Adducts of guanine with chromium(III), iron(III) and oxovanadium(IV) chlorides

The preparation of well-defined adducts of the M(guH)(₂Cl₃ (M = Cr, Fe) and VO(guH)Cl₂ types (guH = neutral guanine), by refluxing ligand and metal chloride mixtures in ethanol-triethyl orthoformate, is reported. Characterization studies suggest that the new complexes are probably linear chain-like polymeric species, involving single bridges of bidentate guH ligands between adjacent metal ions. Bidentate bridging guH is most probably coordinated through the N(7) and N(9) imidazole nitrogens. The chloro ligands present in the adducts are exclusively terminal. Infrared evidence rules out the possibility of coordination of guanine through either of its exocyclic potential binding sites (i.e., CO oxygen and NH₂ nitrogen) [1].     

Manganese(II), iron(II) and nickel(II) chloride complexes with monodeprotonated anionic guanine

Upon refluxing 2:1 mixtures of guanine (guH) and MnCl₂, FeCl₂ or NiCl₂ in a 7:3 (v/v) mixture of ethanol and triethyl orthoformate for 1–2 weeks, partial substitution of gu^? for Cl^? groups occurs, and solid complexes of the M(gu)Cl·2ROH (R = C₂H₅ for M = Mn; R = H for M = Fe, Ni) type are obtained. The new complexes are pentacoordinated and appear to be linear chainlike polymeric species, involving a single-bridged

_n backbone. Coordination number five is attained by the presence of one terminal chloro and two terminal ROH ligands per metal ion. Most probable binding sites of bidentate bridging gu^? are the N(7) and N(9) imidazole ring nitrogens. IR evidence rules out the possibility of coordination of gu^? through any of the exocyclic potential ligand sites (O(6) oxygen or N(2) nitrogen) [1].     

Blätteralkohol (XVI)Blätteralkohol (XVII)

2-Methyl-4, 6-cyclohexadienaldehyde and n-butyraldehyde were treated with sodium in p-xylene to yield the aromatized “leaf alcohol reaction” product, 2-methyl-benzylalcohol, in a better yield than that with the cyclohexadienaldehyde alone. n-Butyric acid isolated from the reaction mixture unequivocally showed the operation of the “crossed Cannizzaro disproportionation” in this reaction, aliphatic aldehyde serving as the hydride donor. 2-Propyl-5-ethyl-4, 6-cyclohexadienaldehyde was obtained by the NaOH/H₂O-EtOH Michael-Aldol condensation of leaf aldehyde, gave 2-propyl-5-ethyl-benzylalcohol along with caproic acid.

On the basis of “leaf alcohol-reaction” mechanism, it was obtained following benzyl-alkohols; 2-methyl-, 2-propyl-, 2-methyl-5-ethyl-, 2-propyl-5-ethyl-benzylalcohol, from leaf alcohol and crotylalcohol.     

Theoretical study on the interaction of titanocene dichloride with deoxyguanosine monophosphate

The completely hydrolyzed titanocene dichloride, [Cp₂Ti(H₂O)₂]²⁺ binding to guanine (G) and phosphate group sites of DNA were investigated by DFT method, with using deoxyguanosine monophosphate (dGMP) as incoming ligand. In the first substitutions, the calculations reveal that the diaquated titanocene binding to O6 shows the lowest activation free energy with 17.9 kcal/mol, closely followed by N7 is 20.5 kcal/mol and the O of phosphate group is 26.3 kcal/mol, respectively. It was also found that all the titanation processes are mildly endothermic. In addition, for the Ti-B(dGMP) in all separated products, the bond dissociation free energies (BDFE) of Ti-O(P, P = phosphate) is higher than those of Ti-N7/O6. In the second substitutions, the reactions leading to the didentate adducts are considered. For bidentate-bridging N7, O6 binding mode, the path of the metal Ti binding to O6 has the lower activation free energy (11.3 kcal/mol) than that of the metal Ti binding to N7 (15.3 kcal/mol). For the bidentate-bridging N7, O(P) binding mode, the path of the metal Ti binding to O(P) has the lower activation free energies (25.3 kcal/mol) than that of the metal Ti binding to N7 (26.2 kcal/mol).     

