Diastereoselective synthesis of cyclopropane amino acids using diazo compounds generated in situ

A simple and high-yielding method for the preparation of cyclopropane amino acids is described. The novel method involves the one-pot cyclopropanation of readily available dehydroamino acids using aryl and unsaturated diazo compounds generated in situ from the corresponding tosylhydrazone salts. It was found that thermal 1,3-dipolar cycloaddition followed by nitrogen extrusion gave the cyclopropane amino acid derivatives with good E selectivity, while reactions in the presence of meso-tetraphenylporphyrin iron chloride gave predominantly the corresponding Z isomers. The synthetic utility of this process was demonstrated in the synthesis of (+/-)-(Z)-2,3-methanophenylalanine [(+/-)-(Z)-1], the anti-Parkinson (+/-)-(E)-2,3-methano-m-tyrosine [(+/-)-(E)-2], and the natural product (+/-)-coronamic acid [(+/-)-3].     

Picryl derivatives of 5-nitro-2,4-dihydro-3H-1,2,4-triazol-3-one

Treatment of 5-nitro-2,4-dihydro-3H-1,2,4-triazol-3-one ( 1 ) with picryl fluoride (PkF) in 1-methyl-2-pyrrolidinone (NMP) gave a mixture of a monopicryl and a dipicryl derivative of 1 in a ratio of 2 :1 , respectively, regardless of the initial concentrations of 1 and PkF. The products were identified as 5-nitro-2-picryl-2,4-dihydro-3H-1,2,4-triazol-3-one ( 2 ) by X-ray crystallography and 5-nitro-2,4-dipicryl-2,4-dihydro-3H-1,2,4-triazol-3-one ( 4 ) by ¹⁵N labeling experiments.     

An improved synthesis of 3,6-diamino-1,2,4,5-tetrazine. II. From triaminoguanidine and 2,4-pentanedione

A new synthesis for the title compound that gives an 80% overall yield was developed. Treatment of triaminoguanidine monohydrochloride ( 1 ) with 2,4-pentanedione ( 2 ) gave 3,6-bis(3,5-dimethylpyrazol-1-yl)-1,2-dihydro-1,2,4,5-tetrazine ( 3 ) in 80–85% yield. Oxidation of 3 with nitric oxide or nitrogen dioxide to 3,6-bis(3,5-dimethyylpyrazol-1-yl)-1,2,4,5-tetrazine ( 4 ) followed by ammonolysis of 4 gave 3,6-diamino-1,2,4,5-tetrazine ( 5 ) in guantitatively yields.     

Enterococcal cytolysin: a novel two component peptide system that serves as a bacterial defense against eukaryotic and prokaryotic cells

The cytolysin is a novel, two-peptide lytic toxin produced by some strains of Enterococcus faecalis. It is toxic in animal models of enterococcal infection, and associated with acutely terminal outcome in human infection. The cytolysin exerts activity against a broad spectrum of cell types including a wide range of gram positive bacteria, eukaryotic cells such as human, bovine and horse erythrocytes, retinal cells, polymorphonuclear leukocytes, and human intestinal epithelial cells. The cytolysin likely originated as a bacteriocin involved with niche control in the complex microbial ecologies associated with eukaryotic hosts. However, additional anti-eukaryotic activities may have been selected for as enterococci adapted to eukaryotic cell predation in water or soil ecologies. Cytolytic activity requires two unique peptides that possess modifications characteristic of the lantibiotic bacteriocins, and these peptides are broadly similar in size to most cationic eukaryotic defensins. Expression of the cytolysin is tightly controlled by a novel mode of gene regulation in which the smaller peptide signals high-level expression of the cytolysin gene cluster. This complex regulation of cytolysin expression may have evolved to balance defense against eukaryotic predators with stealth.     

