Mutations Associated with Functional Disorder of Xanthine Oxidoreductase and Hereditary Xanthinuria in Humans

Xanthine oxidoreductase (XOR) catalyzes the conversion of hypoxanthine to xanthine and xanthine to uric acid with concomitant reduction of either NAD⁺ or O₂. The enzyme is a target of drugs to treat hyperuricemia, gout and reactive oxygen-related diseases. Human diseases associated with genetically determined dysfunction of XOR are termed xanthinuria, because of the excretion of xanthine in urine. Xanthinuria is classified into two subtypes, type I and type II. Type I xanthinuria involves XOR deficiency due to genetic defect of XOR, whereas type II xanthinuria involves dual deficiency of XOR and aldehyde oxidase (AO, a molybdoflavo enzyme similar to XOR) due to genetic defect in the molybdenum cofactor sulfurase. Molybdenum cofactor deficiency is associated with triple deficiency of XOR, AO and sulfite oxidase, due to defective synthesis of molybdopterin, which is a precursor of molybdenum cofactor for all three enzymes. The present review focuses on mutation or chemical modification studies of mammalian XOR, as well as on XOR mutations identified in humans, aimed at understanding the reaction mechanism of XOR and the relevance of mutated XORs as models to estimate the possible side effects of clinical application of XOR inhibitors.     

Characterization of morphology and mechanical properties of block copolymers using atomic force microscopy: Effects of processing conditions

The effect of preparation methods and processing conditions on morphology and mechanical properties of poly(styrene-b-ethylene-co-butylene-b-styrene) (SEBS) triblock copolymer were investigated with atomic force microscopy (AFM) tapping mode and nanomechanical mapping, tensile testing, and gel permeation chromatograph (GPC). It was found that the samples prepared by solution casting and melt processing show large difference in morphology and mechanical properties. High shear rate does not induce alignment of lamellar block copolymer melts but leads to serious degradation of SEBS. As increase of rotational speed from 0 to 400 rpm, the molecular weight including M_n and M_w decreases from 67,100 to 26,000 and 70,000 to 43,000, respectively. Such large molecular weight decrease causes greatly decreased tensil strength but there is almost no evident effect on the well-phase separated morphology and Young's modulus of the SEBS. The Young's modulus distribution revealed by nanomechanical mapping becomes narrow as the increase of rotational speed. The amount of SEBS molecular having higher Young's modulus, which play a very important role in tensile strength of SEBS, also decreases.     

Superior performance of non-activated multi-walled carbon nanotube polymer actuator containing ruthenium oxide over a single-walled carbon nanotube

The electrochemical and electromechanical properties of actuators developed using a non-activated multi-walled carbon nanotube (MWCNT)–ionic liquid (IL) gel electrode containing ruthenium oxide (RuO₂) were compared with only-MWCNT and only-single-walled carbon nanotube (SWCNT) based actuators. The double-layer capacitance of the non-activated MWCNT electrode containing RuO₂ was larger than that of the only-MWCNT electrode. The non-activated MWCNT polymer actuator containing RuO₂ surpassed the performance of the only-MWCNT and only-SWCNT actuators in terms of the strain and maximum generated stress. Both MWCNTs and RuO₂ were required to produce large strain and quick response actuators that surpassed the performance of the only-SWCNT polymer actuator and exhibited characteristics sufficient for practical applications (e.g. tactile display).     

A multi-walled carbon nanotube/polymer actuator that surpasses the performance of a single-walled carbon nanotube/polymer actuator

Actuators were developed using activated and non-activated multi-walled carbon nanotube (MWCNT)–ionic liquid (IL) gel electrodes and compared to a single-walled carbon nanotube (SWCNT)-based actuator with respect to the electrochemical and electromechanical properties. The activated MWCNT–COOH/polymer actuator surpassed the SWCNT/polymer actuator in terms of the generated strain.     

Parameter optimization for the Gaussian model of protein folding

Computational models of protein folding and ligand docking are large and complex. Few systematic methods have yet been developed to optimize the parameters in such models. We describe here an iterative parameter optimization strategy that is based on minimizing a structural error measure by descent in parameter space. At the start, we know the ‘correct’ native structure that we want the model to produce, and an initial set of parameters representing the relative strengths of interactions between the amino acids. The parameters are changed systematically until the model native structure converges as closely as possible to the correct native structure. As a test, we apply this parameter optimization method to the recently developed Gaussian model of protein folding: each amino acid is represented as a bead and all bonds, covalent and noncovalent, are represented by Hooke's law springs. We show that even though the Gaussian model has continuous degrees of freedom, parameters can be chosen to cause its ground state to be identical to that of Go-type lattice models, for which the global ground states are known. Parameters for a more realistic protein model can also be obtained to produce structures close to the real native structures in the protein database.     

