| 1. |
Chiharu ISHII, Takeyuki AKITA, Tomonori KIMURA, Shinsuke SAKAI, Masashi MITA, Tomomi IDE, Yoshitaka ISAKA, Kenji HAMASE, Evaluation of individual variation of D-amino acids in human plasma by a two-dimensional LC-MS/MS system and application to the early diagnosis of chronic kidney disease, Analytical Chemistry, 10.1021/acs.analchem.3c05309, in press, 2024.04. |
| 2. |
Chiharu ISHII, Yosuke TOJO, Komei IWASAKI, Akira FUJII, Takeyuki AKITA, Masanobu NAGANO, Masashi MITA, Tomomi IDE, Kenji HAMASE, Development of a two-dimensional LC-MS/MS system for the determination of proline and 4-hydroxyproline enantiomers in biological and food samples, Analytical Sciences, DOI: 10.1007/s44211-024-00530-w, in press, 2024.04. |
| 3. |
Mai Oyaide, Chiharu Ishii, Takeyuki Akita, Tomonori Kimura, Shinsuke Sakai, Masayuki Mizui, Masashi Mita, Tomomi Ide, Yoshitaka Isaka, Kenji Hamase, Development of a three-dimensional HPLC system for the determination of serine, threonine and allo-threonine enantiomers in the plasma of patients with chronic kidney disease, Journal of Chromatography A, 10.1016/j.chroma.2024.464739, 1719, 464739, 2024.02. |
| 4. |
Hsin-Miao TSAI, Chin-Ling HSIEH, Chiharu ISHII, Takeyuki AKITA, Masashi MITA, Tomomi IDE, Jen-Ai LEE, Kenji HAMASE, Enantioselective analysis of lactate, hydroxybutyrates and malate in human physiological fluids using a three-dimensional HPLC system, Chromatography, 10.15583/jpchrom.2023.015, 44, 105-113, 2023.09. |
| 5. |
Yuri NAGATA, Takeyuki AKITA, Chiharu ISHII, Mai OYAIDE, Masashi MITA, Tomomi IDE, Kenji HAMASE, Development of an enantioselective three-dimensional HPLC system for the determination of alanine, valine, isoleucine, allo-isoleucine and leucine in human plasma and urine, Journal of Pharmaceutical and Biomedical Analysis Open, 10.1016/j.jpbao.2023.100013, 2, 100013, 2023.09. |
| 6. |
Yuri NAGATA, Takeyuki AKITA, Aogu FURUSHO, Chiharu ISHII, Masashi MITA, Kenji HAMASE, Design of novel mixed-mode columns for analysis of amino acids derivatized with 4-fluoro-7-nitro-2,1,3-benzoxadiazole and the evaluation of retention properties, Chromatography, DOI: 10.15583/jpchrom.2023.006, in press, 2023.04. |
| 7. |
Chiharu ISHII, Rin MORINAGA, Miho TAKAHASHI, Masashi MITA, Takeyuki AKITA, Kenji HAMASE, Development of a three-dimensional HPLC system for acidic amino acid enantiomers and determination of their amounts in mice lacking D-aspartic acid oxidase activity, Journal of Pharmaceutical and Biomedical Analysis Open, DOI: 10.1016/j.jpbao.2023.100004, 1, 100004 (2023), 2023.02. |
| 8. |
Chiharu ISHII, Takeyuki AKITA, Masashi MITA, Ryuichi KONNO, Kenji HAMASE, Chiral amino acid analysis in the plasma of B6DAO-/- mice lacking D-amino acid oxidase activity, Chromatography, DOI: 10.15583/jpchrom.2023.002, 44, 39-43 (2023), 2023.01. |
| 9. |
Hsin-Miao TSAI, Chin-Ling HSIEH, Chiharu ISHII, Takeyuki AKITA, Masashi MITA, Tomomi IDE, Jen-Ai LEE Kenji HAMASE, Two-dimensional chiral HPLC analysis of lactate, hydroxybutyrates and malate in human plasma, Chromatography, 10.15583/jpchrom.2022.011, 43, 119-126, 2022.10. |
| 10. |
Chiharu Ishii, Noburo Takizawa, Takeyuki Akita, Masashi Mita, Tomomi Ide, Ryuichi Konno, Kenji Hamase, Single-type reporter multiplexing with A single droplet through bead-based digital microfluidics, JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, 10.1016/j.jpba.2022.114919, 219, 2022.09, With the limited sample volume, the droplet-based microfluidic becomes attractive in biomedical diagnosis, especially for measuring multiple analytes. Usually, for multiplexing by parallel processing, a larger sample volume is required. In our previous study, simultaneously detecting two analytes from a single droplet was first achieved by measuring different fluorescence wavelengths for different analytes. However, the number of detectable analytes could be limited by the spectral resolution of fluorescence. Here a different approach is proposed for multiplexing by sharing a single droplet in multiple sub-assays. Therefore, only a single-type re-porter, i.e., the fluorescence with the same wavelength, is needed for detection of different analytes from a single sample droplet, called single-type reporter multiplexing (STRM). The standard curves of two analytes, human IL-1 beta and human TNF-alpha, are demonstrated. The required sample volume for one measurement is only 520 nL; the total duration of the on-chip process is less than 50 min. The limits of detection (LOD) of human IL-1 beta and human TNF-alpha are about 1.14 and 0.97 pg/mL, respectively. It is shown that the proposed bead-based digital microfluidic immunoassay can achieve multiple analytes detection with low LOD from a single sample droplet using the single-type reporter, which has never been achieved before.. |
| 11. |
