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Catechinopyranocyanidins A and B (cpcA, B) are purple pigments isolated from the seed coat of the small red bean called adzuki in Japanese (Vigna angularis). CpcA and B are known to be responsible for the purple color of an-paste. The quality evaluation of the paste is based on its purple color; therefore, it is important to analyze the contents of cpcA and B in various azuki beans, which differ in the cultivar, production area, and cultivation conditions. The extraction of cpcA and B from dried beans was conducted, followed by high-performance liquid chromatography analysis. The content of cpcA and B in various cultivars from Japan, Korea, China, and Nepal was quantified. The cpcA and B content was the highest in the regular adzuki cultivar from Hokkaido Prefecture (Japan), and that of the beans from Korea and China was low. The content of the pale-colored beans from Nepal was the lowest.

A survey of metalloanthocyanin by in vivo visible spectrum and circular dichroism suggested that blue petals of Salvia macrophylla contain metalloanthocyanins. Chemical analysis of the purified blue pigment proved that the pigment in the petals is protodelphin, which is the same pigment present in the blue petals of Salvia patens composed of malonylawobanin, apigenin 7,4′-diglucosides and Mg2+.

We examined the hemodynamic profile of bioprosthetic aortic valves in patients on hemodialysis (HD), longitudinally, and assess the incidence of adverse changes detected by echocardiography. Of 1,146 consecutive patients with severe aortic stenosis who underwent bioprosthetic aortic valve replacement (AVR), 148 patients had end-stage renal disease requiring HD. Each patient on HD was matched one-to-one with a non-HD patient on the basis of propensity scores. The mean follow-up period was 3.3 years for the HD group and 5.9 years for the non-HD group. Follow-up information was available for 95.2%. Postoperative trends of valve hemodynamics derived from linear mixed-effect models showed significant group vs time interactions between the two groups. Stable hemodynamics was consistently observed in the non-HD group, whereas the HD group showed a decrease of -0.06 cm2/y (95% confidence interval (CI), -0.10 to -0.02) in effective orifice area, an increase of 0.8 mm Hg/year (95% CI, 0.4–1.1) in mean pressure gradient, and an increase of 0.08 m/s/year (95%CI, 0.02–0.13) in peak velocity. Cumulative incidence function of SVD more than stage 2 was significantly higher in the HD group (13.1% vs 3.1% at 5 years, Gray test p = 0.01). In a multivariable Fine-Gray analysis, diabetes was independently associated with SVD more than stage 2 in the HD group (subhazard ratio, 1.91; 95% CI, 1.25–2.89; p = 0.02). Survival free-from stenotic-type SVD was significantly lower in HD patients undergoing bioprosthetic AVR. Diabetes was independently associated with postoperative stenotic-type SVD in HD patients.

Peritonitis carcinomatosa is an advanced and intractable state of gastrointestinal and ovarian cancer, where mechanistic elucidation might enable the development of more effective therapies. Peritoneal dissemination of this type of malignancy has been generally thought to initiate from “milky spots” of primitive lymphoid tissues in the peritoneal cavity. In this study, we offer evidence challenging this idea, based on the finding that tumor implantation and directional dissemination was not required for the presence of milky spots, but rather SCF/CXCL12–expressing niche-like cells located at the border regions of perivascular adipose tissue. Interestingly, we found that peritoneal cavity lavage fluid, which specifically contains peritoneal collagen type IV and plasma fibronectin, dramatically facilitated spheroid formation of murine and human colon cancer cells. Spheroid formation strongly induced the expression of CXCR4 in an Sp1-dependent manner to promote niche-directed metastasis. Notably, disrupting sphere formation or inhibiting Sp1 activity was sufficient to suppress tumor dissemination and potentiated chemosensitivity to 5-fluorouracil. Our findings illuminate mechanisms of peritoneal cancer dissemination and highlight the Sp1/CXCR4/CXCL12 signaling axis as a rational target for the development of therapeutics to manage this intractable form of malignancy. Cancer Res; 76(2); 347–57. ©2016 AACR.

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Corydalis ambigua (Japanese name, Ezoengosaku) flowers bloom with blue to purplish petals in early spring in Hokkaido prefecture. In this study, a mechanism for blue petal coloration by ferric ions and keampferol glycoside was elucidated. Blue petals and cell sap exhibited similar visible (Vis) spectra, with λmax at approximately 600 nm and circular dichroism (CD) with positive exciton-type Cotton effects in the Vis region. Analysis of the organic components of the petals confirmed cyanidin 3-O-sambubioside and kaempferol 3-O-sambubioside as the major flavonoids. Mg, Al, and Fe were detected in petals using atomic emission spectroscopy. Color, Vis absorption, and CD consistent with those of blue petals were reproduced by mixing cyanidin 3-O-sambubioside, kaempferol 3-O-sambubioside, and Fe3+ in a buffered aqueous solution at pH 6.5. Both Fe3+ and flavonol were essential for blue coloration.

