The stability and reactivity of activated acryloylcarbamates as reagents for the synthesis of N‐1 substituted thymine and uracil – an NMR and DFT study

The mechanism of the decomposition of acryloylcarbamates 7a–b yielding highly reactive isocyanates 3a–b was proposed based on NMR measurements and quantum chemical calculations. A good agreement between the experimental kinetic data and DFT calculations allowed us to demonstrate that the stability of 7a–d depends on the presence of methyl in the acryloyl moiety and the position of the nitro group in the nitrophenolic part of the molecule. Furthermore, the reactivity of 7a–d with weakly nucleophilic and sterically hindered 2,4,6‐tri‐tert‐butylaniline was explored by ¹H NMR demonstrating the usefulness of reagents 7a–d offering access to a variety of 1‐N‐substituted uracils and thymines with potentially interesting biological properties. Copyright © 2010 John Wiley & Sons, Ltd.     

Analysis of vibrational spectra of methyl-substituted uracils in the anharmonic approximation

We have analyzed the vibrational spectra of uracil and its methyl-substituted derivatives using the DFT/B3LYP/6-31G(p,d) method, in the anharmonic approximation. We have shown that it is possible to use second-order anharmonic theory of vibrational spectra in predictive calculations for substituted uracils. __________ Translated from Zhurnal Prikladnoi Spektroskopii, Vol. 73, No. 4, pp. 431–436, July–August, 2006.     

Synthesis of novel annulated uracils via domino Knoevenagel-hetero-Diels-Alder reaction in aqueous media

An efficient synthesis of tetracyclic uracil derivatives (polycyclic pyrans) is achieved via domino Knoevenagel-hetero-Diels-Alder reactions of O-propargylated salicylaldehyde derivatives with 1,3-dimethylbarbituric acid in water as solvent in the presence of CuI. The products are formed in good yields.     

Uracil Grafted Carbon Electrode:Electrocatalytic Behavior of Tryptophan,Tyrosine, Catecholamine and Related Compounds

基于尿嘧啶作为一种碱基,具备一定的分子识别能力,制备了一种新颖的尿嘧啶共价修饰电极,用X射线光电子能谱和电化学方法进行了表征,并研究了酪氨酸、色氨酸、儿茶酚胺（如多巴胺,肾上腺素,去甲肾上腺素）及相关的化合物尿酸、抗坏血酸在该电极上的电化学行为,获得相应的氧化电位、电流灵敏度、线性范围和检测限等信息。其中,色氨酸检测线性范围：1.8 - 120 mM,检测限（s/n=3）：0.8 mM;酪氨酸检测线性范围：1.8 - 89mM,检测限（s/n=3）：0.8 mM。实验表明,尿嘧啶修饰电极能催化氧化上述电活性物质,但催化能力不同,据此,我们讨论了尿嘧啶与上述物质的相互作用,详细探讨了催化机理,扩展了对基于分子识别的传感器的研究。     

Density functional study of guanine and uracil quartets and of guanine quartet/metal ion complexes

The structures and interaction energies of guanine and uracil quartets have been determined by B3LYP hybrid density‐functional calculations. The total interaction energy ΔE^T of the C_4h‐symmetric guanine quartet consisting of Hoogsteen‐type base pairs with two hydrogen bonds between two neighbor bases is −66.07 kcal/mol at the highest level. The uracil quartet with C6 H6O4 interactions between the individual bases has only a small interaction energy of −20.92 kcal mol⁻¹, and the interaction energy of −24.63 kcal/mol for the alternative structure with N3 H3O4 hydrogen bonds is only slightly more negative. Cooperative effects contribute between 10 and 25% to all interaction energies. Complexes of metal ions with G‐quartets can be classified into different structure types. The one with Ca²⁺ in the central cavity adopts a C_4h‐symmetric structure with coplanar bases, whereas the energies of the planar and nonplanar Na⁺ complexes are almost identical. The small ions Li⁺, Be²⁺, Cu⁺, and Zn²⁺ prefer a nonplanar S₄‐symmetric structure. The lack of coplanarity prevents probably a stacking of these base quartets. The central cavity is too small for K⁺ ions and, therefore, this ion favors in contrast to all other investigated ions a C₄‐symmetric complex, which is 4.73 kcal/mol more stable than the C_4h‐symmetric one. The distance 1.665 Å between K⁺ and the root‐mean‐square plane of the guanine bases is approximately half of the distance between two stacked G‐quartets. The total interaction energy of alkaline earth ion complexes exceeds those with alkali ions. Within both groups of ions the interaction energy decreases with an increasing row position in the periodic table. The B3LYP and BLYP methods lead to similar structures and energies. Both methods are suitable for hydrogen‐bonded biological systems. Compared with the before‐mentioned methods, the HCTH functional leads to longer hydrogen bonds and different relative energies for two U‐quartets. Finally, we calculated also structures and relative energies with the MMFF94 forcefield. Contrary to all DFT methods, MMFF94 predicts bifurcated C HO contacts in the uracil quartet. In the G‐quartet, the MMFF94 hydrogen bond distances N2 H22N7 are shorter than the DFT distances, whereas the N1 H1O6 distances are longer. © 2000 John Wiley & Sons, Inc. J Comput Chem 22: 109–124, 2001     

