核酸碱基与甘氨酸二肽间氢键作用的最佳位点

优化得到了碱基腺嘌呤、胸腺嘧啶、尿嘧啶、鸟嘌呤及胞嘧啶与甘氨酸二肽分子形成的28个氢键复合物的稳定结构并计算了结合能, 探讨了五种碱基与甘氨酸二肽分子间氢键作用的最佳位点. 本文研究发现: 每种碱基均可以通过不同位点与二肽分子形成氢键复合物, 腺嘌呤、胸腺嘧啶、尿嘧啶、鸟嘌呤及胞嘧啶分别最倾向使用A3、T1、U1、G3及C1位点与甘氨酸二肽分子形成氢键复合物; 碱基分子某位点的质子化反应焓变越负所形成的氢键复合物越稳定, 去质子化反应焓变越小所形成的氢键复合物越稳定; 由氢键复合物的结合能计算得到的稳定性次序与由碱基分子质子化和去质子化反应焓变推得的稳定性次序一致.     

槲皮素与腺嘌呤氢键作用的最佳位点

本文优化得到了16个由槲皮素与腺嘌呤形成的氢键复合物的稳定结构,并计算了它们的结合能.研究发现,在气相和水相中,槲皮素均通过qu1位点与腺嘌呤作用形成稳定的氢键复合物.比较了腺嘌呤与槲皮素形成的氢键复合物、腺嘌呤与胸腺嘧啶形成的Watson-Crick碱基对的相对稳定性.在气相条件下Watson-Crick碱基对更稳定,在水相条件下腺嘌呤与槲皮素形成的氢键复合物更稳定,说明水相条件下腺嘌呤与槲皮素之间的相互作用强于与胸腺嘧啶之间的相互作用.基于标准反应Gibbs自由能变的计算结果估算了水相条件下腺嘌呤与槲皮素形成的氢键复合物和Watson-Crick碱基对的相对平衡浓度.     

取代基对腺嘌呤与胸腺嘧啶氢键复合物体系结合能的影响

优化得到了17个取代胸腺嘧啶与腺嘌呤形成的氢键复合物的结构, 并计算了这些复合物的结合能, 探讨了胸腺嘧啶上不同取代基对结合能的影响. 结果表明, CF₃取代的胸腺嘧啶与腺嘌呤间的结合能大于胸腺嘧啶与腺嘌呤间的结合能, 这可能是屈氟尿苷具有阻止病毒及肿瘤扩散功能的原因所在. SO₃H, CN和NO₂取代的胸腺嘧啶与腺嘌呤间具有更大的结合能, 表明这3个基团取代的胸腺嘧啶也可能具有潜在的抗肿瘤作用. 分子中原子理论与自然键轨道分析表明, 在所有体系中, 氢键N—H…N最强, N—H…O=C次之, C—H…O=C最弱, 轨道作用在氢键作用中占有重要地位.     

取代基对腺嘌呤与胸腺嘧啶氢键复合物体系结合能的影响简

优化得到了17个取代胸腺嘧啶与腺嘌呤形成的氢键复合物的结构,并计算了这些复合物的结合能,探讨了胸腺嘧啶上不同取代基对结合能的影响. 结果表明,CF3取代的胸腺嘧啶与腺嘌呤间的结合能大于胸腺嘧啶与腺嘌呤间的结合能,这可能是屈氟尿苷具有阻止病毒及肿瘤扩散功能的原因所在. SO3H,CN和NO2取代的胸腺嘧啶与腺嘌呤间具有更大的结合能,表明这3个基团取代的胸腺嘧啶也可能具有潜在的抗肿瘤作用. 分子中原子理论与自然键轨道分析表明,在所有体系中,氢键N—H…N最强,N—H…O=C次之,C—H…O=C最弱,轨道作用在氢键作用中占有重要地位.     

精氨酸侧链和核酸碱基间离子氢键作用强度分析

采用MP2/6-31+G(d,p)方法优化得到了22个由精氨酸侧链与碱基尿嘧啶、 胸腺嘧啶、 胞嘧啶、 鸟嘌呤及腺嘌呤形成的氢键复合物的气相稳定结构, 使用包含BSSE校正的MP2/aug-cc-pVTZ方法计算得到了复合物的气相结合能, 通过MP2/6-31+G(d,p)方法和PCM模型优化得到了复合物的水相稳定结构, 采用MP2/aug-cc-pVTZ方法和PCM模型计算得到了复合物的水相结合能. 研究发现, 精氨酸侧链与碱基间的离子氢键作用强度与单体间电荷转移量、 氢键临界点电子密度及二阶作用稳定化能密切相关. 与中性氢键相比, 离子氢键作用具有更显著的共价作用成分. 研究还发现, 精氨酸侧链和碱基间形成的氢键复合物的稳定性次序可以通过氢键受体碱基分子上氧原子和氮原子的质子化反应焓变进行预测, 质子化反应焓变越负, 形成的氢键复合物越稳定.     

