Scientist Stories: David MacMillan, New Chemical Reactions & Developing Asymmetric Organocatalysis

David Macmillan was born in 1968 in Bells Hill, Scotland. He obtained his PhD in 1996 from the University of California, Irvine. He is currently the James McDonnell Distinguished University Professor at Princeton University in the United States. David Macmillan, I now welcome you onto the stage. We are very much looking forward to your lecture.

Okay, I'd like to begin by thanking the Royal Swedish Academy of Sciences. I'd like to thank the Nobel Committee in Chemistry. I'd like to congratulate the other co-recipient of this prize, Benjamin List, and all of the other 2021 Nobel Prize winners. And I'd like to thank you all for your attention this morning. The last 2 months has really been just remarkable for me. It's been an extremely exciting time. And during that time, I've been asked many, many questions. But probably the number one question I've been asked is this one, which is shown here. What is asymmetric organocatalysis? So I thought I'd begin my talk today by breaking down each of these terms. The first term I want to tell you about is catalysis. What is catalysis? Well, catalysis is related to chemical reactions. If you look around you right now, everything is made from a chemical reaction. In fact, if I look in my office, and this is my desk, every component, every material that's in my office is made by a chemical reaction. Now, if we look at all those different chemical reactions and we actually hone in on one of them, for example, this one shown here, this is actually the chemical reaction to make caffeine. This is the molecule which is found in your coffee. It turns out that all chemical reactions require energy. Most chemical reactions do not happen spontaneously. And to represent that, most chemists use what's called an energy diagram. Now, I'm not going to be so technical here. I just want to show you what this energy diagram looks like. And one aspect I like about this is when I teach this to undergraduates, I always explain it in the following way. Imagine every night when you're going home, you actually have to walk over a hill. To walk over a hill to get home would obviously require a lot of energy every single night. What catalysis does, catalysis actually lowers the barrier, and in fact introduces a tunnel to make it so much easier for you to get home every night. And in the same way, it does this for chemical reactions. It makes all chemical reactions easier and faster. So that's exactly what catalysis is. Reactions are easier, faster, and in many cases, allows new chemical reactions to take place. Now, you may ask yourself, does catalysis really impact the world? And it does. And it does in many different interesting ways. But I thought I'd just show you a few. So here's the first one. This is the population of our Earth over the last 1,000 years. And you can see here, it's been pretty stable during that time frame till the beginning of the 20th century. And at that point, you see this rapid inflection. And at this moment, it climbs up to 8 billion people on Earth. Now, it turns out it would not have been possible to have these 8 billion people on Earth without this one catalytic reaction, which is shown here. This is the conversion of nitrogen over to ammonia. Now, you may ask yourself, well, why do we need ammonia? Well, we need ammonia to make food, and we would not have enough food on our planet for those 8 billion people without this one catalytic reaction. And in fact, if you think about your body right now, and you think about all the building blocks that are in your body, 50% of those building blocks contain nitrogens that came from this one catalytic reaction. Now, other ways that catalysis impacts our world is that 90% of industrial-scale chemical reactions at the present time actually use catalysis. And 35% of the world's GDP is also based on catalysis. And this number is actually only going to go up over the next couple of decades as we move towards more and more sustainable processes. Now, if you're wondering, how does catalysis impact your day-to-day life? It does so in many different ways. We've talked already about why we need it to make food, but also we need it to make medicines. We need it for solar cells. We need it for diagnostics. Even the global manufacturing of polymers and materials, we need catalysis. So clearly, catalysis is important for our world. So that's great. That's catalysis. But the next part is, what about asymmetric? What does asymmetric mean? Well, it turns out it's actually pretty easy to describe what asymmetric means to non-chemists. Because most people on Earth have two hands, or you have two feet. And if you look at your two hands, we know that they're in fact mirror images of each other. Those mirror images are similar, but they're still different. They're different because they're not superimposable. Which makes them asymmetric. So how do we know that? Well, we know that, for example, if you were to take a left-hand glove, you know that it fits on your left hand. But if you take that same glove and try to put it on your right hand, you know that your right hand will not recognize that glove. It simply doesn't fit. And that's what you call it being asymmetric. Now, what's really interesting, in organic chemistry, the same phenomenon happens. And these are two organic molecules which are, in fact, mirror images of each other. But they're similar, but they're still different. Which brings up an interesting question. In a lab, how do you differentiate between these two mirror image compounds? And it turns out that's not so easy. In fact, it requires really expensive instruments and requires a pretty long period of time. What's really also interesting about this, however, if you