Hydrangea (Hydrangea macrophylla) is a unique flower because it is composed of sepals rather than true petals that have the ability to change color. In the early 20th century, it was known that soil acidity and Al3+ content could intensify the blue hue of the sepals. In the mid-20th century, the anthocyanin component 3-O-glucosyldelphinidin (1) and the copigment components 5-O-caffeoylquinic, 5-O-p-coumaroylquinic, and 3-O-caffeoylquinic acids (2-4) were reported. Interestingly, all hydrangea colors from red to purple to blue are produced by the same organic components. We were interested in this phenomenon and the chemical mechanisms underlying hydrangea color variation. In this review, we summarize our recent studies on the chemical mechanisms underlying hydrangea sepal color development, including the structure of the blue complex, transporters involved in accumulation of aluminum ion (Al3+), and distribution of the blue complex and aluminum ions in living sepal tissue.

Catechinopyranocyanidins A and B (cpcA and cpcB) are two purple pigments present in the seed‐coat of red adzuki bean, Vigna angularis , of which cpcA is the major pigment, containing two chiral carbons in the catechin part. Their absolute configurations were determined by comparison of their experimental and quantum chemical calculated electronic circular dichroisms (ECDs). These purple pigments are labile on light irradiation and easily decompose to photo‐degraded catechinopyranocyanidins A and B (pdcpcA and pdcpcB), while retaining the stereostructure of the catechin residue. We applied modified Mosher's method for determining the chirality of the secondary alcohol in pdcpcA. Hexamethylation of pdcpcA by diazomethane followed by esterification using (S )‐ and (R )‐MTPACl gave (R )‐ and (S )‐MTPA esters, respectively. By analysis of the NMR spectra of (R )‐ and (S )‐MTPA esters of tetramethylated (+)‐catechin, the chirality of pdcpcA was determined to be 2R , 3S , same as the absolute configuration of cpcA., ファイル公開：2021-05-01

Titanbicus (TB), a hybrid of Hibiscus moscheutos × H. coccineus (Medic.) Walt., has potential to be used as an edible flower. In this study, proximate nutritional content, anthocyanin content, total polyphenol content (TPC), and antioxidant activities in vitro and in vivo were investigated. Three cultivars of TB, namely Artemis (AR), Rhea (R), and Adonis (AD), were used as materials. Protein and carbohydrates were the primary macronutrients, while crude fat and ash were detected in trace amounts. Cyanidin 3-glucoside (Cy3-G) and cyanidin 3-sambubioside (Cy3-Sam), were identified in all TBs. The highest anthocyanin content was observed in AD (47.09 ± 1.45 mg/g extract), followed by R and AR (6.04 ± 0.20 and 2.72 ± 0.11 mg/g extract, respectively). The TPC of AD (225.01 ± 1.97 mg/g extract) was greater than that of AR and R (185.41 ± 3.24 and 144.10 ± 1.71 mg/g extract, respectively). AD exhibited the strongest in vitro antioxidant activity in hydrophilic oxygen radical absorbance capacity, compared to the other two TBs. In addition, AD extract suppressed the generation of reactive oxygen species in caudal fin of wounded zebrafish. Antioxidant activities of AD appeared to be related to its total anthocyanin content, Cy3-G, Cy3-Sam, and TPC. Our findings indicate that TB, particularly the AD cultivar, would be an attractive source of bioactive compounds with antioxidant activities, and can improve both nutritional value and appearance of food.

