The series of the new β-ketoenole dyes ((2E,5Z,7E,9E)-6-hydroxy-2-(alkylamino)-10-phenyldeca-2,5,7,9-tetraen-4-ones) with variation of alkylamino tail groups was synthesized and studied as potential probes for the sensing of protein aggregates amyloid fibrils. The dyes are low fluorescent when free but able to increase their emission intensity in dozens of times in the presence of fibrillar insulin. The fluorescent response of the dye on fibrillar insulin strongly depends on the nature of the alkylamino tail group. For compounds with propylamino (dye 13) and 2-hydroxyethylamino (dye 14) fragments the fluorescence intensity in the presence of fibrillar insulin exceeds that for the native one in 22 and 66 times correspondingly. However dyes demonstrate from low or moderate exceed of the fluorescence intensity in the presence of aggregated lysozyme compared to native one (up to 8.7 times for the dye 53 bearing methyl ester tail group), due to their pronounced sensitivity to native lysozyme. The dyes in complexes with insulin have rather height quantum yield up to 0.15, the large Stokes shifts values (about 100 nm and more), their binding constant values are about 10 5 M -1 . The dye 14 allows fluorescent detection of the insulin amyloid fibrils in the concentration range 1-50 μg/ml. This causes an interest in the future study of the β-ketoenole as prospective fluorescent amyloid-sensitive molecules.
The activity of five hafnium phthalocyanines containing out-of-plane ligands as inhibitors of reaction of insulin fibril formation is studied and correlation between their inhibitory properties and tendency to selfassociation is discussed. Methods. Fluorescence and absorption spectroscopy. Results. For the complexes with weak proneness to self-association PcHfDbm 2 , PcHfPyr 2 , and PcHfBtfa 2 the values of inhibitory activity were estimated as 60-73 %. For phthalocyanines with the pronounced tendency to self-association PcHfPiromelit and PcHfCl 2 the noticeably higher inhibitory activity values (about 95 %) were shown. In the presence of native or fibrilar insulin the destruction of self-associates of metal complex occurs in buffer pH 7.9, Besides upon the conditions of insulin fibrillization reaction (0.1 M HCl) phthalocyanines exist predominantly as monomers. Conclusions. The phthalocyanines with out-of-plane ligands with higher tendency to self-association have shown higher inhibitory activity in the insulin fibril formation comparing with the poorly aggregated metal complexes. At the same time low-order self-associates are not involved directly in th] mechanism of inhibition of insulin fibrillization and the phthalocyanines bind with protein in monomeric form. Tendency of phthalocyanines to self-association in aqueous media seems to be an «indicator» of their proneness to stack with protein aromatic amino-acids and thus of anti-fibrilogenic properties.
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