Miscibility and morphology in crystalline/amorphous blends of poly(caprolactone)/poly(4-vinylphenol) as studied by DSC, FTIR, and C solid state NMR

The miscibility and morphology of poly(caprolactone) (PCL) and poly (4-vinylphenol) (PVPh) blends were investigated by using differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy and ¹³C solid state nuclear magnetic resonance (NMR) spectroscopy. The DSC results indicate that PCL is miscible with PVPh. FTIR studies reveal that hydrogen bonding exists between the hydroxyl groups of PVPh and the carbonyl groups of PCL. ¹³C cross polarization (CP)/magic angle spinning (MAS)/dipolar decoupling (DD) spectra of the blends show a 1 ppm downfield shifting of ¹³C resonance of PVPh hydroxyl-substituted carbons and PCL carbonyl carbons with increasing PCL content. Both FTIR and NMR give evidence of inter-molecular hydrogen bonding within the blends. The proton spin-lattice relaxation in the laboratory frame, T₁(H), and in the rotating frame, T_1ρ(H), were studied as a function of the blend composition. The T₁(H) results are in good agreement with thermal analysis; i.e. the blends are completely homogeneous on the scale of 50-80 nm. The T_1ρ(H) results indicate that PCL in the blends has both crystalline and amorphous phases. The amorphous PCL phase is miscible with PVPh, but the PCL crystal domain size is probably larger than the spin-diffusion path length within the T_1ρ(H) time-frame, i.e. larger than 2-4 nm. The mobility differences between the crystalline and amorphous phases of PCL are clearly visible from the T_1ρ(H) data.     

Toughening of cycloaliphatic epoxy resins by poly(ethylene phthalate) and related copolyesters

Poly(ethylene phthalate) (PEP) and poly(ethylene phthalate–co‐ethylene terephthalate) were used to improve the brittleness of the cycloaliphatic epoxy resin 3,4‐epoxycyclohexylmethyl 3,4‐epoxycyclohexane carboxylate (Celoxide 2021?), cured with methyl hexahydrophthalic anhydride. The aromatic polyesters used were soluble in the epoxy resin without solvents and effective as modifiers for toughening the cured epoxy resin. For example, the inclusion of 20 wt % PEP (MW, 7400) led to a 130% increase in the fracture toughness (K_IC) of the cured resin with no loss of mechanical and thermal properties. The toughening mechanism is discussed in terms of the morphological and dynamic viscoelastic behaviors of the modified epoxy resin system. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 84: 388–399, 2002; DOI 10.1002/app.10363     

Preparation and properties ofgem-dichlorocyclopropane derivatives of long-chain fatty esters

Methyl oleate (18∶1) and linoleate (18∶2) were readily transformed to the correspondinggem-dichlorocyclopropane derivatives in high yield, using triethylbenzylammonium chloride as the phase-transfer catalyst in the presence of aqueous NaOH and CHCl₃. Reaction of dichlorocarbene with methyl 12-hydroxystearate furnished methyl 12-chlorostearate (49%) and 12-O-formylstearate (19%). The hydroxy group in methyl ricinoleate was protected (O-tetrahydropyran-2′-yl) prior to dichlorocyclopropanation of the ethylenic bond. Removal of the protecting group allowed the hydroxy group to be converted to a chloride,O-acetyl, azido orO-formyl function. Treatment of methyl ricinoleate with thionyl chloride, followed by the reaction with dichlorocarbene gave the corresponding 12-chloro-dichlorocyclopropane derivative. The dichlorocyclopropane derivative of oleic acid was transformed to a C₁₉ allenic fatty acid when treated witht-butyl lithium. However, the remaining dichlorocyclopropane derivatives, containing an additional functional group in the alkyl chain, failed to yield the corresponding allenic derivatives. All derivatives were characterized by a combination of spectroscopic and chromatographic techniques, including infrared,¹H nuclear magnetic resonance (NMR), and¹³C NMR spectroscopy.     

Synthesis of novel tri- and tetrasubstituted C<Subscript>18</Subscript> furan fatty esters

A methylene-interrupted C₁₈ keto-acetylenic fatty ester (methyl 12-oxo-9-octadecynoate) was obtained from methyl ricinoleate by bromination-dehydrobromination followed by oxidation. Reaction of methyl 12-oxo-9-octadecynoate with bis(benzonitrile) palladium(II) chloride, allyl bromide, or methyl-allyl bromide furnished methyl 8-[5-hexyl-3-allyl-furan-2-yl]-octanoate (1, 56%) or methyl 8-[5-hexyl-3-(2-methyl-allyl)-furan-2-yl]-octanoate (2, 55%). Reaction of methyl 12-oxo-11-chloro-or 11-fluoro-9-octadeyynoate (prepared from methyl santalbate-methyl 11-E-9-octadecynoate, found in sandalwood, Santalum album, seed oil) with bis(benzonitrile) palladium(II) chloride gave methyl 8-(4-fluoro-5-hexyl-furan-2-yl)-octanoate (3, 50%) or methyl 8-(4-fluoro-5-hexyl-furan-2-yl)-octanoate (4, 50%), respectively. And when methyl 12-oxo-11-chloro- or 11-fluoro-9-octadecynoate was treated with a mixture of bis(benzonitrile) palladium(II) chloride, allyl bromide, or methyl-allyl bromide, the reaction yielded tetrasubstituted C₁₈ furan derivatives, viz, methyl 8-(3-allyl-4-chloro-5-hexyl-furan-2-yl)-octanoate (5, 54%), methyl 8-[4-chloro-5-hexyl-3-(2-methyl-allyl)-furan-2-yl)-octanoate (6, 54%), methyl 8-(3-allyl-4-fluoro-5-hexyl-furan-2-yl]-octanoate (7, 10%), and methyl 8-[4-fluoro-5-hexyl-3-(2-methyl-allyl)-furan-2-yl]-octanoate (8, 10%). The presence of a fluorine atom in the furan derivatives 4, 7, and 8 was readily characterized by the appearance of doublets for carbon nuclei, which were coupled to the fluorine atom in the ¹³C NMR spectra. All furan fatty derivatives from this work were characterized by NMR spectroscopic and mass spectrometric analyses. The yields of compounds 7 and 8 were very low (10%) despite attempts to improve the procedure by increasing the amounts of the reactants and catalyst.