Formation of 1:1 and 2:1 host–guest inclusion complexes of α-cyclodextrin with cycloalkanols: A 1H and 13C NMR spectroscopic study

•Cycloalkanols smaller than c-C5OH form only 1:1 inclusion complex with α-CD.•Cycloalkanols larger than c-C6OH form 2:1 inclusion complex with α-CD.•Binding constants were determined by means of 1H and 13C NMR titration.•The 2:1 inclusion complex is stabilized by hydrogen bonding between two α-CDs.•Two α-CDs with a guest formed the 2:1 inclusion complex in a tail-to-tail manner.

Binding constants (Ka’s) for the formation of inclusion complexes of α-cyclodextrin (α-CD) with cycloalkanols (c-CnOH; n = 4–8) were determined by means of 1H and 13C NMR titration, under two different conditions: (i) only 1:1 host–guest inclusion complexes are formed when the guest is in excess; (ii) the formation of 2:1 inclusion complexes occurs only after that of 1:1 inclusion complexes, when the host is in excess. The results of this work showed that α-CD can include c-C4OH or c-C5OH only when the molar ratio is 1:1; larger ring-sized cycloalkanols such as c-C6OH, c-C7OH or c-C8OH can be included only when the molar ratio is 2:1. These findings, together with those obtained for the four derivatives of α-CD, per-6-O-methyl-α-CD, per-2-O-methyl-α-CD, per-3-O-methyl-α-CD, and per-2,6-di-O-methyl-α-CD, suggested that α-CD forms 2:1 inclusion complexes with c-C6OH, c-C7OH or c-C8OH in a tail-to-tail manner, in which the secondary hydroxy sides of the two CD molecules face each other. Two-dimensional ROESY measurements confirmed our results.

Graphical abstractCyclohexanol, cycloheptanol, and cyclooctanol form 1:1 and 2:1 (host:guest) inclusion complexes with α-CD under the existence of excessive amount of α-CD. The smaller ring-sized cycloalkanols, cyclobutanol and cyclopentanol, form only 1:1 inclusion complex with α-CD. These facts were revealed by 1H and 13C NMR titration methods. The molecular orientation of the 2:1 inclusion complex was estimated to be formed by the tail-to-tail manner.Figure optionsDownload full-size imageDownload as PowerPoint slide