This same group has already noted at least eleven different CycA conformers in methanol/water solution, to give you the idea. Those first two will give you a static view of a crystalline form (which the team obtained in the presence of added KCl), and the NMR is for watching what's going on in solution. In this work the authors used three main techniques to work out the details: X-ray diffraction, neutron diffraction, and NMR.
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And you would have to think that there are a number of closely-spaced low-energy conformations accessible, so you're going to have to deal with that equilibrium when you take measurements, too. CycA is not too soluble in water, which is a hint that a lot of those greasy alkyl side chains are exposed to solvent. But just what it does look like in aqueous solution has been a longstanding problem. That's a 33-membered ring you're looking at (I think), so the one thing you can be sure of is that it doesn't actually look like any reasonable flat structure you can draw. Especially if you want to draw it in a way where you don't have to stretch bonds and jam things together! Like most of these structures it's not a lot of fun to draw. It's a cyclic peptide at heart, with modifications (specifically a lot of N-methylation). The structure's at right (or at least it should be I've been having some hiccups on putting in images around here). Here's a new paperĀ from a group at Tennessee looking at cyclosporin A, which is a good prototype for this kind of thing. But nailing these down is a challenge for analytical chemistry techniques. One of the answers is surely that there are interactions within these molecules (across the interior of the ring space) that stabilize their conformations and arrange the groups on the outside of the ring in particular ways. There's some benefit to macrocyclic space that the "count up the molecular features" approach misses, and a great deal of work has gone into figuring out how that works and how we can made it happen on demand. Some of these things look (from that approach) as if they shouldn't get absorbed from the gut as well as they do and shouldn't penetrate cell membranes as well as they do, either. If you look at many of these natural product macrocycles and start counting up polar groups and the like, the good ol' rule-of-five heuristic or the like, you quickly realize that your rules don't seem to apply too well in this space. There's another effect that we've all been trying to exploit as well. On the other hand, your new cyclic structure could also tie things back so that there's absolutely no way for these groups to get into the right positions any more, and your activity might almost completely disappear. If you can get things arranged into the right places and hold them there with a cyclic structure, you can get really remarkable boosts in activity and selectivity. That means that cyclization (of all sizes) is often a sort of "death or glory" move in medicinal chemistry. That's partly because of entropic factors - with a macrocycle you have "pre-ordered" the molecule and placed its various functional groups and regions in a constrained space compared to what they'd be exploring in an acyclic compound.
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They can cover interesting binding sites on protein targets in cells (thus all those natural products), things that often you can't achieve with acyclic compounds. They can bind smaller species inside the perimeter of their rings, for one thing - everything from ions all the way up to substantial molecules in host/guest complexes. Why do we care about large rings - what's special about them? It turns out that they can have unusual properties, in several ways. A great deal of 20th-century total synthesis work took place in this area for just that reason, and it's not like all those synthetic problems have been solved yet, either.
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Letting bacterial, fungi, and other creatures make and optimize these things for us has long been the rule, since synthetically they can be very challenging, not least in simply closing rings of this size from acyclic percursors. There have long been natural products of this sort and their derivatives in the pharmacopeia, things like erythromycin, cyclosporin, amphotericin B, azithromycin, rapamycin, rifampicin, eribulin.those are a few that come to mind, and there are plenty more. We've been seeing more macrocycle compounds in drug discovery and other areas of chemistry over the years - well, macrocycles that we've made deliberately, that is.