take these same two mirror images and give them to most humans, in this case, this is a Picture of my daughter Emma when she was 3 years old. It turns out even a 3-year-old child can take these two compounds and differentiate them instantly just by smelling them. They can smell the difference between these two compounds. Now, you may be wondering, why is that? Well, that happens because biology, human biology, is made up of building blocks which are one mirror image but not the other one. So for example, proteins, DNA, carbohydrates, hormones, all these building blocks of life are made up of one mirror image, but not the other one. Now, it turns out that has lots of really important biological implications. The easiest one to sort of talk about is with respect to medicine. Because it turns out while your hands can exist as mirror image, it turns out many medicines also can exist as mirror images. And it turns out your body can typically recognize one of those mirror images, but the other mirror image can often be problematic. It can be toxic, it can be dangerous. Now, this is a $100 billion market for our economy, and as such, it's extremely important that we can have access to one of these mirror images of the medicine, but not the other one. And the way you can think about going about doing that would obviously be through catalysis. And this therefore becomes known as asymmetric catalysis, or the desire to make one mirror image selectively without making the other one. Okay, so that's asymmetric. So, the third part of this is organo. What does organo mean? And to explain this, I'm going to take you all the way back to 1996. Why 1996? We'll talk about in a few moments, but we're actually, first of all, we're going to discuss what were the branches of asymmetric catalysis back in 1996. It turns out there were two major branches. The first branch was biocatalysis. Biocatalysis is when you take enzymes from your body or living systems, and you use those to make one mirror image in preference to the other one. The second major branch is metal catalysis. Metal catalysis is a man-made area which uses metals to allow you to make one mirror image selectively. Now, if you're wondering why 1996, well, 1996 is where my part in this story actually begins. In 1996, I was finishing off my PhD studies at UC Irvine, out in California. Now, over the last 2 months, many people have said to me, you must feel extremely lucky, extremely fortunate to have won a Nobel Prize. And I tell them, well, I actually already feel extremely lucky and fortunate because I got to do my PhD studies out in California at UC Irvine. This was a really wonderful, fantastic time for me. And during that time, I was also extremely fortunate that I got to work for this individual. This is Professor Larry Overman. He's just a fantastic chemist. He's an amazing mentor. He's also really just a superb human being. Upon completing my PhD studies, I moved back across America, went to Boston to Harvard. And I went to Harvard to work for Professor David Evans. David Evans is a genius. He's one of the most influential chemists that's existed. And he's someone who is an absolute master in the area of asymmetric chemistry. Catalysis. And I moved to Dave's lab to work in this area. And during that time, I worked on looking at metals to make single mirror imaging compounds. Now, these are some of the metals that Dave's group actually worked on. And during that time, I learned an enormous amount from Dave and from his team. But every single day I was in Dave's lab, I worked in this contraption. This contraption is known as a glovebox. This glovebox is designed to exclude air, it's designed to exclude oxygen, it's designed to exclude moisture. And every single day, I would be in there, I'd be working away for many, many hours. And after about 2 years of working in a glovebox, I started to think to myself, why are we spending so much time in a glovebox every day? To understand that, you have to think about the metal catalysts themselves. So here is your typical metal catalyst. You can actually break it down into 2 components, the left-hand side and the right-hand side is shown here. The right-hand side is the metal. If you think about these metals, it turns out metals in some cases, but not in all cases, they can be expensive, they can be toxic, they can be really difficult to work with. They often have problems being out in the atmosphere, which is why you have to use glove boxes. And in other cases, they're not sustainable. What's really interesting, however, if you look at the other part of the catalyst, this is the organic component. Organic molecules are often inexpensive. They're safe. They're sustainable. They're recyclable. And at that time, I started to think, well, why don't we just simply use the organic part as the catalyst and miss out using the metal? Now, that was something that eventually became known as organocatalysis. OK, so in 1998, the end of my studies at Harvard, I was really fortunate. I landed a job as an assistant professor at Berkeley. But before I got to Berkeley, I stopped off at Caltech to give a lecture. And while I was there, I met with Professor Eric Carrera. And while I was there, Professor Carrera took me to dinner and gave me, to what is till this day, one of the best pieces of advice that anyone ever gave me. He basically said the following. He said, when you get to Berkeley, you're gonna be surrounded by some of the best graduate students in the world. And you have to assume that whatever problem you work on, those students will help you solve that problem, regardless of whether you have a solution to it already or not. And as such, you should work on the one which is of the highest impact you can think of. So with this in mind, I knew what I was going to work on. I