Nucleophilic displacement reactions in carbohydrates : Part XX. Displacements on alkyl α-l-talopyranoside 4-sulphonate derivatives

The azide displacement reaction on methyl 6-deoxy-4-O-methanesulphonyl-2,3-di-O-methyl-α-l-talopyranoside (6) in N,N-dimethylformamide yielded methyl 4,6-dideoxy-2,3-di-O-methyl-α-l-threo-hex-3-enopyranoside (7, ca. 50%), methyl 4,6-dideoxy-2,3-di-O-methyl-β-d-erythro-hex-4-enopyranoside (8, ca. 10%), and methyl 4-azido-4,6-dideoxy-2,3-di-O-methyl-α-l-mannopyranoside (9, ca. 40%). The corresponding azide 14 (20%) and the unsaturated sugars 12 (68%) and 13 (12%) were obtained from a comparable reaction on benzyl 6-deoxy-4-O-methanesulphonyl-2,3-di-O-methyl-α-l-talopyranoside (11).     

Xanthine-7-Ribosides as Adenosine Receptor Antagonists: Further Evidence for Adenosine'S Anti Mode Of Binding

Abstract

With the aid of computer graphics methods, we recently developed a model for the antagonist binding site of the adenosine A₁ receptor (J. Med. Chem. 1990, 33, 1708-1713). According to this model, xanthines should bind to the receptor in a flipped orientation, i.e. the ring atoms N1, N3, N7 and N9 in adenosine coincide with C2, C6, N9 and N7 respectively in theophylline (FIG. la and 1 b). This implicates that the domain where the ribose moiety of adenosine binds must be adjacent to N7 in xanthines, and furthermore that xanthine-7-ribosides should have affinity for the receptor. To further explore the role of the orientation of the ribose moiety in binding to the receptor, we have synthesized and determined the A₁ affinity of the 7-ribosides of theophylline, 13-dipropylxanthine and 1,3-dibutylxanthine (FIG. 1c). The orientation of the ribose moiety was studied with H-NMR spectroscopy and theoretical chemical calculations.     

Tetrahedral 1:1 adducts of guanine with cobalt(II), copper(II) and zinc(II) chlorides

Adducts of the M(guH)Cl₂ type were prepared by refluxing 2:1 molar mixtures of guanine (guH) and MCl₂ (M = Co, Cu, Zn) in ethanol-triethyl orthoformate for 2–3 days. Characterization studies suggest that all three new complexes involve distorted tetrahedral configurations. A linear chainlike polymeric structural type with a single-bridged (-MguH-)_n backbone and two terminal chloro ligands per metal ion (MN₂Cl₂ chromophore) is proposed for these compounds, in view of their poor solubility in organic media, their stoichiometry in conjunction with their tetrahedral symmetry, and the reported crystal structures of 9-methyladenine analogs (M = Co, Zn), which are polymeric with single bridges of the adenine derivative between adjacent metal ions. Bidentate bridging guH coordinates exclusively through ring nitrogens, and is most probably N(7), N(9)-bonded. The possibility of use of exocyclic potential ligand sites of guH (CO oxygen or NH₂ nitrogen) in coordination is ruled out by the infrared evidence [1].     

