Steroid molecules are composed of four carbon rings fused together with
various chemical groups attached. Animals have the right equipment to make these
compounds easily, but for chemists it’s a tougher proposition. The formation of
each ring leads to unwanted by-products that have to be separated off before
another ring can be added.

Gerald Pattenden and his colleagues realised that a type of molecule called a
trienone has the right geometry to form four rings in a chain reaction. The
molecule they chose has an oxygen atom at one end, plus three reactive
carbon-carbon double bonds and a cyclopropane group—a ring of three carbon
atoms—strategically placed along a chain of carbon atoms.

To kick the reaction off, Pattenden’s team uses a radical initiator—an
uncharged molecule with a spare electron. This molecule sends an electron from
the carbon next to the oxygen atom towards the cyclopropane, via the double
bonds. This forms two rings at the oxygen end. The spare electron, which ends up
near the cyclopropane, then unravels this group to form a large third ring. In
the final step, a bridge forms across this large ring to leave the four rings
characteristic of steroids (Chemical Communications, 1998, p 311).

“This is certainly an elegant achievement,” enthuses chemist Dennis Curran of
Pittsburgh University in Pennsylvania. “They may be able to make a whole host of
steroid isomers, including natural ones.”

Pattenden has already made a seven-ring steroid, and is working on an 11-ring
version. “If we can start the cascade at one end and then make it double back on
itself, we might be able to make sheets of rings,” he says. “It might even lead
to new materials such as modified fullerenes.”

Benzyne makes a fleeting appearance in reactions used in industry to
manufacture anything from drugs to explosives. Knowing its structure will help
scientists to fine-tune conditions so that the reactions happen more
efficiently.

Benzyne consists of a ring of six carbon atoms, to which four
hydrogen atoms are attached. żěè¶ĚĘÓƵs have suspected that it contains a
strong, short triple bond between two of the carbons. The molecule appears
fleetingly when ultraviolet light liberates carbon monoxide from a molecule
called benzocyclobutenedione.

Ralf Warmuth, working at the University of California at Los Angeles, mixed
this compound with a hollow, cage-like molecule called a hemicarcerand. When
hemicarcerand is heated, gaps appear in the cage structure, allowing a single
benzocyclobutenedione molecule to squeeze inside. As the mixture cools to room
temperature, the cage closes up, trapping the molecule inside.

Warmuth created benzyne by cooling the cage and its contents to around
–80 °C, and blasting it with ultraviolet light. He then looked at the
structure of its bonds, using nuclear magnetic resonance spectroscopy. “The cold
stops the product reacting with the cage walls just long enough,” he says.

In the current issue of Angewandte Chemie (vol 36, p 1347) Warmuth
reports that rather than containing a triple bond between two of the carbons,
benzyne has three weaker, longer and more unstable double bonds between four
carbons. “The next step will be to crystallise the prisoner in the cage to get
an exact structure,” he says.

Warmuth adds: “There are hundreds of other reactive intermediates with highly
strained multiple bonds just waiting to be trapped and studied in cages.”

While studying the chemistry of gold, Alan Balch of the University of
California at Davis made a compound in which three gold atoms and three organic
units form a ring-shaped molecule. This “organogold” compound emerges from
solution as tiny colourless crystals. When his colleague Ella Fung filtered off
the solvent and washed the crystals with chloroform, she noticed eerie flashes
of intense yellow light.

“Ella came to my office, somewhat shaken by her observation,” says Balch. “So
we called a halt to the experiments, and with Jess Vickery we set about finding
out what was going on.” Balch’s hunch was that the organogold crystals must have
absorbed ultraviolet light from the overhead fluorescent lamps in the laboratory
and that the solvent had somehow liberated the energy.

To test this theory, the team prepared the crystals again and deliberately
gave them a flash of light from a UV lamp. This time when they poured on solvent
they saw a much brighter glow (Angewandte Chemie, vol 36, p 1179). They
also discovered that the glow was very strong with chloroform and
dichloromethane, but very weak with water.

