New designs for inhibitors of the NF-κB: DNA binding

We present a series of new inhibitors of the association between nuclear factor kappa B (NF-B) and the corresponding B site in DNA. They were designed using the lead compound 15-deoxy-^12,14 -prostaglandin J₂ (PGJ2), which is a natural product with demonstrated inhibitory efficiency for this system. First, the binding mode of PGJ2 to NF-B was unraveled by GOLD docking calculation. Subsequently, substitutions were made to PGJ2 to optimize its association with NF-B. Care was taken not to strongly increase the reactivity of the new compounds, and to keep the overall shape, size and hydrophilicity of the lead compound, which should render them a similar bioavailability. Molecular mechanics calculations were performed to decide on the suitability of the substitutions, and to evaluate the energies of association with NF-B. Density functional theory calculations were performed also to study the overall reactivity of the substituted drugs towards NF-B. Important general conclusions were obtained, concerning the improvement of these natural inhibitors; namely, a set of rational methodologies were deduced to improve the association between the PGJ2 derivatives and NF-B, and their efficiency demonstrated by generating a set of substituted complexes, some of them with a very much increased affinity for NF-B, opening new doors to enlarge the therapeutic capabilities of this class of drugs.     

Development of stereoselective nonaqueous capillary electrophoresis system for the resolution of cationic and amphoteric analytes

A stereoselective ion-pair nonaqueous capillary electrophoresis (NACE) method employing the partial filling technique with N-derivatized amino acids, e.g., (R)- and (S)-3,5-dinitrobenzoyl-leucine (DNB-Leu), as chiral selector for the separation of "pseudoenantiomeric" cinchona alkaloid derivatives and other structurally related basic compounds like the enantiomers of mefloquine is presented. Originating from NACE with cinchona alkaloid derivatives as chiral counterions, this method was developed by application of the reciprocity principle of chiral recognition, which was proven to be valid for stereoselective ion-pair capillary electrophoresis (CE). A variety of basic and amphoteric selectands (SAs) could be well resolved. Thereby, the separation was primarily based on stereoselective ion-pair formation of corresponding SA stereoisomers and mobility differences of free and complexed (ion-paired) SAs. Additionally, in the case of diastereomeric SAs, naturally existing mobility differences between the diastereomers played also a role, but was shown by control experiments with racemic DNB-Leu and without selector (SO) to be of minor contribution to overall separation selectivity. Due to its simplicity, speed, and good reproducibility, the established method can be utilized for fast screening of cationic as well as amphoteric chiral compounds, and therefore is a valuable tool in the development of new chiral selectors and chiral stationary phases. Small sample amounts of the SO (4-5 mg) and only analytical amounts of SAs are needed, and about 20-50 compounds per day can be tested.     

Cathodic behaviour of nickel(II) in acetonitrile in the presence of carbon monoxide and substituted phosphines

Summary The reduction of nickel perchlorate in the presence of carbon monoxide and substituted phosphines or diphosphines has been studied in acetonitrile by cyclic voltammetry. The results show that only mono- and bis-carbonylphosphinenickel(O) complexes are formed, while no evidence for the formation of carbonyl-nickel(I) and -nickel(II) species was obtained. Although the oxidation processes are not reversible, a good correlation between the anodic peak potentials relative to nickel(O) complexes and the -donor--acceptor abilities of the phosphines employed was observed.     

On the origin of satellite peaks in valence photoemission from CO ON Cu(110)

The valence-level photoelectron spectrum of CO absorbed on copper surfaces exhibits extra features in the region 10–20 eV below E_F which are attributed to multielectron excitations. We have recorded the satellite intensity as a function of photon energy in the system CO/Cu(110) using synchrotron radiation. It is found that the occurrence of all satellites, including some which are observed for the first time, can be explained in terms of the SCF Xα SW model calculations by Messmer et al.     

Spectrophotometric, EPR and kinetic characterisation of the >N-O* radical from 1-hydroxybenzotriazole, a key reactive species in mediated enzymatic oxidations

Characterisation of the aminoxyl (>N-O*) radical BTNO, generated from 1-hydroxybenzotriazole (HBT) by the one-electron oxidant CAN (a Ce(IV) salt), confirms BTNO as the reactive intermediate in oxidations run with the laccase/HBT system.     

