Strategy for structural elucidation of drugs and drug metabolites using (MS)n fragmentation in an electrospray ion trap

Triple-stage quadrupole (TSQ) electrospray ionization (ESI) tandem mass spectrometry (MS/MS) and ion trap ESI-MS/MS can be used to cleave protonated molecules to produce carbocations and neutral molecules in the positive ion mode. Dissociation products which correspond to protonated forms of neutral fragment molecules can also be trapped and detected. These protonated molecules in turn can cleave via carbocation cleavage, ipso cleavage, onium cleavage or McLafferty or related rearrangements. One can elucidate the structures of metabolites from the differences in m/z ratios of the fragments arising from the original drug compound and its metabolite. This strategy for structural elucidation is further facilitated by estimates of the reactivity of drugs with oxygen diradicals involved in cytochrome P-450 cycles.     

Ratiometric direct detection of nitric oxide based on a novel signal-switching mechanism

A novel fluorescent probe, which could be the first example of a ratiometric molecular probe for direct monitoring of NO production, has been developed using a 'spin-exchange' mechanism.     

Photochemical study of [3(3)](1,3,5)cyclophane and emission spectral properties of [3n]cyclophanes (n = 2-6)

Thephotochemical reaction of [3(3)](1,3,5)cyclophane 2, which is a photoprecursor for the formation of propella[3(3)]prismane 18, was studied using a sterilizing lamp (254 nm). Upon photolysis in dry and wet CH2Cl2 or MeOH in the presence of 2 mol/L aqueous HCl solution, the cyclophane 2 afforded novel cage compounds comprised of new skeletons, tetracyclo[6.3.1.0.(2,7)0(4,11)]dodeca-5,9-diene 43, hexacyclo[6.4.0.0.(2,6)0.(4,11)0.(5,10)0(9,12)]dodecane 44, and pentacyclo[6.4.0.0.(2,6)0.(4,11)0(5,10)]dodecane 45. All of these products were confirmed by the X-ray structural analyses. A possible mechanism for the formation of these photoproducts via the hexaprismane derivative 18 is proposed. The photophysical properties in the excited state of the [3n]cyclophanes ([3n]CP, n = 2-6) were investigated by measuring the emission spectra and determining the quantum yields and lifetimes of the fluorescence. All [3n]CPs show excimeric fluorescence without a monomeric one. The lifetime of the excimer fluorescence becomes gradually longer with the increasing number of the trimethylene bridges. The [3n]CPs also shows excimeric phosphorescence spectra without vibrational structures for n = 2, 4, and 5, while phosphorescence is absent for n = 3 and 6. With an increase in symmetry of the benzene skeleton in the [3(3)]- and [3(6)]CPs, the probability of the radiation (phosphorescence) process from the lowest triplet state may drastically decrease.     

Development of a novel potentiometric titration method for determination of polypropylene degradation

In this study, a novel potentiometric titration of hydroperoxide in degraded polypropylene (PP) is proposed. This titration is quite sensitive compared with the conventional ones such as UV and manual titrations, and its detection limit was about 2 meq/kg. The sensitivity was equal to that of molecular weight measurement by GPC for the degraded PP and, in addition, the volatilization behavior of the hydroperoxide could be detected. This titration was found to be very effective for the determination of PP degradation.     

Photochemistry of 3-aryl-2-isoxazoline1

3-Phenyl-2-isoxazoline (1) was irradiated to give 4-phenyl-2-oxazoline (3), β-aminoaldehyde (14) and benzonitrile from its π-π^* singlet excited state. Several related derivatives afforded similar photoproducts on irradiation. The quantum yields of the photoreactions were dependent on the magnitudes of the singlet energies of the 2-isoxazolines. p-Cyanophenyl-2-isoxazoline (1c) formed a one-to-one photoadduct (22) with benzene.     

Profiling analysis of oligosaccharides in antibody pharmaceuticals by capillary electrophoresis

Carbohydrate chains in glycoprotein pharmaceuticals have important roles for the expression of their biological activities. Therefore, development of an assessment method for the carbohydrate chains is an important parameter for quality control of glycoprotein pharmaceuticals such as newly developed therapeutic antibodies. In this report, we applied capillary electrophoresis with laser-induced fluorescence detection to the analysis of carbohydrate chains after releasing with glycoamidase followed by derivatization with 3-aminobenzoic acid. We found that four major oligosaccharides present in antibody pharmaceuticals were successfully separated with good resolution. The present method showed good precision in both migration times and relative peak areas, and gave comparable accuracy with that using a derivatization method with 8-aminopyrene-1,3,6-trisulfonate.     

Stopped-flow spectrophotometric determination of nM level of Pb(II) using 5,10,15,20-terakis(1-methylpyridinium-4-yl)porphine

A spectrophotometric determination method for nM levels of Pb(II) has been developed using a stopped-flow spectrophotometer with cationic water-soluble porphyrin. The stopped-flow spectrophotometer allows the monitoring of the incorporation reaction of the Pb(II) ion into 5,10,15,20-terakis(1-methylpyridinium-4-yl)porphine (TMPYP) within a narrow time window (2.5 s) at pH 10.5–12.0 before the Pb-TMPYP complex is replaced with other foreign metal ions, since usually the Pb-TMPYP complex is very labile and readily replaced with other metal ions. This improved the selectivity of Pb(II) determination as compared to the conventional spectrophotometric determination of Pb(II) using water-soluble porphyrins.     

Generation of alkoxycarbenium ion pools from thioacetals and applications to glycosylation chemistry

[reaction: see text] Alkoxycarbenium ions have been generated and accumulated as "cation pools" by the low-temperature electrochemical oxidation of alpha-phenylthioethers. Although an unsuccessful attempt to accumulate glycosyl cations was made, a one-pot method for electrochemical glycosylation, which involves anodic oxidation of thioglycosides to generate glycosyl cation equivalents followed by their reactions with glycosyl acceptors, has been developed.     

Improvement of chemical analysis of antibiotics. IX. A simple method for residual tetracyclines analysis in honey using a tandem cartridge clean-up system

A simple, rapid and precise analytical method for the residual tetracyclines in honey has been established using a tandem cartridge clean-up system (prepacked reversed-phase and ion-exchange cartridges) followed by high-performance liquid chromatography. The recoveries of oxytetracycline (OTC), tetracycline (TC), chlortetracycline (CTC) and doxycycline (DC) from honey spiked at a level of 1.0 ppm are 87.1, 85.3, 98.0 and 99.0%, respectively, with coefficients of variation of 1.1-3.9%. The detection limits in honey are 0.02 ppm for OTC and TC, and 0.05 ppm for CTC and DC, respectively. The time required for the analysis of four samples is only 1 h.     

Synthesis of the common left-half part of pectenotoxins

The common left-half [C31-C33(OC1-C7)-C40] part of pectenotoxins has been synthesized convergently from the C31-C35, C36-C40, and C1-C7 parts. The C31-C35 part, prepared via a new route shorter than our previous route, was coupled with the C36-C40 part through reductive lithiation and addition reactions to give an adduct stereoselectively, which was converted to a cyclic acetal corresponding to the C31-C40 part. The left-half was synthesized by a three-step process including esterification of the C31-C40 part with the C1-C7 part.