Unusual selectivity of unprotected aziridines in palladium-catalyzed allylic amination enables facile preparation of branched aziridines

Functionalized branched aziridines can be prepared in high yields and with high levels of regioselectivity using unprotected aziridines as nitrogen sources in palladium-catalyzed allylic amination. High levels of enantioselectivity can be achieved with BINAP on palladium. This methodology allows for strategic placement of an aziridine-containing fragment within a complex molecule environment for further elaboration.     

Comparative study of photodynamic properties of 13,15-N-cycloimide derivatives of chlorin p6

Comparative study of 13,15-[N-(2-hydroxyethyl)]cycloimide chlorin p6 (2), 13,15-(N-acetoxy)cycloimide chlorin p6 (3), 13,15-(N-hydroxy)cycloimide chlorin p6 methyl ester (4) and 13,15-(N-methoxy)cycloimide chlorin p6 methyl ester (5) together with the previously investigated 13,15-[N-(3-hydroxypropyl)]cycloimide chlorin p6 (1) was performed. The dependence of the key photodynamic properties of 1-5 on the introduced substituents was analyzed. The photoinduced cell-killing activity of 4 is 100- and 280-fold higher than that of chlorin p6 and Photogem, respectively, as estimated on A549 human lung adenocarcinoma cells. The activity is reduced eight times in the order 4 > 5 > 1 > 2 > 3. The intracellular accumulation of 1-5 occurs in cytoplasm in a monomeric form bound to the lipids of cellular membranes. This form of 1, 2, 3, 4 and 5 is characterized by the high quantum yield of singlet oxygen generation, which depends on the introduced substituents, 0.66, 0.59, 0.35, 0.51 and 0.73, respectively. The photostability is two-fold less for 1 and four-fold less for 2, 3 and 5 than for 4. The rates of cellular uptake and efflux of 1-5 vary widely, thus providing the way to optimize the pharmacological properties of the photosensitizer (PS) using the respective substituents. Modifying the substituents, 1-5 were targeted to different cellular organelles. The enhanced accumulation in the Golgi apparatus and mitochondria complemented with diffuse staining of intracellular membranous structures is a property of 1-4. Compound 5 accumulates selectively in the lipid droplets and stains weakly perinuclear structures. Temperature-sensitive mechanisms of transport are responsible for the 1-4 uptake. Diffusion can play a role in the internalization of 5 but not of 1-4. Endocytosis via caveolae, clathrin-dependent and adenosine triphosphate-dependent pathways are not noticeably involved in the 1-5 internalization. Independently from their intracellular localization 1, 4 and 5 are highly efficient near-IR PS, which induce predominantly an apoptotic type of cell death under conditions providing ca 50% level of phototoxicity and necrosis at the 100% level of phototoxicity.     

Application of water-soluble polymers as modifiers in electrophoretic analysis of phenols

A review of application of water-soluble cationic, anionic and nonionic polymers as pseudostationary phases in capillary electrophoresis (CE) and micellar electrokinetic capillary chromatography (MEKC) is presented. The effect of the structure of the polymers on the selectivity and efficiency of separation is discussed. A novel specially designed cationic polymer, 2,10-ionene, has been used for the separation of phenols. The polymer has hydrophilic and hydrophobic parts in its backbone. The polymer shows the best selectivity as a modifier in capillary zone electrophoresis (CZE)-mode, which allows the selective determination of both hydrophilic and hydrophobic phenols.     

Metal-containing monomers. Part 1. Spatial and electronic structures of cobalt(II) and nickel(II) complexes with acrylamide and of their polymers

Summary The spatial and electronic structures of the complexes [Co(AAm)₄(H₂O)₂](NO₃)₂ (1), Co(AAm)₄Cl₂ (2), [Ni(AAm)₄(H₂O)₂](NO₃)₂ (3) and Ni(AAm)₄Cl₂ (4), where AAm is acrylamide, and the products of their radical, frontal and post-grafting polymerization have been studied by electronic spectroscopy. The complexes (1), (3) and (4) were found to have pseudooctahedral structures in both the solid and solution phases. A change in the spatial structure of complex (2) was established in going from the crystal (tetragonally distorted octahedral) to solution (tetrahedral). The coordination environment of the metal centre does not change markedly during polymerization of the metal-containing monomers.     

Models of the low-spin iron(III) hydroperoxide intermediate of heme oxygenase: magnetic resonance evidence for thermodynamic stabilization of the d(xy) electronic state at ambient temperatures

The (13)C pulsed ENDOR and NMR study of [meso-(13)C-TPPFe(OCH(3))(OO(t)Bu)](-) performed in this work shows that although the unpaired electron in low-spin ferrihemes containing a ROO(-) ligand resides in a d(pi) orbital at 8 K, the d(xy) electron configuration is favored at physiological temperatures. The variable temperature NMR spectra indicate a dynamic situation in which a heme with a d(pi) electron configuration and planar porphyrinate ring is in equilibrium with a d(xy) electron configuration that has a ruffled porphyrin ring. Because of the similarity in the EPR spectra of the hydroperoxide complexes of heme oxygenase, cytochrome P450, and the model heme complex reported herein, it is possible that these two electron configurations and ring conformations may also exist in equilibrium in the enzymatic systems. The ruffled porphyrinate ring would aid the attack of the terminal oxygen of the hydroperoxide intermediate of heme oxygenase (HO) on the meso-carbon, and the large spin density at the meso-carbons of a d(xy) electron configuration heme suggests the possibility of a radical mechanism for HO. The dynamic equilibrium between the ruffled (d(xy)) and planar (d(pi)) conformers observed in the model complexes also suggests that a flexible heme binding cavity may be an important structural motif for heme oxygenase activity.     

