Möbius环并苯的分子对称性

一般来说, 点群理论认为Möbius带环分子最高的对称性只能是C₂. 本文讨论了由18个苯环组成的环并苯的异构体分子, 包括柱面的Hückel型分子(HC-[18])和扭转180°的Möbius带环分子(MC-[18]). 结果表明除了点对称性外, Möbius带环分子还存在一种可称为环面螺旋旋转(TSR)变换的对称性, 为此还引用了环面正交曲线坐标系. 此外, 还讨论了这些分子关于TSR对称性匹配的原子集和原子轨道(AO)集. 根据TSR对称性的循环群特征, 可以建立此类群的不可约表示及有关特征标. 这类分子的分子轨道(MO)关于TSR群的不可约表示是纯的, 然而所含的相应的原子轨道对称性匹配的线性组合(SALC-AO)成分可以是多种的.     

Aminoglycoside complexation with a DNA.RNA hybrid duplex: the thermodynamics of recognition and inhibition of RNA processing enzymes

Spectroscopic and calorimetric techniques were employed to characterize and contrast the binding of the aminoglycoside paromomycin to three octamer nucleic acid duplexes of identical sequence but different strand composition (a DNA.RNA hybrid duplex and the corresponding DNA.DNA and RNA.RNA duplexes). In addition, the impact of paromomycin binding on both RNase H- and RNase A-mediated cleavage of the RNA strand in the DNA.RNA duplex was also determined. Our results reveal the following significant features: (i) Paromomycin binding enhances the thermal stabilities of the RNA.RNA and DNA.RNA duplexes to similar extents, with this thermal enhancement being substantially greater in magnitude than that of the DNA.DNA duplex. (ii) Paromomycin binding to the DNA.RNA hybrid duplex induces CD changes consistent with a shift from an A-like to a more canonical A-conformation. (iii) Paromomycin binding to all three octamer duplexes is linked to the uptake of a similar number of protons, with the magnitude of this number being dependent on pH. (iv) The affinity of paromomycin for the three host duplexes follows the hierarchy, RNA.RNA > DNA.RNA > DNA.DNA. (v) The observed affinity of paromomycin for the RNA.RNA and DNA.RNA duplexes decreases with increasing pH. (vi) The binding of paromomycin to the DNA.RNA hybrid duplex inhibits both RNase H- and RNase A-mediated cleavage of the RNA strand. We discuss the implications of our combined results with regard to the specific targeting of DNA.RNA hybrid duplex domains and potential antiretroviral applications.     

The application of DNA and RNA G-quadruplexes to therapeutic medicines

The intriguing structural diversity in folded topologies available to guanine-rich nucleic acid repeat sequences have made four-stranded G-quadruplex structures the focus of both basic and applied research, from cancer biology and novel therapeutics through to nanoelectronics. Distributed widely in the human genome as targets for regulating gene expression and chromosomal maintenance, they offer unique avenues for future cancer drug development. In particular, the recent advances in chemical and structural biology have enabled the construction of bespoke selective DNA based aptamers to be used as novel therapeutic agents and access to detailed structural models for structure based drug discovery. In this critical review, we will explore the important underlying characteristics of G-quadruplexes that make them functional, stable, and predictable nanoscaffolds. We will review the current structural database of folding topologies, molecular interfaces and novel interaction surfaces, with a consideration to their future exploitation in drug discovery, molecular biology, supermolecular assembly and aptamer design. In recent years the number of potential applications for G-quadruplex motifs has rapidly grown, so in this review we aim to explore the many future challenges and highlight where possible successes may lie. We will highlight the similarities and differences between DNA and RNA folded G-quadruplexes in terms of stability, distribution, and exploitability as small molecule targets. Finally, we will provide a detailed review of basic G-quadruplex geometry, experimental tools used, and a critical evaluation of the application of high-resolution structural biology and its ability to provide meaningful and valid models for future applications (255 references).     

M(o)bius环并苯的分子对称性

一般来说,点群理论认为M(o)bius带环分子最高的对称性只能是C2.本文讨论了由18个苯环组成的环并苯的异构体分子,包括柱面的Hückel型分子(HC-[18])和扭转180°的M(o)bius带环分子(MC-[18]).结果表明除了点对称性外,M(o)bius带环分子还存在一种可称为环面螺旋旋转(TSR)变换的对称性,为此还引用了环面正交曲线坐标系.此外,还讨论了这些分子关于TSR对称性匹配的原子集和原子轨道(AO)集.根据TSR对称性的循环群特征,可以建立此类群的不可约表示及有关特征标.这类分子的分子轨道(MO)关于TSR群的不可约表示是纯的,然而所含的相应的原子轨道对称性匹配的线性组合(SALC-AO)成分可以是多种的.     

