Main-Chain Optically Active Riboflavin Polymer for Asymmetric Catalysis and Its Vapochromic Behavior

A novel optically active polymer consisting of riboflavin units as the main chain (poly-<b>1</b>) was prepared from naturally occurring riboflavin (vitamin B₂) in three steps. The riboflavin residues of poly-<b>1</b> were converted to 5-ethylriboflavinium cations (giving poly-<b>2</b>), which could be reversibly transformed into the corresponding 4a-hydroxyriboflavins (giving poly-<b>2OH</b>) through hydroxylation/dehydroxylation reactions. This reversible structural change was accompanied by a visible color change along with significant changes in the absorption and circular dichroism (CD) spectra. The nuclear Overhauser effect spectroscopy (NOESY) and CD spectra of poly-<b>2</b> revealed a supramolecularly twisted helical structure with excess one-handedness through face-to-face stacking of the intermolecular riboflavinium units, as evidenced by the apparent NOE correlations between the interstrand riboflavin units and intense Cotton effects induced in the flavinium chromophore regions. The hydroxylation of poly-<b>2</b> at the 4a-position proceeded in a diastereoselective fashion via chirality transfer from the induced supramolecular helical chirality assisted by the ribityl pendants, resulting in a 83:17 diastereomeric mixture of poly-<b>2OH</b>. The diastereoselectivity of poly-<b>2</b> was remarkably higher than that of the corresponding monomeric model (64.5:35.5), indicating amplification of the chirality resulting from the supramolecular chirality induced in the stacked poly-<b>2</b> backbones. The optically active poly-<b>2</b> efficiently catalyzed the asymmetric organocatalytic oxidation of sulfides with hydrogen peroxide, yielding optically active sulfoxides with up to 60% enantiomeric excess (ee), whose enantioselectivity was higher than that catalyzed by the monomeric counterpart (30% ee). In addition, upon exposure to primary and secondary amines, poly-<b>2</b> exhibited unique high-speed vapochromic behavior arising from the formation of 4a-amine adducts in the film

Coupled Flavin-Iodine Redox Organocatalysts: Aerobic Oxidative Transformation from <i>N</i>‑Tosylhydrazones to 1,2,3-Thiadiazoles

A bioinspired two-component redox organocatalyst system using 1,10-bridged flavinium and NH₄I was developed to perform environmentally friendly aerobic oxidative ring formation of 1,2,3-thiadiazoles from <i>N</i>-tosylhydrazones and sulfur. The redox organocatalysis of the flavinium promoted the iodine-catalyzed system without the use of any sacrificial reagents, except for environmentally benign molecular oxygen

Remarkable Enhancement of the Enantioselectivity of an Organocatalyzed Asymmetric Henry Reaction Assisted by Helical Poly(phenylacetylene)s Bearing Cinchona Alkaloid Pendants via an Amide Linkage

A series of novel helical poly­(phenylacetylene)­s bearing amino-functionalized cinchona alkaloid pendant groups connecting to the phenyl rings through an amide linkage were prepared by the polymerization of the corresponding phenylacetylenes using a rhodium catalyst. All of the polymers formed a preferred-handed helical conformation biased by the optically active pendants, resulting in the induced circular dichroism in their π-conjugated polymer backbone regions. The optically active helical polymers efficiently catalyzed the asymmetric Henry reaction of benzaldehydes with nitromethane, giving optically active products up to 94% enantiomeric excess (ee) when the poly­(phenylacetylene) bearing an amino-functionalized quinine pendant group was used as the polymeric organocatalyst; the enantioselectivity was remarkably higher than those catalyzed by the corresponding nonhelical poly­(phenylacetylene) (18% ee) and the monomer (28% ee)

Allosteric Regulation of Unidirectional Spring-like Motion of Double-Stranded Helicates

We report the unprecedented allosteric regulation of the extension and contraction motions of double-stranded spiroborate helicates composed of 4,4′-linked 2,2′-bipyridine (bpy) and its <i>N</i>,<i>N</i>′-dioxide units in the middle of <i>ortho</i>-linked tetraphenol strands. NMR and circular dichroism measurements and an X-ray crystallographic analysis along with theoretical calculations revealed that enantiomeric helicates contract and extend upon the binding and release of protons and/or metal ions at the covalently linked two binding bpy or <i>N</i>,<i>N</i>′-dioxide moieties without racemization, respectively, regulated by a cooperative <i>anti</i>–<i>syn</i> conformational change of the two bpy or <i>N</i>,<i>N</i>′-dioxide moieties. These <i>anti</i>–<i>syn</i> conformational changes that occurred at the linkages are amplified into a large-scale molecular motion of the helicates leading to reversible spring-like motions coupled with twisting in one direction in a highly homotropic allosteric fashion

Effects of rivaroxaban and edoxaban on the collagen-induced phosphorylation of HSP27 in human platelets.

