Influence of the solvent and metal center on supramolecular chirality induction with bisporphyrin tweezer receptors. Strong metal modulation of effective molarity values

We describe the synthesis of a bisporphyrin tweezer receptor 1·H(4) and its metalation with Zn(II) and Rh(III) cations. We report the thermodynamic characterization of the supramolecular chirality induction process that takes place when the metalated bisporphyrin receptors coordinate to enantiopure 1,2-diaminocyclohexane in two different solvents, toluene and dichloromethane. We also performed a thorough study of several simpler systems that were used as models for the thermodynamic characterization of the more complex bisporphyrin systems. The initial complexation of the chiral diamine with the bisporphyrins produces a 1:1 sandwich complex that opens up to yield a simple 1:2 complex in the presence of excess diamine. The CD spectra associated with the 1:1 and 1:2 complexes of both metalloporphyrins, 1·Zn(2) and 1·Rh(2), display bisignate Cotton effects when the chirogenesis process is studied in toluene solutions. On the contrary, in dichloromethane solutions, only 1·Zn(2) yields CD-active 1:1 and 1:2 complexes, while the 1:2 complex of 1·Rh(2) is CD-silent. In both solvents, porphyrin 1·Zn(2) features a stoichiometrically controlled chirality inversion process, which is the sign of the Cotton effect of the 1:1 complex is opposite to that of the 1:2 complex. In contrast, porphyrin 1·Rh(2) affords 1:1 and 1:2 complexes in toluene solutions with the same sign for their CD couplets. Interestingly, in both solvents, the signs of the CD couplets associated with the 1:1 sandwich complexes of 1·Zn(2) and 1·Rh(2) are opposite. The amplitudes of the CD couplets are higher for 1·Zn(2) than for 1·Rh(2). This observation is in agreement with 1·Rh(2) having a smaller extinction coefficient than 1·Zn(2). We performed DFT-based calculations and assigned molecular structures to the 1:1 and 1:2 complexes that explain the observed signs for their CD couplets. Unexpectedly, the quantification of the thermodynamic stability of the two metallobisporphyrin/diamine 1:1 sandwich complexes revealed the existence of interplay between effective molarity values (EM) and the strength of the intermolecular interaction (K(m); N···Zn or N···Rh) used in their assembly. The EM for the N···Rh(III) intramolecular interaction is 3 orders of magnitude smaller than that for the N···Zn(II) interaction, both of which are embedded in the same scaffold of the 1·M(2) bisporphyrin receptor.     

Lab-on-a-bubble: synthesis, characterization, and evaluation of buoyant gold nanoparticle-coated silica spheres

This paper describes the development and preparation of a new class of materials for surface-enhanced Raman scattering (SERS) consisting of gold nanoparticles coated onto hollow, buoyant silica microspheres. These materials allow for a new type of molecular assay designated as a lab-on-a-bubble (LoB). LoB materials serve as a convenient platform for the detection of analytes in solution and offer several advantages over traditional colloidal gold and planar SERS substrates, such as the ability to localize and concentrate analytes for detection. An example assay is presented using the LoB method and cyanide detection. Cyanide binds to SERS-active, gold-coated LoBs and is detected directly from the corresponding SERS signal. The abilities of LoBs and a gold colloid to detect cyanide are compared, and in both cases, a detection limit of ~170 ppt was determined. Differences in measurement error using LoBs versus gold colloid are also described, as well as an assay for 5,5'-dithiobis(2-nitrobenzoic acid) that shows the benefit of using LoBs over SERS analyses in colloids, which are often plagued by particle aggregation.     

Increased glucose concentration in the hippocampus in early Alzheimer's disease following oral glucose ingestion

Glucose is the primary source of energy for brain cells. Because energy storage in the brain is limited, an uninterrupted supply of glucose and its rapid metabolism are essential for normal cognitive function. This study utilized an oral glucose load to examine hippocampal glucose metabolism in early Alzheimer's disease (AD) - a disease characterized by progressive deterioration of cognitive function and glucose hypometabolism. Short echo time 1H MR spectra (20 ms) from the right hippocampus of 8 patients with probable AD, 14 healthy elderly and 14 healthy young adults were compared pre- and post-glucose loading. In contrast to the healthy adults, the AD patients exhibited significantly elevated hippocampal glucose concentrations post-glucose ingestion relative to baseline (P < .01). These results suggest that cerebral glucose hypometabolism in AD leads to an increased steady-state concentration of cerebral glucose. This research demonstrates the feasibility of studying cerebral glucose metabolism in AD with 1H MR spectroscopy.     

