It is not that often that I pick up an interesting purification trick from a chemical biology paper. Yet, this is exactly what happened to me while I was reading the ACS Chemical Biology manuscript by Bernat et al. This intriguing recent work documents the use of boronic acid probes of allosteric modulation of the chemokine CXCR3 receptor. Biological merits of the manuscript aside, I was drawn to the way the authors purified their boronic acid inhibitors. Their solution to the problem involves dry column flash chromatography, the description of which even made its way into the paper’s abstract. Given the focus of the journal, this probably means that the authors were really satisfied with the results. The technique consists of placing a dry bed of silica gel in a sintered glass funnel followed by fraction elution using suction. I have not attempted this methodology myself in the good old days when I was still doing somewhat meaningful research at the bench. I did a bit of digging and discovered a nice paper in the Journal of Chemical Education detailing this method. I actually think my students use this all the time, but I do not recall anything extraordinary about this tool. Now it turns out that it might be just what we need for some of our annoyingly polar boron-containing molecules. By the way, whenever there is something I want to learn in detail, I turn to the Journal of Chemical Education. Therein lies a treasure trove of information because the idea is to publish methods and procedures that are adaptable in undergraduate settings.
One more item of substance that relates to aliphatic boronic acids: during lyophilization, don’t go too crazy in your attempts to rigorously remove water from the purified compound. This is a bad idea as the Le-Chatelier principle will shift things in the direction of boraxine, which is notoriously sensitive to oxidative cleavage of the C-B bond. We like to keep our products somewhat wet. I picked up this tip from Professor Singaram while lecturing at University of California, Santa Cruz, last year.