28 September 2013, 11:45

Chemistry Nobel Prize: complex reactions just a click away

Chemistry Nobel Prize: complex reactions just a click away

Amongst the serious contenders for this year's Nobel Prize in chemistry are Two Scripps Research Institute scientists and a former colleague. The trio, Barry Sharpless, who has already won a Nobel, Russian born Valery Fokin and M.G. Finn now with Georgia Institute of Technology are under consideration for their work in the development of "click chemistry," a field that has produced faster, simpler ways to synthesize molecules for many purposes including pharmaceutical drugs. Andrew Hiller, host of VOR's "The Prism" spoke with Dr. Valery Fokin to hear more about his research.

First, congratulations on both the nomination and also, more importantly, for the contributions of your work.

Thank you. The contribution is I think the most important thing and that is what gives us – the scientists – the satisfaction to see the results of our work being used in the real world and being used by other scientists. Otherwise, it is just a prognosis based some numbers and I think that’s really secondary to the fact that we can see the results of our scientific work being useful.

I understand that you have just come off the plane and you were in Moscow. What were you doing over there?

I’m involved in joint projects with the Moscow Institute of Physics and Technology. It is starting up a new chemistry laboratory of that institute. It is a brand new thing sponsored by the Russian Government by the so-called mega-grant from the Russian Government for the next three years to open up an operational chemistry related to the pharmaceutical research laboratory.

So, this actually stems, probably distantly, from your work in click chemistry. Can you tell me about that, the thing what you may be a contender for the Nobel Prize? Where does the idea for click chemistry come from?

Click chemistry is a concept which was introduced primarily by Barry Sharpless, who is at the Scripps Research Institute and who is my post-doctoral mentor and teacher for about 15 years. The idea of using simple reactions and selecting only the best reactions for making molecules was his brainchild and his idea. My contribution to this field is a reaction which has become the best known click reaction or a reaction which most of the people associate click chemistry with, which is the copper-catalyzed reaction of azides and alkynes or the so-called CuAAC reaction.

Many things which are complex seem to originate from what we observe in nature and click chemistry is no different. In some ways it tries to simulate nature. Can you explain to our listeners how so?

In a way, what happens in nature some of the most complex molecules of life, they are assembled from building blocks and the nature is just a handful of building blocks. To get all the diversity in nature she uses a few connecting reactions to put them together. Those reactions are usually connecting atoms of carbon with atoms which are non-carbon. It is easier to do for various reasons and it is easier to do for us in the laboratory for various reasons, as well. And that's the focus of this chemistry.

So, if we have a good way of connecting many different blocks together reliably under no matter what conditions – it can be in water, it can be organic solvents, in the presence of air, in the presence of many other molecules and biological systems – we do have a reliable process for assembling complexity and diversity. And that’s what this chemistry is about.

Many years ago, in fact, at this point many decades ago my mother was working with the National Eye Institute and she was the scientist who discovered the impact of ultraviolet radiation on our eyes. And when I used to ask her about that, because I was always impressed that every pair of sunglasses in the world has her UV warning on it, she would say – you know, I don’t know that it was worth the bother, for ten years every scientist would come to me and say “no, it is impossible, it is not true, it is not real, your science is wrong”. And for ten years she had to defend it and she said it was a tremendous amount of work. I want to ask you a little bit about the gauntlet of proving your work and what you went through in showing that this works?

Yes, it has been an interesting road because the usual mantra or a very commonly used mantra of modern science is that complex problems require very complex solutions. And when you attack a problem from the angle of simplicity and in a way of orthogonality, not thinking about mimicking anything but really going in a completely different orthogonal way – when it is simple, it is not something which is easily embraced by the scientific community. So is true for most ideas, like you said about your mother’s research on the effects of the UV radiation on our eyes. It takes time until people pick it up and appreciate it, and start using it. I subscribe to it.

We’ve been fortunate and the chemistry, which I have been in, involved has been picked up relatively quickly and many people, including our immediate colleagues and including people away from Scripps, started using the reactions basically second year after the copper-catalyzed cycloaddition, for example, was discovered. And it is still on the rise in pharmaceutical industry, in material science, in academic research. We’ve been fortunate on that.

Is the reason that it’s been so widely accepted is not only that it allows you to do varied experiments, but more experiments and quicker?

It allows you to do varied experiments and you don’t have to be working under very sophisticated conditions. So, you don’t need any special setups. And that’s why it was embraced quickly by chemists, biologists, people who are not really specialists in organic synthesis. So, my goal was to design a reaction or design a process, sometimes toolkits which are now marketed by various companies, which would be very trivial, very simple to use for nonspecialists and would guarantee that it works. That’s the philosophy behind chemistry in general and the philosophy which Barry Sharpless introduced into the field.

We’ve already covered this to a degree, but science is not a solo endeavor. Who have you been working with and who are you working with today?

I’ve been fortunate to have wonderful colleagues at Scripps. And M G Finn and Barry Sharpless have been my closest colleagues over the last decade. But MG Finn just moved to Georgia Tech and I hope that doesn’t really mean that we will not continue our collaboration and interactions. Also, there are plenty of people who’ve been not necessarily collaborating with me continuously but have been either using chemistry or sharing their results and failures. And you are absolutely correct, science is not a solo endeavor anymore. It truly is a synthesis of different expertise and areas.

And I’ve been very privileged to work, for example, with Pr. Craig Hawker from the University of California Santa Barbara on the materials, on dendrimers. I’ve been interacting, although not publishing together with Pr. David Tirrell from Caltech. And I can name a lot of people who really have done a lot of work in this area and contributed in different ways, either by improving or utilizing, or taking different angles and different views on this chemistry. Carolyn Bertozzi, for example, at the University of California Berkeley has done a wonderful work on a related science but in a very different and a very original way.

It seems to me that today we are living in the land of science fiction. And in fact, your work has helped to open some rather impossible doors. I want to ask you, out there in the world of science that’s being researched now, what is amazing you? What are we on the verge of doing or discovering?

Yes, this is an interesting question, especially when you said that we are living in the world of science fiction, because I think any scientific project should start with a little bit of fiction in the beginning. There should be a little imagination and fiction.

And you know, 40 or 50 years ago there was a movie the Incredible Journey. It was one of the first sci-fi movies I think. A group of people was turned into tiny organisms and they were injected into the blood stream of a person. It was done of course for the spying reasons. I don’t remember the exact adventures there, but what was done at that time with the relatively primitive computer graphics I still use it in my presentations as a sort of dream of 50 years ago. To their eyes opened the wonderful picture of what is happening in the blood stream – they could see blood cells, they could see tissues, they could see everything in the human organism.

So, that’s the dream which many of us I think have, and as far as molecules go that’s the dream that I have – to be able to see with my own eyes what is happening in the reaction flask. I don’t think it’ll ever happen and I don’t think I’ll ever become a molecule and jump into a flask and see anything. But that’s what we try to develop and go basically from the place where the events are taking place, where the news are developing into real living system, in living cells, in tissues as it happens not in some frozen sample which is not living anymore, which is a dead structure under the microscope.

So, being able to observe live processes in real time without disturbing the system is still sort of a science fiction but we are getting closer and closer to it. And I think that complex interactions which biological systems present to us are among the most interesting things we can learn with the new tools.

Entering the world of science reality I'm Andrew Hiller for the Prism and the Voice of Russia. And we’ve been joined by is Dr. Valery Fokin who is with the Scripps Research Institute. Thank you so much for your work, your time and your legacy.

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