Yoshihisa Sei

Self-Assembled M24L48 Polyhedra and Their Sharp Structural Switch upon Subtle Ligand Variation

Two Molecular Spheres Viruses form highly symmetrical coat structures, capsids, through the assembly of multiple lower-symmetry protein precursors. Recently, chemists have sought to emulate this process on a smaller scale, relying on the assembly of organic molecular struts and metal ions, rather than proteins. Sun et al. (p. 1144, published online 29 April; see the Perspective by Stefankiewicz and Sanders) now demonstrate that a mixture of palladium ions and V-shaped bridging ligands can self-assemble into a hollow, nearly spherical polyhedron with 24 vertices and a central diameter of 4 nanometers. The assembly process was highly sensitive to the ligand angle; a subtle average decrease generated instead a smaller 12-vertex product. A slight change in ligand geometry determines whether a 12- or 24-vertex polyhedron will form. Self-assembly is a powerful technique for the bottom-up construction of discrete, well-defined nanoscale structures. Large multicomponent systems (with more than 50 components) offer mechanistic insights into biological assembly but present daunting synthetic challenges. Here we report the self-assembly of giant M24L48 coordination spheres from 24 palladium ions (M) and 48 curved bridging ligands (L). The structure of this multicomponent system is highly sensitive to the geometry of the bent ligands. Even a slight change in the ligand bend angle critically switches the final structure observed across the entire ensemble of building blocks between M24L48 and M12L24 coordination spheres. The amplification of this small initial difference into an incommensurable difference in the resultant structures is a key mark of emergent behavior.

DNA and RNA as New Binding Targets of Green Tea Catechins

The significance of catechins, the main constituent of green tea, is being increasingly recognized with regard to cancer prevention. Catechins have been studied for interactions with various proteins, but the mechanisms of the various catechins are not yet elucidated. Based on our previous observation that nucleic acids extracted from catechin-treated cells are colored, we studied whether catechins directly interact with nucleic acids using surface plasmon resonance assay (Biacore) and cold spray ionization-mass spectrometry. These two methods clearly showed that (-)-epigallocatechin gallate (EGCG) binds to both DNA and RNA molecules: the Biacore assay indicated that four catechins bound to DNA oligomers, and cold spray ionization-mass spectrometry analysis showed one to three EGCG molecules bound to single strand 18 mers of DNA and RNA. Moreover, one or two molecules of EGCG bound to double-stranded (AG-CT) oligomers of various nucleotide lengths. These results suggest that multiple binding sites of EGCG are present in DNA and RNA oligomers. Double-stranded DNA (dsDNA) oligomers were detected only as EGCG-bound forms at high temperature, whereas at low temperature both the free and bound forms were detected, suggesting that EGCG protects dsDNA oligomers from dsDNA melting to single-stranded DNA. Because both galloyl and catechol groups of EGCG are essential for DNA binding, both groups seem to hold strands of DNA via their branching structure. These findings reveal for the first time the link between catechins and polynucleotides and will intensify our understanding of the effects of catechins on DNA in terms of cancer prevention.

Iodomesitylene-Catalyzed Oxidative Cleavage of Carbon-Carbon Double and Triple Bonds Using m-Chloroperbenzoic Acid as a Terminal Oxidant

Transition metal-catalyzed oxidative cleavage of carbon-carbon multiple bonds has emerged as a powerful tool in organic synthesis. High-valent oxometals, mostly of Ru, Os, Mn, Mo, W, and Re, were used catalytically as reactive oxygen transfer agents to the multiple bonds. Reported here for the first time are the organocatalytic versions of the oxidative cleavage reactions. Our method involves use of iodomesitylene as an effective organocatalyst, which generates an active aryl(hydroxy)-lambda(3)-iodane 5 in situ, and m-chloroperbenzoic acid (m-CPBA) as a terminal oxidant under metal-free conditions. Cyclic and acyclic olefins as well as aliphatic and aromatic alkynes were smoothly cleaved to carboxylic acids under the organocatalytic conditions.

Preparation of Highly Fluorescent Host–Guest Complexes with Tunable Color upon Encapsulation

Unlike previous coordinative host-guest systems, highly emissive host-guest complexes (up to Φ(F) = 0.5) were successfully prepared upon encapsulation of various fluorescent dyes (e.g., BODIPY and coumarin derivatives) by a Pt(II)-linked coordination capsule in water. Picosecond time-resolved spectroscopy elucidates the photophysical behaviors of the obtained complexes. Notably, the emission color of the fluorescent guest within the capsule can be readily modulated upon pairwise encapsulation with planar aromatic molecules.

