A sulfido-bridged iron(II) compound that resembles a fragment of the active site of the nitrogen-fixing enzyme nitrogenase is capable of cleaving certain N–N bonds [J. Am. Chem. Soc., 126, 4522 (2004)]. In nitrogen-fixing bacteria, the complex iron-molybdenum cofactor of nitrogenase binds and reduces N2. Much effort has been made to design and synthesize small complexes that can catalyze the same reaction. As a step in that direction, a team led by graduate student Javier Vela and assistant professor of chemistry Patrick L. Holland of the University of Rochester now reports the synthesis and isolation of a complex containing a diketiminate-supported Fe–S–Fe core (shown; yellow = sulfur, orange = iron, blue = nitrogen, gray = carbon). The complex's core mimics postulated reactive forms of nitrogenase's iron-molybdenum cofactor. Although it can't bind N2, the complex can reductively cleave the N–N bond of phenylhydrazine. Hydrazine-bound species have been implicated in nitrogenase's catalytic cycle. Holland hopes that study of this and related compounds will lead to a better understanding of bond reduction by pairs of iron atoms.
In Alzheimer's disease, β-amyloid damages mitochondria in neural cells, but the mechanism has been unclear. Now, an international team led by researchers at Cornell University and Columbia University proposes that the enzyme -amyloid-binding alcohol dehydrogenase (ABAD) provides the means by which β-amyloid harms neurons [Science, 304, 448 (2004)]. Hao Wu and colleagues say that β-amyloid forms a complex with ABAD in the mitochondria of nerve cells, distorting the enzyme so it can no longer bind nicotinamide adenine dinucleotide, the cofactor it needs for activity. They hypothesize that the ABAD-β-amyloid interaction "promotes leakage of reactive oxygen species, mitochondrial dysfunction, and cell death." And they suggest that "inhibition of ABAD--amyloid interaction may provide a new treatment strategy against Alzheimer's disease."
Using nanoshell-assisted photothermal therapy, scientists from Rice University and Nanospectra Biosciences selectively and noninvasively destroyed tumors in mice [Cancer Lett., published online April 1, http://dx.doi.org/10.1016/j.canlet.2004.02.004]. Bioengineering professor Jennifer L. West and coworkers injected a dilute solution of nanoshells into mice with tumors. The nanoshells, made of a dielectric silica core surrounded by an ultrathin layer of gold and covered with polyethylene glycol, absorb strongly in the near-infrared. Following injection, the particles circulated and accumulated in the tumors over a six-hour period. The researchers then illuminated the tumors with near-IR laser light, causing the nanoshells to heat up and destroy the tumors. Mice that underwent the treatment showed tumor resorption within 10 days, and all but one lived healthy and tumor-free for more than 90 days. The tumors in the control mice and mice that were exposed to near-IR light but not treated with the nanoshells continued to grow, reaching a diameter of 10 mm in less than two weeks.
A protein chip can be used to optimize metabolic pathways for in vitro metabolic engineering, according to a new report. Chemical engineering professor Gregory Stephanopoulos and postdoctoral associate Gyoo Yeol Jung at Massachusetts Institute of Technology create protein arrays of fusion molecules made of messenger RNA covalently linked to the enzyme it encodes. The fusion molecules are generated in vitro from the corresponding DNA template, so the enzymes don't need to be commercially available. The mRNA end binds to a DNA capture probe on the array surface, and the relative amounts of the enzymes can be adjusted by changing the amount of the capture probe. To demonstrate their approach, the researchers optimized the pathway for the synthesis of trehalose from glucose [Science, 304, 428 (2004)]. They determine the effect of the five enzymes in the pathway by holding the amounts of all but one of the enzymes constant and measuring the rate of trehalose synthesis. They find that the optimum synthesis occurs when three of the enzymes are maintained at maximum activity and the two enzymes at the pathway's branch point are maintained at a 3-to-2 ratio.<br >
Luminescent blue quantum dots have proven to be an elusive target for those hoping to complete the red-green-blue palette of quantum-dot-based light-emitting devices (QD-LEDs) such as flat-panel displays. Previously reported blue quantum dots weren't practical for applications such as blue QD-LEDs and blue QD-biological fluorescence labeling because they were either too small, too unstable, not easily processed, or didn't emit at the desired wavelength—470 nm. Now, chemistry professor Moungi G. Bawendi and colleagues at Massachusetts Institute of Technology have grown (CdS)ZnS core-shell nanocrystals that fit all of the above criteria [Angew. Chem. Int. Ed., 43, 2154 (2004)]. The group makes the blue quantum dots by first growing the CdS core nanocrystals and then coating them with a ZnS shell. With emissions in the 460 to 480-nm range and relatively narrow size distributions, the material is ideal for display applications, according to Bawendi's group.