The chemical and pharmaceutical industries are constantly looking for ways to produce new chemical compounds more quickly, easily and cheaply. One way of achieving this is to design new chemical reactions that are simple and widely applicable. This is exactly what our stipend award holder Rafael Navrátil, who is set to travel to Scripps Research in San Diego in March 2020, will be doing. “As a member of Professor Baran’s team, I will be developing new methods that use electrochemical reactions to easily convert readily available starting materials such as alcohols into new compounds, which could be used in the pharmaceutical industry, for example”, Rafael explains.
Converting alcohols into new compounds through electrochemistry
In March 2020, you will start your one-year research stay as a member of Professor Phil Baran’s group at Scripps Research in San Diego. What are your expectations?
I’m definitely looking forward to it. Of course, Professor Baran commands a lot of respect too. The members of his lab, as well as those of other research groups in the USA, are very committed to their work and they are also more competitive than researchers in the Czech Republic. Professor Baran is known for having spent a huge amount of time in the lab as a student, working overnight and even sleeping in the lab. So I am curious to find out how hard they work in the lab and how well I will handle it. I also feel responsible for making good use of the financial support that I received through the grant.
Did you know about Professor Baran before? Why did you choose this particular lab?
I have followed Professor Baran’s work for nearly a decade, reading his research papers and his team’s blog. So I’ve had a good picture of what he does and why and how for quite some time. He is one of the top figures in chemistry and one of the few who actually advance organic chemistry. About 18 months ago, I started to think about the possibility of working in his lab.
Did you have specific criteria in mind before you made your choice? Was the US a particular goal?
If my choice had been based on a country I would have stayed in Europe, as travelling around the continent is so easy. You just pack your bags and go. America is more of a challenge. My choice was based purely on the research topic and I really liked the projects that Professor Baran’s team is working on. Initially I was a bit worried that he might not accept me because there are obviously many people applying to work with him. But at the same time, I thought I might as well give it a try. Nothing ventured, nothing gained! I wrote him an email and I received a reply almost immediately, saying that I just need to sort out my financing and then I can come. I believe that the experience I will get in his lab will be valuable in the future too.
Are you planning any other research stays or projects?
I am of course considering further research stays. A lot of groups out there are working on fascinating projects that would certainly interest me. But I will see how things are in a year. I also have to think of my wife, who is fortunately willing to come to the US with me now, though she would rather start a family.
In the US, you will be developing new methods and reactions in organic synthesis. Can you explain what that means in more detail?
One of the main research topics that Professor Baran is working on is the development of new methods and reactions in organic chemistry. It may sound a bit odd, but these days it is not so easy to come up with a new reaction which is simple to perform and widely applicable. I may be exaggerating, but everyone knows how to put an expensive metal catalyst into a reaction flask to make a reaction happen. But when it comes to industrial and pharmaceutical applications, these methods are often of limited significance, mostly because of the cost and availability of metals, not to mention the environmental impact. Therefore, I have proposed a new method – a chemical reaction that utilises alcohols as cheap and readily available starting materials and electrochemistry as a reagent for their conversion. This way, we have an opportunity both to create new compounds from alcohols and to have better methods for the preparation of already known compounds. Overall, these reactions would be useful in various fields of chemistry, including pharmaceutical and medicinal chemistry.
What in particular makes your approach innovative?
Similar reactions, albeit ones that do not use alcohols, already exist, but most of them suffer from serious limitations which means that their use is impractical. The cost and toxicity of chemical reagents is a common problem and that is why I have decided to use electrochemistry, which also makes atypical chemical transformations possible. As Professor Baran said himself: “Electricity is the cheapest chemical reagent.” Moreover, using alcohols as starting materials is very advantageous because they are cheap, ubiquitous and, importantly, a large number of natural and biologically active substances are in fact alcohols.
How ambitious is your project? What are the chances of success?
That is difficult to say, but if it were simple and lacking in ambition, surely someone would have already done it. Some parts of the method that I proposed most likely work, as my preliminary theoretical calculations have shown, but we still need to do many experiments, try different variants and figure out the right reaction conditions.
If this is a success, how much will it change the chemistry or the production of new medicines?
The ideal scenario would be that, once completed, the method we have developed finds applications across various areas of synthetic organic, medicinal and materials chemistry. The method would also have the potential for use in the production of medicines, making it significantly simpler and, therefore, cheaper.
Researchers abroad are often more results-oriented.
You completed a five-month research stay at Radboud University in the Netherlands. What are your takeaways from that experience? What were the main differences compared to the science we do here in the Czech Republic?