The original sepal color of Hydrangea macrophylla is blue, although it is well known that sepal color easily changes from blue through purple to red. All the colors are due to a unique anthocyanin, 3-O-glucosyldelphinidin, and both aluminum ion (Al3+) and copigments, 5-O-caffeoyl and/or 5-O-p-coumaroylquinic acid are essential for blue coloration. A mixture of 3-O-glucosyldelphinidin, 5-O-acylquinic acid, and Al3+ in a buffer solution at pH 4 produces a stable blue solution with visible absorption and circular dichroism spectra identical to those of the sepals, then, we named this blue pigment as ‘hydrangea blue-complex’. The hydrangea blue-complex consists of 3-O-glucosyldelphinidin, Al3+, and 5-O-acylquinic acid in a ratio 1:1:1 as determined by the electrospray ionization time-of-flight mass spectrometry and nuclear magnetic resonance spectra. To map the distribution of hydrangea blue-complex in sepal tissues, we carried out cryo-time-of-flight secondary ion mass spectrometry analysis. The spectrum of the reproduced hydrangea blue-complex with negative mode-detection gave a molecular ion at m/z = 841, which was consistent with the results of ESI-TOF MS. The same molecular ion peak at m/z = 841 was detected in freeze-fixed blue sepal-tissue. In sepal tissues, the blue cells were located in the second layer and the mass spectrometry imaging of the ion attributable to hydrangea blue-complex overlapped with the same area of the blue cells. In colorless epidermal cells, atomic ion of Al3+ was hardly detected and potassium adduct ion of 5-O-caffeoyl and/or 3-O-acylquinic acid were found. This is the first report about the distribution of aluminum, potassium, hydrangea blue-complex, and copigment in sepal tissues and the first evidence that aluminum and hydrangea blue-complex exist in blue sepal cells and are involved in blue coloration.

A 3D molecular arrangement and coordination of a minor anthocyanin from red cabbage creates a brilliant blue color., The color of food is critical to the food and beverage industries, as it influences many properties beyond eye-pleasing visuals including flavor, safety, and nutritional value. Blue is one of the rarest colors in nature’s food palette—especially a cyan blue—giving scientists few sources for natural blue food colorants. Finding a natural cyan blue dye equivalent to FD&C Blue No. 1 remains an industry-wide challenge and the subject of several research programs worldwide. Computational simulations and large-array spectroscopic techniques were used to determine the 3D chemical structure, color expression, and stability of this previously uncharacterized cyan blue anthocyanin-based colorant. Synthetic biology and computational protein design tools were leveraged to develop an enzymatic transformation of red cabbage anthocyanins into the desired anthocyanin. More broadly, this research demonstrates the power of a multidisciplinary strategy to solve a long-standing challenge in the food industry.

The first protecting group-free synthesis of N-glycosyl carbamates has been developed through reaction of d-glucose with n-butyl carbamate in acidic aqueous media. The structures of the N-glucosyl carbamates were unambiguously determined by comparison with authentic samples, prepared using the isocyanide method. With this protective group-free method for synthesis of N-glycosyl carbamates in hand, an anomeric pair of N-xylopyranosyl carbamates were prepared and used to assess the anomeric effect of nitrogen in the carbamate group.

UIDB/50006/2020 PTDC/QUI-OUT/29013/2017 MEX/Ref. 288188 SFRH/BD/143309/2019 IF/00225/2015 IF/01355/2014 CEECIND/00466/2017 REQUIMTE/EEC2018/PTDC/QUI-OUT/29925/2017 The aggregation of malvidin 3-O-(6-O-p-coumaroyl) glucoside flavylium cation (OeninCoum) in water is reported. Intra and intermolecular interactions of OeninCoum were characterized by UV–vis absorption, 1H NMR and circular dichroism (CD). Theoretical calculations were also performed to describe the intramolecular interactions. At higher temperature (>60 °C) the intermolecular aggregates are disrupted but CD signal attributed to an intramolecular interaction remains. Moreover, the kinetic and thermodynamic data for Oenin and OeninCoum at 50 °C and 25 °C shows that the increase of temperature stabilizes the quinoidal base of this later. authorsversion published

Hydrangea sepals exhibit a wide range of colors, from red, through purple, to blue; the purple color is a color mosaic. However, all of these colors are derived from the same components: simple anthocyanins, 3-O-glycosyldelphinidins, three co-pigment components, acylquinic acids and aluminum ions (Al3+ ). We show the color mosaic is a result of graded differences in intravacuolar factors. In order to clarify the mechanisms of mosaic color, we performed single-cell analyses of vacuolar pH, and anthocyanin, co-pigment and Al3+ content. From the sepals, a protoplast mixture of various colors was obtained. The cell color was evaluated by microspectrophotometry and vacuolar pH then was recorded by using a pH microelectrode. The organic and Al3+ contents were quantified by micro-HPLC. We found that the bluer the cell, the greater the ratio of 5-O-acylquinic acids and Al3+ to anthocyanins. Furthermore, reproducing experiments were conducted by mixing the components under various pH condition; all the colors could be reproduced in the various mixing conditions. Based on the above, we provide experimental evidence for cell color variation in hydrangea. Our study demonstrates the expression of phenotypic differences without any direct genomic control.

