Extrathermodynamic relations in the binding of charged and neutral substrates to sulfobutylether-β-CDs (SBE-β-CDs) and a 2-hydroxypropyl-β-CD (HP-β-CD)

The thermodynamics of binding of various neutral, cationic and anionic substrates to β-cyclodextrin, a hydroxylpropyl-β-cyclodextrin (HP4M-β-CD) and three sulfobutyl-β-cyclodextrins with varying degrees of total substitution (SBE1M-β-CD, SBE7M-β-CD, and SBE12M-β-CD) were determined by estimating binding constants, using a UV spectrophotometric technique, and temperature variation. linear free energy relation (LFER) plots and enthalpy–entropy Compensation (EEC) plots provided insight into the mechanisms of complexation as did carbon T1 relaxation times using NMR. LFER plots for charged molecules with HP4M-β-CD deviate from the neutral substrates suggesting differences in interaction modes. LFER plots for SBE7M-β-CD show that cationic substrates surprisingly fall within the same linear relationship for neutral substrates while anionic substrates deviate. The EEC plots for HP4M-β-CD show the largest loss of motion and degree of desolvation upon complexation. The interaction with SBE1M-β-CD was similar to that for β-CD. SBE7M-β-CD, and SBE12M-β-CD EEC plots are similar with the least loss of motion upon complex formation, suggesting a more organized and less flexible structure. This is supported by the T1 relaxation times for SBE1M-β-CD, SBE7M-β-CD, and SBE12M-β-CD, which show a critical distance at which the mobility of the side chain is reduced to form an extended cavity. No such evidence was seen with HP4M-β-CD, although the effect of varying of hydroxypropyl substitution was not studied.