Friday Fun: Super-Calcium!

Super-Calcium
Source: Niggemann Group, RWTH Aachen

I like to stroll through journals on quiet mornings, over coffee. After a few months, you start to see trends crop up: The Gold Rush. Carbon-carbon bond cleaving chemistries. Fluorine and boron everywhere.

A new trend almost snuck in under my radar: Calcium catalysis. In the past, a few groups had played around with amino-ene reactions, arylated tertiary alcohols, and made some enantioselective calcium pincer complexes. But I couldn't honestly tell you that I had branded any specific group with the "calcium" label, as opposed to the "palladium" or "organocatalysis" badges worn by many.

Well, the Niggemann group in Aachen, Germany appears to want that distinction. Prof. Meike and her team have released a slew of interesting reactions - Friedel / Crafts, [3+2] cyclizations, cyclopropanations - with more popping up seemingly monthly. But...calcium? The stuff ingrained in our bodies, stapled in the phosphate matrix of our bones and teeth? The stuff I eat in yogurt, milk, and cheese is now a catalyst?

Source: Niggemann Group, RWTH Aachen

Let's dig a bit deeper. To start, Niggemann's group uses a weakly-coordinated calcium complex, calcium (II) bistriflimide. Next, they exchange anions with a quaternary ammonium source, producing the "mixed" catalyst Ca(II) PF6 NTf2, increasing organic solubility. The group claims that this complex exhibits both high selectivity for olefin coordination and stability against air and moisture - both important properties if you're exploring new reactions!

This new catalyst combo, dubbed "Super-Calcium" (with mascot, above), reacts like a wild hybrid of alumnium, gold, and palladium. It activates alcohols as leaving groups (Al). It permits [1,2] hydride shifts (Pd). It's a hard enough Lewis acid to unzip donor-acceptor cyclopropanes, but soft enough to permit hydroarylation (Al / Au). Checking some of the historical calcium-catalysis reactions (above) reveals even more head-scratching reactivity reminiscent of magnesium, titanium, or vanadium.

So, what's really going on here? First, I'd say it's early days: Some deuterium-labeling studies were done on the older reactions, and molecular modeling on this latest batch, but several steps (Vinyl cations? Hydride shifts?) make me wonder exactly how intimately the central calcium atom gets involved. Second, no one yet knows the exact structures of these reagents in solution; look how long it took to figure out LDA!!! Third, Meike's battle cry rings mostly true: reactions exploring the reactivity of early alkali metals (potassium? barium?) remain largely terra incognita.

More reactions will lead to more interest; perhaps a Calcium Craze looms over the horizon? Time will tell.

Happy Friday, Everyone!
-SAO

In Which You are What You Eat

I love food. Always have – both the process of making food (which may be why I’m a synthetic chemist) and the joy of consuming one’s labors (which lab work definitely doesn’t allow!). Recently, however, modern science blurs the line between the stomach and brain. “You are what you eat” no longer just refers to body weight or proper nutrient intake. We humans are superorganisms, meaning that our intestinal microbiology plays a huge role in our everyday lives. Turns out, where you were born, where you live, what you eat, and where you’ve travelled can all influence the metabolic phenotype (appearance) of the bacteria that inhabit your intestinal tract.

Hey baby, what's your gut microbiome?
Credit: Healthy Perceptions blog

Some microbiologists posit that humans can be grouped, not by race, creed, height, or sex, but by “gut profile.”  A recent multi-institution Nature paper, led by Bork and Ehrlich, disclosed three major enterotypes (gut profiles), based on DNA sequencing (of, well, poop) of 22 people from 4 different countries. The scientists try not to paint too broad a picture with this initial result, but note that gut bacteria influence key genes that regulate aging and body mass index, which may suggest microbial management of a wide variety of diseases.

Your gut bacteria also impact your emotions. WSJ’s Jonah Lehrer reports that yogurt – specifically the kind filled with “good” (probiotic) bacteria – can actually cause marked behavioral effects, at least in mice. Probiotic-fed mice showed fewer symptoms of stress and anxiety, even when placed in new situations. An ideal cure for modern social anxiety, right? Unfortunately, no: other scientists interviewed quickly point out neurological patients’ inability to feel fear or stress causes them to make even worse future decisions in similar situations, since they lack the negative feedback from the prior event.

Mmm, gene regulation!
Credit: eating-in.com

Yogurt aside, your salad may also be helping to regulate your genes. Earlier this week, researchers in China disclosed new methods that can detect short strands of plant-derived RNA present in human bodily fluids. The researchers were especially surprised to find certain microRNAs actually inhibited the removal of LDL (low-density lipoprotein, the so-called “bad cholesterol”) from the bloodstream. Overall, the team found about 40 different microRNAs, from at least five different crops, and expects to find many more. Just more news to chew on, while you ruminate over your afternoon snack.