The structure of metallo-DNA with consecutive thymine–HgII–thymine base pairs explains positive entropy for the metallo base pair formation

We have determined the three-dimensional (3D) structure of DNA duplex that includes tandem Hg^II-mediated T–T base pairs (thymine–Hg^II–thymine, T–Hg^II–T) with NMR spectroscopy in solution. This is the first 3D structure of metallo-DNA (covalently metallated DNA) composed exclusively of ‘NATURAL’ bases. The T–Hg^II–T base pairs whose chemical structure was determined with the ¹⁵N NMR spectroscopy were well accommodated in a B-form double helix, mimicking normal Watson–Crick base pairs. The Hg atoms aligned along DNA helical axis were shielded from the bulk water. The complete dehydration of Hg atoms inside DNA explained the positive reaction entropy (ΔS) for the T–Hg^II–T base pair formation. The positive ΔS value arises owing to the Hg^II dehydration, which was approved with the 3D structure. The 3D structure explained extraordinary affinity of thymine towards Hg^II and revealed arrangement of T–Hg^II–T base pairs in metallo-DNA.     

Ab initio investigations on planar (MgO)n clusters (n = 1–5) and their hydrogen adsorption behaviour

Ab initio calculations (B3LYP and PBE-D3) of the structures, stabilities, vibrational, electronic and hydrogen adsorption behaviour of (MgO)_n clusters are performed using 6-311+ + G(d,p) basis set. The planar (MgO)_n clusters are found to be global minima for n ≤ 3 and local minima for n = 4 and 5. In addition, we have also analysed global minimum structures of (MgO)₄ and (MgO)₅. The binding energies suggest that their stabilities increase successively. Vibrational frequencies and IR intensities further support the enhanced stability with an increase in the size of (MgO)_n clusters. The highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) surfaces are used to explain and discuss the electronic properties. Finally, we have demonstrated hydrogen storage capacity of (MgO)_n clusters, considering hydrogen adsorption on planar as well as global minimum (MgO)₄ and (MgO)₅ clusters. We have noticed that four and five H₂ molecules can be easily adsorbed by (MgO)₄ and (MgO)₅ clusters having adsorption energy of 0.13–0.14 eV with mass ratio of 4.76%. Thus, the present study is expected to motivate further the applications of small clusters for efficient hydrogen energy storage.     

Anti-HIV Derivatives of 1-(2,3-Dideoxy-3-N-hydroxyamino-β-D-threo-pentofuranosyl)thymine

Abstract

Representative examples of the title compounds including bicyclic analogs (7–9) in which a perhydro-1,3-oxazine is ortho-fused to the furanose ring, have been prepared in good to excellent yields. Compounds 5 and 7 showed marked activity against HIV-1 and HIV-2 replication in CEM cells (50% inhibitory concentration: 0.80–4.3μg/mL). Their di-O-acetylated (6) and mono-O-acetylated (8) derivatives were considerably less effective. To the best of our knowledge, these β-D-threo anti-HIV nucleoside analogs constitute the first examples of anti-HIV active nucleosides bearing this configuration.     

Heterotrophic bacterial production in Lake Xolotlán (Managua) during 1988–1989

The biomass and production (thymidine incorporation) of heterotrophic bacterioplankton has been assessed from July, 1988, to October, 1989. in Lake Xolotlán, Nicaraqua. Bacterial abundance was high, 2–3.10¹⁰ cells.l^–1, and bacterial biomass averaged ca. 0.75 mg C.l^–1, or roughly 20% of the partivculate organic carbon. Bactrial production averaged between 3.5–5 g C.l^–1.h^–1 and on a areal basis was 650–959 mg C.m^–2.d^–1 or 13–20% ofthe primary production. Although bacterial production (volumetric basis) was typical for eutrophic lakeks, the bacterial specific growth rate was low, the bacteial population doubling time was ca. 1 week, perhaps indicating that there was a low grazing pressure on the bacteria.     

