Winner: 2022 Sir Derek Barton Gold Medal
Professor K. Barry
Scripps Research
For the development of the concept of ‘click’ chemistry, the invention of chemical reactions underpinning this field and the impact this continues to make in chemical biology, drug development and materials science.
Click chemistry is a method of synthesising larger molecules by combining smaller “modular” chemicals together – similar to how Lego bricks might “click” together. Click reactions occur quickly and irreversibly, with minimal by-products created. Click chemistry was first fully described in 2001, and today it is used across all the sciences that use chemistry – chemical biology, drug discovery, materials science, polymer chemistry and more.
Biography
K Barry Sharpless is WM Keck Professor, one of four founding members of Scripps Research’s chemistry department, and Principal Investigator at Skaggs Institute for Chemical Biology. He received his PhD in 1968 from Stanford University followed by postdoctoral studies at Stanford and Harvard Universities. He then served on the Massachusetts Institute of Technology and Stanford chemistry faculties before moving to Scripps in 1990. Sharpless shared the 2001 Nobel Chemistry Prize for his chirally catalysed oxidation reactions. He is now best known as the inventor of ‘click chemistry’, the method he developed in the 1990s for easily and reliably discovering new chemical function, and for the discovery of CuAAC (copper catalysed azide-alkyne cycloaddition), a near-perfect click reaction. His group later discovered SuFEx (sulfur-fluoride exchange), another near-perfect reaction for click chemistry. Honours include: Nobel and Wolf prizes; the American Chemical Society’s Cope, Adams and Priestly awards (the latter being the ACS’s highest); the Royal Society of Chemistry’s Tetrahedon and Organic Division Horizon prizes, and Barton Medal; and, over 20 honorary doctorates and professorships.
I don’t need the approval of others, but, professionally, seeing my chemistries being used by other chemists is as motivational as it is gratifying.
Professor K. Barry Sharpless
Q&A with Professor K. Barry Sharpless
Who or what has inspired you?
My teachers and mentors made me who I am, and I can’t imagine a better upbringing. From undergraduate research with Tom Spencer, I learned chemistry was always fun, and often thrilling. He sent me to work for his own doctoral mentor, E.E. Van Tamelen, considered by many the most creative chemist of his generation, passed on to me the biomimetic approach to synthesis he pioneered. I chose postdocing for Jim Collman despite vT’s strong opposition: he thought time spent at a less than top tier school would diminish job opportunities. That same year Bob Grubbs defied his PhD mentor, Ron Breslow, in order to postdoc with Collman. The issue disappeared when Collman moved to Stanford, where Bob and I were among his first group members and got our hands-on introduction to metal complexes. Only Jim Collman may be more enthusiastic about chemistry than I am, but the breadth of his interests and accomplishments rival those of Derek Barton. All these mentors gave group members their independence, but were always available to help–great environments for young chemists to grow up fast.
What motivates you?
Even by ADHD standards, I’m need extreme excitement. I used to seek out novelty, thrills, and, best of all, the danger of nature at it most physically challenging. I loved being out during hurricanes or in a boat when the sea was big and rough (experiences I get vicariously now on YouTube).
I was a fearless, energetic kid, but also very shy, so I learned to do things on my own.
Growing up indulged and unsupervised in a dysfunctional, loving family meant doing whatever I wanted with the resources I needed. That security probably made me not be motivated by financial rewards. In college I first experienced the excitement of having original ideas, and that high still drives me. I love being the first to notice chemical reactivity that’s hiding in plain site—it happens all the time. Idon’t need the approval of others, but, professionally, seeing my chemistries being used by other chemists is as motivational as it is gratifying. It’s just by chance that chemistry and I, such a good symbiotic match, ever found each other, giving me a career as exciting and thrilling as pre-chemistry experiences were. I lost interest in going to sea and riding dirt bikes after being consumed, and motivated, by chemistry.
What advice would you give to a young person considering a career in chemistry?
Whether you want to change the world or make a pile of money, learn basic chemistry, and learn it well. You’ll be prepared to work in any of the bond-making/bond-breaking sciences, and you will be needed. The reason for studying chemistry first is because chemists can see and imagine direct intrusions by chemical reactions into the target function that is being probed. This is an example of the direct interrogation of a complex system.Good physics is equally portable and employable, but I’m a chemist, so I’m inclined to think the potential for making transformational contributions is greater from our side.With a good informed intuition any case, a lot of ground gets covered and while documenting such chemical effects on your screen’s or assay’s function.Chemistry and physics are bottom up, and you can’t build without a foundation. I’m 81, and I plan to come back and learn physical chemistry first. I want to stay flexible, so I can’t tell you which way I’ll jump after that.
What has been a highlight for you (either personally or in your career)?
Here I am, not wanting to admit I’m past my sell-by date, but I couldn’t feel luckier because of four relationships (and a bonus fifth one, below) with former group members who became, and remain, my most valued clicking collaborators:chemistry doctoral-student-turned-glycobiologist and a colleague since 2015, Scripps Research Professor Peng Wu; the postdoc who discovered SuFFex and now back where he received his PhD, Shanghai Institute of Organic Chemistry Professor Jiajia Dong; joining my group after receiving a Cambridge PhD from my old MIT colleague and friend, Sr Jack Baldwin, Professor John Moses is the first chemist to be appointed (2020) to the Cold Spring Harbor Labs’ faculty, and he’s a click chemist; and, a decade pre-Scripps, becoming my graduate student at MIT in 1980 (leading the AE’s mechanistic studies back then) and in this century co-authoring the original click chemistry paper (contributing the scholarly integrity that made it Angewandte’s most-cited ever), then shared the decision enabling in situ click chemistry, and invented click bioconjugation, Georgia Tech’s School of Chemistry and Biology chair, and the first to hold their James A. Carlos Family Chair for Pediatric Technology, the nonpareil Professor M.G. Finn. It’s comforting, and wonderful, knowing these four are in click chemistry’s future.M.G was only able to make Click chemistry: diverse chemical function from a few good reactions a classic (more than twenty years after publication is remains one of the journal’s top ten downloads) because he had near-perfect, material to work with, attributable to Hartmuth Kolb, the bonus, grown up former group member. I have no doubt Hartmuth would still be one of collaborators who make my life now so rewarding if he hadn’t settled in industry. Present at the beginning of click chemistry and both a founder and its creative developer, Hartmuth was the one who make click chemistry a success.He came to postdoc and immediately lived up to Steve Ley’s nickname, The Panzer Tank. Hartmuth is unique. His drive to take a project to completion and cheerful rescues whenever the rest of us faltered; his matchless foundation in chemical science exploited with such creative flexibility. Twenty years ago we were the three amigos who did the click manifesto and a lot of really good, new and/or useful chemistry. We reunited recently to write a commentary for the launch of Science Synthesis. What a pleasure! And Hartmuth is still the kindest, perennially upbeat and happiest "happy chappy" I know.