A homochiral naphthalenediimide-based building block forms in water a disulfide library of macrocycles containing topological isomers. We attempted to identify each of these isomers, and explored the mechanisms leading to their formation. The two most abundant species of the library were assigned as a topologically chiral Solomon link (60% of the library, as measured by high-performance liquid chromatography (HPLC)) and a topologically achiral figure eight knot (18% by HPLC), competing products with formally different geometries but remarkably similar 4-fold symmetries. In contrast, a racemic mixture of building blocks gives the near-quantitative formation of another new and more stable structure, assigned as a meso figure eight knot. Taken together, these results seem to uncover a correlation between the point chirality of the building block used and the topological chirality of the major structure formed. These and the earlier discovery of a trefoil knot also suggest that the number of rigid components in the building block may translate into corresponding knot symmetry and could set the basis of a new strategy for constructing complex topologies.