Mai Oyaide, Aogu Furusho, Chiharu Ishii, Takeyuki Akita, Masashi Mita, Tomomi Ide, Kenji Hamase, Development of an off-line heart cutting two-dimensional HPLC system for enantioselective analysis of serine, threonine and allo-threonine in human physiological fluids, Journal of Pharmaceutical and Biomedical Analysis, 10.1016/j.jpba.2022.114807, 217, 114807-114807, 2022.08, A highly-selective two-dimensional high-performance liquid chromatographic (2D-HPLC, off-line heart cutting mode) system was developed for the determination of serine (Ser), threonine (Thr) and allo-threonine (aThr) enantiomers in human physiological fluids. Ser, Thr and aThr have a hydroxy group in their side chains, and the development of a simultaneous analytical method with a practically sufficient enantio/chemo-selectivity has been required to clarify their amounts in human physiological fluids. The amino acids in the samples were derivatized with 4-fluoro-7-nitro-2,1,3-benzoxadiazole and were isolated by a reversed-phase column (Singularity RP18, 1.0 x 250 mm) in the first dimension. After the target amino acids were collected, the fractions were manually introduced into an enantioselective column in the second dimension and were detected by their fluorescence. For the second dimension, a Pirkle-type chiral stationary phase (Singularity CSP-013S, 1.5 x 250 mm) was used. The resolution values of the enantiomers obtained by the Singularity CSP-013S column were 7.64 for Ser, 7.58 for Thr and 4.71 for aThr by using the mixture of methanol and acetonitrile containing formic acid as the mobile phases. The developed method was validated and applied to human plasma and urine. In the plasma, the obtained %D values (the percentage of D-form to total amino acid) were 1.7 for Ser, and trace levels of D-aThr and D-Thr were observed. In the urine, the %D values were 48.0 for Ser, 1.6 for Thr and 8.0 for aThr (calculated using D-aThr and L-Thr).. |
| 12. |
Mai OYAIDE, Chiharu ISHII, Akira FUJII, Takeyuki AKITA, Masashi MITA, Masanobu NAGANO, Kenji HAMASE, Enantioselective determination of hydroxy amino acids in Japanese traditional amber rice vinegars, Chromatography, 10.15583/jpchrom.2022.006, 43, 59-65, 2022.05. |
| 13. |
Chiharu Ishii, Noburo Takizawa, Takeyuki Akita, Masashi Mita, Tomomi Ide, Ryuichi Konno, Kenji Hamase, Off-line two-dimensional LC-MS/MS determination of tryptophan enantiomers in mammalian urine and alteration of their amounts in d-amino acid oxidase deficient mice., Journal of pharmaceutical and biomedical analysis, 10.1016/j.jpba.2022.114919, 219, 114919-114919, 2022.09, D-Tryptophan (D-Trp) is one of the minor D-enantiomers of amino acids discovered in microbes and mollusca. In the present study, a highly-selective 2D chiral LC-MS/MS method has been designed and developed focusing on the determination of Trp enantiomers to investigate the presence and regulation of free D-Trp in mammals. The developed system consisted of a reversed-phase separation for the first dimension, an enantioselective separation for the second dimension and also the detection using a triple quadrupole mass spectrometer for the third/fourth dimensions. Using the present method, urinary D-Trp in mammals, including healthy human volunteers and mice, were successfully determined. Although only l-Trp was observed in a mixed urine sample of healthy volunteers, small amounts of D-Trp were detected in the C57BL/6J mice (n = 5, %D=6.18 ± 0.47). In B6DAO- mice lacking the activity of d-amino acid oxidase (DAO), relatively high levels of D-Trp were observed (n = 6, %d=27.43 ± 3.26). The obtained %d values of Trp in the urine of the C57BL/6J mice and B6DAO- mice were confirmed using various enantioselective columns having different separation properties. These results indicate that the urinary D-Trp level is regulated by DAO in mammals, and further investigations, such as tissue distribution and physiological significance of the intrinsic D-Trp, are expected.. |
| 14. |
Aogu FURUSHO, Karina Akemy IKEJIRI, Chiharu ISHII, Takeyuki AKITA, Masashi MITA, Masanobu NAGANO, Tomomi IDE, Kenji HAMASE, Two-dimensional high-performance liquid chromatographic determination of chiral amino acids in food samples and human physiological fluids using fluorescence derivatization with 4-(N,N-dimethylaminosulfonyl)-7-fluoro-2,1,3-benzoxadiazole, Chromatography, DOI: 10.15583/jpchrom.2021.020, 43, 29-35 (2022), 2022.01. |
| 15. |
Manabu Nakazono, Shinkoh Nanbu, Takeyuki Akita, Kenji Hamase, Acridinium Ester Chemiluminescence: Methyl Substitution on the Acridine Moiety, Journal of Oleo Science, https://doi.org/10.5650/jos.ess21186, 70, 11, 1677-1684, 70, (11) 1677-1684 (2021), 2021.11, Methyl groups were introduced on the acridine moiety in chemiluminescent acridinium esters that have electron-withdrawing groups (trifluoromethyl, cyano, nitro, ethoxycarbonyl) at the 4-position on the phenyl ester. The introduction of methyl groups at the 2-, 2, 7-, and 2, 3, 6, 7-positions on the acridine moiety shifted the optimal pH that gave relatively strong chemiluminescence intensity from neutral conditions to alkaline conditions. 4-(Ethoxycarbonyl)phenyl 2, 3, 6, 7, 10-pentamethyl-10λ4-acridine-9- carboxylate, trifluoromethanesulfonate salt showed long-lasting chemiluminescence under alkaline conditions. Acridinium esters to determine hydrogen peroxide concentration at pH 7-10 were newly developed.. |
| 16. |
Chin-Ling Hsieh, Chiharu Ishii, Takeyuki Akita, Akira Fujii, Kazunori Hashiguchi, Masanobu Nagano, Masashi Mita, Jen-Ai Lee, Kenji Hamase, Chiral analysis of lactate in various food samples including Japanese traditional amber rice vinegar and the developmental change during fermentation processes, Chromatography, 10.15583/jpchrom.2021.017, 42, 3, 151-158, 2021.10. |
