A comparative theoretical investigation into the strength of the trigger-bond in the Na+, Mg2+ and HF complexes involving the nitro group of R–NO2 (R = –CH3, –NH2 and –OCH3) or the C = C bond of (E)-O2N–CH = CH–NO2

A comparative theoretical investigation into the change in strength of the trigger-bond upon formation of the Na⁺, Mg²⁺ and HF complexes involving the nitro group of RNO₂ (R?=? –CH₃, –NH₂, –OCH₃) or the C?=?C bond of (E)-O₂N–CH?=?CH–NO₂ was carried out using the B3LYP and MP2(full) methods with the 6-311++G**, 6-311++G(2df,2p) and aug-cc-pVTZ basis sets. Except for the Mg²⁺?π system with (E)-O₂N–CH?=?CH–NO₂ (i.e., C₂H₂N₂O₄?Mg²⁺), the strength of the trigger-bond X–NO₂ (X?=?C, N or O) was enhanced upon complex formation. Furthermore, the increment of bond dissociation energy of the X–NO₂ bond in the Na⁺ complex was far greater than that in the corresponding HF system. Thus, the explosive sensitivity in the former might be lower than that in the latter. For C₂H₂N₂O₄?Mg²⁺, the explosive sensitivity might also be reduced. Therefore, it is possible that introducing cations into the structure of explosives might be more efficacious at reducing explosive sensitivity than the formation of an intermolecular hydrogen-bonded complex. AIM, NBO and electron density shifts analyses showed that the electron density shifted toward the X–NO₂ bond upon complex formation, leading to a strengthened X–NO₂ bond and possibly reduced explosive sensitivity.

Antitubercular activity of α,ω-diaminoalkanes,H2N(CH2)nNH2

A series of 11 α,ω-diaminoalkanes, (H₂N(CH₂)_nNH₂, n = 2–12) have been evaluated for their in vitro antibacterial activity against Mycobacterium tuberculosis H37Rv. Compounds, (H₂N(CH₂)_nNH₂, n = 9–12), exhibited a very good activities in the range 2.50–3.12 μg/mL, which can be compared with that of the first line drug, ethambutol (3.12 μg/mL). These results and a preliminary QSAR study can be considered an important start point for the rational design of new leads for anti-TB compounds.     

Characterization of the Distal Polyadenylation Site of the ?-Adducin (Add2) Pre-mRNA

Most genes have multiple polyadenylation sites (PAS), which are often selected in a tissue-specific manner, altering protein products and affecting mRNA stability, subcellular localization and/or translability. Here we studied the polyadenylation mechanisms associated to the beta-adducin gene (Add2). We have previously shown that the Add2 gene has a very tight regulation of alternative polyadenylation, using proximal PAS in erythroid tissues, and a distal one in brain. Using chimeric minigenes and cell transfections we identified the core elements responsible for polyadenylation at the distal PAS. Deletion of either the hexanucleotide motif (Hm) or the downstream element (DSE) resulted in reduction of mature mRNA levels and activation of cryptic PAS, suggesting an important role for the DSE in polyadenylation of the distal Add2 PAS. Point mutation of the UG repeats present in the DSE, located immediately after the cleavage site, resulted in a reduction of processed mRNA and in the activation of the same cryptic site. RNA-EMSA showed that this region is active in forming RNA-protein complexes. Competition experiments showed that RNA lacking the DSE was not able to compete the RNA-protein complexes, supporting the hypothesis of an essential important role for the DSE. Next, using a RNA-pull down approach we identified some of the proteins bound to the DSE. Among these proteins we found PTB, TDP-43, FBP1 and FBP2, nucleolin, RNA helicase A and vigilin. All these proteins have a role in RNA metabolism, but only PTB has a reported function in polyadenylation. Additional experiments are needed to determine the precise functional role of these proteins in Add2 polyadenylation.     

