Come together

Come together HOW do you ensure that a cancer drug injected into the bloodstream reaches its target without being mauled by enzymes stalking the blood highway? And how do you pack ever greater information on to ever diminishing silicon wafers without causing a "traffic jam" on the chip?

To cope with these miniature problems with major headaches, hope is emerging in the form of a class of molecules called self-assembling molecules. While nature has them in plenty -- DNA being the most celebrated -- chemists and materials scientists are only now tasting success in designing similar molecules (Science, Vol 265, No 5170).

Many drug companies are in the final stages of testing microscopic, self-assembled bubbles that ferry potentially lifesaving drugs to cancer patients. And by getting different molecules to assemble themselves -- like pieces of a jigsaw that recognise and latch on to each other -- into conducting materials, researchers are paving the way for a new generation of molecular microchips.

Getting a hang of how molecules group together by themselves is the major goal of chemists. They are exploring molecules with a "split personality" (see box for related application), molecules that exhibit the self-replicating behaviour of DNA, molecules that embrace each other without forming a chemical bond, and those that assemble into multi-layered structures.

Scientists have known for some time now that amphiphiles -- a class of molecules with watery heads and greasy tails -- can organise themselves into superstructures of single and multiple layers. During the '80s, Helmut Ringsdorf of the University of Mainz chopped these "schizophrenic" molecules into 2 and added other molecules that interlocked by themselves with the broken ends to form a bigger molecule.

In the past few years, Gunter Von Kiedrowski at the University of Frieburg and Julius Rebek Jr at the Massachusetts Institute of Technology fabricated organic molecules that employ the DNA's self-replication technique to construct molecular tennis balls that encapsulate molecules of methane.
In the early '60s Another approach emerges from experiments in the early '60s, when chemists found out that drugs could be smuggled into the body like stowaways in material that mimicked cell membranes. These membranes are made up largely of "schizophrenic" molecules that self-assemble into a sphere called liposome. It is these spheres that researchers customised into drug carriers, which can vary in size from 25-billionth of a metre to more than a millionth of a metre. Today, self-assembling allows chemists to fabricate microscopic drug-carrying bubbles that are not maimed by marauders in the body.

The appeal of self-assembling molecules was a little tarnished when the "delivery trucks" soon broke down under attack from immune cells known as macrophages. How these bodyguards recognise the spheres is still a mystery. But in the late '80s, researchers discovered an effective camouflage for the drug-carriers: glycolipids used by natural membranes.

Thus camouflaged, liposomes are now being used to transport several different types of drugs. But they still cannot deliver their consignments to where they are required, say, a tumour cell. Researchers, however, may soon be able to make them target-specific. Last year, they successfully made an antibody for a mammalian carcinoma "escort" the courier molecule safely to its target destination. Liposomes look promising for drug delivery, but given their chequered track record, researchers are following their career with some scepticism.

In electronics, lathough most self-assembly contraptions are cheaper than existing semiconductors, they cannot yet compete with current technology, which is protected by decades of research and an established manufacturing tradition.

Nonetheless, electronics engineers have no choice but to abandon their top-down approach, in which increasingly minute circuitry is etched onto the surface of a silicon wafer. Their new philosophy is bottom-up, epitomised by self-assembly, using specially designed molecules that can assemble themselves into electronic components.
Mechanical interlocking A group of British researchers is concentrating on molecules that get mechanically interlocked but not chemically bonded. They have found 2 classes of molecules that fit the bill: catenanes, which consist of 2 or more interlocking rings, and rotaxanes, in which one or more rings is threaded onto a dumb-bell-shaped molecule.

The earliest attempts to make rotaxanes and catenanes did not feature molecular recognition. But in the mid-'80s, the British team came up with a technique of locking a linear molecule into a cyclic one. Inspired by that work, in 1992 Douglas Philp of the University of Birmingham made a prototype of a self-assembling family of "smart" molecules that may eventually form the basis of molecular switches.

Pennsylvania State University's Tom Mallouk and others are using self-assembly to fabricate a multi-sliced sandwich of electronically responsive molecules for devices such as solar cells and light-emitting diodes. To make self-assembled sandwiches, says Mallouk, he has to manipulate the chemistry so that "each layer serves as a bed for the next layer". In 1988, Mallouk first did this by stacking a series of molecules on a gold-plated silicon bed.

But it is doubtful whether such applications will ever find a market. Applications like liposomes as couriers for cancer drugs brave competition from conventional therapies such as radiation and chemotherapy. Far more insecure is the future of molecular electronics. Despite its seductive prospects, researchers fear it may never be able to compete with silicon chips on which the electronics industry spends billions of dollars every year.

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