| 17. |
Chin-Ling Hsieh, Takeyuki Akita, Masashi Mita, Tomomi Ide, Jen-Ai Lee, Kenji Hamase, Development of a selective three-dimensional HPLC system for enantiomer discriminated analysis of lactate and 3-hydroxybutyrate in human plasma and urine, JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, 10.1016/j.jpba.2020.113871, 195, 113871-113871, 2021.02, For the enantiomer discriminated determination of lactate (LA) and 3-hydroxybutyrate (3HB) in various complicated samples, a three-dimensional HPLC (3D-HPLC) system has been designed and developed by investigating the separation of the target analytes from unknown substances observed in the real target matrices. LA and 3HB were pre-column derivatized with 4-nitro-7-piperazino-2,1,3-benzoxadiazole for the sensitive fluorescence detection and introduced into the 3D-HPLC system composed of reversed-phase, mixed-mode and enantioselective separations. The present method was validated by calibration curves, precision and accuracy using standard solutions and human samples, and sufficient values were obtained. Using the method, the levels of d-LA, l-LA, d-3Hb and l-3HB were determined, and their concentrations were 9.9, 1004.2, 79.7 and 2.1 μM in the human plasma and 16.0, 86.6, 8.7 and 4.8 μM in the human urine, respectively. The present 3D-HPLC system could selectively determine trace amounts of the target hydroxy acid enantiomers without disturbance of the intrinsic interfering substances in complicated matrices and the applications to various disease samples are expected.. |
| 18. |
Sui-Wen Hsiao, Chiharu Ishii, Aogu Furusho, Chin-Ling Hsieh, Yukiko Shimizu, Takeyuki Akita, Masashi Mita, Tadashi Okamura, Ryuichi Konno, Tomomi Ide, Ching-Kuo Lee, Kenji Hamase, Determination of phenylalanine enantiomers in the plasma and urine of mammals and D-amino acid oxidase deficient rodents using two-dimensional high-performance liquid chromatography, BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS, 10.1016/j.bbapap.2020.140540, 1869, 1, 140540-140540, 2021.01, A two-dimensional (2D) HPLC system focusing on the determination of phenylalanine (Phe) enantiomers in mammalian physiological fluids has been developed. ᴅ-Phe is indicated to have potential values as a disease biomarker and therapeutic molecule in several neuronal and metabolic disorders, thus the regulation of ᴅ-Phe in mammals is a matter of interest. However, the precise determination of amino acid enantiomers is difficult in complex biological samples, and the development of an analytical method with practically acceptable sensitivity, selectivity and throughput is expected. In the present study, a 2D-HPLC system equipped with a reversed-phase column in the 1st dimension and an enantioselective column in the 2nd dimension has been designed, following the fluorescence derivatization of the target amino acid enantiomers with 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F). The analytical method was validated using both plasma and urine samples, and successfully applied to human, rat and mouse fluids. Trace levels of ᴅ-Phe were determined in the plasma, and the %ᴅ values were around 0.1% for all species. In the urine, relatively large amounts of ᴅ-Phe were observed, and the %ᴅ values for humans, rats and mice were 3.99, 1.76 and 5.25%, respectively. The relationships between the enzymatic activity of ᴅ-amino acid oxidase (DAO) and the amounts of intrinsic ᴅ-Phe have also been clarified, and high ᴅ-Phe amounts were observed (around 0.3% in the plasma and around 50% in the urine) in the DAO deficient rats and mice.. |
| 19. |
Manabu Nakazono, Shinkoh Nanbu, Takeyuki Akita, Kenji Hamase, Chemiluminescence of methoxycarbonylphenyl 10-methyl-10λ4 -2,7-disubstituted acridine-9-carboxylate derivatives, Journal of Photochemistry and Photobiology A: Chemistry, 10.1016/j.jphotochem.2020.112851, 403, Article number 112851, 2020.12, Methoxycarbonylphenyl 10-methyl-10λ4-2,7-disubstituted acridine-9-carboxylate derivatives were synthesized, and both their chemiluminescence intensities at pH 7−10 and their chemical stabilities were clarified. The products and generation efficiency of the chemiluminescence reactions were evaluated. 4-(Methoxycarbonyl)phenyl 10-methyl-10λ4-2,7-dimethylacridine-9-carboxylate gave relatively strong chemiluminescence intensities at pH 7−10 and was applied to the measurement of hydrogen peroxide.. |
| 20. |
Aogu FURUSHO, Mintranee OBROMSUK, Takeyuki AKITA, Masashi MITA, Masanobu NAGANO, Pornchai ROJSITTHISAK, Kenji HAMASE, High-performance liquid chromatographic determination of chiral amino acids using pre-column derivatization with o-phthalaldehyde and N-tert-butyloxycarbonyl-D-cysteine and application to vinegar samples, Chromatography, 10.15583/jpchrom.2020.015, 147-151, 41, 147-151 (2020), 2020.10. |
| 21. |
