Novel water-soluble bacteriochlorophyll derivatives for vascular-targeted photodynamic therapy: synthesis, solubility, phototoxicity and the effect of serum proteins

New negatively charged water-soluble bacteriochlorophyll (Bchl) derivatives were developed in our laboratory for vascular-targeted photodynamic therapy (VTP). Here we focused on the synthesis, characterization and interaction of the new candidates with serum proteins and particularly on the effect of serum albumin on the photocytotoxicity of WST11, a representative compound of the new derivatives. Using several approaches, we found that aminolysis of the isocyclic ring with negatively charged residues markedly increases the hydrophilicity of the Bchl sensitizers, decreases their self-association constant and selectively increases their affinity to serum albumin, compared with other serum proteins. The photocytotoxicity of the new candidates in endothelial cell culture largely depends on the concentration of the serum albumin. Importantly, after incubation with physiological concentrations of serum albumin (500-600 microM), WST11 was found to be poorly photocytotoxic (>80% endothelial cell survival in cell cultures). However, in a recent publication (Mazor, O. et al. [2005] Photochem. Photobiol. 81, 342-351) we showed that VTP of M2R melanoma xenografts with a similar WST11 concentration resulted in approximately 100% tumor flattening and >70% cure rate. We therefore propose that the two studies collectively suggest that the antitumor activity of WST11 and probably of other similar candidates does not depend on direct photointoxication of individual endothelial cells but on the vascular tissue response to the VTP insult.     

Protein Adsorption onto Zirconia Modified with Terminally Grafted Polyvinylpyrrolidone

Electroacoustics was used to study SDS-stabilized sunflower oil-in-water emulsions, with oil volume fractions between 2% and 50%. The dynamic mobility of the oil droplets was measured; the size and electric charge on the drops were calculated using formulas derived for dilute and concentrated systems and the results were compared. The relation derived for concentrated systems appears to be valid up to at least 50% provided the particles remain within the size range of the instrument, which shifts upward with rising concentration. Conductivity and pH had little effect on particle properties in the range studied; higher oil volume fraction (φ) had a substantial influence on the particle size produced in a homogenizer, but not on the zeta potential. Both median size and spread decreased with increases in φ. In contrast, both size and charge were hardly affected at volume fractions less than 10%. Dilution of the emulsion with a surfactant solution of the same composition as the water phase changed neither the particle size nor the zeta potential. The temperature of the emulsification process had a significant influence on the particle size but the zeta potential was hardly affected. Surfactant concentration had some effect on size at low volume fractions but not for φ>10%. The electroacoustic method hence could be applied to analyze both the dilute and the concentrated emulsions directly. Copyright 2001 Academic Press.     

High spin mesons and zweig-superconvergence relations

The basic and simplest aspects of duality are used to deduce some decay widths ofJ ^P =3^?, 4⁺... mesons in agreement with available data. This may be of interest when investigating the nature of these mesons and, in particular, whether they are conventional \(q\bar q\) -systems or not.     

Electrospray Ionization Fourier Transform Ion Cyclotron Resonance Mass Spectrometric Study on Sodium Azide Cluster Ions

Introduction Mass spectrometry (MS) has been an important technique for studying size-dependent cluster properties with unparalleled sensitivity, specificity, and versatil-ity.1,2 Especially Fourier transform ion cyclotron reso-nance (FT-ICR) MS offers the benefits of ultra-high mass resolving power, superior mass accuracy, and the ability of affording useful structure information with tandem MS. The introduction of electrospray ionization (ESI) as a gentle mode of ion generation for MS…     

Probing the molecular interaction of chymotrypsin with organophosphorus compounds by 31P diffusion NMR in aqueous solutions

In the present study, we applied for the first time (31)P diffusion NMR to resolve different species obtained by the addition of organophosphorus compounds (OP) such as diisopropyl phosphorofluoridate (DFP) or 1-pyrenebutyl phosphorodichloridate (PBPDC) to alpha-chymotrypsin (Cht). (31)P diffusion NMR was used since the products of these reactions constitute a mixture of OP-covalent conjugates of the enzyme and OP-containing hydrolysis products that have noninformative (1)H NMR spectra. It was shown that the peak, attributed to the covalent native diisopropylphosphoryl-Cht (DIP-Cht) conjugate by chemical shift considerations, has a greater diffusion coefficient (D = (0.65 +/- 0.01) x 10(-5) cm(2) s(-1)) than expected from its molecular mass (approximately 25 kDa). This peak was therefore suggested to consist of at least two superimposed signals of diisopropyl phosphoryl (DIP) pools of high and low molecular weights that happen to have the same chemical shift. This conclusion was substantiated by the use of DMSO-d(6) that separated the overlapping signals. Diffusion measurements performed on the extensively dialyzed and unfolded DIP-Cht conjugate still resulted in a high diffusion coefficient ((0.30 +/- 0.05) x 10(-5) cm(2) s(-1)) relative to the assumed molecular mass. This observation was attributed to a dynamic dealkylation at the OP moiety (i.e., aging) that occurred during the relatively long diffusion measurements, where DIP-Cht was converted to the corresponding monoisopropyl phosphoryl Cht (MIP-Cht) conjugate. Homogeneous aged forms of OP-Cht were obtained by use of DFP and heat-induced dealkylation of DIP-Cht, and by PBPDC that provided the aged form via the hydrolysis of a P-Cl bond (PBP-Cht). The thermally stable aged conjugates enabled a reliable determination of the diffusion coefficients over several days of data acquisition, and the values found were (0.052 +/- 0.002) x 10(-5) cm(2) s(-1) and (0.054 +/-0.004) x 10(-5) cm(2) s(-1) for the MIP-Cht and the PBP-Cht adducts, respectively, values in the range expected for a species with a molecular weight of 25 kDa. The advantages and limitations of (31)P diffusion NMR in corroborating the type of species that prevail in such systems are briefly discussed.     

Hexameric capsules of lipophilic pyrogallolarene and resorcinarene in solutions as probed by diffusion NMR: one hydroxyl makes the difference

[reaction: see text] NMR diffusion measurements were used to characterize the self-assembled molecular capsule of pyrogallolarene 2c in CDCl(3) solutions. The results were compared with the characteristics of the hexameric capsule of 1b. Although both 2c and 1b self-assemble into hexameric capsules, the role of water in these capsules is rather different. It was also found that the capsule of 2c is more stable in polar media than that of 1b.