Concerted Two-Proton-Coupled Electron Transfer from Piceatannol to Electrogenerated Superoxide in ,-Dimethylformamide.

The reactivity of 4-[()-2-(3,5-dihydroxyphenyl)ethenyl]benzene-1,2-diol (piceatannol) toward electrochemically generated superoxide radical anion (O ) was investigated using electrochemistry and in situ controlled-potential electrolytic electron spin resonance (ESR) measurements in ,-dimethylformamide with density functional theory (DFT) calculations. The quasireversible cyclic voltammogram of dioxygen/O , modified in the presence of piceatannol, indicated that the electrogenerated O was scavenged by piceatannol via proton-coupled electron transfer. Differences in the reactivities of piceatannol and 5-[()-2-(4-hydroxyphenyl)ethen-1-yl]benzene-1,3-diol (-resveratrol) toward O , originating from the presence of the benzene-1,2-diol (catechol) moiety, were observed in the voltammograms and ESR measurements.

Reactivity of -Resveratrol toward Electrogenerated Superoxide in ,-Dimethylformamide.

The reactivity of 5-[()-2-(4-hydroxyphenyl)ethen-1-yl]benzene-1,3-diol (-resveratrol) and related compounds toward electrogenerated superoxide radical anion (O) were investigated using electrochemistry, in situ electrolytic electron spin resonance, and in situ electrolytic ultraviolet-visible spectral measurements, in ,-dimethylformamide (DMF) with the aid of density functional theory (DFT) calculations. The quasi-reversible cyclic voltammogram of dioxygen/O was modified by the presence of -resveratrol, suggesting that the electrogenerated O was scavenged by -resveratrol through proton-coupled electron transfer (PCET) via three phenolic hydroxy groups (OH) on the stilbene moiety. The reactivity of -resveratrol toward O characterized by the OHs was experimentally confirmed in comparative analyses using some related compounds, pinosylvin, pterostilbene, -coumaric acid, and so on, in DMF.

Synthetic and computational investigation of neighboring group participation by a nucleophilic disulfide bond.

Disulfide bonds of 2-isocyanatophenyl methyl disulfide and 2--isocyanato-6--(methyldisulfanyl)bicyclo[2.2.1]heptane showed neighboring group participation in the formation of thiocarbamates.

Electrochemical and Mechanistic Study of Reactivities of α-, β-, γ-, and δ-Tocopherol toward Electrogenerated Superoxide in ,-Dimethylformamide through Proton-Coupled Electron Transfer.

Scavenging of superoxide radical anion (O) by tocopherols (TOH) and related compounds was investigated on the basis of cyclic voltammetry and in situ electrolytic electron spin resonance spectrum in ,-dimethylformamide (DMF) with the aid of density functional theory (DFT) calculations. Quasi-reversible dioxygen/O redox was modified by the presence of TOH, suggesting that the electrogenerated O was scavenged by α-, β-, γ-TOH through proton-coupled electron transfer (PCET), but not by δ-TOH. The reactivities of α-, β-, γ-, and δ-TOH toward O characterized by the methyl group on the 6-chromanol ring was experimentally confirmed, where the methyl group promotes the PCET mechanism.

[Basic Study on Organic Electron Transfer Reactions by Electrochemistry Combined with Quantum Chemical Calculations].

This review summarizes the results of the author's basic research on organic electrochemistry conducted at Gifu Pharmaceutical University over about 40 years. After completing graduate school, the author became a research associate in Prof. Tanekazu Kubota's laboratory and started research on molecular spectroscopy in 1983.

Highly Sensitive Fluorescence Detection of Daptomycin in Murine Samples through Derivatization with 2,3-Naphthalenedialdehyde.

A highly sensitive high-performance liquid chromatography method has been developed using the pre-column fluorescent derivatization of daptomycin (DAP) through cyclization of the amino group of ornithine with 2,3-naphthalenedialdehyde. With the proposed method, the limits of detection and quantification of DAP in murine serum were 8 and 3 nmol/L, respectively, and the calibration curve was linear across the examined dynamic range from 8 nmol/L to 1 μmol/L (n = 8, r = 0.9986).