Aogu Furusho, Takeyuki Akita, Masashi Mita, Hiroshi Naraoka, Kenji Hamase, Three-dimensional high-performance liquid chromatographic analysis of chiral amino acids in carbonaceous chondrites, JOURNAL OF CHROMATOGRAPHY A, 10.1016/j.chroma.2020.461255, 1625, 461255-461255, 2020.08, A three-dimensional (3D) HPLC system in combination with fluorescence derivatization has been developed for the highly sensitive and selective analysis of chiral amino acids in extraterrestrial samples. As the targets, alanine (Ala), 2-aminobutyric acid (2AB), valine (Val), norvaline (nVal) and isovaline (iVal), frequently found chiral amino acids in the carbonaceous chondrites, were selected. These amino acids were pre-column derivatized with 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F), and the target analytes were separated from other amino acids and organic compounds by a reversed-phase column in the first dimension. The targets were further separated from interferences by an anion-exchange column in the second dimension, and their enantiomers were separated and determined in the third dimension by a Pirkle-type enantioselective column. The present 3D-HPLC system was validated and applied to the Murchison meteorite and the Antarctic meteorites, and all of the target amino acid enantiomers were clearly observed (0.78-22.33 nmol/g in the Murchison meteorite and 1.79-78.84 nmol/g in the Antarctic meteorites) without severe interferences. The %L values of the non-proteinogenic amino acids were almost 50% in both meteorites, and even the proteinogenic amino acids were almost racemic in the Antarctic meteorites.. |
| 22. |
Manabu Nakazono, Shinkoh Nanbu, Takeyuki Akita, Kenji Hamase, Synthesis, chemiluminescence, and application of 2,4-disubstituted phenyl 10-methyl-10 lambda(4)-acridine-9-carboxylates, DYES AND PIGMENTS, 10.1016/j.dyepig.2019.107628, 170, 2019.11, 2,4-Disubstituted phenyl 10-methyl-10 lambda(4)-acridine-9-carboirylate derivatives were synthesized and the chemiluminescence of each was measured at pH 6-9. The introduction of electron-withdrawing groups at 2,4-positions in the phenyl moiety intensified chemiluminescence. 2,4-(Dimethoxycarbonyl)phenyl 10-methyl-10 lambda(4)-acridine-9-carboxylate trifluoromethanesulfonate salt produced long-lasting chemiluminescence emission, showed maximum chemiluminescence intensities at pH 8 and was used in simple chemiluminescence assays of hydrogen peroxide and choline under neutral conditions. The linear calibration range and detection limit of choline at pH 8 were 0.1-1000 mu M and 0.01 mu M, respectively.. |
| 23. |
Aogu Furusho, Reiko Koga, Takeyuki Akita, Masashi Mita, Tomonori Kimura, Kenji Hamase, Three-Dimensional High-Performance Liquid Chromatographic Determination of Asn, Ser, Ala, and Pro Enantiomers in the Plasma of Patients with Chronic Kidney Disease, ANALYTICAL CHEMISTRY, 10.1021/acs.analchem.9b01615, 91, 18, 11569-11575, 2019.09, The concentrations of several d-amino acids have been reported to significantly increase in the plasma of patients with chronic kidney disease (CKD). However, the amounts of these d-amino acids are low (around 1% of the l-form or lower), and their analyses were complicated by various interfering compounds in many clinical samples. A highly selective analytical method is thus required to perform the accurate and precise determination of these d-amino acids in the plasma of CKD patients. In the present study, a selective 3D-HPLC system equipped with reversed-phase, anion-exchange, and enantioselective columns has been designed and developed for the determination of the asparagine, serine, alanine and proline enantiomers. For the sensitive analysis, amino acids were precolumn derivatized with 4-fluoro-7-nitro-2,1,3-benzoxadiazole and detected by their fluorescence. The system was validated by using human plasma in addition to the standard amino acids, and results with a sufficient linearity, precision, and accuracy were obtained. The 3D-HPLC system was applied to the plasma of patients with different stages of CKD and all of the target d-amino acids were clearly observed without interferences for all 25 tested patients. Good correlations were shown between the kidney function of the patients and the %d values of the target analytes, especially d-Asn and d-Ser, indicating that the present 3D-HPLC method is useful for the sensitive diagnosis of CKD.. |
| 24. |
Chiharu ISHII, Takeyuki AKITA, Masanobu NAGANO, Masashi MITA, Kenji HAMASE, Determination of chiral amino acids in various fermented products using a two-dimensional HPLC-MS/MS system, Chromatography, 10.15583/jpchrom.2019.011, 40, 83-87, 2019.05. |
| 25. |
Chin-Ling HSIEH, Po-Yeh LIN, Takeyuki AKITA, Masashi MITA, Tomomi IDE, Jen-Ai LEE, Kenji HAMASE, Development of a three-dimensional HPLC system for the simultaneous determination of lactate and 3-hydroxybutyrate enantiomers in mammalian urine, Chromatography, 10.15583/jpchrom.2018.021, 25-32, 40, 25-32 (2019), 2019.01. |
| 26. |
Kenji HAMASE, Tatsuhiko IKEDA, Chiharu ISHII, Shoto ISHIGO, Kei MASUYAMA, Takeyuki AKITA, Aogu FURUSHO, Miho TAKAHASHI, Tomomi IDE, Masashi MITA, Determination of Trace Amounts of Chiral Amino Acids in Complicated Biological Samples Using Two-Dimensional High-Performance Liquid Chromatography with an Innovative "Shape-Fitting" Peak Identification/Quantification Method, Chromatography, 10.15583/jpchrom.2018.019, 39(3) 147 - 152 2018, 2018.10. |
