I want one... from chemistry notes

A few days ago jungfreudlich posted pictures of his Element Collection. Very cool, don't you think? You can buy them online here, but probably not on a graduate student's salary :o)

Janus Disks from chemistry notes

What exactly is a Janus disk? Well, with a quick internet search you can easily find several references to Janus, the Roman god of doorways, gates, and beginnings (hence the word January for the first month of the year), but a picture search is actually most revealing. Usually Janus is shown with two different faces that look in opposite directions; one represents the sun and the other symbolizes the moon. Interesting--but what does this have to do with chemistry??

Well after that brief review of Roman mythology, one can easily imagine that a Janus particle is composed of two fused hemispheres of different materials--similar to the bust of Janus pictured above. Depending on their actual shape, Janus particles are placed into three categories: spheres, disks and cylinders. Several potential applications of these two-sided particles have been envisioned. For instance, in solar cells two very different types of molecules (donors and acceptors) must work together and convert light into electron movement; thus, using Janus particles within light harvesting devices might increase solar cell efficiencies. One could also imagine a Janus-scaffold as a drug delivery system; half of the disk might target cancer cells, while the other end would deliver a cytotoxic drug.

Synthesis of Janus structures is a daunting task and only a few examples of non-spherical Janus particles exist in the literature; thus, when I came across this article in JACS today, it caught my attention. Researchers at the University of Bayreuth in Germany have recently succeeded in producing Janus disks utilizing a template-assisted synthesis. Polymers made of polystyrene-block-polybutadiene-block-poly(tert-butyl methacrylate) were self-assembled and then treated with either AIBN or S2Cl2 to crosslink the inner polybutadiene layer; this step preserves the orientation of the polystyrene and poly(tert-butyl methacrylate). Finally, after sonication the Janus disks are obtained in their final form; size of the disks is tunable and ranges from the micro- to nanometer scale. As Janus structures have also been proposed to have potential as surfactants, the effect of these Janus disks on the interfacial tension of liquid-liquid interfaces was studied as well. Compared to their un-crosslinked starting materials, the Janus disks have a remarkable ability to decrease interfacial tension, and therefore future technological applications might include the stabilization of emulsions or encapsulation of molecules.

Picture taken from http://dx.doi.org/10.1021/ja068153v

Aggravating Aggregation from chemistry notes

Anyone interested in the field of high-throughput screening shouldn't miss this article which appeared online in the ASAP section of J. Med. Chem last week. Generally medicinal chemists can avoid false positives in screens by utilizing the well known Lipinski's Rule of Five or other computational methods that identify potential problematic molecules. Unfortunately, compounds that form colloidal aggregates are particularly troublesome; through sequestration of an enzyme from its substrate, these molecules usually appear to be good inhibitors (with IC50 values as low as 1 micromolar) with rather steep dose response curves. As aggregate-based inhibition is abrogated through the use of moderate concentrations of non-ionic detergents such as Triton X-100 (0.01 to 0.1%), Feng and coworkers developed an assay to test 70,563 compounds for detergent-sensitive inhibition. This screen has really opened my eyes to the prevalence of aggregators among screening hits. Astonishingly, of 1274 beta-lactamase inhibitors identified, 1204 were detergent sensitive, indicating an aggregation based mechanism of inhibition for 1.7% of the library! Anyone that has sorted through thousands or hundreds of initial hits will see the advantage of being able to identify or eliminate these artifacts from screens.

Discovering that a molecule is an aggregator is not a death sentence for its future use; as aggregation is concentration and condition dependent, molecules known to aggregate in one screen might not in a different setting. Additionally, several known drugs are aggregators at concentrations below 100 micromolar, including clotrimazole, nicardipine, delavirdine, and benzyl benzoate as pointed out by this 2003 article in J. Med. Chem.