Using density functional theory (DFT) and time-dependent DFT (TD-DFT) methods, the current study reports the role of inserting acyclic and cyclic conjugated π-linkers in bis-N,N-dimethylaniline-based dyes as sensitizers in the dye-sensitized solar cells (DSSCs). Some optical and electron transfer parameters are calculated to accomplish our objective. The results show that increasing number of ethylene π-linker ( CH CH ) enhances light harvesting efficiency but decreases the driving force for electron injection and possibility of dye regeneration with encouraging dye aggregation on the surface of the electrode. Extending the conjugation length of the linker decreases the efficiency, while incorporating some cyclic conjugated linkers has a positive effect on the efficiency through effective coexistence of both direct and indirect mechanisms of electron injection. A comparison with experiment and previous theoretical studies on NKX-2554 (P1) and NKX-2569 (P2) is considered.

International audience; Anthocyanins acylated by hydroxycinnamic acids (HCAs) are fascinating plant pigments that express a variety of red, purple and blue colors by combining multiple structural transformations and molecular interactions. Acylated anthocyanins are also a promising alternative to artificial food colorants. In this work, the mono- and diacylated anthocyanins of red cabbage have been extensively studied by NMR, UV–visible spectroscopy and circular dichroism. Our results show that HCA residues promote π-stacking interactions between the phenolic nuclei, thereby efficiently protecting the cyanidin chromophore against water addition leading to colorless forms. For instance, the rate constant of water addition is ca. 0.3 s−1 for the nonacylated pigment, in the range 0.1–0.2 s−1 for the three monoacylated pigments and of the order of 0.01 s−1 for the three diacylated pigments. By contrast, the rate constant of water elimination and the thermodynamic constants of proton transfer between the cationic, neutral and anionic colored forms are only weakly affected by acylation. Thus, through π-stacking interactions, the diacylated anthocyanins maintain a higher percentage of cationic and neutral colored forms at equilibrium in mildly acidic conditions. In neutral - mildly alkaline conditions, the diacylated anthocyanins adopt persistent anionic forms (very slow water addition), expressing intense blue colors. NMR and CD data suggest that a combination of cyanidin – HCA (intramolecular copigmentation) and cyanidin – cyanidin (selfassociation) interactions operates in the color-stabilizing mechanism, which is also translated in an improved resistance against the long-term color loss in mildly alkaline conditions, signalling the irreversible degradation of the chromophore.

All equilibrium and rate constants of heavenly blue anthocyanin (HBA 1) as well as the derivatives with two (HBA 2) or none (HBA 3) acylated units were determined. The three acylated units of the sugar in position 3 of the peonidin chromophore of HBA 1 are essential to confer the peculiar stability of its purple and blue colors. The sugars generate an efficient protective environment around position 2 (and 4) of the flavylium cation, through an intramolecular sandwich-type stacking that retards 35-fold the hydration reaction (kh) and increases 8.8-fold the dehydration reaction (k–h), when compared with the peonidin chromophore HBA 3. The conjugation of these two rates lowers 308-fold the hydration equilibrium constant (Kh), corresponding to a raise of the energy level of the hemiketal by 14.2 kJ mol–1. Conversely, the pKa of the quinoidal base in HBA 1 is only slightly stabilized in comparison with that of HBA 2 and HBA 3. The energy level of hemiketal increases with the number of acylated units, but the ...

Objective: We introduce Utena’s Brief Objective Measures of 4 Axes for Psychic Function and Energy (UBOM-4), a new brief test battery for evaluating psychic function concerning intellect, emotion, volition, and imagination. To date, insufficient general population data on the UBOM have been collected. This study aimed to establish the normative values for the general population in UBOM-4 and examine the effects of age, sex, and mental health status on the values. Methods: The General Health Questionnaire, 12-item version (GHQ-12) and UBOM-4 were administered to 149 individuals working in or attending professional schools or universities (73 males, 76 females; age: 19 - 65 years). Participants were classified as healthy based on their GHQ-12 responses and psychiatrist interviews. Results: UBOM-4 measures (mean ± SD) were: pulse rate difference (PRD or UBOM-pulse), −0.72 ± 4.31 beats/min; ruler catching time (RCT or UBOM-ruler), 18.42 ± 3.73 cm; degree of randomness (DOR or UBOM-random), 0.94 ± 0.18; mean randomizing time (MRT or UBOM-time), 0.60 ± 0.31 sec. The Baum Test drawings were classified as usual (86%) and unusual patterns (14%). Sex effects were observed for RCT (UBOM-ruler) and DOR (UBOM-random), but not for PRD (UBOM-pulse) and MRT (UBOM-time). Therefore, the normative values for RCT (UBOM-ruler) (males: 17.37 ± 3.25 cm; females: 19.42 ± 3.90 cm) and DOR (UBOM-random) (males: 0.92 ± 0.18; females: 0.95 ± 0.18) should be differentiated by sex. The patterns of the Baum Test drawings were affected by age, with individuals over 51 years showing the unusual pattern more frequently (42%). Discussion: Compared to previous results for healthy individuals, the present results were similar for RCT (UBOM-ruler), DOR (UBOM-random), MRT (UBOM-time), and the drawing pattern, but different for PRD (UBOM-pulse). This difference is probably because PRD is sensitive to test situation habituation, sex of examiner, order of subtests, etc. Thus, PRD (UBOM-pulse) should be measured after the subject-examiner relationship stabilizes. Conclusion: Our results suggest that UBOM-4 can be widely used in clinical settings, utilizing the present results as a reference.

