Differential behavior of amino-imino constitutional isomers in nonlinear optical processes.

A detailed study of the "blocked" amino-imino tautomers derived from N-acridine-substituted 2-aminobenzothiazole--and their effect on the nonlinear optical response--is presented. The synthesis, characterization, and nonlinear optical properties of these frozen tautomers, namely, N-methyl-N-(2-nitroacridin-6-yl)-2-aminobenzothia-zole and 3-methyl-N-(7-nitroacridin-3-yl)-2-iminobenzothiazole, are reported. A theoretical model based on valence-bond theory is also proposed and used to analyze the effects of the nuclear configuration corresponding to each frozen tautomer structure. In the present case, the aromatic form and the allylic-anion-like system of the -N-C-N- group inherent to each isomer are crucial for understanding and analyzing the different responses of each "blocked" tautomer.

Electron-transfer capacity of catechin derivatives and influence on the cell cycle and apoptosis in HT29 cells.

Galloylated and nongalloylated catechin conjugates with cysteine derivatives have been synthesized and evaluated for their capacity to scavenge free radicals and to influence crucial functions (cell cycle, apoptosis) in HT29 colon carcinoma cells. We show that the nonphenolic part of the molecule modified the capacity of catechins to donate hydrogen atoms and to transfer electrons to free radicals. Nongalloylated derivatives did not significantly influence either the cell cycle or apoptosis. Among the galloylated species, 4beta-[S-(O-ethyl-cysteinyl)]epicatechin 3-O-gallate, which showed a high electron-transfer capacity (5 e- per molecule), arrested the cell cycle and induced apoptosis as expected for galloylated catechins such as tea (-)-epigallocatechin 3-O-gallate. 4beta-[S-(N-Acetyl-O-methyl-cysteinyl)]epicatechin 3-O-gallate, which showed the highest hydrogen-donating capacity (10 H per molecule) while keeping the electron-transfer capacity low (2.9 e- per molecule), did not trigger any significant apoptosis. The gallate moiety did not appear to be sufficient for the pro-apoptotic effect of the catechin derivatives in HT29 cells. Instead, a high electron-transfer capacity is more likely to be behind this effect. The use of stable radicals sensitive exclusively to electron transfer may help to design molecules with either preventive scavenging action (high hydrogen donation, low electron transfer) or therapeutic pro-apoptotic activity (high electron transfer).

Effect of new antioxidant cysteinyl-flavanol conjugates on skin cancer cells.

Novel catechin derivatives obtained from grape procyanidins and l-cysteine scavenge free radicals by hydrogen atom donation, rather than electron transfer, and reduce cell viability in A375 and M21 melanoma cells. In particular, 4beta-(S-cysteinyl)epicatechin 3-O-gallate has a free radical scavenging capacity as strong as that of tea (-)-epigallocatechin gallate and causes a significant S-phase cell-cycle arrest in both cell lines at doses higher than 100 microM. The other cysteinyl compounds do not affect normal cell cycle distribution. The gallate derivative also induces apoptosis in melanoma cells more strongly than the other derivatives and the parent (-)-epicatechin do. The gallate compound seems to trigger nuclear condensation and fragmentation, which is confirmed by DNA laddering. Interestingly, they do not induce apoptosis in keratinocytes (HaCaT).

Procyanidin fractions from pine (Pinus pinaster) bark: radical scavenging power in solution, antioxidant activity in emulsion, and antiproliferative effect in melanoma cells.

Pine (Pinus pinaster) bark is a rich source of procyanidin oligomers. From a total polyphenolic extract, we have generated fractions of different procyanidin composition. The mixtures, devoid of gallate esters, were active as free radical scavengers against ABTS(*+), DPPH, and HNTTM. Pine bark fractions were tested for antioxidant activity in solution (hydrogen donation and electron transfer) and emulsion (inhibition of lipid peroxidation) and compared with their galloylated counterparts from grape origin. While galloylation clearly influenced the free radical scavenging efficiency in solution, it did not seem to play a determinant role in protection against lipid peroxidation in emulsion. The fractions were very mild inhibitors of cell proliferation. Because gallate esters appear to interfere with crucial cell functions, gallate free pine procyanidins may be the innocuous chemopreventative agents of choice for many applications in food and skin protection.

Reducing activity of polyphenols with stable radicals of the TTM series. Electron transfer versus H-abstraction reactions in flavan-3-ols.

A new method to test the antioxidant activity of polyphenols by electron transfer reactions to a stable organic free radical, tris(2,4,6-trichloro-3,5-dinitrophenyl)methyl radical (HNTTM), is reported. Therefore, the activity of the natural flavanols, (-)-epicatechin, and two synthetic derivatives, 4beta-(S-cysteinyl)epicatechin and 4beta-(2-aminoethylthio)epicatechin, can be differentiated by their capacity to transfer hydrogen atoms to 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) and to transfer electrons to HNTTM. [structure: see text]