No abstract

The pKa of Eosin Y and Erythrosin B were experimentally and computationally studied in water/DMSO mixtures using UV-Vis spectra, orbital and electrostatic properties to understand the tautomers contribution in the protolithic equilibria.

The correct selection of a dye that has effective action as a photosensitizer is a primary concern for successful therapeutic outcomes. The effectiveness of the photodynamic agent is related to both the targeting of cell membranes and the photochemical yield of the chosen dye. The distributions of xanthene derivatives Eosin Y, Erythrosin B, and Rose Bengal B in vesicles of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) in both liquid-crystalline and gel phases were investigated by fluorescence spectroscopy. Binding constants, fluorescence anisotropy, fluorescence quenching, fluorescence quantum yield, and fluorescence resonance energy transfer at physiological pH conditions were determined. To Erythrosin B and Eosin Y, the iodide quenching rate constant was shown to involve a sphere of action mechanism driven by a specific interaction between Erythrosin B and Eosin Y molecules and the choline head-group of the phospholipid; in contrast, Rose Bengal B was located deep in the membrane and this mechanism was not present. The dyes can be ordered by their penetration depth in the membrane, and this order was found to be Eosin Y < Erythrosin B < Rose Bengal B. These results demonstrate a rational approach for the screening of more active agents for photodynamic therapy based on the affinity between the xanthene derivatives and DPPC vesicles.

No abstract

The alkaline hydrolysis of a series of homologous reactants constituted by two reactive centers bridged by a methylene spacers chain, the 1,n-bis(2-azidepyridinium)alkanes (n = 3, 4, 5, 6, and 8), is investigated. The reaction under pseudo-first-order condition was followed by ultraviolet-visible spectrophotometry. The presence of clear isosbestic point suggests the absence of stable intermediates. However, the intermediates 1-(2-azidepyridinium), n-(2-pyridone)alkanes (monocationic compounds), were isolated and characterized as well the reaction end products 1,n-(2-pyridone)alkanes (noncharged compounds). The kinetic analysis fitted to a two-step consecutive reaction, where the k 1 /k 2 values demonstrate the larger reactivity of the first step over the second one, especially for shorter bridged reactants. The OH − reaction order is one for each step. Although Debye-Hückel law was obeyed, the experimental point at ionic strength zero is much higher than the extrapolated one. In addition, the k 1 values substantially decrease as KCl is added especially for shorter homologous whereas the effect on k 2 is almost negligible. Simple charge density effects as a function of the spacer's length do not explain the observations. On the other hand, from the pronounced anion selectivity inhibition effects on k 1 for the shorter derivatives, the existence of an equilibrium involving a conformer, a "sandwich-type" complex with the OH − between the two pyridinium rings, with an "open-stretched" conformer is proposed. For short-bridged reactants, the complex conformer

The comprehension of the tautomeric and aggregation dynamics of curcumin (Cur) is fundamental to predict clinical responses and to develop biomedical materials in drug delivery science. Although several studies have explored the dynamics of biologically active agents incorporated into drug delivery systems, little information about the influence of these pharmaceutical systems on the tautomeric and aggregation profile of Cur in supersaturated conditions is known. In the present study, HF-3c and B3LYP/6-31+G(d,p) levels of theory were applied to investigate the stabilization capacity of tautomeric components in the micellar blocks of Pluronics F127 and P123. Additionally, the computational modeling provided molecular orbital and theoretical spectra of the components, either after interaction with copolymeric segments or aggregational processes, which is fundamental to understand the critical packing parameters (CPPs) of these materials influenced by Cur incorporation. "Digital chromatography" by multivariate curve resolution-alternating least squares has been explored to obtain the spectra of the pure species under experimental conditions. Scanning and transmission electron microscopy analyses allowed the visualization of Pluronics dynamics related to self-association behavior and their dependence on Cur interaction. Molecular modeling results have shown that Keto tautomer can interact with both hydrophilic poly(ethylene oxide) (PEO) and hydrophobic poly(propylene oxide) blocks comprised of Pluronics. These results suggest that alterations in CPP parameters lead to an increase of hydrophobicity in the cross-sectional area of the PEO block, the most outstanding in F127 copolymer. Therefore, it is possible to see that the changes in CPP parameters lead to an increase in the hydrophobicity in the crosssectional area of the most prominent PEO block in the copolymer F127. There is a strong evidence for the coexistence of complex structures resulting from the interaction between the copolymeric self-association and Cur, which allows us to get a better insight into the architecture of these copolymeric systems when incorporated with hydrophobic compounds.

The self-aggregation process and its overcoming remain a barrier for the employment of many molecules as photosensitizers (PS) in photodynamic therapy (PDT). The B-ring isomer co-produced during the synthesis of the Verteporfin[Formula: see text] (A-ring) is an example. Although both isomers possess similar in vitro/in vivo efficiency, the strong and not well-understood self-aggregation process of the B-ring derivative impairs its clinical use. This paper reports the use of theoretical calculus and its correlation with experimental analysis to find the main differences between the A and B-ring isomers. For that purpose, micelles of Pluronic[Formula: see text] P-123 and Sodium Dodecyl Sulfate were chosen as simple membrane models and possible drug delivery system, as in the case of P-123. At physiological pH, the main reason for the high self-aggregation tendency is associated with the higher (22%) molecular volume of the B ring, which increases the van der Waals interactions. However, at mildly acidic conditions, the B ring possesses a shallow dihedral angle between the methyl ester group and the tetrapyrrolic macrocycle that favors the approach of units in the aggregate. These discrepancies directly affect the binding and stability of the isomers in the micelles. However, P-123 micelles were able to readily incorporate and monomerize/stabilize both PS over long periods. NOESY experiments confirmed a deep location of both PS inside P-123 micelles, which justifies their efficiency in preventing the self-aggregation process. These findings may substantiate new studies involving the marginalized B-ring isomers and encourage new development in formulations for their use in PDT.

No abstract