The reactivity of bromoform with [Au(CH2)2PPh2]2. The completion of the halomethane series CHyX4−y (y=3,2,1,0; X=Cl,Br, I) and reactivity with [Au(CH2)2PPh2]2

The reaction of [Au(CH₂)₂PPh₂]₂ with excess CHBr₃ in benzene initially gives [Au(CH₂)₂PPh₂]₂₋ (CHBr₂)Br. This observation establishes that halomethanes, CH_yX_4−y (y=3,2,1,0; X=Cl, Br, I), react with [Au(CH₂)₂PPh₂]₂ to initially give Au(II) adducts of the general form [Au(CH₂)₂PPh₂]₂₋(CH_yX_3−y)X (y=3,2,1,0) via oxidative addition across the carbon-halogen bond. The order of reactivity inversely follows the order of carbon-halogen bond dissociation energies of haloalkanes. Methyl chloride is the only halomethane of the series that does not give a Au(II) adduct under similar reaction conditions.     

Chiroptical properties of diastereomeric five-coordinate Pt(II)–olefin complexes. Molecular structure of [PtCl2{(S,S)-(E)-CNCHCHCN}(R,R)-{C6H5CH(CH3)N(CH3)CH2}2]·C6H6

The chiroptical properties of five-coordinate diastereomeric complexes of general formula [PtCl₂(R,R)-{C₆H₅CH(CH₃)N(CH₃)CH₂}₂{olefin}], with olefin ligands having electron-withdrawing substituents, have been investigated. The sign of CD bands in the 28 000–30 000 cm⁻¹ region appears to be correlated to the absolute configuration of the prochiral coordinated alkene. Single-crystal X-ray diffraction structure determination has been performed on the single diastereomer [PtCl₂(E-but-2-enedinitrile)(R,R)-{C₆H₅CH(CH₃)N(CH₃)CH₂}₂]· C₆H₆. The compound crystallizes in the monoclinic space group C2 with a = 17.842(2), b = 8.466(1), c = 10.464(1) Å, β = 109.34(1)°, Z = 2. The number of observed reflections was 1943 and the final R and R_w values were 0.020 and 0.028 respectively. Trigonal-bipyramidal geometry is observed around the Pt atom, with the two Cl atoms in axial positions. The unsaturated ligand lies in the equatorial plane disclosing S,S absolute configuration.     

Binuclear rhodium carbonyl halide complexes containing the 1,1-bis(diphenylphosphino)ethene ligand,and the crystal structure of [Rh2Cl2(μ-CO){Ph2PC(CH2)PPh2}2]

Treatment of [RhCl(CO)₂]₂ with 1,1-bis(diphenylphosphino)ethene (dppee) yields the cationic binuclear rhodium complex [Rh₂(μ-Cl)(CO)₂(μ-CO)(dppee)₂]⁺ which may be isolated as the [RhCl₂(CO)₂]⁻ salt at low temperature (230 K) but which readily forms the Cl⁻ salt on allowing the solution to warm to room temperature. On bubbling nitrogen through a solution of this cationic complex at room temperature, the monocarbonyl species, [Rh₂Cl₂(μ-CO)(dppee)₂] is obtained. The crystal structure of this complex has been determined. The crystals are orthorhombic, space group Pnca, a = 29.98(3), b = 23.70(2), c = 14.78(3) Å, Z = 8. Using 3019 unique reflections the structure was refined to R = 0.091. The rhodium-rhodium distance is 2.650(14) Å. Direct rhodium NMR data are reported for these complexes.     