8-Phenyl-5,7-dihydroxyflavylium and 8-methyl-5,7-dihydroxyflavylium were synthesized to observe the 6,8-rearrangement. 8-Phenyl and 8-methyl residues were introduced by Suzuki–Miyaura reaction of 8-iodochrysin, then reduced by LiAlH4 to give the corresponding 3-deoxyanthocyanidins. At pH 1.0 the stable form is the 8-substituted flavylium cation in both compounds. At higher pH values the quinoidal bases are the stable species and some evidence for the 6,8-rearrangement was obtained, but the respective spectral variations are very small. This was overcome by using a modified cyclodextrin (captisol), which favors the formation of the trans-chalcone at the expense of the quinoidal bases. The trans-chalcone was isolated and dissolved in CD3OD/DCl (pD < 1) to give a mixture of the two flavylium isomers. This was confirmed by ESI-MS analysis (recorded in positive ion mode) of the two isomers after separation by HPLC, which gave the same peak ([M]+ m/z 253). The 6-isomer slowly reverts to the most stable 8-isomer. The 6,8-rearrangement was also observed after irradiation of the trans-chalcone (in the presence of captisol) at pH 5. Acidification of this photostationary state gave a mixture of both flavylium cations. The UV/Vis absorption of the flavylium cation (6-isomer) was blueshifted in comparison to the 8-isomer.

To elucidate the effect of soil conditions on the in planta distribution of inorganic elements, an aluminium (Al)-tolerant plant, Hydrangea macrophylla, was cultivated with the addition of Al ion to soils. Freeze-dried stems from the plants were analysed by time-of-flight secondary ion mass spectrometry (dry-TOF-SIMS). Freeze-fixed stems of the plants were analysed by cryo-TOF-SIMS. The inorganic metal content was quantified by inductively coupled plasma atomic absorption spectrometry (ICP-AES). The dry- and cryo-TOF-SIMS mapping analyses showed that in the native sample, inorganic elements are mainly localised in the cortex and pith. Al-treatment [i.e. Al2(SO4)3 administration to the soil] altered the distribution and content of inorganic metals. The actual amount of inorganic elements quantified by ICP-AES showed that Al-treatment on the soil increased the amounts of Na, Mg, Al and Ca and decreased that of K in the stem. The secondary ion counts of inorganic elements in freeze-dried and -fixed samples, determined by dry-/cryo-TOF-SIMS measurements, showed similar variations as that observed with ICP-AES measurements. These results are interpreted as that Al-treatment altered the distribution and amount of inorganic elements in the stems of Al-tolerant H. macrophylla plants.

Synthesis of 8-aryl-3,5,7,3′,4′-penta-O-methylcyanidins from the corresponding quercetin derivatives by reduction with LiAlH4 is reported. Regioselective iodination at the 8-position of penta-O-methylquercetin followed by a Suzuki-Miyaura reaction gave the 8-arylated quercetin derivatives. By the reduction of 8-arylated quercetins using 4 equiv. of LiAlH4 at room temperature for 30 min, the corresponding anthocyanidins were obtained with a good yield.

Five anthocyanins, namely, pelargonidin, cyanidin, delphinidin, petunidin and malvidin 3- O -glucosides, possessing different substitution patterns in the B-ring of the anthocyanidin chromophore were isolated from various plant materials. Dye-sensitized solar cells (DSSCs) were fabricated using the pure pigments, and then their cell colors and conversion efficiencies (η%) were compared. After optimization of the fabrication conditions, all the cells showed 0.6–1.4% conversion efficiency under AM 1.5. Among them, petunidin 3- O -glucoside provided the highest efficiency of 1.42% following the addition of deoxycholic acid (DCA) as an additive; however, removal of the glucosyl unit decreased the efficiency. The cell colors of cyanidin, delphinidin, and petunidin 3- O -glucosides appeared bluer with relatively high η% (>1%) values compared with those of pelargonidin and malvidin 3- O -glucosides. These phenomena may indicate that the former three pigments may attach to TiO 2 through the catechol moiety of the B-ring of the chromophores. Time-dependent density functional theory (TD-DFT) calculations were performed on model systems consisting of anthocyanidin dyes on a (TiO 2 ) 38 cluster to characterize the photo-absorption properties of DSSCs.

