Iodide‐Induced Shuttling of a Halogen‐ and Hydrogen‐Bonding Two‐Station Rotaxane

The first example of utilizing halogen‐bonding anion recognition to facilitate molecular motion in an interlocked structure is described. A halogen‐bonding and hydrogen‐bonding bistable rotaxane is prepared and demonstrated to undergo shuttling of the macrocycle component from the hydrogen‐bonding station to the halogen‐bonding station upon iodide recognition. In contrast, chloride‐anion binding reinforces the macrocycle to reside at the hydrogen‐bonding station.     

A sialylation study of mouse brain gangliosides by MALDI a-TOF and o-TOF mass spectrometry

Matrix-assisted laser desorption/ionization (MALDI) process of sialoglycoconjugates is generally accompanied by different levels of cleavage of sialic acid residues and/or by dehydration, and decarboxylation reactions. Quantitative densitometry of the mouse brain ganglioside (MBG) components separated by high-performance thin layer chromatography (HPTLC) and evidenced by orcinol staining was a basis to verify the ganglioside composition pattern with respect to the relative abundances of individual components in the mixture. A systematic mass spectrometry (MS) sialylation analysis has been carried out to evaluate the feasibility of an axial time-of-flight (a-TOF) MS, equipped with a vacuum MALDI source and an orthogonal-TOF (o-TOF) instrument with an ion source operated at about 1 mbar of N(2). Besides, the esterification by one methyl group of the carboxyl group in sialic acid to increase the stability of the ganglioside species for MALDI MS analysis has been tested and the yield of intact ganglioside species and of the neutral loss of water and carbon dioxide estimated. For the sialylation analysis of native ganglioside mixtures the MALDI o-TOF analysis with 6-azo-2-thiothymine/diammonium citrate (ATT/DAC) as a matrix appears as an optimal approach for ganglioside profiling.     

Highly Active Halogen Bonding and Chalcogen Bonding Chloride Transporters with Non-Protonophoric Activity

Synthetic anion transporters show much promise as potential anti-cancer agents and therapeutics for diseases associated with mis-regulation of protein anion channels. In such applications high activity and anion selectivity are crucial to overcome competing proton or hydroxide transport which dissipates cellular pH gradients. Here, highly active bidentate halogen bonding and chalcogen bonding anion carriers based on electron deficient iodo- and telluromethyl−triazole derivatives are reported. Anion transport experiments in lipid bilayer vesicles reveal record nanomolar chloride transport activity for the bidentate halogen bonding anion carrier, and remarkably high chloride over proton/hydroxide selectivity for the chalcogen bonding anionophore. Computational studies provide further insight into the role of sigma-hole mediated anion recognition and desolvation at the membrane interface. Comparison with hydrogen bonding analogues demonstrates the importance of employing sigma-hole donor motifs in synthetic anionophores for achieving both high transport activity and selectivity.     

Theoretical prediction of linear free energy relationships using proton nucleomers

Values of σ and σ⁺, for use in linear free energy relationships, are determined for para hydrogen atoms having nuclear charges other than 1 (nucleomers). Hammett ρ values for a variety of free energies of activation, reaction, and other extrathermodynamic properties (e.g., vibrational frequencies) are computed therefrom and compared to those computed using typical para functional groups. The nucleomer correlations show excellent qualitative agreement with standard correlations but the quantitative agreement is less good, typically underestimating the standard ρ‐value by 10–60%. Copyright © 2007 John Wiley & Sons, Ltd.     

Synthesis of p-amino-N,N′-dihydroxybenzamidine using a TBDMS protecting group protocol

A synthetic route to p-amino-N,N′-dihydroxybenzamidine is established using a TBDMS protecting group strategy starting with p-nitrobenzhydroxamic acid chloride, which is transformed to O,O′-bis(tert-butyldimethylsilyl)-N,N′-dihydroxybenzamidine. Reduction with sodium dithionite occurs without degradation of the dihydroxyamidine functional group. Deprotection with ammonium fluoride is fast and efficient. This is important because no other possibility to synthesize this derivative has been found up to now. Furthermore, TBDMS protecting group strategy is proved to be adaptable to other substituted N,N′-dihydroxybenzamidines.     

Electrochemical Sensor for the Quantification of Dopamine Using Glassy Carbon Electrodes Modified with Single‐Wall Carbon Nanotubes Covalently Functionalized with Polylysine

We report a dopamine electrochemical sensor based on the modification of glassy carbon electrodes (GCE) with polylysine‐functionalized single‐wall carbon nanotubes (SWCNT‐PLys). The resulting electrodes (GCE/SWCNT‐PLys) showed a significant improvement in the electrooxidation of dopamine with drastic decrease in the peak potentials separation and important enhancement in the associated currents. Dopamine was detected by differential pulse voltammetry‐adsorptive stripping with medium exchange at nanomolar levels even in the presence of high excess of ascorbic and uric acids. The sensor was successfully used for the quantification of dopamine in urine samples enriched with the neurotransmitter.     