Drug delivery of lipophilic pyrenyl derivatives by encapsulation in a water soluble metalla-cage

The self-assembly of 2,4,6-tris(pyridin-4-yl)-1,3,5-triazine (tpt) triangular panels with p-cymene (p-Pr(i)C(6)H(4)Me) ruthenium building blocks and 2,5-dioxydo-1,4-benzoquinonato (dobq) bridges, in the presence of a functionalised pyrenyl derivative (pyrene-R), affords the triangular prismatic host-guest compounds [(pyrene-R) [symbol: see text] Ru(6)(p-Pr(i)C(6)H(4)Me)(6)(tpt)(2)(dobq)(3)](6+) ([(pyrene-R) [symbol: see text] 1](6+)). The inclusion of eight mono-substituted pyrenyl derivatives including biologically relevant structures (a = 1-pyrenebutyric acid, b = 1-pyrenebutanol, c = 1-pyrenemethylamine, d = 1-pyrenemethylbutanoate, e = 1-(4,6-dichloro-1,3,5-triazin-2-yl)pyrene, f = N-hexadecylpyrene-1-sulfonamide, g = pyrenyl ethacrynic amide and h = 2-(pyren-1-ylmethylcarbamoyl) phenyl acetate), and a di-substituted pyrenyl derivative (i = 1,8-bis(3-methyl-butyn-1-yl-3-ol)pyrene), has been accomplished. The carceplex nature of these systems with the pyrenyl moiety being firmly encapsulated in the hydrophobic cavity of the cage with the functional groups pointing outwards was confirmed by NMR ((1)H, 2D, DOSY) spectroscopy and electrospray ionization mass spectrometry (ESI-MS). The cytotoxicities of these water-soluble compounds have been established using human ovarian A2780 cancer cells. All the host-guest systems are more cytotoxic than the empty cage itself [1][CF(3)SO(3)](6) (IC(50) = 23 microM), the most active carceplex [f [symbol: see text] 1][CF(3)SO(3)](6) is an order of magnitude more cytotoxic.

Wide‐Ranging Host Capability of a PdII‐Linked M2L4 Molecular Capsule with an Anthracene Shell

This article reports that an M2L4 molecular capsule is capable of encapsulating various neutral molecules in quantitative yields. The capsule was obtained as a single product by mixing a small number of components; two Pd(II) ions and four bent bispyridine ligands containing two anthracene panels. Detailed studies of the host capability of the Pd(II)-linked capsule revealed that spherical (e.g., paracyclophane, adamantanes, and fullerene C60), planar (e.g., pyrenes and triphenylene), and bowl-shaped molecules (e.g., corannulene) were encapsulated in the large spherical cavity, giving rise to 1:1 and 1:2 host-guest complexes, respectively. The volume of the encapsulated guest molecules ranged from 190 to 490 Å(3). Within the capsule, the planar guests adopt a stacked-dimer structure and the bowl-shaped guests formed an unprecedented concave-to-concave capsular structure, which are fully shielded by the anthracene shell. Competitive binding experiments of the capsule with a set of the planar guests established a preferential binding series for pyrenes≈phenanthrene>triphenylene. Furthermore, the capsule showed the selective formation of an unusual ternary complex in the case of triphenylene and corannulene.

Anti-influenza activity of phenethylphenylphthalimide analogs derived from thalidomide.

Swine-origin influenza A virus has caused pandemics throughout the world and influenza A is regarded as a serious global health issue. Hence, novel drugs that will target these viruses are very desirable. Influenza A expresses an RNA polymerase essential for its transcription and replication which comprises PA, PB1, and PB2 subunits. We identified potential novel anti-influenza agents from a screen of 34 synthesized phenethylphenylphthalimide analogs derived from thalidomide (PPT analogs). For this screen we used a PA endonuclease inhibition assay, a PB2 pathogenicity-determinant domain-binding assay, and an anti-influenza A virus assay. Three PPT analogs, PPT-65, PPT-66, and PPT-67, were found to both inhibit PA endonuclease activity and retard the growth of influenza A, suggesting a correlation between their activities. PPT-28 was also found to inhibit the growth of influenza A. These four analogs have a 3,4-dihydroxyphenethyl group in common. We also discuss the possibility that 3,4-dihydroxyphenethyl group flexibility may play an important functional role in PA endonuclease inhibition. Another analog harboring a dimethoxyphenethyl group, PPT-62, showed PB2 pathogenicity-determinant domain-binding activity, but did not inhibit the growth of the virus. Our present results indicate the utility of the PA endonuclease assay in the screening of anti-influenza drugs and are therefore useful for future strategies to develop novel anti-influenza A drugs and for mapping the function of the influenza A RNA polymerase subunits.

