In-adamantane

31 October 2008 - News

The molecule adamantane shares its name base with adamant reflecting its robust nature. In a recent publication, scientist Karl Irikura argues through in silico experimentation that the so-called in-isomer called in-1-H-F15-adamantane (the almost completely fluorinated derivative) is just as stable (DOI). In this molecule 15 hydrogen atoms are replaced by fluorine and the remaining hydrogen atom is inverted and pointing inwards instead of outwards. Agreed, isomerization to regular out-adamantane is a very exothermic process but the activation energy (the energy barrier the isomerization process has to overcome) is prohibitively high. The molecule also appears impervious to water and oxygen and is stable towards bimolecular reaction. Why perfluorinated? fluorine substitution creates stronger carbon-carbon bonds. The all-hydrogen in-adamantane has a chemical half-life of 2 weeks at dry ice temperature compared to 100 years for the fluorinated one at ambient temperature. To summarize, in-F15-adamantane is a viable molecule in the new HSS doctrine.

But synthesis represents a formidable task. For starters, selectively placing fluorine atoms on adamantane is not that easy. You can add up to three at targeted positions in selective organic reactions (DOI, DOI, DOI) or create perfluoroadamantane with all hydrogens replaced by fluorine in a single F2 aerosol blast (DOI) but even out-1-H-F15-adamantane is elusive let alone the in-isomer.

When it comes to in-molecules, fullerenes are much more likely candidates because of size and surface reactivity. The same people who have brought endohedral hydrogen fullerene or H2@C60 most recently have been able to incorporate ammonia into open-cages fullerenes as well (DOI). Surprisingly however, the hydrogenation of a fullerene from within has yet to be reported.

Novel organic integrated circuit

24 october 2008 - news

Recently, a team of 17 scientists from 7 institutions have demonstrated what they call a bottom-up organic integrated circuit (Smits et al. DOI). The system is based on molecular self-assembly of oligomeric polythiophene molecules on a silicon substrate into a so-called SAMFET which stands for self assemblied monolayer field-effect transistor. Earlier attempts at creating these devices apparently all failed due to defects and poor aromatic stacking. In this particular setup the oligothiophene units form a liquid crystal ordering which certainly helps.

The novel concept was demonstrated in a molecular logic gate as an inverter.

Gift your stuff

23 October 2008 - support charities!

Ideally suited for chemical laboratories, chemical training institutions and the like with a surplus of laboratory equipment or chemical literature: www.giftyourstuff.org Link. You can now donate your surplus inventory to a charity, particularly to schools in developing countries. The new website aims to close the gap between supply and demand. So to you affluent first world laboratory: did you recently bought yourself brand-new microscopes, NMR or HPLC equipment and don't now what to do with the old stuff? Simply leave a message at www.giftyourstuff.org and gift your stuff!
Disclosure: Family relation.

Novel trialkyloxonium salt

17 October 2008 - News updated 02/03/09

The oxonium salt triethyloxonium tetrafluoroborate is a well known alkylating reagent. In this compound three ethyl groups are attached to a positively charged oxygen atom. Recently a novel and remarkably simply oxonium salt based on a triquinacene skeleton with again a central oxygen atom was described by Mark Mascal et al (DOI).

This work is a follow-up on research published in 1996 on azatriquinacenes (DOI) and azaquinanes (DOI) which are both the aza analogues. The oxatriquinane compound was found to be especially stable: it can survive boiling water for at least 70 hours. its synthesis starts from a cyclononatriene.


Update: Haley predicts further alkylation of new oxonium ion to R4O2+ species is possible (DOI)

Grignards on lithium

15 October 2008 - news

The standard routine for synthesising Grignard reagents is adding magnesium metal to a suitable halocarbon. Another method (discovered by Prevost in 1931) is by metal-halogen exchange of a halocarbon with another (simple) Grignard reagent where the X on RX trades places with the MgX on RMgX. In 2004 Knochel found that this particular reaction is accelerated when the Grignard is complexed with simple lithium chloride (DOI). The basics.

The (now commercial Link) THF solution of isopropylmagnesium chloride with lithium chloride (CAS 807329-97-1) is sometimes called a turbo-Grignard.

This reagent is prepared by simply mixing magnesium , isopropyl chloride and lithium chloride in THF. Its enhanced reactivity is attributed to breaking up RMgX polymeric aggregates, improving solubility and R3Mg-Li+ ate complex formation. Adding a crown ether speeds up certain reactions even further by isolating the lithium ion and increasing the negative charge (DOI).

The synthetic utility of Grignards on lithium have been demonstrated in manipulations on aromatic carboxylic acids (DOI). Buchwald examined its use in a Kumada coupling (DOI) and a 2008 patent (Carnegie Mellon University, Link) describes so-called Universal Grignard metathesis Polymerization (GRIM) for application in conjugated polymers (solubility is always key in polymerization) for instance in a poly(fluorene):

In 2006 Knochel synthesized a magnesium superbase variation on lithium tetramethylpiperidide which owing to the presence of LiCl is very THF soluble (DOI). Bases of this type are sometimes called Hauser amides (DOI DOI) after C. Hauser who in 1949 used amides of this type in certain ester condensations.


