Blacksburg, Virginia
DAWN in Blacksburg, Virginia. As the first rays of the Sun creep over the horizon, billions of nature鈥檚 tiny power plants kick into action. In these small molecules, photons of light from the Sun begin to power the chemical reactions which are essential to life. Meanwhile, in my laboratory, the photons are just in time to kick-start my latest molecular machines.
Almost everything on Earth ultimately depends on the Sun for the energy to keep going. Photosynthesis allows green plants to grow by transforming carbon dioxide and water from the atmosphere into organic compounds, producing the biomass that sustains almost all animal life on the planet. But while nature pulls energy directly from sunlight, humans go about things the hard way, digging up coal and drilling for oil and gas-obtaining the energy second-hand.
Solar power is one alternative. Photovoltaic cells can transform sunlight into electricity, but this electricity then has to be fed into other machines to, say, make important chemicals. It would be better to cut out the middleman and copy nature-build our own tiny light-powered chemical factories. So that鈥檚 exactly what chemists are now doing. One of the aims is to use sunlight to generate limitless supplies of green fuel from air and water. Another is to design anticancer molecules that, when activated with laser light, will destroy tumours-while causing fewer unpleasant side effects than some of the drugs currently in use.
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Persuading photons to do useful work presents a challenge. First you鈥檝e got to catch them, then you鈥檝e got to convert their energy into a usable form, and finally, you have to transfer the energy to where it is needed, and make it carry out the desired task. Amazingly, many of these tasks can be performed by a single molecule of the latest synthetic compounds, mimicking the success of nature鈥檚 chemical plants. My group at Virginia Tech and other teams of researchers are now creating synthetic molecules that, when flooded with light, have the potential to carry out a wide range of tasks, such as synthesising useful compounds, generating clean fuels or attacking tumours.
Big is beautiful
The chemicals to carry out these diverse tasks, known as supramolecules, are big. They are made from several distinct units, each with a particular job to do. For example, one unit might absorb photons of light, another transfer the photons鈥� energy, and a third carry out chemical reactions. Because these units can be built separately before being chemically 鈥渃lipped鈥� together, supramolecules are incredibly versatile. Chemists can mix and match the units to create supramolecules that are tailor-made for particular tasks.
One thing all these supramolecules have in common is a light-absorbing unit-essential for receiving photons and soaking up their energy. 鈥淟ight is not a very effective form of energy,鈥� says Devens Gust of Arizona State University鈥檚 Photosynthesis Center. 鈥淚t needs to be converted to other forms.鈥� Some supramolecules do this by 鈥減hoto-initiated charge separation鈥�. The light-absorbing unit captures a photon, and the energy is used to shift an electron from one part of the supramolecule (an electron donor) to another (an electron acceptor). This gives the donor a positive charge and the acceptor a negative charge, and these are stabilised and held apart. The molecule becomes a tiny battery. 鈥淭his preserves some of the photon鈥檚 energy as electrical energy,鈥� says Gust.
Together with his colleagues Thomas Moore and Ana Moore, and postdoctoral associate Gali Steinberg-Yfrach, Gust is using supramolecules to build a molecular-scale solar power plant that emulates the way living organisms generate energy. The Arizona team has built a system that pumps protons into hollow spheres of fatty molecules, called liposomes (see Diagram).
Their supramolecule sits in the membrane of the liposome and generates positive and negative charges when it absorbs light. A porphyrin unit (P) in the supramolecule captures photons and transfers electrons to a naphthoquinone unit (Q) at one end of the molecule, while the positive charge is stabilised on a long carotene chain (C) at the other end. The negative charge is transferred to a carrier molecule (Qs) that then grabs a proton from the surrounding water and drags it inside the membrane. The positive charge from the other end of the supramolecule is then transferred to the carrier molecule, which releases the proton into the water inside the liposome, making the water acidic.