Detection of microcystin–metal complexes by using cryospray ionization-Fourier transform ion cyclotron resonance mass spectrometry☆

Complexes of microcystins (MCs) and metal ions were detected with mass spectrometry. To observe the MCs-metals complexes, CryoSpray ionization ion source was developed and it was equipped on a commercial Fourier transform ion resonance mass spectrometer. Mixtures of two MCs and five metals were applied to Fourier transform ion cyclotron resonance mass spectrometry coupled with CryoSpray. The analyses showed complexes of MC-LR-Fe(II), -Zn, -Cu, -Mg, MC-RR-Fe(II), -Zn, -Cu, and -Mg but MC-LR-Fe(III) and MC-RR-Fe(III) were not observed. Present study suggested that MCs may play roles in metal ion uptake and/or accumulation in the algal cells.

Synergistic effects of multiple treatments, and both DNA and RNA direct bindings on, green tea catechins

This article reviews two main topics: (1) the synergistic effects of multiple treatments with green tea catechin and (2) the direct binding of (−)‐epigallocatechin gallate (EGCG) to both DNA and RNA molecules. Japanese drink green tea throughout the day, so we studied whether multiple treatments of cells with EGCG would enhance the expression of apoptosis‐related genes, such as growth arrest and DNA damage‐inducible gene (GADD153) and cyclin‐dependent kinase inhibitor gene (p21waf1): The results suggest that the synergistic enhancement of both GADD153 and p21waf1 gene expressions by multiple treatments plays a significant role in human cancer prevention with green tea beverage. Our previous observation—that nucleic acids extracted from catechin‐treated cells are colored—allowed us to speculate that catechins directly interact with nucleic acids. Surface plasmon resonance assay (Biacore) indicated that four catechins, EGCG, (−)‐epicatechin gallate (ECG), (+)‐gallocatechin gallate (GCG), and (+)‐catechin gallate (CG), bound to DNA oligomers. Cold spray ionization mass spectrometry (CSI‐MS) analysis showed that one to three EGCG molecules bound to single‐stranded 18 mers of DNA and RNA. Moreover, one or two molecules of EGCG bound to double‐stranded AG:CT oligomers of various nucleotide lengths. Double‐stranded DNA (dsDNA) oligomers were detected only as EGCG‐bound forms at high temperature, whereas at low temperature both the free and bound forms were detected, suggesting that EGCG protects double‐stranded DNA oligomers from double‐stranded melting into single‐stranded DNA. We assume that catechins accumulate in both double‐stranded DNA and RNA molecules through multiple administrations of green tea beverage in in vivo, and that the accumulated green tea catechins play a significant role for human cancer prevention.

A SEC-HPLC-ICP MS hyphenated technique for identification of sulfur-containing arsenic metabolites in biological samples

The present study describes the synthesis and characterization of thioarsenicals using electro-spray ionization-MS and time of flight-MS. Separation of thioarsenicals was found to be better by size-exclusion column compared to anion exchange column coupled with HPLC-inductively coupled argon plasma mass spectrometer (ICP MS). Although four thioarsenicals were confirmed as dimethylthioarsinous acid (m/z=138), methylmonothioarsonous acid (m/z=122), dimethyldithioarsinic acid (m/z=170) and methyltrithioarsonic acid (m/z=188), it is noted that HPLC-ICP MS alone were not sufficient for their identification. Also, none of them was stable with time. This is the first report detailing the synthesis and identification of methyltrithioarsonic acid. Both dimethyldithioarsinic acid and dimethylthioarsinous acid were detected in human nail samples while dimethyldithioarsinic acid was found in urine samples. So, the above technique could be applicable to the identification of sulfur-containing biomolecules in the biological samples.