A rapid HPIC method for the quantitative determination of tetramethylammonium chloride in some aqueous solutions used as food simulants

Summary The present paper reports a rapid HPIC method for the determination of tetramethylammonium chloride in aqueous matrices which are used as food simulants in migration tests. These simulants were: bidistilled water, an aqueous solution of 3% acetic acid, an aqueous solution of 15% ethyl alcohol, a mixed aqueous solution of 3% acetic acid and 15% ethyl alcohol. The method, as developed, has been applied to the determination of unreacted tetramethylammonium chloride residues which are able to migrate from finished epoxy resins which are used as food packaging materials.Research partially supported by National Research Council of Italy, Special Project RAISA, sub-project 4, Paper N^o 695.     

The determination of the gases released during heating of a flame retardant for polymers

The oxidative degradation of HET-acid (1,4,5,6,7,7-hexachlorobicyclo [2.2.1] hept-5-en-2, 3-dicarboxylic acid) is studied by the combination of TG, FTIR, MS and GC-MS. The gases evolved during the decomposition of this flame retardant are investigated on-line by FTIR and by MS. Simultaneously the evolved gases are collected by an adsorbent and, after the thermal experiment, desorbed to release the volatile products for identification using GC-MS. The combination of these techniques offers the unambiguous identification of the evolved products as a function of temperature. The main identified products are CO₂, H₂O, Cl₂, HCl, C₂Cl₄, maleic acid anhydride, HET-acid anhydride, chlorinated cyclic hydrocarbons and chlorinated unsaturated linear hydrocarbons.     

New [g]-fused [1,2,4]triazolo[1,5-c]pyrimidines: Synthesis of pyrido[3,2-e] and [4,3-e][1,2,4]triazolo[1,5-c]pyrimidine,pyrimido[5,4-e][1,2,4]triazolo[1,5-c]pyrimidine and [1,2,4]triazolo[1,5-c]pteridine derivatives

A number of 2-aryl-substituted pyrido[3,2-e] and [4,3-e][1,2,4]triazolo[1,5-c]pyrimidines and [1,2,4]triazolo[1,5-c]pteridines 11,12a,b,e , their corresponding 5-carbonyl derivatives 7,8a,b,e and some pyrimido[5,4-e][1,2,4]triazolo[1,5-c]pyrimidin-5-ones 7,8c,d have been synthesized, according to different pathways. The new tricyclic heterocycles were prepared with the aim of studying their possible benzodiazepine receptors affinity.     

Synthesis, properties and structures of the two “electron rich” cobalt-sulphur clusters [Co6(μ3-S)8(PEt3)6]

The reaction of hydrogen sulphide with [Co(H₂O)₆](BF₄)₂ and triethylphosphine in the presence of sodium tetraphenylborate or tetrabutylammonium hexafluorophosphate gave the paramagnetic clusters [Co₆(μ₃-S)₈(PEt₃)₆](Y) (Y = BPh₄, (1), PF₆, (2)). These compounds can be easily reduced by sodium napthalenide to the diamagnetic species [Co₆(μ₃-S)₈(PEt₃)₆] · 2C₄H₈O (3). The molecular structures of 1 and 3 have been established by single-crystal X-ray diffraction methods. Crystal data: (1) space group P , a = 19.481(9), b = 15.562(7), c = 12.390(b) Å, α = 92.70(8), β = 94.50(7), γ = 94.10(9)°, Z = 2, (3) space group R , a = 11.780(6) Å, α = 92.50(7)°, Z = 1. Both structures were solved by the heavy atom method and refined by full-matrix least-squares techniques to the conventional R factors values of 0.050 for 1 and 0.044 for 3 on the basis of 4251 and 1918 observed reflections, respectively. The two clusters [Co₆(μ₃-S)₈)(PEt₃)₆]^1+,0 are isostructural, the inner core consisting of an octahedron of cobalt atoms with all the faces symmetrically capped by triply bridging sulphur atoms. Each metal centre is additionally linked to a triethylphosphine group so that each cobalt atom is co-ordinated by four sulphur atoms and one phosphorus in a distorted square pyramidal environment. The addition of one electron whilst leaving unchanged the geometry of the inner framework, induces small changes in the structural parameters, the average Co---Co and Co---P distances being 2.794 (3) and 2.162 (2) Å for 1 and 2.817 (3) and 2.138 (2) Å for 3 respectively. Electrochemistry in non-aqueous solvents shows the electron-transfer sequence

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The tricationic species is stable only in the short time of cyclic voltammetric tests.