Manabu Nakazono

Theoretical study of photophysical properties of bisindolylmaleimide derivatives.

The photophysical properties of two bisindolylmaleimide derivatives, 3,4-bis(3-indolyl)-1-H-pyrrole-2,5-dione (arcyriarubin A) and indolo[2,3-a]pyrrolo[3,4-c] carbazole-5,7-(6 H)-dione (arcyriaflavin A), are investigated by using ab initio molecular orbital (MO) and multireference perturbation theory. These compounds are suggested to exist as monovalent anions deprotonated from an indole NH group in aprotic polar solvents. The analysis of MOs shows that the electronic structures of the S(1) and S(2) states are described by the single- or double-electron excitation between the naturally localized MOs on an indole moiety and on the maleimide part. This indicates that the intramolecular charge transfer (ICT) transfer may occur by photoexcitation. The minimum-energy structure of the arcyriarubin A anion is twisted; the dihedral angles between the indole and maleimide rings are 83.4 degrees and 20.2 degrees for the S(1) and S(0) states, respectively. The analysis of the minimum energy path along the coordinate of the twist angle is performed to explore the emission process from the S(1) state. It has been shown that the magnitude of the Stokes shift increases with increasing the twist angle, but the oscillator strength decreases. It has been suggested that the experimentally observed fluorescence arises on the way toward the energy minimum of the S(1) state. The Stokes-shifted emission of arcyriaflavin A is contributed by the S(1)-S(0) electronic relaxation after the excitation in the S(2) state.

Synthesis of poly (3,4,5-trihydroxybenzoate ester) dendrimers and their chemiluminescence

Gallic acid (GA) and gallic acid methyl ester (GM), polyphenol chemiluminescence (CL) compounds, produces light in the presence of alkali and hydrogen peroxide. We synthesized first-generation polyphenol dendrimers with GA units in the periphery and measured their CL for developing a polyphenol compound which has a strong CL intensity. The CL intensities of the poly (3,4,5-trihydroxybenzoate ester) dendrimers 4 and 8 in MeOH are approximately 400- and 600-fold stronger than that of GA, respectively.

Fluorescence and chemiluminescence properties of indolylmaleimides: experimental and theoretical studies.

Various indolylmaleimides (IMs) were synthesized, and their fluorescence (FL) and chemiluminescence (CL) were measured. The substitution at the 2-position of the indole ring and the 3- or 4-position of the maleimide moiety caused an obvious change in the FL and CL of the IMs. An almost on-off switching of the FL of the IMs was observed. The intramolecular charge transfer from the indole moiety to the maleimide moiety occurred in 3-(1H-3-indolyl)-2,5-dihydro-1H-2,5-pyrroledione. In the FL of the IMs, CASPT2 calculations showed deprotonation of the NH group of the indole ring and the maleimide moiety at the excited state. The C[double bond, length as m-dash]C bond in the maleimide moiety was needed for strong CL in the IMs without substitution at the 2-position of the indole ring. The relationships between the FL or CL properties and the structures of the IMs were clarified. These results provide significant information on the rational design of IMs as FL and CL probes.

Theoretical study of photo-physical properties of indolylmaleimide derivatives

Photo-physical properties of bromo-indolylmaleimide (IM-Br), indole-succinimide (IS), and their anions were theoretically investigated compared with the previous theoretical result for indolylmaleimide (IM) [Phys. Chem. Chem. Phys., 2010, 12, 9783]. The energies for the electronic excited states as well as the ground states were computed for these molecules using the multi-reference perturbation calculations based on the second order Rayleigh-Schrödinger perturbation theory (CASPT2) at the cc-pVDZ basis set level. The electron-accepting or electron-donating effect caused by bromine-substitution was discussed in the intra-molecular charge transfer (ICT) mechanism. The order of natural orbitals of the bromine-substituted monovalent anion with a deprotonated indole NH group (I((-))M-Br) was found to be rearranged by the effect of electron-donation, which leads to pseudo-crossing of the potential energy cures of the S(1) and S(2) states. The large stokes shift observed for I((-))M-Br was due to pseudo-crossing. Meanwhile, IM and IM-Br show abnormal deprotonation, which is explained by the charge distribution on the indole and maleimide moieties. Finally, the monovalent anions I((-))M-Br and I((-))M by a deprotonation of the indole NH end and the neutral IS were proposed to be the most feasible candidates corresponding to the experimental spectra in solution.

Design and synthesis of a novel pre-column derivatization reagent with a 6-methoxy-4-quinolone moiety for fluorescence and tandem mass spectrometric detection and its application to chiral amino acid analysis

A new pre-column derivatization reagent with a 6-methoxy-4-quinolone (6-MOQ) moiety for amino acid analysis, 2,5-dioxopyrrolidin-1-yl(2-(6-methoxy-4-oxoquinolin-1(4H)-yl)ethyl) carbonate (6-MOQ-EtOCOOSu), was designed and synthesized. 6-MOQ is a thermo/photostable fluorophore with a high proton-affinity site and sensitive determination could be carried out by a fluorescence detector and also by an electrospray ionization mass spectrometer. Derivatization of amino acids with 6-MOQ-EtOCOOSu was completed within 1 min under mild basic conditions at room temperature. The 6-MOQ derivatives of all chiral proteinogenic amino acids were separated using the combination of three enantioselective columns, Chiralpak QN-AX, Chiralpak ZXIX(+), and KSAACSP-001S, with separation factors of higher than 1.07. The present reagent enables the sensitive determination of amino acid enantiomers, and the values of LLOD using a chiral-HPLC-MS/MS system were 0.05-50 fmol/injection.

