The Father of Supramolecular Chemistry: Jean-Marie Lehn

The Lindau Nobel Laureates meeting has been a fantastic opportunity to mingle with brilliant minds for all over the world who work in widely different areas of science. Yet as a chemist, there were certain interactions which I enjoyed far more than others. Once such interaction was the time that I spent talking to Prof. Lehn. 

I had 15 minutes to 'interview' Jean-Marie Lehn who shared the 1987 Nobel Prize in Chemistry with Donald Cram and Charles Pederson for their development and use of molecules with structure-specific interactions of high selectivity. Prof. Lehn is more commonly known as a father of supramolecular chemistry.

In his lecture that morning, Lehn was his usual charming self when he tried to explain to the people the importance of supramolecular chemistry. "Chemistry is a bridge between Physics and Biology. It tries explain how complexity arose particulate matter", he said with conviction. He then delved into explaining self-organisation and showed the beautiful structures that he has synthesised over the years by the use of weaker non-covalent bonds.

Chemistry is a bridge between Physics and Biology.

My 'interview' lasted well beyond 45 minutes and became more of an informal conversation just after a few questions. It was quite unnerving spending one to one time with a Nobel laureate but Prof. Lehn's personality made me feel at ease. I started with picking up on his mention of the term 'Darwinian Evolution'.

JML: I used the term but what I meant was that Darwinan evolution is limited to the biological aspect but before that happened the molecules themselves had to evolve to enable this further (biological) evolution. My point was to explore the idea of how did atoms come to be able to self-organise.

AR: : If we look at the chemistry of life today do you think there is way of improving it? For example, Nature does photosynthesis in a beautiful manner but the conversion is less than 1%. Do you think there is a chance to improve that?

JML: Sure. Once you look at the schematic representation of the reaction, you could think of ways to improve and perhaps write books on it. But to give you a shorter answer I think there are two approaches that we can take. 

Firstly, we can look at the way of improving the key biochemical processes photosynthesis itself. A lot of energy is lost to keep the plant cool. So maybe we can think of building plants which are more resistant to heat. Genetically modified plants can be one answer and we can imagine more efficient plants, call them ‘energy plants’. And I believe, contrary to what ecologists think, they can still be beautiful plants. 

The other approach is that nature has developed in the course of evolution what we know around us but it is only one expression we know about. Can we have another expression, a better one? So we still convert solar energy into chemical energy with better yield by a completely new process. 

AR: So is it something on the line of Prof. Szostak’s research on the origin of life where he is producing these artificial nucleic bases which can polymerise to form artificial DNA without the need of DNA polymerase? 

JML: No, not really. That is the biological way of doing things and it’s one way but I am thinking of chemical catalysts than can achieve conversion of solar energy into chemical energy. We have worked on that in the late 70’s to early 80’s after the first oil crisis to find catalysts which can split water and I think significant progress has been made. But now, that research has been left aside because oil has become cheap again. 

It is simple reaction and I am convinced that we will be able to do it. Yes but it is also these very simple reactions which can be very hard to master.

AR: Just like we can at least conceptualize the combination of covalent bonds that will lead to an organic molecule through total synthesis, can we have a retrosynthetic way of achieving supramolecular targets?

JML: I think we are already doing it. We call it design. So say we want to build a cylinder. What is a cylinder, two discs held apart by something. Now, (at the molecular level) we think about what can be used to make the discs and what can be made to hold them apart. Then we synthesise them and it works. For example, Makoto Fujita in Japan, Kenneth Raymond and Fraser Stoddart in the USA are all working on similar thing.

We can achieve this by manipulating properly the non-covalent interactions that bring atoms together. I call this the algorithm because it is not just binding but binding according to certain rules. In case of metal ions it is the rules of co-ordination chemistry, rather simple but it is, for me, the algorithm of reading. Even if some people don’t like this (term) because co-ordination chemists will think that co-ordination chemistry has been around for hundred years that that is correct but the way in which metal ions bind is an algorithmic way. A tetrahedron or an octahedron, it is an algorithmic way of reading information. Hyrdogen bonds? Nature has used them since the beginning of life, Adenine & Thymine and Guanine & Cytosine hydrogen bond at 2 or 3 locations and that’s an algorithmic way of binding.

You can also build more complex structures where you can have hydrogen bonds on one face and covalent bonds on the other face. The advantage of metal ions is that from one point it arranges the atoms around it in a certain manner. If we want to achieve the same with hydrogen bonds we need multiple sites. We can do it but it’s a bit more spread out and you need more matter, so to say, to achieve the same result.

So yes, I think we have an established way of achieving our targets. Actually, here is an analogy, a retrosynthetic analysis involves choosing a target and then breaking it down to pieces and in the process of reconstructing it you have reactions. Now in supramolecular chemistry, we do the same by cutting the target into pieces and then in the process of reconstructing it we have non-covalent bonds. 

Lehn enjoying stimulating lectures

AR: Like in Physics we have the CERN where people are working plain curiosity-driven challenges. Similarly, in chemistry what kind of research do you think we should do that we can’t see any applications for but is something that needs to be done?

JML: I have an easy answer to that. It’s not the only answer but it is one answer. So once a guy called me and told me that he is writing a piece in Nature on important problems in science. So he talked to physicists and they said they are studying the rules of the universe, which is a big problem no doubt. He talked to biologists and they said they are studying the rules of life, big problem. Then he asked, so what are chemists doing? I guess what he was trying to say is that we are making new molecules, new materials which is all very good but where is the big problem. I told him that chemist are actually looking at the biggest problems. I mentioned this in my lecture today. Einstein helped us understand some rules of the universe from the theory of relativity but how did this species called Einstein evolve who can think and achieve this for us? What is the process? I have the answer, it’s self-organization. And it is simple, if I may say so. By using the bricks of the universe (atoms) which were built by the laws of the universe we now have such complex organisms.

