A New and Facile Synthesis of Novel Pyrazolothienopyrimidines and Imidazopyrazolothienopyrimidines

4‐Amino‐3‐methyl‐1‐phenyl‐1H‐thieno[2,3‐c]pyrazole‐5‐carboxamide ( 5 ), which was synthesized by an innovative method, was used as a versatile precursor for synthesizing pyrazolothienopyrimidines and imidazopyrazolothienopyrimidines compounds. Reaction of amino thienopyrazole carboxamide 5 with triethyl orthoformate afforded thienopyrazolopyrimidine 6 . Chlorination of the latter compound, using phosphorus oxychloride afforded the chloro pyrazolothienopyrimidine 7 , which underwent nucleophilic substitution reactions with various primary and secondary amines to give the alkyl (aryl) amino pyrimidine compounds 8a–d . On the other hand, the reaction of chloropyrimidine 7 with thiourea afforded the pyrimidine thione compound 9 , which was alkylated with α‐halogentaed compounds to afford the S‐alkylated derivatives 10a–c . Also, chloroacetylation of the amino carboxamide 5 using chloroacetyl chloride yielded the chloromethyl pyrazolothienopyrimidine 12 , which underwent nucleophilic substitu‐ tion reactions with various primary and secondary amines to afford the alkyl (aryl) aminomethyl compounds 13a–f . The latter Compounds underwent Mannich reaction to give imidazopyrimidothieno‐ pyrazoles 14a–c . The newly synthesized compounds and their derivatives were fully characterized by elemental and spectral analysis.     

Fabrication and characterization of pseudo-ceramide-based liposomal membranes

We present a facile and straightforward method to fabricate liposomal membranes with a significantly stable lamellar structure consisting of pseudo-ceramide, fatty acid, and cholesterol. Characterizing their membrane properties, in which we have used differential scanning calorimetry, X-ray diffraction, and FT-IR spectra, enables us to demonstrate that pseudo-ceramide with appropriate amounts of stearic acid and cholesterol can assemble to form a stable lamellar α-phase. Moreover, we show that cholesterol is indeed important and plays a role in controlling the melting entropy of lipid membranes, which is attributed to a disordered molecular packing, thus creating more flexible liposomal membranes. This approach to use pseudo-ceramide offers a useful means to fabricate a variety of biocompatible liposomes with controllable membrane properties, which enlarges their applicability in the field of drug delivery, dermatology, and cosmetics.     

Formation and characterization of mononuclear and dinuclear manganese oxide-dioxygen complexes in solid argon

A manganese atom reacts with dioxygen to form the previously characterized MnO 2 molecule in solid argon under UV-visible light irradiation. Subsequent sample annealing allows the dioxygen molecules to diffuse and to react with MnO 2 to give the (eta (2)-O 2)MnO 2 complex, which is characterized to be a side-on bonded peroxo manganese dioxide complex. The manganese tetraoxide MnO 4, which was predicted to be less stable than the (eta (2)-O 2)MnO 2 isomer, was not observed. However, the (eta (2)-O 2)MnO 2 complex reacts with another weakly coordinated dioxygen to give the (eta (2)-O 2)MnO 4 complex via visible light irradiation, in which the manganese tetraoxide is coordinated and stabilized by a side-on bonded O 2 molecule. Manganese dimer reacts with dioxygen to form the cyclic Mn(mu-O) 2Mn cluster spontaneously upon annealing, which further reacts with dioxygen to give the (eta (2)-O 2) 2Mn(mu-O) 2Mn cluster, a side-on bonded disuperoxide complex with a planar D 2 h structure.     

Affinity and nuclease activity of macrocyclic polyamines and their CuII complexes

