41) The pK values of -8.1 and -6.7 for p-nitrobenzaldehyde and unsubstituted benzaldehyde, respectively, reported by Arnett, Quirk, and Lar-sen40 were determined from enthalpies of protonation in fluorosulfonic acid. These values are comparable with the values of -9.2 and -7.5 obtained by correction of the H0 values at half-protonation determined by Yates and Stewart42 to the scale of Jorgenson and Hartter,43 and the pK of -6.7 for benzaldehyde is in good agreement with that of -6.75 reported by Greig and Johnson.44 Slopes of 0.8 and 1.0 were found by the latter workers for plots of log [)C=0]/[)C=QH+] against H0 for p-methoxybenzaldehyde and unsubstituted benzaldehyde, respectively. The above evidence is inconsistent with the report of Zalewski and Dunn45 that the protonation of benzaldehyde follows H* with a pK of -4.87.(42) K.

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Porphyrias are caused by genetic defects in the heme biosynthetic pathway and are associated with accumulation of high levels of porphyrins that become cytotoxic. Porphyrins, due to their amphipathic nature, spontaneously associate into different nanostructures but very little is known about the effect of porphyrin speciation on the cytotoxic effects of porphyrins. Previously we demonstrated the unique ability of fluorescent biological porphyrins, including protoporphyrin IX (PP-IX), to cause organelle selective protein aggregation, which we posit to be a major mechanism by which porphyrins exerts their cytotoxic effect. Herein, we tested the hypothesis that PP-IX-mediated protein aggregation is modulated by different PP-IX nanostructures via a mechanism that depends on their oxidizing potential and protein binding ability. We demonstrate that PP-IX nanostructure formation is reversible in nature, and that nanostructure size modulates consequent protein oxidation and aggregation potential. We also show that albumin, the most abundant serum protein, preferentially binds PP-IX dimers and enhances their oxidizing ability. Additionally, extracellular albumin protects from intracellular porphyrinogenic stress and protein aggregation by acting as a PP-IX sponge. This work highlights the importance of PP-IX speciation in the context of the porphyrias, and offers insights into potential novel therapeutic approaches.

Es werden z.B. die Reaktionen von Benzaldehyden (mit Chlor, Nitro und Methoxyl als p‐Substituenten) mit Semicarbazid und 2‐Methyl‐3‐thio‐semicarbazid untersucht.

No abstract