Paper #3 comes from a collaboration of chemists at the IBM Almaden Research Center, the Scripps Research Institute, and the Lawrence Berkeley National Laboratory, all in California, and from the Institut für Polymerforschung, Dresden, Germany. Its lead author is the Nobel laureate Barry Sharpless, and it reports the construction of triazole dendrimers by "clicking" together azides and alkynes. The authors claim this to be the best click reaction to date. The reactants, along with a copper catalyst, are stirred at room temperature for a few hours, the solution is filtered, and the yields are almost 100%.

Unlike other dendrimers, these new dendrimers are built from the outside inwards. The branches are formed first and then attached to the central core. More branches can then be added to the outside. The products were characterized by NMR, GPC, and MALDI-TOF mass spectrometry, and they are unique in being highly polar and soluble in organic solvents and alcohol/water mixtures.

The other click paper (#4) comes from Todd Emrick and colleagues at the University of Massachusetts, Amherst. Emrick’s team has produced polyester polymers, hanging from which are pendant acetylene groups. These can then be "clicked" with azides under mild conditions to graft other groups onto the polyester chain leading to materials with biomedical potential. The polyester backbone is particularly suitable in therapeutics for its biocompatibility.

"In general the high yields, absence of by-products, and functional group tolerance of click chemistry makes it of interest to many people. Our paper demonstrates the relative ease of performing the cycloaddition reaction in the presence of other functional groups," Emrick tells Science Watch.

Emrick has been working on aliphatic polyesters since 2001, and in 2004 he reported shelf-stable aliphatic polyesters with pendant 1,2-diols (see B. Parrish, T. Emrick, Macromolecules, 37[16]: 5863-5, 2004). "Functionalizing polyesters is tricky business, due to the labile nature of the polyester backbone," warns Emrick, and says the methodology involving many synthetic steps will find fewer applications. "Our prior methods were cute, but the considerable synthesis involved limits it to drug delivery and other medical uses. The click approach is easier and better."

These medical applications could be in the way of polymer therapeutics in which drugs, such as the anti-cancer camptothecin, would be bonded to the polymer thereby improving their solubility and bio-availability. It is possible by adjusting reaction conditions to tailor the amount of drug on the polyester. For Emrick’s recent paper on camptothecin-functionalized aliphatic polyesters, see B. Parrish and T. Emrick, Bioconjugate Chemistry, 18(1): 263-7, 2007.

Finally in the current Hot Ten we come to paper #6, also from Barry Sharpless. This reports on the unique reactivity of organic compounds in aqueous suspensions. In the past it has often been assumed that an organic reaction had to be performed in an organic solvent, but #6 reveals that reactions involving water-insoluble reactants will nevertheless take place when stirred in an aqueous suspension. Not only do reactions occur, but they give higher yields in shorter times. The solubility of reactants is not the key factor it was once assumed to be. The reaction of the cyclic hydrocarbon quadricyclane with dimethyl azodicarboxylate in toluene solvent takes 24 hours at 80 Celsius to produce a yield of 74%, but "on water" it takes only 10 minutes at room temperature and the yield is 82%. ("On water" is the term which Sharpless has proposed for this type of reaction.)