De novo structure-based design of bisurea hosts for tetrahedral oxoanion guests

This paper presents a computational approach to the deliberate design of improved host architectures. De novo molecule building software, HostDesigner, is interfaced with molecular mechanics software, GMMX, providing a tool for generating and screening millions of potential structures. The efficacy of this computer-aided design methodology is illustrated with a search for bisurea podands that are structurally organized for complexation with tetrahedral oxoanions.     

Mutagenesis of morphinone reductase induces multiple reactive configurations and identifies potential ambiguity in kinetic analysis of enzyme tunneling mechanisms

We have identified multiple reactive configurations (MRCs) of an enzyme-coenzyme complex that have measurably different kinetic properties. In the complex formed between morphinone reductase (MR) and the NADH analogue 1,4,5,6-tetrahydro-NADH (NADH4) the nicotinamide moiety is restrained close to the FMN isoalloxazine ring by hydrogen bonds from Asn-189 and His-186 as determined from the X-ray crystal structure. Molecular dynamic simulations indicate that removal of one of these hydrogen bonds in the N189A MR mutant allows the nicotinamide moiety to occupy a region of configurational space not accessible in wild-type enzyme. Using stopped-flow spectroscopy, we show that reduction of the FMN cofactor by NADH in N189A MR is multiphasic, identifying at least four different reactive configurations of the MR-NADH complex. This contrasts with wild-type MR in which hydride transfer occurs by environmentally coupled tunneling in a single kinetic phase [Pudney et al. J. Am. Chem. Soc. 2006, 128, 14053-14058]. Values for primary and alpha-secondary kinetic isotope effects, and their temperature dependence, for three of the kinetic phases in the N189A MR are consistent with hydride transfer by tunneling. Our analysis enables derivation of mechanistic information concerning different reactive configurations of the same enzyme-coenzyme complex using ensemble stopped-flow methods. Implications for the interpretation from kinetic data of tunneling mechanisms in enzymes are discussed.     

Synthesis and coordination chemistry of phosphine oxide decorated dibenzofuran platforms

A four-step synthesis for 4,6-bis(diphenylphosphinoylmethyl)dibenzofuran (4) from dibenzofuran and a two-step synthesis for 4,6-bis(diphenylphosphinoyl)dibenzofuran (5) are reported along with coordination chemistry of 4 with In(III), La(III), Pr(III), Nd(III), Er(III), and Pu(IV) and of 5 with Er(III). Crystal structure determinations for the ligands, 4·CH(3)OH and 5, the 1:1 complexes [In(4)(NO(3))(3)], [Pr(4)(NO(3))(3)(CH(3)CN)]·0.5CH(3)CN, [Er(4)(NO(3))(3)(CH(3)CN)]·CH(3)CN, [Pu(4)Cl(4)]·THF and the 2:1 complex [Nd(4)(2)(NO(3))(2)](2)(NO(3))(2)·(H(2)O)·4(CH(3)OH) are described. In these complexes, ligand 4 coordinates in a bidentate POP'O' mode via the two phosphine oxide O-atoms. The dibenzofuran ring O-atom points toward the central metal cations, but in every case it is more than 4 ? from the metal. A similar bidentate POP'O' chelate structure is formed between 5 and Er(III) in the complex, {[Er(5)(2)(NO(3))(2)](NO(3))·4(CH(3)OH)}(0.5), although the nonbonded Er···O(furan) distance is reduced to ～3.6 ?. The observed bidentate chelation modes for 4 and 5 are consistent with results from molecular mechanics computations. The solvent extraction performance of 4 and 5 in 1,2-dichloroethane for Eu(III) and Am(III) in nitric acid solutions is described and compared against the extraction behavior of n-octyl(phenyl)-N,N-diisobutylcarbamoylmethyl phosphine oxide (OΦDiBCMPO) measured under identical conditions.     

Role of the uranyl oxo group as a hydrogen bond acceptor

Density functional theory calculations have been used to evaluate the geometries and energetics of interactions between a number of uranyl complexes and hydrogen bond donor groups. The results reveal that although traditional hydrogen bond donors are repelled by the oxo group in the [UO(2)(OH(2))(5)](2+) species, they are attracted to the oxo groups in [UO(2)(OH(2))(2)(NO(3))(2)](0), [UO(2)(NO(3))(3)](-), and [UO(2)Cl(4)](2-) species. Hydrogen bond strength depends on the equatorial ligation and can exceed 15 kcal mol(-1). The results also reveal the existence of directionality at the uranyl oxo acceptor, with a weak preference for linear U═O---H angles.     

