Practical application of new catalytic methods: a concise synthesis of a potent PDE IV inhibitor

An efficient synthesis of a potent PDE IV inhibitor 1 is described. The synthesis is highlighted by two practical and efficient catalytic reactions: a highly selective catalytic palladium mediated carbonylation of the pyridine side chain and an efficient palladium-catalyzed Suzuki-Miyaura coupling of a chloropyridine-N-oxide.     

Design and characterization of a homodimeric antiparallel coiled coil

We report the first successful design of a self-associating antiparallel coiled coil, APH. The simultaneous application of Coulombic and hydrophobic components results in a decided preference for the antiparallel alignment as judged by HPLC, sedimentation equilibrium, and chemical denaturation data. The designed peptide is of comparable stability to naturally occurring leucine zipper peptides and can be expressed in bacteria. These properties of APH suggest potential in vivo protein fusion and biomaterials applications.     

Five-coordinate Fe(III)NO and Fe(II)CO porphyrinates: where are the electrons and why does it matter?

Recent years have seen dramatic growth in our understanding of the biological roles of nitric oxide (NO). Yet, the fundamental underpinnings of its reactivities with transition metal centers in proteins and enzymes, the stabilities of their structures, and the relationships between structure and reactivity remains, to a significant extent, elusive. This is especially true for the so-called ferric heme nitrosyls ([FeNO](6) in the Enemark-Feltham scheme). The Fe-CO and C-O bond strengths in the isoelectronic ferrous carbonyl complexes are widely recognized to be inversely correlated and sensitive to structural, environmental, and electronic factors. On the other hand, the Fe-NO and N-O bonds in [FeNO](6) heme complexes exhibit seemingly inconsistent behavior in response to varying structure and environment. This report contains resonance Raman and density functional theory results that suggest a new model for FeNO bonding in five-coordinate [FeNO](6) complexes. On the basis of resonance Raman and FTIR data, a direct correlation between the nu(Fe)(-)(NO) and nu(N)(-)(O) frequencies of [Fe(OEP)NO](ClO(4)) and [Fe(OEP)NO](ClO(4)).CHCl(3) (two crystal forms of the same complex) has been established. Density functional theory calculations show that the relationship between Fe-NO and N-O bond strengths is responsive to FeNO electron density in three molecular orbitals. The highest energy orbital of the three is sigma-antibonding with respect to the entire FeNO unit. The other two comprise a lower-energy, degenerate, or nearly degenerate pair that is pi-bonding with respect to Fe-NO and pi-antibonding with respect to N-O. The relative sensitivities of the electron density distributions in these orbitals are shown to be consistent with all published indicators of Fe-N-O bond strengths and angles, including the examples reported here.     

OBSERVATIONS ON THE PHOTOSENSITIZED BREAKAGE OF DNA BY 2-THIOURACIL AND 334-nm ULTRAVIOLET RADIATION

Abstract— Breaks induced in purified DNA by 334-nm ultraviolet (UV) radiation are enhanced 30 times when 2-thiouracil (s²Ura) is present during aerobic irradiation. This enhancement by s²Ura is maximally effective at a concentration of about 1 m M. Anoxic irradiation reduces the s²Ura-enhanced breakage by 90%, indicating a Type II photosensitization. Benzoate, glycerol, diazabicyclo[2.2.2.]octane (DABCO) and histidine all inhibit formation of s²Ura photosensitized breaks, unlike diethylenetriaminepenta-acetic acid (DETAPAC) and catalase, which do not. The relationships between the concentration of DABCO. benzoate and histidine and their protection against induction of single strand breaks (SSBs) were similar, with little inhibition below 10 m M and maximal inhibition near 0.1 M for all compounds. Irradiation of the DNA-s²Ura mixture dissolved in D₂O instead of H₂O enhanced the rate of induction of SSBs in DNA by 334-nm light almost five times. Addition of superoxide dismutase (40, 80 and 200 μg/ml) decreased the rate of induction of breaks in DNA by 334-nm radiation plus s²Ura (in H₂O) by about 40%. Boiled superoxide dismutase had no effect.     

Gas-phase complexation of polyethers with halide ions

Gas-phase complexes of halide anions with a variety of crown ethers and acyclic analogs are formed by ion-molecule reactions in the chemical ionization source of a triple-quadrupole mass spectrometer. The ether complexes of iodide, bromide, and chloride dissociate on collisional activation by cleavage of the halide-ether electrostatic hydrogen bonds, resulting in the formation of bare halide anions. By contrast, the fluoride complexes dissociate by loss of HF, which may occur in conjunction or sequentially with losses of ethylene oxide units. This dissociation behavior is similar to that observed for collisionally activated dissociation of [M ? H]^? ions of the crown ethers and suggests that the fluoride ion is capable of promoting an intramolecular proton abstraction within the [M+F]^? complex. This type of dissociation chemistry is only observed for the fluoride ion complexes, and the fluoride ion is the most basic of all the halides. The kinetic method was used to establish orders of relative halide binding strengths, and the trends for the chloride and bromide affinities were 12-crown-4 < triethylene glycol dimethyl ether < 15-crown-5 < tetraethylene glycol dimethyl ether < 18-crown-6 < 21-crown-7 < tetraethylene glycol < pentaethylene glycol < 1,4,7,10,13-pentathiacyclopentadecane.     