To find out exactly why the crystals glow, Balch’s colleague Marilyn Ormstead
used X-ray crystallography to work out the precise structure of the crystals. It
turns out that the gold rings stack together like a pile of coins.

However, each crystal has tiny imperfections or “holes”. Balch says it is
likely that the UV light ejects electrons from certain atoms, and that the
electrons then become trapped in the holes. But when the electrons come into
contact with a solvent, they can flow through the crystallised stacks and are
recaptured by the atoms, releasing energy as photons of visible light.

Some crystals glow when they are squeezed, and others emit light after
exposure to gamma rays. But this is the first time chemists have triggered
fluorescence using a solvent. Balch says this peculiar effect could be put to
use in detectors for potentially hazardous solvents. Prasanna de Silva, an
expert on sensors at Queen’s University in Belfast is fascinated by the finding.
“The phenomenon is very interesting indeed, and has potential for sensing
solvent vapours where a power supply cannot by used for reasons of isolation or
hazard,” he says.

Balch also believes that eventually, the compound could act as a
“rechargeable” energy storage system. Energy could be stored by repeatedly
shining UV light on the compound, and then released by adding a suitable
solvent. “I certainly expect small-scale devices,” says Balch, “but we are far
from them at this early stage.”

Sea creatures use calcium carbonate dissolved in seawater to make their
shells. They cement these mineral building blocks together with organic polymers
such as proteins, polysaccharides and phospholipids on the membranes of their
cells. The organic polymers act as templates for the crystallisation process,
but it is still a mystery how animals produce shells that follow mathematical
functions such as logarithmic and Archimedean spirals.

Chemists interested in biomineralisation have been able to synthesise
shell-like materials for a decade or more (“Crystal engineering: the natural
way”, żěè¶ĚĘÓƵ, 10 March 1990, p 42). But producing the
three-dimensional structure of shells is more difficult. Now Geoffrey Ozin and
his colleagues at the University of Toronto and Neil Coombs of Imagetek
Analytical Imaging, also in Toronto, report creating a random collection of tiny
shells on a synthetic beach (Advanced Materials, vol 9, p 662).

The Canadian team used tetraethylsilicate, a material based on
silica—the stuff of sand—in place of calcium carbonate, and a
soap-like surfactant called cetyltrimethylammonium chloride instead of the
organic polymer templates. They mixed these in water with a little hydrochloric
acid to catalyse the reaction and, over the course of a week, shell-like
structures emerged spontaneously.

With help from Fred Neud, also at the University of Toronto, the scientists
took scanning electron micrographs of the shells as they formed. Their pictures
reveal numerous spirals and what Ozin describes as “gyroid” structures, where
two spirals are joined base to base. The images also show that the synthetic
shells have corrugated ridges, channels and protuberances— much like their
natural counterparts.

“We have the first recorded synthetic examples of shell shapes and a good
idea of how they form,” says Ozin. He believes each tiny shell begins life as a
hexagonal, cylindrical liquid crystal which then evolves into a spiral or gyroid
form as the silica-based molecules are cemented together with varying degrees of
curvature. The early stages of real shell growth could be seeded from similar
structures, says Ozin.

Steven Mann from the University of Bath, who is also working on creating
inorganic structures, thinks the work could be very important. “Inorganic
compounds usually form regular geometrical crystalline shapes,” he says. “Ozin
seems to have succeeded in making a huge range of shapes from inorganic
ł¦´Çłľ±č´ÇłÜ˛Ô»ĺ˛ő.”

Mann believes that Ozin’s technique has the potential to create chemicals
with specific shapes rather than random grains of powder. This would
revolutionise areas as far afield as catalysis and separation of bacterial cells
for analysis. It could even make surgical implants more biocompatible.

Fraser Stoddart and Matthew Fyfe of Birmingham University and their colleagues interwove molecules using a process from “supramolecular” chemistry. Here chemists rely on the fact that some molecules join up like pieces of a jigsaw, just as two single strands of DNA join to form a double helix only if matching pairs of bases are in suitable positions to link up.