Action of trypsin on a nucleoprotein from sturgeon gonads

A nucleoprotein has been isolated from the gonads of the Caspian sturgeon and its composition has been determined. It has been shown that it contains 55% of DNA, 2% of RNA, 36% of protamines, and about 7% of nonprotamine proteins of nonbasic nature. The nucleoprotein has been hydrolyzed with trypsin, and the amino acid compositions of some hydrolysis products have been studied. On the basis of the results obtained, the hypothesis has been put forward of a possible linkage of the DNA with the basic proteins. It has been shown that protamines react with the DNA through the basic amino acid residues located at various regions of their molecules.     

Oxidation of 5-hydroxy-2'-deoxyuridine into isodialuric acid, dialuric acid, and hydantoin products

Oxidation products of cytosine, including 5-hydroxycytosine and 5-hydroxyuracil, are highly susceptible to subsequent oxidation. Here, the oxidation products of 5-hydroxy-2'-deoxyuridine have been studied by NMR and MS analyses. The initial products were diastereomers of isodialuric acid nucleoside. These products subsequently decomposed into corresponding dialuric acid derivatives at neutral pH. The position of the carbonyl and hydroxyl groups, at C5 and C6 for isodialuric acid and at C6 and C5 for dialuric acid derivatives, respectively, was determined by 1H- and 13C NMR analyses. In addition, these analyses revealed that the carbonyl groups of both isodaluric and dialuric acid derivatives exist in their fully hydrated form in aqueous solution. Finally, the dialuric acid derivatives were observed to undergo subsequent decomposition into the corresponding 5-hydroxyhydantoin derivatives. Studies of a trinucleotide containing 5-hydroxyuracil suggest that the reactions described herein for the monomer can be extrapolated to DNA.     

Evaluation of DNA bending models in their capacity to predict electrophoretic migration anomalies of satellite DNA sequences

DNA containing a sequence that generates a local curvature exhibits a pronounced retardation in electrophoretic mobility. Various theoretical models have been proposed to explain relationship between DNA structural features and migration anomaly. Here, we studied the capacity of 15 static wedge‐bending models to predict electrophoretic behavior of 69 satellite monomers derived from four divergent families. All monomers exhibited retarded mobility in PAGE corresponding to retardation factors ranging 1.02–1.54. The curvature varied both within and across the groups and correlated with the number, position, and lengths of A‐tracts. Two dinucleotide models provided strong correlation between gel mobility and curvature prediction; two trinucleotide models were satisfactory while remaining dinucleotide models provided intermediate results with reliable prediction for subsets of sequences only. In some cases, similarly shaped molecules exhibited relatively large differences in mobility and vice versa. Generally less accurate predictions were obtained in groups containing less homogeneous sequences possessing distinct structural features. In conclusion, relatively universal theoretical models were identified suitable for the analysis of natural sequences known to harbor relatively moderate curvature. These models could be potentially applied to genome wide studies. However, in silico predictions should be viewed in context of experimental measurement of intrinsic DNA curvature.     

Crystallographic modelling

Summary The project on crystallographic modelling aims at extending the application of interactive graphics to inorganic structures. Starting from the available expertise in organic and protein modelling, the symmetry of the crystal structure is used not only to draw fixed models of many unit cells of the structure, which as an entity can be interactively manipulated, but also to change details of the structures interactively with retention of the original symmetry. Real-time shifts of atom positions are automatically applied to all symmetryequivalent atoms given the symmetry constraints. This also applies to translations and rotations of groups of atoms. In order to get feedback about these structural changes one can simulate powder diffraction patterns in real-time mode and compare them with the experimental powder patterns. These features are crucial in truly crystallographic modelling, but have not been implemented before in other programs. The program can be used in combination with standard molecular modelling programs and is also interfaced to the Inorganic Crystal Structure Database. Before describing the realization of these features on state-of-the-art hardware, we will review the expertise in molecular modelling and discuss an MS-DOS program to study inorganic crystal structures.     

