Synthesis and characterization of [Pt(COD)Cl(NO3)] and [Pt(COD)(NO3)2] and the use of [Pt(COD)Clx(NO3)2−x] in the preparation of cis[Pt(PPh3)2Clx(NO3)2−x] (x=0, 1, 2) and [Pt(PPh3)3L](NO3) (L=Cl,NO3)

[Pt(COD)Cl₂] (COD=1,5-cyclooctadiene) is a versatile starting material for the synthesis of Pt(II) compounds. The preparations of the new compounds [Pt(COD)Cl(NO₃)], [Pt(COD)(NO₃)₂] and [Pt(PPh₃)₃(NO₃)](NO₃) and also of the known compounds cis[Pt(PPh₃)₂Cl₂], cis [Pt(PPh₃)₂Cl(NO₃)], cis[Pt(PPh₃)₂(NO₃)₂] and [Pt(PPh₃)₃Cl](NO₃)are reported. The compounds are characterized by elemental analysis, ³¹P{¹H} NMR spectroscopy and IR spectroscopy.     

Synthesis and NMR characterization of the novel mixed-ligands Pt(II) complexes Pt(amine)(pyrimidine)X2 and trans,trans-X2(amine)Pt(μ-pyrimidine)Pt(amine)X2 (X = I and Cl)

Mixed-ligand complexes of the type Pt(amine)(pm)I₂, (pm = pyrimidine) were synthesized and characterized by IR spectroscopy and by multinuclear (¹⁹⁵Pt, ¹H and ¹³C) magnetic resonance spectroscopy. The cis compounds were prepared from the reaction of I(amine)Pt(μ-I)₂Pt(amine)I with pyrimidine (1:2 proportion) in water, while the trans isomers were synthesized from the isomerization of the cis complexes in acetone. The cis isomers could not be isolated with several amines, especially the more bulky ones. In ¹H NMR, the pyrimidine protons of the cis compounds were found at lower fields than those of the trans analogs and the J(¹⁹⁵Pt-¹H) coupling constants are slightly larger in the cis geometry. For n-butylamine, the reaction produced also I₂(n-butylamine)Pt(μ-pm)Pt(n-butylamine)I₂. No such dimer could be isolated with the other amines. The compounds Pt(amine)(pm)Cl₂ were also prepared (amine = methylamine and t-butylamine) from the ionic complex K[Pt(amine)Cl₃] using an excess of pyrimidine. The IR and NMR characterization showed that the methylamine compound was a cis-trans mixture, while only the trans isomer was isolated with t-butylamine. When the same reaction was performed using a Pt:pm ratio of 2:1, Cl₂(amine)Pt(μ-pm)Pt(amine)Cl₂ was isolated. The pyrimidine-bridged dimers were identified by IR and multinuclear magnetic resonance spectroscopies as the trans-trans isomers. The trans monomers and dimers showed only one ν(Pt-Cl) band. The ¹⁹⁵Pt NMR signals of the dimers were found close to those of the monomer trans-Pt(amine)(pm)Cl₂.     

DNA cleavage and binding selectivity of a heterodinuclear Pt–Cu(3-Clip-Phen) complex

The synthesis and nuclease activity of a new bifunctional heterodinuclear platinum–copper complex are reported. The design of this ditopic coordination compound is based on the specific mode of action of each component, namely, cisplatin and Cu(3-Clip-Phen), where 3-Clip-Phen is 1-(1,10-phenanthrolin-3-yloxy)-3-(1,10-phenanthrolin-8-yloxy)propan-2-amine. Cisplatin is not only able to direct the Cu(3-Clip-Phen) part to the GG or AG site, but also acts as a kinetically inert DNA anchor. The nuclease activity of this complex has been investigated on supercoiled DNA. The dinuclear compound is not only more active than Cu(3-Clip-Phen), but is also capable of inducing direct double-strand breaks. The sequence selectivity of the mononuclear platinum complex has been investigated by primer extension experiments, which reveal that its interaction with DNA occurs at the same sites as for cisplatin. The Taq polymerase recognizes the resulting DNA damage as different from that for unmodified cisplatin. The sequence-selective cleavage has been investigated by high-resolution gel electrophoresis on a 36-bp DNA fragment. Sequence-selective cleavages are observed in the close proximity of the platinum sites for the strand exhibiting the preferential platinum binding sites. The platinum moiety also coordinates to the other DNA strand, most likely leading only to mono guanine or adenine adducts. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Heteropolymetallic complexes of 1,1′-bis(diphenylphosphino)ferrocene (dppf). IV. Solvolytic behavior and cytostatic properties towards the KB cell-line of dppf and 1,2-bis(diphenylphosphino)ethane cis-complexes of Pt(II) and Pd(II)