The preparation and characterization of novel cocylic(arylene disulfide) oligomers

A series of homo‐ and cocyclic(arylene disulfide) oligomers were synthesized under high dilution conditions by the catalytic oxidation of arylenedithiols with oxygen in the presence of a copper‐amine catalyst in DMAc. The aryl groups contained moieties such as sulfone, ether, and ketone. The free radical ring‐opening polymerization of these cyclic(arylene disulfide) oligomers led to the formation of linear poly(thio arylene)s. The homo‐ and cocyclic(arylene disulfide) oligomers were characterized by gradient high pressure liquid chromatography (HPLC), get permeation chromatography (GPC), ¹H‐NMR, and differential scanning calorimetry (DSC) methods. These cocyclic(arylene disulfide) oligomers except those containing sulfone moiety had lower melt flow temperature as low as 140 °C and therefore could readily undergo free radical ring‐opening polymerization under mild conditions. The glass transition temperatures of these cocyclics ranged from 72.3 to 190.0 °C, while the glass transition temperatures of the polydisulfides derived from these cocyclics ranged from 78.4 to 194.5 °C. In this article, a new method of preparing arylene dithiols 4,4′‐oxybis(benzenethiol) and diphenylmethane‐4,4′‐dithiol is reported. Copyright © 2003 John Wiley & Sons, Ltd.     

SYNTHESIS OF POLYMERS CONTAINING N-N LINKAGES

The N-N linkage in hydrazine is thermally stable when it is tetrasubstituted and there are electron-withdrawinggroups attached to the nitrogen atoms. Our research on the synthesis of polymers contaning N--N linkages is reviewed. TheN,N-bisimide structure has been introduced in the backbone of polymers as well as a pendant group in poly(aryl ether)s togive very thermoxidatively stable polymers with very high glass transition temperatures. Most of the polymers form tough,flexible films. N-Aminotriazoles also form stable imides by reaction with anhydrides and these N-imidotriazole groups havebeen introduced as pendent groups on poly(aryl ether)s. The polymers are highly fluorescent materials. Three methods for thesynthesis of polymers containing the tetrasubstituted-azine structure will be discussed: (1) oxidative coupling of bisimines;(2) condensation of bishydrazones with diketones; (3) poly(aryl ether azines) from the azine formed from 4-fluorobenzo-phenone by reaction with salts of bisphenols.     

A study of enthalpic relaxation of a liquid crystal

A liquid crystal, BL038, which was observed not to crystallize, has a glass transition at 215 K and a nematic to isotropic transition at 380 K. Samples aged below the glass transition at various temperatures T _a, exhibited an endotherm at the transition which developed with extent of ageing time, t _a. We attribute this endotherm to the relaxation of the glass towards the equilibrium liquid. The progress of the relaxation process was measured using differential scanning calorimetry. On subsequent reheating, the aged glass showed an apparent shift in the glass transition to higher temperatures. The endotherm was used to define the extent of enthalpic relaxation and the maximum value observed was found to increase initially then decrease, with the extent of undercooling from the glass transition temperature, Δ T, passing through a maximum for a Δ T = 15 K. From the temperature dependence of the relaxation times, an apparent activation enthalpy for the relaxation process of 85 ± 10 kJ mol^-1 was determined. The small value of the activation enthalpy compared with that found in the ageing of polymers reflects differences in the molecular species involved in relaxation processes.     

Thermochemistry of Sr2Ce(1-x)Pr(x)O4 (x = 0, 0.2, 0.5, 0.8, and 1): variable-temperature and -atmosphere in-situ and ex-situ powder X-ray diffraction studies and their physical properties

A novel family of metal oxides with a chemical formula of Sr(2)Ce(1-x)Pr(x)O(4) (x = 0, 0.2, 0.5, 0.8, and 1) was developed as mixed oxide ion and electronic conductors for solid oxide fuel cells (SOFCs). All of the investigated samples were synthesized by the ceramic method at 1000 °C in air and characterized by powder X-ray diffraction (PXRD), selected area electron diffraction (SAED), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), and electrochemical impedance spectroscopy (EIS). Ex-situ PXRD reveals that the Sr(2)PbO(4)-type Sr(2)CeO(4) decomposes readily into a mixture of perovskite-type SrCeO(3) and rock-salt-type SrO at 1400 °C in air. Surprisingly, the decomposed products are converted back to the original Sr(2)PbO(4)-type Sr(2)CeO(4) phase at 800 °C in air, as confirmed by in-situ PXRD. Thermal decomposition is highly suppressed in Sr(2)Ce(1-x)Pr(x)O(4) compounds for Pr > 0, suggesting that Pr improves the thermal stability of the compounds. Rietveld analysis of PXRD and SAED supported that both Pr and Ce ions are located on the 2a site in Pbam (space group no. 55). The electrical transport mechanism could be correlated to the reduction of Pr and/or Ce ions and subsequent loss of oxide ions at elevated temperatures, as shown by TGA and in-situ PXRD. Conductivity increases with Pr content in Sr(2)Ce(1-x)Pr(x)O(4). The highest total conductivity of 1.24 × 10(-1) S cm(-1) was observed for Sr(2)Ce(0.2)Pr(0.8)O(4) at 663 °C in air.     

HostDesigner: a program for the de novo structure-based design of molecular receptors with binding sites that complement metal ion guests

This paper describes a novel approach to the discovery of host structures with binding sites that complement targeted metal ion guests. This approach uses a de novo structure-based design strategy that couples molecular building algorithms with scoring functions to prioritize candidate structures. The algorithms described herein have been implemented in a program called HostDesigner, the first structure-based design software specifically created for the discovery of metal ion receptors. HostDesigner generates and evaluates millions of candidate structures within minutes, rapidly identifying three-dimensional architectures that position binding sites to provide an optimal interaction with the metal ion.