Macrocycles are molecules made of large rings of atoms. Despite being relatively big and flexible, the molecules don't always stay "floppy" -- they can actually lock themselves into specific shapes and geometries.
In manufacturing, controlling the three-dimensional shapes of macrocycles is critical. It helps decide, for example, whether the aroma in a perfume is unique or whether a prescription drug will work on a particular disease.
Model chiral macrocycle (shown in blue) in the catalytic pocket of the enzyme CALB (shown in grey, catalytic serine 105 colored in green [PDB ID 5GV5]). The figure was generated using The PyMOL Molecular Graphics System, Version 1.2r3pre, Schrödinger, LLC. The docking of the macrocycles was carried out with the Fitted program from the Forecaster computational platform.
Credit: Université de Montréal
But for synthetic chemists, those who study the construction of molecules, controlling the topology of the large rings has not been a straightforward process - until now, that is, thanks to research done at Université de Montréal.
In a study published today in Science, a team led by chemistry professor Shawn Collins reports they have succeeded in using a natural process called biocatalysis to control the shapes of macrocycles.
And that could be a boon for the making of pharmaceuticals and electronics, they say.
"The shapes of the macrocycles we have made is what makes them special -- they are what we call planar chiral," said Collins. "And the planar chiral topology controls how the molecules interact with nature. In general, macrocycles with planar chirality are underexplored, because chemists usually have a lot of trouble making them."
Until now, they had two choices: perform multi-step syntheses that are tedious and wasteful, or they could exploit methods that employ catalysts based on elements that are toxic, expensive and non-abundant in the Earth's crust, such as ruthenium and rhodium.
Both approaches have long frustrated chemists, and Collins' team looked for an alternative. They found it in biocatalysis, a process that uses enzymes, biological and typically non-toxic catalysts, as a solution to preparing planar chiral macrocycles.
Remarkably, even though chemists had never before explored biocatalysis for the synthesis of planar chiral macrocycles, it turned out there was a commercially available product that could prepare the macrocycle: a lipase enzyme called CALB.
Using it, the biocatalysts were able to shape the macrocycles in often near-perfect selectivity, even though the enzyme had not evolved for that purpose.
Importantly, Collins and his team came up with a synthetic plan that involved using simple molecular building blocks to "decorate" macrocycles with functionality. "Functionality are handles, or simple groups of atoms that be easily transformed into arrangements that are more complex," Collins explained.
"Our hope is that the macrocycles can now be tailored to impact industry. Planar chiral macrocycles have already been known to act as antibiotics and anticancer agents. Applications in electronic materials -- in lasers and display devices, for example -- could be possible using the approach."
About this study
Biocatalytic synthesis of planar chiral macrocycles," by Shawn Collins et al, was published Feb. 21, 2020, in Science.
Jeff Heinrich | EurekAlert!
Turning carbon dioxide into liquid fuel
06.08.2020 | DOE/Argonne National Laboratory
Tellurium makes the difference
06.08.2020 | Friedrich-Schiller-Universität Jena
Scientists at the Fraunhofer Institute for Laser Technology ILT have come up with a striking new addition to contact stamping technologies in the ERDF research project ScanCut. In collaboration with industry partners from North Rhine-Westphalia, the Aachen-based team of researchers developed a hybrid manufacturing process for the laser cutting of thin-walled metal strips. This new process makes it possible to fabricate even the tiniest details of contact parts in an eco-friendly, high-precision and efficient manner.
Plug connectors are tiny and, at first glance, unremarkable – yet modern vehicles would be unable to function without them. Several thousand plug connectors...
An international research team has found a new approach that may be able to reduce bone loss in osteoporosis and maintain bone health.
Osteoporosis is the most common age-related bone disease which affects hundreds of millions of individuals worldwide. It is estimated that one in three women...
Traditional single-cell sequencing methods help to reveal insights about cellular differences and functions - but they do this with static snapshots only...
“Core-shell” clusters pave the way for new efficient nanomaterials that make catalysts, magnetic and laser sensors or measuring devices for detecting electromagnetic radiation more efficient.
Whether in innovative high-tech materials, more powerful computer chips, pharmaceuticals or in the field of renewable energies, nanoparticles – smallest...
An international research team with Prof. Cornelia Denz from the Institute of Applied Physics at the University of Münster develop for the first time light fields using caustics that do not change during propagation. With the new method, the physicists cleverly exploit light structures that can be seen in rainbows or when light is transmitted through drinking glasses.
Modern applications as high resolution microsopy or micro- or nanoscale material processing require customized laser beams that do not change during...
23.07.2020 | Event News
21.07.2020 | Event News
07.07.2020 | Event News
06.08.2020 | Earth Sciences
06.08.2020 | Power and Electrical Engineering
06.08.2020 | Life Sciences