Aggregation of a Benzoporphyrin Derivative in Water/Organic Solvent Mixtures:  A Mechanistic Proposition

Abstract

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.

Spectroscopic, Morphological, and Mechanistic Investigation of the Solvent‐Promoted Aggregation of Porphyrins Modified in meso‐Positions by Glucosylated Steroids

“…where Ext 0 , Ext ∞ and Ext t are the extinctions at initial, final and time t , respectively,29, 30 k 0 and k c the “uncatalysed” and “catalysed” reaction rates, m the nucleation factor (i.e., the minimum number of aggregated porphyrin monomers acting as a “nucleation seeds”, formed during the first delay period) and n the fractal growth factor. A value of n >1 indicates the occurrence of cooperative catalysed aggregate growth.…”

Self-Aggregation of 5,10,15,20-Tetrakis(4-Methoxyphenyl)porphyrin (Tmpp): Spectroscopic Studies and Multivariate Analyzes

“…17,18 Estudos de agregação de porfirinas e compostos análogos em diferentes solventes e misturas água/solvente são realizados com frequên-cia, para melhor compreensão do estado de agregação e propriedades das espécies autoassociadas em sistemas modelo simples de diferentes polaridades. 19 A extensão da formação de monômeros é dependente da constante dielétrica do meio, como exemplo a adição de álcool a sistemas aquosos favorece a formação de monômeros pela diminuição da polaridade da mistura e aumento da constante dielétrica. 20 A formação de espécies agregadas pode ser caracterizada por téc-nicas espectroscópicas, como espectroscopia de absorção eletrônica e espalhamento de luz ressonante (RLS).…”

Influência de diferentes sistemas de solvente água-etanol sobre as propriedades físico-químicas e espectroscópicas dos compostos macrocíclicos feofitina e clorofila α

“…Estas bandas apresentam comprimento de onda em torno de 600 nm, portanto dentro da "janela fototerapêutica" relativa à Terapia Fotodinâmica (TFD), 8 e por este motivo constituem uma importante classe de compostos empregados em TFD. [9][10][11][12] Esta possibilidade tem estimulado os estudos sobre as propriedades fotofísicas de clorinas substituídas e não-substituídas. 13,14 Entretanto, clorinas como a clorofila a têm uma longa cadeia apolar (Figura 1), o que confere elevado caráter hidrofóbico à sua estrutura, característica responsável pela maior tendência à autoagregação apresentada por esses compostos em solventes polares como, por exemplo, a água.…”