Preparation and structural characterization of methylmercury(II) complexes of the minor tRNA-base 7-methylguanine

Methylmercury(II) complexes of 7-methylguanine (7mguaH) have been isolated from aqueous solution in the pH range 1-12 and structurally characterized. 1:1 complexes [(7mgua)HgCH₃]·2H₂O and [(7mguaH)HgCH₃][NO₃]· H₂O with respectively N1 - and N9-coordination (X-ray analyses) were obtained from solutions in the respective pH ranges 9–12 and 1–4. A 2:1 complex [(7mgua)(HgCH₃)₂][NO₃] with N1,N9-coordination (X-ray) may be prepared in the intermediate pH range 4–7. Two 3:1 complexes were isolated: [(7mgua)(HgCH₃)₃][NO₃]₂ from strongly acid solution (pH = 1–3), and [(7mguaH₋₁)(HgCH₃)₃][NO₃] in the pH range 7–9. Whereas an X-ray analysis establishes N1,N3,N9-coordination for the former species in the solid state, the ¹H NMR data suggest N2,N3,N9-coordination for the former and N2,N2,N9-coordination for the latter species in d₆-DMSO solution.     

Effects of Photosystem II Herbicides on the Photosynthetic Membranes of the Cyanobacterium Aphanocapsa 6308

The effects of the photosystem II herbicides diuron (3-(3,4-dichlorophenyl)-1,1-dimethylurea) and atrazine (2-chloro-4-ethylamino-6-isopropylamino-s-triazine) on the photosynthetic membranes of a cyanobacterium, Aphanocapsa 6308, were compared to the effects on a higher plant, Spinacia oleracea. The inhibition of photosystem II electron transport by these herbicides was investigated by measuring the photoreduction of the dye 2,6-dichlorophenol-indophenol spectrophotometrically using isolated membranes. The concentration of herbicide that caused 50% inhibition of electron transport (I₅₀ value) in Aphanocapsa membranes for diuron was 6.8 × 10⁻⁹ molar and the I₅₀ value for atrazine was 8.8 × 10⁻⁸ molar. ¹⁴C-labeled diuron and atrazine were used to investigate herbicide binding with calculated binding constants (K) being 8.2 × 10⁻⁸ molar for atrazine and 1.7 × 10⁻⁷ molar for diuron. Competitive binding studies carried out on Aphanocapsa membranes using radiolabeled [¹⁴C]atrazine and unlabeled diuron revealed that diuron competed with atrazine for the herbicide-binding site. Experiments involving the photoaffinity label [¹⁴C]azidoatrazine (2-azido-4-ethylamino-6-isopropylamino-2-triazine) and autoradiography of polyacrylamide gels indicated that the herbicide atrazine binds to a 32-kilodalton protein in Aphanocapsa 6308 cell extracts.     

Synthesis and crystal structure of macrocyclic di-n-butyltin(IV) complex with 2-mercapto-4-methyl-5-thiazoleacetic acid, {[n-Bu2Sn(O2CCH2C4H3NS)SS(C4H3NSCH2CO2)Sn n-Bu2]O}2

A novel macrocyclic di-n-butyltin(IV) complex 1 was synthesized by the reaction of di-n-butyltin(IV) oxide and 2-mercapto-4-methyl-5-thiazoleacetic acid. Characterization of the complex 1 was achieved using elemental analysis, IR, ¹H, ¹³C and ¹¹⁹Sn NMR spectra and X-ray diffraction. X-ray data of the complex 1 revealed that it is an unusual macrocycle containing the bridging-S-S-linkages and tetranuclear ladder based on a planar four-membered Sn₂O₂ ring. In the so-called ladder structure, there are two distinct tin environments, the endocyclic tin atom is best described as five-coordinate and the exocyclic tin atom as six-coordinate.     

Characterisation of metal binding sites for 8-azaadenine. Formation and X-ray structural analysis of methylmercury(II) complexes

The compounds [(CH₃Hg)AAdH]NO₃ (1) and [(CH₃Hg)AAd]·4H₂O (2) have been isolated from aqueous 1:1 solutions of CH₃HgOH and 8-azaadenine (AAdH) at respective pH values of 2 and 5. Their structures have been established by X-ray structural analysis. N9 is the metal binding site in both complexes. Alteration of the metal to ligand ratio to 2:1 at a pH of 5 allows the preparation of [(CH₃Hg)₂AAd]NO₃·H₂O (3) in which the base is coordinated at both N3 and N9. The compound [(CH₃Hg)₃AAdH₋₁]NO₃ (4), in which N1, N6 and N9 function as binding sites for the CH₃Hg⁺ cation, is formed in a 3:1 solution at a pH of 6.5. X-ray structural analyses have been performed on 3 and 4. N8 takes part in weak intermolecular secondary bonds to symmetry related Hg9 atoms in all four complexes. The relevance of the structures to an understanding of the basicities of the nitrogen atoms in 8-azaadenine and their alteration upon metal coordination of N9 and N6 is discussed.     

