Synthesis of the ladybug alkaloids (±)-propyleine and (±)-isopropyleine. Modification of the published structure of propyleine

The total syntheses of the ladybug alkaloids (±)-propyleine and (±)-isopropyleine are described. Evidence that the alkaloid propyleine is actually a rapidly interconverting mixture of propyleine and a previously unknown isomer isopropyleine is presented.     

High-yield solvothermal formation of magnetic CoPt alloy nanowires

One-dimensional (1D) magnetic nanomaterials have attracted much attention recently because of their applications in magnetic recording and spintronics. Nevertheless, it remains a challenge to prepare free-standing magnetic nanowires in high yield. This Communication reports the successful high-yield synthesis of an interesting 1D ferromagnetic CoPt alloy by direct decomposition of platinum acetylacetonate and cobalt carbonyl compound in ethylenediamine solvent through a solvothermal reaction. The CoPt alloy nanowires obtained have a tunable diameter of 10-50 nm and a length along the longitudinal axis of up to several microns, depending on crystallization temperature and reaction time. A unique formation mechanism involving coarsening and ripening under solvothermal conditions was discovered. This research opens new opportunities in synthesizing nanomaterials through low-temperature solvothermal processes.     

Channel flow cell studies on the evaluation of surface pretreatments using phosphoric acid or polymaleic acid for calcite stone protection

The dissolution kinetics of surface-pretreated and weathered calcite was investigated in dilute acid using a channel flow cell with microdisk detection. Two pretreatments were studied, polymaleic acid and phosphoric acid. Treatment with polymaleic acid was shown to significantly passivate calcite but to a lesser extent than the phosphoric acid and the former coating was found to be less effective for protection of calcite from acid attack. However, treatment of calcite with phosphoric acid resulted in the passivation of calcite from acid attack which strongly inhibited dissolution, an effect that was enhanced even further after exposure to the environment.     

Electrophotographic and microwave photodielectric studies on titanium dioxide pigments in the solid state

In this paper, we report some novel preliminary findings on the photoactivity of titanium dioxide pigments using photoconductive and microwave dielectric techniques. A variety of pigment types were investigated by both methods, including the two crystalline forms of titanium dioxide, anatase and rutile, and a variety of coated pigments. Analysis of the data obtained indicates that there are possible relationships between the photoconductive and photodielectric results, and that these may be used to characterize the pigment types rapidly. Photoconductive measurements were carried out on pigmented films of poly(N-vinylcarbazole) (PVK). Uncoated pigments were found to be more photoconductive than coated pigments with the anatase modification being the more active. It is believed that the pigments act as “trapping” sites to the holes produced by PVK, and that the more photoactive the pigment, the easier it is to regenerate the holes. Various factors influence the band gap of the pigment and these have a significant effect on the photoactivity and photoconductivity of the pigment samples. These include the presence of traps and recombination centres (present as coatings on the surface of the pigment particle) and impurities which can act as acceptors or donors.

Microwave dielectric measurements were carried out on the different anatase and rutile pigments, each exhibiting a different microwave resonant frequency loss depending on the nature of the crystalline modification and the coating. However, on illumination on the pigments with polychromatic light in the microwave cavity, the resonant frequency losses exhibit shifts, the nature of which depend on the pigment type and the coating. Thus the anatase pigments exhibit greater responses than the rutile pigments, particularly with regard to the shift in the resonant frequency values and the change in the Q factor of the resonant peak. The resonant frequency values of the anatase samples are also higher than those obtained for the rutile samples. Furthermore, the frequency shifts are in opposite directions, with the anatase modification exhibiting a more rapid shift to lower frequencies and rutile a slower shift to higher frequencies. It appears that, when the anatase samples are irradiated, their dielectric properties change from those characteristic of a conductor-like material to those of an insulator-like material. However, these changes are reversible once the illumination is terminated. With the rutile samples, irradiation increases the resonant frequency values and hence their dielectric constants. Thus the pigments appear to become more like conductors.     