Large gallanes and the PSEPT theory: a theoretical study of Ga n H n+2 clusters (n?=?7–9)

Do alanes Al(n)H(n+2) and gallanes Ga(n)H(n+2) satisfy the polyhedral skeletal electron pair theory (PSEPT)? Taking into account previous work on this question, this paper provides a convincing answer and proposes the reformulation of the (n + 1) electron pairs rule of Wade and Mingos (W-M) for such systems. Following recent studies of tetra-, penta-, hexa-, hepta-, octa-, and nonaalanes as well as valence-isoelectronic/related gallanes, in this paper we present an analysis of the hydrides of aluminum and gallium A(n)H(n+2) (A = Al, Ga and n = 7-9). The aim is still to examine the applicability of PSEPT, especially the W-M rule, to these clusters. Exploration of the total potential energy surfaces (PESs) of hepta-, octa-, and nonagallanes shows that the absolute minima have a nido-like polyhedron arrangement. Unlike the smaller Ga(n)H(n+2) (n = 4, 5, 6), it seems that the size of the cluster largely dictates its preferred geometry. Although none of them have closed (totally triangular) cages, these clusters exhibit significant compactness, comparable to borane double anions, B(n)H(n) (2-), which are the archetypes for the PSEPT theory.     

Aliphatic substituents in place of thymine methyl promote zig-zag character of the poly(dA-dT)·poly(dA-dT) backbone

This work compared circular dichroism and phosphorus n.m.r. of poly(dA-dU)·poly(dA-dU), poly(dA-dT)·poly(dA-dT), poly(dA-ethyl⁵dU)·poly(dA-ethyl⁵dU), and poly(dA-butyl⁵dU)·poly(dA-butyl⁵dU) at low-salt and in concentrated caesium chloride and caesium fluoride solutions. It is demonstrated that growing bulk of the substituent increases the conformationl anomaly residing in the purine(3′–5′)pyrimidine steps while the backbone is less affected in the pyrimidine (3′–5′)purine steps. As the length of the substituent increases, conformation of the polynucleotides alters more dramatically at increasing concentrations of caesium cations. At high CsF concentrations, all the polynucleotides adopt a novel conformer which we call X-DNA and its formation is promoted by larger substituents. The X-DNA conformation of poly(dA-butyl⁵dU)·poly(dA-butyl⁵dU) gives two phosphorus n.m.r. resonances separated as much as in the case of the left-handed zig-zag Z-DNA double helix of poly(dG-dC)·poly(dG-dC) but X-DNA and Z-DNA differ qualitatively by an opposite dinucleotide repeat. Phosphorus n.m.r. spectra of poly(dA-dT)·poly(dA-dT) and poly(dA-butyl⁵dU)-poly(dA-butyl⁵dU) differ quantitatively at high CsF concentrations, which may reflect conformational variability of the X-DNA backbone. Poly(dA-butyl⁵dU)·poly(dA-butyl⁵dU), but not poly(dA-ethyl⁵dU)·poly(dA-ethyl⁵dU) and the related polynucleotides with shorter substituents in position 5 of uracil, exhibits one more reversible transition at very high caesium fluoride concentrations. It is accompanied by polynucleotide associations and has a slow kinetics. This transition may involve one more radical change in the double helix architecture from X-DNA into another conformation.     

9-(2-Deoxy-ß-D-xylofuranosyl)adenine and 1-(2-Deoxy-ß-D-xylofuranosyl)thymine: Phosphorylation and Stability

Abstract

Phosphorylation of 1-(2-deoxy-β-D-xylofuranosyl)thymine (1) or 9-(2-deoxy-β-D-xylofuranosyl)adenine (3) with phosphoryl chloride gives the cyclic 3′,5′-phosphates (2 and 4a) but not the 5′-monophosphates 8a or 8b. The latter are obtained by phosphorylation of the 3′-0-benzoylated 2′-deoxy-β-D-xylonucleosides (7a, b) and subsequent base-catalyzed removal of the benzoyl groups. Compound 3, as the parent dA, depurinates in acidic medium, a reaction which is facilitated in the case of the N⁶-benzoyl derivative 9b and reduced after the introduction of an amidine protecting group. N-Glycosylic bond hydrolysis of 2′-deoxy-β-D-xylofuranosyl nucleosides is enhanced by a factor of two compared to 2′-deoxy-β-D-ribofuranosyl nucleosides.     

