Non-Enzymatic Template-Directed Recombination of RNAs

RNA non-enzymatic recombination reactions are of great interest within the hypothesis of the “RNA world”, which argues that at some stage of prebiotic life development proteins were not yet engaged in biochemical reactions and RNA carried out both the information storage task and the full range of catalytic roles necessary in primitive self-replicating systems. Here we report on the study of recombination reaction occuring between two 96 nucleotides (nts) fragments of RNAs under physiological conditions and governed by a short oligodeoxyribonucleotide template, partially complementary to sequences within each of the RNAs. Analysis of recombination products shows that ligation is predominantly template-directed, and occurs within the complementary complex with the template in “butt-to-butt” manner, in 1- or 3- nts bulges or in 2–3 nts internal loops. Minor recombination products formed in the template-independent manner are detected as well.     

2'-3'-Diphenylfurano(4',5':3,4)Xanthones

Synthesis of furanoxanthones carrying phenyl substituents in the 2' and 3'-positions has been undertaken on the basis of the appreciable antifertility activity associated with 2',3'-diphenylbenzofurans. 1,3-dihydroxy-, 1,3-dihydroxy-6-methyl- and 1,3-dihydroxy-5-methyl-xanthones were condensed separately with benzoin in the presence of polyphosphoric acid at 110 degrees to give the desired 2',3'-diphenylfurano(4',5':3,4)xanthones.     

3’-脱氧-3’-~(18)F-氟代胸腺嘧啶核苷的合成研究

采用TRACERlab FXF-N自动化合成装置制备了肿瘤显像剂3’-脱氧-3’-18F-氟代胸腺嘧啶核苷(18F-FLT)。以3-N-t-叔丁氧羰基-1-[5’-O-(4,4’-二甲氧基三苯甲基)-2’-脱氧-3’-O-(4-硝基苯磺酰基)-β-D-苏型-呋喃戊糖基]胸苷为前体,经过亲核氟化、盐酸水解两步反应及HPLC分离纯化制备18F-FLT,研究了不同因素对合成效率的影响。结果表明,总合成时间约55 min,未校正18F衰变情况下,放射化学产率约25%,放化纯度大于95%。     

Extraction of Pb2+ with p-tert-butylcalix [4]-, [5]-, [6]Arene Carboxylic Acid Ligands and their Monomeric Counterpart: A Thermodynamic Approach

Studies on extraction equilibrium constants at different temperatures and thermodynamic parameters of solvent extraction of Pb²⁺ ion with carboxylic acid derivatives of different ring size calixarenes and structure related monomeric compound have been carried out. The extraction equilibrium constants corresponding to calix[n]arene (n?=?4, 5, 6) derivatives decrease in the order [5]arene > [6]arene > [4]arene. In all cases, the complexation process is primarily enthalpy driven. The favorable enthalpic contribution for extraction of Pb²⁺ is in the order hexamer ≈ monomer > tetramer > pentamer. However, the unfavorable entropic loss follows the order: monomer > hexamer > tetramer > pentamer. Overall stability of the host-guest complex is the function of entropy-enthalpy compensation and the free energy of complexation is minimum for the pentamer, followed by tetramer ≈ hexamer and monomer. Although the carboxylic acid derivative of calix[4]arene is more preorganized than the calix[5]arene derivative, extraction of Pb²⁺ ion with the tetramer passes through greater entropic loss than that with the pentamer and the degree of preorganization of calix[4]arene derivative is far from perfect for the complexation and extraction of Pb²⁺ ion. As compared to tetrameric and hexameric counterparts, the structural features of the carboxylic acid derivative of calix[5]arene prior to complexation contribute much to interact with the Pb²⁺ ion and form a thermodynamically stable complex. Supplementary materials are available for this article. Go to the publisher's online edition of Solvent Extraction and Ion Exchange to view the supplemental file.     

