Carba-closo-dodecaborates as Superchaotropic Anions

The host-guest chemistry of the 1-carba-closo-dodecaborate anion (CB₁₁H₁₂ ^-) and its 12-monosubstituted derivatives (R = I, Ph, Et, Bu, and OH) with cyclodextrins (CDs) has been studied, a class of weakly coordinating polyhedral boron cluster anions that have already found applications in catalysis and as ionic liquids. These mono-anions bind surprisingly tightly (K_a  ≈ 10⁵ M^-1) to the hydrophobic cavity of CDs, particularly the smallest α-CD and  β-CD homologues. This binding propensity closely resembles the binding of larger boron clusters, decaborates and dodecaborates (B₁₀X₁₀ ^2- and B₁₂X₁₂ ^2-, with X = Cl, Br, and I) as well as metallacarboranes (Co(C₂B₉H₁₁)₂ ^-), which has been attributed to the superchaotropic properties of these large, charge-dispersed anions. The thermodynamic signature of the encapsulation of 1-carba-closo-dodecaborates by CDs is consistent with the chaotropic effect as dominant driving force, that is, the binding is strongly enthalpically driven (ΔH down to -19 kcal mol^-1). The binding of the parent CB₁₁H₁₂ ^- mono-anion exceeds the binding of the isosteric B₁₂H₁₂ ^2- di-anion to the three CD homologues by 2-3 orders of magnitude, which indicates a higher chaotropicity, as expected when an ion has a lower charge density. The results position CB₁₁H₁₂ ^- as the smallest superchaotropic ion known to date, an assignment that was confirmed through its strong effect on the cloud point of a nonionic polymer (hydroxypropylcellulose). The CB₁₁H₁₂ ^- ion was subsequently also tested as a chaotropic transmembrane carrier, and it was found to be active in delivering hydrophilic peptides (Arg₈ and phalloidin) through lipid bilayer membranes, in artificial liposomes as well as live CHO-K1 cells. The binding and transport activities of the different superchaotropic boron cluster anions correlate well with their volume and surface charge density, as descriptors of their chaotropicity.