Science Concentrates DRUG DEVELOPMENT CHEMICAL BONDING
▸ Hydrogens set a short-distance record Two atoms are said to “touch” each other when they come closer together than the sum of their respective van der Waals radii. The van der Waals radius for hydrogen, for example, is 120 pm, meaning that the closest two nonbonded hydrogen atoms normally get is 240 pm. But intermolecular hydrocarbon H•••H contacts can be pushed to less than 160 pm, reports a team led by Peter R. Schreiner of Justus Liebig University (J. Am. Chem. Soc. 2017, DOI: 10.1021/ jacs.7b01879). The researchers studied crystals of tri(3,5-tert-butylphenyl)methane dimers at 20 K using neutron and X-ray dif-
H•••H
Tri(3,5-tert-butylphenyl)methane dimer fraction, measuring the distance between the central methane hydrogens as 156.7 pm. They also probed the crystal and gas-phase structures computationally. Their results suggest that, besides crystal packing, other forces must also contribute to the tight contact. Schreiner and coworkers point to the tert-butyl groups as the stabilizing influence: Because the tert-butyl groups are highly polarizable, their electron clouds can orient to induce temporary dipoles that allow for attractive London dispersion forces between the dimer’s molecules to hold them closely together.—JYLLIAN KEMSLEY
Plant-derived compounds block sperm tail whipping When sperm cells go swimming, their tails O normally wag symmetrically. But once sperm get near an egg, their tails start OCH3 whipping forcefully. This extra effort improves the cells’ chance of penetrating the egg’s viscous surroundings to start fertilH O ization. A rush of calcium ions through an ion channel called CatSper triggers this HO change in tail motion. A study describes how hormones in males and females can Pristimerin regulate the opening of CatSper, as well as reports two plant-derived compounds that inhibit activation of the ion channel H and could serve as novel contraceptives (Proc. Natl. Acad. Sci. USA 2017, DOI: 10.1073/pnas.1700367114). Nadja ManH nowetz, Melissa R. Miller, and Polina V. H Lishko of the University of California, HO Berkeley, found that both testosterone H and hydrocortisone—the pharmaceutical version of the hormone cortisol—inhibit Lupeol CatSper opening. Relatively high testosterone levels and chronic stress, which increases cortisol levels, are known to lower fertility in women. The team also tested two plant triterpenoids that have anecdotal evidence of impairing fertility: pristimerin, found in a vine used in traditional Chinese medicine, and lupeol, found in mangoes. Both reduced CatSper activation. All these molecules block CatSper activation by inhibiting an enzyme called ABHD2. This enzyme degrades a compound in sperm that turns off CatSper. The researchers next plan to test the contraceptive properties of pristimerin and lupeol in nonhuman primates.—MICHAEL TORRICE
diagnostics and drug delivery applications. The latest example is a “DNA slingshot” designed by researchers at the University of Montreal and the University of Rome Tor Vergata. Led by Rome’s Francesco Ricci, the researchers first created a DNA clamp from two synthetic DNA strands to encapsulate a third strand. The team conjugated antigenic peptides to the ends of
the clamp strands, meaning every clamp is equipped to recognize specific antibodies. When two peptides find their target, the clamp strands elongate to span the familiar Y-shaped arms of the antibody. When the DNA clamp loosens, the interior strand is released like a wet noodle from a slingshot (Nat. Commun. 2017, DOI: 10.1038/ ncomms15150). This DNA-based platform
NANOMATERIALS
Gene therapy and personalized medicine are probably the first things that come to mind when people think about DNA and health care. But a growing number of researchers are viewing DNA as a functional and flexible material to build nanomachines with potential in medical
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C&EN | CEN.ACS.ORG | MAY 22, 2017
Peptides anchored to a DNA clamp bind with an antibody, unfolding the assembly into a slingshot that releases a DNA “bullet.” Dots and lines represent different base pairing motifs present in the nanomachine.
CREDIT: NAT. COMMUN.