Synthesis and characterization of copolymers with alternating 1,4-bis(5'-acetyl-2'-thienyl)benzene or 1,3-bis(5'-acetyl-2'-thienyl)benzene chromophore and disiloxane units

Summary Activated (Ph₃P)₃RuH₂CO (Ru) catalyzed copolymerization of 1,4-bis(5'-acetyl-2'-thienyl)benzene (I) and 1,3-divinyltetramethyldisiloxane (II) yields alt-copoly[3,3,5,5-tetramethyl-4-oxa-3,5-disila-1,7-heptanylene/2',2"-diacetyl-5',5"-(1,4-benzene)-3',3"-bis (thiophenylene)] (III). On the other hand, Ru catalyzed copolymerization of 1,3-bis(5'-acetyl-2'-thienyl)benzene (IV) and II fails. Nevertheless, Ru catalyzed reaction of IV with excess vinylpentamethyldisiloxane (V) yields 1,3-bis(4'-pentamethyldisiloxy-ethyl-5'-acetyl-2'-thienyl)benzene (VI). VI undergoes acid catalyzed siloxane equilibration polymerization to give alt-copoly[3,3,5,5-tetramethyl-4-oxa-3,5-disila-1,7-heptanylene/2',2"-diacetyl-5',5"-(1,3-benzene)-3',3"-bis(thiophenylene)] (VII) and hexamethyldisiloxane. Copolymers III and VII have been characterized. Received: 26 July 1999/Revised version: 12 October 1999/Accepted: 12 October 1999     

Rhodium‐Catalyzed [5+2] Cycloaddition of 3‐Acyloxy‐1,4‐enyne with Alkene or Allene

We recently developed a completely new type of Rh‐catalyzed [5+2] cycloaddition by using 3‐acyloxy‐1,4‐enyne (ACE) as the 5‐carbon building block. In this update, we show that ACE can undergo intramolecular [5+2] cycloaddition with either an alkene or an allene in the presence of an appropriate rhodium catalyst and ligands to afford bicyclic compounds with multiple stereogenic centers. In most cases, cis‐fused bicyclo[5.3.0]decadienes are prepared highly diastereoselectively.

     

Phenanthroline derivatives with improved selectivity as DNA-targeting anticancer or antimicrobial drugs

Phenanthroline derivatives are of interest due to their potential activity against cancer, and viral, bacterial, and fungal infections. In a search for highly specific antitumor and antibacterial compounds, we report the activities of 1,10-phenanthroline-5,6-dione (phendione or L(1)), dipyrido[3,2-a:2',3'-c]phenazine (dppz or L(2)), and their corresponding platinum complexes ([PtL(1)Cl2] and [PtL(2)Cl2]), and provide the solid-state 3D structure for [PtL(1)Cl2]. It is generally known that a toxic metal ion coordinated to an active organic moiety leads to a synergistic effect; however, we report herein that the platinum complexes [PtL(1)Cl2] and [PtL(2)Cl2] have weaker activities relative to those of the free ligands, especially against bacteria. Testing these agents against a variety of human cancer cell lines revealed that L(1) and [PtL(1)Cl2] were at least as active as cisplatin against several of the cell lines (including a cisplatin-resistant cell line). The absence of antibacterial activity of [PtL(1)Cl2] removes the detrimental effect of phenanthrolines toward intestinal flora, suggesting a highly promising new strategy for the development of anticancer drugs with reduced side effects.     

Zn2+ complexes of di- and tri-nucleating azacrown ligands as base-moiety-selective cleaving agents of RNA 3',5'-phosphodiester bonds: binding to guanine base

The ability of the dinuclear Zn2+ complex of 1,4-bis[(1,5,9-triazacyclododecan-3-yloxy)methyl]benzene (L(1)) to promote the cleavage of the phosphodiester bond of dinucleoside-3',5'-monophosphates that contain a guanine base has been studied over a narrow pH range from pH 5.8 to 7.2 at 90 degrees C. Comparative measurements have been carried out by using the trinuclear Zn2+ complex of 1,3,5-tris[(1,5,9-triazacyclododecan-3-yloxy)methyl]benzene (L(2)) as a cleaving agent and guanylyl-3',5'-guanosine (5'-GpG-3') as a substrate. The strength of the interaction between the cleaving agent and the starting material has been elucidated by UV spectrophotometric titrations. The speciation and binding mode have been clarified by potentiometric titrations with hydrolytically stable 2'-O-methylguanylyl-3',5'-guanosine and 1H NMR spectroscopic measurements with guanylyl-3',5'-guanosine. The results show that the guanine base is able to serve as a site for anchoring for the Zn2+-azacrown moieties of the cleaving agents L(1) and L(2), analogously to uracil base. The interaction is, however, weaker than with the uracil base and, hence, only the 5'-GpG-3' site (in addition to 5'-GpU-3' and 5'-UpG-3' sites) is able to markedly modulate the phosphodiester cleavage by the Zn2+ complexes of di- and trinucleating azacrown ligands containing an ether oxygen as a potential H-bond-acceptor site.     

