In 1960, Wasserman synthesized a molecule in which two rings are held together like links in a chain. This molecule, which is called a catenane, is a topological isomer of the separated rings, which highlighted that molecules could be topologically non-trivial. This insight has found wider implications in biochemistry, where the topology of knotted and catenated proteins and oligonucleotides is thought to play a significant role in their properties, but it also led to the assumption that the stereochemistry of catenanes that are chiral due to the orientation of their rings is inherently topological in nature. Here we show that this assumption is incorrect by synthesizing an example that contains the same fundamental stereogenic unit but whose stereochemistry is Euclidean. Thus, we can unite the stereochemistry of catenanes with that of their topologically trivial cousins, the rotaxanes, paving the way for a more unified approach to their discussion.Topology and topological are often misapplied in chemistry to mean "shape", perhaps through confusion with topography and topographical respectively 1 . Formally, chemical topology finds its roots in mathematical topology 2 , the study of the properties of networks, surfaces, and objects under topologically allowed transformations. To consider the topology of a molecule, its structure is reduced to labelled vertices (the atoms) and edges (bonds between them) to generate a molecular graph 1 . One of the first applications of topology in chemistry was to enumerate the available isomers of higher order alkanes (CnH2n+2) 3 and there is continued interest in how molecular topology can be used to digitize and analyze chemical structures and their properties 4 . Conversely, the ultimately incorrect proposal by Lord Kelvin that atoms were knotted vortices in the aether motivated Tait to develop a systematic categorization of knots 5 .If only covalent bonding interactions are included 6,7 , the key difference between a chemical topologist's graph and a chemist's structural diagram is that the former does not consider molecular rigidity or geometry; when considering its topology, a molecular graph can be distorted arbitrarily provided the bonds are not broken or pass through one anotherall other transformations are valid, including the stretching of bonds and Commented [SG1]: E4. Title (15 words, 150 characters)Reviewers #1 and #3 both comment on the titleboth find it confusing, and I have to say that I agree with them. Although both suggest alternative titles, I'm afraid that neither meet our formatting requirements. I've included further guidance below.Response: we have reworded the title.To avoid unwieldy titles, we ask that you use no punctuation and no more than 15 words and 150 characters. Multi-part titles separated by dashes or colons (or similar), such as the one suggested by Reviewer #1, are not allowed. I've doublechecked with our copy editors and have been very firmly told that inverted commas and quotation marks (such as those in the titles suggested by Reviewers #1...

To consider the topology of a molecule its structure is reduced to labelled vertices (the atoms) and edges (bonds between them) to generate a molecular graph . If only covalent bonding interactions are included , , such graphs are like the structural diagrams commonly employed to describe molecules, except that in topological terms, atomic geometry is largely irrelevant; most molecules can be represented as a two-dimensional network and most covalent stereogenic units are topologically irrelevant. In 1960, Wasserman synthesized a molecule in which two rings are held together like in a chain, which is a topological isomer of the separated components, leading to the realization that molecules could be topologically non-trivial. This insight found wider implications in biochemistry and materials science but also led to the assumption that the stereochemistry of chiral catenanes is inherently topological in nature. We show this is incorrect by synthesizing an example whose stereogenic unit is identical to previous reports but whose stereochemistry is Euclidean. Thus, we can unite the stereochemistry of catenanes with that of their topologically trivial cousins, the rotaxanes, paving the way for a unified approach to their discussion.

To consider the topology of a molecule its structure is reduced to labelled vertices (the atoms) and edges (bonds between them) to generate a molecular graph . If only covalent bonding interactions are included , , such graphs are like the structural diagrams commonly employed to describe molecules, except that in topological terms, atomic geometry is largely irrelevant; most molecules can be represented as a two-dimensional network and most covalent stereogenic units are topologically irrelevant. In 1960, Wasserman synthesized a molecule in which two rings are held together like in a chain, which is a topological isomer of the separated components, leading to the realization that molecules could be topologically non-trivial. This insight found wider implications in biochemistry and materials science but also led to the assumption that the stereochemistry of chiral catenanes is inherently topological in nature. We show this is incorrect by synthesizing an example whose stereogenic unit is identical to previous reports but whose stereochemistry is Euclidean. Thus, we can unite the stereochemistry of catenanes with that of their topologically trivial cousins, the rotaxanes, paving the way for a unified approach to their discussion.

To consider the topology of a molecule, its structure is reduced to labelled vertices (the atoms) and edges (bonds between them) to generate a molecular graph. If only covalent bonding interactions are included, such graphs are like the structural diagrams commonly employed by chemists atomic geometry is irrelevant; most molecules can be represented as a two-dimensional network and most stereoisomers are topologically identical. In 1960, Wasserman synthesized a molecule in which two rings are held together like in a chain, which is a topological isomer of the separated rings, highlighting that molecules could be topologically non-trivial. This insight has found wider implications in biochemistry but it also led to the assumption that the stereochemistry of catenanes that are chiral due to the orientation of their rings is inherently topological in nature. We show this is incorrect by synthesizing an example whose stereochemistry is Euclidean. Thus, we can unite the stereochemistry of catenanes with that of their topologically trivial cousins, the rotaxanes, paving the way for a more unified approach to their discussion.