Confinement of Polar Solvents within β-Cyclodextrins

Abstract

Using molecular dynamics techniques, we examined equilibrium and dynamical characteristics pertaining to the solvation of a single beta-cyclodextrin (CD) in water and in dimethylsulfoxide (DMSO). Compared to its global minimum structure, the overall shape of the solute in solution is reasonably well preserved. While in aqueous solutions, the average number of solvent molecules retained within the central cavity of the oligosaccharide is close to 5, for DMSO, that number reduces to approximately 1. No evidence of significant orientational correlations of the trapped molecules were found in either solvent. The main contributions to the hydrogen-bond (HB) connectivity between the solute and the bulk phases are due to the more distal HO6-O6 hydroxyl groups, acting as HB donors and acceptors. The average residence time for retained DMSO was found to be in the nanosecond range, and it is, at least, 1 order of magnitude longer that the one observed for water. We also analyzed the characteristics of the solvation of the beta-CD in an equimolar water-DMSO mixture. In this environment, we found a preferential localization of a single DMSO molecule in the interior of the CD and a very minor retention of water. In the mixture, the characteristic time of residence of the trapped DMSO molecule increases by a factor of approximately 2. The observed difference was rationalized in terms of the fluctuations of the local concentrations of the two species in the vicinity of the CD top and bottom rims.

Molecular View into the Cyclodextrin Cavity: Structure and Hydration

“…The water occupancy determined from the geometric method matches very well with the experimental value for α-CD and γ-CD, but the computed water occupancy inside β-CD is lower than the experimental value by two water molecules. A couple of MD simulations have reported the water coordination number determined from the cylindrical rdf, definitely a better approximation than a spherical rdf, as 4.85 39 and 5, 40 respectively. The water sites reported by the diffraction study of α-CD and γ-CD crystals are completely inside their respective cavities; the former being a small well-defined cavity and in the latter, rims were occluded by the neighboring CD molecules in the crystal packing.…”

“…Numerous MD simulation studies have investigated the conformational dynamics and hydration of native and substituted CDs using various force fields like CVFF, 35 CSFF/CHARMM, 36 − 40 GROMOS, 41 − 44 GLYCAM98, 45 q4mdCD, 46 and OPLS. 47 , 48 The accuracy of the MD results, indeed, depends on the reliability of the underlying molecular model.…”

Diffusivity of α-, β-, γ-cyclodextrin and the inclusion complex of β-cyclodextrin: Ibuprofen in aqueous solutions; A molecular dynamics simulation study

“… [51] , Rodriguez et al. [85] , and Shikata et al. [86] the residence time of water molecules in the CD cavity was investigated by MD simulations and experimental techniques.…”

Host–Guest‐Mediated DNA Templation of Polycationic Supramolecules for Hierarchical Nanocondensation and the Delivery of Gene Material

“…The thermodynamic signature of supramolecular‐complex formation between heptamine 1 and the ditopic adamantane hosts was examined by isothermal titration calorimetry (ITC) at 25 °C in aqueous solution containing 2 % DMSO. The presence of DMSO as a cosolvent is expected to strongly decrease the K values relative to pure water, given the known affinity of DMSO molecules for the β‐CD cavity 44. 45 Yet, we can reasonably expect that this presence of DMSO would affect the inclusion of all guests 2 a – h in a similar manner because these molecules share the same adamantane motif, thus allowing a comparison of the relative stability of the corresponding complexes.…”

“…The thermodynamic signature of supramolecular-complex formationb etween heptamine 1 and the ditopic adamantane hosts was examined by isothermal titration calorimetry (ITC) at 25 8Ci na queous solution containing 2% DMSO.T he presence of DMSO as ac osolvent is expected to strongly decrease the K values relative to pure water,g iven the known affinity of DMSO molecules for the b-CD cavity. [44,45] Yet, we can reasonably expect that this presence of DMSO would affect the inclusion of all guests 2a-h in as imilar manner because these molecules share the same adamantane motif, thus allowing acomparisono ft he relative stability of the corresponding complexes.T he ethylenediamide-linked bisadamantane representative 2b could not be assayed,e ven under thesec onditions, due to solubility problems. In all the other cases, the thermograms (see Figure S1 in the Supporting Information) fitted well with am odel of n equal and independentb inding sites and were indicative of entropyd riven (DS > 0) endothermic processes (DH > 0), which is in agreement with hydrophobic interactions as the drivingf orce for complex formation, thus leading to 2:1s toichiometries.…”