Ions gone to seed

by David Bradley

Remember the crystal garden of school science in which a seed crystal (usually of copper sulphate) is used to grow a bigger and bigger crystal from a saturated solution of the salt?
   Italian chemists have now carried out the grown-up version of that technique to crystallise an organometallic zwitterion that has until now remained stubbornly dissolved.
   Dario Braga and his colleagues at the Universities of Bologna and Sassari have devised a method for preparing seeds - either by dehydration or grinding - which means it might now be possible to crystallise intractable materials. In addition, the technique opens up the possibility of controlling the outcome of a crystallisation process to make a particular form of a compound in the solid state.
   While finding new ways to crystallise materials that can already be crystallised may seem a fruitless task, producing a seed in a particular polymorphic form might allow one to mirror that form in the final product. This is particularly important in areas such as pharmaceuticals where different polymorphic forms can have different physiological and pharmacodynamic profiles. Braga's example uses the organometallic zwitterion [Co(III(eta-5-C5H4CO2H)(eta-5 -C5H4CO2)], which has until now proved obstinately impossible to crystallise in an anhydrous state.

   The Italian team used a rearguard action to produce seed crystals of the zwitterion, which carries a separated positive and negative charge on the same unit, so they could then use them to produce fully-grown crystals. They began with the hydrated form of the zwitterion, which is crystallisable to form yellow, sword-like crystals, and blasted it with heat at 506K. This removes the water and then induces a phase transition in which the dehydrated form adopts the polymorphic structure of the elusive zwitterion.
   The resulting 'microcrystals' just a few micrometres across could then be used to produce single crystals by seeding the initial aqueous solution which gave the hydrated pseudo-polymorph and let it evaporate in the air, explains Braga - just like the school crystal garden in other words. According to Braga, the technique might be used 'to develop strategies to "trick " crystallisation processes that (spontaneously) lead to precipitation of (kinetically favoured and/or thermodynamically more stable) pseudo-polymorphs encapsulating solvent molecules in an unpredictable manner.' This is often a problem in the crystal engineering of molecular materials, he adds, overcoming it might lead to novel materials for magnetic and optical applications, or molecule storage and exchange, as required for solid state sensors or catalysis. (Chemical Communications, 1999, 1949)

Cleaner reaction comes off the shelf

A way to cut the carcinogen out of a promising reaction equation could open up the scheme to countless syntheses that are much safer, according to US chemists.
  Veeraraghavan Ramachandran and his team at Purdue University, in West Lafayette, Indiana have found they can make the vinylalumination reaction work without the carcinogenic reagent HMPA (hexamethylphosphoramide).
  Vinylalumination is more than a decade old but has stayed in the notebook rather than on the bench because it relies on a potent carcinogen for a critical step. However, the promise of efficient carbon-carbon bond forming for a whole variety of synthetic procedures based on carbonyl compounds meant it could not be left to languish. Previous efforts to replace HMPA have increased costs so been commercially unviable. Now, Ramachandran and colleagues have come up with a new methodology that uses NMO (4-methylmorpholine N-oxide) instead of HMPA. NMO is relatively cheap, they say, and has none of the medical nor environmental risks associated with its predecessor so could open up vinylalumination to various industrial applications. For example, in the synthesis of alpha-methylene-gamma-butyrolactones, precursors to putative anticancer drugs. NMO also has the added benefit of producing higher yields.
  Vinylalumination forms carbon-carbon bonds between vinylaluminium derivatives and electrophiles, to create Morita-Baylis–Hillman type products but without the limitations of that particular reaction. For instance, the Morita-Bayliss-Hillman reaction usually only works with reactive electrophiles, such as carbonyls and imines, it is rather slow and it cannot handle substitution at the second carbon of the vinyl group.
  The reaction involves adding an aluminium reagent (DIBAL-H) (diisobutylaluminium hydride)> across and acetylene group attached to a carbonyl. Without HMPA or NMO the DIBAL-H would reduce the carbonyl. The result is an olefin bearing a reactive aluminium atom, which can then be reacted with other materials, such as benzaldehyde or N-protected benzaldimine to produce an allyl alcohol or amine, respectively. The latter has been used in the synthesis of docetaxel (Taxotere) analogues, says Ramachandran. (Chemical Communications. 1999, 1979) 

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Elemental Discoveries
December 1999 Feature-length Issue

