Simultaneous determination of FL118 and W34 in rat Blood by LC–MS/MS: Application to pharmacokinetic studies

W34 is a prodrug of FL118, and it can be converted to FL118 via a hydrolysis reaction. In this report, a highly sensitive LC–MS/MS method using a C₁₈ column was validated and used for the simultaneous determination of W34 and FL118 in rat blood. A stepwise gradient elution with 0.1% formic acid in water and acetonitrile was employed. The assays were linear over a concentration range of 0.50–50.0 ng/ml for both W34 and FL118. The accuracy of the validation method ranged from 89.74 to 98.94% for W34 and from 88.61 to 94.60% for FL118. The precision was within 7.15% for W34 and 9.63% for FL118. Extraction recoveries of W34 were 94.56–100.49 and 87.67–106.32% for FL118. No significant matrix effects for both W34 and FL118 were observed in blood. The assay has been successfully applied to biological samples obtained from a stability and pharmacokinetic study of W34 and FL118.     

Improved sulfoalkylbetaine‐based organic‐silica hybrid monolith for high efficient hydrophilic interaction liquid chromatography of polar compounds

A novel sulfoalkylbetaine‐based zwitterionic organic‐silica hybrid monolith was synthesized by using 3‐dimethyl‐(3‐(N‐methacrylamido) propyl) ammonium propane sulfonate (DMMPPS, neutral sulfoalkyl‐betaine monomer). The added amount of zwitterionic monomer was significantly increased when DMMPPS was used instead of the conventionally used acidic sulfoalkyl‐betaine monomer, that is, the N,N‐dimethyl‐N‐ methacryloxyethyl‐N‐(3‐sulfopropyl) ammonium betaine, and this led to a significantly improved hydrophilicity of the monolith. The DMMPPS‐based organic‐silica hybrid monolith exhibited good mechanical stability and excellent separation performance. About ～20 μm plate height (corresponding to column efficiency of ～50 000 plates/m) was obtained for nucleoside at the linear velocity of 1 mm/s. The proposed monolithic column was successfully applied to separate purines/pyrimidines, nucleotides, and tryptic digest of bovine hemoglobin in a nano‐HILIC mode, and the results demonstrated that such monolith has the potential for separation of a variety of hydrophilic substances.     

超球坐标下Li原子基态能量的快速收敛计算

将Ｌｉ原子２Ｓ态的波函数分解为两项之积，ψ＝ＸΦ，Ｘ＝ｅｘｐ［－α（ｒ１＋ｒ２＋ｒ３）］，而Φ向以九维超球谐为投影函数而构造的Ｓ３置换群的二维不可约表示的基函数展开。Ｓｃｈｒｏｄｉｎｇｅｒ方程转化为一起球径耦合微分方程。再利用广义Ｌａｇｕｅｒｒｅ函数展开法对其求解，从而得到一广义能量本征方程，给出了库仑势及有关超球角函数在非对称九维超球谐之间矩阵元的简单解析式，可由一起几何函数４Ｆ３：（Ａ，Ｂ，Ｃ，Ｄ；Ｅ，Ｆ，Ｇ；１）的线性组合表示。取超球谐函数的子集（ｌ１＝ｌ２＝ｌ３＝０），基态１２Ｓ的本征能量在超球角方向的收敛速度加快，首次用非变分法得到了优于Ｈａｒｔｒｅｅ－Ｆｏｃｋ精度的基态能量。结果表明本文给出的方法是对直接超球谐广义Ｌａｇｕｅｒｒｅ函数展开法（ＨＨ－ＧＬＦ）的一个非常有效的改进。     

基于倾斜相位的抗振动干涉面形测量

环境振动会在干涉测量过程中产生随机倾斜、移相误差,导致测量精度下降。为了降低环境振动对移相干涉测量的影响,提出了一种基于倾斜相位的抗振动干涉面形测量方法。首先,利用Fourier变换将干涉图变换到频域;然后,利用频域细分操作对峰值坐标进行亚像素精度定位,求解出振动倾斜平面;最后,利用最小二乘法计算出待测面的相位分布。实验结果表明,本方法与同步移相法的复原结果具有高度一致性,波面峰谷值和均方根值的偏差较小;且本方法无需对硬件进行改动,可为振动环境下的移相干涉测量提供一种低成本、高精度的解决方案。     

Urinary metabolites of cinobufagin in rats and their antiproliferative activities