▸ ‘DNA slingshot’ targets drug delivery
is inexpensive and is readily adaptable to accommodate peptides to recognize biomarkers specific to certain diseases, Ricci says. Although the slingshot shoots DNA currently, the team is working to load it with other molecules, including cancer therapeutics.—MATT DAVENPORT
TISSUE ENGINEERING
▸ Artificial ovary restores fertility in mice Young women with cancer can face a loss of fertility as a result of their treatment. In response, researchers are trying to make artificial ovaries that could be implanted in women who are experiencing trouble getting pregnant. A team of researchers at Northwestern University led by Ramille N. Shah and Teresa K. Woodruff now reports that it has made a prosthetic ovary by 3-D printing a cross-linked gelatin scaffold and seeding it with isolated ovarian follicles, that house immature egg cells (Nat. Commun. 2017, DOI: 10.1038/ncomms15261). Because
SYNTHESIS
A small-scale reactor for light-driven chemistry Seeking a way to standardize light-driven chemistry, researchers at Princeton University, led by David W. C. MacMillan, teamed up with scientists and engineers at Merck & Co., led by Ian W. Davies, to create a small-scale reactor to use for photochemical transformations (ACS Cent. Sci. 2017, DOI: 10.1021/acscentsci.7b00159). When a new reaction fails or performs poorly, there can be some ambiguity as to why that is, Davies explains. “We wanted to remove that ambiguity so that when we set up reactions and report them, they are set up consistently and are reproducible,” Davies says. The resulting reactor turns out to speed up many known light-driven reactions and boosts yields to boot. The researchers attribute this ability to the reaction vessel’s increased and highly uniform exposure to photons in the reactor. The system works with vials ranging from 2 to 40 mL. This new benchtop reactor Different light sources can be swapped out, will enable researchers to so photochemistry can be done at different more consistently carry out wavelengths. Merck has made the reactor plans photochemical reactions. publicly available, so any company could commercialize it. One company, Penn Optical Coatings, is currently taking orders for the reactor and plans to begin shipping it in August at a cost of $4,900 per reactor.—BETHANY HALFORD
inconveniently revert back to the starting materials, which means researchers often end up reaching for bromides, chlorides, or fluorides instead. A team has now developed a new N-iodoamide radical precursor capable of direct C–H bond iodination that REAGENTS seems to have overcome the challenge of easily making iodoalkanes (J. Org. Chem. 2017, DOI: 10.1021/acs.joc.7b00557). The achievement was made possible by combining the experience in C–H activation chemistry of Peter R. Schreiner’s group at Justus Liebig University and the experience in developing reactive nitrogen-centered molecules of Mark Gandelman’s group at Technion—Israel Institute of Technology. Alkyl halides are go-to starting reagents for The researchers found via mechanistic and synthetic organic chemists. Researchers tend to value iodoalkanes the most because spectroscopic studies that light-activated iodo-3,5,5-trimethylhydantoin is the only they possess the weakest carbon-halogen compound so far that forms a nitrogen-cenbonds and are the most easily functionaltered radical capable of serving as a stable ized. Yet making alkyl iodides is thermodynamically unfavorable, and the reaction can iodine donor for direct C–H iodinations. They show that the N-iodoamide reagent O can be used to iodinate a range of linear and H3C N N I cyclic aliphatic C–H bonds. The reagent is also capable of iodinating benzylic C–H O bonds, including carrying out the “missing” I Iodoamide radical precursor iodine version of the popular Wohl-Ziegler White light reaction.—STEVE RITTER than mouse follicles, says Christiani A. Amorim, a researcher at Catholic University of Louvain who is also trying to make artificial ovaries.—CELIA ARNAUD
CREDIT: MERCK & CO. (PHOTOREACTOR); NAT. COMMUN. (FOLLICLE)
In this scanning electron micrograph, an ovarian follicle is wedged underneath three layers of 60° scaffold struts. the shape of the follicle is crucial for egg maturation and ovulation, the researchers constructed scaffolds with support layers at 30°, 60°, or 90° angles. They found that the follicles survive better in scaffolds with smaller angles and tighter pores because those scaffolds provide more contact points to stabilize the follicles. The researchers implanted the optimized follicle-seeded scaffolds in mice whose ovaries had been surgically removed. After implantation, the mice were able to mate and bear young naturally. The follicles functioned properly, producing the hormones needed for egg maturation, ovulation, and pregnancy. Whether similar artificial ovaries will work in humans remains to be seen because human follicles are more difficult to keep alive after isolation
▸ Nitrogen-based radical conquers challenging iodoalkane synthesis
MAY 22, 2017 | CEN.ACS.ORG | C&EN
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