Professor K. Barry Sharpless HonFRSC

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.

Even by ADHD standards, I 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 sight — it happens all the time. 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. 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.

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.

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.

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 Sir 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.