was going to work on organocatalysis. I knew that because of these advantages. We knew we could make them from nature's building blocks. We knew that these molecules should not be sensitive to air or moisture. They should be inexpensive. These same types of catalysts should be easy to handle. You wouldn't have to use a glove box because they can exist happily out in our environment. And then lastly, they should be sustainable. They should be recyclable, and they're nontoxic. But this was not the main reason I was interested in doing organocatalysis. The part that I was interested in was the following idea. Instead of trying to develop one organocatalyst that would work for one transformation, I was really interested in the idea, could we develop an organocatalyst that could work for hundreds of different reactions? And maybe this could become a field of asymmetric catalysis. Now, that in and of itself was a pretty grandiose idea. The only problem is, I had absolutely no idea how to do it. But that's OK, because Eric Carrera told me it'd be fine. I'd have great graduate students. They would help me solve this problem. OK, so in 1998, off I went to Berkeley. Started my research group, and this is one of my first photographs of that group. I really love this photograph. It's taken at 10 past 10 on a Friday night. You can see this young group in there doing research, trying to have an impact. And during that time, one of the graduate students in the group by the name of Tristan Lambert— Tristan is now a very successful professor over at Cornell University, but back as a first-year graduate student, he asked me a very simple question. He said, what is the mechanism of reductive amination? And I was a new professor. I was all excited to answer this. I ran to the board, and I wrote, well, we take a carbonyl. You take an amine, and it reversibly forms an iminium ion. And it's only when it's the iminium ion does it have the electronic configuration that it's reactive enough to do the subsequent chemistry. And right there, right then, is when I had my eureka moment. Because I suddenly realized you could use this idea for organocatalysis. More specifically, you could take these alpha-beta unsaturated carbonyls with amines and reversibly form iminium ions. And in many ways, this should emulate a field of catalysis that had already been successful using metals. Now, to sort of show this in a slightly more conventional way, if you think of these two equations as shown in this slide as being simultaneous, the one on the top is one that uses metals. And it turns out there's hundreds of reactions that have been developed using that concept. But the one at the bottom, there was basically no examples using organic catalysts to do that. But yet, if these were simultaneous equations, they both should be successful. And if that's the case, then organocatalysts should work for many different types of transformations, such as Mukayama-Michael, nitrogen cycle additions. The list would go on and on and on of all the possible reactions for organocatalysis. But at that time, there really weren't any. So we had to pick one of these, one of these we wanted to test it on. And what we chose was the Diels-Alder reaction. Now, the Diels-Alder reaction is really famous to all chemists. It deservedly won the Nobel Prize in 1950 because it allowed you to take relatively simple molecules and build ring systems very much in a straightforward fashion that could be used in natural products, that could be used in medicines, that could actually be used in materials. We decided this reaction would be a great platform or a great venue on which to test our new organocatalysis concept. So we decided to use exactly that. So as shown here, this is actually the notebook page from Kateria Wren. She was a first-year graduate student in my group. She was the first person in my group to test this idea. And these are, in fact, the components of a Diels-Alder reaction. And you can see in the middle above the arrow, that would be the organocatalyst. So we tested it, we ran the reaction, and if we scroll all the way at the bottom, you'll see the result, which is highlighted. It says, "Not racemic." Not racemic. That was unbelievably exciting to us. Not racemic means it makes one mirror image in preference to the other one. I was so excited when I saw this result, I went into my office, closed the door, jumped up and down for about 5 minutes, called my wife and said, "I think we're going to get tenure. We just got a really, really exciting result." exciting result. But when my feet came back to ground, I walked back in the lab and I realized that you can see at the top of this slide, it says an initial result, 48% EE. What does that mean? Well, that meant in terms of the mirror images, there was a 48% excess of one mirror image over the other one. And for the chemistry community to take this seriously, that number actually has to be about 90%. So we had a decision to make. Did we want to publish this? Or did we want to try and go for a catalyst and go for the gusto and get to 90%? Well, we decided to do the latter, and I can tell you that was 6 of the most nerve-wracking months of my life. But during that time, we eventually got to a catalyst that we thought was interesting. This is what's called the imidazolinones. We're interested in imidazolinones really for 2 major reasons. The first one was they're really inexpensive. If you look at these molecules, they're actually made from phenylalanine, which is a sort of building block of life. It's an amino acid that's combined with acetone. Acetone is actually paint stripper. But the other reason we really liked them, we thought if we put these together and made a catalyst, they should be good at being able to generate the production of one mirror image in