Simultaneous determination of major components of Huangqi–Honghua extract in rat plasma using LC–MS/MS and application to a pharmacokinetic study

A sensitive and reliable LC–MS/MS method was developed and validated for simultaneous quantification of the major components of Huangqi–Honghua extact in rat plasma, including hydroxysafflor yellow A (HSYA), astragaloside IV (ASIV), calycosin‐7‐O‐β‐d ‐glucoside (CAG), calycosin, calycosin‐3′‐O‐glucuronide (C‐3′‐G) and calycosin‐3′‐O‐sulfate (C‐3′‐S). After extraction by protein precipitation with acetonitrile and methanol from plasma, the analytes were separated on a Hypersil BDS C₁₈ column by gradient elution with acetonitrile and 5 mM ammonium acetate. The detection was carried out on a triple quadrupole tandem mass spectrometer equipped with electrospray ionization source switched between negative and positive modes. HSYA was monitored in negative ionization mode from 0 to 4.9 min, and ASIV, CAG, calycosin, C‐3′‐G and C‐3′‐S were determined in positive ionization mode from 4.9 to 10 min. The lower limits of quantification of the analytes were 6.25 ng/mL for HSYA, 0.781 ng/mL for CAG and 1.56 ng/mL for ASIV and calycosin. The intra‐ and inter‐assay precision (RSD) values were within 13.43%, and accuracy (RE) ranged from ?8.75 to 9.92%. The validated method was then applied to the pharmacokinetic study of HSYA, ASIV, CAG, calycosin, C‐3′‐G and C‐3′‐S in rat after an oral administration of Huangqi–Honghua extract.     

Cycloparaphenylene (CPP) series are molecular models for graphene armchair edges: trends in their aromaticity and cyclic conjugation are evaluated

Cycloparaphenylene ([r]CPP) and cyclacene ([r]CA) series are models for short carbon nanotubes. It is shown that armchair edges in model cycloparaphenylenes possess greater aromaticity and cyclic conjugation than do zigzag edges in model cyclacenes. According to Aihara’s bond resonance energy (BRE) and Bosanac and Gutman energy effect (ef) measurements, cycloparaphenylenes are twice as aromatic as cyclacenes. The general solution of all eigenvalues of all members of the cycloparaphenylene series is given. The origin of the recurrence of some eigenvalues are determined.     

Theory of chemical bonds in metalloenzymes XXII: a concerted bond-switching mechanism for the oxygen–oxygen bond formation coupled with one electron transfer for water oxidation in the oxygen-evolving complex of photosystem II

ABSTRACT

QM(UB3LYP)/MM(AMBER) calculations were performed for the locations of the transition structure (TS) of the oxygen–oxygen (O–O) bond formation in the S₄ state of the oxygen-evolving complex (OEC) of photosystem II (PSII). The natural orbital (NO) analysis of the broken-symmetry (BS) solutions was also performed to elucidate the nature of the chemical bonds at TS on the basis of several chemical indices defined by the occupation numbers of NO. The computational results revealed a concerted bond switching (CBS) mechanism for the oxygen–oxygen bond formation coupled with the one-electron transfer (OET) for water oxidation in OEC of PSII. The orbital interaction between the σ-HOMO of the Mn(IV)₄–O₍₅₎ bond and the π*-LUMO of the Mn(V)₁=O₍₆₎ bond plays an important role for the concerted O–O bond formation for water oxidation in the CaMn₄O₆ cluster of OEC of PSII. One electron transfer (OET) from the π-HOMO of the Mn(V)₁=O₍₆₎ bond to the σ*-LUMO of the Mn(IV)₄–O₍₅₎ bond occurs for the formation of electron transfer diradical, where the generated anion radical [Mn(IV)₄–O₍₅₎]^-? part is relaxed to the ?Mn(III)₄?…?O₍₅₎^- structure and the cation radical [O₍₆₎=Mn(V)₁]⁺ ? part is relaxed to the ⁺O₍₆₎–Mn(IV)₁? structure because of the charge-spin separation for the electron-and hole-doped Mn–oxo bonds. Therefore, the local spins are responsible for the one-electron reductions of Mn(IV)₄->Mn(III)₄ and Mn(V)₁->Mn(IV)₁. On the other hand, the O₍₅₎^- and O₍₆₎⁺ sites generated undergo the O–O bond formation in the CaMn₄O₆ cluster. The Ca(II) ion in the cubane- skeleton of the CaMn₄O₆ cluster assists the above orbital interactions by the lowering of the orbital energy levels of π*-LUMO of Mn(V)₁=O₍₆₎ and σ*-LUMO of Mn(IV)₄–O₍₅₎, indicating an important role of its Lewis acidity. Present CBS mechanism for the O–O bond formation coupled with one electron reductions of the high-valent Mn ions is different from the conventional radical coupling (RC) and acid-base (AB) mechanisms for water oxidation in artificial and native photosynthesis systems. The proton-coupled electron transfer (PC-OET) mechanism for the O–O bond formation is also touched in relation to the CBS-OET mechanism.     