Action of trypsin on a nucleoprotein from sturgeon gonads

A nucleoprotein has been isolated from the gonads of the Caspian sturgeon and its composition has been determined. It has been shown that it contains 55% of DNA, 2% of RNA, 36% of protamines, and about 7% of nonprotamine proteins of nonbasic nature. The nucleoprotein has been hydrolyzed with trypsin, and the amino acid compositions of some hydrolysis products have been studied. On the basis of the results obtained, the hypothesis has been put forward of a possible linkage of the DNA with the basic proteins. It has been shown that protamines react with the DNA through the basic amino acid residues located at various regions of their molecules.M. V. Lomonosov Moscow State University. Translated from Khimiya Prirodnykh Soedinenii, No. 4, pp. 549–553, July–August, 1979.     

Host-lattice effects on the electron spin resonance spectra of copper(II) complexes in diluted and undiluted forms

ESR spectra of the Cu²⁺ ion, doped in a di-[(2-aminoethyl)amine)]-di-isothiocyanato-cadmate(II) lattice in its single-crystal form, have been investigated. Cd(den) (SCN)₂ has unusual coordination, in that two separate CdN₆ and CdN₄S₂ entities are present in the unit cell. Cu²⁺ substitutes predominantly for the CdN₆ structural unit, and spectra recorded at both ambient and liquid-nitrogen temperatures are fitted to a spin-Hamiltonian of orthorhombic symmetry. In contrast, the weak spectral lines corresponding to the Cu²⁺ ions which substitute for the CdN₄S₂ structural unit are characteristic of axial symmetry. A single-crystal study was also made on di-[(2-aminoethyl)amine]-di-isothiocyanato- copper(II), in which the Cu₂₊ ion has a coordination number of five and “C_2v” point symmetry. A comparison of the spectral features shown in the two lattices was made and some interesting conclusions are drawn.     

Theoretical analysis of antisense duplexes: determinants of the RNase H susceptibility

The structure and dynamic properties of different antisense related duplexes (DNA x RNA, 2'O-Me-DNA x RNA, 2'F-ANA x RNA, C5(Y)-propynyl-DNA x RNA, ANA x RNA, and control duplexes DNA x DNA and RNA x RNA) have been determined by means of long molecular dynamics simulations (covering more than 0.5 micros of fully solvated unrestrained MD simulation). The massive analysis presented here allows us to determine the subtle differences between the different duplexes, which in all cases pertain to the same structural family. This analysis provides information on the molecular determinants that allow RNase H to recognize and degrade some of these duplexes, whereas others with apparently similar conformations are not affected. Subtle structural and deformability features define the key properties used by RNase H to discriminate between duplexes.     

吡咯亚胺配体与过渡金属的反应性及其催化烯烃聚合

在经典的Brookhart吡啶双亚胺后过渡金属烯烃聚合催化剂基础上,用吡咯五元环代替吡啶六元环骨架可得到具有不同电子效应的新型吡咯亚胺配体.通过吡咯环特殊的电子效应和位阻效应可设计出种类繁多的有别于吡啶亚胺配体的配合物.综述了吡咯亚胺配体与前过渡金属(Ti,Zr等)、后过渡金属(Fe,Co,Ni,Pd等)、稀土金属(Y...     

Unsaturated Molecules Containing Main Group Metals

Molecules in which there are neighboring electrophilic and nucleophilic centers are unusually reactive. Oligomerization can be prevented only by bulky groups attached to the main group metal atom that would act as electron pair acceptor, or to the basic non-metal atom. The basic and the acid centers behave as a single unit in chemical reactions; the system is similar to a “double bond” whose π-electron density is largely concentrated at one atom. The unsaturated nature of these molecules can be seen in (for example) their addition reactions with hydrogen compounds of non-metals, or in reactions that are distantly related to cycloadditions at homopolar double bonds. The selection of suitable reaction partners leads to polycyclic, cage-like molecules containing metal atoms. If these atoms possess lone pairs (as is usual in the lower oxidation states of the third and fourth main groups), these can be utilized to form bonds to further (Lewis acid) metal centers. In some cases large assemblies can be built up from polycyclic systems in this way; a characteristic of these assemblies is a one-dimensional array of metal atoms. Commonly occurring structural features of the polycyclic species are tetrahedra, trigonal bipyramids and cubes.     

