Antiviral properties of cage compounds. New prospects

The published data of the last 15 years on the antiviral activity and the mechanism of action of cage compounds are integrated and described systematically. The considerable interest in the cage compounds as antiviral agents is related to the specific features of the spatial structure of this class of derivatives and high lipophilicity and rigidity of the carbon cage, which allows these molecules to easily penetrate through the lipid layer of biological membranes. Data on the ion channel structure of influenza A and hepatitis C viruses and docking data for some cage structures to these channels are presented. Data on the antiviral properties of cage compounds against RNA genome viruses, the influenza A virus and its mutant strains, hepatitis C virus, human immunodeficiency viruses, and other RNA-containing viruses, are presented. The efficiency of cage compounds against the DNA-genome viruses, herpes virus, cytomegalovirus and orthopoxviruses, is demonstrated. The proven participation of aminoadamantanes in the suppression of early stages of the influenza virus life cycle suggests that efficient inhibitors of not only the influenza virus but also other RNA- and DNA-containing viruses could be found among the cage molecules.     

Molecular mechanics calculations of 10-vertex boron cage compounds

The model proposed earlier for molecular mechanics calculations of 7- and 12-vertex boranes, carboranes, and metallocarboranes has been extended to the case of 10-vertex borane cage compounds. To use the MM3 program with the standard connectivity file, and to avoid program alterations, the 10-vertex cages of the molecules were presented as a superposition of four formally independent fragments. Interactions between the fragments were described with a Hill-like potential, with the parameters adjusted for valence interactions. Standard values for the bond lengths and bond angles in the 10-vertex boron cage have been found by statistical analysis of X-ray data on borane cage compounds stored in the Cambridge Structural Database. Several substituted neutral molecules and anions have been considered, and good agreement of the calculated and experimental data has been obtained. Using the approach developed, the unknown structure of the [mu-B20H16O(CH2)4O(CH2)2CH(CH3)2]3- ion has been calculated.     

Chiral cage molecules generated by regioselective O-alkylation of a doubly-bridged calix[8]arene

A calix[8]arene doubly-bridged at the 1,5-phenol units and 3,7-phenol units has a cage structure with D_2d symmetry. Regioselective introduction of methyl groups into the residual 2,4,6,8-phenol units affords five different cage compounds: that is, three racemic compounds, one meso compound, and one achiral compound. This paper reports systematic studies on the preparation methods of these new cage compounds and spectroscopic classification of their molecular symmetries. The results indicate that these compounds have a latent potential as a platform for designing chiral cage molecules with an ionophoric inner cavity.     

Self-assembly of frameworks with specific topologies: construction and anion exchange properties of M3L2 architectures by tripodal ligands and silver(I) salts

Three five-component architectures, compounds 3, 4, and 5 were obtained by self-assembly of tripodal 1,3,5-tris(imidazol-1-ylmethyl )-2,4,6-trimethylbenzene (6) and 1,3,5-tris(benzimidazol-2-ylmethyl)benzene (7) ligands with silver(I) salts. The structures of these novel complexes have been determined by X-ray crystallography. The results of structural analysis indicate that these frameworks have same M3L2 components, but different structures. Compounds 3 and 4 are both M3L2 type cage-like complexes, while the 5 is an open trinuclear complex. The complex 3 is a cylindrical cage with simultaneous inclusion of a perchlorate anion inside of the cage as a guest molecule. Such guests can be exchanged for other anions through the open edge of the cage as evidenced by crystal structure of 4. The results demonstrate that the molecular M3L2 type cage can act as a host for anions and provide a nice example of supramolecular architectures with interesting properties and possible applications.     

Highly CO2-selective organic molecular cages: what determines the CO2 selectivity

A series of novel organic cage compounds 1-4 were successfully synthesized from readily available starting materials in one-pot in decent to excellent yields (46-90%) through a dynamic covalent chemistry approach (imine condensation reaction). Covalently cross-linked cage framework 14 was obtained through the cage-to-framework strategy via the Sonogashira coupling of cage 4 with the 1,4-diethynylbenzene linker molecule. Cage compounds 1-4 and framework 14 exhibited exceptional high ideal selectivity (36/1-138/1) in adsorption of CO(2) over N(2) under the standard temperature and pressure (STP, 20 °C, 1 bar). Gas adsorption studies indicate that the high selectivity is provided not only by the amino group density (mol/g), but also by the intrinsic pore size of the cage structure (distance between the top and bottom panels), which can be tuned by judiciously choosing building blocks of different size. The systematic studies on the structure-property relationship of this novel class of organic cages are reported herein for the first time; they provide critical knowledge on the rational design principle of these cage-based porous materials that have shown great potential in gas separation and carbon capture applications.     