Rational Molecular Design towards Vis/NIR Absorption and Fluorescence by using Pyrrolopyrrole aza‐BODIPY and its Highly Conjugated Structures for Organic Photovoltaics

Pyrrolopyrrole aza‐BODIPY (PPAB) developed in our recent study from diketopyrrolopyrrole by titanium tetrachloride‐mediated Schiff‐base formation reaction with heteroaromatic amines is a highly potential chromophore due to its intense absorption and fluorescence in the visible region and high fluorescence quantum yield, which is greater than 0.8. To control the absorption and fluorescence of PPAB, particularly in the near‐infrared (NIR) region, further molecular design was performed using DFT calculations. This results in the postulation that the HOMO–LUMO gap of PPAB is perturbed by the heteroaromatic moieties and the aryl‐substituents. Based on this molecular design, a series of new PPAB molecules was synthesized, in which the largest redshifts of the absorption and fluorescence maxima up to 803 and 850 nm, respectively, were achieved for a PPAB consisting of benzothiazole rings and terthienyl substituents. In contrast to the sharp absorption of PPAB, a PPAB dimer, which was prepared by a cross‐coupling reaction of PPAB monomers, exhibited panchromatic absorption across the UV/Vis/NIR regions. With this series of PPAB chromophores in hand, a potential application of PPAB as an optoelectronic material was investigated. After identifying a suitable PPAB molecule for application in organic photovoltaic cells based on evaluation using time‐resolved microwave conductivity measurements, a maximized power conversion efficiency of 1.27 % was achieved.     

Site-Selective Supramolecular Complexation Activates Catalytic Ethane Oxidation by a Nitrido-Bridged Iron Porphyrinoid Dimer

Development of supramolecular methods to further activate a highly reactive intermediate is a fascinating strategy to create novel potent catalysts for activation of inert chemicals. Herein, a supramolecular approach to enhance the oxidizing ability of a high-valent oxo species of a nitrido-bridged iron porphyrinoid dimer that is a known potent molecular catalyst for light alkane oxidation is reported. For this purpose, a nitrido-bridged dinuclear iron complex of porphyrin-phthalocyanine heterodimer 3 ⁵⁺, which is connected through a fourfold rotaxane, was prepared. Heterodimer 3 ⁵⁺ catalyzed ethane oxidation in the presence of H₂O₂ at a relatively low temperature. The site-selective complexation of 3 ⁵⁺ with an additional anionic porphyrin (TPPS⁴⁻) through π–π stacking and electrostatic interactions afforded a stable 1:1 complex. It was demonstrated that the supramolecular post-synthetic modification of 3 ⁵⁺ enhances its catalytic activity efficiently. Moreover, supramolecular conjugates achieved higher catalytic ethane oxidation activity than nitrido-bridged iron phthalocyanine dimer, which is the most potent iron-oxo-based molecular catalyst for light-alkane oxidation reported so far. Electrochemical measurements proved that the electronic perturbation from TPPS⁴⁻ to 3 ⁵⁺ enhanced the catalytic activity.     

Assessing the nucleophilic character of 2-amino-4-arylthiazoles through coupling with 4,6-dinitrobenzofuroxan: Experimental and theoretical approaches based on structure-reactivity relationships

A kinetic study of the reactions of potentially bioactive 2-amino-4-arylthiazoles with highly reactive 4,6-dinitrobenzofuroxan (DNBF) is reported herein in acetonitrile solution. The complexation reaction was followed by recording the UV–vis spectra with time at λ_max = 482 nm. Electronic effects of substituents influencing the rate of reaction have been studied using structure-reactivity relationships. It is shown that the Hammett plot relative to the reaction of DNBF with 2-amino-4-(4-chlorophenyl)thiazole exhibit positive deviation from the log k₁ versus σ correlation, while it showed excellent linear correlation in terms of Yukawa–Tsuno equation. It has be noticed that the nonlinear Hammett plot observed for 2-amino-4-(4-chlorophenyl) thiazole is not attributed to a change in rate-determining step but is due to nature of electronic effect of substituent caused by the resonance of stabilization of substrates. The second-order rate constant (k₁) relating to the bond C–C and C-N forming step of the complexation processes of DNBF with 4-substituted-aminothiazoles and 2-amino-5-methyl-4-phenylthiazole, respectively, is fit into the linear relationship log k = s_N (N + E), thereby permitting the assessment of the nucleophilicity parameter (N) of the 2-amino-4-arylthiazoles of the range (4.90 < N < 6.85). 2-amino-4-arylthiazoles is subsequently ranked by positioning its reactivity on the general nucleophilicity scale developed recently by Mayr and coworkers (2003) leading an interesting and a direct comparison over a large domain of π-, σ -, and n-nucleophiles. The global electrophilicity/nucleophilicity reactivity indexes of the 2-amino-4-arylthiazoles have been investigated by means of a density functional theory (DFT) method. .     