| 27. |
Chiharu Ishii, Takeyuki Akita, Masashi Mita, Tomomi Ide, Kenji Hamase, Development of an online two-dimensional high-performance liquid chromatographic system in combination with tandem mass spectrometric detection for enantiomeric analysis of free amino acids in human physiological fluid, JOURNAL OF CHROMATOGRAPHY A, 10.1016/j.chroma.2018.07.076, 1570, 91-98, 2018.10, An automated two-dimensional HPLC-MS/MS system was designed and developed for the highly selective determination of trace levels of d-amino acids. As the targets, frequently observed ones in mammalian physiological fluids, Ala, Asp, Glu, Leu, Pro and Ser, were selected because these d-amino acids are the potential biomarkers for the early and sensitive diagnoses of various diseases. The target analytes were derivatized with 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F), then isolated by a reversed-phase column in the first dimension. The NBD-amino acid fractions were automatically collected into the multi-loop device, and introduced into the enantioselective column in the second dimension to separate the d- and l-forms followed by detection by an MS/MS. The obtained resolution values of the enantiomers were 1.87-5.17 and the calibration lines, precision and accuracy were practically sufficient. By using the present 2D HPLC-MS/MS system, trace levels of d-amino acids in complex biological matrices were determined without disturbance by the intrinsic interfering compounds, and successfully applied to the analysis of the human clinical samples (plasma and urine).. |
| 28. |
Aogu FURUSHO, Reiko KOGA, Takeyuki AKITA, Yurika MIYOSHI, Masashi MITA, Kenji HAMASE, Development of a highly-sensitive two-dimensional HPLC system with narrowbore reversed-phase and microbore enantioselective columns and application to the chiral amino acid analysis of the mammalian brain, Chromatography, 10.15583/jpchrom.2018.007, 39, 83-90, 2018.04. |
| 29. |
Nutchaya SEREEKITTIKUL, Reiko KOGA, Takeyuki AKITA, Aogu FURUSHO, Roland REISCHL, Masashi MITA, Akira FUJII, Kazunori HASHIGUCHI, Masanobu NAGANO, Wolfgang LINDNER, Kenji HAMASE, Multi-dimensional HPLC analysis of serine containing chiral dipeptides in Japanese traditional amber rice vinegar, Chromatography, 10.15583/jpchrom.2018.002, 39, 59-66, 2018.03. |
| 30. |
Chin-Ling Hsieh, Reiko Koga, Aogu Furusho, Takeyuki Akita, Masashi Mita, Tomomi Ide, Jen-Ai Lee, Kenji Hamase, Enantioselective and simultaneous determination of lactate and 3-hydroxybutyrate in human plasma and urine using a narrow-bore online two-dimensional high-performance liquid chromatography system, JOURNAL OF SEPARATION SCIENCE, 10.1002/jssc.201701283, 41, 6, 1298-1306, 2018.03, For the enantioselective and simultaneous analysis of lactate and 3-hydroxybutyrate, a validated online two-dimensional high-performance liquid chromatography system using 4-nitro-7-piperazino-2,1,3-benzoxadiazole as a fluorescent derivatization reagent has been developed. For the reversed-phase separation in the first dimension, a Capcell Pak C18 ACR column (1.5 × 250 mm, particle size 3 μm) was used, and the target fractions were isolated by their hydrophobicity. In the second dimension, a polysaccharide-coated enantioselective column, Chiralpak AD-H (2.0 × 250 mm, 5 μm), was used. The system was validated by the calibration curve, intraday precision, interday precision, and accuracy using standards and real human samples, and satisfactory results were obtained. The present method was applied to human plasma and urine, and in the plasma, trace amounts of d-lactate (8.4 μM) and l-3-hydroxybutyrate (1.0 μM), besides high levels of l-lactate (860.9 μM) and d-3-hydroxybutyrate (59.4 μM), were successfully determined. In urine, trace levels of d-lactate (3.7 μM), d-3-hydroxybutyrate (2.3 μM), and l-3-hydroxybutyrate (3.3 μM) in addition to a relatively large amount of l-lactate (15.4 μM) were observed. The present online two-dimensional high-performance liquid chromatography system is useful for the simultaneous determination of all the lactate and 3-hydroxybutyrate enantiomers in human physiological fluids, and further clinical applications are ongoing.. |
| 31. |
Naoto Hayashi, Akifumi Kanda, Taku Kamoto, Hiroyuki Higuchi, Takeyuki Akita, EFFECT OF ARYL SUBSTITUENTS ON INTRAMOLECULAR CYCLIZATION OF 2,2 '-BIPHENOQUINONES, HETEROCYCLES, 10.3987/COM-08-S(D)57, 79, 865-872, 2009.04, Effect of aryl substituents on intramolecular cyclizations of 3,3',5,5'-tetraaryl-2,2'-biphenoquinones (Ar = phenyl (1a) and 4-methoxyphenyl (1b)) has been studied. In benzene, 1a gave 2,4,6,8-tetraphenyldibenzofuran-1-ol (10) gradually as a main product, indicating the phenyl substituents preferred to stabilize the intermediate by delocalization of the negative charge rather than that of the positive one. In contrast, the reaction of 1b occurred spontaneously in order to give a complex mixture, which should be due to 4-methoxyphenyl substituent at the 3 position.. |
| 32. |