A fluorescent molecular imaging probe with selectivity for soluble tau aggregated protein

Soluble forms of aggregated tau misfolded protein, generally termed oligomers, are considered to be the most toxic species of the different assembly states that are the pathological components of neurodegenerative disorders. Therefore, a critical biomedical need exists for imaging probes that can identify and quantify them. We have designed and synthesized a novel fluorescent probe, pTP-TFE for which binding and selectivity profiles towards aggregated tau and Aβ proteins were assessed. Our results have shown pTP-TFE to be selective for early forms of soluble tau aggregates, with high affinity of dissociation constants (K_d) = 66 nM, and tenfold selectivity over mature tau fibrils. Furthermore, we found that pTP-TFE is selective for tau over Aβ aggregates and had good cell permeability. This selectivity of pTP-TFE towards early forms of aggregated tau protein ex vivo was also supported with studies on human brain tissue containing tau and Aβ pathology. To the best of our knowledge, this is the first fluorescent molecule to be reported to have this form of selectivity profile, which suggests that pTP-TFE is a unique probe candidate for imaging-based detection of early stages of Alzheimer''s disease and other tauopathies.

pTP-TFE imaging probe can distinguish soluble tau aggregated proteins from other aggregated proteins enabling earlier detection of neurodegenerative diseases.     

Stereocontrolled synthesis of cis-dibenzoquinolizine chlorofumarates: curare-like agents of ultrashort duration

The quaternizations of dibenzoquinolizines 9 and 14 with 3-halo-1-propanols are highly cis-selective (94-100% cis), results consistent with the N-methylation of O-methylcapaurine (7b), but in contrast to the proposed trans-stereochemistry of dibenzo[a,h]quinolizine methiodide 10 and the analogous quaternizations of 1-benzyl- and 1-phenylisoquinoline congeners 5b and 5c. In this report, we describe stereoselective preparation of the unique cis-dibenzoquinolizinium propanols 15 and 16and their transformation into bis- and mixed-onium chlorofumarates 19, 20ab, and 26. Dibenzo[a,g]quinolizinium propanol 15 was prepared enantioselectively in three steps from dihydroisoquinoline 11. Asymmetric transfer hydrogenation of 11 in the presence of triethylamine/formic acid and Noyori's chiral ruthenium catalyst 12 produced R-(-)-5',8-dimethoxynorlaudanosine (13) in 98% yield and 87% ee. Pictet-Spengler cyclization of 13 in formalin/formic acid afforded the dibenzo[a,g]quinolizine 14 in 65% yield. Quaternization of 14 with 3-chloro-1-propanol under Finkelstein conditions generated cis-dibenzoquinolizinium propanol 15 in 85% yield with >94% cis-selectivity. The cis-dibenzo[a,h]quinolizinium propanol 16 was obtained as a single stereoisomer by reaction of the known tetramethoxyquinolizine 9 with neat 3-iodo-1-propanol. Bis-onium chlorofumarates 18 and 19 and the mixed-onium derivative 20ab were prepared by a pool synthesis procedure from (1R)-trans-6a, 16, and chlorofumaryl chloride (17). Mixed-onium alpha-chlorofumarate 26 was synthesized from (1S)-trans-6d, 15 and (+/-)-trans-2,3-dichlorosuccinic anhydride (22), employing a recently disclosed chlorofumarate mixed-diester synthesis. The title compounds (19, 20ab, and 26) displayed curare-like effects of ultrashort duration in rhesus monkeys.     

