spacetime for mulation of closed-time path for multi-particle states.     

Synthesis of mesocyclic and macrocyclic polythioethers using the cesium dithiolate technique

The mesocyclic trithioethers, 1,4,7-trithiacyclodecane, 1,4,7-trithiacycloundecane, 1,4,8-trithiacycloundecane, and 1,5,9-trithiacyclododecane; the mesocyclic trithioether ketones, 1,4,7-trithiacyclodecan-9-one; 1,4,8-trithiacycloundecan-6-one, and 1,5,9-trithiacyclododecan-3-one; and the mesocyclic trithioether alcohols, 1,4,7-trithiacyclodecan-9-ol, 1,4,8-trithiacycloundecan-6-ol, and 1,5,9-trithiacyclododecan-3-ol, have been synthesized using the cesium dithiolate technique. In some cases, the corresponding macrocyclic hexathioether was isolated from the reaction mixture in addition to the mesocyclic trithioether; 1,4,7,11,14,17-hexathiacycloeicosane, 1,4,7,11,14,17-hexathiacycloeicosan-9,19-dione, 1,4,7,12,15,18-hexathiacyclodocosane, and 1,5,9,13,17,21-hexathiacyclotetracosane. Single-crystal X-ray structures have been determined for 1,5,9-trithiacyclododecan-3-ol and 1,4,7,12,15,18-hexathiacyclodocosane. For 1,5,9-trithiacyclododecane-3-ol, the compound crystallizes in the monoclinic space group, C2/c, with a = 10.5926( 9 ) Å, b = 15.582(2) Å, c = 13.6015(8) Å, β = 98.186(6)⁰, Z = 8, and R = 0.038. The macrocycle, 1,4,7,12,15,18-hexathiacyclodocosane, crystallizes in the orthorhombic space group, Pbca, with a = 21.406(5) Å, b = 9.810(2) Å, c = 10.225(2) Å, Z = 4, and R = 0.020.     

Electric Double Layer in Water-Organic Mixed Solvents: Titania in 50% Ethylene Glycol

Ethylene glycol (EG) and its mixtures with water are popular components of nanofluids used as heat transfer fluids. The stability of nanofluids against coagulation is correlated with their zeta potential. The electrophoretic mobility of titania nanoparticles in 50-50 w/w EG was studied as a function of the concentration of various solutes. HCl, NaOH, SDS and CTMABr at concentrations up to 0.01 M are strong electrolytes in 50% EG, that is, the conductance of their solutions is proportional to the concentration. HCl, NaOH and CTMABr were very efficient in inducing a high zeta potential for titania in 50% EG. NaOH induced a negative zeta potential in excess of 70 mV, and HCl and CTMABr induced a positive zeta potential in excess of 70 mV at concentrations below 10⁻⁴ M. Apparently, HCl, NaOH and CTMABr are also more efficient than SDS in terms of nanofluid stabilization against coagulation. An overdose of base (>1 mM) results in depression of the negative zeta potential. This result may be due to the specific adsorption of sodium on titania from 50% EG.     

Gas hydrate single-crystal structure analyses

The first single-crystal diffraction studies on methane, propane, methane/propane, and adamantane gas hydrates SI, SII, and SH have been performed. To circumvent the problem of very slow crystal growth, a novel technique of in situ cocrystallization of gases and liquids resulting in oligocrystalline material in a capillary has been developed. With special data treatment, termed oligo diffractometry, structural data of the gas hydrates of methane, acetylene, propane, a propane/ethanol/methane-mixture and an adamantane/methane-mixture were obtained. Cell parameters are in accord with reported values. Host network and guest are subject to extensive disorder, reducing the reliability of structural information. It was found that most cages are fully occupied by a guest molecule with the exception of the dodecahedral cage in the acetylene hydrate which is only filled to 60%. For adamantane in the icosahedral cage a disordered model is proposed.     

Advances in ultra-high load polymer-supported peptide synthesis with phenolic supports: 2. Use of ‘hydrazinolysis-hplc’ to check for racemization on c-terminal amino acid loading and to determine peptide homogeneity during synthesis with selectively labile c-terminal anchoring linkages

2, 4-Dinitrophenyl-L-phenylalanine has been coupled to L-, D-, and DL-amino acid phenyl esters pendant upon a polymer matrix. The esters had been prepared by di-isopropylcarbodiimide-mediated condensation, catalyzed by 4-dimethylaminopyridine. Reverse phase high pressure liquid chromatography (HPLC), using elution solvents consisting of 10 vol.-% trifluoroacetic acid in water/acetonitrile mixtures, has been used to investigate the 2,4-dinitrophenyl L-L and L-D dipeptide mixtures obtained on hydrazinolysis of each of the dipeptide-matrix assemblies. ‘Hydrazinolysis-HPLC’ has been used also to determine intermediate peptide homogeneity in ultra-high load solid (gel) phase synthesis with Boc amino acids. Cross-linked poly(N-[2-(4-hydroxyphenyl)ethyl]acrylamide) and two derived polymers incorporating spacer groups have been used as supports. The spacer groups made possible peptide C-terminal attachment by either HF-labile benzyl ester or HF-labile cyclohexyl ester bonds, while still incorporating the phenolic ester linkage susceptible to rapid hydrazinolytic scission.