Synthesis, reactivity, electrochemical behavior, and crystal structure of a family of multivalent metal carbido-carbonyl clusters based on the rh(10)(c)(2)au(4-6) framework

Six metal carbido-carbonyl clusters have been isolated and recognized as members of a multivalent family based on the dioctahedral Rh(10)(C)(2) frame, with variable numbers of CO ligands, AuPPh(3) moieties, and anionic charge: [Rh(10)(C)(2)(CO)(x)(AuPPh(3))(y)](n-) (x = 18, 20; y = 4, 5, 6; n = 0, 1, 2). Anions [Rh(10)(C)(2)(CO)(18)(AuPPh(3))(4)](-) ([2](-)) and [Rh(10)(C)(2)(CO)(18)(AuPPh(3))(4)](2-) ([2](2-)) have been obtained by the reduction of [Rh(10)(C)(2)(CO)(18)(AuPPh(3))(4)] (2) under N(2), while [Rh(10)(C)(2)(CO)(18)(AuPPh(3))(5)](-) ([3](-)) was obtained from [Rh(10)(C)(2)(CO)(20)(AuPPh(3))(4)] (1) by reduction under a CO atmosphere. [3](-) can be better obtained by the addition of AuPPh(3)Cl to [2](2-). [Rh(10)(C)(2)(CO)(18)(AuPPh(3))(6)] (4) is obtained from [3](-) and 2 as well by the reduction and subsequent addition of AuPPh(3)Cl. The molecular structures of [2](2-) ([NBu(4)](+) salt), [3](-) ([NMe(4)](+) salt), and 4 have been determined by single-crystal X-ray diffraction. The redox activities of complexes 1, 2 and [3](-) have been investigated by electrochemical and electron paramagnetic resonance (EPR) techniques. The data from EPR spectroscopy have been accounted for by theoretical calculations.     

Simultaneous analysis of classical neuroleptics, atypical antipsychotics and their metabolites in human plasma

A high-performance liquid chromatographic method has been developed for the simultaneous determination of classical neuroleptics (chlorpromazine, haloperidol, loxapine and clotiapine), atypical antipsychotics (clozapine, quetiapine and risperidone) and their active metabolites (N-desmethylclozapine, clozapine N-oxide and 9-hydroxyrisperidone) in human plasma. Separation was obtained by using a C8 reversed-phase column and a mobile phase composed of 70% aqueous phosphate buffer containing triethylamine at pH 3.0 and 30% acetonitrile. The UV detector was set at 238 nm and amitriptyline was used as the internal standard. A careful pre-treatment procedure of plasma samples was developed, using solid-phase extraction with cyanopropyl cartridges, which gives high extraction yields (>or=93%). The limits of quantitation (LOQ) were always lower than 2.6 ng mL-1 and the limits of detection (LOD) were always lower than 0.9 ng mL-1 for all analytes. The method was applied with success to plasma samples from schizophrenic patients undergoing polypharmacy with two or more different antipsychotics. Precision data and accuracy results were satisfactory and no interference from other central nervous system (CNS) drugs was found. Hence the method is suitable for the therapeutic drug monitoring (TDM) of the analytes in psychotic patients' plasma.     

Metabolic profiling for the identification of Huntington biomarkers by on‐line solid‐phase extraction capillary electrophoresis mass spectrometry combined with advanced data analysis tools

In this work, an untargeted metabolomic approach based on sensitive analysis by on‐line solid‐phase extraction capillary electrophoresis mass spectrometry (SPE‐CE‐MS) in combination with multivariate data analysis is proposed as an efficient method for the identification of biomarkers of Huntington's disease (HD) progression in plasma. For this purpose, plasma samples from wild‐type (wt) and HD (R6/1) mice of different ages (8, 12, and 30 weeks), were analyzed by C₁₈‐SPE‐CE‐MS in order to obtain the characteristic electrophoretic profiles of low molecular mass compounds. Then, multivariate curve resolution alternating least squares (MCR‐ALS) was applied to the multiple full scan MS datasets. This strategy permitted the resolution of a large number of metabolites being characterized by their electrophoretic peaks and their corresponding mass spectra. A total number of 29 compounds were relevant to discriminate between wt and HD plasma samples, as well as to follow‐up the HD progression. The intracellular signaling was found to be the most affected metabolic pathway in HD mice after 12 weeks of birth, when mice already showed motor coordination deficiencies and cognitive decline. This fact agreed with the atrophy and dysfunction of specific neurons, loss of several types of receptors, and changed expression of neurotransmitters.