Determinants of the host-guest interactions between α-, β- and γ-cyclodextrins and group IA, IIA and IIIA metal cations: a DFT/PCM study

The most widely used native cyclodextrins are alpha-, beta- and gamma-cyclodextrins containing six, seven or eight alpha-D-glucopyranoside units in the ring, respectively. Although the ligation properties of these host molecules have been extensively studied, a number of questions regarding their metal binding and selectivity remain unaddressed: to what extent do the size and flexibility of the host alpha-, beta- and gamma-cyclodextrins influence their metal affinity/selectivity? Which metal is the most preferred binding partner of alpha-, beta- and gamma-cyclodextrins? How do the charge, size and preferred coordination number of the metal cation shape its interactions with the host cyclodextrin? Can the guest metal cation inflict structural alterations in the host molecule and, if so, how do these changes correlate with the metal's properties? In the present study, by employing density functional theory (DFT) calculations combined with polarizable continuum model (PCM) computations, we try to answer these questions by evaluating the thermodynamic parameters of the IA, IIA and IIIA group metal binding to alpha, beta- and gamma-cyclodextrins. We assess how the interaction between the two binding partners depends on (1) the size, valence state and preferred coordination number of the guest metal cations, (2) the size and flexibility of the host molecule, and (3) the dielectric properties of the environment. The series of group IA (Na+ and Rb+), IIA (Mg2+ and Sr2+) and IIIA (Al3+ and In3+) metal cations have been chosen for the task as they allow us to study the effect of various metal parameters (variable charge, ionic radius and coordination number) on the strength and form of the interactions with the host cyclodextrins.