The mechanism of double proton transfer in dimers of uracil and 2-thiouracil--the reaction force perspective

The intermolecular double proton transfer in dimers of uracil and 2-thiouracil is studied through density functional theory calculations. The reaction force framework provides the basis for characterizing the mechanism that in all cases has been associated to a dynamic balance between polarization and charge transfer effects. It has been found that the barriers for proton transfer depend upon the nature of the acceptor atoms and its position within the seminal monomer. Actually, the change in the nature of the hydrogen bonds connecting the two monomers along the reaction coordinate may favor or disfavor the double-proton transfer.     

Photophysical Deactivation Mechanisms of the Pyrimidine Analogue 1-Cyclohexyluracil

The photophysical relaxation mechanisms of 1-cyclohexyluracil, in vacuum and water, were investigated by employing the Multi-State CASPT2 (MS-CASPT2, Multi-State Complete Active-Space Second-Order Perturbation Theory) quantum chemical method and Dunning’s cc-pVDZ basis sets. In both environments, our results suggest that the primary photophysical event is the population of the S11(ππ*) bright state. Afterwards, two likely deactivation pathways can take place, which is sustained by linear interpolation in internal coordinates defined via Z-Matrix scans connecting the most important characteristic points. The first one (Route 1) is the same relaxation mechanism observed for uracil, its canonical analogue, i.e., internal conversion to the ground state through an ethylenic-like conical intersection. The other route (Route 2) is the direct population transfer from the S11(ππ*) bright state to the T23(nπ*) triplet state via an intersystem crossing process involving the (S11(ππ*)/T23(nπ*))STCP singlet-triplet crossing point. As the spin-orbit coupling is not too large in either environment, we propose that most of the electronic population initially on the S11(ππ*) state returns to the ground following the same ultrafast deactivation mechanism observed in uracil (Route 1), while a smaller percentage goes to the triplet manifold. The presence of a minimum on the S11(ππ*) potential energy hypersurface in water can help to understand why experimentally it is noticed suppression of the triplet states population in polar protic solvent.     

HIV-1 RT抑制剂研究I.1,3-二苄基-6-(3,4-环氧丁基)尿嘧啶的合成

报道了1,3-二苄基-6-(3,4-环氧丁基)尿嘧啶的合成新方法.以6-甲基尿嘧啶(1)为起始物,经1,3-二苄基-6-甲基尿嘧啶(2)及未见文献报道的1,3-二苄基-6-(3-丁烯基)尿嘧啶(3)和1,3-二苄基-6-(3-羟基-4-溴丁基)尿嘧啶(4),首次高收率合成了1,3-二苄基-6-(3,4-环氧丁基)尿嘧啶(5),并对其化学结构进行了表征.     

Synthesis of poly(alkylene phosphate)s bearing uracil moiety in the main chain

Poly(alkylene phosphate)s bearing regularly distributed uracil moiety in the main chain have been obtained. The synthetic procedure consists of condensation of bis(diethylamino)-methoxyphosphine with N¹,N³-bis(2′-hydroxyethyl) uracil followed by oxidation, dealkylation, and transformation to the resulting sodium polysalt. The final polymer ($\bar M_n \approx 10^4 $) as well as the intermediate products were characterized by ¹H-, ¹³C-, and ³¹P-NMR spectroscopy.     

Structure and Reactivity of Uracil Derivatives. 2. Ambident Nucleophilic Reactivity of 5-Diazouracil

On the basis of 3-21G type ab initio calculations we have studied all the possible complexes of 5-diazouracil with boron trifluoride. The most stable of these are the systems with the BF₃ coordinated at the 3, 9, and 10 positions of the heterocyclic molecule.