Traditional chemistry is so last year. Welcome to the world of mechanochemistry, where reactions that were thought impossible – indeed, that are impossible when attempted in more conventional ways – become possible, and where brand-new avenues of exploration are opening up.
Even if the last time you entered a chemistry lab was way back in high school, chances are you’ll remember spending a lot of time mixing various liquids together – perhaps over a trusty Bunsen burner – waiting impatiently for something exciting to happen, like the colors changing or a powdery precipitate appearing.
Many chemical reactions have traditionally called for a solvent, and selecting the correct one for your purposes is a vital part of the process – but there are ways to get two substances to interact without dissolving them first. One is by introducing mechanical forces into the mix, known as mechanochemistry.
“Exotic chemistry”
“Although introduced by W. H. Ostwald at the end of the 19th century, mechanochemistry has been often regarded as exotic chemistry,” write the authors of a 2022 review on the subject. “This is beginning to change.”
Usually, the energy needed to fuel a chemical reaction comes from the addition of light, heat, and/or electricity. “Almost all kinds of energy can be applied for the initiation of chemical reactions or for heating of reaction mixtures,” explains a 2011 paper. Instead of any of these, however, mechanochemistry relies on mechanical forces – for example, physically grinding two solid substances together with a mortar and pestle.
The advantages of this approach include that it works for solids that aren’t actually soluble, or in cases where the use of a solvent would interfere with the reaction (or could be hazardous to the human experimenter).
As well as the mortar and pestle – an oldie but still a goodie – there are some slightly more modern tools available for today’s discerning mechanochemist. Ball mills are a common option, large grinders filled with hard balls that pummel chosen materials down into tiny particles. These come in various different types – with different milling materials, rotational frequencies, etc – so you can customize them to your particular experiment. Using a machine rather than relying on a human being’s grinding ability means you get a more consistent result.
It all sounds quite simple – mash two things together with enough force and a chemical reaction might occur – but the reality is there’s a lot of complex chemistry going on beneath the surface, a lot of it not fully understood.
“Understanding mechanochemical transformations is a problematic task precisely because of the profound differences between conventional solution chemistry and the chemistry activated by mechanical forces,” reads the 2022 review.
A study in 2019 sought to try and learn more about what’s actually happening to the particles when substances undergo a mechanochemical reaction. The international team used computer modeling to simulate the co-crystallization of aspirin and another painkilling drug, meloxicam, revealing what they described as “striking new insights”. Although both drugs were being combined in their solid crystal forms, with no solvent added, only minimal energy was needed to get them to start mixing.
“What struck me was that the crystals behave like putty – they almost seem like plasticine and they’re amorphous at these contacts. When you pull them apart there’s a connective neck of molecules in between the two crystals,” co-corresponding author Professor Stuart James told Chemistry World.
“I see this as being near the start of a new research area,” he added, and it seems the International Union of Pure and Applied Chemistry (IUPAC) agreed, naming reactive extrusion (AKA mechanochemistry) as one of the 10 chemical innovations forecast to change the world as part of its centenary celebrations.
A greener future
One of the drivers behind the increased interest in mechanochemistry is that it could be used to make existing synthesis processes both safer and more sustainable.
Solvents often make up the vast majority of a reaction mixture. Unfortunately, most of the industrial solvents we use don’t have fantastic green credentials.
Add to this the fact that many are hazardous to human health, and bring with them complicated logistics around storage and transportation, and you can quickly see why being able to eliminate the solvents would be attractive.
Mechanochemical reactions may also progress more quickly than conventional reactions, increasing efficiency.
All this to say, mechanochemistry is not in itself a simple solution to all our problems, but it could certainly be an important part of making chemistry “greener”.
Making the impossible possible
The other aspect of mechanochemistry that’s generated real buzz is its potential to open up completely new ways of synthesizing materials.
“Back in the 1990s [...] studies showed that mechanochemically promoted reactions proceed along synthetic pathways different from those described in the solution,” explains the 2022 review.
The authors warn that only using mechanochemistry to enhance chemical reactions and processes that we’re already familiar with would be “an incomprehensible underestimation and a potentially dangerous mistake.”
“In short,” they add, “mechanochemistry is a challenging opportunity to explore hitherto uncharted territories of chemical space.”
One of several examples involves a class of molecules that have been recognized for their potential in pharmaceutical products and herbicides: N-sulfonylguanidines. Synthesizing these compounds is very difficult using a traditional solvent-based approach, but researchers have observed that adding mechanical energy into the mix can overcome these issues and yield much more of the useful product.
Proponents of mechanochemistry believe there could be many other such reactions that have been consigned to the “impossible” pile, but which might merit another look using mechanochemical techniques.
The impossible made possible, and it’s greener too? Well, IUPAC did say that mechanochemistry might change the world.