Cinobufagin was one of the important cardenolidal steroids and a major component of Chan'Su, a famous traditional Chinese medicine. The urinary metabolites of cinobufagin after single oral doses of 25?mg?kg?1 in rats were investigated. Eleven metabolites were isolated and purified by liquid-liquid extraction, open-column chromatography, medium-pressure liquid chromatography, as well as semi-preparative high-performance liquid chromatography. Their structures were elucidated by chemical and various spectroscopic methods, which were identified as desacetylcinobufagin (M-1), 3-oxo-desacetylcinobufagin (M-2), 3-oxo-cinobufagin (M-3), 3-epi-desacetylcinobufagin (M-4), 3-epi-12β-hydroxyl desacetylcinobufagin (M-5), 5β-hydroxyl cinobufagin (M-6), 5β-hydroxyl desacetylcinobufagin (M-7), 12β-hydroxyl cinobufagin (M-8), 1β,12β-dihydroxyl cinobufagin (M-9), 12β-hydroxyl desacetylcinobufagin (M-10) and 1β,12β-dihydroxyl desacetylcinobufagin (M-11), respectively. Among them, M-1 was the main urinary metabolite of cinobufagin with a yield of 17.7%. Most metabolites were hydroxylated products of cinobufagin at C-1β, 5β and 12β positions, as well as deacetylated products at C-16. Except M-1, M-4 and M-7, the other eight metabolites were novel in vivo metabolites of cinobufagin. Some metabolites showed potential cytotoxicity against human hepatoma cells (HepG2) and human leukaemia (K562, HL-60) cells; however, their cytotoxicities generally decreased after metabolic conversion.     

Improving reliability of a shared supplier with competition and spillovers

Supplier reliability is a key determinant of a manufacturer’s competitiveness. It reflects a supplier’s capability of order fulfillment, which can be measured by the percentage of order quantity delivered in a given time window. A perfectly reliable supplier delivers an amount equal to the order placed by its customer, while an unreliable supplier may deliver an amount less than the amount ordered. Therefore, when suppliers are unreliable, manufacturers often have incentives to help suppliers improve delivery reliability. Suppliers, however, often work with multiple manufacturers and the benefit of enhanced reliability may spill over to competing manufacturers. In this study, we explore how potential spillover influences manufacturers’ incentives to improve supplier’s reliability. We consider two manufacturers that compete with imperfectly substitutable products on Type I service level (i.e., in-stock probability). The manufacturers share a common supplier who, due to variations in production quality or yield, is unreliable. Manufacturers may exert efforts to improve the supplier’s reliability in the sense that the delivered quantity is stochastically larger after improvement. We develop a two-stage model that encompasses supplier improvement, uncertain supply and random demand in a competitive setting. In this complex model, we characterize the manufacturers’ equilibrium in-stock probability. Moreover, we characterize sufficient conditions for the existence of the equilibrium of the manufacturers’ improvement efforts. Finally, we numerically test the impact of market characteristics on the manufacturers’ equilibrium improvement efforts. We find that a manufacturer’s equilibrium improvement effort usually declines in market competition, market uncertainty or spillover effect, although its expected equilibrium profit typically increases in spillover effect.     

A Graphene Oxide–Based Sensing Platform for The Label-free Assay of DNA Sequence and Exonuclease Activity via Long Range Resonance Energy Transfer

Graphene oxide (GO) was introduced as an efficient quencher for label-free and sensitive detection of DNA. Probe DNA (pDNA) was mixed with ethidium bromide (EB) and graphene oxide (GO). The interaction between EB and GO led to the fluorescent quenching. Upon the recognition of the target, EB was intercalated into duplex DNA and kept away from GO, which significantly hindered the long range resonance energy transfer (LrRET) from EB to GO and, thus, increased the fluorescence of EB. The changes in fluorescent intensity produced a novel method for sensitivity, and specificity detection of the target. Based on the structure-switching of aptamers, this strategy could be conveniently extended for detection of other biomolecules, which had been demonstrated by the detection of exonuclease activity.     

Theoretical studies to understand surface chemistry on carbon anodes for lithium-ion batteries: how does vinylene carbonate play its role as an electrolyte additive?

