Binding of solutes to macromolecules is often influenced by steric effects caused by the 3D structures of both binding partners. In this study, the 1:1 alpha-cyclodextrin (alpha CD) binding constants (K-a1) for 70 organic chemicals were determined to explore the solute-structural effects on the alpha CD binding. K-a1 was measured using a three-part partitioning system with either a headspace or a passive sampler serving as the reference phase. The K-a1 values ranged from 1.08 to 4.97 log units. The results show that longer linear aliphatic chemicals form more stable complexes than shorter ones, and that the position of the functional group has a strong influence on K-a1, even stronger than the type of the functional group. Comparison of linear and variously branched aliphatic chemicals indicates that having a sterically unhindered alkyl chain is favorable for binding. These results suggest that only one alkyl chain can enter the binding cavity. Relatively small aromatic chemicals such as 1,3-dichlorobenzene bind to alpha CD well, while larger ones like tetrachlorobenzene and 3-ring aromatic chemicals show only a weak interaction with alpha CD, which can be explained by cavity exclusion. The findings of this study help interpret cyclodextrin binding data and facilitate the understanding of binding processes to macromolecules. (C) 2016 Elsevier Inc. All rights reserved.