碱基腺嘌呤与多肽酰胺间氢键作用的最佳位点

正确理解核酸碱基和蛋白质多肽间的作用机制有助于人们利用这些生物分子有效地进行分子设计,进而制备具有特殊纳米结构和功能的生物分子材料.本文优化得到了碱基腺嘌呤与N-甲基乙酰胺、甘氨酸二肽、丙氨酸二肽形成的20个氢键复合物的结构并计算了结合能,探讨了腺嘌呤与多肽酰胺间氢键作用的最佳位点.研究发现:腺嘌呤可以使用两个不同位点(A1位点和A2位点)与N-甲基乙酰胺形成N―H…N型或者N―H…O=C型氢键复合物,腺嘌呤使用A1位点与N-甲基乙酰胺形成的N―H…N型氢键复合物更稳定;二肽分子可以使用主链上两个不同位点(丙氨酸的Ala7位点和Ala5位点或者甘氨酸的Gly7位点和Gly5位点)与腺嘌呤形成含有N―H…N和N―H…O=C两条氢键的复合物,二肽分子使用Ala7或Gly7位点与腺嘌呤形成的氢键复合物更稳定;腺嘌呤与多肽间的氢键作用强于其与N-甲基乙酰胺的作用.基于分子中的原子理论与自然键轨道计算结果分析了氢键作用的本质.     

二乙二醇二甲基丙烯酸酯交联的胸腺嘧啶分子印迹聚合物纤维素支撑膜对核酸碱基分子选择性研究

使用光度分析法探讨了功能单体9-乙烯腺嘌呤和模板分子胸腺嘧啶在甲醇中的结合作用。在此基础上，以二乙二醇二甲基丙烯酸酯为交联剂，纤维素膜为支持体，制备了分子印迹聚合物膜。通过扫描电镜观察并比较了分子印迹聚合物膜、非分子印迹聚合物膜和纤维素载体膜通道的差异，以胸腺嘧啶、尿嘧啶、胞嘧啶、鸟嘌呤和腺嘌呤为底物，评价了印迹聚合物膜的渗透选择性。结果表明分子印迹膜对模板分子胸腺嘧啶及结构类似物尿嘧啶呈现高的选择性，与用乙二醇二甲基丙烯酸酯为交联剂制备的分子印迹膜比较，也呈现高的扩散速率和选择性，因此该膜对生物样品DNA完全水解产物胸腺嘧啶和RNA水解产物尿嘧啶的识别展现了良好的应用前景。     

带电组氨酸侧链与DNA碱基间非键作用强度的理论研究

采用MP2方法和6-31+G(d,p)基组优化得到了带有一个正电荷的组氨酸侧链与4个DNA碱基间形成的18个氢键复合物的气相稳定结构, 从文献中获取了组氨酸侧链与DNA碱基间形成的12个堆积和T型复合物的气相稳定结构, 使用包含基组重叠误差(BSSE)校正的MP2方法和aug-cc-pVTZ基组及密度泛函理论M06-2X-D3方法和aug-cc-pVDZ基组计算了这些复合物的结合能. 研究结果表明, 包含BSSE校正的M06-2X-D3方法和aug-cc-pVDZ基组能够给出较准确的结合能; 气相条件下, 组氨酸侧链与同种DNA碱基间的离子氢键作用明显强于堆积作用和T型作用, 组氨酸侧链最易通过离子氢键与胞嘧啶C和鸟嘌呤G作用形成氢键复合物, 组氨酸与胞嘧啶C和鸟嘌呤G间的T型作用强于与腺嘌呤A和胸腺嘧啶T间的离子氢键作用; 水相条件下, 组氨酸侧链与同种DNA碱基间的离子氢键作用仍明显强于堆积作用和T型作用, 组氨酸侧链更易与胞嘧啶C和鸟嘌呤G相互作用形成氢键复合物, 但是最强的组氨酸侧链与胞嘧啶C间的T型作用明显弱于与腺嘌呤A和胸腺嘧啶T间的离子氢键作用, 说明水相条件下组氨酸侧链与DNA碱基间主要通过离子氢键作用形成氢键复合物.     

