Physicochemical properties and membrane interactions of per(6-desoxy-6-halogenated) cyclodextrins

Per(6-iodo-6-desoxy) cyclodextrins are synthesis intermediates used in the design of the cation chelating per(3,6-anhydro) cyclodextrins. The modifications of the properties of these molecules resulting from the nature of the halogen substituant and also the number of osidic building blocks were investigated by varying both factors, using 1H and 31P-NMR and EPR spectroscopies. These nearly water insoluble molecules exhibits no complexing properties (for both ionic and apolar structures) but can be partially solubilized in micelles of detergent (sodium dodecyl sulfate) and also in phospholipid vesicles. Dipolar connectivity (nOesy) NMR experiments show that they are embedded at the chain level of the micelles/vesicles, without any inclusion complex formation. Changing the number of glucose building blocks (6,7 or 8) or/and the nature of the halogen nuclei at the positions 6 strongly modify cyclodextrin affinities and membrane interactions. For instance the per(6-bromo-6-desoxy)-cyclomaltohexaose (ABR) and -cyclomaltoheptaose (BBR) exhibit a selective affinity for cobalt (apparent Ka of 2500 and 790M(-1), respectively). In terms of interactions with membranes, alpha derivatives induce sterical hindrance at the phosphorus level while destructuring the chains. Other derivatives are located deeper and rigidify the most superficial part of the chain, suppressing the jump in membrane fluidity at transition temperature.