Zur Reaktion von 2-Aminothiophen-3-carbonitrilen mit Heterocumulenen

The Reaction of 2-Aminothiophene-3-carbonitriles with Heterocumulenes . The reaction of 2-aminothiophene-3-carbonitriles ( 1 ) with phenyl isothiocyanate does not yield the expected thieno[2,3-d]pyrimidine derivatives but the substituted dithieno-[2′,3′:4, 3][2′,3′:8, 9]pyrimido[3, 4-a]pyrimid-7-thiones ( 4 ). The compounds 4 also may be synthesized from 1 and thiophosgene. Analogously, from 1 and phenyl isocyanate the substituted dithieno[2′,3′:4, 3][2′,3′:8, 9]pyrimido[3, 4-a]pyrimid-7-ones ( 9 ) arise in small yields. They are better obtainable from 1 and phosgene. Carbon disulphide react with 1 in pyridine to form a mixture of the thieno[2, 3-d]pyrimid-2, 4-dithione ( 10 ) and the condensed compound 4 . The ratio of products depends on the substituents in the 4, 5-position of 1 . The structures are investigated by n.m.r.-spectroscopy.      

Elongation and Contraction of Scallop Sarcoplasmic Reticulum (SR): ATP Stabilizes Ca2+-ATPase Crystalline Array Elongation of SR Vesicles

The Ca²⁺-ATPase is an integral transmembrane Ca²⁺ pump of the sarcoplasmic reticulum (SR). Crystallization of the cytoplasmic surface ATPase molecules of isolated scallop SR vesicles was studied at various calcium concentrations by negative stain electron microscopy. In the absence of ATP, round SR vesicles displaying an assembly of small crystalline patches of ATPase molecules were observed at 18 µM [Ca²⁺]. These partly transformed into tightly elongated vesicles containing ATPase crystalline arrays at low [Ca²⁺] (≤1.3 µM). The arrays were classified as ‘’tetramer’’, “two-rail” (like a railroad) and ‘’monomer’’. Their crystallinity was low, and they were unstable. In the presence of ATP (5 mM) at a low [Ca²⁺] of ~0.002 µM, “two-rail” arrays of high crystallinity appeared more frequently in the tightly elongated vesicles and the distinct tetramer arrays disappeared. During prolonged (~2.5 h) incubation, ATP was consumed and tetramer arrays reappeared. A specific ATPase inhibitor, thapsigargin, prevented both crystal formation and vesicle elongation in the presence of ATP. Together with the second part of this study, these data suggest that the ATPase forms tetramer units and longer tetramer crystalline arrays to elongate SR vesicles, and that the arrays transform into more stable “two-rail” forms in the presence of ATP at low [Ca²⁺].     

Reaction of cytidine nucleotides with cyanoacetylene: support for the intermediacy of nucleoside-2',3'-cyclic phosphates in the prebiotic synthesis of RNA

A robust and prebiotically plausible synthesis of RNA is a key requirement of the "RNA World" hypothesis, but, to date, no such synthesis has been demonstrated. Monomer synthesis strategies involving attachment of preformed nucleobases to sugars have failed, and, even if activated 5'-nucleotides could be made, the hydrolysis of these intermediates in water makes their efficient oligomerisation appear unlikely. We recently reported a synthesis of cytidine-2',3'-cyclic phosphate 1 (C>p) in which the nucleobase was assembled in stages on a sugar-phosphate template. However, 2',3'-cyclic nucleotides (N>p's) also undergo hydrolysis, in this case giving a mixture of the 2'- and 3'-monophosphates. This hydrolysis has previously been seen as making the, otherwise promising, oligomerisation of N>p's seem as unlikely as that of the 5'-activated nucleotides. We now find that cyanoacetylene, the reagent used for the second stage of nucleobase assembly in the synthesis of C>p, also reverses the effect of the hydrolysis by driving efficient cyclisation of C2'p and C3'p back to C>p. Excess cyanoacetylene also derivatises the nucleobase, but this modification is reversible at neutral pH. These findings significantly strengthen the case for N>p's in a prebiotic synthesis of RNA.     

