‘Making MOFs is the most fun I have ever had in the lab’ | Opinion

I’ll admit that there are years after I really feel a extra private reference to the chemistry Nobel than others. That’s not the widespread criticism that lots of the latest awards have been pointed extra within the biology course. I’ve tried by no means to have a gatekeeper mentality about chemistry. You can find yourself being so protecting of some Zone of Purity that you just don’t realise simply how small it’s develop into and what number of fascinating and helpful issues there are simply outdoors it.

But I’m an natural chemist at coronary heart, and I’ve additionally managed to maintain a connection to bench work throughout my profession. So I used to be pleased to see the 2025 award to Susumu Kitagawa, Richard Robson, and Omar Yaghi for metal-organic frameworks (MOFs). Even essentially the most relentless mental sentries should admit that this was actually chemistry. What’s extra, it partakes of inorganic, natural, bodily, and analytical branches all on the identical time. But what made me smile was figuring out that I had really gone into the lab and made some MOFs with my very own arms, and picked up x-ray information on a lot of them, too.

That was for a particular undertaking a couple of years in the past, when the corporate I used to be working for referred to as for uncommon drug discovery concepts that didn’t match into any of the prevailing classes. I’m all the time prepared for somebody to ask me a query like that, and I instantly considered some work that had been just lately printed by Makoto Fujita and his group on the University of Tokyo, Japan. The MOF area had been (and nonetheless is!) placing a variety of work into the concept of visitor molecules contained in the chambers and channels of those odd crystalline supplies. What Fujita’s staff discovered was that some MOFs might act as unexpectedly orderly storage websites for such molecular friends, in a kind of ‘one per room’ resort plan. If you soaked these into the MOF after which collected x-ray information, you bought each the construction of the MOF framework but additionally information on the visitor molecules. These had been now such an everyday repeating a part of the crystalline framework that they produced diffraction information of their very own, permitting their constructions to be solved as nicely.

The parade of yellow, inexperienced, purple, crimson, and colourless crystals in all types of varieties was dazzling

The thrilling factor about this was that it could possibly be utilized on a really small scale, and to compounds that had been tough or unattainable to crystallise by themselves beneath ambient situations. My ideas instantly turned to metabolites in drug discovery: enzyme-altered variations of our drug candidates produced within the liver and different tissues, with difficult-to-predict constructions and stereochemistry – and normally obtainable solely in very small quantities. Why not use MOF crystals to nail all these questions down in a single cross? So I set about attempting to see how basic the phenomenon was and the way it could possibly be utilized.

And let me let you know, making the MOFs themselves was fairly probably essentially the most enjoyable I’ve ever had within the lab. You mix steel salts and the multi-pronged natural ligands in some high-boiling solvent and warmth them up for a day or two, and should you’re fortunate you begin rising vivid, glowing crystals on the edges of the tubes. Just seeing issues crystallise from such sturdy solvents at excessive temperatures was odd sufficient – usually such situations would dissolve virtually something. But the parade of yellow, inexperienced, purple, crimson, and colourless crystals in all types of varieties was dazzling. Then you’d soak out the unique solvents and soak in options of take a look at drug substances, and it was off to the x-ray lab (or the synchrotron!) to see what you had.

Making new issues is a basic pleasure of bench chemistry, and I’ve by no means skilled such a concentrated model of it as this

What I discovered was that you might certainly get a few of these issues to order themselves inside among the MOF crystals, however we might discover no helpful basic methods. It was a procession of sporadic one-off outcomes, and never even all the successes had been profitable sufficient. The downside wanted rather more work and sources than I might give it, sadly. But Fujita’s lab and others have continued through the years and have made actual progress, and I nonetheless have hopes for the overall concept.

I used to be dissatisfied in that outcome, however I nonetheless discovered the work very satisfying and compelling. Making new issues is a basic pleasure of bench chemistry, and I’ve by no means skilled such a concentrated model of it as this. What chemist doesn’t take pleasure in crystals in all their varieties? No, I might be glad to fail once more like this: aiming at a excessive aim and having an amazing time doing it. Scientia experientia est, and over 40 years within the lab I don’t suppose I’ve ever felt extra like a scientist than I did then.