The stability constants of Cu(II) complexes that consist of either an oxaaza macrocycle with two triamine moieties linked by dioxa chains, or two macrocyclic ligands with a polyamine chain which are connecting the 2 and 9 positions of phenanthroline, have been determined by means of potentiometric measurements. The results are compared to those reported for other ligands with a similar molecular architecture. Of the complexes that contain phenanthroline in their macrocycle, the Cu(II) ion of the complex with the smallest and most rigid macrocycle (L3) has an unsaturated coordination sphere, while in the complex with the largest macrocycle (L5) the Cu(II) ion is coordinatively almost saturated. These results are corroborated by the crystal structure of the [CuL5](ClO4)2 complex. The affinity of the ligands and the complexes towards nucleic acids was studied by measuring the changes in the melting temperature, which showed that the affinity of the macrocyclic ligands towards double-stranded DNA or RNA is generally smaller than that of their linear analogues that bear a similar charge, with a strong preference for polyA-polyU, a model for RNA. However, the complexes of two of the changed macrocyclic ligands which contain a phenanthroline unit (L4, L5) showed a distinctly larger increase in their melting temperature deltaTm with DNA (polydA-polydT), which is reversed again in favor of RNA upon metallation to the dinuclear copper complex with L5. Experiments with supercoiled plasmid DNA showed a particularly effective cleavage with a mononuclear Cu(II) complex that contains a phenanthroline unit (L6). Related ligands showed less activity towards DNA, but not so towards the biocidic bis(p-nitrophenyl)phosphate (BNPP). In both cases (with DNA and BNPP) the activity seemed to increase with decrease of coordinative saturation of the Cu(II) ion, with the exception of one particular ligand (L6). Experiments with radical scavengers in the DNA experiments showed some decrease in cleavage, which indicates the participation of redox processes.     

卟啉钴分子筛的制备,表征和催化性能的研究

用液－固相分步合成法将新型四卤四甲基卟啉诱捕在经Ｃｏ＾２＋交换的ＮａＸ分子筛超笼内，利用索式提取器洗净分子筛外表面吸附的卟啉后，采用ＵＶ－Ｖｉｓ、ＩＲ、ＳＥＭ、ＤＴＡ、Ｘ射线衍射分析、吸附等手段对诱捕在超笼内的卟啉予以表征。进一步对比研究了卟啉、分子筛和诱捕卟啉分子筛的催化性能。结果表明，卟啉与分子筛结合后，催化活性大大提高。     

Elucidating the biosynthesis of chitin filaments and their configuration with specific proteins and electron microscopy

To deepen the knowledge of chitin synthesis, a yeast mutant has been used as a model. Purified chitin synthase I-containing vesicles (chitosomes) with a diameter of 85 to 120 nm are identified by electron microscopy to eject tiny fibers upon addition of UDP-N-acetylglucosamine. The filigree of extruded filaments fused gradually into a large three-dimensional network, which is degradable by a chitinase. The network is targeted and restructured by the Streptomyces chitin-binding protein CHB1, which has a very high affinity only for alpha-chitin. Within the chitosomes, filaments are found to be highly condensed within consecutive oval fibroids, which are specifically targeted by the alpha-chitin-binding protein. The presented data give new insights to the generation of chitin filaments with an antiparallel (alpha) configuration. [image: see text]     

Effective interaction parameter of linear/star polymer blends and comparison with that of linear/linear and star/star blends

The authors present a detailed study of the microscopic parameters, which control the miscibility in binary linear/star polymer blends. The effective interactions of linear/star polymer blends are studied by means of Monte Carlo simulations and comparison is made with linear/linear and star/star blends, which they also determined. Using the bond fluctuation model on a simple cubic lattice, the authors are able to simulate symmetric linear/linear, star/star, and, for the first time, linear/star blends with a moderate number of arms. The simulations were performed at a volume fraction of occupied lattice sites phi=0.5, which corresponds to dense polymer mixtures for this algorithm. In particular, we study star/star blends with 4, 8, and 12 arms and the respective linear/linear blends as well as linear/star blends, all having the same total number of units equal to 73 and 121. The authors find that linear/star blends are more miscible than the corresponding linear/linear blends, which is in agreement with recent experimental and theoretical results. They find that linear/star mixtures are less miscible than star/star blends, a result which is also verified by theoretical findings.     

Interactions of mono- and divalent metal ions with aspartic and glutamic acid investigated with IR photodissociation spectroscopy and theory

The interaction of metal ions with aspartic (Asp) and glutamic (Glu) acid and the role of gas-phase acidity on zwitterionic stability were investigated using infrared photodissociation spectroscopy in the spectral range 950-1900 cm (-1) and by hybrid density functional theory. Lithium ions interact with both carbonyl oxygen atoms and the amine nitrogen for both amino acids, whereas cesium interacts with both of the oxygen atoms of the C-terminus and the carbonyl oxygen of the side chain for Asp. For Glu, this structure is competitive, but a structure in which the cesium ion interacts with just the carbonyl oxygen atoms is favored and the calculated spectrum for this structure is more consistent with the experimentally measured spectrum. In complexes with either of these metal ions, both amino acids are non-zwitterionic. In contrast, Glu*Ca (2+) and Glu*Ba (2+) both adopt structures in which Glu is zwitterionic and the metal ion interacts with both oxygens of the C-terminal carboxylate and the carbonyl oxygen in the side chain. Assignment of the zwitterionic form of Glu is strengthened by comparisons to the spectrum of the protonated form, which indicate spectral features associated with a protonated amino nitrogen. Comparisons with results for glutamine, which adopts nearly the same structures with these metal ions, indicate that the lower Delta H acid of Asp and Glu relative to other amino acids does not result in greater relative stability of the zwitterionic form, a result that is directly attributed to effects of the metal ions which disrupt the strong interaction between the carboxylic acid groups in the isolated, deprotonated forms of these amino acids.     

