Synthesis and biological activity of novel mitomycin C analogs derived from mitomycin A

A variety of mitomycin C analogs were synthesized from mitomycin A and their biological activities were studied. Mitomycin A ( 1 ) underwent nucleophilic displacement reactions involving intramolecular hydrogen migrations upon treatment with nitrogen nucleophiles bearing mobile hydrogens, but the mode of hydrogen migration depended on the nature of the nucleophiles. The reaction with alkoxyamines gave compounds 6 and 7 which have the 5H-6-alkoxyimino-4,7-dione structure in ring A of 1 . However, the reaction with hydroxylamine and benzoylhydrazine afforded compounds 11 and 13 which have the 4-hydroxy-6-hydroxyimino-7-one structure and the 4-hydroxy-6-hydrazono-7-one structure, respectively, in ring A of 1 . These products were converted into various types of mitomycin C derivatives by methylation with methyl iodide or dimethyl sulfate. The mechanistic features of these reactions are discussed. The in vitro and in vivo biological activities were tested by using P388 leukemia and Sarcoma 180 tumor cells. Several of the synthesized compounds exhibited better activity than that of mitomycin C.     

H NMR in μc-Si:H

NMR, IR, ESR, Raman scattering and X-ray diffraction measurements were performed in μc-Si:H prepared by various methods. Results of H NMR in some films are qualitatively similar to those i n a-Si:H, but the NMR lines exhibit a motional narrowing. Other films which exhibit sharp IR peaks exhibit H NMR signal shape different from that in a-Si:H.     

CO Gas‐free Intramolecular Cyclocarbonylation Reactions of Haloarenes Having a C‐Nucleophile through CO‐Relay between Rhodium and Palladium

We describe transfer carbonylation reactions of 2‐bromoarenes that contain a carbon‐nucleophile using aldehydes as a substitute for CO, leading to the formation of indanone derivatives. The transformation proceeds efficiently under Rh^I/Pd⁰‐hybrid catalytic conditions consisting of two discrete transition metals, rhodium and palladium, which catalyze the decarbonylation of aldehydes and the subsequent carbonylation of bromoarenes using the resulting carbonyl moiety, respectively. The majority of the abstracted CO is transferred directly to the product via a CO‐relay process from rhodium to palladium.     

Protonation states of buried histidine residues in human deoxyhemoglobin revealed by neutron crystallography

The protonation states of buried histidine residues in human deoxyhemoglobin were unambiguously identified by using a neutron crystallographic technique. Unexpectedly, the neutron structure reveals that both the alpha- and beta-distal histidines (Hisalpha58 and Hisbeta63) adopt a positively charged, fully (doubly) protonated form, suggesting their contribution to the Bohr effect. In addition, the neutron data provide an accurate picture of the alpha1beta1 hydrogen-bonding network and allow us to observe unambiguously the nature of the intradimeric interactions at an atomic level.     

Accumulation of photofrin in lesions of airway stenosis rabbit models

Airway stenosis in childhood is resistant to conventional treatments. Endoscope-assisted photodynamic therapy (PDT) is a potent candidate for the therapeutic modality owing to the easy approach to the tracheal lesion and low degree of invasiveness. The aim of the present study was to examine whether a photosensitizer preferentially accumulates in the lesion of airway stenosis in order to explore the possible applicability of PDT. The tracheal mucosa of rabbits was scraped off, and the rabbits were intravenously administered with Photofrin. The tissue concentration of Photofrin was quantitatively measured by fluorometric analysis. Granulation formation was seen in the mucosa-deprived lesion, causing airway stenosis. Photofrin concentration in the granulation tissue was four-fold higher than that in the intact trachea and 10-fold higher than that in the liver, spleen, skin and muscle. Photofrin preferentially accumulated in the lesion of airway stenosis. A preliminary experiment on PDT using transtracheal illumination showed an amelioration of airway stenosis, resulting in reduction in respiratory stridor.     

Controlled Polymerization of Protic Ionic Liquid Monomer by ARGET‐ATRP and TERP

The direct synthesis of structurally well‐defined protic polymeric ionic liquid (PIL) with controlled molecular weight and molecular weight distribution is examined using N,N‐diethyl‐N‐(2‐methacryloylethyl) ammonium bis(tri‐fluoromethylsulfonyl)imide (DEMH‐TFSI) as a monomer. Three polymerization methods, namely, atom transfer radical polymerization (ATRP), activators regenerated by electron transfer (ARGET)‐ATRP, and organotellurium‐mediated living radical polymerization (TERP) are employed in this study. While the polymerization by ATRP is slow and does not reach high monomer conversion that under ARGET‐ATRP and TERP proceeds smoothly and affords structurally well‐defined poly(DEMH‐TFSI)s. TERP is especially efficient for the control and poly(DEMH‐TFSI)s with low to high molecular weights ( = 49 100–392 500) and narrow molecular weight distributions (/ = 1.17–1.46) are obtained. These results represent the first example of synthesis of a structurally well‐defined protic, ammonium PIL by direct polymerization of the protic ionic liquid monomer. The polymerization of N,N‐diethyl‐N‐(2‐methacryloylethyl)‐N‐methylammonium bis(trifluoromethylsulfonyl)imide (DEMM‐TFSI), which possesses a quaternary ammonium salt, also proceeds in a highly controlled manner under TERP conditions. A diblock copolymer, polystyrene‐block‐poly(DEMH‐TFSI), is also successfully synthesized by TERP.

     

Bulk superconducting phase with a full energy gap in the doped topological insulator Cu(x)Bi₂Se₃

The superconductivity recently found in the doped topological insulator Cu(x)Bi?Se? offers a great opportunity to search for a topological superconductor. We have successfully prepared a single-crystal sample with a large shielding fraction and measured the specific-heat anomaly associated with the superconductivity. The temperature dependence of the specific heat suggests a fully gapped, strong-coupling superconducting state, but the BCS theory is not in full agreement with the data, which hints at a possible unconventional pairing in Cu(x)Bi?Se?. Also, the evaluated effective mass of 2.6m(e) (m(e) is the free electron mass) points to a large mass enhancement in this material.     

Magnetic Field Effect on the Cathodic Potential Oscillation of Zinc Electrode in Alkaline Solution

The magnetic field effect (0?C0.47?T) on cathodic potential oscillation of a zinc cathode in an alkaline solution was studied. By applying a magnetic field, the oscillation interval increased. The oscillation was quenched at 0.47?T. In situ bore-scope observation of the cathode during electrolysis in magnetic fields revealed that the solution convection induced by the Lorentz force causes the observed effect.