Because of my lab’s current interests in co-crystals I have been trying to read the literature in this area. One recent paper I came across describes a well-executed study that has some… well, I am not kidding, magic (almost) in it. The paper hails from Bucar and co-workers in Cambridge. According to the authors, efforts to generate a co-crystal between caffeine and benzoic acid have consistently failed over the past six (!) decades. Bucar’s team was no exception to this ill fate, but not for their lack of trying. It is hypothesized that, despite the anticipated stability of the resulting material, a high kinetic barrier to co-crystal formation accounts for this lack of success. For decades, this kinetic barrier has hindered the formation of what should be a very thermodynamically stable co-crystal form. When the authors tried to improve their chances using a heteronuclear seed (a caffeine/substituted benzoic acid was used in this capacity), they finally succeeded in growing the long-awaited caffeine/benzoic acid co-crystals. This achievement aside, it is what happened afterwards that caught my attention. Apparently, ever since the first successful crystallization, the crystals would always form after numerous attempts to rigorously clean the glassware by scrubbing it with all sorts of potions (acids, bases, bleach, you name it) and deliberately NOT using the aforementioned seeds any longer. In other words, the authors could not replicate their NEGATIVE results from the past. Please read the paragraph starting with “One possible explanation for the unexpected…”. Imagine this: you try for a long time, you get nowhere, and then you finally reach your crystalline Nirvana. Form that point on, your lab gets its “mojo” in that those chemicals that used to never co-crystallize, would from now on ALWAYS co-crystallize. According to the authors, these results speak to the exceptionally strong seeding capacity of the complex they used in order to obtain co-crystals. I think we need some of this in our lab too! We need some of this pixie dust, guys…


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