The reactivity of air-stable pyridine- and pyrimidine-containing diarylamine antioxidants

We recently reported a preliminary account of our efforts to develop novel diarylamine radical-trapping antioxidants (Hanthorn et al. J. Am. Chem. Soc.2012, 134, 8306-8309), wherein we demonstrated that the incorporation of ring nitrogens into diphenylamines affords compounds that display a compromise between H-atom transfer reactivity to peroxyl radicals and stability to one-electron oxidation. Herein, we report the results of thermochemical and kinetic experiments on an expanded set of diarylamines (see the accompanying paper, DOI: 10.1021/jo301013c ), which provide a more complete picture of the structure-reactivity relationships of these compounds as antioxidants. Nitrogen incoporation into a series of alkyl-, alkoxyl-, and dialkylamino-substituted diphenylamines raises their oxidation potentials systematically with the number of nitrogen atoms, resulting in overall increases of 0.3-0.5 V on going from the diphenylamines to the dipyrimidylamines. At the same time, the effect of nitrogen incorporation on their reactivity toward peroxyl radicals was comparatively small (a decrease of only 6-fold at most), which is also reflected in their N-H bond dissociation enthalpies. Rate constants for reactions of dialkylamino-substituted diarylamines with peroxyl radicals were found to be >10(7) M(-1) s(-1), which correspond to the pre-exponential factors that we obtained for a representative trio of compounds (log A ～ 7), indicating that the activation energies (E(a)) are negligible for these reactions. Comparison of our thermokinetic data for reactions of the diarylamines with peroxyl radicals with literature data for reactions of phenols with peroxyl radicals clearly reveals that diarylamines have higher inherent reactivities, which can be explained by a proton-coupled electron-transfer mechanism for these reactions, which is supported by theoretical calculations. A similar comparison of the reactivities of diarylamines and phenols with alkyl radicals, which must take place by a H-atom transfer mechanism, clearly reveals the importance of the polar effect in the reactions of the more acidic phenols, which makes phenols comparatively more reactive.     

Influence of PCL and PHBV on PLLA Thermal and Mechanical Properties in Binary and Ternary Polymer Blends

PLLA, PCL and PHBV are aliphatic polyesters which have been researched and used in a wide range of medical devices, and all three have advantages and disadvantages for specific applications. Blending of these materials is an attractive way to make a material which overcomes the limitations of the individual polymers. Both PCL and PHBV have been evaluated in polymer blends with PLLA in order to provide enhanced properties for specific applications. This paper explores the use of PCL and PHBV together with PLLA in ternary blends with assessment of the thermal, mechanical and processing properties of the resultant polymer blends, with the aim of producing new biomaterials for orthopaedic applications. DSC characterisation is used to demonstrate that the materials can be effectively blended. Blending PCL and PHBV in concentrations of 5–10% with PLLA produces materials with average modulus improved by up to 25%, average strength improved by up to 50% and average elongation at break improved by 4000%, depending on the concentrations of each polymer used. PHBV impacts most on the modulus and strength of the blends, whilst PCL has a greater impact on creep behaviour and viscosity. Blending PCL and PHBV with PLLA offers an effective approach to the development of new polyester-based biomaterials with combinations of mechanical properties which cannot be provided by any of the materials individually.     

