Ab initio quantum chemistry studies on the coding properties of cytosine derivatives generated by hydroxyl radical in aerobic conditions

The coding properties of four free radicals derived cytosine modifications were characterised by ab initio quantum chemistry method. The dimers geometry was optimised without any restrictions. The analysis was focused on the pairs consisting of a standard DNA base and one of the following cytosine derivatives: 5,6-dihydroxycytosine (1); 5,6-dihydroxyuracil (2); uracil glycol (3); and isodialuric acid (4). The presented data allow to conclude that all studied derivatives are able to form the most stable pairs with guanine. However, other pairs are also possible. In non-polar conditions the 5,6-dihydroxycytosine (1) pair with cytosine in addition to a normal pairing with guanine. This may stand for CG transversion. The significant impact of the environment polarity on the dimers stabilisation energy was observed. The potential mispairing is enriched in the polar conditions The 5,6-dihydroxyuracil (2) and isodialuric acid (4) may form stable pairs also with adenine. This may lead to CT transition. The mispairing of uracil glycol (3) was found as insignificant.     

尿嘧啶和5-溴尿嘧啶的低温热容

采用综合物性测量系统(PPMS)的热容测量模块在1.9-300 K温度区间内对两种药物中间体(尿嘧啶和5-溴尿嘧啶)的低温热容进行了测量与研究. 结果表明, 在测量温区内两种化合物的低温热容随温度的上升而逐步增加, 无任何热异常现象产生; 在相同温度下, 5-溴尿嘧啶的热容数值始终高于尿嘧啶. 利用低温热容理论模型对热容数据进行了拟合, 并计算得到了0-300 K温区的摩尔熵变、焓变等热力学函数. 此外, 通过热容拟合数据计算得到的尿嘧啶和5-溴尿嘧啶在298.15 K的标准摩尔规定熵分别为(132.48±1.32)和(165.39±1.65) J·K^-1·mol^-1.     

M-RNA碱基复合物(M=Ca~+和Mg~+)特征振动的密度泛函理论分析

采用密度函数理论的B3LYP交换关联能泛函在6-311+G(2df,2p)基组水平上,优化计算了Ca+,Mg+与RNA碱基嘧啶各同分异构体形成稳定复合物的结构,发现其中C1M,T1M和U1M(M=Ca+和Mg+)为最稳定复合物,并对这些复合物红外振动进行了计算.计算结果显示碱基嘧啶单体主要存在的两个红外特征振动,是由环振动和环外氧原子及与其成键的环上碳原子之间产生伸缩振动引起的.当形成复合物时,由于离子的参与,使单体碱基分子的振动情况发生了改变,主要表现在离子倾向于与环外负电子原子N和O原子成键,使与离子直接作用环外原子参与的特征振动频率减小,谱线红移;不与离子直接作用环外原子引起的特征振动频率增大,谱线蓝移.     

Tertiary amine effect: synthesis of some novel spirosubstituted pyrido[2,3-d]pyrimidines

5-Formyl-6-tertiaryamino uracils 3 prepared from 6-chloro-5-formyl uracil derivative 1 react with barbituric acids 4 in the presence of base catalyst to afford a novel class of spirosubstituted pyrido[2,3-d]pyrimidines 5 via 1,6-electro-cyclisation in excellent yields.     

尿嘧啶和5-氯尿嘧啶1S0→1S2跃迁动态结构的共振拉曼光谱

采用含时量子波包理论的简单模型对5-氯尿嘧啶和尿嘧啶的共振拉曼光谱开展了强度分析拟合, 获得了1(π, π*)激发态的几何结构变化动态特征. 结果表明, 尿嘧啶1S0→1S2跃迁的动态结构特征因5-位氯原子取代而改变. 5-氯尿嘧啶的动态结构特征主要沿C5=C6伸缩振动+C6H12 弯曲振动和N3H9/N1H7弯曲振动+N1C6伸缩振动反应坐标展开, 而尿嘧啶的动态结构特征主要沿嘧啶环的伸缩振动+C5H11/C6H12/N1H7弯曲振动和C4=O10伸缩振动反应坐标展开. π和π*轨道中氯原子的pz电子参与嘧啶环的p-π共轭作用导致了在1(π, π*)激发态上5-氯尿嘧啶的振动重组能更多地配分给嘧啶环的弯曲振动模式和C5=C6伸缩振动模式. 尿嘧啶在甲醇中的激发态动态结构特征与在水中的基本一致, 但波包沿C5H11/C6H12/N1H7弯曲振动+N1C6伸缩振动(υ12)和环呼吸振动(υ17)反应坐标的运动明显增强.     

