Catechol-Containing Hydroxylated Biomimetic 4-Thiaflavanes as Inhibitors of Amyloid Aggregation

The study of compounds able to interfere in various ways with amyloid aggregation is of paramount importance in amyloid research. Molecules characterized by a 4-thiaflavane skeleton have received great attention in chemical, medicinal, and pharmaceutical research. Such molecules, especially polyhydroxylated 4-thiaflavanes, can be considered as structural mimickers of several natural polyphenols that have been previously demonstrated to bind and impair amyloid fibril formation. In this work, we tested five different 4-thiaflavanes on the hen egg-white lysozyme (HEWL) amyloid model for their potential anti-amyloid properties. By combining a thioflavin T assay, atomic force microscopy, and a cell toxicity assay, we demonstrated that such compounds can impair the formation of high-order amyloid aggregates and mature fibrils. Despite this, the tested 4-thiaflavanes, although non-toxic per se, are not able to prevent amyloid toxicity on human neuroblastoma cells. Rather, they proved to block early aggregates in a stable, toxic conformation. Accordingly, 4-thiaflavanes can be proposed for further studies aimed at identifying blocking agents for the study of toxicity mechanisms of amyloid aggregation

Macromolecular non-releasing additives for safer food packaging: application to ethylene/α-olefins and propylene based polymers

Some innovative solutions are proposed to the problem of the unavoidable physical migration of antioxidants from plastic films for packaging, in order to minimize the consequent undesirable effect of food contamination. In previous exploratory tests, phenolic antioxidant co-units were achieved and incorporated into polyethylene chain and now the work is extended to create new families of polymeric additives properly designed for specific material. An effective route was designed to synthesize the functionalized comonomer, analogues of commercial 2,6-t-butyl-4-methoxy-phenol (BHA), containing eight methylene units as spacer between the aromatic ring and the polymerizable olefinic double bond (C8). Ethylene/1-hexene/C8 terpolymers, with 1-hexene concentration in the typical range found in commercial polyethylene grades, and propylene/C8 copolymers with microstructure similar to those of commercial packaging polypropylenes were produced. A careful 13C NMR study was conducted for the precise determination of the functionalized comonomer content on all terpolymer and copolymer samples. The samples melt blended with additive-free commercial LDPE and PP matrices, individually, were analyzed in terms of thermal and thermo-oxidative stability and compared with LDPE and PP films containing the traditional BHA additive analogue. The results demonstrate that, in either way, the polymeric additives exert a very positive effect on the degradation temperature of the polymeric matrices, retarding the thermo-oxidative sequence of reaction

Síntesis y (co)polimerización de (co)monómeros que contienen diferentes unidades de forma helicoidal

Los helicenos son unos compuestos únicos debido a su estructura y a las propiedades que derivan de dicha estructura, así como de su disposición electrónica. El término heliceno comprende una gran variedad de compuestos dependiente del esqueleto de la molécula, podemos estudiar diferentes heterohelicenos como thia[n]helicenos, aza[n]helicenos or oxa[n]helicenos. A parte de por su peculiar estructura los helicenos destacan por el gran número de usos que pueden tener: desde ligandos en catálisis asimétrica hasta fármacos capaces de interaccionar con la doble hélice de ADN pasando por sustancias electroactivas útiles en el almacenamiento de información o en la fabricación de baterías. Vinculado con este último punto, recientemente diversos grupos han estudiado la idea de sintetizar polímeros con cadenas laterales que contengan distintos grupos electroactivos para el almacenamiento de energía u otras aplicaciones relacionadas. En este trabajo de fin de máster se ha buscado obtener distintos monómeros que contengan unidades heteroheliceno los cuales permitan obtener polímeros y copolímeros con ramificaciones laterales que posean diferentes helicenos terminales. Una vez obtenidos dichos polímeros helicénicos se estudiará la formación de los correspondientes radicales. Para el proceso de polimerización se han utilizado dos reacciones diferentes: una de ellas es la polimerización RAFT, la cual se basa en una polimerización radicalaria controlada. Además de homopolímeros permite obtener copolimeros bloque en nuestro caso un bloque de PEG hidrófilo y otro de polimetacrilato con unidad heliceno hidrófobo. El otro tipo de polimerización realizada es la Ring Opening Metathesis Polymerization, esta reacción se basa en el uso del catalizador de Grubbs, un complejo organometálico de Rutenio que permite polimerizar dobles enlaces presentes en anillos como es el caso del norborneno, el ciclopenteno o el ciclohexeno

Resolution of a Configurationally Stable Hetero[4]helicene

We have developed an efficient chemical resolution of racemic hydroxy substituted dithiaaza[ 4]helicenes (DTA[4]H) 1(OH) using enantiopure acids as resolving agents. The better diastereomeric separation was achieved on esters prepared with (1S)-()-camphanic acid. Subsequent simple manipulations produced highly optically pure ( 99% enantiomeric excess) (P) and (M)-1(OH) in good yields. The role of the position where the chiral auxiliary is inserted (cape- vs. bay-zone) and the structure of the enantiopure acid used on successful resolution are discussed

Proton–electron transfer pathways in the reactions of peroxyl and dpph radicals with hydrogen-bonded phenols

none4noThe kinetics of the reaction of peroxyl and dpph radicals with phenols H-bonded to N-bases have been studied for the first time. Electron-transfer processes are observed in MeCN but only with the dpph radical.noneR. Amorati; S. Menichetti; C. Viglianisi; M. C. FotiR. Amorati; S. Menichetti; C. Viglianisi; M. C. Fot

From catechol-tocopherol to catechol-hydroquinone polyphenolic antioxidant hybrids

Multidefence antioxidants represent a valuable solution for the protection against oxidative stress. From the planned synthesis of a catechol-tocopherol hybrid, we isolated a catechol-hydroquinone hybrid through a BBr3-mediated benzochromene-fluoren-1-ol transposition. The compound prepared showed a remarkable chain-breaking antioxidant in the catechol portion, while the very sensitive hydroquinone moiety revealed to be an efficient generator of hydroperoxyl radicals