Molecular torus group

Generally speaking, the highest symmetry of M?bius cyclacene molecule possesses the C₂ symmetry based on the theory of point group according to the previous works. However, based on the topology principle, the fundamental group of M?buis strip is an infinite continuous cyclic group and its border is made up of twice of the generator. Of course, the M?bius strip-like molecule is associated with a finite discrete cyclic symmetry group. For the cyclacene isomers constructed by several (n) benzene rings, these isomers include: the common cylinder Hückel cyclacene (HC-[n]) molecules, the M?bius cyclacene (MC-[n]) molecules by twisting the linear precursor one time (180°), and the multi-twisted M?bius strip-like cyclacene (M ^m C?[n]) molecules by twisting the linear precursor m times (m × 180°). The relevant results suggest that in addition to the point symmetry, there is a new kind of symmetry called the torus screw rotation (denoted as TSR). In this article, we take the M ^m C?[n] molecules as examples to discuss their TSR group and point group symmetry, and the relative symmetry adaptive atom sets as well as their atomic orbital (AO) sets. Here, the Cartesian coordinates is not quite fit for the investigation of these AOs, so it is replaced by either the torus orthogonal curvilinear coordinates (for M ^m C?[n] molecule) or the cylinder orthogonal curvilinear coordinates (for HC-[n] molecule). According to the features of cyclic group, the character table of the irreducible representation of the TSR group could be constructed easily. Some other relevant point-group symmetries maybe also belong to the molecule, so its symmetry maybe called as the torus group symmetry. For multi-twisted M?bius strip-like molecule, there are some correlations in topology characteristics.     

新型含芳氧乙酸酯基三唑酮类化合物的合成及生物活性研究

通过芳氧乙酸与2-溴-4,4-二甲基-1-(1H-1,2,4-三唑-1-基)-3-戊酮反应, 合成了14个新型含芳氧乙酸酯基三唑酮类化合物. 所有化合物均经核磁、元素分析确证, 部分化合物进行了红外和质谱的测定. 生物活性测试表明部分化合物具有良好的生物活性.     

Side Methyl Groups Control the Conformation and Contribute to Symmetry Breaking of Isoprenoid Chromophores

Ab initio DFT computations reveal that the essential structural and photophysical features of the conjugated π‐electron system of retinal and carotenoids are dictated by “innocent” methyl substituents. These methyl groups shape the conformation and symmetry of the isoprenoid chromophores by causing a sigmoidal distortion of the polyene skeleton and increasing its flexibility, which facilitates fitting to their binding pockets in proteins. Comparison of in vacuo conformations of the chromophores with their native (protein‐bound) conformations showed, surprisingly, that the peripheral groups and interactions with the protein environment are much less significant than the methyl side groups in tuning their structural features. The methyl side groups also contribute to a loss of symmetry elements specific to linear polyenes. In effect, the symmetry‐imposed restrictions on the chromophore electronic properties are disabled, which is of tremendous relevance to their photophysics. This is evidenced by their non‐negligible permanent dipole moments and by the simulated and experimentally measured circular dichroism spectra, which necessarily reflect the chirality of the conjugated π‐electron system.     

The structure of a TNA-TNA complex in solution: NMR study of the octamer duplex derived from alpha-(L)-threofuranosyl-(3'-2')-CGAATTCG

TNA (alpha-( l)-threofuranosyl-(3'-2') nucleic acid) is a nucleic acid in which the ribofuranose building block of the natural nucleic acid RNA is replaced by the tetrofuranose alpha-( l)-threose. This shortens the repetitive unit of the backbone by one bond as compared to the natural systems. Among the alternative nucleic acid structures studied so far in our laboratories in the etiological context, TNA is the only one that exhibits Watson-Crick pairing not only with itself but also with DNA and, even more strongly, with RNA. Using NMR spectroscopy, we have determined the structure of a duplex consisting entirely of TNA nucleotides. The TNA octamer (3'-2')-CGAATTCG forms a right-handed double helix with antiparallel strands paired according to the Watson-Crick mode. The dominant conformation of the sugar units has the 2'- and 3'-phosphodiester substituents in quasi-diaxial position and corresponds to a 4'-exo puckering. With 5.85 A, the average sequential P i -P i+1 distances of TNA are shorter than for A-type DNA (6.2 A). The helix parameters, in particular the slide and x-displacement, as well as the shallow and wide minor groove, place the TNA duplex in the structural vicinity of A-type DNA and RNA.     

