Multidimensional Click Chemistry

Probably the biggest impact of this chemistry will be to enable others to make discoveries which I think click chemistry did with the original CuAAC reaction - it was enabling technology.

Research can be hard work – whether it’s good chemistry or not – it still takes a lot of effort, you have to spend hours in the lab so enthusiasm to do that, along with having a goal is good research culture. It’s also important to be open minded – don’t say no. If a student has an idea, let them do it, and they will flourish that way. 

Click chemistry is a discovery method driven by the reliable formation of robust connections, but this also extends beyond molecules, where connecting key people and collaborators are equally important.

In the same way that different fragments contribute unique properties to the molecules they form, each collaborator brings their own individual vision and skills to a project.

A good example is in our recent development of the SOF₄-derived polymers. The SuFEx chemistry that Suhua Li developed allowed us to make quite special polymers. Still, as synthetic chemists, we had no firm idea about the structure of these materials until Han’s team (Netherlands, China, and Saudi Arabia) used their skills and techniques to elucidate the material’s helical form.

The extra bonus is that you also get to hang out with amazing people like Barry....

Bacteria don’t make mistakes until they're dying, then they make a hell of a lot of mutations. In comparison, viruses are sloppy the whole way through and are constantly mutating. So we have to be right behind them – they mutate, that’s fine, we mutate too. We can change one group in our recipe for a treatment, and we’ve got another compound. That’s what we think will happen – and there’s no reason why not. The compounds are not going to be suddenly toxic just because one little group was changed, so we have got to be fast. Quickness is needed, especially with things like cancer, which mutates like crazy. An individual patient might need a particular twist on their drug and it could even be that easy – we could sample a few different versions of a drug and see which would give them the most effect. 

You're not confident when you're young – I wasn't and I had to prove myself as I felt insecure. I always take a risk and that's probably my saving grace, but I think most people have learned that do ‘fancy’ things and to try and be elegant and impressive when you write about it, but actually, the more elegance you have in your paper, then the more trouble you're in because you spend a lot of time being proud of the development of something which may be a curiosity. It’s always good to be moving on, no matter how successful you are at something, you need to have a drive to move on. I always move on for re-activity’s sake – I’m always looking for that perfect reaction, and that’s probably been my biggest strength.

If you want to learn, you certainly don't want to do your postdoc research for somebody in the same field as your initial training – that is not a good idea and just shows how political people have become. You want to collaborate with people in totally different fields – like chemical engineers, polymer science or in biology. There is a new generation coming up and these young people are going to teach others to find collaborators in different fields. I used to visit all the labs at Stanford that my friends were in and I would ask them what they were doing. They would tell me all about their project and next thing you know, two graduate students have solved each other’s problems, because I knew something they didn’t know, and vice versa. Once you’re good at something, use what you’re good at, but don’t concentrate on it. 

We are largely influenced by the old German chemistry, especially those reactions and procedures documented in the 40-volumn Houben-Weyl Methoden der Organischen Chemie. In our team, Prof. Sharpless with his experience and expertise has been an inspiration.

Chemistry is at the centre of natural and applied sciences. The breakthroughs in chemistry have brought medicines and polymers to the world. The rapidly growing applications of our multidimensional SuFEx click chemistry in drug discovery and materials science is a perfect reflection of the contributions of chemistry to the world in general. We anticipate that the development of multidimensional SuFEx click chemistry will make new medicines more affordable and their discovery faster.