preference to the other one. And when we tested that, that's exactly what happened. We could now achieve 90% excesses of one and the other in these Diels-Alder reactions. So again, this was an extremely exciting day in lab. And at this point, we know we have to tell the world. As a young professor, you now have to write a manuscript, and you really want to sort of climb up to the highest rooftop and shout this out as much as possible, how important you think this is. And in fact, when I look back on my first manuscript, I can see I really felt that in this opening paragraph. In this opening paragraph, I first of all talk about why I think this is going to have potential impacts on society. For academia, for industry, and for the economy. The second thing I did in this opening paragraph, I gave this whole idea a name. I called it organocatalysis. Now you might wonder, organocatalysis, why does it matter you gave something a name? What's in a name? But it turns out naming things is really, really important. For example, you can go back to Jöns Jacob Berzelius, a very famous Swedish chemist, very famous scientist. And while he was a tremendously successful researcher, he was also the person that came up with so much vocabulary and so much terms that allow our field to have basically an identity at the present time. Words such as catalysis, proteins, polymer, even organic versus inorganic. And the importance of terms have carried forward even into the modern era. For example, things such as machine learning, nanotechnology, organocatalysis. These are umbrella terms which really allow you to describe fields that allow them to gel and grow beneath those different types of areas. But the third part of this opening paragraph of the manuscript, which I'm most proud of, is that we introduced the concept of a generic activation mode. Now, you may wonder, what is a generic activation mode? But that's really just the idea of saying that this idea of catalysis should work not for one reaction, but for many, many chemical reactions. So obviously, we had to go off and test that. So if you remember, we've just performed the Diels-Alder reaction, which is shown here. So now we're ready to test it in other reactions, and we try it, and it goes bam, bam, nothing. It comes to a screeching halt. And this is something that happens in science quite often, where you get proof of concept using one catalyst, but you suddenly realize it's not going to take you all the different directions you want to go in. So now we have to go off and design a second-generation catalyst. Now, with this in mind, I was very fortunate to have really two fantastic young graduate students in my group by the name of Joel Austin and Chris Bortz. And what they did was they performed molecular engineering on this first catalyst. They effectively took away two carbons, then they introduced four carbons in a different shape. This was sort of precision engineering. To try and describe this, to to non-chemists that don't, or to put it in another context, one way I thought I could do this is to talk about, for example, this footballing god, Zlatan Ibrahimović, who is someone who is a precision footballer who does precise things and achieves really fantastic outcomes. One example of this is this goal he scores where, you can see here, he does an overhead kick from almost 40 yards out to score this goal. Now, okay, he wasn't playing against a team that was particularly good, But the point here is he performs a precision technique to score a beautiful outcome, a really beautiful goal. And we were interested, could we do the same with our catalyst? So we set out to test this. This was our first-generation catalyst. We had 3 reactions. We now moved to our second-generation catalyst, as shown here. And now we're off to the races. Things really start taking off like gangbusters. At this stage, we were also very fortunate that Karl Anker Jørgensen and Hayashi, introduced another family of catalysts, which were also really valuable for iminium catalysis, and again, completely expanded this area. All right. Now, at this point, what we've introduced is iminium catalysis. And basically, at the same time, there was all this beautiful work coming from Ben List and Carlos Barbas, really expanding beautifully enamine catalysis. But I don't want to give you the impression we were the only people who were doing this. In fact, we certainly weren't even the first ones to do it. There was many other people who were sort of working in this area, and I want to point those out. For phase transfer catalysis, there was Doling, Lygo, Marioka, and O'Donnell. In Lewis base catalysis, there was Denmark, Isecki, and Windberg. In terms of nucleophilic catalysis, there was Fu and Videus. In terms of peptide and partial peptide synthesis, there was Kelowna, Inoue, Julia, and Miller. In carbene catalysis, there was Anders Lieper and Tom Rovis. And in terms of hydrogen bonding catalysis, there was Corey and Jacobson. Ketone catalysis, there was Shi and Yang. And one part I want to mention, which I think is absolutely critical, if it wasn't for the contributions of all these people, this field simply would not exist. And I certainly wouldn't be standing here right now giving this speech. Okay, so at this stage, we started thinking about what other directions we could take organocatalysis into. And one thing we thought of was, wouldn't it be interesting if you could take iminium and enamine catalysis and and put them in the same vessel. And you might wonder, why on earth would you want to do that? Well, it turns out we were interested in emulating the way that nature makes molecules. It turns out what nature does, nature actually takes enzymes in a sort of biochemical assembly line, and in multiple catalytic reactions, takes simple