Characterization of new Pt(IV)–thiazole complexes: Analytical,spectral, molecular modeling and molecular docking studies and applications in two opposing pathways

New thiazole derivatives were synthesized and fully characterized, then coordinated with PtCl₄ salt. Also, the newly synthesized Pt(IV) complexes were investigated analytically (elemental and thermogravimetric analyses), spectrally (infrared, UV–visible, mass, ¹H NMR, ¹³C NMR, X‐ray diffraction) as well as theoretically (kinetics, modeling and docking). The data extracted led to the establishment of the best chemical and structural forms. Octahedral geometry was the only formula proposed for all complexes, which is favorable for d⁶ systems. The molecular ion peaks from mass spectral analysis coincide with all analytical data, confirming the molecular formula proposed. X‐ray diffraction (XRD) and scanning electron microscopy (SEM) allowed discrimination of features between crystalline particles and other amorphous morphology. By applying Gaussian09 as well as HyperChem 8.2 programs, the best structural forms were obtained, as well as computed significant parameters. Computed parameters such as softness, hardness, surface area and reactivity led us towards application in two opposing pathways: tumor inhibition and oxidation activation. The catalytic oxidation for CO was conducted over PtO₂, which was yielded from calcination of the most reactive complex. The success of catalytic role for synthesized PtO₂ was due to its particulate size and surface morphology, which were estimated from XRD patterns and SEM images, respectively. The antitumor activity was tested versus HCT‐116 and HepG‐2 cell lines. Mild toxicity was recorded for two of the derivatives and their corresponding complexes. This degree of toxicity is more favorable in most cases, due to exclusion of serious side effects, which is coherently attached with known antitumor drugs.     

Anti-neuraminidase activity of chemical constituents of Balanophora involucrata

Balanophora involucrata J. D. Hooker has been known to possess potential anti-inflammatory and antibacterial activities; however, its antiviral activity has not been evaluated so far. In order to find new neuraminidase inhibitors (NAIs), the neuraminidase (NA) inhibition activity of different B. involucrata extracts was evaluated. In this study, an in vitro NA inhibition assay was performed to identify which extract of B. involucrata exhibits (maximal) inhibitory activity against NA. Ultra high performance liquid chromatography/quadrupole time-of-flight–tandem mass spectroscopy (MS/MS) and molecular docking techniques were used to identify the specific compounds responsible for the anti-influenza activity of the extract, and to explore the potential natural NAIs. The ethyl acetate extract of B. involucrata exhibited significant inhibitory activity against NA with 50% inhibitory concentration (IC₅₀) value of 159.5 μg/mL. Twenty compounds were identified according to the MS/MS spectra; among them two compounds (quercitrin and phloridzin) showed obvious inhibitory activity against NA, with IC₅₀ of 311.76 and 347.32 μmol/L, respectively. This study suggested that B. involucrata can be a potential natural source of NAIs and may be useful in the fight against ferocious influenza viruses.     

Simple and Precise Quantification of Iron Catalyst Content in Carbon Nanotubes Using UV/Visible Spectroscopy

Iron catalysts have been used widely for the mass production of carbon nanotubes (CNTs) with high yield. In this study, UV/visible spectroscopy was used to determine the Fe catalyst content in CNTs using a colorimetric technique. Fe ions in solution form red–orange complexes with 1,10-phenanthroline, producing an absorption peak at λ=510 nm, the intensity of which is proportional to the solution Fe concentration. A series of standard Fe solutions were formulated to establish the relationship between optical absorbance and Fe concentration. Many Fe catalysts were microscopically observed to be encased by graphitic layers, thus preventing their extraction. Fe catalyst dissolution from CNTs was investigated with various single and mixed acids, and Fe concentration was found to be highest with CNTs being held at reflux in HClO₄/HNO₃ and H₂SO₄/HNO₃ mixtures. This novel colorimetric method to measure Fe concentrations by UV/Vis spectroscopy was validated by inductively coupled plasma optical emission spectroscopy, indicating its reliability and applicability to asses Fe content in CNTs.