Buffers for the Physiological pH Range: Thermodynamics of the Second Dissociation of N-(2-Hydroxyethyl)piperazine-N′-2-hydroxypropanesulfonic Acid From 5 to 55°C

The second acidic dissociation constants pK ₂ of the ampholyte N-(2-hydroxyethyl) piperazine-N-2-hydroxypropanesulfonic acid (HEPPSO) have been determined at seven temperatures from 5 to 55°C from emf measurements utilizing hydrogen and silver–silver chloride cells without liquid junction. The thermodynamic quantities, G°, H°,S°, and C _p ^o have been calculated from the temperature coefficient of pK ₂. At 25°C, the pK ₂ = 8.042 and at 37°C, pK ₂ = 7.876; hence, buffer solutions of HEPPSO and NaHEPPSOate are important for pH control in the region close to that of clinical fluids (blood serum). Conventional pH values from 5 to 55°C as well as those obtained from liquid junction correction at 25 and 37°C have been reported for three buffer solutions with the compositions (molality scale): (1) equimolal mixture of HEPPSO (0.04 m) + NaHEPPSOate (0.04 m) + NaCl (0.12 m); (2) HEPPSO (0.08 m) + NaHEPPSOate (0.08 m); and (3) HEPPSO (0.08 m) + NaHEPPSOate (0.08 m) + NaCl (0.08 m).     

Rapid intramolecular interactions between organic isocyanates and hexafluorobut-2-yne on a dirhodium centre; X-ray crystal structure of (η-C5H5)2Rh2 {μ2(η3-C(CF3)C(CF3)C(O)N(Ph)}

Complexes of formula (η-C₅H₅₂Rh₂{CF₃C₂CF₃ · RNCO} have been prepared by three methods, from reactions between organic isocyanates and (η-C₅H₅)₂Rh₂(CO)(CF₃C₂CF₃) or (η-C₅H₅)₂Rh₂(CO)₂(CF₃C₂CF₃); by treatment of (η-C₅H₅)₂Rh₂(CO)(CF₃C₂CF₃) with organic azides; and by oxidation with Me₃NO of the organic isocyanide in (η-C₅H₅)₂Rh₂(CO)(CNR)(CF₃C₂CF₃). The crystal and molecular structure of the complex (η-C₅H₅)₂Rh₂{CF₃C₂CF₃ · RNCO} with R = Ph has been determined from single crystal X-ray diffraction data. This reveals that the isocyanate has condensed with the hexafluorobut-2-yne to form an amide ligand of the form C(CF₃)C(CF₃)C(=O)N(R); this bridges the two rhodium atoms in a μ₂η³-manner.     

Dyeing uric acid crystals with methylene blue

The growth of anhydrous uric acid (UA) and uric acid dihydrate (UAD) crystals from supersaturated aqueous solutions containing methylene blue, a cationic organic dye, has been investigated. Low concentrations of dye molecules were found to be included in both types of crystal matrixes during the growth process. Incorporation of dye into UA crystals occurs with high specificity, affecting primarily [001] and [201] growth sectors, while UAD crystals grown from solutions of similar dye concentration show inclusion but little specificity. The orientation of the UA-trapped species was determined from polarization data obtained from visible light microspectrometry. To achieve charge neutrality, a second anionic species must also be included with the methylene blue into UA and UAD crystal matrices. Under high pH conditions, crystallization of 1:1 stoichiometric mixtures of methylene blue and urate yields methylene blue hexahydrate (MBU.6(H2O). The crystal structure of MBU.6(H2O) reveals continuous pi-pi stacks of planes of dye cations and urate anions mediated by water molecules. This structure provides an optimal geometry for methylene blue-urate pairs and additional support for the incorporation of these dimers in uric acid single-crystal matrices. The strikingly different inclusion patterns in UA and UAD demonstrate that subtle changes in the crystal surfaces and/or growth dynamics can greatly affect recognition events.     

Syntheses and structures of three new scandium selenites: Sc2(SeO3)3·H2O, Sc2 (SeO3)3·3H2O and CsSc3(SeO3)4 (HSeO3)2·2H2O

Three new hydrated scandium selenites have been hydrothermally synthesized as single crystals and structurally and physically characterized. Sc₂(SeO₃)₃·H₂O crystallizes as a new structure type containing novel ScO₇ pentagonal bipyramidal and ScO₆₊₁ capped octahedral coordination polyhedra. Sc₂(SeO₃)₃·3H₂O contains typical ScO₆ octahedra and is isostructural with its M₂(SeO₃)₃·3H₂O (M=Al, Cr, Fe, Ga) congeners. CsSc₃(SeO₃)₄(HSeO₃)₂·2H₂O contains near-regular ScO₆ octahedra and has essentially the same structure as its indium-containing analogue. All three phases contain the expected pyramidal [SeO₃]^2- selenite groups. Crystal data: Sc₂(SeO₃)₃·3H₂O, M_r=524.85, trigonal, R3c (No. 161), , , , Z=6, R(F)=0.018, wR(F²)=0.036; Sc₂(SeO₃)₃·H₂O, M_r=488.82, orthorhombic, P2₁2₁2₁ (No. 19), , , , , Z=4, R(F)=0.051, wR(F²)=0.086; CsSc₃(SeO₃)₄(HSeO₃)₂·2H₂O, M_r=1067.60, orthorhombic, Pnma (No. 62), , , , , Z=4, R(F)=0.035, wR(F²)=0.070.     

The structure and maximum number of maximum independent sets in trees

A subset of vertices is a maximum independent set if no two of the vertices are joined by an edge and the subset has maximum cardinality. in this paper we answer a question posed by Herb Wilf. We show that the greatest number of maximum independent sets for a tree of n vertices is We give the families of trees on which these maxima are achieved. Proving which trees are extremal depends upon the structure of maximum independent sets in trees. This structure is described in terms of adjacency rules between three types of vertices, those which are in all, no, or some maximum independent sets. We show that vertices that are in some but not all maximum independent sets of the tree are joined in pairs by the α-critical edges (edges whose removal increases the size of a maximum independent set). The number of maximum independent sets is shown to depend on the structure within the tree of the α-critical edges.