molecules and makes very complex ones. We started to ask, could we do exactly the same thing, but instead of using enzymes, could we actually use small organic molecules to do exactly the same catalytic cascades. So in this context, we took a relatively simple molecule, as the one shown in the top left here, and we put it through these 3 catalytic cycles that all sequentially fed into each other to generate the molecule which is shown in the bottom right-hand side of the slide. Now, that molecule is much more complex than the one in the top left, and the reason it's so much more complex is we're trying to make the molecule shown in this slide, which is called strychnine. Now, you've probably heard of the word strychnine before. It's actually a very dangerous molecule. It's actually a poison. It's really a rat poison. And you may wonder why on earth we were trying to make rat poison. Well, it turns out this rat poison, strychnine, is actually a molecular benchmark that people in the field of total synthesis use from which to benchmark their technologies against. And using this cascade catalysis, we were able to, in fact, make it in a very rapid 12 steps. Now, other ways we started to think about ways we could do exciting and new things with organocatalysis was the idea, could we merge it with other types of reactivity? The next type of reactivity we became interested in was organic radicals. So this is Moses Gomberg. He was the person who discovered radicals in 1901, and has this really wonderful statement in his manuscript, which says, "This work will be continued, and I wish to reserve the field for myself." Well, clearly, that did not happen. All of the chemistry world started to use radicals. And the reason was because, as the name suggests, radicals allow you to do radical things. They allow you to achieve radical reactivity.. And so we became really interested in, could you merge this with organocatalysis? So this was actually work that was conceived of and executed on by a really fantastic graduate student in my group by the name of Teresa Beeson. What Teresa did was she said, I should be able to make these same enamines, but instead of using these enamines to do chemistry, what if we actually plucked an electron out to change its reactivity? Now that's a radical. This radical should allow you to do many, many different new types of chemical reactions. And that turned out to be exactly the case. We published many new types of processes using what's called this SOMOCatalysis. But this actually became a stepping stone for us to think about, could we actually take radicals and organocatalysis and make it even more sustainable in terms of how you would actually perform these transformations? And in this context, we became really excited about the fact of being able to sort of harness visible light. With organocatalysis. Now, harnessing visible light is something that inorganic chemists have been working on for almost 3 decades. And the idea here was to try and harness the light that would come from the sun and use that as energy to power the planet. We became interested in the idea, could we take that knowledge that they had developed, but now transport it into the organic world? And once it was in the organic world, start to think about doing a thing called photoredox catalysis. This would allow us to make new bonds. This would allow us to perform new types of transformations that could have a whole variety of different applications. Now, it turns out this was actually work that was performed in collaboration with a wonderful postdoc in my group by the name of Dave Nisivich. And this is basically what we were attempting, as shown in this slide. We're taking light bulbs. We're taking organocatalysis. And then, at the right moment, we simply switch on the light. We switch on the blue LED., and new chemistry starts to happen. Now, what's really exciting about photoredox is that it became a field in and of itself. It actually became a field as, as large as organocatalysis. And that's something that we are very much proud to be a part of. Now, in terms of thinking about this, the part that's really exciting is we've been really lucky as a group to be involved with organocatalysis. And we've also been really lucky to be involved with this field of photoredox catalysis. But it's been really exciting to see that organocatalysis effectively created this bridge, at least in our lab, into photoredox catalysis. In fact, if you think about it, it really was a catalyst that allowed photoredox catalysis field to come together, again, at least in our lab. OK, so at this point, another question that a lot of people ask me, what about applications of organocatalysis? And I'm going to show you just a few. The first one is in the area of fragrances, perfumes. It turns out perfumes are used on an enormous scale across the world every single day. And Firmenich, this company that's in Switzerland, in Geneva, are very successful at performing and producing many of these different perfumes. And one of the ones which is actually shown here is produced by combining organocatalysis with photoredox. This actually makes Lily of the Valley. It turns out Firmenich, also in northern India, make 300 metric tons of this beautiful rose-smelling perfume also using organocatalysis. Okay, so that's perfumes. What other areas can you use organocatalysis for? Well, you can actually use it in terms of materials, and actually for the recyclable plastic economy. This is some very important work that's being conducted by Bob Waymouth and James Hedrick. And many of you probably know that plastics are polluting our oceans. And what Bob and James are doing is they're using organocatalysis to effectively break down polymers back down to monomers, which can then be used again to remake