Carbon atoms love to hook up. Their versatile ability to bond with each other as well as atoms of other elements is why all known life is made of the stuff. And it doesn’t end with biology. Synthetic organic materials abound—from OLED displays to antibiotics.
Still manufacturing new organic molecules can be, to put it mildly, complicated. Although the most advanced organic molecular assembly takes place inside our cells, chemists have spent the last half century or so becoming highly skilled at stepwise synthesis of complex molecules in the lab as well.
A few years ago, University of Bristol researchers led by Professor Varinder Aggarwal described a method for making carbon chains as if they were on an assembly line—a step-by-step process that was both dependable and precise.
Much of the difficulty in the synthesis of organic molecules is that undesired side reactions occur during nearly every reaction. The more likely components are to react with new building blocks in unintended ways, the more unwanted compounds are produced at each step. This results in a soup of byproducts that are difficult to separate from the desired substance, especially when dealing with structurally similar molecules like chains.
In biological systems, reaction steps are tightly controlled by enzymes, effectively eliminating byproducts at each step. Chain molecules, for example, are passed from one enzyme to the next, each adding a piece to the growing chain. Similarly, the University of Bristol team’s molecular assembly line sequentially builds carbon-based molecules piece by piece, allowing for unprecedented control.
In a recent paper in the journal Nature, the team said they’ve taken the process to the next level. They’re now able to closely regulate not only molecular composition, but also molecular shape. By slightly altering the chemical mix in the assembly line process they can make molecules that are alternatively linear or helical (like a winding staircase).
As stated in the abstract, “This work should facilitate the rational design of molecules with predictable shapes, which could have an impact in areas of molecular sciences in which bespoke molecules are required.”
What’s the upshot of all this?
While the composition of molecules is important, their three-dimensional structure is essential when it involves interactions with the components in cells. In fact, lack of spatial control can be deadly. In the 1960s, a pharmaceutical drug named thalidomide existed in two mirror image forms—while one treated morning sickness, the other caused serious birth defects.
Additionally, spatial control is essential to the production of advanced materials like polymers. Cellulose and amylose (a component of starch) are both biological polymers that different only in their spatial orientation of one bond, resulting in linear and helical structures, respectively.
But developing molecular factories that can churn out specific molecules with precision is not just about control, but speed and scale…just like human-scale manufacturing.
It’s a bit like rapid prototyping using 3D printers. These days, manufacturers can go from design to prototype in a day instead of a month. That means they get to run more permutations in a shorter amount of time, thus improving the final design.
Furthermore, the field of combinatorial chemistry has been incorporating robots for years to perform large permutations of organic synthesis for new compound discovery. This includes rapid screening and characterization methods of very small quantities, which minimizes cost and waste. A process that incorporates a high-precision molecular assembly line would be most welcome in this burgeoning arena.
Looking ahead, new organic compounds may go from model to molecule much faster using the University of Bristol assembly-line synthesis or some other similar method. This would allow scientists to more rapidly imagine, synthesize, and test new molecular configurations.
And the faster that happens, the faster new organic materials and technologies can be further discovered.