Laser desorption ion trap mass spectrometry of self-assembled monolayers

It is demonstrated that laser desorption ion trap mass spectrometry (LD-ITMS) can be successfully applied to the chemical analysis of a monolayer of adsorbates on a solid surface. Negative ion spectra obtained from LD-ITMS of self-assembled monolayers adsorbed from solutions of alkanethiols (CH₃(CH₂)_nSH with N = 5, 9, and 15) onto polycrystalline gold surfaces displayed clear ion peaks corresponding to the sulfonate adsorbate species. Sulfonate ions with the general formula CH₃(CH₂)_nSO⁻₃ were detected at m/z 165, 221, and 305, respectively, and were derived from the partial oxidation of the corresponding alkanethiol self-assembled monolayers. Little fragmentation and no clustering was observed in these mass spectra. These results indicate that the sensitivity of LD-ITMS is sufficient to allow its application to a wide array of problems in surface science.     

Fuzzy structure-activity relationships

While quantitative structure-activity relationships attempt to predict the numerical value of the activities, it is found that statistically good predictors do not always do a good job of qualitatively determining the activity. This study shows how Fuzzy classifiers can be used to generate Fuzzy structure-activity relationships which can more accurately determine whether or not a compound will be highly inactive, moderately inactive or active, or highly active. Four examples of these classifiers are presented and applied to a well-studied activity dataset.     

Unraveling σ and π Effects on Magnetic Anisotropy in cis‐NiA4B2 Complexes: Magnetization,HF‐HFEPR Studies,First‐Principles Calculations,and Orbital Modeling

By using complementary experimental techniques and first‐principles theoretical calculations, magnetic anisotropy in a series of five hexacoordinated nickel(II) complexes possessing a symmetry close to C_2v, has been investigated. Four complexes have the general formula [Ni(bpy)X₂]ⁿ⁺ (bpy=2,2′‐bipyridine; X₂=bpy ( 1 ), (NCS^?)₂ ( 2 ), C₂O₄^2? ( 3 ), NO₃^? ( 4 )). In the fifth complex, [Ni(HIM₂‐py)₂(NO₃)]⁺ ( 5 ; HIM₂‐py=2‐(2‐pyridyl)‐4,4,5,5‐tetramethyl‐4,5‐dihydro‐1H‐imidazolyl‐1‐hydroxy), which was reported previously, the two bpy bidentate ligands were replaced by HIM₂‐py. Analysis of the high‐field, high‐frequency electronic paramagnetic resonance (HF‐HFEPR) spectra and magnetization data leads to the determination of the spin Hamiltonian parameters. The D parameter, corresponding to the axial magnetic anisotropy, was negative (Ising type) for the five compounds and ranged from ?1 to ?10 cm^?1. First‐principles SO‐CASPT2 calculations have been performed to estimate these parameters and rationalize the experimental values. From calculations, the easy axis of magnetization is in two different directions for complexes 2 and 3 , on one hand, and 4 and 5 , on the other hand. A new method is proposed to calculate the g tensor for systems with S=1. The spin Hamiltonian parameters (D (axial), E (rhombic), and g_i) are rationalized in terms of ordering of the 3 d orbitals. According to this orbital model, it can be shown that 1) the large magnetic anisotropy of 4 and 5 arises from splitting of the e_g‐like orbitals and is due to the difference in the σ‐donor strength of NO₃^? and bpy or HIM₂‐py, whereas the difference in anisotropy between the two compounds is due to splitting of the t_2g‐like orbitals; and 2) the anisotropy of complexes 1 – 3 arises from the small splitting of the t_2g‐like orbitals. The direction of the anisotropy axis can be rationalized by the proposed orbital model.     

Influence of ion bombardment on growth and properties of PLD created DLC films

A hybrid PLD system with ion bombardment of films was developed. Growing DLC films were modified during the laser deposition (10 J?cm^?2) by argon ions with energy in the range from 40 eV to 210 eV and cathode current of 0.15 A and 0.5 A. The content of sp² “graphitic” and sp³ “diamond” bonds was measured using XPS. Sp³ bonds changed from 60 % to 81 %. We found the highest sp³ content for energy of 40 eV. Hardness (and reduced Young’s modulus) were determined by nanoindentation and reached 49 GPa (277 GPa). Film adhesion was studied using the scratch test and was up to 14 N for titanium substrates. Relations among deposition conditions and measured properties are presented.