Key structural features in cis-carane, (+)-3-carene,cis-pinane, (+)-α-pinene,and (−)-β-pinene influencing red turpentine beetle primary attraction when released with ethanol

1. In US Pacific Northwest ponderosa pine forests the primary attraction order shown previously for red turpentine beetle, Dendroctonus valens (Coleoptera: Curculionidae: Scolytinae), is (−)-β-pinene+ethanol > (+)-3-carene+ethanol > (+)-α-pinene+ethanol. The monoterpenes are bicyclic C₁₀H₁₆ isomers containing one 6-carbon ring with one double bond. Both pinenes have a 4-carbon second ring and differ only by their endocyclic or exocyclic double bond. The (+)-3-carene second ring has 3-carbons; its double bond is endocyclic like (+)-α-pinene.
2. Ring system and double bond influences on primary attraction were evaluated by hydrogenating (+)-3-carene and (+)-α-pinene to cis-carane and cis-pinane, respectively. Field test primary attraction strengths were (−)-β-pinene+ethanol > cis-carane+ethanol > cis-pinane+ethanol > ethanol.
3. In combination with ethanol (i) a double bond is not required in either ring system to attract D. valens, (ii) the cis-carane bicyclic 3, 6-carbon ring system provides stronger beetle attraction than the cis-pinane 4, 6-carbon bicyclic ring system, and likely structural basis for stronger (+)-3-carene attraction over (+)-α-pinene, (iii) adding an exocyclic double bond to the 4, 6-carbon ring system elevates attraction above the 3, 6-carbon ring system with no double bond, and (iv) the 4, 6-carbon ring system is a much stronger attractant with an exocyclic rather than endocyclic double bond.

     

A New Synthesis of 7-Methyl-8-Oxoguanosine

Abstract

A new, facile synthesis of 7-methyl-8-oxoguanosine is reported. 2-Chloro-7-methylpurine-6, 8-dione (5) was silylated with hexamethyldi-silazane and the silylated intermediate, 6, glycosylated with 1-0-acetyl-2, 3, 5-tri-0-benzoyl-D-ribofuranose to yield 2-chloro-7-methyl-9-(2′, 3′,-5′-tri-0-benzoyl-β-D-ribofuranosyl) purin-6, 8-dione (8). Deprotection of 8 with sodium hydroxide in aqueous methanol gave 2-chloro-7-methyl-9-(β-D-ribofuranosyl) purine-6,8-dione (9), which was aminated with liquid ammonia or methanolic ammonia to yield 7-methyl-8-oxoguanosine (3).     

Actions of the Klenow fragment of DNA polymerase I and some DNA glycosylases on chemically stable analogues of N7-methyl-2′-deoxyguanosine

N7-methyl-9-deaza-dG was synthesized and incorporated into oligonucleotides. Thermal melting studies showed that replacement of dG by N7-methyl-9-deaza-dG only slightly decreased DNA duplex stability. Replication of DNA templates containing N7-methyl-9-deaza-dG and the related 7-methyl-7-deaza-dG and 7-deaza-dG by the Klenow fragment of Escherichia coli DNA polymerase I was examined. The dNTP misinsertion frequencies on all three templates were comparably low, although the 7-methyl group significantly slowed down the turnover rates of the polymerase when dCTP was incorporated. The stabilities of N7-methyl-9-deaza-dG and 7-methyl-7-deaza-dG against the actions of formamidopyrimidine DNA glycosylase (Fpg) and human alkyladenine DNA glycosylase (hAAG) were also examined. N7-methyl-9-deaza-dG was stable in the presence of both enzymes. In contrast, 7-methyl-7-deaza-dG was cleaved by Fpg, and possibly by hAAG but at an extremely slow rate. This study suggests that N7-alkyl-9-deaza-dG is a better analogue than 7-alkyl-7-deaza-dG for cellular studies.     