Chemiluminescence change of polyphenol dendrimers with different core molecules

Second generation polyphenol dendrimers (PDs) with different core molecules were synthesized, and their chemiluminescence (CL) was measured by reacting the PDs with H2O2 under alkaline conditions. All of the PDs showed a strong CL, more than 120-fold greater than that of gallic acid. Various CL intensities of the PDs were obtained using different core molecules in the PDs. The distance between each dendron in the PD structure is crucial in the PD CL intensity.

The chemiluminescence mechanism of 3,4-bis(3-indolyl)-1H-pyrrole-2,5-dione, and the characteristics of chemiluminescence developed in the reaction with CH3CNH2O2NaOH

The chemiluminescence (CL) mechanism of 3,4-bis(3-indolyl)-1H-pyrrole-2,5-dione (IPD) was investigated using liquid chromatography electrospray ionization mass spectrometry (LC-ESI-MS) of the products formed after the IPD CL reaction. We found that IPD produced strong CL via the decomposition of dioxetane formed after oxidation of the maleimide and indole moieties in the presence of CH(3)CN, H(2)O(2) and NaOH. The IPD CL was used for evaluating the antioxidant effect on curcumin and epigallocatechin gallate.

Novel styrylbenzene derivatives for detecting amyloid deposits

BACKGROUND Various styrylbenzene compounds were synthesized and evaluated as mainly Aβ amyloid sensors. These compounds, however, cannot be used for detecting amyloid deposition in peripheral nerves because of the inherent sensitivity of the compounds. These compounds often generate false positives especially in the basement membrane of blood vessels in histochemical studies. To overcome these problems, we must first synthesize other styryl compounds for detecting amyloid fibrils in tissues. METHODS A wide variety of symmetrical and unsymmetrical styrylbenzene derivatives were synthesized and then these compounds were used to detect amyloid fibrils in autopsy and biopsy samples from patients with various systemic and localized forms of amyloidosis such as familial amyloidotic polyneuropathy (FAP), senile systemic amyloidosis (SSA), amyloid A (AA) amyloidosis, localized AL amyloidosis, and Alzheimers disease. RESULTS 1-Methoxy-2,5-bis-styrylbenzene and 2-(2-(2-fluoroethoxy)ethoxy)ethoxy)-2,5-bis-styrylbenzene (EEEFSB) detected amyloid fibrils in both in vitro and in vivo histopathological studies. 1-Methoxy-2,5-bis-styrylbenzene also showed a high strength of fluorescence with amyloid deposition in peripheral nerves in a patient with FAP. CONCLUSIONS 1-Methoxy-2,5-bis-styrylbenzene and EEEFSB may prove a useful tool for diagnosing amyloidosis, not only in a histochemical study but also in whole body amyloid positron emission tomography (PET) imaging.

Fluorescence properties of 2-aryl substituted indoles

The fluorescence properties of 2-phenylindole, 2-naphthylindole and 2-anthracenylindole were investigated. 2-Anthracenylindole was newly synthesized by Suzuki-Miyauras coupling. The fluorescence quantum yield of 2-phenylindole was the highest and the fluorescence emission maximum wavelength of 2-anthracenylindole was the longest. The ab initio quantum chemical calculation of the 2-anthracenylindole showed that the HOMO and LUMO of 2-anthracenylindole were localized in the anthracene moiety.

Strongly Chemiluminescent Acridinium Esters under Neutral Conditions: Synthesis, Properties, Determination, and Theoretical Study

Various novel acridinium ester derivatives having phenyl and biphenyl moieties were synthesized, and their optimal chemiluminescence conditions were investigated. Several strongly chemiluminescent acridinium esters under neutral conditions were found, and then these derivatives were used to detect hydrogen peroxide and glucose. Acridinium esters having strong electron-withdrawing groups such as cyano, methoxycarbonyl, and nitro at the 4-position of the phenyl moiety in phenyl 10-methyl-10λ4-acridine-9-carboxylate trifluoromethanesulfonate salt showed strong chemiluminescence intensities. The chemiluminescence intensity of 3,4-dicyanophenyl 10-methyl-10λ4-acridine-9-carboxylate trifluoromethanesulfonate salt was approximately 100 times stronger than that of phenyl 10-methyl-10λ4-acridine-9-carboxylate trifluoromethanesulfonate salt at pH 7. The linear calibration ranges of hydrogen peroxide and glucose were 0.05-10 mM and 10-2000 μM using 3,4-(dimethoxycarbonyl)phenyl 10-methyl-10λ4-acridine-9-carboxylate trifluoromethanesulfonate salt at pH 7 and pH 7.5, respectively. The proposed chemiluminescence reaction mechanism of acridinium ester via a dioxetanone structure was evaluated via quantum chemical calculation on density functional theory. The proposed mechanism was composed of the nucleophilic addition reaction of hydroperoxide anion, dioxetanone ring formation, and nonadiabatic transition due to spin-orbit coupling around the transition state (TS) to the triplet state (T1) following the decomposition pathway. The TS which appeared in the thermal decomposition would be a rate-determining step for all three processes.