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)

Abstract

The thermodynamics of binding of various neutral, cationic and anionic substrates to β-cyclodextrin, a hydroxylpropyl-β-cyclodextrin (HP_(4M)-β-CD) and three sulfobutyl-β-cyclodextrins with varying degrees of total substitution (SBE_(1M)-β-CD, SBE_(7M)-β-CD, and SBE_(12M)-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 T_1 relaxation times using NMR. LFER plots for charged molecules with HP_(4M)-β-CD deviate from the neutral substrates suggesting differences in interaction modes. LFER plots for SBE_(7M)-β-CD show that cationic substrates surprisingly fall within the same linear relationship for neutral substrates while anionic substrates deviate. The EEC plots for HP_(4M)-β-CD show the largest loss of motion and degree of desolvation upon complexation. The interaction with SBE_(1M)-β-CD was similar to that for β-CD. SBE_(7M)-β-CD, and SBE_(12M)-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 T_1 relaxation times for SBE_(1M)-β-CD, SBE_(7M)-β-CD, and SBE_(12M)-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 HP_(4M)-β-CD, although the effect of varying of hydroxypropyl substitution was not studied.

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