A team of chemists at the Van ‘t Hoff Institute for Molecular Sciences of the University of Amsterdam, the Netherlands, has designed and synthesized a new class of molecules: quasi[1]catenanes. These pretzel-like molecules consist of two molecular rings ‘oppositely’ coupled at a central carbon atom. The research is published in the journal Nature Communications.
![Sketches of the quasi[1]catenane and quasi[1]rotaxane geometries: these are, together with the two regular ring systems, all available from a single quaternary carbon precursor; by starting from compound (5) in which four linear-chain ring precursors are connected to the same central tetrahedral carbon atom, after closure of the perpendicularly arranged rings, two spiro geometries may be envisioned; besides the regular spiro bicycle (1), after double-backfolding ring closure, the inverted spiro configuration is obtained giving quasi[1]catenane (2); alternatively, by installation of large stoppers at the end of the two linear chain fragments, next to the regular closure to give (4), cyclization via backfolding gives access to the mechanically locked quasi[1]rotaxane (3) conformation. Image credit: Steemers et al, doi: 10.1038/ncomms15392.](https://cdn.sci.news/images/enlarge3/image_4894e-Quasi-1-catenanes.jpg)
Sketches of the quasi[1]catenane and quasi[1]rotaxane geometries: these are, together with the two regular ring systems, all available from a single quaternary carbon precursor; by starting from compound (5) in which four linear-chain ring precursors are connected to the same central tetrahedral carbon atom, after closure of the perpendicularly arranged rings, two spiro geometries may be envisioned; besides the regular spiro bicycle (1), after double-backfolding ring closure, the inverted spiro configuration is obtained giving quasi[1]catenane (2); alternatively, by installation of large stoppers at the end of the two linear chain fragments, next to the regular closure to give (4), cyclization via backfolding gives access to the mechanically locked quasi[1]rotaxane (3) conformation. Image credit: Steemers et al, doi: 10.1038/ncomms15392.
“Lasso peptides are small proteins that, as their name indicates, consist of a molecular ‘loop’ around a molecular ‘rope’. They were first isolated from bacteria at the turn of the current century.”
“Recently, DNA analysis has revealed that lasso peptides are quite common in the realm of bacteria. Their biological function is to act as an antibiotic against other microorganisms, which makes them a potential new class of antibiotics,” the researchers said.
“The fact that 15 years after the discovery of lasso peptides synthetic chemists have not yet been able to develop a strategy leading to their unique molecular architecture underpins the complexity of these molecules.”
“The bottleneck here is that the rope is usually tightly bound within the loop.”
“This distinguishes lasso peptides from rotaxanes for which the British-American chemist Sir Fraser Stoddart shared the 2016 Nobel Prize in Chemistry.”
“During rotaxane synthesis the rope is ‘pulled’ through the loop.”
Since this is impossible for lasso peptide synthesis, Prof. van Maarseveen and co-authors used a different approach, forcing the loop to close in the right place around the rope.
“This turned out to be quite an undertaking,” they said.
“Eventually we managed to create a molecular scaffold assisting the synthesis in such a way that the loop correctly forms around the rope.”
To demonstrate the power of their method, the scientists applied the scaffold to also force both ends of the rope to form a second loop.
This resulted in the synthesis of a whole new class of molecules that they coined quasi[1]catenanes.
The next step for the team is to introduce easily breakable bonds in the quasi[1]catenane, so that the rings can be unlocked.
_____
Luuk Steemers et al. 2017. Synthesis of spiro quasi[1]catenanes and quasi[1]rotaxanes via a templated backfolding strategy. Nature Communications 8, article number: 15392; doi: 10.1038/ncomms15392