Most recently in 2008 Garcia-Alvarez et al. determined by x-ray crystallography the molecular structure of this base, which is found to have a nonplanar LiClMgCl ring with the TMP part firmly attached to Mg (and not Li) and with no less than three solvatating THF molecules (DOI).

From it is confirmed that it is a molecular halide and not a salt.

And the winners are......

8 October 2008 - even more biochemists

You will never see a non-biochemist cheer loudly whenever a biochemist wins the Nobel Prize in Chemistry. If only Nobel had the inspiration to create a separate Nobel Prize in Biology, biochemists would compete with primate scientists but not with chemists. Never mind, the 2008 winners are Roger Y. Tsien, Osamu Shimomura and Martin Chalfie and typically for the last two Wikipedia was totally unprepared and had to start a bio-page post-haste well after the Swedish announcement was made (also see earlier post). The prize has something to do with a green fluorescent protein and glow-in-the-dark pigs.

As a public service the ISI Web of Knowledge is mined for data. Roger Tsien co-published 152 articles (punching in RY Tsien, excluding reviews) in the last 20 years (ISI for some reason does not go back any further than that) and the top 6 most cited reads as follows:
* 1011 citations: ''Fluorescent Indicators for Cytosolic Calcium Based on Rhodamine and
Fluorescein Chromophores'' (1989) (Link) (open access)
* 988 citations: Fluorescent indicators for Ca2+ based on green fluorescent proteins and calmodulin (1997) (Link) about a marriage between GFP and calmodulin.
* 836 citations: Crystal structure of the Aequorea victoria green fluorescent protein (1996) (DOI). Breakthrough work by Tsien on GFP inner workings
* 817 citations: A monomeric red fluorescent protein (2002) (DOI) (open access)
* 785 citations: Emptying of intracellular Ca2+ stores releases a novel small messenger that stimulates Ca2+ influx (1993) (DOI)
* 733 citations: Wavelength mutations and posttranslational autoxidation of green fluorescent protein (1994) (Link) (open access).

Repeating the same feat for Shimomura proofs to be more difficult. Having just one initial, ISI lumps together a group of people called O. Shimomura and it is impossible to find out who the real Osamu Shimomura is. If you can label journal articles with a single DOI code surely you can label unique authors as wel.

In any event excluding all O. Shimomura's active in the physical or social sciences and skipping reviews we get to 30 articles over 20 years acknowledging that the man is retired with this top 3:
* 101 citations: Semi-synthetic aequorins with improved sensitivity to Ca2+ ions (1989 - Link - open access)
* 95 citations Recombinant aequorin and recombinant semi-synthetic aequorins. Cellular Ca2+ ion indicators (1992 Link - open access)
* 87 citations The crystal structure of the photoprotein aequorin at 2.3 angstrom resolution ( 2000 - DOI)

In the meanwhile Shimomura's original 1962 publication (Pubmed) is nowhere to be found on the internet! Publisher Wiley put out a self-congratulating press release (Link) notifying the reader one of the fresh Nobel prize winners did publish in Wiley's Journal of Cellular and Comparative Physiology but Wiley apparently has not bothered yet to make this journal accessible. It would have been a nice gesture to publish Shimomura's 1962 article together with the press release. Regrettably this blog owes you the perfect recipe for extracting GFP from jellyfish.

Finally, Chalfie's top-cited 1994 article dwarfs that of his two colleagues: 2838 citations for Green fluorescent protein as a marker for gene expression (DOI).

Quite a number of the articles mentioned here are open-access (hurray!) and it could have (2) been more: the journal Science) otherwise very generous open-access policy (requires user login but free) extends from 1997 to 2007 which is not enough to be able to include two Science articles, the ones from 1994 and 1996. Interestingly the 1996 pnas Tsien article has the disclaimer The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked advertisement.

Phase-vanishing reactions

6 October 2008 - overview updated 20 Oct.

Phase-vanishing reactions are triphasic reactions with a middle organofluorine phase through which reagent is slowly transported from the dense bottom-reagent phase to the phase on top containing substrate. As a result the reaction can be moderate and easier to control and at completion the reagent phase has vanished.

This concept as introduced in 2002 by Ryu et al. (DOI) can be demonstrated in a very simple experiment. Bromine (high density), perfluorohexane and a mixture of cyclohexane in cyclohexane (low density) are placed in a test tube forming three layers. After leaving the tube for two days in the dark the bromine layer has vanished and trans-dibromocyclohexane can be recovered from the cyclohexane layer in a 81% yield. Compare that to the 1932 OrgSynth procedure for the same reaction that requires slow addition of bromine at a low temperature (OS 12:26).

