DOSY-NMR and Raman Investigations on the Self-Aggregation and Cyclodextrin Complexation of Vanillin

Vanillin (4-hydroxy-3-methoxybenzaldehyde) is a phenolic aldehyde with limited solubility in water; in this work we investigate its self-aggregation, as well as its complexation equilibria with β-cyclodextrin by using Nuclear Magnetic Resonance (NMR) and Vibrational Spectroscopy. In particular, Diffusion-Ordered NMR (DOSY) measurements allowing to detect diffusional changes caused by aggregation/inclusion phenomena, lead to a reliable estimate of the equilibrium constants of these processes whilst Raman spectroscopy was used to further characterize some structural details of vanillin self-aggregates and inclusion complexes. Although the self-association binding constant of vanillin in water was found to be low (Ka 10), dimeric species are not negligible within the investigated range of concentration (3-65 mM); on the other hand, no apparent formation of β-cyclodextrin self-aggregates was detected by DOSY measurements on aqueous solutions of β-cyclodextrin at different concentrations (2-12 mM). Finally, the binding of vanillin with β-cyclodextrin, as measured by DOSY technique within a narrow range of concentrations (2-15 mM) by assuming the existence of only the monomeric 1:1 vanillin/β-CD complex, was about an order of magnitude higher (Kc  90) than self-aggregation. However, the value of the equilibrium constant for this complexation was found to be significantly affected by the analytical concentrations of the host and guest system, thus indicating that Kc is an "apparent" equilibrium constant.anillin (4-hydroxy-3-methoxybenzaldehyde) is a phenolic aldehyde with limited solubility in water; in this work we investigate its self-aggregation, as well as its complexation equilibria with β-cyclodextrin by using Nuclear Magnetic Resonance (NMR) and Vibrational Spectroscopy. In particular, Diffusion-Ordered NMR (DOSY) measurements allowing to detect diffusional changes caused by aggregation/inclusion phenomena, lead to a reliable estimate of the equilibrium constants of these processes whilst Raman spectroscopy was used to further characterize some structural details of vanillin self-aggregates and inclusion complexes. Although the self-association binding constant of vanillin in water was found to be low (Ka 10), dimeric species are not negligible within the investigated range of concentration (3-65 mM); on the other hand, no apparent formation of β-cyclodextrin self-aggregates was detected by DOSY measurements on aqueous solutions of β-cyclodextrin at different concentrations (2-12 mM). Finally, the binding of vanillin with β-cyclodextrin, as measured by DOSY technique within a narrow range of concentrations (2-15 mM) by assuming the existence of only the monomeric 1:1 vanillin/β-CD complex, was about an order of magnitude higher (Kc  90) than self-aggregation. However, the value of the equilibrium constant for this complexation was found to be significantly affected by the analytical concentrations of the host and guest system, thus indicating that Kc is an "apparent" equilibrium constant.