尿嘧啶、水合尿嘧啶的结构和振动性质研究

基于从头计算方法和半经验势分子动力学,通过计算尿嘧啶分子及其水合尿嘧啶分子运动轨迹的速度自关联函数的傅立叶变换,给出了这些分子的振动频率。通过求解Hessian矩阵,鉴别出这些分子每一个振动频率的振动模式。对孤立的尿嘧啶分子,计算结果能够和实验数据符合。对水合尿嘧啶分子中,尿嘧啶分子的结构和振动频率的改变做了讨论。Based on an ab initio calculation and a semiempirical method, the structural and vibrational frequencies of Uracil and hydrated Uracil are studied by using the Fourier transform of velocity autocorrelation function of trajectories of molecular dynamics simulations. The finite difference harmonic method is also used to assign the vibrational frequency of each mode. It is found the calculation frequencies are in good agreement with the experiment data. The structural and vibrational frequencies of Uracil in hydrated form is discussed.     

Biochemical Characterization of Uracil-DNA Glycosylase from Pyrococcus furiosus

We report the characterization of a uracil-DNA glycosylase(UDG) from the hyperthermophilic archaea Pyrococcus furiosus(P. furiosus). P. furiosus UDG(PfUDG) has high sequence similarity to the families IV and V UDGs(thermostable UDG family and PaUDG-b family). PfUDG excises uracil from various DNA substrates with the following order: U/T≈U/C>U/G≈U/AP≈U/->U/U≈U/I≈U/A. The optimal temperature and pH value for uracil excision by PfUDG are 70 ℃ and 9.0, respectively. The removal of U is inhibited by the divalent ions of Fe, Ca, Zn, Cu, Co, Ni and Mn, as well as a high concentration of NaCl. The phosphorothioates near uracil strongly inhibit the excision of uracil by PfUDG. Interestingly, pfuDNA(Pyrococcus furiosus DNA) polymerase, which tightly binds the uracil- carrying oligonucleotide, does not inhibit the excision by PfUDG, suggesting PfUDG in vivo functions as the repair enzyme to excise uracil damage in genome.     

1-(2’-烷硫基乙氧基)甲基尿嘧啶及其氧化物的合成

采用 3 0 %H2 O2 /DEAD的试剂组合 ,用于将硫醚及亚砜的衍生物氧化成砜类物质的反应 ,合成了1 ( 2 烷硫基乙氧基 )甲基尿嘧啶及其氧化物 ,产物结构经元素分析、1HNMR和IR进行表征 ,并研究了其抗癌活性     

Interaction of the uracil dipole-bound electron with closed-shell systems (Ar and N2)

A very diffuse, but spatially confined, electron trapped in a dipole–bound state of a polar molecule provides an excellent target for testing the interaction of a localized electron positioned outside the molecular frame of its host molecule with other atomic or molecular systems. In this work we use ab initio calculations to investigate systems where a dipole–bound electron attached to a uracil molecule is interacting with an N₂ molecule and an Ar atom. Neither of the two systems forms a stable anion and in the aducts they form with the dipole–bound electron the electron becomes suspended between the uracil molecule and Ar or N₂. Calculations are performed to determine the vertical electron detachment energies of these anions and to determine the molecular rearrangements occurring when the excess electron is removed from them.Contribution to the Jacopo Tomasi Honorary Issue     

One‐pot New Barbituric Acid Derivatives Derived from the Reaction of Barbituric Acids with BrCN and Ketones

