N-[2,4-二取代-5-(3-甲基-2,6-二氧-4-三氟甲基-1,2,3,6-四氢嘧啶-1-基)苯基]酰亚胺类化合物的合成及除草活性

脲嘧啶类化合物具有显著的除草活性. 设计并合成了10个未见文献报道的N-[2,4-二取代-5-(3-甲基-2,6-二氧-4-三氟甲基-1,2,3,6-四氢嘧啶-1-基)苯基]酰亚胺类化合物, 其化学结构经1H NMR, IR, HPLC/MS和元素分析表征. 初步生物活性测定结果表明, 该类化合物具有一定的除草活性, 如9a, 9b, 9c, 9f, 9g和9h在有效成分75 g/hm2剂量下, 茎叶处理对苘麻(Abutilon theophrasti Medic )、刺苋(Amaranthus spinosus)等双子叶杂草的抑制率达90%以上.     

LC‐MS/MS method for simultaneous analysis of uracil, 5,6‐dihydrouracil, 5‐fluorouracil and 5‐fluoro‐5,6‐dihydrouracil in human plasma for therapeutic drug monitoring and toxicity prediction in cancer patients

The chemotherapeutic drug 5‐fluorouracil (5‐FU) is widely used for treating solid tumors. Response to 5‐FU treatment is variable with 10–30% of patients experiencing serious toxicity partly explained by reduced activity of dihydropyrimidine dehydrogenase (DPD). DPD converts endogenous uracil (U) into 5,6‐dihydrouracil (UH₂), and analogously, 5‐FU into 5‐fluoro‐5,6‐dihydrouracil (5‐FUH₂). Combined quantification of U and UH₂ with 5‐FU and 5‐FUH₂ may provide a pre‐therapeutic assessment of DPD activity and further guide drug dosing during therapy. Here, we report the development of a liquid chromatography–tandem mass spectrometry assay for simultaneous quantification of U, UH₂, 5‐FU and 5‐FUH₂ in human plasma. Samples were prepared by liquid–liquid extraction with 10:1 ethyl acetate‐2‐propanol (v/v). The evaporated samples were reconstituted in 0.1% formic acid and 10 μL aliquots were injected into the HPLC system. Analyte separation was achieved on an Atlantis dC₁₈ column with a mobile phase consisting of 1.0 mm ammonium acetate, 0.5 mm formic acid and 3.3% methanol. Positively ionized analytes were detected by multiple reaction monitoring. The analytical response was linear in the range 0.01–10 μm for U, 0.1–10 μm for UH₂, 0.1–75 μm for 5‐FU and 0.75–75 μm for 5‐FUH₂, covering the expected concentration ranges in plasma. The method was validated following the FDA guidelines and applied to clinical samples obtained from ten 5‐FU‐treated colorectal cancer patients. The present method merges the analysis of 5‐FU pharmacokinetics and DPD activity into a single assay representing a valuable tool to improve the efficacy and safety of 5‐FU‐based chemotherapy. Copyright © 2012 John Wiley & Sons, Ltd.     

Primary Fragmentation Pathways of Gas Phase [M(Uracil−H)(Uracil)]+ Complexes (M=Zn,Cu, Ni,Co, Fe,Mn, Cd,Pd , Mg,Ca, Sr,Ba, and Pb): Loss of Uracil versus HNCO

Complexes formed between metal dications, the conjugate base of uracil, and uracil are investigated by sustained off‐resonance irradiation collision‐induced dissociation (SORI‐CID) in a Fourier transform ion cyclotron resonance (FTICR) mass spectrometer. Positive‐ion electrospray spectra show that [M(Ura?H)(Ura)]⁺ (M=Zn, Cu, Ni, Co, Fe, Mn, Cd, Pd, Mg, Ca, Sr, Ba, or Pb) is the most abundant ion even at low concentrations of uracil. SORI‐CID experiments show that the main primary decomposition pathway for all [M(Ura?H)(Ura)]⁺, except where M=Ca, Sr, Ba, or Pb, is the loss of HNCO. Under the same SORI‐CID conditions, when M is Ca, Sr, Ba, or Pb, [M(Ura?H)(Ura)]⁺ are shown to lose a molecule of uracil. Similar results were observed under infrared multiple‐photon dissociation excitation conditions, except that [Ca(Ura?H)(Ura)]⁺ was found to lose HNCO as the primary fragmentation product. The binding energies between neutral uracil and [M(Ura?H)]⁺ (M=Zn, Cu, Ni, Fe, Cd, Pd ,Mg, Ca, Sr Ba, or Pb) are calculated by means of electronic‐structure calculations. The differences in the uracil binding energies between complexes which lose uracil and those which lose HNCO are consistent with the experimentally observed differences in fragmentation pathways. A size dependence in the binding energies suggests that the interaction between uracil and [M(Ura?H)]⁺ is ion–dipole complexation and the experimental evidence presented supports this.     