A practical, fast, and high-yielding aziridination procedure using simple Cu(II) complexes containing N-donor pyridine-based ligands

Four-coordinate dichlorocopper(II) complexes derived from di(2-pyridyl)methanes or pyridine itself exhibit high catalytic activity in aziridination of regular olefins with PhINTs in weakly coordinating chloroform in the presence of 1-2 equiv of NaBArF4 (BArF4- = tetra[3,5-di(trifluoromethyl)phenyl]borate). High yields of aziridines exceeding 90% can be obtained with a 1:1 olefin/PhINTs ratio and 1-5 mol % catalyst loading for such reactive olefins as styrene, tri- and tetramethylethylene. For cis-cyclooctene, indene, methyl acrylate, methyl methacrylate, vinyl methyl ketone, tert-butylethylene, and neopentylethylene, as well as for 1-hexene and cyclopentene, yields of corresponding aziridines vary from 44% to 83%. The catalytic activity and efficiency of the reported copper complexes decrease moderately in the absence of NaBArF4.     

Angular ligand constraint yields an improved olefin aziridination catalyst

[reaction: see text] The use of a pyridinophane, a macrocycle composed of three pyridines linked, via all ortho positions through CH(2) or CH(2)CH(2) groups, bound to copper, gives good performance (rate and yield) catalyzing the conversion of substituted aliphatic olefins and PhINTs to aziridines. Advantages also derive from using CH(2)Cl(2) solvent and the weakly coordinating anions BAr(4)(-) (Ar = C(6)H(5) or 3,5-C(6)H(3)(CF(3))(2)). Reactions are complete in minutes at 20 degrees C, and yields are almost quantitative for olefins not bearing secondary allylic CH bonds; however, cis-cyclooctene gives only the aziridine despite the allylic hydrogens.     

Novel chiral three-dimensional iron(III) compound exhibiting magnetic ordering at T(c) = 40 K

The preparation and crystal structure determination of the iron(III) compound of formula [(NH(4))(2)[Fe(2)O(ox)(2)Cl(2)].2H(2)O](n) (1) (ox = oxalate dianion) are reported here. Complex 1 crystallizes in the orthorhombic system, space group Fdd2, with a = 14.956(7) A, b = 23.671(9) A, c = 9.026(4) A, and Z = 8. The structure of complex 1 consists of the chiral anionic three-dimensional network [Fe(2)O(ox)(2)Cl(2)](2-) where the iron(III) ions are connected by single oxo and bisbidentate oxalato groups. The metal-metal separations through these bridging ligands are 3.384(2) and 5.496(2) A, respectively. Ammonium cations and crystallization water molecules are located in the helical pseudohexagonal tunnels defined by iron atoms. The longest iron-iron distance in the pseudohexagonal tunnel is 15.778(2) A whereas the shortest one is 8.734(2) A. The iron atoms are hexacoordinated: a terminal chloro ligand and five oxygen atoms, that of the oxo group and four from two cis coordinated oxalate ligands, build a distorted octahedral environment around the metal atom. The Fe-O(oxo) bond distance [1.825(2) A] is significantly shorter than the Fe(III)-O(ox) [average value 2.103(4) A] and Fe(III)-Cl bond distances [2.314(2) A]. Magnetic susceptibility measurements of 1 in the temperature range 2.0-300 K reveal the occurrence of a susceptibility maximum at 195 K and a transition toward a magnetically ordered state in the lower temperature region with T(c) = 40 K. The strong antiferromagnetic coupling through the oxo bridge (J = -46.4 cm(-1), the Hamiltonian being H = -JS(A).S(B)) accounts for the susceptibility maximum whereas a weak spin canting of approximately 0.3 degrees due to the antisymmetric magnetic exchange within the chiral three-dimensional network is responsible for the magnetic ordering. The values of coercive field (H(c)) and remnant magnetization (M(r)) obtained from the hysteresis loop of 1 at 5 K are 4000 G and 0.016 micro(B).     

Efficient enantiomeric analysis of primary amines and amino alcohols by high-performance liquid chromatography with precolumn derivatization using novel chiral SH-reagent N-(R)-mandelyl-(S)-cysteine

Novel N-acylated-(S)-cysteine derivative-N-(R)-mandelyl-(S)-cysteine (R-NMC), containing additional chiral center, aromatic and polar alpha-substituents in contrast to the traditionally used enantiomerically pure thiols, has been demonstrated to be an efficient SH-reagent for enantiomeric HPLC analysis of primary nonfunctionalized amines and amino alcohols after precolumn derivatization with o-phthalaldehyde. The R-NMC-derived isoindoles as well as adducts formed using traditional SH-reagents had a characteristic absorption maximum at 340 nm with a molar absorbance 6000 M(-1) cm(-1), were stable during the HPLC-analysis and highly fluorescent allowing to detect 1 fmol of amino compound. Using diastereomeric R-NMC all tested amino alcohols were resolved effectively as well as nonfunctionalized amines, some of which were not resolved by a direct method on a chiral phase. Applying traditional enantiomeric N-acetyl-(S)-cysteine (NAC) only some isoindoles formed by aliphatic amino alcohols have been separated satisfactorily. The enhanced selectivity for R-NMC-derived isomers has been achieved, obviously, due to the involvement of the substituents at an extra chiral center into additional intramolecular interactions.