The novel cis-platinum(II) complexes [(dppe)Pt(μ-OH)]₂(BF₄)₂ and [(dppe)Pt(DMF)₂](BF₄)₂ have been prepared and characterized by ³¹P NMR, together with cis-[(dppe)Pt(μ-Cl)]₂(BF₄)₂, both in poorly and strongly coordinating solvents (dppe = 1,2-bis(diphenylphosphino)ethane). All these complexes and their dppf analogs (dppf = 1,1′-bis(diphenylphosphino)ferrocene) as well as (dppf)PtCl₂, (dppe)PtCl₂, (dppf)PdCl₂, [(dppf)Pd(μ-Cl)]₂(BF₄)₂ and [(dppf)Pd(μ-OH)]₂(BF₄)₂ have been tested as antiproliferating agents towards Eagle's KB cell-line. Their activity is compared with that of free diphosphine ligands. For Pt(II) complexes, the ID₅₀ figures are found to be higher than those observed for free dppf and dppe. On the contrary, the activity of the palladium dppf complexes is substantially identical to that of free diphosphine.     

Crystal structures of three thiourea (tu) complexes of Pt(II): trans-[(tu)2Pt(NH3)2]Cl2, trans-[(tu)2Pt(CH3NH2)2]Cl2·3H2O and [Pt(tu)4]Cl2

The structures of three Pt(II) thiourea complexes, trans-[(tu)₂Pt(NH₃)₂]Cl₂ (1), trans-[(tu)₂Pt(CH₃NH₂)₂]Cl₂·3H₂O (2) and [Pt(tu)₄]Cl₂ (3), have been determined by X-ray diffraction and refined to R = 0.049 for 1026 reflections (1), R = 0.057 for 2547 reflections (2) and R = 0.046 for 2792 reflections (3). All the compounds crystallize in the space group P2₁/c and have cell dimensions: a = 5.437(1), b = 6.450(1), c = 17.980(3) Å, β = 96.05(2)°, Z = 2 (compound 1); a = 9.225(1), b = 15.404(2), c = 12.601(2) Å, β = 105.39(2)°, Z = 4 (compound 2); and a = 9.051(6), b = 10.203(6), c = 18.263(8) Å, β = 91.12(8)°, Z = 4 (compound 3). The unit cell of 1 and 3 contains only a single type of cation, while that of 2 is formed from two independent cations. In 1 and 2 the coordination spheres of the Pt atoms are rather similar, with angles close to 90° and coplanarity of the metal and respective donor atoms. Instead, in 3 the four sulfur atoms, which surround the Pt, display a slight distortion (0.06 Å from the mean plane) towards tetrahedral.     

Study of Pt(II)-aromatic amines complexes of the types cis- and trans-Pt(amine)2I2, [Pt(amine)4]I2 and I(amine)Pt(μ-I)2Pt(amine)I

Pt(II) complexes of the types cis- and trans-Pt(amine)₂I₂ with amines containing a phenyl group were synthesized and studied mainly by IR and multinuclear (¹⁹⁵Pt, ¹H and ¹³C) magnetic resonance spectroscopies. The compounds are not very soluble. In ¹⁹⁵Pt NMR spectroscopy, the cis isomers were observed at slightly lower fields than the trans analogues (average Δδ = 11 ppm) in acetone. In ¹H NMR, the NH groups were also found at slightly lower fields in the cis isomers. The coupling constants ²J(¹⁹⁵Pt-¹HN) varied from 53 to 85 Hz and seem slightly smaller in the trans configuration. The ¹³C NMR spectra of most of the complexes were measured. No coupling constants J(¹⁹⁵Pt-¹³C) were detected due to the low solubility of the compounds. The cis isomers containing a phenyl group on the N atom could not be isolated except for Ph-NH₂ which was shown to be a mixture of isomers in acetone. The tetrasubstituted ionic compounds [Pt(amine)₄]I₂ for the less crowded ligands were also studied mainly by NMR spectroscopy in aqueous solution. The ¹⁹⁵Pt chemical shifts vary between −2855 and −2909 ppm. The coupling constants ³J(¹⁹⁵Pt-¹H) are about 40 Hz. The iodo-bridged dinuclear species I(amine)Pt(μ-I)₂Pt(amine)I were also synthesized and characterized. Two isomers are present in acetone solution for most of the compounds. Their δ(Pt) signals were observed at about −4000 ppm and their coupling constants ²J(¹⁹⁵Pt-¹HN) are around 69 Hz.     

