Porphyrin and its chemical cousins are well known as
providing the central unit in the likes of chlorophyll, haemoglobin and vitamin
B12. Israeli chemists have now found that if they stack these disk-shaped
molecules together and crystallise the product they can produce a unique lattice
structure with large channels running through it that might be useful in drug
delivery materials.
The resulting material is, surprisingly for a porous organic solid,
stable up to a temperature of 360K. Most attempts at producing porous organic
materials while successful at low temperatures come unstuck on warming as the
material collapses. 'Commonly, organic crystalline materials with such large
pores are not stable even at room temperature,' explains Israel 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 porhyrin 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'. (Chemical Communications, 1999, 1961)
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 Ruehlemann 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 seesaw 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
Ruehlemann 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
Ruehlemann. 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.
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.
Within a hair’s breadth
To make such devices, chemists are adapting techniques used in the microelectronics industry, ie microlithography and micromachining, for squeezing millions of transistors on to a silicon chip. Similarly, chemists have been able to etch narrow channels and conduits on slivers of glass and plastic to form chemical mixing and separating systems for tiny samples. Several thousand channels can be packed into a single chip and electrodes fed in while nanolitres or less of a sample are sucked or pumped into the system. The channels, which are up to 50 hundredths of a millimetre wide, are a fraction of a hair's width across so fluids flow by capillary action. However, electrical probes can be used to 'drive' materials such as solvent and chemical sample down particular capillary channels so that they mix at specific points in the chemical 'circuit'. The speed at which different chemicals move in an electric field will depend on their electrical charge, molecular weight and other properties so tiny amounts of different products, such as protein fragments or DNA, can be tapped off from the capillary one after the other even in a complicated mixture. By using fluorescent markers the researchers can 'see' the molecules emerge using a detector unit, which itself might be just a centimetre square and hooked up to a computer.
Plug and play
The UK's 'lab-on-a-chip’ (LOC) consortium coordinated by Stephen Haswell of Hull University hopes to make the UK the leader in the field. Its members include research groups led by, Andreas Manz at Imperial College London, chemical engineer Ron Pethig's group at Bangor University, Jonathan Cooper of the Bioelectronics Research Centre at the University of Glasgow and teams at the universities of Hull, Cardiff and Newcastle and UMIST. Companies such as Unilever, GlaxoWellcome, Epigem, Kodak, Faraday Foresight NW, Optokem, Windsor Scientific, Kalibrant, MSTB and the Laboratory of the Government Chemist (LGC) also form part of the consortium. The total budget for the project is likely to be ca £3.2m of which the UK Government is contributing £1.33{}m and the remainder coming from the industrial partners. One of the main aims of the LOC consortium in developing analytical and synthetic lab-on-a-chip devices is to ensure the kits are compatible so that devices can be integrated like 'plug-and-play' computer components.
Manz and his colleague Andrew de Mello have recently built an LOC chemical amplifier, which converts a few strands of DNA into many more using the polymerase chain reaction (PCR). The sample containing a small amount of DNA is pumped through a single channel in the chemical microchip and passes through different temperature zones, which repeatedly heat and cool the DNA. This process doubles the number of DNA molecules. In the normal-size laboratory, this is a slow process taking ca three hours to achieve amplification of the DNA to detectable concentrations. Manz’s ‘LOC’ amplifier can get to the same levels in 90{}s.
Over in the US, Fred Regnier and his colleagues at Purdue University in Indiana have built a micro-mixing device with an internal volume of just 100 picolitres. This is built up of criss-crossed channels 5 micrometres across. The channels form a tiny whirlpool of 2 picolitre volume as the materials mix under the action of an electric current. Such mixers will be central to many LOCs.
LOC reactors
Microscale reactor plants were first thought of in the 1970s by scientists at ICI. But only now are chemists realising the advantages. The main impetus comes from safety, health and environmental issues as well as the possibility of distributed manufacturing so that large-scale plants involved in transporting and handling huge volumes of often hazardous liquids will become obsolete and replaced by small units that synthesise chemicals on demand.
Ray Allen and his group at Sheffield University, for example, have recently demonstrated the conversion of methane to methanol in a microreactor. Allen's team has built a silicon membrane microreactor - an LOC on a board - that operates at medium temperatures. Significant quantities of methanol can be produced quickly and simply by adding more boards to make a reactor block rather than increasing the volume of a reaction flask. This work is an important starting point for the development of microscale reactions such as the oxygenation of hydrocarbons to produce alcohols, anhydrides and ketones, all useful industrial reactions.
The main advantage of microreactor systems would ultimately be safety. Since each microreactor in a chemical plant would only carry a small volume of materials at a time the risk of serious explosion if things go wrong is greatly reduced. Contrast that with a thousand-litre steel flask whose contents are being boiled under pressure. In addition, if a board breaks down it can be pulled out and replaced quickly without interrupting the overall process.
Many chemists hope that the lab-on-a-chip will do for chemistry what the silicon chip integrated circuit did for electronics. While there is a lot of hype surrounding the technology, laboratory equipment will shrink and become much cheaper and better. We will in the next few years begin to see consumer devices too, for chemical analysis, which will become commonplace in the home, at the doctors' surgery and in the workplace where tests can be carried out quickly and easily for all kinds of compounds of dietary, medical and environmental importance.
Some of the devices possible with lab-on-a-chip technology
Medical diagnostics kit - glucose monitor for diabetics is implanted under skin to release automatically insulin when needed
Chemical analysers - for sampling and testing materials in a chemical factory and personal sensor devices to alert workers to exposure to hazardous chemicals instantly
Biosensors for measuring physiologically important species in medical tests, such as markers for cancer cells, brain chemicals in diseases such as Alzheimer's and Parkinson's, and ionic imbalances caused by kidney problems, all for more immediate diagnosis
DNA probe - for the Human Genome Project, forensics, paternity suits etc - US companies such as Affymetrix and Nanogen are at the forefront of commercial devices of this kind
Environmental test kit - analysis of pollutants, such as pesticides and natural chemical indicators, such as molecules released by algae
Blood gas analyser on a chip - for monitoring vital signs during surgery Miniaturised chemical reactor - huge arrays of integrated chips for manufacturing fine chemicals. Teams, such as Klavs Jensen's at Massachussetts Institute of Technology and Wolfgang Ehrfeld's at IMM Mainz in Germany are making big advances in the microreactor field