Junzo Hirano, Kenji Hamase, Takeyuki Akita, Kiyoshi Zaitsu, Structural and photophysical properties of novel dual fluorescent compounds, 1-aryl-substituted 6-methoxy-4-quinolones, LUMINESCENCE, 10.1002/bio.1044, 23, 5, 350-355, 2008.09, Dual fluorescent compounds are useful platforms for the development of ratiometric probes and sensors. We have developed a new series of dual fluorescent compounds, 1-aryl-substituted 6-methoxy-4-quinolones, and investigated their structural and photophysical properties. The X-ray crystallographic analysis and ab initio quantum chemical calculations revealed that the developed compounds exhibited 60-75 degrees twisted structures. The dual fluorescence of the compounds were observed in polar solvents, and the ratiometric fluorescence responses to alterations in the acidity and temperature were obtained. Copyright (C) 2008 John Wiley & Sons, Ltd.. |
| 33. |
Takeyuki Akita, Noboru Koga, Magnetic properties of dendritic polycarbenes substituted by bulky peripheral groups, Polyhedron, 10.1016/j.poly.2005.03.067, 24, 16-17, 2321-2325, 2005.11, As photo-reactive precursors of high-spin organic compounds sterically separated from surroundings by bulky peripheral groups, diphenyldiazomethane derivatives substituted by tetrakis{3,5-bis(benzyloxy)benzyloxy} groups 1, by tetrakis[3,5-bis{3′,5′-bis(benzyloxy)benzyloxy}bezyloxy] groups 2, and nonakisdiazo compound associated with ferromagnetic spin couplers substituted by dodecakis{3,5-bis(benzyloxy)benzyloxy} groups 3, were prepared and their magnetic properties after irradiation in their own condensed films were investigated. Field dependences of magnetization and temperature dependences of χT value after irradiation of 1 and 2 clearly exhibited that spin centers i.e., diphenylcarbene parts of 1 and 2 were magnetically isolated from surrounding molecules each other by steric hindrance of the peripheral bulk substituents even in the neat films. In the case of 3, some part of molecules interacted antiferromagnetically with neighboring molecules but a fatal strong antiferromagnetic interaction was also avoided.. |
| 34. |
Junzo Hirano, Kenji Hamase, Takeyuki Akita, Kiyoshi Zaitsu, Crystal structure of 6-methoxy-4-quinolone, C10H9NO2·2H2O, Analytical Sciences: X-ray Structure Analysis Online, 10.2116/analscix.21.x45, 21, 3, x45, 2005.01, The title compound, 6-methoxy-4-quinolone (3), was synthesized by the oxidation of 5-methoxyindole-3-acetic acid (2), and its crystal structure was determined by X-ray diffraction analysis. The compound crystallized in the monoclinic system, space group P21/n, with cell parameters of a = 4.547(2)Å, b = 16.328(8)Å, c = 13.731(4)Å, β = 92.38(2)°, and Z = 4. The final residual factor was 0.064. 2005. |
| 35. |
Junzo Hirano, Kenji Hamase, Takeyuki Akita, Kiyoshi Zaitsu, Crystal structure of N-[(6-methoxy-4-oxo-1,4-dihydroquinolin-3-yl) methyl]-2,2-dimethylpropanamide, Analytical Sciences: X-ray Structure Analysis Online, 10.2116/analscix.20.x115, 20, 3, x115-x116, 2004.01, The crystal structure of N-[(6-methoxy-4-oxo-1,4-dihydroquinolin-3-yl)methyl]-2,2-dimethylpropanamide (2) was determined by X-ray diffraction analysis. The compound crystallized in the triclinic system, space group P1, with cell parameters of a = 7.829(3)Å, b = 8.995(4)Å, c = 10.646(5)Å, α = 85.86(2)o, β = 86.99(1)o, γ = 88.00(2)o, and Z = 2. The structure was refined by full-matrix least-squares to final values of R1 = 0.049 and wR2 = 0.103. The intermolecular hydrogen bonds of the type N-H···O were observed in the structure. 2004. |
| 36. |
Jingping Zhang, Madoka Suehiro, Akira Sakane, Satoru Karasawa, Takeyuki Akita, Noboru Koga, Theoretical study on the exchange interaction between metal ion and organic radical through pyridine, bipyridine and terpyridine ligands, Molecular Crystals and Liquid Crystals, 10.1080/10587250210747, 376, 431-436, 2002.12, Ab initio total energy calculations with the DFT framework based on the geometries obtained by X-ray data were carried out for five complexes composed by copper(II) ion and organic radicals (eg. aminoxyl and carbene) through pyridine, bipyridine and terpyridine rings. It was found that the copper(II) complex having radical substituted at 4-position of aromatic ligand favors ferromagnetic coupling between organic radical and paramagnetic copper(II) ion.. |
| 37. |
T Akita, N Koga, Magnetic properties after irradiation of poly(m-phenyleneethynylene) having diazo and nitronylnitroxide groups and its model compounds, POLYHEDRON, 10.1016/S0277-5387(01)00638-6, 20, 11-14, 1475-1477, 2001.05, In order to achieve a pure organic high-spin molecule, poly(m-phenyleneethynylene) derivative 1 having diazo groups and nitronyl nitroxide moieties alternately were designed. Its three model compounds, diphenylacetylene derivative 2, bis(phenylethynyl)benzene derivative 3, and oligomeric compound 4 having partial structure of 1 have been prepared by the coupling reaction of ethynyl derivatives of phenylnitronylnitroxide and iodo derivatives of diphenyldiazomethane. Field dependence of magnetization after irradiation of 2 and 3 in frozen solutions suggested that the photo-generated species have quartet and quintet ground states with J/k(B), values of + 1.75 and + 1.09 K, respectively. However, spin interaction between carbene and nitronylnitroxide through 3,3-diphenylacetylene moiety is not strong enough to form high-spin chain having long correlation length for 4. (C) 2001 Elsevier Science Ltd. All rights reserved.. |