Anisotropic domain switching in Pb(Mg1/3Nb2/3)O3‐0.30PbTiO3 single crystals with rhombohedral structure

Anisotropic domain switching paths in [001]‐, [011]‐, and [111]‐poled Pb(Mg_1/3Nb_2/3)O₃‐0.30PbTiO₃ single crystals were studied by in situ polarized light microscopic driven by an antiparallel electric field. Orientation‐dependent electric field induced polarization and strain behaviors were investigated systematically. For [001]‐oriented crystals, only one‐step 71° switching occurred during the domain switching process, resulting in the appearance of stripe domain walls whose traces on (001) plane were along 45° or 135° with respect to [100] direction. But for [011]‐oriented samples, a two‐step 71° switching was observed during 109° switching and the projections of formed twin domain walls on the (011) plane are along 35.3° or 144.7° with respect to [01] direction. Moreover, a three‐step 71° switching was found during 180° switching in [111]‐oriented samples. It was demonstrated by the produced domain walls whose projections on the (10) plane are along 35.3°, 90° or 160.6° with respect to [11] direction. The energetically motivated mechanism based on multistep polarization switching process was also proposed to explain the anisotropic domain switching paths. Our results provided a visualized observation on the ferroelectric domain switching process and also laid the solid foundations for controlling polarization order parameter in ferroelectric single crystals.     

A Phosphine‐Catalyzed Regioselective [3+2] Cycloaddition of Ethyl 5,5‐Diarylpenta‐2,3,4‐trienoate with Aromatic Aldehydes and α,β‐Unsaturated Carbonyl Compounds

Tributylphosphine‐catalyzed regioselective [3+2] cycloadditions between ethyl 5,5‐diarylpenta‐2,3,4‐trienoate 1 and various aromatic aldehydes 2 to produce a wide variety of polysubstituted 2,5‐dihydrofurans 3 , and between 1 and β‐unsubstituted α,β‐unsaturated carbonyl compounds 5 to give polysubstituted cyclopentenes 6 with a quaternary carbon center, are reported. In both cases the reaction partners approach each other via the sterically less hindered orientation to afford the target products in excellent regioselectivity. The reaction mechanism involved first the generation of a zwitterionic intermediate between the butatriene 1 and PBu₃. For the formation of 2,5‐dihydrofurans 3 , the preferred cyclization mode encompassed the nucleophilic attack of the α‐position of butatriene to the aldehydic carbon of 2 , followed by the ring closure between the aldehydic oxygen of 2 and the γ‐position of butatriene, which is the first report of a normal [3+2] cycloaddition between cumulenes and aldehydes. For the formation of cyclopentenes 6 , the reaction involved attack of the γ‐position of the butatriene to the electron‐deficient β‐position of the α,β‐unsaturated carbonyl compounds 5 , followed by the ring closure between the α‐position of 5 and the α‐position of butatriene, which shows a different regioselectivity to the previously reported [3+2] cycloadditions between butatriene and olefins.

     

微波促进碳酸钾催化一锅法合成2-氨基-3氰基-4-芳基-4H-苯并色烯衍生物

微波辐射下,乙醇溶剂中K₂CO₃催化芳甲醛、丙二腈和α-萘酚（或β-萘酚）三组分一锅法快速合成了一系列2-氨基-3-氰基-4-芳基-4H-苯并[h]色烯或苯并[f]色烯衍生物。以苯甲醛、丙二氰与α-萘酚的反应为模板反应,通过单因素实验方案优化了反应的工艺条件。结果表明：反应物各10 mmol,催化剂K₂CO₃ 1 mmol,溶剂无水乙醇15 ml,采用微波功率500 W,80℃回流反应 5 min,2-氨基-3-氰基-4-苯基-4H-苯并[h]色烯（4a）的收率83.6%。在上述最佳条件下,利用取代苯甲醛代替苯甲醛,4H-苯并[h]色烯衍生物(4)产率为65.8%~89.4%。 利用β-萘酚代替α-萘酚,4H-苯并[f]色烯衍生物(6)产率为67.5%~82.9%,合成产物通过熔点和红外光谱表征其结构。     