Imido,amino and amido coordination of diaminouracil to rhenium(V)

Reaction of equimolar quantities of cis-[ReO₂I(PPh₃)₂] with 5,6-diamino-1,3-dimethyl-2,4-dioxopyrimidine (H₂ddd) in acetonitrile led to the formation of [Re(ddd)(Hddd)I(PPh₃)₂] (ReO₄) (1). A single-crystal X-ray crystal structure shows that ddd is coordinated as a monodentate through the doubly deprotonated amino nitrogen and is therefore present as an imide. The chelate Hddd is coordinated as a bidentate via a neutral amino nitrogen atom, trans to the imido nitrogen, and a singly deprotonated amido nitrogen atom, trans to the iodide.     

Analysis of Pseudouridine by Fluorescence Spectrometry

Abstract

Fluorescence spectral properties of pseudouridine, an important biological indicator, have been measured for the first time in this study. The fluorescence quantum yield is maximal in aqueous solution with pH values above 9 with spectral properties characteristic of 5 alkyl substituted uracil derivatives. Chromatographic analysis shows the fluorescence is associated only with the pseudouridine peak. The concentration dependence of fluorescence is linear from 4 to 45 micromolar at pH 11.5. The excitation maximum is about 295 nm and the emission is broad with a maximum at about 390 nm. Addition of pseudouridine to urine extracts gives a linear increase in fluorescence with increasing pseudouridine concentration.     

Ruthenium(II/IV) complexes with potentially tridentate Schiff base chelates containing the uracil moiety

Herein we report the synthesis and characterization of trans-[Ru^IICl₂(PPh₃)₃] with potentially tridentate Schiff bases derived from 5,6-diamino-1,3-dimethyl uracil (H₂ddd) and two 2-substituted aromatic aldehydes. In the diamagnetic ruthenium(II) complexes, trans-[RuCl(PPh₃)₂(Htdp)] (1) {H₂tdp = 5-((thiophen-3-yl)methyleneamino)-6-amino-1,3-dimethyluracil} and trans-[RuCl(PPh₃)₂(Hsdp)] (2) {H₂sdp = 5-(2-(methylthio)benzylideneamino)-6-amino-1,3-dimethyluracil}, the Schiff base ligands (i.e. Htdp and Hsdp) act as mono-anionic tridentate chelators. Upon reacting 5-(2-hydroxybenzylideneamino)-6-amino-1,3-dimethyluracil (H₃hdp) with the metal precursor, the paramagnetic complex, trans-[Ru^IVCl₂(ddd)(PPh₃)₂] (3), was isolated, in which the bidentate dianionic ddd co-ligand was formed by hydrolysis. The metal complexes were fully characterized via multinuclear NMR-, IR-, and UV–Vis spectroscopy, single crystal XRD analysis and conductivity measurements. The redox properties were probed via cyclic voltammetry with all complexes exhibiting comparable electrochemical behavior with half-wave potentials (E_½) at 0.70 V (for 1), 0.725 V (for 2), and 0.68 V (for 3) versus Ag|AgCl, respectively. The presence of the paramagnetic metal center for 3 was confirmed by ESR spectroscopy.     

Surface resistance measurements at the metal/electrolyte interface of Ag(100) and Ag(111) thin film electrodes

The conductivity of thin film metal electrodes with a thickness of the order of the mean free path of the conduction electrons (50 nm at 300 K) is sensitive to several processes on the metal surface (e.g. adsorption and desorption of ions). We developed epitaxially grown Ag(100)/MgO(100) and Ag(111)/TiO₂(110) electrodes of 20 nm thickness. The change in the surface resistance of Ag(100) thin film electrodes during adsorption of the halide ions Cl⁻, Br⁻ and I⁻ shows the different strengths of specific adsorption. We investigated the phase transition of thiocyanate (SCN⁻) on Ag(100) electrodes by combining the surface resistance method with voltammetric, capacitance and ex-situ XPS measurements. The influence of adsorbed uracil on the resistance of Ag(100) films was demonstrated. The surface resistance is very sensitive to small concentrations of metal cations (e.g. Tl⁺). The surface resistance of Ag(100) and Ag(111) thin film electrodes shows the typical difference in the stripping potential of Tl⁺ of about 100 mV.     

Theoretical analysis of the addition of hydroxylamine to uracil and 5-fluorouracil as a model for the thymidylate synthase reaction

In the present paper we report a quantum chemical (PM3) investigation of reagents, transition structures, intermediates and final products of the nucleophilic addition of hydroxylamine to uracil (U) and 5-fluorouracil (FU). This reaction serves as a model for the more complex enzymatic methylation of 2′-deoxyuridine-5′-monophosphate (dUMP) and 5-fluoro-2′-deoxyuridine-5′-monophosphate (FdUMP) by thymidylate synthase. From the analysis of the frontier orbitals of the isolated and complexed species, as well as from the calculation of activation barriers, we propose that nucleophilic attack usually proceeds after formation of an initial complex between U (or FU) and one neutral and one protonated molecule of hydroxylamine. Our results give some insight into the mechanism of these reactions and account for the higher rate of addition of hydroxylamine to FU, compared to U. The main connection between the chemical simulation and the biological scheme is that in both reactions hydrogen bonding residues are found to be necessary to assist catalysis.