NMR elucidation of some ligands derived from the pentacycloundecane skeleton

The complete NMR elucidation of three novel pentacycloundecane (PCU)-derived ligands is reported. 2D NMR techniques are used to overcome the problem of major overlapping of methine signals on the cage skeleton. The compounds were synthesized as potential ligands to be used in asymmetric catalysis. They represent the first instance where aromatic moieties have been attached directly to the cage skeleton using lithiation techniques. The X-ray crystal structure of one of the ligands was obtained. The X-ray structure was helpful in determining the potential NOESY interactions within the set of molecules. For the other ligands a high level Density Functional Theory (DFT) optimization was performed [B3LYP/6-31+g(d)] to visualize possible NOE interactions. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Staudinger reaction at in-bridgehead positions of phosphorus macrobicyclic compounds

Reaction of in,in-phosphite 1 with thiophosphoryl azide 2 affords in,in-dithiophosphate 3, in,in-thiophosphate-imidophosphate 4, and in,in-phosphite-imidophosphate 5. Compounds 4 and 5 are the first examples of the modification of in-bridgehead positions in macrobicyclic compounds with groups larger than methyl. The benzaldehyde arms of the in-substituent in 4 and 5 jut out of the cage bars. In 4 they are trapped between the macrocyclic arms to give the NMR spectra of a Cs-symmetric solution-state structure. In contrast, in 5 the benzaldehyde arms can move between the gaps of the cage. This results in 1H and 13C NMR spectra which are consistent for a compound with C3v symmetry. In,out-diimidophosphate 7 is obtained in moderate yield by reaction of in,out-phosphite 6 with thiophosphoryl azide 2. Its in-benzaldehyde moieties are not fixed between the cage arms, but can freely move from one gap to the next as is indicated by NMR measurements.     

Synthesis, Chemistry, and Applications of Heterocyclic Cage Compounds (V)

The synthesis and chemistry of polycyclic of cage compounds have attracted considerable attention in recent years. The vast majority of the work reported in this area has dealt with carbocylic cage compounds. On the other hand, the synthesis and chemistry of heterocyclic cage compounds have received less attention. Recently, we envisioned that studies on the synthesis and chemistry of heterocyclic cage compounds can greatly expand the scopes and utilities of cage compounds.1 As part of a program that involves the synthesis, chemistry, and application of heterocyclic cage compounds, we report here the synthesis of new thia-oxa-cage compounds and the chemical nature of these thia-cages.     

Higher 1,3,2-Diazaphosphacyclanes: V. Synthesis, Structure, and Chemical Features of 4,5;7,8-Dibenzo-1,3,2-diazaphosphocanes

A procedure was developed for preparing 4,5;7,8-dibenzo-1,3,2-diazaphosphocanes containing trivalent and pentavalent phosphorus atoms. The structure of the compounds was determined by NMR spectroscopy and single crystal X-ray diffraction. The conformational transitions of the diazaphosphocanes in solution were analyzed. First data were obtained on transformations of the obtained eight-membered heterocycles.     

Electronic and structural investigations of gold clusters doped with copper: Aun-1Cu- (n=13-19)

We have obtained the ground state and the equilibrium geometries of Au(n) (-) and Au(n-1)Cu(-) in the size range of n=13-19. We have used first principles density functional theory within plane wave and Gaussian basis set methods. For each of the cluster we have obtained at least 100 distinct isomers. The anions of gold clusters undergo two structural transformations, the first one from flat cage to hollow cage and the second one from hollow cage to pyramidal structure. The Cu doped clusters do not show any flat cage structures as the ground state. The copper doped systems evolve from a general 3D structure to hollow cage with Cu trapped inside the cage at n=16 and then to pyramidal structure at n=19. The introduction of copper atom enhances the binding energy per atom as compared to gold cluster anions.     

