The effect of host size on binding in host-guest complexes of cyclodextrins and polyoxometalates

Harnessing flexible host cavities opens opportunities for the design of novel supramolecular architectures that accommodate nanosized guests. This research examines unprecedented gas-phase structures of Keggin-type polyoxometalate PW12O403- (WPOM) and cyclodextrins (X-CD, X = alpha, beta, gamma, delta, epsilon, zeta) including previously unexplored large, flexible CDs. Using ion mobility spectrometry coupled to mass spectrometry (IM-MS) in conjunction with molecular dynamics (MD) simulations, we provide first insights into the binding modes between WPOM and larger CD hosts as isolated structures. Notably, gamma-CD forms two distinct structures with WPOM through binding to its primary and secondary faces. We also demonstrate that epsilon-CD forms a deep inclusion complex, which encapsulates WPOM within its annular inner cavity. In contrast, zeta-CD adopts a saddle-like conformation in its complex with WPOM, which resembles its free form in solution. More intriguingly, the gas-phase CD-WPOM structures are highly correlated with their counterparts in solution as characterized by nuclear magnetic resonance (NMR) spectroscopy. The strong correlation between the gas- and solution phase structures of CD-WPOM complexes highlight the power of gas-phase IM-MS for the structural characterization of supramolecular complexes with nanosized guests, which may be difficult to examine using conventional approaches. Supramolecular structural binding motifs of cyclodextrins and polyoxometalates probed by gas-phase ion mobility spectrometry and molecular dynamics simulations, which are highly correlated to solution-phase counterparts.