In a follow-up Ryu (DOI) reacted tin tetrachloride thiophene and the acid chloride of acetic acid in a three-phase Friedel-Crafts acylation. When the reagent phase is less dense than the fluorous phase as in thionyl chloride (for the chlorination of alcohols) a U-tube replaces the ordinary test tube (DOI). When additionally water is added as an acid scavenger for certain reactions, the system becomes quadraphasic (DOI)

At least one older concept exploiting U-tubes is known: Cram in 1979 used this setup with chiral crown ether shuttling one amine salt enantiomer from water phase A to B (DOI).

The concept is a nice detour from tried and tested biphasic reactions using a phase transfer catalyst and has been picked up by other chemical investigators. Iskra et al. react chlorine and alkenes through a u-tube setup (DOI). Jana et al. (DOI) mix in 1,2-dibromoethane when the reagent phase alone is less dense than the fluorous phase as an alternative to a u-tube solution But Curran et al (DOI) identifies an extractive mechanism for this particular setup.

Podgorsek et al. give benzylic brominations a try (DOI) and Windmon et al. extend the scope to halolactonization reactions(DOI)

A 4 layer stacked reactor is showcased with from bottom to top a layer of bromine, a perfluorohexane layer, an ionic liquid layer forming a new brominating reagent (tridecylmethylphosphonium tribromide) and a higher alkane layer containing 2-hexene (Ma et al. DOI).



In a most recent contribution Windmon et al. report on a solvent-free tandem phase vanishing reaction (DOI) with cyclopentadiene and dimethylfumarate reacting in a (fast) regular Diels-Alder reaction in the top phase in presence of a iodine monochloride bottom layer providing halogen for a (slow) iodolactonization.


In this particular setup care had to be taken to control the exothermic DA reaction. The quote from the report that the reaction inadvertently went out of control (stirring was set too high and iodine monochloride and Diels–Alder adduct came into a direct contact). The temperature was so high that all of the FC-72 evaporated. is one for the bad luck in science and being honest about it category. But are PV-reactions not supposed to prevent these things from happening? A solution to this problem must be near at hand. Did anyone say W-tube solution?

Perkins mauve reinvestigated

4 October 2008 - news (updated Oct. 19)

A Portuguese/English team has took it upon themselves to collect a bunch of Perkin mauve relics from several museums dated between 1856 and 1906, to put them through a series of chemical tests (DOI) with some surprising results. Several team members had in 2007 already identified a couple of new components in the Mauve mix (DOI) but now it turns out the dye consists of at least 13 derivatives of the same 7-amino-5-phenyl-3-(phenylamino)phenazin-5-ium core only differing with respect to methyl substitution pattern.

The new study also reveals two different production processes. In original samples (dated 1856 and onwards) the phenazinium cation is accompanied by a sulfate anion. This salt is amorphous and poorly water-soluble. In 1862 Perkin replaced sulfate by an acetate ion making the dye more soluble and to improve crystallinity he increased the amount of O-toluidine in the formulation.

interestingly a sample cherished by the Science Museum (Link) as the original stuff turned out to be post 1862 material. A Mauveine specimen also in possession by the science museum and now declared genuine was donated by Perkin's daughter (or granddaughter, the article is fuzzy at this point) in 1947.

Update: in another case of what we can call chemical archeology, samples from the famous 1953 Miller-Urey experiment have been re-analysed by Johnson et al. via HPLC / Time-of-flight mass spectroscopy at the sub-picomolar (<10-12 M) level revealing many more amino acids than Miller (obviously using less sophisticated equipment) himself had reported (DOI). This new finding however does not change the significance of the Miller experiments.

Nobel prize 2008 predictions

3 October 2008 - News

As October 8 (11:45 a.m.) is nearing, it is time to predict the Nobel prize in chemistry 2008 (Link). Thompson Scientific has some credibility when it comes to guessing it right (Link) so here they are: Charles Lieber (Nanotechnology), Krzysztof Matyjaszewski (Atom Transfer Radical Polymerization) and the inevitable biochemist Roger Tsien (Indo-1, fluorescent probes).

But would these people also be the people's popular choice? Lets query Wikipedia. All three individuals have a biography page but interestingly only Tsien has just one citation on the Indo-1 page. For the others not a single one. This is a general Wikipedia drawback: it tends to be more about the people than about the science. Take for instance last years winner Gerhard Ertl with an extensive bio page but hardly anything specific on his particular contribution to science (exception : the Haber process). Or take the 2006 winner Roger D. Kornberg with modest mentions on the mediator or lipid bilayer pages. The 2005 winners fair better because there exists an extensive olefin metathesis page. An especially sad case is the 1999 winner Ahmed Zewail: the Femtochemistry page is very modest.

Lets return to the other contestants on the Thompson page and factor in Wikipedia popularity. The two chemists with a certain Wiki following are James Fraser Stoddart (for example see molecular switch) and George M. Whitesides. See you on October eight!.