Partial structure of the human α2(IV) collagen chain and chromosomal localization of the gene (COL4A2)

Summary We have isolated a 2.1-kb cDNA clone from a human placental library encoding part of the 2 chain of collagen IV, a major structural protein of basement membranes. The DNA sequence encodes 446 amino acids in the triplehelical domain plus the 227 amino acids of the carboxy-terminal globular domain. The latter structure is composed of two homologous subdomains and is highly conserved between the 1 and 2 chains. The triple-helical domain contained seven interruptions of the Gly-X-Y repeat and these interruptions were in general larger than their counterparts in the 1 chain. DNA from human rodent hybrid cell lines was analyzed under conditions in which there was no cross-hybridization of the 2(IV) cDNA probe with the gene for the 1(IV) collagen chain. An Eco RI fragment characteristic of the 2 chain had a concordance of 0.97 with chromosome 13. This result was confirmed and extended with in situ localization of the gene at 13q34. Since the 1(IV) gene has previously been localized to 13q34, the two type IV collagen genes reside in the same chromosome region (13q34), possibly in a gene cluster. The presence of the genes for type IV collagen chains on chromosome 13 excludes a primary role for these genes in adult polycystic kidney disease and X-linked forms of hereditary nephritis.     

125Te Mössbauer spectra of the intercalation compound (Te2)2(I2)

The quadrupole split asymmetric ¹²⁵Te Mössbauer spectrum recorded from the compound (Te₂)₂(I₂), in which monomolecular planar layers of iodine molecules are intercalated between layers of tellurium, is a reflection of the distorted environment of tellurium atoms in a two-dimensional layered compound in which the elongated flat crystals are preferentially orientated. The differences between the Mössbauer parameters recorded from (Te₂)₂(I₂) and those recorded from elemental tellurium and the tellurium(0) species in the compound Te₃Cl₂ are associated with small differences between the environments of tellurium in the three compounds. The Mössbauer spectra recorded from (Te₂)₂(I₂) are consistent with a recently proposed model on which the electronic band structure of (Te₂)₂(I₂) has been derived.     

Emission polarization study of the interaction of stellacyanin with tris(2, 2′-bipyridine)osmium(II)

The association of Os(bpy)₃²⁺ and stellacyanin was investigated by measuring the emission polarization of the excited state of the complex [*Os-(bpy)₃²⁺]. At high protein concentration (≥1 mM) Os(bpy)₃²⁺ appears to bind weakly to reduced stellacyanin and to oxidized stellacyanin to a lesser extent. These results are consistent with those obtained in a previous kinetic study on the redox quenching of *Ru(bpy)₃²⁺ by stellacyanin [1]. On excitation at 480 nm, the limiting polarization (P_o) of the *Os(bpy)₃²⁺ emission at 715 nm is 0.100. From P_o we concluded that (1) protein-bound Os(bpy)₃²⁺ has considerable rotational freedom independent of the protein-probe complex, and (2) the emission dipole of *Os(bpy)₃²⁺ is at ∼45° to the C₃ molecular axis.     

The nature of stabilization of the tandem DNA duplex pTGGAGCTG · (pCAGC+(Phn-NH-(CH2)3-NH)pTCCA) basing on the UV, CD, and two-dimensional NMR spectroscopy data

The properties and the three-dimensional structure of the tandem DNA duplex pTGGAGCTG·(pCAGC+(PhnL)pTCCA) in aqueous solution, where L is an amino linker and Phn is anN-(2-hydroxyethyl)phenazinium residue, were studied spectrophotometrically and by two-dimensional¹H NMR spectroscopy (COSY and NOESY). When a tandem complex involving a Phn residue-bearing oligonucleotide is formed, the dye aromatic system intercalates into the double helix at the nick site and takes part in two stacking interactions: a strong one (3.5–4 Å) with the T⁵-A¹² base pair of its own duplex moiety and a weak one (4–5 Å) with the C⁴-G¹³ pair of the adjoining duplex (mainly with the C⁴ base). This arrangement of the dye residue, providing a cross-interaction of the phenazinium moiety with the base pairs of the adjacent duplex structures, results in the stabilization of the whole tandem complex.     

