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It’s tricky to go more than a few minutes without running into a machine of some sort. Whether it was the toaster you made breakfast with, the train you took into town, or the machine you’re staring at right now to watch this video.

The idea of machines taking over the world isn’t post-apocalyptic fiction… it’s already happened. They’ve transformed society and improved our quality of life. So if advances in engineering have gotten us this far, from mass producing refrigerators to traveling to the moon, what’s next?

Many chemists are actually thinking a lot smaller: making machines out of molecules. It takes some chemical know-how to control motion on a microscopic scale. But tiny machines could revolutionize everything from medicine to materials science, where molecular processes play a big role.

A machine is basically any device that takes some energy input into at least one moving part, each with a distinct function. And these parts come together to produce a useful motion as an output, called work. Think of an old watch.

All those interconnecting cogs are arranged to make the hands on its face rotate just the right amount to keep time. Now, there are some obvious advantages to making machines smaller, like being able to transport them more easily and make them move more precisely. In 1959, the Bongo-playing, safe-cracking, Nobel Prize winning physicist Richard Feynman talked about “the problem of manipulating and controlling things on a small scale.” And by small, we’re talking a few millionths of a millimeter small — machines made up of one or a few molecules.

Twenty years later, nanotechnology pioneer Eric Drexler came across a transcript of Feynman’s lecture on machines. He developed some of the ideas further, and in 1981, he published a paper called “Molecular. Engineering.” Drexler imagined molecule-sized machines that could manipulate the reactants of chemical processes on an atomic scale, and even build new materials from the molecules up.

Which would be huge! Just think about how engineers have managed to shrink electrical components over the last few decades, turning computers the size of buildings into cell phones. And shrinking mechanical components could unlock a similar kind of revolution.

But building nanoscale machines comes with totally different challenges than the ones that many engineers deal with. For starters, when you get down to the size of molecules, objects don’t act the way we’re used to on everyday scales. Like, without careful design, a molecular nut and bolt couldn’t be twisted apart easily.

The electrostatic forces between the molecules, called Van Der Waals forces, would attract them together a lot more than friction affects ordinary nuts and bolts. I mean, these are the forces that help gecko feet stick to ceilings and stuff. Another problem is that it’s trickier to get the components of a molecular machine to move the way you want.

A tiny molecule of air bumping into a piston in your car engine doesn’t really change the way it moves. But that same air molecule might send a molecular machine flying or even destroy it. Even if the damage isn’t that extreme, the constant bombardment from nearby molecules — called thermal noise — could make the components move around randomly.

And that could make controlling their motions pretty difficult… even though that’s what we need to do for molecular machines to be useful. And finally, most molecules are linked together with chemical bonds, which form because of electrical attraction between molecules. There are different kinds of chemical bonds, but they tend to be fairly rigid and don’t allow for free movement between the two parts — the kind of movement that pretty much all machines rely on!

For example, imagine a bunch of water molecules locked into the crystal structure of an ice cube, or even clumped together in liquid water. Each negatively charged oxygen atom is attracted to the positively charged hydrogen atoms of nearby water molecules — forming hydrogen bonds between them. So to build molecular machines, engineers have to figure out how to utilize what’s called a mechanical bond, which your basic chemistry textbook maybe didn’t mention.

And in a mechanical bond, the shape of the molecules links them. The individual parts of each molecule aren’t strongly attracted to one another, but they can’t separate entirely without breaking the chemical bonds between the atoms within one of the molecules. Kind of like how your key can’t accidentally come off your key ring even though they aren’t physically connected.

And scientists had created linked molecules like this as early as the 1960s. They were called catenanes — chains of two or more connected rings of atoms. So researchers knew that catenanes existed, but they were rare and really difficult to produce for scientific studies, let alone anything practical.

At least until 1983, when French chemist Jean-Pierre Sauvage made an unexpected discovery. Sauvage was originally studying chemical reactions that were driven by ultraviolet light. And one of those processes involved C-shaped molecules that attached themselves to copper ions.

While modeling the reaction, he realized that by tweaking the method, he could produce catenanes from those molecules in much larger numbers than ever before. The trick started with getting a copper ion to bond to the inside of a ring-shaped molecule. Then, a C-shaped molecule can thread through the ring and attach to the same copper ion.

In the right kind of environment, another C-shaped molecule can chemically bond to the first one, creating a second interlocking ring! The final part of Sauvage’s chemical process was to pop that copper ion out. And voila: two molecular rings in one mechanically bound structure.

Those rings can freely rotate relative to one another, just like you’d want in a machine. Sauvage even extended the process to make knotted chemicals and more complicated chains. To set things in motion, in 1994 Sauvage’s team found a way to use that catenane with a sandwiched copper ion to rotate one of the rings around the other.

