Chemistry in textbooks is taught to be rigid and stuff, something that doesn’t change, a sort of choreography in which the molecules know their steps and dance exactly as expected as you change the conditions, no surprises, and no drama, just pure statistics and understanding.
And when the Cambridge scientists set up a Friedel-Crafts reaction, something done so often for drugs, they attempted drug modification just as any other scientist would, except the molecules didn’t dance to their steps this time.
The molecules arranged themselves in the complete opposite order that was expected of them, an experiment thought to have failed, instead turned into a new realisation - one where the researchers dug into a new type of reaction, the “Anti-Friedel-Crafts” reaction.
To put the reactions simply, the ‘classic’ Friedel-Crafts reaction helps researchers add molecules or groups of them at specific spots at the start of the reaction before letting the reaction continue to form a drug. The new Anti-Friedel-Crafts reaction allows researchers to add and modify molecules or groups of them later in the reaction. This new reaction isn’t a failure of the classic one, but rather a new perspective of it, a reaction that disproves the logic of the classic one simply because it is fundamentally a different one, just disguised to be similar.
Now you might ask: Why is this so important for drug discovery?
Changing even one position, one molecule can make a molecule undergo a fundamental change, turning a drug from a medicine to toxin, affecting not just the potency of a drug, but also its side effects, how long it lasts, and even whether it reaches the right areas of your body. The Friedel-Crafts reaction is classic not just because it is widely known but because it is the most convenient and the most efficient to do, but that was before the Anti-Friedel-Crafts reaction was found. The Anti-Friedel-Crafts reaction gives chemists something of a shortcut, it lets them access the drugs molecular structure much faster and change them much faster, with better conditions and under less pressurising circumstances. This means:
New variations of drugs that were unavailable to experiment due to the nature of the classic Friedel-Crafts reaction
Faster research of chemical structures
An easier method of experimenting with molecular structures
The Anti-Friedel-Crafts reaction is chemistry’s way of reminding us that chemistry isn’t as rigid as our textbooks and education make us believe, that chemistry is still as unexplored as physics, that reactions that were thought to be known inside-out can still give us unexpected surprises and that a chemical failure in labs aren’t just an experimental failure but an opportunity to take. Past chemical breakthroughs occurred in the limelight of failure, and expectations of a reaction does not make it inevitable, it is simply an expectation.
Because sometimes, the most important discoveries don’t happen when everything goes right; they happen when failure throws itself at us and we keep looking anyway.