New synthesis of seven-coordinate complexes of molybdenum(II) and tungsten(II) containing bidentate phosphorus ligands, [MI2(CO)3{Ph2P(CH2)nPPh2}] (n = 1–6)

A new high yielding synthesis of the seven-coordinate complexes [MI₂(CO)₃{Ph₂P(CH₂)_nPPh₂}] (M = Mo and W; n = 1–6) is described. The procedure involves reacting the complexes [MI₂(CO)₃(NCMe)₂] in CH₂Cl₂ with an equimolar amount of the bidentate phosphorus ligand. The low temperature (−70 °C) ¹³C NMR spectra of the complexes [Wl₂(CO)₃{Ph₂P(CH₂)_nPPh₂}] (n = 3 and 5) indicates that the geometry is capped octahedral with a carbonyl ligand in the unique capping position.     

Synthesis of the Selenium Analog of the Cytokinin 6-(3-Methyl-2-Butenylamino)-2-Methylthio-9-(β-D-Ribofuranosyl)Purine

Abstract

6-(3-methyl-2-butenylamino)-2-methylthio-9-(β-D-ribofuranosyl)purine (1) is a naturally occurring nucleoside with potent cytokinin activity. It has been isolated and identified in the t-RNA of E. coli,^1,2 the t-RNA from wheat germ^3,4 and from Staphylococcus epidermidis.⁵ In addition, compound 1 has been found in t-RNA species corresponding to each of six amino acids whose codons start with uridine, i.e., t-RNA^Cys     

H-2-Controlled polymorphism of the γ chain of Slp (sex-limited protein)

A genetic polymorphism detected by the O'Farrell two-dimensional technique (isoelectric focusing and SDS-PAGE) of the murine sex-limited protein (Slp) is described and shown to map to theH-2 complex. The Slp charge variation was found to be in the chains. Inbred strains carrying theH-2 ^w7 andH-2 ^wr7 haplotypes, which are derived from a wild mouse, had Slp- chains with pI = 6.55 (Slp-l^b). All other inbred strains, bearingH-2ij,H-2 ^s ,H-2 ^p ,H-2 ^d ,H-2 ^u , as well as three additional Slp-constituive wild females captured in Chile, had Slp- chain with pI = 6.71 (Slp-l^a).     

The reactions of organosulfur transfer reagents with Fe2(CO)9 and the synthesis of the Fe2(CO)6 derivative of α-lipoic acid

Treatment of Fe₂(CO)₉ with sulfur-transfer reagents of the types ImideSSImide and RSSImide where H-imide = phthalimide, succinimide, benzimidazole, morpholine and piperazine, and R  CH₂Ph and CMe₃ leads to cleavage of both the sulfursulfur bond and the sulfurnitrogen bond to give Fe₃(CO)₉S₂ in varying yields, some Fe₂(CO)₆S₂ plus low yields of the appropriate dimers of the type Fe₂(CO)₆(SR)(SR′), where R = R′ = phthal imido, CH₂Ph, CMe₃ and R = CH₂Ph, CMe₃, R′ = phthalimido. The naturally occurring cyclic disulfide D,L-α-lipoic acid, its methyl ester and amide react with Fe₂(CO)₉ to give Fe₂(CO)₆ derivatives wherein the sulfursufur bond has been broken.     

Combination of Azidothymidine (AZT) and (E)-5-(2-Bromovinyl)-2′-deoxyuridine (BVDU) Inhibits the Replication of Herpes Simplex Virus Type 1 (HSV-1) and Type 2 (HSV-2) and Varicella Zoster Virus (VZV) Strains That Are Deficient in the Expression of the Viral Thymidine Kinase (tk)

Abstract

Combinations of high concentrations of AZT with BVDU, acyclovir (ACV) or ganciclovir (GCV) show antagonism against TK⁺ HSV-1, but not TK⁺ VZV strains, in cell cultures. When BVDU and AZT were used in combination against TK^? HSV-1, TK^? HSV-2 and TK^? VZV strains, a pronounced inhibition of viral replication was observed. This potentiating effect was not seen if AZT was combined with ACV or GCV.