To elucidate the role of vinylene carbonate (VC) as a solvent additive in organic polar solutions for lithium-ion batteries, reductive decompositions for vinylene carbonate (VC) and ethylene carbonate (EC) molecules have been comprehensively investigated both in the gas phase and in solution by means of density functional theory calculations. The salt and solvent effects are incorporated with the clusters (EC)nLi+(VC) (n = 0-3), and further corrections that account for bulk solvent effects are added using the polarized continuum model (PCM). The electron affinities of (EC)nLi+(VC) (n = 0-3) monotonically decrease when the number of EC molecules increases; a sharp decrease of about 20.0 kcal/mol is found from n = 0 to 1 and a more gentle variation for n > 1. For (EC)nLi+(VC) (n = 1-3), the reduction of VC brings about more stable ion-pair intermediates than those due to reduction of the EC molecule by 3.1, 6.1, and 5.3 kcal/mol, respectively. This finding qualitatively agrees with the experimental fact that the reduction potential of VC in the presence of Li salt is more negative than that of EC. The calculated reduction potentials corresponding to radical anion formation are close to the experimental potentials determined with cyclic voltammetry on a gold electrode surface (-2.67, -3.19 eV on the physical scale for VC and EC respectively vs experimental values -2.96 and -2.94 eV). Regarding the decomposition mechanisms, the VC and EC moieties undergo homolytic ring opening from their respective reduction intermediates, and the energy barrier of VC is about one time higher than that of EC (e.g., 20.1 vs 8.8 kcal/mol for (EC)2Li+(VC)); both are weakly affected by the explicit solvent molecules and by a bulk solvent represented by a continuum model. Alternatively, starting from the VC-reduction intermediate, the ring opening of the EC moiety via an intramolecular electron-transfer transition state has also been located; its barrier lies between those of EC and VC (e.g., 17.2 kcal/mol for (EC)2Li+(VC)). On the basis of these results, we suggest the following explanation about the role that VC may play as additive in EC-based lithium-ion battery electrolytes; VC is initially reduced to a more stable intermediate than that from EC reduction. One possibility then is that the reduced VC decomposes to form a radical anion via a barrier of about 20 kcal/mol, which undergoes a series of reactions to give rise to more active film-forming products than those resulting from EC reduction, such as lithium divinylene dicarbonate, Li-C carbides, lithium vinylene dicarbonate, R-O-Li compound, and even oligomers with repeated vinylene and carbonate-vinylene units. Another possibility starting from the VC-reduction intermediate is that the ring opening occurs on the unreduced EC moiety instead of being on the reduced VC, via an intramolecular electron transfer transition state, the energy barrier of which is lower than that of the former, in which VC just helps the intermediate formation and is not consumed. The factors that determine the additive functioning mechanism are briefly discussed, and consequently a general rule for the selection of electrolyte additive is proposed.     

A comparative electron correlation treatment in H(2)S-benzene dimer with DFT and wavefunction-based ab initio methods

The S₀ (X¹A′), T₁ (a³A″), S₁ (A¹A″), T₂ (b³A′), and S₂ (B¹A′) states of the (trans-)HONO molecule were studied by using the CASSCF and CASPT2 methods. The CASPT2(//CASPT2) adiabatic and vertical excitation energy values are in good agreement with available experimental data. The CASPT2//CASSCF potential energy curves (PECs) calculations indicate that: (i) all the five states correlate with the products of OH (X²Π) + NO (X²Π); (ii) along each of the T₁, S₁, and T₂ PECs there is a minimum followed by a transition state (barrier); and (iii) the repulsive S₂ PEC crosses the T₂, S₁, and T₁ PECs. The geometries and relative energies for the stationary points along these PECs were calculated at the CASPT2(//CASPT2) level, and the calculations predict that the barrier height value for S₁ is negligibly small (0.0018 eV).     

PHGLF calculations of heliumlike three-body systems

By expanding the atomic wave function in potential harmonics (PH ) and generalized Laguerre functions (GLF ), we derived the recurrence relation of the expansion coefficients and then performed calculations for four He-like three-body systems. In comparison with the complete set calculation (HHGLF ), we find that the errors in eigenenergies introduced by the PHGLF scheme are approximately 0.00033, 0.00025, 0.00022, and 0.00021 au for the ground-state H⁻, He, Li⁺, and Be²⁺ systems, respectively, and that for excited states the error is slightly higher and decreases with the grand angular momentum. The present results indicate that the PHGLF scheme is such an efficient means to reduce the degeneracy of the hyperspherical harmonics (HH ) for three-body problems that it can give more satisfactory results than can the HHGLF method with much smaller eigenmatrices. © 1995 John Wiley & Sons, Inc.