The controversy I wrote about last week, about whether (some) enzymes work by using extremely fast movements (rather than by putting things into their place and letting them do their thing) may remind some folks of the supposed medieval arguments about angels dancing on the heads of pins. But it also reminds me a bit of some other arguments in organic chemistry over the years. The horrible prototype is, of course, the norbornyl cation.
There was a time when people would simply leave the room when that topic came up, because they knew that they were in for another round of fruitless wrangling. Was its structure that of two rapidly interconverting standard carbocations, or a single bridged "non-classical" one that broke the previously accepted rules? George Olah and H. C. Brown, Nobel laureates both, were on opposite sides of that one, but every physical organic chemist from about 1950 to about 1980 probably had to take a stand one way or the other. (It is commonly accepted that Olah's side won), but the arguments got pretty esoteric by the end. Update: the battle was first joined by Saul Winstein, who did not live to see his proposal vindicated by Olah's spectroscopic studies).
Another one, which came along a few years later, was the "synchronous / asynchronous" mechanism of the Diels-Alder reaction. Do the new bonds in that one form at the same time, or does one form, and then the other? That one involved the physical organic people again, as well as plenty of computational chemists. I stopped following the debate after a while, but I believe that the final reckoning was that most standard Diels-Alder reactions were synchronous, within the limits of detection, but that messing with the electron density of the two reactants could easily push the reaction into asynchronous (or flat-out stepwise) territory.
So why does this level of detail matter? The problem is, chemistry is all about things like bond formation and bond breaking, and about interactions between individual molecules (and parts of molecules) that change the energies of the systems involved. And those things are nothing but picky details, all the way down. Thermodynamics, which runs chemical reactions and runs the rest of the universe, is the most rigorous branch of accounting there is. Totaling up those energies to see which side of the ledger wins out can easily involve the fate of single water molecules, or even to single protons, and you don't get much pickier than that.
This sort of thing is one argument used against the feasibility of molecular nanotechnology. How are we to harness such fine distinctions, at such levels? But it's worth remembering that we ourselves, and every other living creature, are nanotech machines at heart. Our enzymes are constantly breaking bonds, twisting single molecules, altering reaction rates, and generating specific, defined molecular products. If they weren't, we'd fall right over. We eventually fall over anyway, because none of these machines work perfectly. But they work pretty well, and they make our own chemical efforts look like stone axes and deer-bone hammers.
So we may find getting down to this level of things to be a lot of work, and hard to understand, and frustrating to deal with. But that's where we're going to have to be if we're ever going to do real chemistry, the kind that's that's indistinguishable from magic.