CATALYSIS
▸ Thioimidates for fast and selective polymerizations Researchers have found a new family of organocatalysts that promote rapid and highly selective ring-opening polymerizations of lactones and carbonates. Previous organocatalysts for ring-opening polymerization have been either fast or selective, but not both, according to Robert M. Waymouth and coworkers at Stanford University and IBM’s Almaden Research Center, who developed the new reaction (Nat. Chem. 2016, DOI: 10.1038/nchem.2574). The anionic thioimidate catalysts are generated by using an alkoxide to deprotonate a thiourea. Waymouth and coworkers note that the catalysts are bifunctional—they simultaneously activate the lactone or carbonate monomer and the growing polymer chain end. This mechanism accounts for the reaction’s high selectivity for chain formation, which M+ S– leads to well-deR1 R2 fined polymer N N H structures with Anionic thioimidate high melting catalyst points and narrow M+ is Na+, K+, or imidazolium molecular weight distributions. Waymouth says the team is using the catalysts to generate oligomers for biomedical applications, and he speculates that similar bifunctional anionic catalysts might prove useful for other types of reactions.—STU
BORMAN
BIOCATALYSIS
CREDIT: ADAPTED FROM NAT. MAT E R. (NANOMATERIALS)
▸ Engineered enzyme delivers branched tryptophans
ONCOLOGY
Hydrogel patch attacks tumors in multiple ways Cancer can be persistent and difficult to treat effectively, but cancer researchers can be just as persistent and difficult. João Conde and Natalie Artzi of Massachusetts Institute of Technology and coworkers have set an example in developing a nanoparticle-containing hydrogel patch that shows promising efficacy against colorectal cancer by attacking tumors in multiple ways (Nat. Mater. 2016, DOI: 10.1038/nmat4707). When implanted at tumor sites in mice, the patch delivers several treatments as the gel breaks down over time. Gold nanospheres in the patch carry two components: siRNAs that turn off KRas,
Gold nanosphere
Gold nanorod
Near infraredinduced heat
= Linker = Cancer cell-localizing peptide
= Anti-KRas siRNA with fluorecent group = Cytoplasmlocalizing peptide
= Avastin
= Fluorecent group
A hydrogel patch loaded with these nanomaterials could be a new model for battling cancer. which is an oncogene that makes cells cancerous, and a cytoplasm-localizing peptide that helps optimize siRNA activity. Gold nanorods in the patch carry the antibody drug Avastin, which blocks cancer cell growth. The nanorods also generate tumor-damaging heat when a phototherapy probe shines near-infrared light on them. Both the nanospheres and nanorods include a tumor-localizing peptide and a fluorescent group for imaging the nanoparticles. In the mice, the patch eradicated tumors completely. And when administered after surgical tumor removal, the patch prevented cancer recurrence. “Future studies will focus on utilizing colonoscopy equipment to deliver our therapeutic platform in a minimally invasive manner,” Artzi says.—STU BORMAN
Dressing up amino acids by adding new substituent groups to them can introduce β-methyltryptophan analogs in just one novel catalytic and medicinal properties. step (J. Am. Chem. Soc. 2016, DOI: 10.1021/ Adding a methyl group to tryptophan’s β jacs.6b04836). Andrew R. Buller, Frances carbon, however, H. Arnold, and has proven difcolleagues at OH ficult and ineffiCalifornia InstiO cient. A research tute of TechnolH2N NH team has now ogy discovered OH used directed that a subunit of Threonine O evolution to protryptophan synEngineered H2N N enzyme duce an enzyme thase can conH OH that catalyzes struct β-methylβ-Methyltryptophan tryptophan from Indole the synthesis of
indole and the amino acid threonine, but the activity was weak. So they randomly mutated the enzyme, looked for mutants with increased production of β-methyltryptophan, and then recombined genes coding for the most active variants. The researchers ended up with an enzyme that had eight mutations and was 1,000 times as active in making β-methyltryptophan as the natural tryptophan synthase. Incorporating substituted indoles led to a whole family of β-branched tryptophans.—
LOUISA DALTON, special to C&EN AUGUST 1, 2016 | CEN.ACS.ORG | C&EN
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