Preparation of N-Ethyl-2'-deoxyguanosine-d as an Internal Standard for the Electrospray Ionization-Tandem Mass Spectrometric Determination of DNA Damage by Acetaldehyde.

The deuteration of N-ethyl-2'-deoxyguanosine (Et-dG), which is a DNA adduct generated from acetaldehyde, was studied by the addition reaction of acetaldehyde-d to 2'-deoxyguanosine (dG) in deuterium oxide (DO), with the aim to obtain an isotope internal standard for the liquid chromatography/tandem mass spectrometry (LC/MS/MS) quantitation of Et-dG. The replacement of the dG C-8 hydrogen atom by a deuteron atom took place at 50°C in DO and afforded a mixture of Et-dG-d and Et-dG-d. Et-dG-d, which was stable in aqueous solutions, was prepared by incubating the mixture in HO at 60°C for 48 h.

Complementary Effect of Intra- and Intermolecular Hydrogen Bonds on Electron Transfer in β-Hydroxy-Anthraquinone Derivatives.

We have carried out an electrochemical and theoretical study on the relationship between electron transfer (ET) and hydrogen bonding in 11 different 9,10-anthraquinone (AQ) derivatives, including β-hydroxy AQs and their methoxylated analogs, in the presence of hydrogen donors in acetonitrile (ACN). The complementary effects of the intra- and intermolecular hydrogen bonds (HBs) on ET were studied by analyzing the complex formation constants derived from the intermolecular HB. Our results revealed that the inductive effect of the β substituent that indirectly controls the charge distribution on the AQ carbonyl oxygen, and steric hindrance at the β position, affect the complex formation constants.

Effect of High Blood Glucose Level on the Antimicrobial Activity of Daptomycin against Staphylococcus aureus in Streptozotocin-Induced Diabetic Mice.

Daptomycin is active against Staphylococcus aureus including methicillin-resistant S. aureus (MRSA), demonstrating efficacy in the treatment of infections in diabetic patients. However, daptomycin degrades in 5% glucose solution, and data on the efficacy of daptomycin in hyperglycemic patients are limited.

Synthesis of -β-Amidevinyl Benziodoxolones from the Ethynyl Benziodoxolone-Chloroform Complex and Sulfonamides.

The synthesis of -β-amidevinyl benziodoxolones from the ethynyl benziodoxolone-chloroform complex and sulfonamides is reported. Evidence indicates that highly reactive unsubstituted ethynyl benziodoxolone undergoes Michael addition of sulfonamides, including sterically demanding acyclic amino acid derivatives. The synthesis of selectively deuterated -β-amidevinyl benziodoxolones and investigation of ethynyl-λ-iodane reactivity are also described.

Preparation of Cyclic-1,N-propano-2'-deoxyguanosine-d as an Internal Standard for ESI-MS/MS Determination of DNA Damage from Acetaldehyde.

Cyclic-1,N-propano-2'-deoxyguanosine-d (CPr-dG-d) was prepared as an isotopic internal standard (IS) for electrospray ionization tandem mass spectrometry (ESI-MS/MS) quantification of CPr-dG in DNA as a candidate cancer risk marker of acetaldehyde intake, mainly from drinking. The deuterated compound was reasonably synthesized from acetaldehyde-d and 2'-deoxyguanosine in deuterium oxide (DO), preventing the deuterium atoms of acetaldehyde-d from being substituted by hydrogen atoms, which occurred seriously in aqueous synthesis media via keto-enol tautomerism. Furthermore, another deuterium atom was added from DO to form CPr-dG-d.

[Improvement of the Non-aqueous Titration Method in the Japanese Pharmacopoeia for a Purpose of Advancement in Experimental Safety Using Alternative Solvents].

