Effect of the presence of beta-cyclodextrin on the solution behavior of procaine hydrochloride. Spectroscopic and thermodynamic studies

The effect of the addition of beta-cyclodextrin (CD) to the aqueous solutio ns of the local anesthetic drug, procaine hydrochloride, has been fully inv estigated by means of spectroscopic (UV-vis, steady-sate fluorescence, and NMR) and thermodynamic (density and speed of sound) studies. The global pic ture of the results indicates that procaine hydrochloride penetrates the CD cavity by the wider ring, -NH2 group end first, allowing up to the aromati c ring of the drug inside the cavity, with a 1:1 stoichiometry. A new model has been proposed to determine binding constants from UV-vis spectra, when the addition of CD provokes a wavelength shift instead of an absorbance in crease. The association constant, obtained from both emission fluorescence and UV-vis data, ranges from 400 to 200 M-1, on going from 15 to 40 degrees C. A linear decrease of the affinity of the cyclodextrin by the drug with temperature drives the enthalpy (Delta H degrees = -19 +/- 5 kJ mol(-1)) an d the entropy (Delta S degrees = -15 +/- 7 J K-1 mol(-1)) changes of the bi nding process to negative values. These values indicate that the encapsulat ion of procaine hydrochloride by beta-cyclodextrin is an exothermic and ent halpy governed process, with a balance between van der Waals contacts, hydr ophobic effect, and solvent reorganization being mainly responsible for the overall stability of the complex. The thermodynamic study has shown that i n the reorganization of water molecules after the association of the CD and the drug, four to five water molecules are expelled from the CD cavity and four to five water molecules are removed from the hydration shell of proca ine.