It is lovely weather here in Boston, and we are all enjoying it very much. In fact, a friend of mine recently found a patch of wild blueberries, and so this past weekend I made some blueberry pie. Yum!

This little excursion also got me thinking about pi more generally. In my undergraduate days, my study partners and I really struggled in physical chemistry. We had homework assignments every night (unusual for a class at my university) and, even more strangely, we were given the numerical answers. We just had to figure out how to get them. After many weeks of trying all possible equations that we knew for every problem, one of us had an insight: as long as we used pi somewhere, somehow, we could always get to the right answer – sometimes you had to multiply by pi, sometimes dividing, etc., but always pi. We called this the pi factor. (Then the struggle was to figure out why we needed pi in each case… is this the why factor??)

On a related note, I often see papers where an unexpected increase in binding affinity, or the critical requirement of a phenyl ring on a small molecule inhibitor, or similar, is simply explained by invoking pi-stacking. This is interesting to me: since it is often extremely difficult to provide quantitative (or even qualitative) data to confirm or refute the presence of pi-stacking (especially in large/complex systems), I wonder if some shout-outs to this interaction are just another way that people are using the pi factor? In this case, as something that makes intuitive sense, but will not likely need to be anything more than a vague reference?

Perhaps as we continue to learn about this fundamental intermolecular interaction, and methodologies continue to improve, it will not be so easy to call on pi in any ill-defined way. As long as it doesn’t jeopardize my dessert…

Catherine (associate editor, Nature Chemical Biology)