取代基对1-甲基尿嘧啶与N-甲基乙酰胺氢键复合物中氢键强度的影响

使用密度泛函理论B3LYP方法和二阶微扰理论MP2方法对由1-甲基尿嘧啶与N-甲基乙酰胺所形成的氢键复合物中的氢键强度进行了理论研究, 探讨了不同取代基取代氢键受体分子1-甲基尿嘧啶中的氢原子对氢键强度的影响和氢键的协同性. 研究表明: 供电子取代基使N－H…O＝C氢键键长r(H…O)缩短, 氢键强度增强; 吸电子取代基使N－H…O＝C氢键键长r(H…O)伸长, 氢键强度减弱. 自然键轨道(NBO)分析表明: 供电子基团使参与形成氢键的氢原子的正电荷增加, 使氧原子的负电荷增加, 使质子供体和受体分子间的电荷转移量增多; 吸电子基团则相反. 供电子基团使N－H…O＝C氢键中氧原子的孤对电子轨道n(O)对N－H的反键轨道σ^*(N－H)的二阶相互作用稳定化能增强, 吸电子基团使这种二阶相互作用稳定化能减弱. 取代基对与其相近的N－H…O＝C氢键影响更大.     

儿茶素-胞嘧啶分子间相互作用的密度泛函研究

采用密度泛函理论的B3LYP方法,在6-31+G*基组水平上研究了儿茶素-胞嘧啶分子间相互作用机制,得到稳定的儿茶素-胞嘧啶复合物11个.计算结果表明氢键对于复合物的稳定性起着重要的作用,并且当复合物形成2个或更多的氢键时,氢键的类型及强度共同决定着复合物的稳定性.我们还应用了分子中的原子(AIM)理论和自然键轨道(NBO)理论对这11种复合物中氢键的性质和特征进行了分析.通过研究发现,所有的氢键复合物进行基组重叠误差(BSSE)校正后的相互作用能为-17.35～-43.27kJ/mol,相互作用能主要由氢键所贡献.振动分析显示,氢键的形成使相对应键的对称伸缩振动频率减小,说明这些复合物中形成的氢键都是正常的红移型氢键,与实验结果相一致.     

Investigation of proton transport tautomerism in clusters of protonated nucleic acid bases (cytosine, uracil, thymine, and adenine) and ammonia by high-pressure mass spectrometry and ab initio calculations

The energetics of the ion-molecule interactions and structures of the clusters formed between protonated nucleic acid bases (cytosine, uracil, thymine, and adenine) and ammonia have been studied by pulsed ionization high-pressure mass spectrometry (HPMS) and ab initio calculations. For protonated cytosine, uracil, thymine, and adenine with ammonia, the measured enthalpies of association with ammonia are -21.7, -27.9, -22.1, and -17.5 kcal mol-1, respectively. Different isomers of the neutral and protonated nucleic acid bases as well as their clusters with ammonia have been investigated at the B3LYP/6-31+G(d,p) level of theory, and the corresponding binding energetics have also been obtained. The potential energy surfaces for proton transfer and interconversion of the clusters of protonated thymine and uracil with ammonia have been constructed. For cytosine, the experimental binding energy is in agreement with the computed binding energy for the most stable isomer, CN01-01, which is derived from the enol form of protonated cytosine, CH01, and ammonia. Although adenine has a proton affinity similar to that of cytosine, the binding energy of protonated adenine to ammonia is much lower than that for protonated cytosine. This is shown to be due to the differing types of hydrogen bonds being formed. Similarly, although uracil and thymine have similar structures and proton affinities, the binding energies between the protonated species and ammonia are different. Strikingly, the addition of a single methyl group, in going from uracil to thymine, results in a significant structural change for the most stable isomers, UN01-01 and TN03-01, respectively. This then leads to the difference in their measured binding energies with ammonia. Because thymine is found only in DNA while uracil is found in RNA, this provides some potential insight into the difference between uracil and thymine, especially their interactions with other molecules.     

肾上腺素与二甲亚砜氢键作用的理论研究

The hydrogen bond is one of the most important intermolecular interactions playing an important role in intermolecular recognition processes essential to most biological systems. Adrenaline is an important catecholamine neurotransmitter in the mammalian central nervous system. Dimethyl sulphoxide can carry with it drugs across membranes. The geometries of adrenaline and six stable 1 : 1 complexes formed between adrenaline and dimethyl sulphoxide were optimized by Berny method at PM3 level and thus were optimized by density functional theory（B3LYP method）at the 6-31G,6-31G*,and 6-31+G* level respectively to obtain accurate structures. Single-point energies of all optimized molecular geometries were calculated to discuss the energies and structural parameters between reactants and products. All the binding energies have been corrected by the zero point vibrational energies（ZPVE）at varied basis set levels from 6-31G to 6-31 + G*. The results indicated that stronger hydrogen-bonded complexes were formed by molecular interaction between adrenaline and dimethyl sulphoxide. The calculation results can be better used to explain some experimental phenomena.     