In situ electrochemical ESR and voltammetric studies on the anodic oxidation of para-haloanilines in acetonitrile

An in situ electrochemical electron spin resonance (ESR) study on the electro-oxidation of para-chloroaniline, para-bromoaniline, and para-iodoaniline dissolved in acetonitrile at gold electrodes is reported. ESR spectra obtained using a tubular flow cell reveal the presence of a paramagnetic dimer product derived from para-aminodiphenylamine, during oxidative electrolysis, suggesting the coupling of reactive electrogenerated radical cations with neutral parent haloaniline molecules. The ESR signal intensity behaves in a manner expected for a radical species reacting with second-order kinetics, suggesting the paramagnetic dimer is, itself, unstable. The theory describing the ESR signal intensity flow rate behavior for this reaction mechanism is developed for the tubular arrangement and used to extract mechanistic and kinetic data from the experimental results for the cases of para-chloroaniline and para-bromoaniline. Further mechanistic aspects, including proton and halide ion expulsion during dimerization, are explored voltammetrically and with the aid of digital simulations using Digisim. Comparison of the ESR signal and voltammetric measurements suggests that an additional mechanism operates which does not lead to paramagnetic products. Additionally, the in situ electrolysis of N,N-dimethyl-para-bromoaniline is reported to generate the stable radical cation of N,N,N',N'-tetramethylbenzidine, and a mechanism of electro-oxidation is, thus, proposed.     

Polynuclear manganese grids and clusters—A magnetic perspective

High nuclearity paramagnetic, spin-coupled transition metal clusters and grids are fascinating chemists and physicists partly because of their structural beauty, and the challenge of creating them, but also because of their novel physical properties. Magnetic interactions between the spin centers are a primary focus. This review will examine a selection of Mn(II) polynuclear grids and clusters, with nuclearities in the range Mn₄ to Mn₉. Theoretical treatments of the magnetic properties are discussed, and approaches to solving the exchange problem for ‘large’ spin systems related to computational difficulties. A freely available software package (MAGMUN4.1) is presented as a means of dealing simply with spin-coupled clusters in general, and symmetry reduction methods are discussed briefly as a means of dealing with ‘large’ spin systems.     

Simulations of time-dependent fluorescence in nano-confined solvents

The time-dependent fluorescence of a model diatomic molecule with a charge-transfer electronic transition in confined solvents has been simulated. The effect of confining the solvent is examined by comparing results for solutions contained within hydrophobic spherical cavities of varying size (radii of 10-20 angstroms). In previous work [J. Chem. Phys. 118, 6618 (2002)] it was found that the solute position in the cavity critically affects the absorption and fluorescence spectra and their dependence on cavity size. Here we examine the effect of cavity size on the time-dependent fluorescence, a common experimental probe of solvent dynamics. The present results confirm a prediction that motion of the solute in the cavity after excitation can be important in the time-dependent fluorescence. The effects of solvent density are also considered. The results are discussed in the context of interpreting time-dependent fluorescence measurements of confined solvent systems.     

Determination of low-level residual ethylene oxide by using solid-phase microextraction and gas chromatography

Current methods of analysis for ethylene oxide (EO) in medical devices include headspace and simulated-use extractions followed by gas chromatography with either a packed or a capillary column. The quantitation limits are about 0.5-1.0 microg/g for a packed column and about 0.1-0.2 microg/g for a capillary column. The current allowable levels of EO on medical devices sterilized with EO gas as outlined in International Organization for Standardization (ISO) 10993-7 may be significantly reduced from current levels by applying the ISO Draft International Standard 10993-17 method for establishing allowable limits. This may require EO test methods with detection and quantitation limits that are much lower than those of the currently available methods. This paper describes a new method that was developed for the determination of low-level EO by solid-phase microextraction using the direct-immersion method. Factors such as temperature and stirring were found to affect absorption efficiency and absorption time. A low extraction temperature (about 6 degrees C) was found to be more efficient than room-temperature extraction. Stirring was found to reduce absorption time by about 50%. Under these conditions, detection and quantitation limits of 0.002 and 0.009 microg/g, respectively, were obtained by using a capillary column. As a result, this method makes compliance with lower EO limits feasible.