Science Concentrates

Relief without side effect

The nonsteroidal compound shown—dubbed compound A—may lead to a new class of anti-inflammatory agents, a study suggests (Proc. Natl. Acad. Sci. USA, published online, dx.doi.org/10.1073/pnas.0505554102). It binds to the glucocorticoid receptor but does not elicit all the events that follow binding of glucocorticoid steroids. For example, glucocorticoid binding stops the production of inflammatory compounds. For this reason, glucocorticoids such as dexamethasone are effective anti-inflammatory agents. But the binding of most ligands triggers other events that lead to side effects-such as osteoporosis and metabolic disorders-in the treatment of inflammatory diseases. According to the study, by Guy Haegeman at Ghent University, in Belgium, and coworkers, compound A stops acute inflammation in an animal model but does not lead to hyperglycemia, an adverse side effect induced by dexamethasone. Identification of compounds such as compound A, which are called dissociated ligands because their binding of the glucocorticoid receptor triggers certain events selectively, is an important research goal for steroid pharmacology, the researchers write.

Observation of d-orbital aromaticity

Aromaticity is a fundamental concept in planar cyclic hydrocarbons that has been expanded to organometallic complexes and all-metal clusters. Aromaticity typically is restricted to and bonding, but computational evidence indicates that transition-metal clusters can have delocalized bonds involving d orbitals. Lai-Sheng Wang and his coworkers at Washington State University, Richland, and Pacific Northwest National Laboratory now report the first experimental evidence for d-orbital aromaticity (Angew. Chem. Int. Ed., published online Oct. 17, dx.doi.org/10.1002/anie.200502678). The team created M₃O₉ (M = Mo, W) clusters by laser vaporization of the metals in the presence of O₂, then separated the oxide species in a mass spectrometer and characterized them by using photoelectron spectroscopy. On the basis of their experimental and computational data, the researchers conclude that d orbitals of the three coplanar metal atoms form an unoccupied molecular orbital at the center of the neutral clusters that is occupied by one or two electrons in the M₃O₉^- or M₃O₉^2- anion, respectively. Large resonance energies, equal metal-metal bond distances, and other attributes confirm that the anions are aromatic, Wang and coworkers say.

Solar cells go inorganic

Researchers have introduced a new type of solar cell, once limited to the theoretical realm, that is composed entirely of inorganic nanocrystals. Though the efficiency of the inorganic cells, 2.9%, is less than the average of 15% of commercial solar cells, the development may lead to a class of energy-conversion devices that is less expensive and more stable than its traditional silicon-based brethren. UC Berkeley chemistry professor A. Paul Alivisatos' team spin-cast two films of rod-shaped inorganic nanocrystals-the first composed of CdTe and the second, CdSe-onto indium tin oxide glass coated with alumina (Science 2005, 310, 462). When the cell is exposed to sunlight, electronic charges transfer between the CdTe and CdSe layers. The inorganic devices may also outperform solar cells made from organic materials, absorbing a wider range of light frequencies.

Gilded bacteria sense moisture

Chemical engineers at the University of Nebraska, Lincoln, have designed and fabricated a humidity sensor made from living bacteria and gold nanoparticles (Angew. Chem. Int. Ed. 2005, 44, 6668). Vikas Berry and Ravi F. Saraf prepared the hybrid nanoelectronic device by depositing gram-positive bacteria on a silicon substrate with lines of gold electrodes. The bacteria form bridges spanning the electrodes. The two researchers coated the deposited bacteria with a monolayer of poly(L-lysine)-coated gold nanoparticles. They then applied a voltage across the electrode pairs and measured the current across the bacterial bridges. They showed that a humidity increase from 0% to 20% leads to a more than 40-fold decrease in the current. The decrease is induced by moisture, which causes the bacterial membrane to swell and increase the distance between the individual gold nanoparticles. Our sensor is the first example of a nanodevice that integrates physical nanomaterials with a live microorganism, Saraf says. However, once made, the living part is not critical for the device to function. He adds that the device is more sensitive than current humidity sensors for low-humidity environments.

Antibiotics and hearing loss

Gentamicin and other amino-glycoside antibiotics can damage auditory tissue and cause irreversible hearing loss in children whose mothers took the drug during pregnancy. Now, a team led by Federico Kalinec of the House Ear Institute, Los Angeles, has determined how gentamicin causes this damage (Proc. Natl. Acad. Sci. USA, published online, Oct. 20, dx.doi.org/10.1073/pnas.0508053102). Tests with pregnant guinea pigs and with auditory cells showed that the antibiotic increased production of a protein coded by the Harakiri gene. This increased expression could be responsible for killing sensory cells in the inner ear of the guinea pigs' offspring. The researchers believe that gentamicin (which includes the structures shown) increases protein production in part by suppressing a cellular pathway involving c-Jun N-terminal kinase (JNK). The researchers prevented ear cell death in mothers and newborns by giving pregnant guinea pigs L-carnitine. This compound apparently halted cell death by reversing gentamicin's inhibition of the JNK pathway. L-Carnitine, which had no effect on gentamicin's antibiotic properties, is safe for humans.