Natural resonance structures and aromaticity of the nucleobases

Natural resonance theory (NRT) and nucleus- independent chemical shift (NICS) analyses have been applied to the standard nucleobases adenine, guanine, cytosine, uracil, and thymine. The molecular electron densities were obtained from density functional theory calculations at the B3LYP level and ab initio calculations at the HF, MP2, and CCD levels. Compared with the dominance of the two Kekulé structures in benzene, the structural modifications in the forms of endocyclic heteroatoms and exocyclic substituents introduce various degrees of charge separation in nucleobases. As a result, the leading resonance structures for cytosine, uracil, and thymine are found to be covalent structures, but their weightings decrease to ~30% in the NRT expansion. For adenine and guanine, the covalent structures have weightings of ~20%, and the leading ionic resonance structures have weightings of as high as about 8%. Methods that include electron correlation effects, B3LYP, MP2, and CCD, give smaller weightings for the covalent structures than HF. However, MP2 and CCD results often include “strange” resonance structures with connections between unbonded vicinal atoms, making DFT at the B3LYP level the better choice for calculating these molecules’ electron density. The NICS at the ring center shows that the six-membered rings in cytosine, uracil, thymine, and guanine are nonaromatic with NICS within − 3 to − 1 ppm, while it is − 7.3 ppm for the six-membered ring in adenine. The NICS of the five-membered rings of adenine and guanine is around − 12 ppm, a slight decrease from the value of − 15.0 ppm for pyrrole.     

C6H5—H…X分子间氢键的理论计算

利用密度泛函理论B3LYP方法, 在6-311+G(3df,2p)水平上对C6H5—H…X型分子间氢键进行了几何构型优化、氢键相互作用能、电子密度分布等计算. 其中C6H6为质子供体, HCOH、H2O、NH3、CH2NH和HCN为质子受体. 从电荷布居分析、自然键轨道等角度详细地讨论了C6H5—H…X 体系中, 共轭π键、O和N的不同键型结构对氢键形成的影响以及孤电子对与C—H 反键轨道之间的相互作用(n→σ*)等.     

Interactions of nucleobases with alkali earth metal cations--electrospray ionization mass spectrometric study

Interactions of nucleobases with alkali earth metal cations have been studied by electrospray ionization mass spectrometry (ESI-MS). Nucleobases containing at least one oxygen atom form stable complexes with alkali earth metal cations. This phenomenon can be explained on the grounds of the well known theory of hard and soft acids and bases. Uracil and thymine make complexes only when in their deprotonoted forms. The cations of great radii (Sr(2+), Ba(2+)) are more prone to form complexes of stoichiometry 1:1 with uracil and thymine than the cations of small radii (Mg(2+), Ca(2+)). On the other hand, Mg(2+) forms complexes of stoichiometry 2:1 and 3:2 with uracil and thymine. Gas-phase stabilities of the 1:1 complexes are higher for the cations of small radii, in contrast to the solution stabilities. For cytosine and 9- methylhypoxantine the 1:1 complexes of their deprotonated forms are observed at higher cone voltage as a result of HCl molecule loss from the complexes containing the counter ion (Cl(-)). In solution, more stable complexes are formed with metal cations of low radii. Gas-phase stability of the complexes formed by deprotonated 9- methyl-hypoxantine increases with increasing metal cation radius.     

Density Functional Theory Study on Interaction between Catechin and Thymine

The interacting patterns and mechanism of the catechin and thymine have been investigated with the density functional theory Becke's three-parameter nonlocal exchange functional and the Lee, Yang, and Parr nonlocal correlation functional (B3LYP) method by 6-31+G*basis set. Thirteen stable structures for the catechin-thymine complexes have been found which form two hydrogen bonds at least. The vibrational frequencies are also studied at the same level to analyze these complexes. The results indicated that catechin interactedwith thymine by three different hydrogen bonds as N-H…O、C-H…O、O-H…O and the complexes are mainly stabilized by the hydrogen bonding interactions. Theories of atoms in molecules and natural bond orbital have been adopted to investigate the hydrogen bondsinvolved in all systems. The interaction energies of all complexes have been corrected for basis set superposition error, which are from -18.15 kJ/mol to -32.99 kJ/mol. The results showed that the hydrogen bonding contribute to the interaction energies dominantly. The corresponding bonds stretching motions in all complexes are red-shifted relative to that of the monomer, which is in agreement with experimental results.