Spotlights Cite This: J. Am. Chem. Soc. XXXX, XXX, XXX−XXX
pubs.acs.org/JACS
Spotlights on Recent JACS Publications
Downloaded via UNIV OF LOUISIANA AT LAFAYETTE on October 7, 2018 at 11:32:23 (UTC). See https://pubs.acs.org/sharingguidelines for options on how to legitimately share published articles.
■
■
THE BEST OF BOTH WORLDS: IMPLICIT−EXPLICIT SOLVATION IN MODELING
CATION−π INTERACTION AIDS CATALYTIC DIARYLMETHANE SYNTHESIS Diarylmethanes are important building blocks for pharmaceuticals. One attractive route for their synthesis is through toluene derivatives, as these compounds are readily available as solvents and common reagents. Past researchers have functionalized toluenes with arylboronic acids using copper catalysts to trigger radical reactions at a benzylic C−H bond, but this approach, while elegant, can be difficult to optimize. Marisa C. Kozlowski, Patrick J. Walsh, and their colleagues have developed a new catalytic method to produce diarylmethanes via deprotonation of toluenes (DOI: 10.1021/ jacs.8b05143). The reaction uses a K(NIXANTPHOS)Pd catalyst and an additional potassium cation to activate various toluenes for benzylic C−H deprotonation and subsequent cross-coupling with an aryl bromide. The reaction tolerates a variety of bromides and toluenes, making it easier to optimize. Calculations of the energy of several possible transition states suggest that cation−π interactions between a potassium cation and the aromatic ring of the toluenes increase the acidity of the benzylic hydrogens, enabling deprotonation by potassium bis(trimethylsilyl)amide, a base too weak to deprotonate toluene. This acidification strategy could also be useful for other reactions, opening up new routes for synthesis. Melissae Fellet, Ph.D.
Scientists use computational models all the time to calculate the structures and activities of chemicals or biological molecules. But these models are just thatmodels, which need to be validated against experimental results. One of the most important variables is the solvent: get the solvent wrong, and simulated molecules will not match reality. Fahmi Himo and co-workers have simulated the behavior of a cavitand, a self-assembling cup-shaped molecule that can act as a container, and in the process probed the limits of some common solvent models (DOI: 10.1021/jacs.8b06984). In experimental work, a cavitand can house hydrophobic guests in either a 1:1 or 2:1 host:guest ratio. Initial density function theory calculations using a so-called “implicit solvent” model bore little relation to experimental reality. As a next step, the researchers instead use a mixed approach, adding in a significant number of “explicit” water molecules to the implicit solvent strategy. The result is in much better agreement with experiment, though the explicit−implicit modeling still does not correctly simulate an empty cavitand in water, suggesting that further iterations are needed. Erika Gebel Berg, Ph.D.
■
■
STUDY SHEDS LIGHT ON ANTICANCER PROPERTIES OF RARE SPONGE PEPTIDE
IRON-CLAD STRATEGY FOR NON-DIRECTED OXIDATION OF ALIPHATIC C−H BONDS Transforming the right C−H bond into a C−O moiety has profound effects on the physical properties a molecule, making methods for these reactions invaluable synthetic tools. However, organic compounds contain many C−H bonds, and oxidizing the right one without some directing strategy has proven difficult. In a new Perspective, M. Christina White and Jinpeng Zhao highlight the advances their group has made in developing non-directed methods for selectively hydroxylating aliphatic C−H bonds (DOI: 10.1021/jacs.8b05195). In the past, methods for the selective, non-directed oxidation of aliphatic C−H bonds were thought impossible outside of enzymes. This changed with the development of a new Fe catalyst, Fe(PDP), that enabled the first non-directed hydroxylation of aliphatic C−H bonds on a preparative scale. The expansion of this reactivity led to the development of a diverse range of Fe(PDP)-catalyzed oxidation reactions, revealing the site-selectivity rules of this system that allowed these reactions to be predictable, even in complex settings. The authors also highlight the new generations of this system that display complementary catalyst-controlled selectivity and address future challenges in this area of research. Elizabeth Meucci
A pair of structurally unique peptides, known as yaku’amides A and B, were first isolated from a rare deep-sea sponge and show strong activity against a broad range of human cancer cell lines. Whenever natural products show promising anticancer activity, researchers interested in further exploring the compounds’ pharmaceutical potential need access to large quantities of the drug for further testing. In cases such as the yaku’amides, where the source of the compounds is not abundant in nature, this can only be achieved by synthesizing the chemicals in a laboratory. Masayuki Inoue and co-workers had previously described the total synthesis of yaku’amides A and B, and now these researchers report insights into the cellular targets and mechanism of action of these peptides (DOI: 10.1021/ jacs.8b07339). The researchers perform structure−activity relationship studies on one of the peptides by creating 14 analogues with differing chiralities of amino acids and evaluating their biological activities. By conducting cell imaging studies and pull-down assays, the team determines that the compound accumulates in the mitochondria of cancer cells in vitro, inhibiting ATP production and subsequently slowing down cell growth. The study highlights the need for robust synthetic routes for preparing architecturally complex chemical probes isolated from scarce natural sources. Christine Herman, Ph.D. © XXXX American Chemical Society
A
DOI: 10.1021/jacs.8b10444 J. Am. Chem. Soc. XXXX, XXX, XXX−XXX
