Influence of Pu(IV) complex formation with 1,2-diaminocyclohexanetetraacetic acid on the reduction rate of quadrivalent plutonium

The behaviour of the complex ion formed by quadrivalent plutonium with 1,2-diaminecyclohexanetetraacetic acid (DCTA) in reductive media is studied.     

Deazapurine solid-phase synthesis: combinatorial synthesis of a library of N3,N5,C6-trisubstituted pyrrolo[3,2-d]pyrimidine derivatives on cross-linked polystyrene bearing a cysteamine linker

Solid-phase methodology for the preparation of pyrrolo[3,2-d]pyrimidine-6-carboxylates with diversity at the N3 pyrmidine nitrogen has now been elaborated to allow for the generation of pyrrolopyrimidine libraries with members possessing diversity at the N3, N5, and C6 positions. The diversification of the N5 position was achieved by treating the parent resin-bound pyrrolo[3,2-d]pyrimidines 3 with an alkyl halide in the presence of Cs2CO3 in DMF. Modification of the C6 carboxylate of resin-bound pyrrolopyrimidines 3-5 was first achieved by hydrolysis of the benzyl ester using LiOH in a mixture of THF/H2O/MeOH. Further alteration of the C6 position of resin-bound pyrrolo[3,2-d]pyrimidine-6-carboxylic acids 6-8 was then performed by activation with triphosgene and treatment with an amine to furnish resin-bound pyrrolo[3,2-d]pyrimidine-6-amides. Twenty-two pyrrolo[3,2-d]pyrimidines 1a-v with different substituents at the N3, N5, and C6 positions were obtained in yields of 21-83% and purities of 61-98% after cleavage from the solid support.     

Application of isotope dilution method for mass- and alpha-spectrometric determination of burn-up and uranium,plutonium and transplutonium element content in VVER-440 spent fuel

In this report the procedures and the methodology of our versions of alpha- and mass-spectrometric techniques for destructive analysis of VVER spent fuel are discussed. These techniques allow the determination of the content of americium and curium isotopes with relative error 3–5%, that of plutonium isotopes with error ≤1% and of uranium isotopes ?0.3–0.4%. They allow one to determine the fuel burn-up using¹⁴⁸Nd monitor with relative error not exceeding 2% at confidence level P=0.95. The investigation was directed at the increase of sensitivity of analysis to ensure that the amount of analysed material should be equivalent to ～1 mg of irradiated uranium at mean burn-up values. These techniques are based on the isotope dilution method.     

Novel methyl helianthrones as photosensitizers: synthesis and biological evaluation

A combination of light, oxygen and a photosensitizer is used to induce death of cancer cells by photodynamic therapy. In this study, we have synthesized several new methyl helianthrone derivatives and compared their phototoxicity with that of hypericin. In contrast to hypericin, methyl helianthrones are soluble in aqueous solutions and have a broad range of light absorbance, which allows the use of polychromatic light. Structural modifications of methyl helianthrone demonstrated that substitution of hydrogen atoms of methyl helianthrone at Positions 2 and 5 with Br atoms or methylation of its phenolic hydroxyls, significantly increases the corresponding singlet oxygen quantum yield and their phototoxicity toward alphaT3-1, M2R and LNCaP cells. The phototoxicity of some of these compounds was similar to that of hypericin. Methyl helianthrones, like hypericin, accumulated mainly in the perinuclear region as evident by confocal microscopy. Irradiation of cells pretreated with methyl helianthrone derivatives generates intracellular reactive oxygen species and lipid free radicals, as shown by a fluorescentic probe and electron paramagnetic resonance methods, respectively. The phototoxicity of these methyl helianthrones as well as their ability to oxidize membrane lipids were significantly decreased on addition of specific Type-II inhibitors, suggesting the involvement of singlet oxygen as the main oxidant.     

Deazapurine solid-phase synthesis: construction of 3-substituted pyrrolo[3,2-d]pyrimidine-6-carboxylates on cross-linked polystyrene bearing a cysteamine linker

The first solid-phase methodology for the preparation of pyrrolo[3,2-d]pyrimidines is presented. Merrifield resin bearing a cysteamine "traceless" linker was treated with 4-oxo-N-(PhF)proline benzyl ester (10; PhF = 9-(9-phenylfluorenyl)) to provide resin-bound aminopyrrole 20, which was treated with ethyl, phenyl, 4-phenoxyphenyl, and 2,4-dimethoxyphenyl isocyanates to furnish resin-bound ureidopyrroles 21a-d. Resin-bound pyrrolo[3,2-d]pyrimidines 22a-d were then obtained by acylation of 21 using trichloroacetyl chloride in dioxane followed by treatment with Cs2CO3 in DMF. Cleavage of pyrrolo[3,2-d]pyrimidines 22a-d from the resin was achieved in two steps, by oxidation of the sulfur to the sulfone followed by beta-elimination in the presence of t-BuONa. Four pyrrolo[3,2-d]pyrimidines, 24a-d, with different alkyl and aryl substituents at the N3 pyrimidine nitrogen, were thus obtained in overall yields of 42-50% and purities of 90-100%.     

