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.     

Interaction of quinones with three pyrimidine bases: A laser flash photolysis study

The interaction between three different pyrimidine bases, uracil (U), cytosine (C) and thymine (T) and two quinones, 2-methyl-1,4-naphthoquinone or menadione (MQ) and 9,10-anthraquinone (AQ) have been studied using laser flash photolysis technique in organic homogeneous medium. The three pyrimidines have revealed a difference in their extent of reactivity towards the quinones, which has been attributed to their structural difference. Our works have revealed that the difference in structural dimension of the quinones is also responsible for affecting the reactivity of these pyrimidines in homogeneous medium.     

Palladium-catalyzed direct 5-arylation of 1,3-dimethyluracil with aryl bromides: an electrophilic metalation-deprotonation with electrophilic arylpalladium intermediate

An efficient method of palladium-catalyzed direct 5-arylation of 1,3-dimethyluracil was developed with a various range of aryl bromides including electron-deficient aryl bromides. 5-Aryluracil derivatives were obtained in moderate to good yields regioselectively most likely via an electrophilic metalation-deprotonation process.     

Use of Pd-catalyzed Suzuki-Miyaura coupling reaction in the rapid synthesis of 5-aryl-6-(phosphonomethoxy)uracils and evaluation of their inhibitory effect towards human thymidine phosphorylase

A number of new 5-aryl substituted pyrimidine acyclic nucleoside phosphonates were synthesized and tested for their ability to inhibit human TP. Their rapid synthesis using Pd-catalyzed Suzuki-Miyaura coupling reactions of various arylboronic acids with 5-bromo-4-(phosphonomethoxy)-2,6-dibutoxypyrimidine was successfully applied. For a series of 5-aryl-6-phosphonomethoxyuracils, an increased inhibitory effect was determined. This effect is supported by the results found for 4-fluorophenyl (K_i^dThd=4.89±0.62) and 3-nitrophenyl (K_i^dThd=3.98±0.46) substituents.     

Relationship between trans-column eddy diffusion and retention in liquid chromatography: Theory and experimental evidence

Experimental results demonstrate that trans-column eddy diffusion depends on the retention of compounds. The combination of elution profiles recorded in different points of the exit column cross-section and of the height equivalent to a theoretical plate (HETP) of small molecules clearly show a strong link between retention and column performance in liquid chromatography. These results validate a new model of trans-column eddy diffusion in packed columns. The contribution to the column HETP of the trans-column eddy diffusion term decreases with increasing retention factor from k′ = 0 to k′ = 3 above which it becomes negligible. The best column performance in RPLC is observed for the most retained compounds. This is due to the combination of the lack of a residual trans-column eddy diffusion contribution and the vanishing contribution of the instrument to band broadening.     

Modifying a graphene layer by a thymine or a uracil nucleobase: DFT studies

The hybridizations of a graphene layer by a thymine and a uracil nucleobase have been investigated by performing density functional theory (DFT) calculations. The isolated and hybrid structures have been firstly stabilized to reach the minimum energy and the electronic properties have been subsequently evaluated for the optimized structures. The structural and atomic scale parameters indicated that the tip of graphene is important in determining the properties of new hybrids. Moreover, different effects of thymine and uracil nucleobases have been identified in the hybrid structures. Quadrupole coupling constants have been evaluated to characterize the atomic scale properties, in which the most notable effects of hybridizations have been observed for the atoms close to the linking regions whereas negligible effects have been seen for other atoms.     

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     

Structural basis for molecular recognition,theoretical studies and anti-bacterial properties of three bis-uracil derivatives

Three bis-pyrimidine compounds (1, 2 & 3) have been synthesized by the reaction of 6-[(dimethylamino)methyleneamino]-1,3-dimethyluracil with three different aldehydes viz. p-methoxybenzaldehyde, p-nitrobenzaldehyde, and 2-thiophenecarboxaldehyde in aqueous media in presence of ‘green surfactant’ followed by recrystallization in EtOH. The compounds are characterized by elemental analyses, NMR and single crystal X-ray diffraction. N–H?O hydrogen bonds and weak C–H?O interactions are the main non-bonding interactions in the molecular structures of the three compounds. Details of the synthesis, spectroscopic data and structures of the three compounds are presented. Furthermore, we have rationalized some relevant noncovalent interaction involving the aromatic moieties by means of DFT calculations. Finally, we have also analysed the anti-bacterial properties of compounds 1–3 and compared to Ofloxacin drug. The anti-bacterial activity has been tested against Klebsiella pneumoniae, Staphylococcus aureus and Pseudomonas aeruginosa. All compounds are found to possess from moderate to good anti-bacterial properties (MIC 25–100 μg/ml).     

Uracil-coumarin based hybrid molecules as potent anti-cancer and anti-bacterial agents

In the current report, we have rationally designed a series of uracil-coumarin based bifunctional molecular hybrids roped by 1,2,3-triazole moiety. The designed compounds were synthesized and tested against a panel of six human cancer cell lines namely Colo-205, MCF-7, A-549, PA-1, PC-3 and Hela cells by Sulforhodamine B assay. The results indicated that the hybrid molecules can specifically inhibit the MCF-7 cancer cell proliferation amongst which A-2 was found to be most potent hybrid (GI₅₀ = 1.55 µM) with fluorine atom as R with two carbon chain length between triazole and coumarin moieties. Cell cycle analysis revealed that A-2 significantly arrest the G2/M phase to inhibit proliferation of MCF-7 cells. Due to its mitotic arrest, A-2 was further analyzed to predict its various binding interactions within the active site of tubulin, which revealed its best binding pattern within the vinblastine binding site. In addition to this, antibacterial potential of all the synthetics was also evaluated which resulted in two hit lead molecules A-2 (MIC = 11.7 μg/mL) and A-3 (MIC = 7.23 μg/mL) that can significantly inhibit the bacterial strain Staphylococcus aureus comparable to that of standard drug levofloxacin (MIC = 3.12 μg/mL). Binding interactions within the active site of dihydrofolate reductase (DHFR) were also streamlined by using molecular docking studies. Overall studies revealed some interesting features of synthetics to be active which stated that, the compounds with electronegative atom on R and compounds with two carbon chain length between triazole and coumarin showed best results.     

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.