Synthesis of (±)-Homosarkomycin and (±)-Rosaprostol

(±)-Homosarkomycin (2) and (±)-rosaprostol (3) were synthesized from (±)-methyl 2-oxo-bicyclo[3.1.0]hexane-1-carboxylate (1) by using the nucleophilic ring opening reaction on the double-activated cyclopropane ring as the key step.     

Synthesis of (±)-Lamprolobine and (±)-Epilamprolobine

(±)-Lamprolobine, the (+)-enatiomer of which was isolated from the leaves of Lamprolobium fruticosum, and (±)-epilamprolobine were synthesized from δ-valerolactam.     

Synthesis and NMR characterization of the novel mixed-ligand Pt(II) complexes cis- and trans-Pt(Ypy)(pyrimidine)Cl2 and trans,trans-Cl2(Ypy)Pt(μ-pyrimidine)Pt(Ypy)Cl2 (Ypy = pyridine derivative)

Mixed-ligand complexes of the type cis- and trans-Pt(Ypy)(pm)Cl₂ where Ypy = pyridine derivative and pm = pyrimidine were synthesized and characterized by IR spectroscopy and by multinuclear (¹⁹⁵Pt, ¹H and ¹³C) magnetic resonance spectroscopy. The cis compounds were prepared from the reaction of K[Pt(Ypy)Cl₃] with pyrimidine (1:1 proportion) in water, while most of the trans isomers were synthesized from the isomerization of the cis compounds. The cis isomers could not be isolated with the Ypy ligands containing two -CH₃ groups in ortho positions. When the aqueous reaction of K[Pt(Ypy)Cl₃] with pyrimidine was performed in a Pt:pm ratio = 2:1, the pyrimidine-bridged dinuclear species were formed. Only the most stable trans-trans isomers could be isolated pure. In IR spectroscopy, the cis monomers showed two ν(Pt-Cl) bands, while the trans monomers and dimers showed only one ν(Pt-Cl) band. The ¹⁹⁵Pt NMR signals of the cis monomers were found at slightly higher fields than those of the corresponding trans isomers. The δ(¹⁹⁵Pt) of the dimers were found close to those of the trans monomers. The NMR results were interpreted in relation to the solvent effect, which seems important in these complexes. The coupling constants J(¹⁹⁵Pt-¹H) and J(¹⁹⁵Pt-¹³C) are larger in the cis geometry. The crystal structures of the compounds cis-Pt(2,4-lut)(pm)Cl₂, trans-Pt(2,6-lut)(pm)Cl₂ and trans,trans-Cl₂(2,6-lut)Pt(μ-pm)Pt(Ypy)Cl₂ were studied by X-ray diffraction methods and the results have confirmed the configurations suggested by IR and NMR spectroscopies.     

Syntheses of (±)-Epoformin (Desoxyepoxydon) and (±)-Epiepoformin (Desoxyepiepoxydon)

Boron is an essential nutrient for plants, but it is toxic in excess. Transgenic rice plants expressing an Arabidopsis thaliana borate efflux transporter gene, AtBOR4, at a low level exhibited increased tolerance to excess boron. Those lines with high levels of expression exhibited reduced growth. These findings suggest a potential of the borate transporter BOR4 for the generation of high-boron tolerant rice.     

Synthesis and characterization of β-diketiminate germanium(II) and tin(II) bromides

The equimolar reaction of a β-diketiminate lithium salt LLi(OEt₂) [L = HC(CMeNAr)₂; Ar = 2,6-iPr₂C₆H₃] with either GeBr₂ or SnBr₂ in diethyl ether affords the synthetically useful monomeric β-diketiminate-element halides LGeBr (1) and LSnBr (2), respectively. Both are soluble in hydrocarbon solvents, stable in inert atmosphere, and have been characterized by elemental analysis, NMR spectroscopy, and single-crystal X-ray diffraction analysis.     

Synthesis of ( ± )-Methyl Epijasmonate and ( ± )-Methyl Cucurbate

A novel synthesis of ( ± )-methyl epijasomonate (2) and the first synthesis of ( ± )-methyl cucurbate (4) were achieved starting from 2-allylcyclohexane-1,3-dione (8). The synthetic epimer 2 had a stronger jasmin flavor than the trans-isomer 1 with 95% purity.     