Abundance and degree of dispersion of genomic d(GA) n ·d(TC) n sequences

Summary The abundance of d(GA) _n ·d(TC) _n tracts was determined in genomes of rodents and primates. Dot blot hybridization assays revealed that such tracts constitute 0.40%, 0.30%, and 0.40%, respectively, of the rat, hamster, and mouse genomes, but only 0.07% and 0.05% of the human and monkey genomes. A plaque hybridization assay of rat and human genomic libraries showed that 37% and 16%, respectively, of the recombinant phages in these libraries contain d(GA) _n ·d(TC) _n tracts. A survey of sequences stored in the GenBank data bank showed that a significant fraction of the stored rodent genes (about 2.0%) contain long d(GA) _n ·d(TC) _n tracts (n> 30) with <10% mismatching. The primate genes contain only shorter tracts (n<15) with <10% mismatching. In addition, the rodent and the primate genes contain tracts with larger degrees of mismatching. The chicken, which represents an entirely different branch of the evolutionary tree, was found to be as low in d(GA) _n ·d(TC) _n tracts as the primates. It is suggested that a common ancestor of the rodents has acquired the ability to amplify d(GA) _n ·d(TC) _n tracts.     

Robert (Robin) Hill (1899–1991)

Obituary

Robert (Robin) Hill (1899–1991)     

A Structural Transition in d(AT) n ·d(AT) n Inserts within Superhelical DNA

Abstract

We have constructed plasmids carrying d(AT)_n·d(AT)_n inserts of different lengths. Two- dimensional gel electrophoresis patterns show that an increase in the negative superhelicity of these DNAs brings about a structural transition within the inserts, resulting in a reduction of the superhelical stress. However, this reduction corresponds to the expected values neither for cruciform nor for the Z form. Those DNA topoisomers in which the structural transition had occurred proved to be specifically recognizable by single-strand-specific endonuclease SI, with the cleavage site situated at the centre of the insert. These data, as well as kinetic studies, suggest that the cloned d(AT)_n·d(AT) _n sequences adopt a cruciform rather than the Z-form structure. We discuss plausible reasons of the discrepancy between the observed superhelical stress release and that expected for the transition of the insert to the cruciform state.     

Synthesis of (–)-Muricatacin

The synthesis of (–)-muricatacin starting from 1-bromododecane and 2-pentyn-l-ol is described. 2-Pentadecyn-1-ol (4), which was prepared from 1-bromododecane (2) and 2-pentyn-1-ol (3), was converted to epoxy alcohol 6 through a two-step reaction sequence, 6 being successively submitted to tosylation, iodination, chain extension with tert-butyl lithioacetate, and acid-catalyzed cyclization to give (–)-muricatacin (1a). Recrystallization afforded optically pure 1a.     

Apparent relative retention of the phosphatidylethanolamine molecular species 18:0–20:5(n−3), 16:0–22:6(n−3) and the sum 16:0–20:4(n−6) plus 16:0–20:3(n−9) in the liver microsomes of pig on an essential fatty acid deficient diet