<p>PRP was pretreated with various doses of rivaroxaban (A) or edoxaban (B) for 15 min, and then stimulated by 1.0 μg/ml collagen or vehicle for 5 min. The reaction was terminated by the addition of ice-cold EDTA (10 mM) solution. The lysate of platelets was subjected to Western blot analysis using antibodies against phospho-specific HSP27 (Ser-78 and Ser-82), total HSP27 or GAPDH. Representative results of rivaroxaban from ten healthy donors (A) and results of edoxaban from five healthy donors (B) are presented. The histogram shows quantitative representation of the collagen-induced levels obtained from laser densitometric analysis. The phosphorylation levels are expressed as the fold increase to the basal levels presented as lane 1. Each value represents the mean ± SEM. *p<0.05, compared to the value of the vehicle alone, and **p<0.05, compared to the value of collagen alone.</p

Effect of rivaroxaban on the collagen-induced phosphorylation of p38 MAP kinase in human platelets.

<p>PRP was pretreated with various doses of rivaroxaban for 15 min, and then stimulated by 1.0 μg/ml collagen for 5 min. The reaction was terminated by the addition of ice-cold EDTA (10 mM) solution. The lysate of platelets was subjected to Western blot analysis using antibodies against phospho-specific p38 MAP kinase, p38 MAP kinase or GAPDH. Representative results obtained from ten healthy donors are presented. The histogram shows quantitative representation of the collagen-induced levels obtained from laser densitometric analysis. The phosphorylation levels are expressed as the fold increase to the basal levels presented as lane 1. Each value represents the mean ± SEM. N.S. designates no significant difference between the indicated pairs.</p

Effects of rivaroxaban and edoxaban on the collagen-induced phosphorylation of p44/p42 MAP kinase in human platelets.

<p>PRP was pretreated with various doses of rivaroxaban (A) or edoxaban (B) for 15 min, and then stimulated by 1.0 μg/ml collagen or vehicle for 5 min. The reaction was terminated by the addition of ice-cold EDTA (10 mM) solution. The lysate of platelets was subjected to Western blot analysis using antibodies against phospho-specific p44/p42 MAP kinase, p44/p42 MAP kinase or GAPDH. Representative results of rivaroxaban from ten healthy donors (A) and results of edoxaban from five healthy donors (B) are presented. The histogram shows quantitative representation of the collagen-induced levels obtained from laser densitometric analysis. The phosphorylation levels are expressed as the fold increase to the basal levels presented as lane 1. Each value represents the mean ± SEM. *p<0.05, compared to the value of the vehicle alone, and **p<0.05, compared to the value of collagen alone.</p

Representative data showing the effect of collagen on platelet aggregation and HSP27 phosphorylation (Ser-78) in platelets in patients after rivaroxaban administration.

<p>PRP was stimulated by various doses of collagen for 5 min, and the reaction was terminated by the addition of ice-cold EDTA (10 mM) solution. The black line indicates the percentage of transmittance of each sample (PRP recorded as 0%, and PPP was recorded as 100%). The blue line indicates small aggregates (9–25 μm); the green line, medium aggregates (25–50 μm); the red line, large aggregates (50–70 μm). The distributions (%) of aggregated particle size were measured by AUC of each particle size. The lysates of platelets were subjected to Western blot analysis using antibodies against HSP27, or phospho-specific HSP27 (Ser-78). Representative results obtained from five patients before rivaroxaban administration (A) and after the administration for 2 days (B). In the lower panel, the histogram shows quantitative representation of the collagen-induced phosphorylation levels obtained from laser densitometric analysis. The levels are expressed as the fold increase to the basal levels presented as lane 1. Each value represents the mean ± SEM. *p<0.05, compared to the value of the vehicle alone.</p

Representative data showing the effect of rivaroxaban on platelet aggregation induced by collagen.

<p>PRP was pretreated with various doses of rivaroxaban for 15 min, and then stimulated by 1.0 μg/ml collagen or vehicle for 5min. The reaction was terminated by the addition of ice-cold EDTA (10 mM) solution. Platelet aggregation was detected by an aggregometer with laser scattering system. The black line indicates the percentage of transmittance of each sample (PRP recorded as 0%, and PPP was recorded as 100%). The blue line indicates small aggregates (9–25 μm); the green line, medium aggregates (25–50 μm); the red line, large aggregates (50–70 μm). The distributions (%) of aggregated particle size were measured by AUC of each particle size. Representative results obtained from ten healthy donors are presented.</p

Effect of rivaroxaban on the collagen-stimulated PDGF-AB secretion from human platelets.

<p>PRP was pretreated with 1000 ng/ml of rivaroxaban or vehicle for 15 min, and then stimulated by 1.0 μg/ml collagen or vehicle for 5 min. The reaction was terminated by the addition of ice-cold EDTA (10 mM) solution. The conditional mixture was centrifuged at 10,000 x g at 4°C and the supernatants were then subjected to an ELISA for PDGF-AB. Values for unstimulated platelets have been subtracted from each data point. Results from ten healthy donors are shown. Each value represents the mean ± SEM. N.S. designates no significant difference between the indicated pairs.</p