This sets up a 鈥減roton gradient鈥� between the inside and outside of the liposome that is a form of stored energy. The energy can then be released to drive biological processes. Photosynthetic bacteria, for example, use a flow of protons across the cell membrane to drive the synthesis of adenosine triphosphate (ATP), the molecule that carries energy around living organisms. 鈥淥ur synthetic system also produces biological energy in this way,鈥� says Gust. 鈥淭he next stage of our work will be to combine our liposomes with the enzyme ATP synthase to artificially produce ATP using solar energy.鈥�
Jean-Pierre Sauvage from the University of Strasbourg in France is also building supramolecules containing porphyrin light-absorbing groups. By combining these with other light-absorbing groups based on ruthenium atoms, he has produced very stable charge separation-a stable molecular battery. This gives more time to use the electrons generated before the charge dissipates. Vincenzo Balzani of the University of Bologna in Italy has built similar light-harvesting systems that use ruthenium and osmium complexes to capture photons (鈥淕reener way to solar power鈥�, New 杏吧原创, 12 November 1994, p 30). These are very efficient at generating positive and negative charges and funnelling the energy to specific locations within the supramolecule.
Charge separation is all very well if you only need one electron to drive your reaction. But suppose you need more than one? This problem is being tackled by my group. We are building photo-initiated electron collectors-groups that will stockpile negative charge. These electron collectors can also take on the role of reaction sites, allowing us to design supramolecules to carry out many chemical transformations.
Supramolecules that collect electrons are complicated devices. The collector needs to be attached to two or more light absorbers through a bridging unit. And to provide the positive charge generated by charge separation with somewhere to go, each light absorber must also be joined to an electron donor group that stabilises the charge. Bringing together electrons at the collector also poses problems. Negative charges repel each other and this might prevent further electrons reaching an already negatively charged collector. In addition, the first electron to reach the collector might change the chemical bonds around the unit and disrupt the paths of other incoming electrons.
Charging up
My group has overcome these problems to design the first functioning molecular device for photo-initiated electron collection. We were able to spatially separate two light-absorbing units, allowing them to work independently. Students Sharon Molnar and Girlie Nallas Sison built a supramolecular system in 1994 that consists of two light-absorbing units coupled to a central electron collector via two bridging units.
Our system consists of two ruthenium-based light absorbers, each of which captures a photon and sends an electron to a central iridium-based collector. The electrons are transferred by two bridging groups that act both as connector units and as sites to hold electrons next to the iridium atom. Although it is a fairly simple system, this supramolecule proved that electrons can be collected in a single molecule-a major advance in supramolecular chemistry. And because these supramolecules are simply different units clipped together to perform a function, we have since been able to modify our design by swapping the chemical groups used as light absorbers and electron collectors.
This breakthrough means that new reaction sites can be designed and plugged into the supramolecule. When an electron collector is 鈥渇ull鈥�, it can act as a site for chemical changes. Many different reactive sites can be hooked up. 鈥淥nce the light absorption and electron transfer system is in place,鈥� says chemist Thomas Meyer of the University of North Carolina at Chapel Hill, 鈥渁lmost any molecular-level catalyst can be incorporated.鈥�
Elizabeth Bullock, who is part of our team at Virginia Tech, is designing groups that, having collected electrons, change shape. This could open up the reactive site in a supramolecule, making it accessible to small molecules. We might even be able to produce a site of a specific shape and size. One of our goals is to design sites that will behave like an enzyme, selectively reacting with only one molecule.
Losing connections
The latest supramolecules feature an atom of the metal rhodium as the electron collection and reaction site. A single atom might not seem to offer too many shape-changing possibilities, but the overall shape of the molecule depends on how many other groups are bound to the rhodium atom. This can change when the rhodium atom collects electrons.
Like all metals, rhodium atoms鈥� appetite for having groups attached to them depends on how many electrons they have. In our supramolecule, the rhodium atom prefers to have six bonds with other groups. But after electron collection it now prefers to have only four bonds. As a result, it disconnects two of the original groups. Depending on which groups are disconnected, the shape of the whole molecule can change.