| 38. |
Yves Pontillon, Takeyuki Akita, Andre Grand, Keiji Kobayashi, Eddy Lelievre-Berna, Jacques Pécaut, Eric Ressouche, Jacques Schweizer, Experimental and theoretical spin density in a ferromagnetic molecular complex presenting interheteromolecular hydrogen bonds, Journal of the American Chemical Society, 10.1021/ja991042u, 121, 43, 10126-10133, 1999.11, The association of phenylboronic acid (no unpaired electron, compound 1) with the free radical phenyl nitronyl nitroxide (PNN, S = 1/2 , compound 2) constitutes an interheteromolecular hydrogen bonding system displaying ferromagnetic intermolecular interactions. We have investigated its spin density distribution to visualize the pathway of these magnetic interactions. This complex crystallizes at room temperature in the monoclinic space group P21/n. The unit cell includes one pair (1 + 2). The molecule (1) bridges two radicals (2) by hydrogen bonds OH···ON: the two different hydrogen bond lengths are quite similar (1.95 and 1.92 Å). Infinite chains of this run along the b-axis. In this structure the methyl groups of the PNN are randomly distributed in two different configurations. Below T = 220 K the compound undergoes a crystallographic phase transition due to the ordering of these methyl groups. We have determined the low-temperature structure using both X- ray and neutron diffraction. The new space group is P1̄. The global structure is preserved and infinite chains still run along the b-axis, but the unit cell now comprises two different pairs (1 + 2) instead of one, with four different hydrogen bond OH···ON distances: 1.96 and 1.84 Å for the first pair, 1.96 and 1.91 Å for the second pair. The spin density of this complex was measured at T = 1.8 K (H = 4.6 T) by polarized neutron diffraction. The data were treated using both maximum entropy approach and wave function modeling. As in the isolated PNN, the main part of the spin density is located on the O-N-C-N-O fragment of each radical in the unit cell. However, compared to the isolated case, a significant difference exists: a large unbalance is observed between the two oxygen atoms of each radical. Moreover, a positive contribution is found on the two hydrogen atoms involved on the OH···ON hydrogen bonds of each phenylboronic acid molecule. The stronger contribution corresponds to the longer hydrogen bonds. On the radical the stronger reduction is observed on the oxygen atoms involved in the shorter hydrogen bonds. The experimental results are compared to those obtained by density functional theory (DFT) calculations: on the whole, the experimental effects have been reproduced. However, if there is a good qualitative agreement, from the quantitative point of view, the DFT results are still very far from the experimental ones.. |
| 39. |
Satoru Karasawa, Yoko Sano, Takeyuki Akita, Noboru Koga, Tetsuji Itoh, Hiizu Iwamura, Pierre Rabu, Marc Drillon, Photochemical formation of ferrimagnetic chains from a pair of polymeric complexes made of octahedral bis(hexafluoroacetylacetonato)manganese(II) with diazodi(4-pyridyl)methane in the cis and trans configurations as repeating units, Journal of the American Chemical Society, 10.1021/ja981293n, 120, 39, 10080-10087, 1998.10, Two kinds of 1:1 manganese complexes a and b of bis(hexafluoroacetylacetonato)manganese(II) coordinated with diazodi(4- pyridyl)methane (1) were prepared. Complexes a and b crystallize in the orthorhombic space group Pbca and in monoclinic C2/c, respectively. Two pyridyl nitrogen atoms from two different molecules of 1 are coordinated in the cis and trans configurations to the manganese ion to form helical and zigzag infinite chains of octahedral manganese complexes in complexes a and b, respectively. The magnetic susceptibilities (χmol) of both crystals before and after irradiation were measured on a SQUID susceptometer and revealed χ(mol)T vs T plots characteristic of ferrimagnetic chains after irradiation for 97 h; interaction between the manganese(II) ion and the photogenerated carbene is antiferromagnetic in both complexes. The antiferromagnetic exchange coupling parameters (J) in the photolyzate of complex a and b were estimated by a theoretical treatment through a procedure of extrapolation by using small rings to be J/k(B) = -34.8 ± 0.8 and -24.4 ± 0.5 K, respectively. Maximum χ(mol)T values of 210 at 5 K for cis- and 246 emu·K·mol-1 at 1.9 K for trans complexes correspond to correlation lengths of 186 and 218 manganese-carbene S = 3/2 units, respectively.. |
| 40. |
Takeyuki Akita, Keiji Kobayashi, Intermolecular spin-coupler
Ferromagnetic spin interactions through hydrogen bond in the complexes of arylboronic acids with aryl nitronyl nitroxides, Molecular Crystals and Liquid Crystals, 10.1080/10587259708044574, 306, 257-264, 1997.01, Two crystalline complexes, the complex of p-fluorophenylboronic acid with phenyl nitronyl nitroxide (2) and the complex of p-nitrophenylboronic acid with p-dimethylaminophenyl nitronyl nitroxide (3), were prepared. Both of those complexes as well as the complex of phenylboronic acid with phenyl nitronyl nitroxide (1) exhibit ferromagnetic spin interactions (1: J/kB=+0.65 K, 2: J/kB=+0.58 K, 3: J/kB=+1.35 K). The results are discussed based on the X-ray crystal structure.. |