I think we tend to overestimate foreign scientists, particularly students. I don’t believe, for example, that students in the Netherlands are better at organic chemistry than students here; perhaps quite the reverse! The main difference, apart from better English, is that researchers in other countries often work on far more interesting and relevant scientific problems and they are more results-oriented, which all eventually leads to publishing in better scientific journals. However, such research often does not go into much depth. Discover something fast, present a possible application for it, but spend less time on explaining how it actually works the way it does. Unfortunately, that seems to be the trend nowadays – everything is accelerating and we are under pressure to produce a lot of results in a short period of time.
Why did you decide to apply for a grant from the Experientia Foundation?
I had known about the grant for some time – already back when I was a master’s student. However, I became more interested toward the end of my PhD studies and I realized that this grant is actually one of the easiest to obtain.
How would you rate the application process? Do you have any recommendations for other applicants?
From my personal perspective, the whole application process was simple. Obviously, the hardest thing is to develop the project itself. My recommendation is that applicants should allow themselves enough time for this. First you need to come up with a good and sufficiently ambitious idea, which you can sometimes do in five minutes, but also (more often!) not. What takes far more time is to read through the literature on the topic to see if anyone has already done something similar and put the idea into a broader context. Another recommendation would be that the project should not resemble the research projects that the applicant has already been working on. No one will financially support a project which is just a continuation of previous work.
How long did it take you, then?
I started thinking about it in more detail when I was in the Netherlands in fall 2018. I knew I would finish my PhD within a year and that I should start looking for a postdoctoral position. Around Christmas 2018, I had the topic worked out. And then I worked hard on it for about a month, putting everything down in its final form.
I love constantly discovering and learning new things
Why do you do science – chemistry?
That is a good question, which I sometimes ask myself too. I have always enjoyed chemistry and I participated in student Chemistry Olympiads competitions. When I was deciding where I should go to university, I was quite sure about it and applied to the UCT in Prague.
What do you like about scientific work?
Constantly discovering and learning new things.
What keeps you going when the lab work is not going well?
I always work on multiple projects simultaneously, trying to find out what will work and what won’t. If you are stuck on a problem for a long time, it’s better to move on, work on something else and not waste valuable time. When I was doing my PhD, more than half of the ideas and projects I came up with did not work. Many people focus on one goal, one problem, trying to crack it at all costs. If I run into obstacles, I evaluate what goal I would have achieved if I had succeeded in the end. This is often the moment when I realize that the time and effort are simply not worth it, so instead I move on to work on something else. Sometimes I do not give up completely but rather try to find a completely different way of solving the problem.
Do you have a scientific role model?
During my studies at the University of Chemistry and Technology, my supervisor, Dr. Tomáš Martinů, was someone I could call a role model. He had a great attitude to science, an excellent work ethic and an eye for detail. He would always make sure that all experiments and explanations made perfect sense. Before I started working in his lab, I told him that I really did not know anything about experimental work and that I only knew chemistry on paper, to which he said: “It doesn’t matter, even a trained monkey can do experiments in a lab.” He was very patient, he took care of his students, explaining everything right down to the smallest detail.
Can you imagine setting up your own research group at some point?
It is tempting, but right now I am a bit worried that I don’t have a research topic broad enough for a large research project. Right now, I have many ideas for smaller projects, each of which could yield an article or two. I am also discouraged by the amount of bureaucracy it would require. But I would certainly enjoy supervising students, working with them, creating and discovering new things together.
What do you do for fun outside of research?
In my free time, I am particularly interested in landscape and nature photography. Unfortunately, the more time I spend in science, the less time I spend on photography. Sometimes after work, I enjoy exploring wines during wine tasting events, which also give me an excellent opportunity to meet interesting people.
Rafael Navrátil
was born in Ústí nad Labem. He received a bachelor’s degree in Chemistry and Chemical Technology and master’s degree in Organic Chemistry both from the University of Chemistry and Technology in Prague. He completed his PhD studies in Organic Chemistry at the Faculty of Science, Charles University in Prague in 2019 under the supervision of Professor Jana Roithová. He is currently a postdoctoral researcher in the group led by Ondřej Baszczyński at the Faculty of Science, Charles University in Prague – the first research team to receive a start-up grant from the Experientia Foundation. In March 2020, Rafael will begin his one-year research stay with Professor Phil Baran at Scripps Research in San Diego. The Experientia Foundation supported Rafael’s research stay with a stipend of CZK 1,270,000 (51,650 USD).