The 2016 Chemistry Nobel has gone to Jean-Pierre Sauvage, J. Fraser Stoddart, and Bernard (Ben) Feringa for their work on molecular-sized machinery. This field has been growing steadily over the last quarter of a century, fueled by advances in synthetic organic techniques, analytical instrumentation, and the imaginations of the people who are practicing it. Fundamentally, they’ve been trying to physically link our macroscopic world with the molecular-level one by bringing what we know about macroscale structures and engineering down to that size.
If this reminds you of Richard Feynman’s famous “Plenty of Room at the Bottom” nanotechnology lecture, that’s for good reason. Conceptually, we can now see that Feynman starting things rolling back in 1959 with that talk, although for at least another 25 years it was thought of as a minor series of speculative thought experiments, if referenced at all. Note that that editorial mentions how journals now actually have to discourage Feynman references in the first paragraphs nanotech papers, since it’s become such a cliché! But here I’ve fallen into it as well, and so did the Nobel folks in their scientific background piece on today’s award. It’s hard not to – while Feynman got some things wrong, the stuff he got right is downright visionary for 1959.
But it was during the 1980s that today’s laureates demonstrated that synthetic chemistry could start to be treated from an engineering standpoint. I well remember when Sauvage demonstrated the first practical synthesis of catenanes, structures of two two interlocked molecular rings. It was seen as an interesting curiosity, a “Well, who’da thought” story of surely no practical use whatsoever. Catenanes (and the related rotaxanes) had been demonstrated back in the 1960s in what were felt to be low-yielding syntheses of zoo objects. That feeling has followed the whole field ever since, and the work of today’s awardees is no exception. “Well, that’s a really neat demonstration of what odd structures we chemists can make. Gosh. But why?” This award should help answer that one, for those who still need the answer.
Looked at from another direction, it’s a bit strange that some of this work wasn’t taken more seriously. Host-guest complexation has been a big area of research for many years now, with applications in pharmaceuticals, materials science, optics and other areas. Consider cyclodextrins, which came on big during the 1980s and have never gone away. When they complex a small molecule in their interior space, what you’re seeing is an “incomplete rotaxane”, where things just haven’t quite threaded out of both ends of the tube. When you get to thinking about those structures, then you can start wondering about whether some system could be built that slides such a tube or ring in a controlled manner along a long chain, or whether the interior species rotates and how, or what would happen if you used different sorts of molecular interactions to accomplish the complexation (perhaps things sensitive to pH, or light, or added electrons?), or if the interactions themselves could serve as some sort of on/off switch, or if these systems could reversibly extend and contract. . .the number of experiments you can think up in this field is huge, but note that all the ones I’ve just described have already been investigated in various ways by (among others) the labs of the three Nobel awardees! See that scientific summary linked above for details – as usual, it’s an excellent overview of the work.
Mentioning a mechanical switch brings up another analogy that shows how important this sort of work is. What, in the end, is a receptor on a cell surface other than a mechanical switch? An agonist molecule binds, physically binds, the transmembrane helices shift around on each other in ways that we’re finally starting to really understand, which exposes different protein surfaces in the cell-side region below, setting off a cascade of signaling. Its easy (too easy) to picture this as a sort of circle-with-a-curvy-arrow abstraction on a page, but that’s not what’s going on. Small molecules and proteins are physical objects, and many of their most important interactions are accomplished by physical slotting, shifting, ratcheting, and rotating. What else can accurately describe the RNA polymerase complex that’s moving along the DNA of your cells right now?
Today’s award is a recognition of these facts, and of science’s attempt to mimic them for our own purposes. Atom-by-atom nanotechnology may or may not be possible, but molecule by molecule? That’s what keeps us walking around. If we can learn to build machines on that level, there is no telling what we might eventually be able to accomplish. I think that the reluctance to make that connection in some people is an unrealized leftover of vitalism, the feeling that the machinery of living cells is somehow “different”. It isn’t. It chunks and rattles and slides, and we can study it, understand it, and mimic it, and we can build things that evolution has never explored at all.
One thing I do want to finish up with is recognition of some of the many other people in this field who aren’t on today’s award. It’s well-chosen, but it’s also a big field, and there have been a lot of contributors. I’m thinking particularly of T. Ross Kelly’s molecular ratchet, Jim Tour’s nanocar work (an area also explored by Feringa), and Julius Rebek‘s host-guest investigations, but there are many more. And there will be many more in the years to come.