The mechanism of borohydride reductions. Reactions of gas phase borohydride ion with carbonyl groups by ion cyclotron resonance spectroscopy.

The reaction between BH₄^? and CH₂O has been investigated in the gas phase using ion cyclotron resonance spectroscopy. No hydride transfer from BH₄^? to the carbonyl group is observed, however a novel reaction between enolate ions and diborane has been observed.     

Formation of highly excited hydrogen atoms in a beam-foil interaction

The production of highly excited hydrogen atoms by passing a proton beam though a thin carbon foil has been investigated within the energy range 5–30 keV. The population of atoms in states with principal quantum number, n, between 14 and 25 have been determined using the field ionization technique and found to scale as n^?4.35±0.2.     

Negative-ion-negative-ion neutralization-reionization (−NR−)

There are four neutralization-reionization processes which can be studied. In the first two, gaseous cations are collisionally reduced and the resulting fast neutrals are either oxidized by collisional electron removal (NR) or reduced further by collisional electron attachment (NR^?). In the third and fourth processes, gaseous anions are collisionally oxidized and the resulting fast neutrals are either oxidized further by collisional electron removal (^?NR) or reduced by collisional electron attachment (^?NR^?). These four processes are illustrated briefly using the interrelated species [SF₅]⁺ and [SF₅]^?. Negative-ion-negative-ion neutralization-reionization (^?NR^?) processes are illustrated for [CH₃O]^?, [C₂H₅O]^?, [CO₃]^? and [HCO₃]^? and compared with ^?NR processes. In addition, collisional electron attachment ionization of fast neutrals formed in unimolecular fragmentation of cations is illustrated. The ^?NR^? studies of [CO₃]^? and [HCO₃]^? show that both CO₃ and HCO₃ are stable neutral species with lifetimes greater than 0.7 μs.     

High-throughput analysis of everolimus (RAD001) and cyclosporin A (CsA) in whole blood by liquid chromatography/mass spectrometry using a semi-automated 96-well solid-phase extraction system

A semi-automated solid-phase extraction (SPE) liquid chromatography/mass spectrometry (LC/MS) procedure was validated for the simultaneous determination of everolimus (RAD001) and cyclosporin A (CsA) in human blood. Whole blood samples (350microL) were pretreated with acetonitrile/zinc sulfate mixture to precipitate the sample proteins. The samples were centrifuged and the resulting supernatants were manually transferred to a 96-well plate format. All subsequent sample transfer and solid phase extraction was automated using a Tomtec Quadra 96 workstation. Samples were analyzed by LC/MS using an atmospheric pressure chemical ionization (APcI) interface. In order to enhance sensitivity, the MS method used negative ion mode for RAD001 ([M]-) and its internal standard and positive ion mode for CsA ([M + H]+) and its internal standard. The lower limit of quantitation was 0.375 ng.ml(-1) for RAD001 and 6.95 ng.ml(-1) for CsA. The reproducibility of the method was evaluated by analyzing six replicates at five or more quality control (QC) levels over the nominal concentration range 0.375 to 253 ng.ml(-1) for RAD001 and 6.95 to 1,530 ng.ml(-1) for CsA. The inter- and intra-day accuracy was found to range from 89.7 to 114% with precision (% CV) of less than 12% for both compounds. The sensitivity, small sample volume needed and high sample throughput of this method make it an attractive option for pharmacokinetic studies in pediatric patients.     

Effect of Dimethyl Sulfoxide and Dimethylformamide on the Stability of 4-Halo-8-quinolinols

Summary. Polyhalo-8-quinolinols with chlorine or bromine in position 4 were not stable in DMSO or DMF. The degradation product from 4,5-dichloro-8-quinolinol was 5-chloro-4,8-quinolindiol and the major product from 4,5-dibromo-8-quinolinol was 3,5-dibromo-4,8-quinolindiol. 4,5,7-Trichloro- and 4,5,7-tribromo-8-quinolinols yielded similar hydrolytic products, and for the bromo compound, a rebrominated product in DMSO. In DMF rebromination did not occur. In pyridine-d₅ these reactions did not take place, indicating a special ability of DMSO and DMF to cause such hydrolysis at position 4 of 4-halo-8-quinolinols.Received December 13, 2002; accepted January 7, 2003 Published online June 23, 2003     

Gymnangiamide, a cytotoxic pentapeptide from the marine hydroid Gymnangium regae

A cytotoxic aqueous extract from the marine hydroid Gymnangium regae provided a novel linear pentapeptide, designated gymnangiamide (1). The planar structure of 1 was elucidated by interpretation of spectral data as well as chemical degradation and derivatization studies. In addition to the amino acids isoleucine and phenylserine, this peptide contained N-desmethyldolaisoleuine, O-desmethyldolaproine, and alpha-guanidino serine, three residues that have not previously been reported in a natural product. The absolute configurations of the constituent amino/guanidino acids were determined by chemical degradation and derivatization, followed by HPLC and LC-MS comparison with authentic standards. Gymnangiamide (1) was moderately cytotoxic against a number of human tumor cell lines in vitro.