Pathway Complexity in Nanotubular Supramolecular Polymerization: Metal-Organic Nanotubes with a Planar-Chiral Monomer.

Here, we report an anomalous pathway complexity in the supramolecular polymerization of a chiral monomer, which displays an unusual chiroptical feature that does not follow any of the known stereochemical rules such as "chiral self-sorting" and "majority rule". We newly developed a planar-chiral ferrocene-cored tetratopic pyridyl monomer FcL, which underwent AgBF4-mediated supramolecular polymerization to give nanotubes FcNTs composed of metal-organic nanorings FcNRs. Although FcNRs must be homochiral because of a strong geometrical constraint, FcNRs were formed even efficiently from racemic FcL and AgBF4. Detailed studies revealed the presence of two competing pathways for producing homochiral FcNRs as the constituents of FcNTs: (i) spontaneous cyclization of initially formed acyclic polymers -[FcL-Ag+]n- and (ii) template (FcNR)-assisted cyclization via a Ag+···Ag+ metallophilic interaction. The dominance of the two pathways changes depending on the %ee of chiral FcL. Namely, when the %ee of FcL is high, -[FcL-Ag+]n- must contain sufficiently long homochiral sequences that can be readily cyclized into FcNRs. Meanwhile, when the %ee of FcL is low, the homochiral sequences in -[FcL-Ag+]n- must be short and therefore are hardly eligible for spontaneous cyclization. Why were FcNRs formed? Even though the probability is very low, homochiral -[FcL-Ag+]n- can be statistically generated and undergo spontaneous cyclization to give FcNRs minutely. We found that FcNRs can be amplified by heterochirally templating their own synthesis using metallophilic interaction. Because of this stereochemical preference, the growth of FcNRs into FcNTs via the template-assisted mechanism occurs only when both (R,R)FcL and (S,S)FcL are present in the polymerization system.

Metallothionein-enriched hepatocytes are resistant to ferric nitriloacetate toxicity during conditions of glutathione depletion.

Metallothionein (MT) is involved not only in heavy metal homeostasis/detoxification but also in radical scavenging, yet the relevance to other antioxidant systems and physiological significance under oxidative stress has not been clarified. We studied that ability of MT, induced by zinc and cadmium, to protect against oxidative damage induced by ferric nitrilotriacetate (Fe-NTA) in glutathione depleted primary cell cultures. Treatment with Fe-NTA resulted in significant decreases in cell survival and increases in medium LDH activity in control cells following depletion of glutathione. The toxic effects of Fe-NTA were modulated in Zn-MT-enriched cells. In glutathione-depleted cells, but not in non-treated cells, Cd-binding properties of cellular Zn-MT decreased with increasing concentration of Fe-NTA. Both Zn-MT and Cd-MT-enriched cells were resistant to higher doses of Fe-NTA. These results indicate that MT may act a cellular radical scavenger in the absence of GSH. Thus, MT may function as a secondary antioxidant in a cellular protection system.

Studies on Ergothioneine. IX. Ergothioneine Stimulates Mouse Spermatozoa and Fertilization in vitro: (ergothioneine/fertilization/acrosome reaction/sperm penetration).

The effects of ergothioneine on spermatozoa and ova were investigated in vitro and in vivo. Spermatozoa were treated with ergothioneine in vitro, and injected into the uterine cavity of female mice immediately after the induction of superovulation. The ova were recovered 24 hr later and assessed for fertilization. Preincubation of spermatozoa with ergothioneine resulted in a significant increase in the fertilization rate. When ova were inseminated in the same manner in vitro with spermatozoa treated with 0.1 or 1.0 mM of ergothioneine, the penetration rate was significantly increased. These results suggest that ergothioneine is effective in inducing both capacitation and the acrosome reaction of mouse spermatozoa. Ergothioneine at concentrations of 0.1 and 1.0 mM in the preincubation medium was also effective in inducing the acrosome reaction of guinea pig spermatozoa. However, it had no significant effect on the development of 2-cell ova in vitro.

Triglyceride accumulation by peroxisome proliferators in rat hepatocytes.

Peroxisome proliferators (PxPs) induce peroxisomal beta-oxidation (Px-ox) in the liver of rodents and have a hypolipidemic function. To investigate hypolipidemic effect of PxPs, the relationship between TG fluctuation and Px-ox activity, as an indicator of the function of PxPs, was studied in primary cultured rat hepatocytes. Nafenopin (Nf) treatment of hepatocytes caused an increase in Px-ox activity in association with cellular TG accumulation in a time-dependent manner with a coefficient of r=0.918. This relationship between the activity and cellular TG were obtained using structurally diverse PxPs with a correlation coefficient of r=0.747. Treatment of the hypolipidemic drug, but non-PxP Pravastatin, decreased TG in the medium, but did not have the effects on cellular TG and Px-ox activity. The total amount of TG and diacylglycerol acyltransferase activity, the last enzyme in the TG de novo synthesis pathway, were not affected by Nf treatment. When hepatocytes were cultured with Brefeldin A, cellular TG was accumulated, the same as with Nf, however, Px-ox activity was not enhanced. Nf treatment markedly decreased the level of apolipoprotein B (apo B) in very low density lipoprotein (VLDL) fractions prepared from conditioned media and increased that of cellular apoB by Western blot analysis. Microsomal triglyceride transfer protein activity was not influenced by Nf. Together, with regards to TG lowering effect of PxPs, it is suggested that PxPs cause hepatocellular accumulation of TG without effects on TG biosynthesis and VLDL construction, and they might have inhibitory effect on VLDL secretion process.