There has always been a strong urge among scientists to learn from nature — to replicate natural processes, recreate natural environments or grow naturally-occurring substances. Nature is known to function in an effective, efficient and sustainable manner. Mimicking nature is expected to bring in effectiveness and sustainability in man-made processes and products as well.
But nature also has vast resources at its command that provide the enabling atmosphere to achieve efficiency or sustainability. That enabling atmosphere is not always easily accessible to human beings without incurring a cost.
For example, there are several naturally-occurring enzymes that facilitate complex biochemical reactions in living organisms during which a particular desirable molecule might be produced.
Human beings can replicate some of these reactions in laboratories or even on an industrial scale, to produce the same desirable molecule, but for that to happen, they first have to access those enzymes. Producing those enzymes can add several layers in the original objective of reproducing the biochemical reactions to get the desired molecule. This is time-consuming and can lead to wastage and cost escalations.
This year’s Nobel Prize in Chemistry has gone to three scientists who, through their work, have made a strong case for adopting an alternative approach to producing new complex molecules in the laboratory or industry, which minimises waste and increases overall efficiency.
Carolyn Bertozzi and Barry Sharpless of the United States and Morten Meldal of Denmark have been given the Prize for developing the relatively recent field of ‘Click Chemistry’ and demonstrating its vast potential in the pharmaceutical and other industries.
“Click these days is most commonly associated with a mouse click. Well, this has got nothing to do with that. The name has instead been taken from the click sound that airline seat belts make when they are fastened. The idea is that while trying to produce any particular compound or a complex molecule, one must look for starting molecules that easily react with each other. In other words, look for molecules that easily fit into each other, or ‘click’ with each other. It makes the resultant chemical reaction more efficient,” said Sayam Sen Gupta, a professor of chemical sciences at IISER Kolkata who has worked in this field and collaborated with Sharpless in the past.
Sharpless, who is the originator of the concept of ‘Click Chemistry’, has now won the Nobel Prize for the second time, making him only the fifth scientist to achieve this distinction. His previous Nobel Prize had come in 2001 in recognition of a different kind of work.
Around the same time that he won his first Nobel, Sharpless, along with a few collaborators, published a paper making a case for adopting a simpler approach to carrying out chemical reactions, even if that meant junking the methods that mimicked nature.
He emphasised on the need to replicate nature’s efficiency, not necessarily its processes, or even products. It was fine even if ‘Click Chemistry’ was not able to produce the exact molecules found in nature. It would be adequate to synthesise other molecules that performed the same functions, Sharpless argued.
“Those days he used to give a lot of talks on this new idea of his. And at many places, he used to carry an airline seat belt to demonstrate what he meant by getting the right fit of reactants. The reacting molecules should be in a made-for-each-other kind of situation for this particular reaction, so that the reaction was irreversible and 100 per cent efficiency was achieved,” Sen Gupta said.
Sen Gupta explained why the idea of ‘Click’ Chemistry is so appealing. “In the pharmaceutical industry, for example, which uses a lot of naturally occurring but industrially synthesised molecules, every kilogram of a drug produced results in the generation of nearly 25-100 kg of chemical waste. This is clearly not an efficient outcome,” he said.
Sharpless was not just developing the ideas or identifying the criteria that would qualify a reaction to be called ‘Click’ reaction. He went ahead and found the first chemical reaction that satisfied the criteria he had laid out for ‘Click’ reactions.
It was a modification to a chemical reaction that had been known for 40 years. This reaction was meant to produce a nitrogen-containing cyclic compound that was used as a building block for a variety of molecules in the drug industry. The usual process also produced several by-products. However, Sharpless discovered that the use of copper as a catalyst eliminated the by-products altogether and only the desired chemical was produced.
Interestingly, around the same time, this discovery was also reported by Morten Meldal, a Danish scientist working independently on some pharmaceutical substances. Meldal’s discovery was accidental, but once he realised the implications, he experimented with other molecules as well, and obtained quite a few successes.
These initial successes generated a lot of interest, and several other ‘Click’ reactions were found by different researchers. The next big breakthrough in this field came a few years later, when Carolyn Bertozzi showed in 2004 that ‘Click’ Chemistry could work in the chemical processes happening in the living cells as well. She went on to develop a few ‘click’ reactions that work inside living organisms.
Bertozzi’s methods, which she has repeatedly refined over the years, have shown the promise of treating advanced cancer. Cancer drugs based on her approach are now undergoing clinical trials.
The Nobel Prize committee said that the work of the three scientists, besides being “elegant, clever, novel and useful”, also sought to bring the “greatest benefit to humankind”.
“This year’s Prize in Chemistry deals with not overcomplicating matters, instead working with what is easy and simple. Functional molecules can be built even by taking a straightforward route,” Johan Aqvist, the chair of the Nobel Prize Committee for Chemistry, was quoted as saying in the official statement.