Chemists have already made self-assembling molecules that use one kind of recognition site, or “motif”. For instance, several years ago, Stoddart and his colleagues managed to thread ring-shaped molecules onto strand-like molecules (żěè¶ĚĘÓƵ, Science, 14 March 1992, p 18). This happened spontaneously because negatively charged oxygen atoms on the rings are attracted to positive ions on the strands.

Now the researchers have taken the process further. “We are now mixing the motifs to create more intricate designer materials,” says Stoddart. Making use of two types of molecular recognition, they have encouraged molecules to interlace to form a “woven” polymer.

They started with ring-like molecules called crown ethers, which they threaded onto strands containing a positively charged ammonium ion carrying two carboxyl (COOH) groups. They mixed the two components in solution and let the solvent slowly evaporate. Within days, crystals of a supermolecule formed. The team reports in the latest issue of Angewandte Chemie (vol 36, p 735) that the carboxyl groups on the ends of the “threads” locked together as hydrogen bonds formed between them.

According to supramolecular chemist Ed Constable of the Institute of Inorganic Chemistry in Basel, Switzerland, this technique takes chemists one step further towards reproducing the ingenious chemistry of nature. “Biological molecules are assembled making use of myriad different recognition events,” he says. “Chemists are learning from biology.”

George Whitesides, Dong Qin and Younan Xia produce their light valves by
polymerising dimethylsiloxane while it is in contact with a silicon surface
etched with microscopic pyramid-shaped pits. The resulting plastic sheet has
tiny raised pyramids on its surface which make it opaque. Applying pressure to
the tip of a pyramid deforms it and lets light pass through its base. Xia says
the switching happens in less than a millisecond.

In a large TV screen, each pyramid could be illuminated with either red,
green or blue light. Piezoelectric crystals attached to the pyramids would
squeeze them in response to the TV signal and let the necessary light
through.

According to Ralph Nuzzo, an expert in the chemistry behind display
technology at the University of Illinois at Urbana-Champaign, the technique
offers advantages over screens assembled from thousands of tiny units. Once the
patterned silicon surface has been made, large numbers of plastic screens could
be “printed” straight from it. “You do all the tough stuff only once,” says
Nuzzo.

The amount of light transmitted by the polymer could also be used to measure
pressure. And squashed light valves in smart windows could be depressurised at
night, turning the windows opaque and doing away with the need for blinds.

Chemists have used porous minerals called zeolites for many years as
molecular sieves for separating molecules—only small molecules with
certain shapes can fit through the holes. Zeolites can also be used to trap
molecules so that they can be analysed. Alternatively, they can act as catalysts
and speed up chemical reactions. This is because when a molecule is trapped in a
small space, its structure may change slightly in a way that makes it more
reactive.

Zeolites, however, come with a limited range of pore shapes and sizes which
restricts their versatility. Chemists would like to create “designer zeolites”,
solids with tailor-made pores for a wide range of uses.

Now Richard Weiss and his colleagues at Georgetown University in Washington
DC have found a way to make gels that harden into porous materials. They have
found several gelling agents, such as tetraoctyldecylammonium bromide (TOAB),
which can turn organic compounds into jelly.

The researchers mixed TOAB with a brew of either styrene—the building
blocks of polystyrene —or methyl methacrylate, which is used to make
Perspex. They added a polymerising agent, then heated the mixture until the
solids dissolved. As the mixture cooled, the TOAB molecules formed a mesh,
creating a gel. Next, they blasted it with ultraviolet light to trigger a
polymerisation reaction that made the gel solidify.

By heating the gel in an alcohol solvent, they were able to boil off the
stringy TOAB molecules, leaving a solid material with micrometre-sized channels
and pores where the TOAB had been. Weiss says that in future, this kind of
material could be used in the same way as zeolites.

“We have demonstrated the principle,” says Weiss, “but to put it into
industrial practice will require a lot of engineering.” Unlike zeolites, the new
materials break down at high temperatures. But with more work, Weiss hopes to
tailor the size and shape of the channels so that they can be put to use as
low-temperature “sieves” and catalysts in a wide range of reactions.