An efficient conversion of rutin to the corresponding anthocyanin, cyanidin 3-O-rutinoside, was established. Clemmensen-type reduction of rutin gave a mixture of flav-2-en-3-ol and two flav-3-en-3-ols, which were easily oxidised by air to give the anthocyanin. The interconversion reactions of these flavonoids provide insight into their biosynthetic pathway.

The bluish-purple petals of Chinese bellflower, Platycodon grandiflorum (kikyo in Japanese), contain platyconin (1) as the major anthocyanin. Platyconin (1) is a polyacylated anthocyanin with two caffeoyl residues at the 7-position, and its color is stable in a diluted, weakly acidic aqueous solutions. HPLC analysis of the fresh petal extract showed the presence of several minor pigments. Photo-diode array detection of minor pigments suggested that some of these were polyacylated anthocyanins. To establish the relationship between structure and stability of the acylated anthocyanins and to obtain information on their biosynthetic pathways, minor pigments were isolated from the petals, and their structures were determined by MS and NMR analyses. Four known (2–5) and three new anthocyanins (6–8) were identified, which contained a delphinidin chromophore, and four of these (5–8) were diacylated anthocyanins, in which the acyl-glucosyl-acyl-glucosyl chain was attached at the 7-O-position of the delphinidin chromophore. These diacylated anthocyanins exhibited a bluish-purple color at pH 6, which was stable for more than a week.

penta-O-Methylquercetin (2) was prepared by permethylation of quercetin (1). Selective demethylation of 2 using either BBr3 or BCl3/TBAI ( tetra-butylammonium iodide) gave five O-methylquercetins (3-6), with satisfactory yields. The reaction can be easily scaled-up. We established an efficient and large-scale preparation of O-methylquercetins.

The small red bean, Vigna angularis, is primarily used to produce the “an-paste” component of Japanese sweets. Through the manufacturing process, the red seed-coat pigment is transferred to the colorless “an-particles”, imparting a purple color. However, the major pigment in the seed coat has not yet been identified, although it is historically presumed to be an anthocyanin. Here, we report the isolation and structural determination of two hydrophobic purple pigments in the seed coat via instrumental analysis and derivatization. The new pigments, catechinopyranocyanidins A and B, contain a novel pyranoanthocyanidin skeleton condensed with a catechin and cyanidin ring system, and no sugar moieties. Catechinopyranocyanidins A and B are diastereomers with a different configuration at the catechin moiety, and both are purple in color in strongly acidic-to-neutral media. Catechinopyranocyanidins A and B are very stable under dark conditions, but, labile to light and decompose to colorless compounds. Thus, these pigments exhibit quite different chemical properties compared to simple anthocyanidins.

Oenothera flower petals change color during senescence. When in full bloom, the flowers of O. tetraptera are white and those of O. laciniata and O. stricta are yellow. However, the colors change to pink and orange, respectively, when the petals fade. We analyzed the flavonoid components in these petals as a function of senescence using HPLC-DAD and LC-MS. In all three species, cyanidin 3-glucoside (Cy3G) was found in faded petals. The content of Cy3G increased in senescence. In full bloom (0 h), no Cy3G was detected in any of the petals. However, after 12 h, the content of Cy3G in O. tetraptera was 0.97 &micro, mol/g fresh weight (FW) and the content of Cy3G in O. laciniata was 1.82 &micro, mol/g FW. Together with anthocyanins, major flavonoid components in petals were identified. Quercitrin was detected in the petals of O. tetraptera and isosalipurposide was found in the petals of O. laciniata and O. stricta. The content of quercitrin did not change during senescence, but the content of isosalipurposide in O. laciniata increased from 3.4 &micro, mol/g FW at 0 h to 4.8 &micro, mol/g FW at 12 h. The color change in all three Oenothera flowers was confirmed to be due to the de novo biosynthesis of Cy3G.