In this study, we attempted to improve the non-aqueous titration method using N,N-dimethylformamide (DMF) in the Japanese Pharmacopoeia seventeenth edition (JP XVII) for advancement in experimental safety. As an alternative solvent for DMF, we demonstrate titrations using dimethyl sulfoxide (DMSO), which has similar properties as and much higher safety than DMF. Five drugs (i.

Study on Redox Properties and Cytotoxicity of Anthraquinone Derivatives to Understand Antitumor Active Anthracycline Substances.

This study demonstrates the relation between the redox properties and cytotoxicity of anthraquinone derivatives with a hydroxyl and methoxy group. The redox behavior of the anthraquinone derivatives was initially observed via cyclic voltammetry and their characteristics were investigated using molecular orbital calculations. The cytotoxicity of the anthraquinone derivatives was then evaluated using human leukemia HL-60 and HO resistant HP100 cells, and its correlation with the redox properties of these compounds was investigated.

Feasibility of Trypsin Digestion as a Sample Preparation for Daptomycin Quantification in Murine Skeletal Muscles.

It is important to evaluate the amount of daptomycin (DAP) distributed to skeletal muscles to elucidate the mechanisms related to penetration and side effects, such as myopathies. However, no attempt has been made to measure DAP concentrations in skeletal muscles. The study's aim to investigate the feasibility of trypsin digestion, as a muscle sample preparation technique for the determination of DAP in murine skeletal muscle, was evaluated in conjunction with a conventional HPLC-UV analysis.

Increased Plasma Adenosine Concentration in the Subacute Phase May Contribute to Attenuation of Left Ventricular Dilation in the Chronic Phase in Patients With Acute Myocardial Infarction.

Background: Changes in the plasma adenosine concentration and the effects on left ventricular (LV) function and remodeling in patients with acute myocardial infarction (AMI) remain unclear.

Methods and results: In 58 patients with AMI and 14 subjects without cardiac disease (controls), we measured the plasma adenosine concentration by LC-MS/MS. Blood samples were taken from the antecubital vein on days 0, 1, 7, and 14 after AMI, and from the controls on admission.

Evaluation of Type-A Endonucleases for the Quantitative Analysis of DNA Damage due to Exposure to Acetaldehyde Using Capillary Electrophoresis.

The substrate selectivities of three endonucleases were studied quantitatively using capillary zone electrophoresis to find one giving N-ethyl(Et)-2'-deoxyguanosine-5'-monophosphate (5'-dGMP) and cyclic 1,N-propano(CPr)-5'-dGMP from DNAs damaged by acetaldehyde (AA). Six 2'-deoxyribonucleoside-5'-monophosphates to be quantified in the hydrolysis solutions of DNAs, namely, Et-5'-dGMP, CPr-5'-dGMP, and four authentic ones, were completely separated using a 100 mM borate running buffer solution having an optimized pH of 9.67.

Organic dye-catalyzed radical ring expansion reaction.

Herein, we reported an attractive method for synthesizing medium-sized rings that are catalyzed by erythrosine B under fluorescent light irradiation. This synthetic approach featured mild conditions, a facile procedure, a broad substrate scope, and moderate-to-good yields.

Endogenous Adenosine May Be Related to Left Ventricular Dysfunction, Dilation, and Wall Thinning in Patients With Heart Disease.

Background: The role of endogenous adenosine in cardiac patients is still unclear, so we investigated the relationship between the plasma adenosine concentration and left ventricular (LV) function, LV dilation and LV wall thinning in cardiac patients.

Methods and results: In 97 cardiac patients, with angina pectoris, old myocardial infarction, dilated or hypertrophic cardiomyopathy, and valvular heart disease, plasma adenosine concentrations were measured using the LC-MS/MS system, and the LV function, LV end-diastolic dimension (LVDd), LV posterior wall thickness (LVPWth), and interventricular septum thickness (IVSth) were assessed by echocardiography. The plasma adenosine concentration was significantly higher in patients with a LV ejection fraction (EF), an indicator of the LV systolic function, <47% compared with those with LVEF ≥47% (P=0.