PbO—Fe2O3-V2O5-P2O5玻璃结构与性能研究

钒、铁磷酸盐玻璃作为一种半导体材料受到许多研究者的关注。选择了PbO-V2O5-P2O5、PbO-Fe2O3-P2O5和PbO-Fe2O3-V2O5-P2O5三组玻璃系统,研究了V2O5和Fe2O3对磷酸盐玻璃结构和性能的影响。通过红外光谱(IR)和差热分析(DTA)发现,V2O5和Fe2O3对磷酸盐玻璃结构的影响不同,Fe2O3不但会降低[PO4]基团的桥氧数,还会打断P=O双键,以[FeO4]形式参加网络结构,使玻璃结构趋于稳定。     

Aromatic polyamides bearing ether and isopropylidene or hexafluoroisopropylidene links in the main chain

Two multiring, flexible dicarboxylic acids, 4,4'-[isopropylidenebis(1,4-phenylene)dioxy] dibenzoic acid (3) and 4,4'-[hexafluoroisopropylidenebis(1,4-phenylene)dioxyldibenzoic acid (3-F), were synthesized through the nucleophilic fluorodisplacement ofp-fluorobenzonitrile by the dipotassium bisphenolates of the corresponding bisphenol precursors followed by alkaline hydrolysis. Two series of aromatic polyamides 5_a–k and 5_a–k-F containing both ether and isopropylidene or hexafluoroisopropylidene linkages between phenylene units were prepared by direct polycondensation of diacids 3 and 3-F, respectively, with various aromatic diamines using triphenyl phosphite and pyridine as condensing agents in aN-methyl-2-pyrrolidone (NMP) solution containing dissolved calcium chloride. The resulting polyamides of 5 and 5-F series have inherent viscosities of 0.92–1.29 dL/g and 0.60–0.92 dL/g, respectively. Most of these polymers are amorphous in nature, are soluble in polar solvents such as NMP,N,N-dimethylacetamide (DMAc), andN,N dimethylformamide (DMF), and can afford tough and flexible films by solution casting. Differential scanning calorimetry shows T_gs ranging from 175 to 239 °C for the 5 series polyamides and ranging from 172 to 267 °C for the 5-F series polymers. Both classes of polyamides show good thermal stability, with the 5-F series polyamides being more stable.     

Synthesis and antitumor molecular mechanism of agents based on amino 2-(3',4',5'-trimethoxybenzoyl)benzo[b]furan: inhibition of tubulin and induction of apoptosis

Induction of apoptosis is a promising strategy that could lead to the discovery of new molecules active in cancer chemotherapy. This property is generally observed when cells are treated with agents that target microtubules, dynamic structures that play a crucial role in cell division. Small molecules such as benzo[b]furans are attractive as inhibitors of tubulin polymerization. A new class of inhibitors of tubulin polymerization based on the 2-(3',4',5'-trimethoxybenzoyl)benzo[b]furan molecular skeleton, with the amino group placed at different positions on the benzene ring, were synthesized and evaluated for antiproliferative activity, inhibition of tubulin polymerization, and cell-cycle effects. The methoxy substitution pattern on the benzene portion of the benzo[b]furan moiety played an important role in affecting antiproliferative activity. In the series of 5-amino derivatives, the greatest inhibition of cell growth occurred if the methoxy substituent is placed at the C6 position, whereas C7 substitution decreases potency. The most promising compound in this series is 2-(3',4',5'-trimethoxybenzoyl)-3-methyl-5-amino-6-methoxybenzo[b]furan (3 h), which inhibits cancer cell growth at nanomolar concentrations (IC(50) =16-24 nM), and interacts strongly with tubulin by binding to the colchicine site. Sub-G(1) apoptotic cells in cultures of HL-60 and U937 cells were observed by flow cytometric analysis after treatment with 3 h in a concentration-dependent manner. We also show that compound 3 h induces apoptosis by activation of caspase-3, -8, and -9, and this is associated with cytochrome c release from mitochondria. The introduction of an α-bromoacryloyl group increased antiproliferative activity with respect to the parent amino derivatives.     

