Modified normal-phase ion-pair chromatographic methods for the facile separation and purification of imidazolium-based ionic compounds

Imidazolium- and oligo(imidazolium)-based ionic organic compounds are important in the design of room-temperature ionic liquid materials; however, the chromatographic analysis and separation of such compounds are often difficult. A convenient and inexpensive method for effective thin-layer chromatography (TLC) analysis and column chromatography separation of imidazolium-based ionic compounds is presented. Normal-phase ion-pair TLC is used to effectively analyze homologous mixtures of these ionic compounds. Subsequent separation of the mixtures is performed using ion-pair flash chromatography on normal-phase silica gel, yielding high levels of recovery. This method also results in a complete exchange of the counter anion on the imidazolium compounds to the anion of the ion-pair reagent.     

Effects of reverberation and masking on speech intelligibility in cochlear implant simulations

Two experiments investigated the impact of reverberation and masking on speech understanding using cochlear implant (CI) simulations. Experiment 1 tested sentence recognition in quiet. Stimuli were processed with reverberation simulation (T=0.425, 0.266, 0.152, and 0.0 s) and then either processed with vocoding (6, 12, or 24 channels) or were subjected to no further processing. Reverberation alone had only a small impact on perception when as few as 12 channels of information were available. However, when the processing was limited to 6 channels, perception was extremely vulnerable to the effects of reverberation. In experiment 2, subjects listened to reverberated sentences, through 6- and 12-channel processors, in the presence of either speech-spectrum noise (SSN) or two-talker babble (TTB) at various target-to-masker ratios. The combined impact of reverberation and masking was profound, although there was no interaction between the two effects. This differs from results obtained in subjects listening to unprocessed speech where interactions between reverberation and masking have been shown to exist. A speech transmission index (STI) analysis indicated a reasonably good prediction of speech recognition performance. Unlike previous investigations, the SSN and TTB maskers produced equivalent results, raising questions about the role of informational masking in CI processed speech.     

Carbene or zwitterion? Competition in organoplatinum complexes

The reaction of a known dimeric dicarbene complex of platinum with a number of ligands results in four new platinum complexes. The structure of the new complexes is described: one complex must exist as a neutral complex with no charge separation, and the other three are assigned a charge-separated (zwitterionic) structure, rather than a carbene form, on the basis of comparative 13C NMR shifts.     

Detection of Trace Heavy Metal Ions Using Carbon Nanotube‐ Modified Electrodes

A sensitive voltammetric method for detection of trace heavy metal ions using chemically modified carbon nanotubes (CNTs) electrode surfaces is described. The CNTs were covalently modified with cysteine prior to casting on electrode surfaces. Cysteine is an amino acid with high affinities towards some heavy metals. In this assay, heavy metals ions accumulated on the cysteine‐modified CNT electrode surfaces prior to being subjected to differential pulse anodic stripping voltammetry analysis. The resulting peak currents were linearly related to the concentrations of the metal ions. The method was optimized with respect to accumulation time, reduction time and reduction potential. The detection limits were found to be 1 ppb and 15 ppb for Pb²⁺ and Cu²⁺ respectively. The technique was used for the detection of Pb²⁺ and Cu²⁺ in spiked lake water. The average recoveries of Pb²⁺ and Cu²⁺ were 96.2% and 94.5% with relative standard deviations of 8.43% and 7.53% respectively. The potential for simultaneous detection of heavy metal ions by the modified CNTs was also demonstrated.     

trans‐Dioxocyclam (1,4,8,11‐tetraazacyclotetradecane‐2,9‐dione) dihydrate and its NiII complex

The crystal structures are reported of trans‐dioxocyclam dihydrate, C₁₀H₂₀N₄O₂·2H₂O, a structural isomer of the well known cis‐dioxocyclam, and of its novel Ni complex, (1,4,8,11‐tetra­aza­cyclo­tetra­decane‐2,9‐dionato‐κ⁴N)­nickel(II) dihydrate, [Ni(C₁₀H₁₈N₄O₂)]·2H₂O, the first example of a trans­ition metal complex of this ligand. Both mol­ecules lie on crystallographic centres of inversion. The free ligand has two of its N atoms turned outwards from the ring and hydrogen bonded to water mol­ecules. A major conformational change takes place in the complex in which the ligand binds in a trans tetradentate fashion, as suggested by the electronic spectrum. The nickel(II) ion is low spin, although the electronic spectrum of the complex in water indicates an equilibrium mixture of low‐spin and high‐spin species. The irreversible electrochemical oxidation of [NiL¹] (L¹ is deprotonated trans‐dioxocyclam, C₁₀H₁₈N₄O₂) in water occurs at a potential of 0.964 V [versus SHE (standard hydrogen electrode)], which is very similar to that for the Ni–cis‐dioxocyclam complex.     

Spanning paths in infinite planar graphs

Let G be a 4-connected infinite planar graph such that the deletion of any finite set of vertices of G results in at most one infinite component. We prove a conjecture of Nash-Williams that G has a 1-way infinite spanning path. © 1996 John Wiley & Sons, Inc.     

Mipsagargin: The Beginning—Not the End—of Thapsigargin Prodrug-Based Cancer Therapeutics

Søren Brøgger Christensen isolated and characterized the cell-penetrant sesquiterpene lactone Thapsigargin (TG) from the fruit Thapsia garganica. In the late 1980s/early 1990s, TG was supplied to multiple independent and collaborative groups. Using this TG, studies documented with a large variety of mammalian cell types that TG rapidly (i.e., within seconds to a minute) penetrates cells, resulting in an essentially irreversible binding and inhibiting (IC₅₀~10 nM) of SERCA 2b calcium uptake pumps. If exposure to 50–100 nM TG is sustained for >24–48 h, prostate cancer cells undergo apoptotic death. TG-induced death requires changes in the cytoplasmic Ca²⁺, initiating a calmodulin/calcineurin/calpain-dependent signaling cascade that involves BAD-dependent opening of the mitochondrial permeability transition pore (MPTP); this releases cytochrome C into the cytoplasm, activating caspases and nucleases. Chemically unmodified TG has no therapeutic index and is poorly water soluble. A TG analog, in which the 8-acyl groups is replaced with the 12-aminododecanoyl group, afforded 12-ADT, retaining an EC₅₀ for killing of <100 nM. Conjugation of 12-ADT to a series of 5–8 amino acid peptides was engineered so that they are efficiently hydrolyzed by only one of a series of proteases [e.g., KLK3 (also known as Prostate Specific Antigen); KLK2 (also known as hK2); Fibroblast Activation Protein Protease (FAP); or Folh1 (also known as Prostate Specific Membrane Antigen)]. The obtained conjugates have increased water solubility for systemic delivery in the blood and prevent cell penetrance and, thus, killing until the TG-prodrug is hydrolyzed by the targeting protease in the vicinity of the cancer cells. We summarize the preclinical validation of each of these TG-prodrugs with special attention to the PSMA TG-prodrug, Mipsagargin, which is in phase II clinical testing.