Kensuke Okuda

Inhibition of E. coli growth by fullerene derivatives and inhibition mechanism

Cationic ammonium fullerene derivatives (C60-bis(N, N-dimethylpyrrolidinium iodide) and C60-bis(N-methylpiperazinium iodide)) suppressed E. coli growth, whereas an anionic derivative (C60-dimalonic acid) did not. Both cationic derivatives inhibited E. coli dioxygen consumption. Inhibition of energy metabolism is concluded to be a mechanism of the growth inhibition effect of fullerene derivatives.

Respiratory chain inhibition by fullerene derivatives: hydrogen peroxide production caused by fullerene derivatives and a respiratory chain system.

Fullerene is a new type of carbon allotrope. We have shown that the fullerene derivative C(60)-bis(N,N-dimethylpyrrolidinium iodide), a regio isomer mixture, inhibited Escherichia coli growth and dioxygen uptake caused by E. coli and glucose. This result indicates that the mechanism of the bacteriostatic effect is the inhibition of energy metabolism. In this study, we isolated two regio isomers of C(60)-bis(N,N-dimethylpyrrolidinium iodide) and studied their effect on E. coli growth and on respiratory chain activity. In dioxygen uptake caused by the inner-membrane and NADH, the effect of fullerene derivatives was biphasic. At low concentrations of both fullerene derivatives, dioxygen uptake was inhibited, whereas at high concentrations, it was increased. At high concentrations, consumed dioxygen was converted to H(2)O(2). An electrochemical study revealed that reduced fullerene derivatives react with dioxygen. This activity was closely related to a redox property of the isomers.

An Uncharged Amine in the Transition State of the Ribosomal Peptidyl Transfer Reaction

The ribosome has an active site comprised of RNA that catalyzes peptide bond formation. To understand how RNA promotes this reaction requires a detailed understanding of the chemical transition state. Here, we report the Brønsted coefficient of the alpha-amino nucleophile with a series of puromycin derivatives. Both 50S subunit- and 70S ribosome-catalyzed reactions displayed linear free-energy relationships with slopes close to zero under conditions where chemistry is rate limiting. These results indicate that, at the transition state, the nucleophile is neutral in the ribosome-catalyzed reaction, in contrast to the substantial positive charge reported for typical uncatalyzed aminolysis reactions. This suggests that the ribosomal transition state involves deprotonation to a degree commensurate with nitrogen-carbon bond formation. Such a transition state is significantly different from that of uncatalyzed aminolysis reactions in solution.

Synthesis of various water-soluble C60 derivatives and their superoxide-quenching activity

Abstract In order to examine the utility of fullerene as a medicinal application, we evaluated the reaction between fullerene derivatives and active oxygen species in vitro. This paper describes the synthesis of various water-soluble C60 derivatives (cationic and anionic) and evaluation of their superoxide (O2 −) quenching activity. Cationic C60 derivatives showed fairly high efficiency.

Inhibitory effect of fullerene derivatives on glutathione reductase

Fullerene derivatives which have carboxylic acid moiety effectively inhibited glutathione reductase activity. Preincubation of the reductase and fullerene derivative at 37°C enhanced the inhibition activity.

Effect of hexasulfobutylated C60 on the isolated aortic ring of guinea pig

The effects of hexasulfobutylated C60 (FC4S) and monomalonic acid C60 (MMA C60), the fullerene C60 derivatives, on isolated endothelium-containing or endothelium-denuded aorta of guinea pig were studied pharmacologically in vitro. In the endothelium-containing preparation of the aortic rings, phenylephrine (PHE) elicited contracture and acetylcholine (ACh) elicited a relaxing effect on the PHE-precontracted preparation. In the PHE-precontracted preparation, MMA C60 (10 µmol/l) did not elicit a relaxing effect on the PHE-precontracted preparation. However, MMA C60 (10 µmol/l) significantly reduced the maximum response of the relaxation elicited by ACh. FC4S itself significantly relaxed the PHE-precontracted aortic rings. ACh-induced relaxation in PHE-precontracted endothelium-containing strips of the aortic rings was significantly potentiated if pretreated with FC4S (10 µmol/l). In the denuded aortic rings, FC4S did not elicit the relaxing effect in the PHE-precontracted preparation. The relaxing effect of FC4S on the PHE-precontracted preparation was not altered when superoxide dismutase (250 units/ml) was pretreated. However, the relaxing effect was reduced when N(G)-nitro-L-arginine methyl ester (L-NAME, 1 mmol/l) or methylene blue (1 µmol/l) was pretreated. These results demonstrated that the vasorelaxation effect of FC4S on the PHE-precontracted aortic ring is partly dependent on the release of nitric oxide (NO) or an NO-derived substance from the vascular endothelium.

