for "product inhibition" by performing the transfer hydrogenation of the phenyl substrate 4a in the presence of 1 equivalent of n-pentyl product 5f . After 24 hours, we observed full conversion of 4a to the respective product 5a with 93% ee, which is why we can rule out product inhibition as the origin for the low reactivity of alkyl substituted products (see further below for a study on the relative affinity of 4a, 4f, 5a and 5f for the catalyst). In a slightly different competition experiment, we combined the phenyl substrate 4a with the n-pentyl substrate 4f and observed no detectable transfer hydrogenation of 4a, along with only 2% conversion of 4f into 5f after 24 hours. This experiment indicates that the presence of the alkyl substrate 4f in the reaction medium "poisons" the catalyst for the otherwise reactive substrate 4a, for which a possible explanation is that the alkyl substrate binds to the binding pocket with higher affinity, yet with no turnover (Supplementary Fig. ). Further 1 H and P NMR experiments allowed a comparison of the affinity of substrates 4a and 4f, as well as the hydrogenated products 5a and 5f, towards the catalyst (S)-PO4H-[9]CPP. In sequential titration experiments between these four species, we determined that quinoline 4f exhibited by far the highest affinity with entire affinity series being: 5a < 4a < 5f < 4f (Supplementary Fig. -14; independently corroborated by ESI-MS, see Supplementary Fig. ). Thus, the products bind less strongly to the catalyst than the substrates, which is a prerequisite for high turnover numbers in supramolecular catalysis that is easily plagued by product inhibition. The particularly strong binding of alkyl substrates to the binding pocket of the nanohoop catalyst (S)-PO4H- [9]CPP however represents a problem, because it prevents catalytic turnover. At this point, we can only speculate on the specific reason is for the lack of turnover in the nanohoop cavity. A complexation-induced pKa shift could prevent the very first step in the catalytic cycle, which is the protonation of the quinoline and the formation of a tightly bound ion pair, yet this seems unlikely, because alkyl-substituted quinolines are more basic than their aryl-substituted counterparts. Moreover, the structure of the ternary complex with the Hantzsch ester or its corresponding pyridine may be significantly different for alkyl substrates. However, we did not observe indications to this end in qualitative experiments focusing on the Hantzsch ester concentration and the spiking of reactions with the pyridine. Further mechanistic work on specific non-covalent effects in the nanohoop cavity is clearly needed and currently ongoing.