High-Affinity Binding of Metallacarborane Cobalt Bis(dicarbollide) Anions to Cyclodextrins and Application to Membrane Translocation

Abstract

Metallacarboranes are a class of inorganic boron clusters that have recently been recognized as biologically active compounds. Herein, we report on the host–guest complexation of several cobalt bis­(1,2-dicarbollide) anions (COSANs) with cyclodextrins (CDs) in aqueous solution. The binding affinities reach micromolar values, which are among the highest known values for native CDs, and exceed those for neutral hydrophobic organic guest molecules. The entrapment of the COSANs inside the cavity of CDs was confirmed using NMR and UV–visible spectroscopy, mass spectrometry, cyclic voltammetry, and isothermal titration calorimetry. Complexation by CDs greatly influences the photophysical and electrochemical properties of COSANs. In combination with indicator displacement assays, a label-free fluorescence-based method was developed to allow real-time monitoring of the translocation of COSANs through lipid bilayer membranes.

Face‐Fusion of Icosahedral Boron Hydride Increases Affinity to γ‐Cyclodextrin: closo,closo‐[B21H18]− as an Anion with Very Low Free Energy of Dehydration

“…The K a values obtained by ITC for the complexation of B21 (as sodium salt) with β‐CD and γ‐CD were found to be (1.3±0.1) ×10 5 and (1.8±0.5) ×10 6 M −1 , respectively. These values are on the same order of magnitude as those measured for meta ‐COSAN, twice higher than those obtained for the most tightly binding single icosahedron, i. e., B 12 Br 12 , 2−[11] and they significantly exceed the affinities of other “mononuclear” borate clusters or carboranes . The same trend applies for the B 12 H 12 2− cluster, whose association constant with γ‐CD is even smaller, by three orders of magnitude .…”

“…Nevertheless, regardless of the absolute variation, the Δ G ′ values show a very good linear correlation with the experimentally determined binding free energies (Δ G 0 values, R 2 =0.94, n =8, see Chart 1), which demonstrates that the computational model picks up essential contributions to the driving force of the host‐guest complexation process. Besides the correctly reproduced overall trend, the model predicts salient experimental details, namely ( i ) the strongest binding (most negative Δ G ′ values) for B21 and meta ‐COSAN, ( ii ) the significantly stronger binding of meta ‐COSAN than ortho ‐COSAN, and ( iii ) the maximal binding for X=Br in the B 12 X 12 2− series.…”

“…High‐affinity (micromolar) binding in aqueous solution has recently been documented between various COSANs and CDs . However, the closo ‐B 12 H 12 2− cluster, the smaller building block of B21 , only exhibits a lower affinity (millimolar) to γ‐CD .…”

“…We also used a computational model to gain deeper insight into the binding of B21 to γ‐CD and expanded this investigation, for comparison, to other compounds with icosahedral γ‐CD binding motifs, specifically ortho ‐COSAN, meta ‐COSAN ( ortho and meta define the positions of the respective C atoms in the COSAN framework), B 12 H 11 NH 3 − , B 12 H 12 2− , B 12 Cl 12 2− , B 12 Br 12 2− , and B 12 I 12 2− . For all these compounds, association constants ( K a ) are known under the same conditions (as sodium salts, in H 2 O) and a predominant 1 : 1 binding stoichiometry can be assumed …”

“…Indeed, despite the assigned dihydrogen bonds, B21 and meta ‐COSAN did not have highly negative Δ E values, which indicated that these dihydrogen bonds are not very strong, and are not the major driving force for complexation. It is worth noting that COSANs can exist as three rotamers ( cisoid , gauche , and transoid ) that differ in dipole moment, and among which the cisoid one is presumed to dominate in polar media …”