Quantitative understanding of guest binding enables the design of complex host-guest behavior.

We report a detailed binding study addressing both the thermodynamics and kinetics of binding of a large set of guest molecules with widely varying properties to a water-soluble M4L6 metal-organic host. The effects of different guest properties upon the binding strength and kinetics were elucidated by a systematic analysis of the binding data through principal component analysis, thus allowing structure-property relationships to be determined. These insights enabled us to design more complex encapsulation sequences in which multiple guests that were added simultaneously were bound and released by the host in a time-dependent manner, thus allowing multiple states of the system to be accessed sequentially. Moreover, by inclusion of the pH-sensitive guest pyridine, we were able to further extend our control over the binding by creating a reversible pH-controlled three-guest sequential binding cycle.