After it picks up two electrons, the rhodium atom in one of our supramolecules loses two chloride groups, leading to a dramatic change in shape. Instead of forming a three-dimensional complex around the rhodium, the attached groups now form a flat molecule (see Diagram). The rhodium atom becomes accessible to small molecules, and can use its two spare electrons to catalyse a chemical reaction.
We are designing supramolecular systems based on this idea that will catalyse the production of clean fuels using sunlight. Some of the rhodium and iridium supramolecules we have designed can break down carbon dioxide to produce carbon monoxide. The chemical transformation is caused by the two electrons on the rhodium or iridium atom jumping onto the CO2 molecule. A similar process can break down water molecules to generate hydrogen. We are looking at producing supramolecules containing platinum to catalyse this reaction.
Both carbon monoxide and hydrogen can be burnt as clean fuels, producing only carbon dioxide and water respectively. In fact, our molecules might even be used to convert seawater directly into hydrogen, generating fuel from a virtually limitless resource. Meyer is also working on similar light-powered chemical reactors that could produce oxygen and hydrogen from water. He also sees more complex reactions being possible, for example to produce epoxide compounds, which are used in glues and polymers. 鈥淭hese are appealing targets since we have already developed well-defined molecular catalysts,鈥� he says.
Clearly, to make the molecule carry out the desired chemical changes, it is vital to pick the right reaction site. But this is not the only part of the supramolecule that my group is modifying. The humble bridging groups that connect the light-absorbing units, electron donors and electron collectors can also play a useful role. We are currently working on a supramolecular anticancer agent that uses a bridging unit to bind to DNA in tumours.
Matt Milkevitch, Pat Boyer and Lee Williams in my group, in collaboration with biologist Brenda Shirley, are building molecules containing three units linked to each other-a light-absorbing unit, a bridging unit and an active site. We hope these devices will work as light-absorbing anticancer agents, attacking tumours when they are irradiated with light.
The bridging unit is designed to allow the supramolecule to bind weakly to a strand of DNA before the active unit attacks. The bridging unit does this by 鈥� intercalation鈥�-a type of stacking interaction that can occur between large flat molecules and the DNA double helix. The helix is like a twisted ladder, with rungs made from the base pairs which encode genetic information. Our unit is designed to slide in between two rungs of the ladder.
Attacking tumours
W. Rorer Murphy Jr of Seton Hall University in South Orange, New Jersey, has shown that metal complexes of the bridging unit we use can intercalate very rapidly into DNA. This weak, reversible intercalation localises our supramolecules at the tumour, and holds them there long enough for us to use light to activate a slower binding step between the DNA and the active site.
Our active site has a platinum atom at its heart, similar to the active component of the anticancer drug cisplatin. The platinum atom is attached to two chlorine atoms that are lost when the platinum binds to DNA. Losing the chlorine atoms is the difficult bit. However, since we have already been able to make the rhodium reaction site in another of our supramolecules lose two chlorine atoms when it absorbs light, it should be possible to make our platinum-based anticancer system do the same.
This is where the light-absorbing unit comes in. By clipping it to the bridging unit, we could design supramolecules that bind to DNA only after activation with light. These drugs would only be 鈥渟witched on鈥� at the tumour site by exposure to laser radiation-the resulting strong bond between the platinum atom and the DNA bases would prevent the DNA unzipping and replicating, and so stop the tumour cells multiplying. This would be a major advance in platinum-based drugs as it could eliminate some of the toxic side effects caused when they attack healthy areas of the body.
Another advantage of our systems is that they can be activated by a broad range of wavelengths. We can 鈥渢une鈥� light absorbers to capture photons at certain wavelengths, so it should be possible to activate these supramolecular anticancer drugs with near-infrared light. The body is more transparent to near-infrared light than to visible light, so a near-infrared laser could be used to activate the drug at tumour sites deep within the body.
From light-activated anticancer drugs to miniature light-powered chemical plants, the number of uses for supramolecular systems is expanding rapidly. Chemists are also increasing the range of components that can be clipped together. Dawn in Blacksburg could soon see a whole new range of synthetic molecular factories swing into action.