Solubilization of steviolbioside and steviolmonoside with gamma-cyclodextrin and its application to selective syntheses of better sweet glycosides from stevioside and rubusoside

1,4-alpha-Glucosylation at the 13-O-glycosyl moiety of stevioside (S) and rubusoside (RU) results in a significant increase of sweetness. Saponification of the 19-COO-beta-glucosyl linkage of S and RU yielded steviolbioside (SB) (= 13-O-beta-sophorosyl-steviol) and steviolmonoside (SM) (= 13-O-beta-glucosyl-steviol), respectively, both of which are poorly soluble in an acetate buffer. It was found that the solubilities of SM and SB in the buffer solution were remarkably increased in the presence of gamma-cyclodextrin (gamma-CD). SB was solubilized in the buffer solution with the aid of gamma-CD, and the solution was subjected to 1,4-alpha-transglucosylation by using a cyclodextrin glucanotransferase-starch system to give a mixture of products which were glucosylated at the 13-O-glycosyl moiety. This mixture was acetylated, and the acetate was subjected to chemical beta-glucosylation of 19-COOH followed by deacetylation to afford compounds which have superior sweetness to S. In the same way, derivatives with superior sweetness were selectively prepared from RU through SM.     

Conversion of glucosamine to galactosamine and allosamine derivatives: control of inversions of stereochemistry at C-3 and C-4.

The reactions of sodium benzoate with a series of trimesylates derived from glucosamine have been examined in an attempt to gain facile access to galactosamine analogues. Trimesylate 17, in which the amino group was protected as a phthalimide, underwent double displacement at positions 4 and 6 to give the dibenzoate 18 with the desired galactosamine configuration. In contrast, trimesylates 21 and 27, in which the amino groups were protected as acetamides, unexpectedly underwent double displacement at positions 3 and 6, giving products 22 and 28, respectively, with allosamine configurations.     

Structure and some reactions of coriose

Coriose was obtained in a higher yield from the root of Coriaria japonica. The structure, -altro-3-heptulose (I) was determined by the sodium borohydride reduction which yielded volemitol (II) and -glycero- -altro-hepitol (IV). Other reactions in agreement with this structure (I) were also carried out: The oxidative degradation of coriose in cold alkali produced a pentanolactone syrup which was reduced to ribose, while the degradation at elevated temperature gave a hexanolactone syrup which yielded ribose on treatment with ferric acetate-hydrogen peroxide. The rearrangement of coriose in alkali at room temperature to 2-heptuloses was investigated. Lead tetraacetate oxidation of coriose produced -glyceraldehyde and -glyceric acid.     

Cooperative and anticooperative mixed trimers of HCl and methanol

In the hydrogen-bonded complex between two HCl molecules and one methanol unit, there are two isomers with similar energies. A cyclic isomer profits from hydrogen bond cooperativity, whereas a converging structure, in which both HCl molecules bind to the lone pairs of methanol, profits from the good acceptor quality of methanol. The latter compensates for anticooperative three-body forces, which arise from the competition of the HCl units for acceptor electron density. This theoretical prediction is supported by FT-IR spectra of supersonic jet expansions, in which both mixed trimers are tentatively assigned along with the mixed dimer of HCl and methanol based on their O–H and Cl–H stretching bands.     

Multivalency and the mode of action of bacterial sialidases

Although complex modular proteins are encountered frequently in a variety of biological systems, their occurrence in biocatalysis has not been widely appreciated. Here, we describe that bacterial sialidases, which have both a catalytic and carbohydrate-binding domain, can hydrolyze polyvalent substrates with much greater catalytic efficiency than their monovalent counterparts. The enhancement of catalytic efficiency was due to a much smaller Michaelis constant and rationalized by a model in which the catalytic and lectin domains interact simultaneously with the polyvalent substrate, leading to an enhancement of affinity. Inhibition studies have shown that galactosides released by the action of the sialidase can act as the ligand for the lectin domain. This knowledge has been exploited in the design of a potent polyvalent inhibitor of the sialidase of Vibrio cholerae, which displayed exquisite selectivities for sialidases that have a lectin domain.     

寡聚噻吩取代的9,9'-螺二芴的合成和表征

以四种溴化的9,9'-螺二芴为原料,设计合成了一系列新型的寡聚噻吩取代的9,9'－螺二芴。其结构均经1^H,13^CNMR,MS,FT-IR或元素分析确证。通过核磁工振氢谱分析,我们对该类化合物芳环质了的化学位移进行了归属。热重差热分析表明,由于螺二芴的引入,该类化合物具有较高的玻璃化转变温度和明显改善的无定型性。初步的光学性能研究表明,该类化合物寡聚噻吩相比,其荧光效率明显增强,并且随着寡聚噻吩与螺二芴连接位置的不同,其光学性能也有明显差异。     

Oxidation state and proton doping level in copolymers of 2-aminobenzoic acid and 2-methoxyaniline