Porphyrin sieves

Goldberg of Tel-Aviv University, 'they often deteriorate even below room temperature.'
   Finding stable porous materials will allow chemists to create tailor-made molecular sieves and selective catalysts simply by tweaking the functional groups that line the channels. Only select smaller molecules can then enter and be trapped for either separation, sensing or catalytic purposes.
   Goldberg and his team have previously studied the packing of porphyrins guided by the presence of a second smaller molecule, which acts as a template for the formation of a lattice. The templated approach, they found, resulted in sponge-like materials in which the pores are scattered through the crystal because the porphyrins do not stack neatly and remain occupied by the template. They designed a building block they hoped would lend itself to a more regular arrangement through multiple hydrogen bonding and porphyrin stacking interactions. The unit they came up with was an aquazinc tetra(4-carboxyphenyl) porphyrin building block.
   They realised that regardless of the porphyrin's design they would still have to rely on a templating agent to nucleate and maintain the open lattice structure as the product crystallised. After much trial and error, team member Yael Diskin-Posner devised an experimental procedure that would work. He first dissolved the tetra(4-aminophenyl)porphyrin in nitrobenzene and poured it into the bottom of a glass tube. Then added a layer of ethylene glycol above this solution, and finally a third layer of the zinc porphyrin dissolved in methanol was placed on top.
   The zinc porphyrin slowly diffused into the bottom layer and after several days, the team saw a phase separation which produced tiny needle-shaped crystals of ZnTCPP in the bottom solution.
   When they took a close look at the crystals with X-ray diffraction they could clearly see regular, wide channels in the crystal rather than scattered pores. The X-ray study also demonstrated the multiple hydrogen bonding and the stacking of the porphyrins held in order by van der Waals stacking forces between each 'disk'. (You can download the full paper in PDF here if you have subscriber access: Chemical Communications, 1999, 1961) 

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Ocean in Motion

By analyzing the sludge deep in the ocean floor, German scientists believe they can find important clues about ice ages and how their coming and going depend on ocean currents. They recently reported molecular evidence of a 'see-saw' effect that involves ocean currents that push cold Arctic water southward along the ocean bottom and force warm tropical water northward.
   Carsten Rühlemann of Bremen University and colleagues have correlated the quantity and type of the molecular remains of marine algae that exist in sea sediment with changes in the temperature of Caribbean surface waters. These rose from 2 degrees to 2.5 degrees Fahrenheit around the time of two especially cold eras about 15,000 and 12,000 years ago, during a long ice age.
   Theory has it that as polar ice melts during warmer periods, Arctic waters become less dense, sink to the bottom more slowly and reduce the deep-sea southern flow. This means more hot water stays in the tropics, cooling the Arctic region back down see-saw fashion.
   According to the German team the sea sediment suggests that a major current flowing south - the thermohaline circulation - blocked cold waters from heading south the tropics making the tropical waters warmer, which then flowed north to melt the polar ice caps. The findings seem to support the idea that environmental changes that alter the circulation of North Atlantic waters can have a rapid and profound effect on climate.
   The researchers point out that these waters were relatively warm when the North Atlantic towards the tropics itself was cold during the Younger Dryas and add that this would fit in with the larger global thermohaline circulation current being blocked. This carries water from warmer regions to cold areas around the globe. If it is somehow blocked its heat mixing power is lost. The tropical oceans stay warm while other regions can chill out. According to Rühlemann it is now well accepted that 'the sudden release of huge amounts of glacier meltwater through the St. Lawrence River drainage system can block the thermohaline circulation.'
   Today there is evidence that global warming might switch off another ocean current - the North Atlantic Drift - which brings warm water to Northwest Europe from the Gulf Stream. 'Modern environmental changes, such as global warming, could warm surface waters or increase rainfall in the North Atlantic or release glacier melt water decreasing the density of the surface water,' adds Rühlemann. Rapid changes in density of the North Atlantic may affect ocean circulation and lead to a weakening of the Gulf Stream.
   According to climate expert Jeff Severinghaus of the University of California at San Diego, however, the authors conclusion may not be correct. 'Their evidence is consistent with the theory that the thermohaline circulation changed, but not that it was the cause of the change,' he explains, 'it is possible that the climate change itself caused the thermohaline circulation to change.' There may be no telling whether we should get the woolly jumpers out or slap or head for the beach. (You can access the full paper if you have subscriber rights: y, 1999, 402, 511)

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The ever-shrinking laboratory

It sounds like the stuff of science fiction but chemists are working on shrinking their entire laboratories by anything up to a million times so that they can put them on a chip, similar to those found in computers. Already manufacturers are developing tiny gas chromatography systems for separating and analysing mixtures, DNA sequencers and protein analysers for molecular biologists working on the Human Genome Project, and medical diagnostic devices all no bigger than a thumbnail.
   Downsizing the laboratory will have countless benefits. For instance, much smaller samples will be used in testing, requiring less solvents and reduced materials costs. Small also means portable - imagine an environmental chemist taking an entire analytical laboratory into the field in a briefcase to test for pollutants in a river or contaminated soil on an industrial site. With the 'lab-on-a-chip', as it has been tagged, they would be able to get a result there and then without having to waste time by sending samples back to the 'lab'. Think how useful that will be to forensic police for analysing DNA samples from body fluids at the scene of a crime.

Read on in Part 2