Machine automatically assembles complex molecules at the microscopic level

The synthesis of complex small molecules in the laboratory is specialized and intricate work that is both difficult and time-consuming. Even highly-trained chemists can take many years to determine how to build each one, let alone discover and describe its functions. In an attempt to improve this situation, a team of chemists at the University of Illinois claim to have created a machine that is able to assemble a vast range of complex molecules at the push of a button.

A specific class of structures, complex small molecules are readily found in nature and are intrinsic to research in a wide range of scientific fields. In medicine, for example, many of the latest medications have been derived from the manipulation of small molecules. In the biological sciences, small molecules are often used to help reveal the interior mechanisms of tissues and cells. Even non-organic electronic technologies such as semiconductors, including solar cells and LEDs, require the creation and use of these miniature assemblies.

The Illinois team believes that this new style of molecular creation has the potential to vastly increase the speeds at which molecules can be built and, in turn, quickly allow greater and more efficient drug development technologies and other scientific disciplines that rely on a supply of complex molecules.

"We wanted to take a very complex process, chemical synthesis, and make it simple," said professor Martin Burke, a Howard Hughes Medical Institute Early Career Scientist, and leader of the research team. "Simplicity enables automation, which, in turn, can broadly enable discovery and bring the substantial power of making molecules to nonspecialists."

This may prove a boon to research labs everywhere, particularly given that much of the work in complex molecular structures is impeded simply because of the inordinate amount of time and effort to produce these molecules.

"Up to now, the bottleneck has been synthesis," said professor Burke. "There are many areas where progress is being slowed, and many molecules that pharmaceutical companies aren’t even working on, because the barrier to synthesis is so high."

A large impetus for Burke and his team's work was solving this bottleneck. To do this, they looked at what the major impediments were to the complex molecule creation process and realized that they needed to take a very complex process and simplify it.

The researchers started with the basics by breaking down the construction of complex molecules into even smaller constituent elements that could then be more easily assembled. As these elements all possess the same interconnecting chemical connectors, these simple structures could then all be relatively simply joined back together using a single reaction.

The team has compared this process with the method of joining interconnecting plastic blocks that children play with: they may all be different shapes and sizes, but they have a common connecting system that allows them all to be easily and securely snapped together. These aren't esoteric, expensive, difficult to obtain chemical building blocks, but, according to the team, many of them are available commercially, straight off the shelf.

The nuts and bolts of this system of complex molecule assembly relies on an automated "catch-and-release" method that the researchers devised. In this method, the system joins each building block one at a time, then washes away the excess chemicals used in the process before moving on to add the next one in the sequence.

The researchers report that they have been able to show that their device can build 14 separate classes of small complex molecules, which also included those composed of especially difficult to make ring-type structures, all in the same automated process.

"Dr. Burke’s research has yielded a significant advance that helps make complex small molecule synthesis more efficient, flexible and accessible," said Miles Fabian of the National Institutes of Health’s National Institute of General Medical Sciences, which partially funded the research. "It is exciting to think about the impact that continued advances in these directions will have on synthetic chemistry and life science research."

The short video below includes an explanation by Dr Burke regarding this new technology.

Details of this research were recently published in the journal Science.

Source: University of Illinois