Interaction between RNA segment (adenine‐uracil) and model of protein unit (formamide): A density‐functional theory study

Various possible structures of adenine‐uracil‐formamide hydrogen‐bond complexes were optimized at 6‐311++G(d,p) level, and the binding energies of these complexes were also calculated at DFT B3LYP/6‐311++G(d,p) level. Eight stable cyclic structures being involved in the interaction are found on the potential energy surface. By analyzing the structure, NPA charge and interaction energy of complexes, we obtain the most stable geometry structure. The results show that the interactions between formamide and adenine‐uracil (A‐U) base pair affect the stabilities of the base pairs. © 2009 Wiley Periodicals, Inc. Int J Quantum Chem, 2010     

Tautomerism in 5-Bromouracil: Relationships with Other 5-Haloderivatives and Effect of the Microhydration

A comparative analysis on the effect of the water on the molecular structure and spectroscopy of 5-halogenated uracils was carried out. Solvent effects were considered by using a variable number (1–10) of explicit water molecules surrounding the 5-halouracil derivatives in order to simulate the first hydration shell. More than 300 cluster structures with water were analyzed. B3LYP and MP2 quantum chemical methods were used. For cases where literature data are available, the computed values were in good agreement with previous experimental and theoretical studies. Several general conclusions were underlined.     

Sensing System Integrating Lanthanum Hydroxide Nanowires with Copper(II) Ion for Uracil and its Application

Abstract

A sensing system for uracil was constituted by using lanthanum hydroxide nanowires (LNW) as a modifier to obtain LNW modified carbon paste electrode (LNW/CPE) and by introducing copper(II) ion into supporting electrolyte to transform electroinactive uracil to electroactive uracil‐Cu(II) complex. The voltammetric behaviors of uracil in the presence of Cu(II) ion at LNW/CPE were investigated. A reduction peak of the uracil‐Cu(II) complex at ?0.18 V was the two‐electron reduction of Cu(II) ion in the uracil‐Cu(II) complex; while a new oxidation peak at 0.22 V was the one‐electron oxidation of the uracil‐Cu(I) complex. Additionally, the voltammetric responses of all the complexes at LNW/CPE were more sensitive than that at carbon and multiwall carbon nanotube paste electrodes, which resulted from both the large surface effect of LNW and the chemical coordination of uracil with La(III) ion in LNW. With the sensitive oxidation peak of the uracil‐Cu(I) complex at LNW/CPE, a linear range of 4.0×10^?9?3.0×10^?8 mol/l for uracil was obtained along with a detection limit of 2.0×10^?10 mol/l. The proposed system was evaluated by the determination of uracil derivatives, anticancer drug 5‐flurouracil, in pharmaceutical preparations.     

Acoustic and volumetric studies of uracil in aqueous urea solution at different temperatures

Volumetric, viscometric and ultrasonic studies of uracil in an aqueous urea solution in varying concentration of 2, 3 and 5?M have been carried out at 298, 308 and 318?K. The uracil concentration in the aqueous urea solution varies from 0.05% to 0.4%. Density (ρ), viscosity (η) and sound speed (u) have been measured. The experimental data are used for computing various thermodynamic and acoustic parameters, namely apparent molar volume, isentropic compressibility, apparent isentropic compressibility, relative association, intermolecular free length, acoustic impedance, viscous relaxation time, hydration number, Gibb's free energy, classical absorption coefficient of the solution and viscosity data have been further analysed in the light of Masson's equation and Jones–Dole's equations, respectively. The results have been discussed in terms of solute–solute and solute–solvent interaction and the structural changes of the solutes in solutions. The effect of variation of temperature on these interactions has also been investigated.     

Photochemical behaviour of 5-perfluoroalkenyl uracils

Phototransformations of derivatives of 5-fluoroalkenyl uracils depend strongly on the fluorinated substituents. 1,3-Dimethyl-5-trifluorovinyluracil when irradiated in water with UV light (λ>300 nm) gives 1,3-dimethyl-(5,6-dihydrourac-6-yl)-difluoroacetic acid as the only product, while the analogous 1,3-dimethyl-5-(E-pentafluoropropenyl)uracil isomerizes to its Z isomer. It is suggested that the first transformation is thermodynamically controlled while the second one is kinetically controlled, the difference being due to torquoselectivity.