The blue sepal color of hydrangea is due to a metal complex anthocyanin composed of 3-O-glucosyldelphinidin (1) and an aluminum ion with the co-pigments 5-O-caffeoylquinic acid (2) and/or 5-O-p-coumaroylquinic acid (3). The three components, namely, anthocyanin, Al3+ and 5-O-acylquinic acids, are essential for blue color development, but the complex is unstable and only exists in aqueous solution. Furthermore, the complex did not give analyzable NMR spectra or crystals. Therefore, many trials to determine the detailed chemical structure of the hydrangea-blue complex have failed to date. Instead, via experiments mixing 1, Al3+ and 2 or 3 in a buffered solution at pH 4.0, we obtained the same blue solution derived from the sepals. However, the ratio was not stoichiometric but fluctuated. To determine the composition of the complex, we tried direct observation of the molecular ion of the complex using electrospray-ionization mass spectrometry. In a very low-concentration buffer solution (2.0 mM) at pH 4.0, we reproduced the hydrangea-blue color by mixing 1, 2 and Al3+ in ratios of 1:1:1, 1:2:1 and 1:3:1. All solution gave the same molecular ion peak at m/z = 843, indicating that the blue solution has a ratio of 1:1:1 for the complex. By using 3, the observed mass number was m/z = 827 and the ratio of 1, 3 and Al3+ was also 1:1:1. A mixture of 1, 3-O-caffeoylquinic acid (4) and Al3+ did not give any blue color but instead was purple, and the intensity of the molecular ion peak at m/z = 843 was very low. These results strongly indicate that the hydrangea blue-complex is composed of a ratio of 1:1:1 for 1, Al3+ and 2 or 3.

An efficient and versatile synthesis of 5-O-acylquinic acids from commercially available (−)-quinic acid was accomplished. We designed p-methoxybenzyl quinate as a key intermediate, and two problems, the esterification of the sterically hindered 5-OH group for the concise divergent synthesis and the low yield of the final deprotection step, were solved. For the first problem, we improved Tanabe's method, TsCl/NMI-mediated esterification using free carboxylic acids, by the addition of i-Pr2NEt. For the second problem, we established a TFA- or BCl3/C6HMe5-catalyzed deprotection reaction for the final deprotection step. 5-O-Acylquinic acids were synthesized in seven steps with 45–60% overall yield.

The pigment, tecophilin, in blue flowers of Tecophilaea cyanocrocus was isolated and the structure was determined to be 3-O-(6-O-α- l -rhamnopyranosyl-β- d -glucopyranosyl)-7-O-(6-O-(4-O-(2-O-(4-O-β- d -glucopyranosyl-(E)-caffeoyl)-6-O-(4-O-β- d -glucopyranosyl-(E)-caffeoyl)-β- d -glucopyranosyl)-(E)-caffeoyl)-β- d -glucopyranosyl)delphinidin. The reproduction experiment of the same color as petals according to the results of chemical analysis and measurement of vacuolar pH of blue cells clarified that the blue color solely develops by tecophilin without interaction of metal ions nor co-pigments. 1H NMR analysis and CD spectrum indicate the co-existence of clockwise intermolecular self-association of the delphinidin nuclei and intramolecular π–π stacking between the chromophore and caffeoyl residues to derive bathochromic shift of the absorption spectrum and stabilize the color by preventing hydration reaction.

DS-8587 is a novel broad-spectrum fluoroquinolone with extended antimicrobial activity against both Gram-positive and Gram-negative pathogens. In this study, we evaluated the in vitro and in vivo antibacterial activity of DS-8587 against multidrug-resistant (MDR) Acinetobacter baumannii. The MIC range of DS-8587 against MDR A. baumannii was 0.25-2 mg/L. These DS-8587 MICs were a minimum of 16-fold or 8-fold more potent than ciprofloxacin or levofloxacin, respectively. Bactericidal activity, a 3 log10 reduction from the initial bacterial counts, was observed within 2 h for 1593644 and 4 h for 1593684 after exposure to DS-8587. Therapeutic efficacy of DS-8587 in the murine calf muscle model was observed at 256 mg/kg. The analysis of the pharmacokinetic and pharmacodynamic index revealed that the AUC/MIC ratio showed the best correlation with efficacy. The total and free drug AUC/MIC value required for a static effect was 29.4 and 14.1, respectively. These data indicate DS-8587 would be an effective agent against MDR A. baumannii infection.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The blue petal color of the cornflower (Centaurea cyanus) is caused by protocyanin, a kind of metalloanthocyanin, which is a self-assembled supramolecular metal complex pigment. Protocyanin is composed of six molecules of anthocyanin, six molecules of flavone, one ferric ion, and one magnesium ion. The ferric ion is essential for blue color development. Here, we identify the vacuolar iron transporter gene (CcVIT) from the blue petals of C. cyanus and its function is identified and characterized. The CcVIT transcript was observed only in the petals. Its amino acid sequence is highly homologous to the Arabidopsis thaliana (AtVIT1) and Tulipa gesneriana (TgVit1) vacuolar iron transporters. Heterologous expression of the CcVIT gene in yeast indicated that the corresponding gene product transports ferrous ion into vacuoles. Analysis of purple mutant-line petals clarified that the anthocyanin and flavone components were the same as those found in plants with blue petals, but the amount of iron ions in the colored cells decreased, and consequently the amount of blue protocyanin was reduced. The CcVIT gene was expressed even in purple mutant petals, however, an amino acid substitution (A236E) occurred in that case. This change in the CcVIT gene sequence also resulted in loss of iron transport activity. The CcVIT protein thus plays a critical role in the blue coloration of cornflower petals.

