The first isolation of a stable metal complex containing a nitrogen-centered organic radical raises the tantalizing possibility that metal-associated aminyl radicals might play a role in biology. A variety of enzymes use transition metals to generate phenoxyl amino acid radicals capable of catalyzing oxidation reactions. But the corresponding metal-associated, nitrogen-centered amino acid radicals--for instance, those based on tryptophan or histidine--have not yet been shown to exist in enzymes. Now, a Swiss team led by Hansjörg Grützmacher of the Swiss Federal Institute of Technology, Zurich, has managed to isolate and characterize a transition-metal complex capable of supporting a stable nitrogen-centered radical (shown; rhodium(I) is red, nitrogen is blue, and carbon is black) [Science, 307, 235 (2005)]. Crystallographic data, electron paramagnetic resonance spectra, and density functional theory calculations show that the radical is centered on the aminyl nitrogen (above Rh in figure). The isolation of this mimic of a metal-associated, nitrogen-centered amino acid radical suggests that metalloenzymes might make use of aminyl radicals.
A new study combines the imaging capabilities of secondary ion mass spectrometry (SIMS) with sample preparation techniques used in matrix-assisted laser desorption ionization (MALDI) MS. The technique, known as matrix-enhanced (ME) SIMS, provides a larger mass range than normal SIMS imaging can analyze and better spatial resolution than MALDI imaging can achieve. Sander R. Piersma and coworkers at the Institute for Atomic & Molecular Physics and Free University Amsterdam employed the standard MALDI matrix 2,5-dihydroxybenzoic acid and SIMS with an indium ion gun to obtain images of cholesterol and a neuropeptide called APGWamide in tissue slices of a freshwater snail [Anal. Chem., 77, 735 (2005)]. ME-SIMS increases the mass range to which SIMS can be applied, allowing the higher spatial resolution of SIMS to be applied to peptides in tissue samples.
A novel methodology for preparing allyl amino acid derivatives could find widespread use in the synthesis of biologically significant compounds. Joe Sweeney at the University of Reading, in England, and coworkers have shown that acyclic allylic ammonium ylides derived from glycine can be rearranged to generate a variety of amino acid analogs in good yields and with high diastereo- and enantioselectivity. The team used the method to accomplish a new, rapid, and efficient synthesis of (R)-allyl glycine (shown) in 86% overall yield and more than 95% enantiomeric purity. [J. Am. Chem. Soc., published online Dec. 21, http://dx.doi.org/10.1021/ja043768i]. "The key reaction is a rearrangement process in which the ylide's C–N bond is broken and a new C–C bond is formed," Sweeney explains. "The allyl group is transferred with high stereoselectivity from nitrogen to carbon under the influence of a chiral auxiliary," Sweeney says. "The methodology will enable the synthesis of a wide range of allyl glycine analogs, many of which show promise as enzyme inhibitors," he adds.
Huntington's disease is caused by a mutation in the gene that codes for huntingtin. Mutated huntingtin contains extra polyglutamine (polyQ), an alteration that causes the protein to misfold and aggregate into clumps. Researchers haven't yet settled whether the neurodegeneration that results from the disease is caused by these huntingtin aggregates, by the toxicity of smaller precursors, or by some other mechanism. Aleksey G. Kazantsev of Massachusetts General Hospital, in Charlestown, and colleagues have now identified a small molecule that inhibits polyQ-dependent aggregation [Proc. Natl. Acad. Sci. USA, 102, 892 (2005)]. The compound substantially reduces neurodegeneration in an insect model of Huntington's disease. The researchers believe that this evidence supports the aggregation hypothesis. This compound (below) and three others "represent four previously uncharacterized chemical scaffolds and are strong lead compounds for the development of therapeutics" for the disease, Kazantsev's team notes.
A research team has greatly extended the range of chemical elements whose concentrations can be made to oscillate in the laboratory. Concentration oscillations of a wide range of chemical species play an important role in biological systems. Early studies on chemical oscillations were restricted to just two oscillating reaction systems that had been discovered by chance. A group led by Irving R. Epstein of Brandeis University later developed a systematic design algorithm that expanded this number to dozens of reaction systems, but only a few elements were included--those having multiple stable oxidation states. Now, Epstein and coworkers at Eötvös University, Budapest, have developed a method that extends the range of chemical oscillations to elements having only a single stable oxidation state, such as aluminum, fluorine, and calcium [Nature, 433, 139 (2005)]. The extension "may lead to reactions that are useful for coupling to or probing living systems or that help us to understand new mechanisms by which periodic behavior may arise," they write.