An unprecedented mixed valence cobalt(III)/cobalt(II) ion-pair complex ([CoCO3(bipy)2]2[Co(DCA)2]⋅16H2O) with two novel water tapes

An unprecedented mixed valence cobalt(III)/cobalt(II) ion-pair complex, [CoCO₃(bipy)₂]₂[Co(DCA)₂]⋅16H₂O (1) [bipy = 2,2′-bipyridine, DCA = demethylcantharidate, exo-1,4-epoxy-cyclohexyl-2,3-dicarboxylate group, (C₈H₈O₅)^2 −], has been synthesized and characterized by elemental analysis, IR, UV–vis, Thermogravimetric analysis (TGA) and single crystal X-ray diffraction. The crystal structure of 1 consists of three independent molecular moieties: [CoCO₃(bipy)₂]⁺, [Co(DCA)₂]^2–, and water molecules of crystallization. Interestingly, two novel water tapes, one comprises of alternate cyclic water tetramer and octamer, the other is constructed by alternate cyclic water hexamer and carboxylate–water hybrid octamer [(H₂O)₂(COO)₂]^2 −, have been detected for the first time in the host framework of 1. The two novel water tapes are linked together by the DCA and carbonate ligands via hydrogen bonds into a 2D water layer, and then the water layers assemble complex ions ([CoCO₃(bipy)₂]⁺ and [Co(DCA)₂]^2 −) through hydrogen bonds, π–π interactions and electrostatic interactions to form the overall 3D metal–organic framework structure.     

A Synergic Blend of Newly Isolated <Emphasis Type="Italic">Pseudomonas mandelii</Emphasis> KJLPB5 and [hmim]Br for Chemoselective 2° Aryl Alcohol Oxidation in H<Subscript>2</Subscript>O<Subscript>2</Subscript>: Synthesis of Aryl Ketone or Aldehydes via Sequential Dehydration-Oxidative C=C Cleavage

Abstract  

Pseudomonas mandelii KJLPB5 is reported for the oxidation of aryl alcohols in ionic liquid [hmim]Br (1-hexyl-3-methyl imidazolium bromide) with H₂O₂. With a slight alteration of reaction conditions, the developed protocol leads either to (i) chemoselective oxidation of 2° aryl alcohols over 1° and aliphatic counterparts or (ii) direct one pot-two step sequential conversion of 2° aryl alcohols into corresponding one or two carbons shorter aryl aldehydes through oxidative cleavage pathway, thus providing a new facet to metal-free oxidations. The key operational parameters such as substrate concentration, incubation temperature, incubation time, ionic liquid type and ionic liquid concentration are also optimized.     

Synthesis of Nb2O5 and Ta2O5 nanopowders by means of an endo-templating method

Finding efficient templates for the nanostructuring of materials is a key point. Here, the niobium (V) - and tantalum (V) oxide ceramics nanopowders have been synthesized by a hard-templating approach by using the tricalcium phosphate biomaterial (Ca₃(PO₄)₂.xH₂O) as template agent. The oxide ceramics were investigated by X-ray Diffraction (XRD), Fourier Transform Infrared (FTIR) spectroscopy, nitrogen physisorption and Scanning Electron Microscopy (SEM). It was observed that the surface properties (specific surface areas, pore volumes) of the Nb₂O₅ and Ta₂O₅ powders were strongly dependent of the amount of the Ca₃(PO₄)₂.xH₂O template previously used in the preparation of the [oxide ceramics/template] composites. For instance, with a Ca₃(PO₄)₂.xH₂O/ceramic salt weight ratio ranging from 0 to 1, the specific surface areas of Nb₂O₅ and Ta₂O₅ were gradually enhanced of 48–166 m²/g and 5–84 m²/g, respectively. The pore volumes were increased as well. The use of the eco-friendly tricalcium phosphate material (Ca₃(PO₄)₂.xH₂O) as template in the hard-templating approach may be suitable and efficient in the aim of synthesizing materials with enhanced surface properties.