Stability of benzoporphyrin photosensitizers in water/ethanol mixtures: pKa determination and self-aggregation processes

• Published in: Journal of physical organic chemistry Vol. 24; no. 2; pp. 155 - 161
• Main Authors: Tessaro, André Luiz, Batistela, Vagner Roberto, Gracetto, Augusto César, Moisés de Oliveira, Hueder Paulo, Sernaglia, Rosana Lazara, de Souza, Vagner Roberto, Caetano, Wilker, Hioka, Noboru
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01-02-2011
• Subjects: aggregation; benzoporphyrin; chemometry; photodynamic; pKa
• ISSN: 0894-3230; 1099-1395
• DOI: 10.1002/poc.1721

Benzoporphyrin monoacid derivatives, here named B3A and B3B, are promising new drugs for photodynamic therapy. Although both isomers show interesting characteristics as photosensitizing compounds, they have some distinct physicochemical properties such as the tendency to self‐aggregate in water‐rich media. Because pH drives the presence of each species, the pKa of these compounds assumes strategic importance. However, traditional micro‐titration methods and UV–Vis absorption techniques fail to give reliable pKa values due to the characteristics of this highly complex system, such as the precipitation of hydrophobic species, close pKa values, and high absorption band superposition. In the present work, chemometric tools are employed to evaluate pKa, and the kinetic tendency of monomers to undergo self‐aggregation is investigated. In solvent mixtures at low water percentage in ethanol, both B3A and B3B are stabilized in a monomeric state. However, in mixtures with a high water content, self‐aggregation takes place, mainly under a mild pH acid condition (3 < pH < 6), in which the prevalent protolytic species of both isomers is the neutral charged form, compounds with carboxylic and porphyrin free‐base groups. It is demonstrated that both isomers can undergo aggregation following a self‐catalytic mechanism, which is 2000 times slower to B3A than B3B. For B3A, the aggregation is manifested by a decrease in the monomer band with the aggregation band probably superposed to that of the monomer. For B3B, together with the decrease in the monomer band, a new band related to self‐aggregates is observed. Copyright © 2010 John Wiley & Sons, Ltd.
Benzoporphyrin monoacid derivatives, here named B3A and B3B, are promising new drugs for photodynamic therapy. Although both isomers show interesting characteristics as photosensitizing compounds, they have some distinct physicochemical properties, such as the tendency to self‐aggregate in water‐rich media. Because pH drives the presence of each species, the pKa of these compounds assumes strategic importance.