Click Chemistry: On atoms and molecules

Chemistry means molecules, physics is what happens between molecules. Together, they form life’s fundamentals,” he says.
Morten P Meldel and Phaedria Marie St HIlaire.
Morten P Meldel and Phaedria Marie St HIlaire.

CHENNAI: They click. Morten P Meldel and Phaedria Marie St HIlaire.

Not just as husband and wife but as humans working in their respective spheres.

While Phaedria, who calls herself ‘stubborn’, used her sense of justice to work among women of colour in Denmark and the Nordic countries, what inspired the calm, musically-inclined Morten was the structural beauty of organic compounds. “To me, it is all atoms and molecules bound together in a system that captures the sun’s energy and comes to life. Chemistry means molecules, physics is what happens between molecules. Together, they form life’s fundamentals,” he says.

The Nobel laureate’s love for chemistry stemmed from the time he spent as a kid in farms his family owned. The visuals of natural objects and the geometry behind them bemused him, got stored in him as indelible memory, and urged him to explore deeper the intricate chemistry that bound the elements together. “It gave me joy to think of chemistry this way and has always kept me joyful,” he says.

What also caught his eye was the astounding harmony in the organic bonds. Such a sense of inquisitiveness and visual memory led him towards click chemistry for which he won the Nobel Prize in Chemistry in 2022 with US scientists Carolyn Bertozzi and Karl Barry Sharpless.

Click, as the name sounds, is a kind of a game of lego where the molecules are bolted together to form organic conglomerates. The molecules are ‘clicked’ together in such a way that there are no residues like in a natural chemical process. The developing branch of chemistry has several applications, in pharma, to address climate change, and for targeted medical interventions for crucial diseases.

Morten’s analysis of how nature makes its compounds and how they can be replicated in a laboratory also reflects his inclusiveness where he finds a way to bring people to a unified forum where they could function together. “This is the reason why we are together,” says Phaedria, who founded the Professional Women of Colour network in 2019 that addresses issues among women of colour, minorities in Europe, and helps them merge with the larger Danish society which has reservations in accepting people from diverse backgrounds.

Chemistry, like music, manifests the elemental unity in nature, according to Morten, who loves music enough to make the instruments he plays. This is also the reason why he helps talents from different cultures find forums in Denmark where they can work to their full potential. “Nature’s chemistry is a symphony. Humans need to align their tunes to that,” he says, explaining the philosophy that led to his research. “Our discovery arrived as we were working individually on the topic. Soon, we found our research study expanding to bring about such a pioneering turn in science that could show us several new doors into the study of many natural chemical formations even inside the human body.”

For Morten, the Nobel Prize is a way to reach out to the authorities and press upon them the need to notch up the prospects of scientific study into organic chemistry. To Phaedria, her husband’s Nobel is a way she can further communicate the organic need for equality. “So, laurels are just platforms to let your voice be heard, but what is important are the values that go behind your work,” they say.

Morten and Phaedria were in Thiruvananthapuram to attend the ongoing one-month-long Global Science Festival of Kerala. Their tour also included lectures to students and researchers at IISER and Kerala University where Morten spoke of the relevance of an ecosystem, internal and external, that could help in deep study of sciences.

‘India has a great environment for research’

Is the Nobel for the work on Click and bioorthogonal a recognition of resurgence of pure chemistry?

Indeed. It is a ‘return to the roots’ kind of scene. We have had biochemistry taking over anything related to chemistry research, and institutes who claimed themselves to be doing research in chemistry were in fact working on biochemical or biotechnological questions. I feel such institutes should call themselves biotechnology institutes rather than chemistry research centres.

In such a context, our team’s findings helped bring the stream science back to its elements. We are now looking deep into molecules, finding designs of their structure, working with it, and even going ‘nano’. So there is a resurgence of pure chemistry where the molecule is the base material.

How do you see your finding as — a pure chemistry one or an applied one?

It is elemental, but has path-breaking applications. A study into the molecules and its structures led to us finding that molecules can be brought together to form units that can be ‘clicked’ together with bolts. And this can be used as what you may call ‘molecular robots’ that act like controls to set right many aberrations in biological systems that have so far remained impenetrable, like inside the organs, inside the cells, etc. Such a study of its applications is going on especially to treat illnesses such as cancer, where targeted treatment is the key. We are not there yet, but pacing up towards it. So click combines molecular functions and sets the scene for biological processes. So it can be used in all natural sciences and medicine.

How did the finding come about? Was it the aim or was it something found in the way that changed the scene?

Such discoveries are not planned. Serendipity is a very huge part of science. We cannot expect something to happen. We spot them because we keep our eyes open. And that is the biggest value a researcher should have. Observation. And then empathy to understand why it should be pursued for a larger good. Then of course, there should be the courage because without that, the change in path cannot be traversed. I value these in my team more than factual knowledge.

In our case, we worked independently, but our work complemented one another’s. The copper catalyst that I used to bolt the molecules in the first click reaction based on the concept was modified into a sugar-based one so that it could be used in human interventions. So there was chemistry between our individual works that yielded the ‘click’.

Why should young researchers focus on pure chemistry?

The challenges we face today are the indicators of where work needs to be done. If we combine those challenges, that will help define framework of our studies. The generation to which I belong cannot solve some of these challenges, say the environmental one. But there are lots to look deep into about how to tackle the problems. Lot of work is needed in areas that are important for the future such as sustainable materials, textiles, energy, transport, food. You have to search at the elemental level for these, and for that there is a need for children to be groomed to study chemistry by observation and understanding the geometry of things around. New age technologies like AI are not enough, and a lot of visualisation and imagination are necessary.

Good research happens because it comes from an inner thirst to know and the ability to bring varied experiences on the platform required. It is also essential to get out of our comfort zones once in a while.

How equipped are research centres and educational institutions to spearhead such studies?

My Nobel gave me a forum to initiate a communication channel with the politicians on how important such researchers are for the world and hence the need for them to be funded properly. In India, from my visits to higher education centres such as Indian Institute of Science, Education and Research (IISER), I found that there is great infrastructure and environment for research. Infrastructure is the alpha and omega of research and that is there for the young researchers to make good use of. It’s heartening that such institutions are being supported, which will pave the way for good work that will show results in about 20 years.

Europe, in fact, could learn from such models.

Morten P Meldel, professor at the University of Copenhagen, Denmark, was awarded Nobel Prize for the development of click chemistry and bioorthogonal chemistry along with K Barry Sharpless and Carolyn Bertozzi. Click chemistry is about snapping together molecular building blocks. Morten developed a chemical reaction termed the copper-catalysed azide-alkyne cycloaddition. The use of this finding is said to be path-breaking.

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