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The thermoresponsive microjet

27 March 2014 - Making It move XIV

microjet.PNGIn our ongoing making-it-move coverage (previous episode here) now the thermoresponsive microjet as reported by Magdanz here. We have seen hydrogen peroxide / metal / vesicle based micro-swimmers before but the dimension added is on-demand weaponisation. Key is the vesicle construction material. It consists of a polymer bilayer of poly(N-isopropylacrylamide-4-acryloylbenzophenone) (PNIPAM-BA) dip-coated with polycaprolactone. This film was cross-linked by irradiation across a photo-mask, uncross-linked material was rinsed off and finally a platinum layer was added by sputter coating. The resulting trilayer reversibly folds into 30 micron diameter tubes and unfolds again below and above 28°C in water by a process of swelling and unswelling. In a hydrogen peroxide solution at low temperatures the tubes behave as microjets propelled by oxygen bubbles. Increasing the temperature above 28°C makes the tubes unfold and the movement stops.

Industrial artemisinin

22 March 2014 - Many thanks to Bill and Melinda

artemisinin  As reported back in 2012 here chemical company Sanofi and the Bill and Melinda Gates Foundation have joined forces (Sanofi the know-how and Bill the money) to increase production of the important antimalarial drug artemisinin. In a recent OPRD publication Sanofi chemists present a commercial-scale (no-loss no profit) production line with a capacity of 60 tonnes, starting from yeast-produced artemisinic acid. Here is the summary.
In step one from artemisinic acid to dihydroartemisinic acid (a dehydrogenation) the Wilkinson catalyst was deemed too expensive and replaced by ruthenium chloride (R)-DTBM-Segphis (a modified segphos). Scale: 600 Kg, 90% diastereoselectivity. The compound was next activated with ethylchloroformate and potassium carbonate in dichloromethane to the anhydride. The photochemical step consisted of adding tetraphenylporphyrin as a sensitizer and trifluoroacetic acid in dichloromethane. The subsequent Schenck ene reaction / Hock rearrangement requires two equivalents of singlet oxygen. Where the prior art yielded 41% of product, this photochemical solution pushes out 55%. Side note: the article does not really explain why the acid was activated, the Seeberger procedure does not include this step. Remaining challenge: product isolation was accomplished by simultaneous DCM distillation - solvent replacement with n-heptane and crystallisation. Pretty amazing when considering this is still industrial production at the hundreds of kilogram scale and the final product is a labile peroxide!
Please do admire the photochemical reactor pic embedded in the article. At the Sanofi plant in Garessio (Italy) it is Christmas every day of the year.

A molecule cannot be rare

15 March 2014 - Reviewers sleeping on the job

rare fullerenes Xiao 2014.PNGThanks to tetrahedral carbon the number of possible molecules that can exist seems infinite. Any child can take a piece of paper and draw a completely unique molecule on it and name it after itself, sticking to the basic rules of valence, multiple bonding and some common sense with regard to cluttering. Synthesising the molecule in question is of course another matter. Can a molecule therefore be rare? No. Yang Xiao et al. in a recent publication however seem to differ, they titled it "Regioselective Electrosynthesis of Rare 1,2,3,16-Functionalized Fullerene Derivatives". Nothing wrong with the publication itself: a fullerenoindole (itself the adduct of fullerene and an aniline) was electroreduced and the dianion subjected to benzyl bromide. The benzyl group ended up exclusively at the 16-position and a proton (derived from stray water) at the 3-position. Congratulations on the regioselectivity achieved but obtaining a "rare" molecule by decorating a fullerene with any number of substituents is not an accomplishment. If the reaction was not regioselective at all you would have ended up with many more "rare" molecules. Let's reserve rarity to animals uncovered by biologists in remote parts of the world or a Da Vinci painting. "Rare" has no business in chemistry.

That is uranium from seawater.

11 March 2014 - aqua mining

uranyl from seawater Zhu 2014.PNGThe sea is worth money. It contains 3.2 mg per tonne of uranium in the form of uranyl and no one owns it yet. But how to extract it? The competition is stiff. Seawater is (still) basic and abundant carbonate ions chelate well to uranium. Calcium ions are also abundant and compete with uranyl based on size. Lu Zhu et al. argue that complexation of uranyl with dedicated protein is the way to go and describe a novel strategy here. In step one a protein database was computationally screened for proteins that are able to accommodate a uranyl cation in a pocket. The assumption is that ligand substructures coordinate to uranium as a hexagonal bipyramid or a pentagonal bipyramid. This work yielded 12,000 candidates. Additional assumptions were made: a degree of hydrogen bonding thrown in, some residue mutations allowed and a ligand oxygen to uranium bond length preset. That filter eventually rounded up around 5000 proteins.

The ultimate super uranyl-binding protein (SUP) that came up in the search was at one time sourced from the otherwise very unremarkable methanobacterium thermoautotrophicum, an anaerobe that can be found in sewage sludge. The binding affinity is sufficient and can even improve with strategic mutations in the protein. The affinity for other ions such as calcium, copper or the vanadyl ion is far less. In synthetic seawater it was possible to retrieve 17% uranyl in 30 minutes from a 13 nM solution with SUP fused with a maltose binding protein on amylose resin.