Attempts at a better understanding of the cell membrane organization and functioning need to assess the physical properties which partly depend (i) on the positional distribution of the fatty acids in the membrane phospholipids (PLs) and (ii) on the way by which the PL molecular species are affected by exogenous fatty acids. To do that, the effects of essential (polyunsaturated) fatty acid (EFA) deficiency and enrichment were studied in the liver microsomes of piglets feeding on either an EFA-deficient diet or an EFA-enriched diet containing hydrogenated coconut oil or a mixture of soya + corn oils, respectively. After derivatization, the diacylated forms of choline and ethanolamine PLs were analyzed using a combination of Chromatographic techniques and fast-atom bombardmentmass spectrometry. The dinitrobenzoyl-diacylglycerol derivatives corresponding to the molecular species of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were identified. It appears that three factors brought about a marked apparent relative retention: the nature of (i) the base of the polar head, (ii) fatty acids at the sn−1 position and (iii) fatty acids at the sn−2 position. The highest apparent relative retentions were displayed by the 18:0–20:5(n−3)-PE and 16:0–22:6(n−3)-PE. It is noteworthy that the behavior of 20:3 n−9 — which is synthesized during the EFA-deficient diet by the same bioconversion system as 20:4 n−6 — was very similar to that of 20:4 n−6 during the formation of PC and PE molecular species and that the molecular species of PE containing 20:4(n−6) and 20:3(n−9), gathered together as metabolical homologues, were also apparently retained, particularly in association with 16:0. Present observations are consistent with some others showing retention or preferential distribution of EFA in PE and suggest that specific acyltransferase(s), ethanolamine phosphotransferase and methyltransferase would be mainly involved for PE and PC formation in liver endoplasmic reticulum. Fast-atom bombardment-mass spectrometry of intact phospholipids enables us to show that there is no very long chain dipolyunsaturated phospholipid in liver endoplasmic reticulum.     

DNA binding by Ru(II)–bis(bipyridine)–pteridinyl complexes

The interactions of five bis(bipyridyl) Ru(II) complexes of pteridinyl-phenanthroline ligands with calf thymus DNA have been studied. The pteridinyl extensions were selected to provide hydrogen-bonding patterns complementary to the purine and pyrimidine bases of DNA and RNA. The study includes three new complexes [Ru(bpy)(2)(L-pterin)](2+), [Ru(bpy)(2)(L-amino)](2+), and [Ru(bpy)(2)(L-diamino)](2+) (bpy is 2,2'-bipyridine and L-pterin, L-amino, and L-diamino are phenanthroline fused to pterin, 4-aminopteridine, and 2,4-diaminopteridine), two previously reported complexes [Ru(bpy)(2)(L-allox)](2+) and [Ru(bpy)(2)(L-Me(2)allox)](2+) (L-allox and L-Me(2)allox are phenanthroline fused to alloxazine and 1,3-dimethyalloxazine), the well-known DNA intercalator [Ru(bpy)(2)(dppz)](2+) (dppz is dipyridophenazine), and the negative control [Ru(bpy)(3)](2+). Reported are the syntheses of the three new Ru-pteridinyl complexes and the results of calf thymus DNA binding experiments as probed by absorption and fluorescence spectroscopy, viscometry, and thermal denaturation titrations. All Ru-pteridine complexes bind to DNA via an intercalative mode of comparable strength. Two of these four complexes-[Ru(bpy)(2)(L-pterin)](2+) and [Ru(bpy)(2)(L-allox)](2+)-exhibit biphasic DNA melting curves interpreted as reflecting exceptionally stable surface binding. Three new complexes-[Ru(bpy)(2)(L-diamino)](2+), [Ru(bpy)(2)(L-amino)](2) and [Ru(bpy)(2)(L-pterin)](2+)-behave as DNA molecular "light switches."     

Charge Transport in Poly(dG)–Poly(dC) and Poly(dA)–Poly(dT) DNA Polymers

We investigate the charge transport in synthetic DNA polymers built up from single type of base pairs. In the context of a polaronlike model, for which an electronic tight-binding system and bond vibrations of the double helix are coupled, we present estimates for the electron-vibration coupling strengths utilizing a quantum-chemical procedure. Subsequent studies concerning the mobility of polaron solutions, representing the state of a localized charge in unison with its associated helix deformation, show that the system for poly(dG)–poly(dC) and poly(dA)–poly(dT) DNA polymers, respectively possess quantitatively distinct transport properties. While the former supports unidirectionally moving electron breathers attributed to highly efficient long-range conductivity, the breather mobility in the latter case is comparatively restrained, inhibiting charge transport. Our results are in agreement with recent experimental results demonstrating that poly(dG)–poly(dC) DNA molecules acts as a semiconducting nanowire and exhibit better conductance than poly(dA)–poly(dT) ones.