Reaction of cyclic β‐dicarbonyl compounds such as pyrimidine‐(1H,3H,5H)‐2,4,6‐trione (BA), 1,3‐dimethyl pyrimidine‐(1H,3H,5H)‐2,4,6‐trione (DMBA) and 2‐thioxo‐pyrimidine‐(1H,3H,5H)‐4,6‐dione (TBA) with cyanogen bromide in acetone and 2‐butanone in the presence of triethylamine afforded a new class of stable heterocyclic spiro[furo[2,3‐d]pyrimidine‐6,5′‐pyrimidine]2,2′,4,4′,6′(3H,3′H,5H)‐pentaones (dimeric forms of barbiturate) at 0 °C and ambient temperature. Structure elucidation was carried out by X‐ray crystallographic, ¹H NMR, ¹³C NMR, two dimensional NMR, FT‐IR spectra, mass spectrometry and elemental analysis. The mechanism of product formation is discussed. The reaction of DMBA with cyanogen bromide in the presence of triethylamine also afforded trimeric form of barbiturate of uracil derivatives in good yield. The reaction of selected acyclic β‐dicarbonyl compounds with cyanogen bromide in the presence of triethylamine in acetone and/or diethyl ether has also been investigated under the same condition. Diethyl malonate and ethyl cyanoacetate brominated and also ethyl acetocetate both brominated and cyanated on active methylene via cyanogen bromide.     

Preparation and reaction of uracil substituted cyclen and cyclam: formation of tricyclic guanidinium and dihydroimidazolium salts

Di-uracil substituted cyclen derivatives were prepared by the reaction of cyclen with 6-chloro-1-methyluracil or 6-chloro-1,3-dimethyluracil. The reaction of cyclam with 6-chloro-1,3-dimethyluracil gave a similar di-uracil substituted cyclam. The 1,7-di-uracil substituted cyclen was converted to the tricyclic guanidinium salt and acylurea upon heating in DMSO in the presence of weak acid. The 1,8-di-uracil substituted cyclam gave a tricyclic dihydroimidazolium salt under the same conditions. These reactions can be explained by an intramolecular uracil ring-breaking reaction mechanism.     

Design and synthesis of novel 5,6-bisindolylpyrimidin-4-ones structurally related to ruboxistaurin (LY333531)

2,3-Bis(1-methyl-1H-indol-3-yl) methyl-3-oxopropionate is a key intermediate in the synthesis of a new family of LY333531 analogues. Base-mediated cyclocondensation with thiourea afforded novel 5,6-bis(1-methyl-1H-indol-3-yl)-2-thioxo-2,3-dihydropyrimidin-4(1H)-one, which was efficiently converted to the pyrimidin-2,4(1H,3H)-dione congener. Synthesis of a six-membered K-252c analogue, 5,6-bis(1-methyl-1H-indol-3-yl)pyrimidin-4(3H)-one, is also described.     

Stereoselective intramolecular hetero Diels-Alder reactions of 1-oxa-1,3-butadienes: a novel approach for the synthesis of complex annulated uracils

The intramolecular hetero Diels-Alder reactions of 1-oxa-1,3-butadienes 4, obtained from salicylaldehyde 1 via O-allylation followed by Knoevenagel condensation with barbituric acids 3 in the presence of hydrochloric acid as catalyst, affords the tetracyclic uracil derivatives 5 and 6 in a stereoselective manner and high overall yields.     

Investigation of the fluorescence quenching of 2,3-diazabicyclo[2.2.2]oct-2-ene (DBO) by certain substituted uracils

The fluorescence quenching of 2,3-diazabicyclo[2.2.2]oct-2-ene (DBO) by a series of uracils has been studied in water and acetonitrile solvents using steady-state and time-resolved fluorescence techniques. The steady-state fluorescence quenching technique has been performed in three different pHs (i.e. 4, 8 and 12). The bimolecular quenching rate constant (k_q) increases with increase in pH of uracils. In acidic pH, a pure hydrogen atom abstraction is proposed as the quenching mechanism. This is supported by a pronounced solvent deuterium isotope effect. Electron transfer from the anionic form of uracil to the excited state of DBO is proposed as a mechanism for quenching in basic pH on the basis of highly exergonic thermodynamics obtained from the Rehm-Weller equation. The variation of k_q is explained on the basis of the electronic effect of substitution in uracils as well.