用分子动力学模拟水合物储氢

用分子动力学(MD)模拟方法系统研究了结构Ⅰ型(SⅠ)和结构H型(SH)氢气水合物中氢气的占据情况并确定了氢气水合物的稳定结构: SⅠ水合物氢气分子数小胞中为2, 大胞中为3; SH水合物氢气分子数小胞中为2, 中胞中为2, 大胞中为11. 分析了稳定情况下水合物各胞腔内氢气分子之间的径向分布函数(RDF), 得出了氢气分子在各胞腔内的稳定位置. 由稳定位置得到了稳定结构下氢气水合物的储氢质量分数: SⅠ为5.085%, SH为6.467%. 与实验对比得出结论: SH水合物稳定结构下的储氢能力最强.     

Synthesis and NMR elucidation of novel penta-cycloundecane amine derivatives as potential antituberculosis agents

The synthesis and NMR elucidation of five novel penta-cycloundecane amine derivatives are reported. These compounds are potential antituberculosis agents. The (1)H and (13)C spectra showed major overlapping of methine signals of the cage skeleton making it extremely difficult to elucidate these compounds. The overlapping occurs as a result of the additions made to the carbonyl carbon (C-8/C-11) of the cage. The two-dimensional NMR technique proved to be a useful tool in overcoming this problem. All compounds reported are meso compounds thereby not only simplifying the NMR structure elucidation, but also making it indeed possible.     

Phosphorus and Arsenic Chalcogenides as Reagents Toward Transition Metal-Ligand Systems

Abstract

The compounds obtained by reacting the P₄S₃, P₄Se₃ and As₄S₃ cage molecules with various transition metal-ligand moieties are reported. The transition metal-ligand systems are bound either to the intact molecules or to fragments (hexa- or tri-atomic) originating from the cage molecules. Such compounds provide examples of selective activation of cage molecules by metal moieties.     

Tuning the Composition of Guest Molecules in Clathrate Hydrates: NMR Identification and Its Significance to Gas Storage

Gas hydrates represent an attractive way of storing large quantities of gas such as methane and carbon dioxide, although to date there has been little effort to optimize the storage capacity and to understand the trade‐offs between storage conditions and storage capacity. In this work, we present estimates for gas storage based on the ideal structures, and show how these must be modified given the little data available on hydrate composition. We then examine the hypothesis based on solid‐solution theory for clathrate hydrates as to how storage capacity may be improved for structure II hydrates, and test the hypothesis for a structure II hydrate of THF and methane, paying special attention to the synthetic approach used. Phase equilibrium data are used to map the region of stability of the double hydrate in P–T space as a function of the concentration of THF. In situ high‐pressure NMR experiments were used to measure the kinetics of reaction between frozen THF solutions and methane gas, and ¹³C MAS NMR experiments were used to measure the distribution of the guests over the cage sites. As known from previous work, at high concentrations of THF, methane only occupies the small cages in structure II hydrate, and in accordance with the hypothesis posed, we confirm that methane can be introduced into the large cage of structure II hydrate by lowering the concentration of THF to below 1.0 mol %. We note that in some preparations the cage occupancies appear to fluctuate with time and are not necessarily homogeneous over the sample. Although the tuning mechanism is generally valid, the composition and homogeneity of the product vary with the details of the synthetic procedure. The best results, those obtained from the gas–liquid reaction, are in good agreement with thermodynamic predictions; those obtained for the gas–solid reaction do not agree nearly as well.     

Reduction potentials of cage-structure halogen derivatives : A method for predicting yields of organolithium compound formation

E_p reduction potentials for eight different cage structure RX halides have been measured by cyclic voltammetry between -2.25 and -3.00 V (± 0.02 V). These E_p are considered good approximations of the SET values. They correlate well with the relative stability of the corresponding halides expressed in terms of perester thermolysis constants. It is proposed to use these potentials to estimate and predict yields of organolithium compounds from cage structure halide derivatives.     