Because the rings aren’t uniform, they’ll adjust to more electrically stable positions if the charge of that ion changes. So when that copper ion gets an electron ripped off in a chemical reaction, one of the rings will rotate 180 degrees. And it’ll twist back if the copper ion recaptures an electron.

This motion is really important to master if we want to build molecular machines with rotating parts — for instance, something with a molecular propeller that can swim through liquids. Around the same time, across the English channel, chemist James Fraser Stoddart was making progress with a different chemical mechanism. Stoddart was well acquainted with the laws of attraction.

You’re probably familiar with the basics, too: positively charged chemical structures are attracted to negatively charged ones. And that’s how his team created a molecular machine called a rotaxane, a ring linked onto a thread. Back in 1991, Stoddart’s group made a nearly closed ring of atoms with a lack of electrons.

They also made a rod shaped molecule with two electron-rich sites and bulky silicon-based end-caps. When put together, electrostatic attraction made the ring thread onto the axle, where it could be closed off to form a complete ring with a chemical reaction. And although the positively charged ring was attracted to the negatively charged sites on the axle, it wasn’t locked in place too tightly with chemical bonds.

Because we’re talking about molecules here, when the ring had a certain amount of heat energy, it had energy to move around. So the researchers could make the ring hop between the two negatively charged spots on the axle, while those bulky groups kept it from sliding off. In 1994, Stoddart got even more precise and created two chemically different sites on the axle structure based on molecules called benzidine and biphenol groups.

Those groups have different electric and chemical properties depending on the acidity — or pH — of the surrounding environment. In an acidic environment, the benzidine group becomes positively charged, repelling a ring so it sits on the biphenol group. So basically, these researchers figured out how to control a ring’s movement on an axle in multiple ways!

His group also used the principles behind these axles to make a molecular elevator that can raise itself a few nanometers, and even a molecular muscle that can stretch and contract kind of like our own muscle cells. Now, lots of components in normal machines, like the cogs in a watch or wheels on a car, rely on continuously rotating elements. Sauvage’s ring could rotate in response to an input, but couldn’t provide a continuous, controlled output like a motor.

In 1999, though, the organic chemist Ben Feringa and his group in the Netherlands achieved just that. They developed a double-sided molecule that acted a bit like motor blades. As we’ve mentioned, thermal noise makes it tricky to control how a molecular component moves.

But Feringa’s molecule was based on two methyl groups that were designed to only rotate one way around. Every time a pulse of UV light hits one of the methyl groups, it absorbs the light and converts it into kinetic energy. The hit methyl group then rotates around an axis and bends over the other methyl group until it snaps past — so it’s blocked from spinning backwards.

And presto, you’ve got the world’s first molecular motor. As if that wasn’t cool enough, in 2011 Feringa and his group even took it even further and used this technique to build a nano-car with four rotating wheels. Between them, Sauvage, Stoddart, and Feringa used clever designs and special environments to solve some of the problems we were having with very basic molecular machines.

And in 2016, they were collectively awarded the Nobel Prize in Chemistry for their work. We’ve only just begun exploring other machines we might be able to make on the nanoscale. And we know there are plenty of options, because nature has been building them for billions of years.

Like, right now in your body, super complex molecular machines made of proteins are doing all kinds of things to keep you going. Like, your myosins walk along tracks of muscle fiber, pulling them to help you contract your muscles. And other cells, like sperm or certain bacteria, have built-in molecular motors to make their flagella spin around, so they can move through fluids.

And those are just two of many examples, so scientists have plenty of inspiration for future inventions. And some researchers have proposed that molecular machines could be used to deliver drugs in the body. For example, mesoporous particles have lots of little holes that release their contents in response to ultrasound waves — kind of like little salt shakers.

Filled with the right drugs, we could load these particles onto a molecular transport machine to, like, dose tumors with cancer-fighting molecules. Other researchers have developed a gel with those molecular motors we mentioned, by attaching them to a tangle of long chains of molecules called polymers. When you shine a light on the material or heat it up, the motors reel in the fibers like fishing line, which shrinks the volume of the gel.

Because those motors are storing energy in the form of those bundled up molecules, if we could find a way to extract the energy back out, this could be a step towards a new kind of solar battery! All that said, we have a long way to go before we’re building molecular machine factories, or anything beyond these basic experiments. It’s still tricky to make these tiny machines in large quantities.

And there may be other problems with making a bunch of individually developed components work together. But after more research, we might have molecular mechanisms in our scientific tool-kits — and machines to help us at every scale of life. Thanks for watching this episode of SciShow!

If you want to learn more about engineering on a microscopic scale, check out our episode where we explain how the genetic engineering technique CRISPR works. And if you want to keep learning about all kinds of science with us, go to youtube.com/scishow and subscribe. [♪OUTRO].