Orienting Tetramolecular G‐Quadruplex Formation: The Quest for the Elusive RNA Antiparallel Quadruplex

DNA and RNA G‐quadruplexes (G4) are unusual nucleic acid structures involved in a number of key biological processes. RNA G‐quadruplexes are less studied although recent evidence demonstrates that they are biologically relevant. Compared to DNA quadruplexes, RNA G4 are generally more stable and less polymorphic. Duplexes and quadruplexes may be combined to obtain pure tetrameric species. Here, we investigated whether classical antiparallel duplexes can drive the formation of antiparallel tetramolecular quadruplexes. This concept was first successfully applied to DNA G4. In contrast, RNA G4 were found to be much more unwilling to adopt the forced antiparallel orientation, highlighting that the reason RNA adopts a different structure must not be sought in the loops but in the G‐stem structure itself. RNA antiparallel G4 formation is likely to be restricted to a very small set of peculiar sequences, in which other structural features overcome the formidable intrinsic barrier preventing its formation.     

Significant effects of phosphorylation on relative stabilities of DNA and RNA sugar radicals: remarkably high susceptibility of h-2' abstraction in RNA

The roles of nucleic acid radicals in DNA and RNA damage cannot be properly understood in the absence of knowledge of the C-H bond strengths depicting the energy cost to generate each of these radicals. However, previous theoretical studies on the relative energies of different nucleic acid radicals are not fully convincing mainly because of the use of oversimplified model compounds. In the present study we chose nucleoside 3',5'-bisphosphates as model compounds for DNA and RNA, in which the effects of both the nucleobase and phosphorylation were taken into consideration. Using the newly developed ONIOM-G3B3 methods, we calculated the gas-phase bond dissociation enthalpies and solution-phase bond dissociation free energies of all the carbohydrate C-H bonds in the model compounds. It was found that the monoanionic phosphate group (OPO3H-) was a better radical stabilization group than the OH group by 1.3 kcal/mol, whereas the neutral phosphate group (OPO3H2) was a significantly worse radical stabilization group than OH by 4.4 kcal/mol. Due to these reasons, the relative thermodynamic susceptibility of H-abstraction from deoxyribonucleotides and ribonucleotides varied considerably depending on the phosphorylation state and the charge carried by the phosphate groups. Strikingly, the bond dissociation free energy of C2'-H in ribonucleotides was dramatically lower than that of all the other C-H bonds by 5-6 kcal/mol regardless of the phosphorylation state and the charge carried by the phosphate group. This explained the previous experimental finding that radiation damage of RNA occurs mainly via H-abstraction at H-2'. A model study suggested that the strength of the hydrogen bonding interaction between the 2'-OH and 3-phosphate groups should dramatically increase from ribonucleoside 3',5'-bisphosphate to its C2' radical. The strengthened hydrogen bonding stabilized the C2' radical, rendering the C2'-H bond of RNA extraordinarily vulnerable to H-abstraction.     

Inclusion Complexes of Gossypol with 2-Pentanone, 3-Pentanone, and 2-Hexanone

Inclusion complexes of gossypol with 2-pentanone, 3-pentanone, and 2-hexanone were prepared by crystallization from the corresponding ketone and hexane, and their structures were determined by low-temperature X-ray diffraction. All three compounds crystallize in monoclinic systems and have a 2:1 gossypol-to-solvent molar ratio. Both gossypol–pentanone complexes crystallize in C2/c space groups, and the solvent cavities in these structures have C₂ symmetry. The 3-pentanone molecule, which has C₂ symmetry, sits symmetrically within the cavity, while the 2-pentanone molecule, which lacks C₂ symmetry, takes two equally probable orientations within the cavity. Both structures are similar to previously reported gossypol inclusion complexes formed with small esters and 3-hexanone. The distal positioning of the carbonyl group in 2-hexanone does not allow it to fit into the same solvent cavity that exists in the pentanone structures. In the gossypol-2-hexanone complex, the solvent cages are skewed, and the C₂ site symmetry is lost. As a result, the structure crystallizes in a Cc space group and has a larger asymmetric unit and unit cell. Although the 2-hexanone structure retains many of the features of the gossypol–pentanone complexes, this is the first report of a gossypol inclusion compound with this extended structure.