Several flowers of Tulipa gesneriana exhibit a blue color in the bottom segments of the inner perianth. We have previously reported the inner-bottom tissue-specific iron accumulation and expression of the vacuolar iron transporter, TgVit1, in tulip cv. Murasakizuisho. To clarify whether the TgVit1-dependent iron accumulation and blue-color development in tulip petals are universal, we analyzed anthocyanin, its co-pigment components, iron contents and the expression of TgVit1 mRNA in 13 cultivars which show a blue color in the bottom segments of the inner perianth accompanying yellow- and white-colored inner-bottom petals. All of the blue bottom segments contained the same anthocyanin component, delphinidin 3-rutinoside. The flavonol composition varied with cultivar and tissue part. The major flavonol in the bottom segments of the inner perianth was rutin. The iron content in the upper part was less than that in the bottom segments of the inner perianth. The iron content in the yellow and white petals was higher in the bottom segment of the inner perianth than in the upper tissues. TgVit1 mRNA expression was apparent in all of the bottom tissues of the inner perianth. The result of a reproduction experiment by mixing the constituents suggests that the blue coloration in tulip petals is generally caused by iron complexation to delphinidin 3-rutinoside and that the iron complex is solubilized and stabilized by flavonol glycosides. TgVit1-dependent iron accumulation in the bottom segments of the inner perianth might be controlled by an unknown system that differentiated the upper parts and bottom segments of the inner perianth.

Malignant ascitis (MA) is a highly intractable and immunotherapy-resistant state of advanced gastrointestinal and ovarian cancers. Using a murine model of MA with CT26 colon cancer cells, we here determined that the imbalance between the VEGF-A/vascular permeability factor and its decoy receptor, soluble fms-like tryrosine kinase receptor-1 (sFLT-1), was a major cause of MA resistance to dendritic cell (DC)-based immunotherapy. We found that the ratio of VEGF-A/sFLT-1 was increased not only in murine but also in human MA, and F-gene–deleted recombinant Sendai virus (rSeV/dF)-mediated secretion of human sFLT-1 by DCs augmented not only the activity of DCs themselves, but also dramatically improved the survival of tumor-bearing animals associated with enhanced CTL activity and its infiltration to peritoneal tumors. These findings were not seen in immunodeficient mice, indicating that a VEGF-A/sFLT-1 imbalance is critical for determining the antitumor immune response by DC-vaccination therapy against MA. Mol Cancer Ther; 10(3); 540–9. ©2011 AACR.

Dendritic cells (DC)-based immunotherapy is a potent anticancer modality. In DC-based immunotherapy, allogeneic DC may be an alternative source, but the usefulness of allogeneic DC in DC-based immunotherapy is still controversial. When used for immunotherapy, three factors may affect the efficiency of an allogeneic DC-driven antitumour response: (1) survival time, which is affected by T-cell alloresponses; (2) major histocompatibility complex incompatibility with the host cells in the context of antigen presentation; and (3) the role of host-derived professional antigen-presenting cells (pAPC). In addition, it is unclear which injection route is preferable when using allogeneic DC. In this study, we demonstrate that semi-allogeneic DC, which share half of the genes of the recipient, are more effective when used via the intratumoural (i.t.) injection route, rather than the subcutaneous (s.c.) injection route, for the induction of efficient antitumour effects and the generation of a significant tumour-specific CD8+ T-cell response. The i.t. route has the advantage of not requiring ex vivo pulsation with tumour lysates or tumour antigens, because the i.t.-injected DC can engulf tumour antigens in situ. Allogeneic bone marrow transplantation (BMT) models, which permit us to separately assess the three factors described previously, show that while all three factors are important for efficient antitumour effects, the control of the alloresponse to injected DC is the most crucial for host-derived pAPC to function well when DC are administered intratumourally. This information may be useful for DC-based cancer immunotherapy under circumstances that do not allow for the use of autologous DC.