AR: So is it the origin of life research in chemistry which you’d classify under this category?

JML: No, actually before the beginning of life. The research of looking into how did we come from particulate matter to condensed matter to organised matter and then to life. These steps, we know that they exist because we exist. We realise that we are still very far from complexity of biological systems, very far. But Rome wasn’t built in day, right?

AR: We students are fascinated by these big questions and it may be one of the reasons we chose to do science but in the daily life in the lab the problems are different. We work on one reaction for days to make it work with little progress. How do you think students can deal with such situations?

JML: I think this is a very good question. And I am bit embarrassed when I talk this way because I know we have young students working in the lab and yes we have big ideas but then they also have to clean flasks and mix compounds. So I think we have to realise that there are lot of nitty-gritty things in the lab that we have to do every day but at the same time we have to realise that we are part of a big project to understand what’s going on (in the world), why we are here and how did we come about. 

AR: What motivated you in the lab during such phases?

JML: Let’s be honest. It were small steps. Being able to make the compound that you wanted to and realising that oh yes, I got it. But all this is part of the big picture. To the young people I’d say that you must focus. Think that you are part of a big construction called science and you are not just a chemist but you are scientist. Be modest but proud. Modest because you know you will not be able to solve other problems because your life is too short. But be proud because you are contributing to it. Some people will bring a small stone to the building and some people will bring a big one but nevertheless no one can take that stone away from you. Yes, you will be happier if you bring a big stone but not everyone has the right occasion or has the right person at the right place at the right moment to be able to do that. 

AR: Today, all of scientific research in countries like USA, UK, France and more is funded by less than 1% of GDP. Why is that number so low if science makes such a big impact on the progress of the nation? What can be done to change it?

JML: We are still apes and are fighting all around the world. We are in the prisons of dogmatism, fundamentalism and religion.  Let me say that clearly. We must learn to be rational. At the end of the game, what matters the most is education. 

AR: Is it just education though?

JML: Depends on what kind of education. We have to learn to be conscious of the people around. We also want to live well. I know it’s hard. I know that sitting around in these surroundings is real nice but there are people in cities that I do not want to mention who are living in terrible conditions. We have to grasp this. Thinking that let’s do away with armed forces is idealism because even if we should, we cannot.

AR: Because if we cut down on funding the department of defence then we can use that to do science. What is science doing to improve world peace? 

JML: I think we need to be patient (about achieving world peace). The pace at which science has progressed has been too fast for human behaviour to adapt to it. As I said we are still apes. A part of our brain is still a paleo-brain and many of reactions come from our fight or flight instinct. As long as this part of the brain can take over control the rational part of the brain (we will face these problems). Some people will jump up at what I am going to say now but I think at some point of time we will have to change our brains. 

AR: So do you believe in what Martin Rees has said “To be able to overcome the big challenges of humanity we will need a more evolved human being”?

JML: Oh yes. I totally agree with him. I have spoken a lot to him. We are a result of evolution at given point in space and time, why then should we be the end of evolution? We are obviously not. We are just a point but with a fantastic advantage. Thanks to science we now have been able to (gain) better understanding of how things work. So in the future it will be possible to have possibilities to change ourselves, it will be difficult. But in the future, we will have that ability.

Our science is only 200 years old, I cannot imagine what we will be capable of in 1000 years from now. We will definitely not be the same anymore. 

AR: It is nice to hear from a Nobel laureate that he supports genetic modification and as such other transhumanistic notions. 

JML: Modifying ourselves is a natural process because we are a product of nature and what we do is a product of nature. Therefore, if one day we have three time bigger brain and two hearts instead of one (because one is not enough) then this is all part of nature. 

He then leaned back and made a comment about the weather and I took that as a clear signal of continuing the conversation.

AR: This is the fourth time that you have come to the Lindau meetings and second time since they became international. How has been your experience?

JML: You cannot compare the experience of before and after they became international, it's totally different. I've attended 2 out 3 interdisciplinary meeting and I quite enjoy them as I get to meet fellow laureates from the other fields. Listening to pioneers in other fields is quite stimulating.

Then, he asked me a few questions about my background and where I come from. When I mentioned Nashik, his eyes lit up and he said, "I know Nashik, I had recently given a public lecture in Mumbai and there was whole bus full of people who had come from Nashik to attend it."

He told me about his position on the Reliance Industries' Innovation Council which also distinguished people like Grubbs (Nobel Prize in Chemistry 2005), Whitesides, Mashelkar and Mukesh Ambani, the CEO himself."I go to Mumbai every year to give a lecture", he said. Incidentally, Mashelkar, Ambani and Manoj Modi (who Lehn praised) are all graduates from my alma-mater, the Institute of Chemical Technology in Mumbai.

AR: So do you enjoy it there?

JML: Oh yes, I quite like going to India. Whenever I have the chance, I try to combine the various invitations that I have with travelling. For instance, in 2009, we drove from Bangalore to Mumbai via Hampi and this year I had a talk in Kanpur and from there we went to Khajuraho and Orchha and to Delhi as we will flew out from there. Orchha was a very beautiful place with the temples and palaces. It was a rather small place and I like small places compared to big cities. 

AR: It’s been fantastic talking to you and I take great inspiration from your life story. From a small town in France as a son of a baker, you have gone on to achieve a lot.

Personally, I take a lot more than just this talk and the inspirational story of Prof. Lehn's life. In that short conversation I've had a sneak preview of how a chemist of his standing thinks about the various aspects of science and life. I will carry this as a strong reminder throughout my academic career.