Pyrimidine N-oxides. Preparation of 6-chloro-2,4-diaminopyrimidine 3-N-oxide and its reactions

The peroxyacid oxidation of 6-chloro-2,4-diaminopyrimidine ( 1 ) led to two products, 6-chloro-2,4-diaminopyrimidine 3-N-oxide ( 2 ) and 2,4-diamino-5,6-dichloropyrimidine 3-N-oxide ( 3 ). The assignment of structure of both of these compounds was made on the basis of ir, uv, nmr, and mass spectral data. A discussion of the pathways involved in the formation of 3 is presented.     

A mass spectrometry screening method for antiaggregatory activity of proteins covalently modified by combinatorial library members: application to sickle hemoglobin

A homogeneous assay, based on electrospray mass spectrometry, is described for identifying compounds in a combinatorial library that covalently modify a protein and thereby enhance its solubility. The technique is based on measuring the distribution of modified proteins in the supernatant versus aggregate. Compounds having the greatest anti-aggregatory activity are those with the highest supernatant/aggregate ratio. Mass is used as a marker to identify which covalent modifier in the library is involved. An exploratory study is presented which demonstrates that the antisickling activity of a family of isothiocyanates, as measured by the standard C(sat) assay, correlates well (r(2) = 0.98) with the mass spectrometry analysis of the supernatant/aggregate distribution. The technique has potential for screening libraries capable of covalently modifying other proteins of clinical interest, e.g., Alzheimer's, Huntington's, and various prion related diseases.     

Some Isoperimetric Inequalities in Electrochemistry and Hele Shaw Flows

Isoperimetric inequalities are applied to a moving-boundaryproblem for doubly-connected domains. This problem occurs forexample in electrochemistry, in which case the domains in questionare the electrolyte of an electrolytic cell. The two electrodessurrounding the electrolyte are assumed to grow or dissolve,at different rates in general, by electrochemical reaction.We obtain optimal estimates showing, for example, that the leastchange in volume of each electrode always occurs in sphericalsymmetry.     

Carbon nanotube-modified microelectrodes for simultaneous detection of dopamine and serotonin in vivo

Dopamine and serotonin are important neurotransmitters that interact in the brain. While dopamine is easily detected with electrochemical sensors, the detection of serotonin is more difficult because reactive species formed after oxidation can adsorb to the electrode, reducing sensitivity. Carbon nanotube treatments of electrodes have been used to increase the sensitivity, promote electron transfer, and reduce fouling. Most methods have focused on nanotube coatings of large electrodes and slower electrochemical techniques that are not conducive to measurements in vivo. In this study, we investigated carbon-fiber microelectrodes modified with single-walled carbon nanotubes for the co-detection of dopamine and serotonin in vivo. Using fast-scan cyclic voltammetry, S/N ratios for the neurotransmitters increased after nanotube coating. Electrocatalytic effects of nanotubes were not apparent at fast scan rates but faster kinetics were observed with slower scanning. Nanotube-modified microelectrodes showed significantly less fouling after exposure to serotonin than bare electrodes. The nanotube-modified electrodes were used to monitor stimulated dopamine and serotonin changes simultaneously in the striatum of anesthetized rat after administration of a serotonin synthetic precursor. These studies show that nanotube-coated microelectrodes can be used with fast scanning techniques and are advantageous for in vivo measurements of neurotransmitters because of their greater sensitivity and resistance to fouling.