Design and synthesis of peptides that bind alpha-bungarotoxin with high affinity

BACKGROUND: Alpha-bungarotoxin (alpha-BTX) is a highly toxic snake venom alpha-neurotoxin that binds to acetylcholine receptor (AChR) at the neuromuscular junction, and is a potent inhibitor of this receptor. We describe the design and synthesis of peptides that bind alpha-BTX with high affinity, and inhibit its interaction with AChR with an IC(50) of 2 nM. The design of these peptides was based on a lead peptide with an IC(50) of 3x10(-7) M, previously identified by us [M. Balass et al., Proc. Natl. Acad. Sci. USA 94 (1997) 6054] using a phage-display peptide library. RESULTS: Employing nuclear magnetic resonance-derived structural information [T. Scherf et al., Proc. Natl. Acad. Sci. USA 94 (1997) 6059] of the complex of alpha-BTX with the lead peptide, as well as structure-function analysis of the ligand-binding site of AChR, a systematic residue replacement of the lead peptide, one position at a time, yielded 45 different 13-mer peptides. Of these, two peptides exhibited a one order of magnitude increase in inhibitory potency in comparison to the lead peptide. The design of additional peptides, with two or three replacements, resulted in peptides that exhibited a further increase in inhibitory potency (IC(50) values of 2 nM), that is more than two orders of magnitude better than that of the original lead peptide, and better than that of any known peptide derived from AChR sequence. The high affinity peptides had a protective effect on mice against alpha-BTX lethality. CONCLUSIONS: Synthetic peptides with high affinity to alpha-BTX may be used as potential lead compounds for developing effective antidotes against alpha-BTX poisoning. Moreover, the procedure employed in this study may serve as a general approach for the design and synthesis of peptides that interact with high affinity with any desired biological target.     

Random replicators with high-order interactions

We use tools of the equilibrium statistical mechanics of disordered systems to study analytically the statistical properties of an ecosystem composed of N species interacting via random mutual interactions, as well as via deterministic self-interactions of order p>/=2. We show that the main effect of increasing the order of the interactions among the species is to make the system less competitive, in the sense that the fraction of extinct species is greatly reduced. In addition, we find that for p>2 there is a threshold value which gives a lower bound to the concentration of the surviving species, preventing then the existence of rare species and, consequently, increasing the robustness of the ecosystem to external perturbations.     

Functionalization of polystyrene. III. Synthesis of polymeric thiol reagents

The synthesis of polymer-bound thiol reagents, supported on macroporous 4% divinylbenzene co-polymer (Amberlite XE-305), via three synthetic approaches is described: (i) Alkylation or acylation of XE-305 with 3-nitro-4-halogen-substituted benzyl chloride or benzoyl halide yielding 3-nitro-4-halobenzene-bound species, followed by substitution of the activated polymeric halogen atom with sulfur (see Scheme 1). (ii) Formation of a thiol ether by a direct substitution of an active polymeric halogen by reaction with benzylthiol, followed by chlorination, thiolation, and reduction (see Scheme 2). (iii) Attachment of a prepared tailor-made disulfide to aminomethyl function of a polymeric support, followed by reduction (see Scheme 3). The polymers were tested for their free-thiol content by 5, 5′-dithiobis(2-nitrobenzoic acid) (Ellman's reagent¹²) in DMF. Their thiolytic activity was investigated in the removal of 2-nitrophenylsulphenyl (Nps) group from Nps-protected amino acid (Scheme 4). Site-site interaction between the polymer-bound thiol with its activated halide precursor to yield polymeric sulfide during displacement reaction, and the interconversion of the polymeric thiols into polymeric disulfides at equilibrium or during reaction with Nps-amino acids, observed, and is attributed to the flexibility of the polymeric matrices.     

2-vinylpyrroles and pyrrolo[3,2-d]pyrimidines from direct addition of aldehydes to 4-amino-pyrrole-2-carboxylate derivatives

A new methodology for the direct preparation of 2-vinylpyrroles is presented. Treatment of 4-amino-pyrrole-2-carboxylates 5a-c and 6a-d with aliphatic aldehydes and TFA furnished 2-vinylpyrroles 2a-k in 9-87% yields. Under similar conditions ureidopyrroles 5a-c reacted with aryl aldehydes to provide pyrrolo[3,2-d]pyrimidines 1a-d in 28-63% yields.     

On the mechanism of the photodomain effect in ferroelectrics

The influence of nonequilibrium electrons on the domain structure and switching of ferroelectrics (photodomain effect) has been investigated in ferroelectric crystals and ceramics. In the present paper, this effect is observed and explained as a result of the domain walls screening in frame ofYshibashi-Takagi theory.