N‐Butylpyridinium undecachlorocarbadodecaborate and comparison with similar compounds

The title compound, C₉H₁₄N⁺·CHB₁₁Cl₁₁⁻, was obtained in the course of our continuing studies of the low‐melting salts of closo‐ and nido‐carborane cage anions with alkylpyridinium and dialkylimidazolium cations. The title compound is the first example of a pyridinium salt of a perchlorinated carborane anion. The structure consists of one N‐butylpyridinium cation counterbalanced by one perchlorinated carborane cage anion per asymmetric unit. By changing the counter‐ion, different packings are observed, and to try to understand this the new structure is compared with five similar compounds.     

丙烯腈在聚丙烯上接枝共聚

丙烯腈在聚丙烯上非均相接枝共聚，得杨梅形氰基树脂。研究了接枝共聚条件对单体转化率和接枝率的影响。表观聚合速度可表示为，碰撞频率因子和聚合活化能分别是1．36×1011s-1和99．2kJ．mol-1。从光学显微镜观察到改性树脂在水中接枝连束的分布状态。丙烯腈和二乙烯基苯在聚丙烯上接校共聚，再经二甲苯率取，得笼形氰基树脂。二乙烯基苯在单体中的相对含量对树脂的溶胀性能和笼孔尺寸有很大的影响，制取功能材料时应予适当调节。扫描电镜照片展示了笼形树脂的笼腔和网络结构形态。     

Synthesis and properties of isoxazolo[60]fullerene-donor dyads

A series of isoxazolo[60]fullerenes has been prepared in one pot from aldoximes under microwave irradiation. Several donors and acceptors were used as substituents. The absorption and emission spectra of these compounds in polar solvents suggest a weak charge-transfer interaction between the oxygen atom of the isoxazoline moiety and the C(60) cage, as well as a stronger interaction between the donor and the fullerene cage when the attached groups are p-N,N-dimethylaniline or ferrocene. The electrochemical properties of the compounds were investigated and they show the same or better acceptor character than C(60) in all cases. Theoretical calculations support the results obtained. Solvent effects in the (1)H NMR spectra have been determined and provide useful information concerning the polarization of dyads.     

Quantum mechanical study on the facial selectivity of dioxa and trioxa cage molecules

High facial selectivity (>99%) of nucleophilic addition to the carbonyl groups of the title compounds (1 and 2) has been achieved for the novel trioxa cage 2, but not for the dioxa 1. Similar experimental observations were made for the carbene addition to the double bonds of cage compounds, 3 and 4. Calculations were carried out for the cage compounds and their reaction transition structures, with LiH as a nucleophile and :CCl(2) as an attacking carbene. The calculated facial preference for nucleophilic and carbene addition agreed well with experimental results. The origins of facial selectivity are examined from the viewpoints of structure, frontier orbitals, and molecular electrostatic potential of the reactants, as well as strain, electrostatic, and hyperconjugation effects in the transition state. For dioxa cages, the structural facial difference around the reaction center is minor, but the electronic difference of syn and anti faces generated by the two remote oxygen atoms is clearly demonstrated via frontier orbital and MEP analyses. For trioxa cages, the close proximity of the third ether oxygen (O(s)) to the reaction center brings large structural and electronic changes around the reaction center. The calculated electrostatic and strain energy differences of syn and anti transition structures are significantly larger for trioxa cages than for the dioxa cages. Therefore, they both contribute to the enhanced facial selectivity of trioxa compounds. Finally, analysis of hyperconjugative stabilization in transition structures reveals the danger of relying solely on Cieplak or Anh models in rationalization of facial selectivity, especially when nonequivalent steric and electrostatic effects as those present in the trioxa systems are involved.     

Synthesis,Chemistry and Applications of Heterocyclic Cage Compounds (V)

The synthesis and chemistry of polycyclic cage compounds have attracted considerable attention in recent years.¹ The vast majority of the work reported in this area has dealt with caybocyclic cage compounds. On the other hand, the synthesis and chemistry of heterocyclic cage compounds have received less attention. Recently, we have accomplished the synthesis of a series of oxa-cage compounds and performed the chemical transformations of these oxa-cage compounds.² As part of a program that involves the synthesis,chemistry and applications of heterocyclic cage compounds we report here the synthesis of heterocyclic cage compounds 1-12. We also wish to report the applications of compounds 7-12 on the π-facial selectivities. Studies on the cation-binding properties of compounds 1 and 2 and other oxa-cages are undertaken.