High-performance liquid chromatographic assay of indomethacin in porcine plasma with applicability to human levels

A high-performance liquid chromatography (HPLC) assay is described for the determination of indomethacin in porcine plasma using acetonitrile to precipitate plasma proteins and for the one-step extraction. Calibration curves (using the internal standard method) are linear (r2 > 0.98) over the concentration range of 50.0 to 3000 ng/mL in both mobile phase and plasma. Precision, expressed as the inter- and intraday coefficient of variation (n = 5), is < 7% on the same day and < 5% between days at each plasma control sample of 300, 1000, and 3000 ng/mL, respectively. System precision, calculated as the coefficient of variation (n = 5), is < 7% at 3000 ng/mL of indomethacin, and the limit of quantitation in plasma is 50 ng/mL. The absolute recovery for both indomethacin and the internal standard (mefenamic acid) from plasma is over 97% (n = 3), and the concentrations do not deviate more than -2.9% to 2.4% from their actual values. The specificity of the method is confirmed. This technique is thus reported to be both rapid and specific. The real advantage is the small sample volume required (500 microL), which allows it to be considered for the quantitation of indomethacin in plasma from paediatric patients.     

On the determination of underivatised fatty alcohol ethoxylates by electrospray ionisation-mass spectrometry

The oligomers of fatty alcohol ethoxylates (FAEs) exhibit large sensitivity differences in mass spectrometry with electrospray ionisation (ESI-MS) and atmospheric pressure chemical ionization (APCI). Standards of the oligomers from m=1 to 7 ethylene oxide units (EOs) and linear alkyl chains from n=10 to 18 carbon atoms were infused to examine the relative sensitivities or response factors in several media. The response factors of the [M+H]+ and [M+Na]+ peaks in 9:1 acetonitrile/water and methanol/water media containing acid buffers increased following irregular patterns when n and m increased. In methanol/water the response factors depended on the parity of m, being larger than the average trend for the oligomers with an even value of m with respect to those having an odd value. This was attributed to the presence of an uncompensated C-O-C or C-O-H dipole in the former oligomers. The advantages of using ESI over APCI and of measuring the [M+H]+ peaks in an acid methanol/water medium containing 0.1 M HCl are discussed. The advantages and limitations of using models of the response factors to evaluate oligomer concentrations with a reduced set of selected standards are examined. The determination of underivatised FAEs using acid media was made compatible with previous HPLC separation by implementing either a triconcentric nebulizer fed with an acid liquid sheath, or a capillary T-union inserted between the column outlet and the biconcentric nebulizer, and fed with an acid stream provided by a syringe pump.     

A maximum-likelihood procedure for estimating psychometric functions: Thresholds, slopes, and lapses of attention

Green [J. Acoust. Soc. Am. 87, 2662-2674 (1990)] suggested an efficient, maximum-likelihood-based approach for adaptively estimating thresholds. Such procedures determine the signal strength on each trial by first identifying the most likely psychometric functions among the pre-proposed alternatives based on responses from previous trials, and then finding the signal strength at the "sweet point" on that most likely function. The sweet point is the point on the psychometric function that is associated with the minimum expected variance. Here, that procedure is extended to reduce poor estimates that result from lapses in attention. The sweet points for the threshold, slope, and lapse parameters of a transformed logistic psychometric function are derived. In addition, alternative stimulus placement algorithms are considered. The result is a relatively fast and robust estimation of a three-parameter psychometric function.     

Spectral processing of two concurrent harmonic complexes

In a concurrent profile analysis task, each of the two observation intervals was the sum of two harmonic complexes. In the first interval one of the harmonic complexes had a flat spectrum and the other had a broad spectral peak at 1 kHz. In the second interval, the association between the spectral profiles and the complexes was either consistent with the first interval, or inconsistent so that profile changes (flat versus peaked) could be created in both of the complexes. In two experiments, thresholds and psychometric functions for detecting the profile change were measured in terms of the spectral peak's magnitude as functions of three types of segregation cues: Difference in fundamental frequency, onset asynchrony, and difference in interaural time difference between the two complexes. Decreasing the magnitude of each cue led to higher thresholds, and shallower psychometric functions whose upper asymptotes often failed to reach 100% correct. The patterns of the threshold and psychometric functions varied across cue types and across individual listeners. The results suggest that informational masking is present in the concurrent profile analysis task. Segregation cues appear to contribute to the release from informational masking, but the process depends on listening strategies adopted by individual listeners.