EFFECTS OF S-TRIAZINES ON PROTEIN AND FINE STRUCTURE OF COTYLEDONS OF BUSH BEANS

A significant increase in protein content of bean cotyledons resulted by applications of 0.5 ppm of atrazine (2-chloro-4-ethylamino-6-isopropylamino-s-triazine), simazine [2-chloro-4,6-bis(ethylamino)-s-triazine], terbutryn (2-methylmercapto-4-ethylamino-6-isobutylamino-.s-triazine), or GS-14254 (2-methoxy-4-isopropylamino-6-butylamino-s-triazine) to the foliage of 5-6 week old bean plants grown in a controlled environment or field conditions. Aen electron microscopic study indicated that in the cotyledonary cells s-triazines inducd a 2-fold increase in the number of cisternae of rough endoplasmic reticulum. These treatments also increased the number of vesicles, which apparently contain protein, and the amount of cytoplasmic ribosomes.     

Preparation, X-ray structure and solution behavior of [Ag(9-EtGH-N7)2]NO3·H2O (9-EtGH=9-ethylguanine)

The preparation and X-ray structure of [Ag(9-EtGH-N7)₂]NO₃·H₂O(9-EtGH=neutral 9-ethylguanine) is reported. The compound crystallizes in the triclinic system, space group P with a=7.063(6), b=7.153(3), c=11.306(10) Å, α=83.36(6), β=76.66(7), γ=81.44(6)°. The cation is centrosymmetric with Ag(I) coordinated via two N7 positions and Ag---N7 bond lengths of 2.11(1) Å. Applying ¹⁰⁹Ag NMR spectroscopy, complex formation constants for both the 1:1 complex (log β₁=0.6) and the title compound (log β₂=1.6) in Me₂SO have been determined.     

Synthesis and structures of mono and binuclear nickel(II) thiolate complexes of a dicompartmental pseudo-macrocycle with N(imine)2S2 and N(oxime)2S2 metal-binding sites

The reaction of [Ni(pftp)] [pftp = N,N-propane-1,3-diyl-(6-formyl-4-methyliminatothiophenolato)] with hydroxylamine hydrochloride in the presence potassium acetate in MeOH resulted in the formation of the complex [Ni(LH₂)] [L = N,N-propane-1,3-diyl-(4-methyl-2-methyliminato-6-methyloxime-thiophenolato)] in good yield. A single crystal X-ray diffraction structural determination showed a mononuclear nickel(II) complex with the new acyclic ligand LH₂ that had been functionalised with two oxime groups containing an empty N(oxime)₂S₂ pocket to which another metal ion could be added. A further reaction of [Ni(LH₂)] with NiCl₂·6H₂O, triethylamine and ammonium hexafluorophosphate in MeOH gave a dark red product that yielded red crystals of [Ni₂(LH)]PF₆·DMF via slow recrystallisation from a DMF/PrⁱOH solvent mixture. A single crystal X-ray diffraction study of these crystals confirmed the presence of a dinuclear nickel(II) complex linked by a dithiolato-bridge. Both nickel(II) ions exhibited square-planar geometry where the metal centres are coordinated in two distinct cis-S₂N(imine)₂ and cis-S₂N(oxime)₂ binding sites provided by the new dicompartmental oxime/thiolate-containing ligand LH.     

