Journal of Physical Chemistry A, Vol.108, No.43, 9384-9389, 2004
Aggregation of a benzoporphyrin derivative in water/organic solvent mixtures: A mechanistic proposition
The kinetics of the aggregation process of DiesterB, a homologous coproduct generated in Verteporfin synthesis (the drug used in the medication Visudyne applied in photodynamic therapy), was investigated by visible spectrophotometry in several aqueous organic solvents (dimethyl sulfoxide (DMSO), acetonitrile, dioxane, methanol, and ethanol). The monomeric form of DiesterB is stable in pure organic solvents, showing a characteristic peak at 690 nm. In water-rich medium, an aggregation process is induced, giving rise to a new band in the 720-740 nm region. In aqueous DMSO and acetonitrile solvents this process is very fast and leads to the formation of dimers, while in dioxane-, methanol-, and ethanol-water mixtures the absorption intensities show a sigmoidal time profile, suggesting a slow initial reaction (lag phase) followed by a rapid aggregation (log phase), characteristic of autocatalyzed reactions. The proposed final species in these solvents is a trimer as the main aggregate (supported by resonance light scattering and small-angle X-ray scattering experiments). The experimental absorbance values, taken at monomer or aggregate peaks during the reaction, were fitted using a nonconventional treatment proposed by Pasternack. This model allows evaluating two rate constants, due to a first (k(0), noncatalytic) and a second (k(c), catalytic) step, as well as a parameter (m), related to the size and amount of the catalyst nucleus. Although the model was originally applied to large porphyrin arrays growing on templates, an excellent accordance was obtained between its formalism and our kinetic experimental data. The global mechanism seems to start with a dimeric nucleus formation (lag phase), which acts, despite its small amount, as a catalytic center driving to trimers (log phase). The effects caused by water content and DiesterB concentration on the kinetic results support the proposed multistep equilibrium. The absence of isosbestic points during the process reinforces the presence of more than one step. The most unusual feature is the effect of the temperature on the rate constants. As the temperature is raised, the constants increase up to a maximum, and decrease for higher temperatures. The effect is more pronounced for k(c) than for the k(0) rate constant. The model proposed states that at high temperatures the equilibrium is shifted toward monomers, reducing the catalyst nucleus formation and resulting in an overall reaction velocity decrease.