Biological function of modified nucleotides T_(54) and ψ_(55) of yeast tRNA~(Ala)

The 3' half molecule of yeast tRNAAla (nucleotides 36-75) was hybridized with a DNA fragment (5'GGAATCGAACC 3') and the hybrid was then digested with E. coli RNase H (from Boehringer). The enzyme can specifically cleave the 3' half molecule at the 3' side of nucleotide ψ55, thus a fragment C36-ψ55 was prepared. The 3'-terminal T or Tψ of this fragment was removed by one or two cycles of periodate oxidation and $-elimination. The products were fragments C36-T54 and C36-G53. Three yeast tRNAAla fragments C56-A76, U55-A76 (with ψ55 replaced by U), U54-A76 (with T54ψ55 replaced by UU) were synthesized and ligated with three prepared fragments (C36-ψ55 C36-T54 and C36-G53) respectively by T4 RNA ligase. The products were further ligated with the 5' half molecule (nu-cleotides 1-35). Using this method, one reconstituted yeast tRNAAla (tRNAr) and two yeast tRNAAla analogs: (i) tRNAa with U55 instead of ψ55; (ii) tRNAb with U54U55 instead of T54ψ55 were synthesized. The charging and incorporation activi     

Antioxidant and Cytoprotective Activity of Oxydiacetate Complexes of Cobalt(II) and Nickel(II) with 1,10-Phenantroline and 2,2′-Bipyridine

Biological Trace Element Research - The antioxidant properties of oxydiacetate complexes of cobalt(II) and nickel(II) with 1,10-phenantroline and 2,2′-bipyridine have been investigated...     

Structure and ultrastructure of the silk glands and spinneret of Helicoverpa armigera (Hübner) (Lepidoptera: Noctuidae)

This study provides comprehensive documentation of silk production in the pest moth Helicoverpa armigera from gland secretion to extrusion of silk thread. The structure of the silk glands, accessory structures and extrusion apparatus are reported. The general schema of the paired silk glands follows that found for Lepidoptera. Morphology of the duct, silk press, muscle attachments and spigot are presented as a three-dimensional reconstruction and the cuticular crescent-shaped profile of the silk press is demonstrated in both open and closed forms with attendant muscle blocks, allowing advances in our knowledge of how the silk press functions to regulate the extrusion of silk. Growth of the spigot across instars is documented showing a distinctive developmental pattern for this extrusion device. Its shape and structure are related to use and load-bearing activity.     

Characterization of Nuclear Localization Signals (NLSs) and Function of NLSs and Phosphorylation of Serine Residues in Subcellular and Subnuclear Localization of Transformer-2β (Tra2β)

The serine/arginine-rich (SR) proteins are one type of major actors in regulation of pre-mRNA splicing. Their functions are closely related to the intracellular spatial organization. The RS domain and phosphorylation status of SR proteins are two critical factors in determining the subcellular distribution. Mammalian Transformer-2β (Tra2β) protein, a member of SR proteins, is known to play multiple important roles in development and diseases. In the present study, we characterized the subcellular and subnuclear localization of Tra2β protein and its related mechanisms. The results demonstrated that in the brain the nuclear and cytoplasmic localization of Tra2β were correlated with its phosphorylation status. Using deletional mutation analysis, we showed that the nuclear localization of Tra2β was determined by multiple nuclear localization signals (NLSs) in the RS domains. The point-mutation analysis disclosed that phosphorylation of serine residues in the NLSs inhibited the function of NLS in directing Tra2β to the nucleus. In addition, we identified at least two nuclear speckle localization signals within the RS1 domain, but not in the RS2 domain. The nuclear speckle localization signals determined the localization of RS1 domain-contained proteins to the nuclear speckle. The function of the signals did not depend on the presence of serine residues. The results provide new insight into the mechanisms by which the subcellular and subnuclear localization of Tra2β proteins are regulated.     

Comparative studies of α-lactalbumin and lysozyme: The proteins of kangaroo (Megaleia rufa and Macropus giganteus) and horse (Equus caballus)

Summary As part of a study of the whey proteins of various mammals, a comparison is made of the -lactalbumins and lysozymes of the kangaroo and horse. In the milk of the red kangaroo (Megaleia rufa) there is only one -lactalbumin and it occurs throughout lactation, but no lysozyme has been detected. There are two -lactalbumins in the milk of the grey kangaroo (Macropus giganteus), one, designated -lactalbumin Zone B, is present throughout lactation; the second, designated -lactalbumin Zone A, is present only in late lactation. One lysozyme is also present. The milk of the horse (Equus caballus) contains one -lactalbumin and at least one lysozyme. Partial amino acid sequences are proposed from sequence determination and from analyses of tryptic peptides compared with the known sequences of other -lactalbumins and lysozymes.