Considerations about the Use of a Loading Dose of Daptomycin in a Neutropenic Murine Thigh Infection Model with Methicillin-Resistant Staphylococcus aureus Infection.

Previous clinical studies have showed the clinical benefits of the initiation of treatment with a daptomycin (DAP) loading dose, but only a few studies have evaluated its antimicrobial benefits. We evaluated the efficacy of a DAP loading dose against methicillin-resistant Staphylococcus aureus (MRSA) infections in a neutropenic murine thigh infection model. Three MRSA isolates (DAP MIC: 0.

Progress in a selective method for the determination of the acetaldehyde-derived DNA adducts by using HILIC-ESI-MS/MS.

Acetaldehyde (AA), which is present in tobacco smoke, automobile exhaust gases and alcohol beverage, is a mutagen and carcinogen. AA reacts with 2'-deoxyguanosine (dG) in DNA to form N-ethyl-dG (EtdG) and cyclic, 1, N-propano-dG (CPrdG), which are considered to have a critical role in carcinogenesis induced by AA. In this study, we have developed a highly sensitive method for the quantitation of the two AA-derived DNA adducts by using liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) in which hydrophilic interaction chromatography (HILIC) employing mobile phases of high organic solvent concentration was selected to improve the ionization efficiency in the ESI process.

PTBP1-associated microRNA-1 and -133b suppress the Warburg effect in colorectal tumors.

It is known that pyruvate kinase in muscle (PKM), which is a rate-limiting glycolytic enzyme, has essential roles in the Warburg effect and that expression of cancer-dominant PKM2 is increased by polypyrimidine tract-binding protein 1 (PTBP1), which is a splicer of the PKM gene. In other words, PKM2 acts as a promoter of the Warburg effect. Previously, we demonstrated that the Warburg effect was partially established by down-regulation of several microRNAs (miRs) that bind to PTBP1 and that ectopic expression of these miRs suppressed the Warburg effect.

Anti-Oncogenic gem-Dihydroperoxides Induce Apoptosis in Cancer Cells by Trapping Reactive Oxygen Species.

Organic gem-dihydroperoxides (DHPs) and their derived peroxides have attracted a great deal of attention as potential anti-cancer agents. However, the precise mechanism of their inhibitory effect on tumors is unknown. To determine the mechanism of the inhibitory effects of DHPs, we examined the effects of DHPs on leukemia K562 cells.

Importance of Proton-Coupled Electron Transfer from Natural Phenolic Compounds in Superoxide Scavenging.

The superoxide O2(·-) scavenging reaction of (+)-catechin (Cat), quercetin (Que), rutin, and α-tocopherol (α-TOH) as natural phenolic compounds is investigated on the basis of electrochemical and ESR spectral measurements with the aid of density functional theory (DFT) calculations. Reversibility of the O2/O2(·-) redox couple is significantly affected by the presence of the phenolic compounds. The catechol moiety of Cat, Que, and rutin plays an essential role in concerted proton-coupled electron transfer (PCET) to HO2(·) derived from O2(·-) to give H2O2 and the corresponding o-benzoquinone radical anions.

Simple Pretreatment and HILIC Separation for LC-ESI-MS/MS Determination of Adenosine in Human Plasma.

A simple pretreatment method and separation mode for the LC-ESI-MS/MS determination of adenosine in human plasma have been developed. Deproteinization by acetonitrile and ultrafiltration followed by chromatographic separation with a hydrophilic interaction chromatographic (HILIC) column give a highly sensitive MS/MS response without ionic suppression caused by the matrix compounds in human plasma. In addition, the presence of ammonium acetate in the mobile phase contributes to high sensitivity in MS/MS detection, facilitating the ionization of adenosine.

MicroRNA-124 inhibits cancer cell growth through PTB1/PKM1/PKM2 feedback cascade in colorectal cancer.

Altered levels and functions of microRNAs (miRs) have been associated with carcinogenesis. In this study, we investigated the role of miR-124 in colorectal adenoma (CRA) and cancer (CRC). The expression levels of miR-124 were decreased in CRA (81.