Adenine complexes with divalent 3d metal chlorides

Upon refluxing 2:1 mixtures of adenine (adH) and divalent 3d metal chloride hydrates in a 7:3 (v/v) mixture of ethanol-triethyl orthoformate for several days, partial substitution of ad^? for Cl^? ligands occurs, and solid complexes of the M(ad)Cl· 2H₂0 (M = Mn, Zn), Fe₂(ad)(adH)₂Cl₃·2H₂O, M(ad)- (adH)Cl·H₂O (M = Co, Cu) and Ni₂(ad)₃Cl·6H₂O types are eventually isolated [1]. It is probably of interest that during analogous previous synthetic work, involving interaction of ligand and salt in refluxing ethanol, no substitution reactions between Cl^? and ad^? took place, and MCl₂ adducts with neutral adH were reportedly obtained. Characterization studies suggest that the new complexes reported are linear chainlike polymeric species, involving single adenine bridges between adjacent M²⁺ ions. Terminal chloro, adenine and aqua ligands complete the coordination around each metal ion. The new Ni²⁺ complex is hexacoordinated, whilst the rest of the complexes are pentacoordinated. Most likely binding sites are considered to be N(9) for terminal unidentate and N(7), N(9) for bridging bidentate adenine [1].     

Structural Differences between the Avian and Human H7N9 Hemagglutinin Proteins Are Attributable to Modifications in Salt Bridge Formation: A Computational Study with Implications in Viral Evolution

Influenza A hemagglutinin (HA) is a homotrimeric glycoprotein composed of a fibrous globular stem supporting a globular head containing three sialic acid binding sites responsible for infection. The H7N9 strain has consistently infected an avian host, however, the novel 2013 strain is now capable of infecting a human host which would imply that the HA in both strains structurally differ. A better understanding of the structural differences between the avian and human H7N9 strains may shed light into viral evolution and transmissibility. In this study, we elucidated the structural differences between the avian and human H7N9 strains. Throughout the study, we generated HA homology models, verified the quality of each model, superimposed HA homology models to determine structural differences, and, likewise, elucidated the probable cause for these structural differences. We detected two different types of structural differences between the novel H7N9 human and representative avian strains, wherein, one type (Pattern-1) showed three non-overlapping regions while the other type (Pattern-2) showed only one non-overlapping region. In addition, we found that superimposed HA homology models exhibiting Pattern-1 contain three non-overlapping regions designated as: Region-1 (S157₁-A160₁); Region-3 (R262₁-S265₁); and Region-4 (S270₁-D281₁), whereas, superimposed HA homology models showing Pattern-2 only contain one non-overlapping region designated as Region-2 (S137₁-S145₁). We attributed the two patterns we observed to either the presence of salt bridges involving the E114₁ residue or absence of the R141₁:D77₁ salt bridge. Interestingly, comparison between the human H7N7 and H7N9 HA homology models showed high structural similarity. We propose that the putative absence of the R141₁:D77₁ salt bridge coupled with the putative presence of the E114₁:R262₁ and E114₁:K264₁ salt bridges found in the 2013 H7N9 HA homology model is associated to human-type receptor binding. This highlights the possible significance of HA salt bridge formation modifications in viral infectivity, immune escape, transmissibility and evolution.     

Repeated use of Bacillus subtilis cell walls for copper binding

Purified cell walls from Bacillus subtilis were repeatedly suspended in 5 mm CuCl₂ and, after removing unbound Cu, were suspended in 1% (v/v) HNO₃ to release bound Cu. The walls were then regenerated by washing in H₂O. After five cycles, copper binding actually increased slightly, probably due to enhanced exposure of binding sites in the walls. Thus bacterial walls may be used repeatedly for metal removal during bioremediation of heavy metal pollution.R.J.C. McLean is with the Department of Biology, Southwest Texas State University, 601 University Drive, San Marcos, TX 78666-4616, USA A.M. Campbell is with the Department of Chemical Engineering, Queen's University, Kingston, Ontario, K7L 3N6, Canada. P.T. Khu is with the Department of Mining Engineering, Queen's University, Kingston, Ontario, K7L 3N6, Canada. A.T. Persaud, L.E. Bickerton and D. Beauchemin are with the Department of Chemistry, Queen's University, Kingston, Ontario, K7L 3N6, Canada.