N-[5-(1-Naphth­yl)pyrimidin-4-yl]acetamide oxime

In the asymmetric unit of the title compound, C16H14N4O, there are two crystallographically independent molxadecules, which are connected to each other by O—H⋯N hydrogen bonds, forming a molxadecular chain. The neighboring chains are linked into a layer through π–π stacking interxadactions.

EFFECTS OF HEXASULFOBUTYLATED C60 ON THE GASTRIC CIRCULAR MUSCLE OF GUINEA PIG

The effects of hexasulfobutylated (FC4S), the fullerene derivative on the contraction of smooth muscle were tested pharmacologically on the circular muscle of stomach of guinea pigs. The effects of monomalonic acid C60 (MMA C60) on the same preparations were compared. The effects of those compounds on the taenia coli, portal vein and vas deferens of guinea pigs were also tested. The FC4S did, while MMA C60 did not elicit contracture of the circular muscle of stomach and taenia coli. Both FC4S and MMA C60 did not elicit contraction on the portal vein and on the vas deferens of the guinea pig. Prazosin (0.5 μM) or propranolol (0.5 μM) did not alter the FC4S elicit contracture of the circular muscle of stomach. However, atropine (0.01, 0.1 and 1 μM), tetrodotoxin (0.1 μM) or low calcium medium decreased reversibly the FC4S elicited contracture of the circular muscle of stomach. The effect of FC4S on the contracture of the gastric muscles was also tested using various muscarinic receptor subtype antagonists. 4-DAMP (1 μM), muscarinic M3 receptor antagonist, and tropicamide (1 μM), muscarinic M4 receptor antagonist, did not alter the contracture elicited by FC4S. Pirenzepine (0.1 μM), muscarinic M1 receptor antagonist, and methoctramine (0.25 μM), muscarinic M2 receptor antagonist, significantly decreased the FC4S elicited contracture of the circular muscle. Atropine (1 μM) or tetrodotoxin (0.1 μM) completely blocked the FC4S elicited contracture of the circular muscle of stomach. It is concluded that FC4S elicited contracture of the circular muscle of stomach. The effect may be due to FC4S acts on the cholinergic cells existed in the gastric muscle and indirectly activating the tetrodotoxin dependent releasing of the transmitters from the cells, then, activating the muscarinice M1, M2 receptors in the muscle eliciting the contractures.

[(Z)-2-(3-Methyl-1,2,4-oxadiazol-5-yl)-2-(1-naphthyl)ethenylamino]formaldehyde oxime 1,4-dioxane hemisolvate

In the asymmetric unit of the title compound, C16H14N4O2·0.5C4H8O2, there are two crystallographically independent oxime molxadecules and one solvent molxadecule. Each oxime molxadecule has intraxadmolecular N—H⋯O and N—H⋯N hydrogen bonds, which make the non-H atoms approximately coplanar except for the naphthyl groups. The two independent molxadecules are connected to each other by O—H⋯N hydrogen bonds, forming a dimer. Dimers are linked into a layer through C—H⋯O, C—H⋯N and C—H⋯π interxadactions. There is π-stacking of approximately parallel oxadiazole rings, with a centroid–centroid distance of 3.6234u2005(9)u2005A and a dihedral angle of 8.90u2005(6)°. Dioxane C and H atoms are disordered over two sites each, with occupancy factors of ca 0.78:0.22.