UV-vis spectra of homopolymers and copolymers of 2-aminobenzoic acid (OAB) and 2-methoxyaniline (OMA) were analyzed in order to obtain information about the oxidation state and proton doping level of these polymers. Dimethyl sulfoxide (DMSO) was used as a solvent in which protonated forms of polyanilines are preserved and a mixture of N-methyl-2-pyrrolidone and triethylamine (0.5 %) as a solvent (NMP/TEA) in which polyanilines are assumed to be non-protonated. Polymers were prepared in the emeraldine salt form, externally doped with HCl. It was found that only external doping is eliminated in NMP/TEA while internal doping by carboxylate groups bound in OAB units remains operative. Since doped quinoid units do not contribute to the quinoid band (Q-band at 630 nm), the intensity ratio of the Q-band and benzenoid band (B-band at 320 nm) cannot be simply correlated with the oxidation state of poly(OMA-co-OAB) copolymers in contrast to poly(OMA) and polyaniline. Spectra of copolymers with less than 60 % of OMA units as well as those of poly(OAB) in DMSO and NMP/TEA are almost identical due to internal doping, which is proposed to lead to structures in which main-chain protons are coulombically bound with immobile carboxylate anions. In the spectra of copolymers with less than 60 % of OMA units, a well-resolved band occurs at 500 nm, which can be ascribed to alternating or close-to-alternating sequences of OMA and OAB units.     

Electrochemical Characterization and Quantification of the Strong Antioxidant and Antitumor Agent Pomiferin

The electrochemical behavior of pomiferin, a natural isoflavone with significant antioxidant, antidiabetic and antitumor properties, is reported here for the first time at a glassy carbon electrode (GCE). In order to understand the redox processes of this compound, its response was compared with the nonantioxidant isoflavone osajin. Based on cyclic and square‐wave voltammetric methods it was observed that pomiferin presents a quasireversible anodic peak, which was attributed to the oxidation of the catechol group, and that is strongly influenced by pH. This anodic process yields a well‐defined DPV response, which can be used for the analytical determination of this potential pharmotherapeutic isoflavone.     

Production and Analysis of the Physicochemical Properties of the Pyrolytic Oil Obtained from Pyrolysis of Different Thermoplastics and Plastic Mixtures

The constant search for the proper management of non-degradable waste in conjunction with the circular economy makes the thermal pyrolysis of plastics an important technique for obtaining products with industrial interest. The present study aims to produce pyrolytic oil from thermoplastics and their different mixtures in order to determine the best performance between these and different mixtures, as well as to characterize the liquid fraction obtained to analyze its use based on said properties. This was carried out in a batch type reactor at a temperature of 400 °C for both individual plastics and their mixtures, from which the yields of the different fractions are obtained. The liquid fraction of interest is characterized by gas chromatography and its properties are characterized by ASTM standards. The product of the pyrolysis of mixtures of 75% polystyrene and 25% polypropylene presents a yield of 82%, being the highest, with a viscosity of 1.12 cSt and a calorific power of 42.5 MJ/kg, which has a composition of compounds of carbon chains ranging between C6 and C20, for which it is proposed as a good additive agent to conventional fuels for industrial use.     

Comparative study of synonymous codon usage variations between the nucleocapsid and spike genes of coronavirus, and C-type lectin domain genes of human and mouse

Coronaviruses (CoVs) are single-stranded RNA viruses which contain the largest RNA genomes, and severe acute respiratory syndrome coronavirus (SARS-CoV), a newly found group 2 CoV, emerged as infectious disease with high mortality rate. In this study, we compared the synonymous codon usage patterns between the nucleocapsid and spike genes of CoVs, and C-type lectin domain (CTLD) genes of human and mouse on the codon basis. Findings indicate that the nucleocapsid genes of CoVs were affected from the synonymous codon usage bias than spike genes, and the CTLDs of human and mouse partially overlapped with the nucleocapsid genes of CoVs. In addition, we observed that CTLDs which showed the similar relative synonymous codon usage (RSCU) patterns with CoVs were commonly derived from the human chromosome 12, and mouse chromosome 6 and 12, suggesting that there might be a specific genomic region or chromosomes which show a more similar synonymous codon usage pattern with viral genes. Our findings contribute to developing the codon-optimization method in DNA vaccines, and further study is needed to determine a specific correlation between the codon usage patterns and the chromosomal locations in higher organisms.