polymers, making polymers and plastics completely recyclable and completely sustainable, which is obviously extremely important. But the area in which organocatalysis is probably most heavily used is that towards making medicines, or developing medicines. I'm just going to show you one example. This is talcedupan. It's actually used to treat chronic migraines. This particular molecule, this particular medicine, is actually made, and it's made using organocatalysis. And in fact, it uses the iminium catalysis I talked about at the beginning of my talk to make one of the mirror images in preference to the other one. But the last thing I want to talk about with respect to the value of organocatalysis is this slide which is shown here. We call this democratizing catalysis. Now, this is an aspect of organocatalysis I certainly did not see coming. I think it may be one of the most important aspects of organocatalysis. And it is that organocatalysis is extremely affordable, and cheap, and accessible fuel to the whole world. And this means if you go across every continent that exists in the world right now, people are being educated about organocatalysis using these different systems. They are so inexpensive to the point that it's really straightforward for people not just to learn about using them, but actually to do their own research. So when I think about where the next big idea in organocatalysis is going to come from, I realize it's not going to be about resources. It's not going to be about funding. It's going to be about who in the world has the best idea, regardless of which country they come from. OK, now people often ask me, what does the future hold for organocatalysis? And to be honest with you, I really don't have an answer to that question. But what I do know is that we have to provide for our ever expanding global population in a responsible way. And that includes catalysis. Catalysis has to be sustainable as we go forward. So clearly, this will involve using organocatalysis and biocatalysis, but it will also include things like photocatalysis and electrocatalysis. It's going to be essential that we move to these types of catalysis if we're going to create sustainable technologies for our planet. Okay, so that's my last chemistry slide. I want to finish off by thanking the people who, first of all, did this work. I talked about the people already from Berkeley. We moved to Caltech, where we actually did most of our organocatalysis research. And I want to thank all the people who are shown on this slide here. This was a fantastic group to work with. And I also want to thank also all my friends and the faculty members out at Caltech. In 2006, we actually moved over to Princeton. We continued our organocatalysis work., and also we started doing lots of photoredox as well. And again, I have to thank this phenomenal group, these phenomenal teams I was lucky to work with during that time frame. In terms of other people I have to thank, I have to thank this woman. This is my wife, Jean. She's the love of my life. She is an amazing person. She's an amazing chemist. She's an amazing mother. But more than anything, she's my best friend, and this journey, honestly, would not have been the same without her being there. So I have to thank her so much. I also have to thank my family. This is Danielle, this is Lauren, this is Emma. This is us having a boogie on the Harbour Bridge in Sydney, which was a lot of fun that day. And I also have to thank Julie. Julie is my unique and wonderful mother-in-law who's been an amazing supporter through all of our times as we went all through all these different stages of our life. In terms of other people I have to thank, I have to thank my siblings, Ian and Lorraine. Many people have heard this story that I would not have went to university if it wasn't for my brother going there first. But I think people haven't heard the story that I wouldn't have survived university if it wasn't for my sister Lorraine. So I just want to say to them, I love you both, and I can't wait to celebrate with both of you. Other people I have to thank, I have to thank educators that basically, first of all, the educators all over Scotland who work very tirelessly to take people like me and try to put them into a better spot. I have to thank the teachers at the Stevenson Primary, Belsall Academy, and I have to thank the faculty and staff at University of Glasgow. And again, without these people, I certainly wouldn't be standing on this stage. The last part is I want to dedicate this talk, and I want to dedicate this talk to 3 people who are not here. The first person I want to dedicate this to, I've already mentioned, and that's Carlos Barbas. Carlos was a pioneer of organocatalysis. He was right there at the beginning. With myself and Ben. Unfortunately, he was taken away from us too early in 2014, and over the last 2 months, I think about Carlos every single day. And it would have been so wonderful if Carlos had been here to celebrate this with both myself and Ben. The last people I want to dedicate this to are my mom and dad. This is a very difficult thing for me, but basically, someone recently said to me, 'How would your mom and dad feel about this? Would they have been proud? Would they have been proud of you winning this prize?' And I said that I don't have the words, I can't articulate how proud they would be, I just can't get there. But the one thing I can tell you, as a 7-year-old boy in Scotland, there's no way I could imagine I'd be standing on this stage giving this speech, but I think my mom and dad could have, because they were unbelievably supportive, and they believed that myself and my family, we could go absolutely anywhere. And for that, I'm incredibly grateful. With that, I want to thank you for your attention. Thanks a lot.