Multivariate analysis of protolytic and tautomeric equilibria of Erythrosine B and its ester derivatives in ionic and non-ionic micelles

Abstract

Erythrosine B (ERY) is a xanthene dye that has been widely used in recent years as a photoactive drug for Photodynamic Therapy. However, application of ERY and its derivatives as photosensitizer drugs depend not only on their singlet oxygen quantum yield, but also on their hydrophobicity, and photoactive protolytic and tautomeric species. In this work, the objective was to evaluate the acid-base equilibria of ERY and its derivatives: erythrosine methyl ester (ERYMET); erythrosine butyl ester (ERYBUT) and erythrosine decyl ester (ERYDEC), in biomimetic media (micelles of SDS and CTAB) as well as in some drug delivery systems of triblock copolymer Poloxamer (P-123 and F-127). All protolytic chemical equilibria were studied by employing chemometric multivariate analysis based on the Imbrie's Q-Mode Factor Analysis and k-Matrix methods. Tautomeric equilibria were evaluated taking into account of possible chemical structures and electronic spectroscopic approximations. Results from ester derivatives presenting only one protolytic equilibrium (at the phenolate group) and two possible tautomers, allow us to determine that protolytic equilibria follow the sequence pKaCOOH < pKaOH in SDS media for ERY by structure comparison. On the other hand, CTAB and polaxamers inverted the acidity of ERY protolytic groups (pKaOH < pKaCOOH) due to changes in the tautomeric equilibrium due to a lactone formation for the dyes neutral protolytic species inside the micelles. Chemometric approaches provided detailed analyses of protolytic/tautomeric equilibria of ERY. Through this, we achieved a deeper understanding of how ERY and its derivatives are affected by microenvironments in biomimetic and drug delivery systems.