| 41. |
Takeyuki Akita, Keiji Kobayashi, Magnetic properties of nitronyl nitroxide radicals substituted in phenylboronic acid
The BOH⋯O hydrogen bond as a constituent unit of a one-dimensional suprastructure exhibiting a ferromagnetic spin interaction, Advanced Materials, 10.1002/adma.19970090414, 9, 4, 346-349, 1997.01. |
| 42. |
Takeyuki Akita, Yasuhiro Mazaki, Keiji Kobayashi, Ferromagnetic spin interaction in a crystalline molecular complex formed by inter-heteromolecular hydrogen bonding
A 1:1 complex of phenyl nitronyl nitroxide radical and phenylboronic acid, Journal of the Chemical Society, Chemical Communications, 10.1039/C39950001861, 18, 1861-1862, 1995.09, A crystalline molecular complex derived from phenyl nitronyl nitroxide and phenylboronic acid exhibits a ferromagnetic spin interaction (J = +0.65 K) below 30 K: X-ray analysis reveals the crystal structure to be constituted of a one-dimensional array of two component molecules linked alternately by the NO ⋯ HOB hydrogen bond.. |
| 43. |
Junpei Fujita, Yoshihisa Matsuoka, Kenji Matsuo, Masakazu Tanaka, Takeyuki Akita, Noboru Koga, Hizu Iwamura, Molecular structure and magnetic properties of N,N-bis {4-methoxy-3,5-bis(N-tert-butyl-N-oxyamino)phenyl} aminoxyl. An approach to a stable and high-spin pentaradical, Chemical Communications, 10.1039/a704160h, 24, 2393-2394, 1997.01, A stable pentaradical, N,N-bis(4-methoxy-3,5-bis(N-tert-butyl-N-oxyamino)phenyl)]aminoxyl, is prepared and its ground state determined to be a sextet (S = 5/2) by SQUID magnetization measurements of the pentaradical diluted in poly(vinyl chloride) matrix.. |
| 44. |
Takeyuki Akita, Yasuhiro Mazaki, Keiji Kobayashi, Ferromagnetic spin interaction through the interheteromolecular hydrogen bond
A 1:1 crystalline complex of phenylboronic acid and phenyl nttronyl nitroxide, Molecular Crystals and Liquid Crystals, 278-279, 39-45, 1996.12, A crystalline molecular complex derived from phenyl nitronyl nitroxide (1) and phenyl boronic acid (2) exhibits a ferromagnetic spin interaction (J= +0.65 K) below 30 K: An X-ray analysis revealed the crystal structure constituted of one-dimensional array of two component molecules linked alternately by the NO-HO-B hydrogen bonds. The NO-HO-B-OH - ON linkage was suggested to act as a path for ferromagnetic spin coupling. An unusual formation of nitrosonium salt (3) was found in the reaction of 1 and BF3. Its molecular and crystal structures were determined.. |
| 45. |
Takeyuki Akita, Keiji Kobayashi, Intramolecular spin-interactions between two nitronyl nitroxide or imino nitroxide radical units linked to thieno[2,3-b]thiophene and thieno[2,3-b]thieno[3',2'-d]thiophene chromophores, Tetrahedron, 10.1016/0040-4020(96)00324-9, 52, 20, 6893-6902, 1996.05, Diradical species 1N, 1I, 2N, and 2I, in which two nitronyl nitroxide (N) or imino nitroxide (I) radical centers are attached to thieno[23-b]thiophene (1) and thieno[23-b]thieno[3' 2' -d]thiophene (2) chromophores, respectively, were prepared and their intramolecular exchange interactions were investigated in frozen solutions by means of ESR spectroscopy and magnetic susceptibility measurements at cryogenic temperature. Temperature dependence of the ESR signal intensities due to the triplet state revealed that bis(nitronyl nitroxide) radicals, 1N and 2N, are ground-state singlet species with quite small singlet-triplet gaps. In bis(imino nitroxide) radical 1I the spin interaction was antiferromagnetic and the singlet-triplet gap was estimated to be 2J/kB= -18 K. On the other hand, bis(imino nitroxide) 21 was revealed to be a singlet-triplet degenerate species. These results are discussed in terms of the intramolecular NO - S contact along with corroboration by the semi-empirical MO calculations.. |
| 46. |
Takeyuki Akita, Yasuhiro Mazaki, Keiji Kobayashi, Noboru Koga, Hiizu Iwamura, Crystal structures and magnetic properties of nitronyl nitroxide and imino nitroxide radicals attached to thieno[3,2-b]- and thieno[2,3-b]thiophene rings, Journal of Organic Chemistry, 60, 7, 2092-2098, 1995.04, Nitronyl nitroxide (ONC=NO) and imino nitroxide (NCNO) free radicals joined to isomeric thieno-[3,2-b]thiophene and thieno[2,3-b]thiophene, respectively, were prepared and their crystal structures and magnetic properties were investigated. In all crystals of four free radical species, the ON-C-NO moieties are in the same plane as the thienothiophene ring. The coplanarity is associated with the extremely short intramolecular contact between the oxygen atom in the NO group and the sulfur atom in the thienothiophene ring. The free radicals attached to thieno[3,2-b]thiophene are arranged in a chain structure with short intermolecular NO-S contacts, while the free radicals linked to thieno[2,3-b]thiophenes make dimers with a face-to-face pairing by the use of the NO-S contacts. Among four radical species, thieno[3,2-b]thiophene-substituted nitronyl nitroxide exhibits a weak ferromagnetic interaction (J = +0.11 K/kB, H = -2JSiSj) below 40 K as revealed by a SQUID susceptometer, while others are antiferromagnetic.. |