Martinus Feiters and his colleagues at the University of Nijmegen have
developed a similar technique using compounds called gluconamides as gelling
agents. Both teams describe their results in the latest issue of Chemical
Communications (issue 6, p 543 and 545).

AS WE approach the end of the millennium, is the end of the world nigh? War
and political strife confront us at every turn, ominous comets streak the sky
and our food is tainted. To top it all, a new breed of diseases is about to
overwhelm us.

Consultant physician Frank Ryan describes the real threat of the coming
plague. High in the mountains of New Mexico in May 1993, a mysterious virus
began to attack the Navajo population. Almost every one of the 13 victims of the
initial outbreak died within a few hours of contracting what turned out to be a
new strain of hantavirus. More cases have been cropping up in the region. Most
worrying is that the disease is carried by a widespread American rodent, the
charmingly named deer mouse.

Ryan takes us through the drama of discovery, the people, the high-security
research establishments, the uncoiling of viral RNA and the eventual pinning
down of a new species—though this is a kind of biodiversity we can do
without.

Emerging infections are not new. But the newer intruders do seem to be
getting a grip; more people are suffering from encephalitic and arthritic
viruses, haemorrhagic fevers, diarrhoea-causing infections, human T cell
leukaemia virus, Legionella, Lyme disease, toxic shock syndrome, HIV,
flesh-eating bacteria and Ebola. Add to this the growing threat posed by the
evolution of drug resistance in pathogens such as the tuberculosis bacterium,
and one is soon persuaded that plague is fast becoming the most threatening of
the Four Horsemen of the Apocalypse.

Ryan challenges the notion that certain questions are too appalling to
contemplate. They must be faced. The most alarming is whether the whole human
species is under threat from a pandemic virus or bacterium. As we encroach on
the last remaining acres of wilderness in the world, will a new virus, the
equivalent of an airborne HIV, say, sweep us into oblivion?

We may hope that most of these new infections will behave as recent outbreaks
of Ebola, Legionella and Lyme disease—and even Escherichia coli
—have done so far, restricting their life cycles to a closed shop of
unlucky individuals. But Ryan is certain of one thing: the Universe is not
benign and we must do everything in our power to mitigate the danger.

Hundreds of drugs, such as the painkiller ibuprofen, are chiral compounds. In other words, their molecules can exist in two forms-one left-handed, the other its right-handed mirror image. Because the body’s receptors and enzymes are themselves chiral, the different forms can have dramatically different effects. Left-handed ibuprofen, for instance, is three times as strong as its counterpart. In other drugs, the mirror image may have dangerous side effects.

Chemists would like to be able to create just one form of such drugs in order to reduce the dose or banish their side effects. But the alcohols that are a common building block of many drugs can often only be produced as a mixture of both forms. And because the two forms are chemically identical, they are very difficult to separate.

Now Ryoji Noyori of Nagoya University and his colleagues at the Research and Development Corporation in Toyota report in the latest issue of Angewandte Chemie (vol 36, p 285) that they have made a catalyst that can do the trick. The catalyst, a compound that contains the metallic element ruthenium, is relatively easy to make.

The ruthenium complex is itself chiral, allowing it to grab hold of a hydrogen atom from only the desired chiral form of an alcohol, turning it into a ketone (see Diagram). The unwanted form of the alcohol is left behind unchanged, and can be chemically removed. When the researchers reverse the reaction, the catalyst returns the hydrogen to the ketone to give only the desired alcohol form. The chiral alcohol is 98 per cent pure, which is very high for such a simple and cheap method.FIG-mg20742401.GIF

The team reports that the reaction works well with many alcohols. “Our asymmetric catalyst is among the most versatile,” says Noyori. His team has prepared one chiral form of an immunosuppressant used to discourage the rejection of transplants. “But it is still at an academic level,” he adds.

Graham Hutchings of the Leverhulme Trust in Liverpool says the catalyst is a promising method for separating the molecules. “This appears to be a very neat way,” he says.