Comparison of Structurally-Related Alkoxide, Amine, and Thiolate-Ligated M (M= Fe, Co) Complexes: the Influence of Thiolates on the Properties of Biologically Relevant Metal Complexes

Mechanistic pathways of metalloenzymes are controlled by the metal ion’s electronic and magnetic properties, which are tuned by the coordinated ligands. The functional advantage gained by incorporating cysteinates into the active site of non-heme iron enzymes such as superoxide reductase (SOR) is not entirely understood. Herein, we compare the structural and redox properties of a series of structurally-related thiolate, alkoxide, and amine-ligated Fe(II) complexes in order to determine how the thiolate influences properties critical to function. Thiolates are shown to reduce metal ion Lewis acidity relative to alkoxides and amines, and have a strong trans influence thereby helping to maintain an open coordination site. Comparison of the redox potentials of the structurally analogous compounds described herein shows that alkoxide ligands favor the higher-valent Fe³⁺ oxidation state, amine ligands favor the reduced Fe²⁺ oxidation state, and thiolates fall somewhere in between. These properties provide a functional advantage for substrate reducing enzymes in that they provide a site at the metal ion for substrate to bind, and a moderate potential that facilitates both substrate reduction and regeneration of the catalytically active reduced state. Redox potentials for structurally-related Co(II) complexes are shown to be cathodically-shifted relative to their Fe(II) analogues, making them ineffective reducing agents for substrates such as superoxide.     

Assessing fine-root biomass and production in a Scots pine stand – comparison of soil core and root ingrowth core methods

Soil core and root ingrowth core methods for assessing fine-root (< 2 mm) biomass and production were compared in a 38-year-old Scots pine (Pinus sylvestris L) stand in eastern Finland. 140 soil cores and 114 ingrowth cores were taken from two mineral soil layers (0–10 cm and 10–30 cm) during 1985–1988. Seasonal changes in root biomass (including both Scots pine and understorey roots) and necromass were used for calculating fine-root production. The Scots pine fine-root biomass averaged annually 143 g/m² and 217 g/m² in the upper mineral soil layer, and 118 g/m² and 66 g/m² in the lower layer of soil cores and ingrowth cores, respectively. The fine-root necromass averaged annually 601 g/m² and 311 g/m² in the upper mineral soil layer, and 196 g/m² and 159 g/m² in the lower layer of soil cores and ingrowth cores, respectively. The annual fine-root production in a Scots pine stand in the 30 cm thick mineral soil layer, varied between 370–1630 g/m² in soil cores and between 210 – 490 g/m² in ingrowth cores during three years. The annual production calculated for Scots pine fine roots, varied between 330–950 g/m² in soil cores and between 110 – 610 g/m² in ingrowth cores. The horizontal and vertical variation in fine-root biomass was smaller in soil cores than in ingrowth cores. Roots in soil cores were in the natural dynamic state, while the roots in the ingrowth cores were still expanding both horizontally and vertically. The annual production of fine-root biomass in the Scots pine stand was less in root ingrowth cores than in soil cores. During the third year, the fine-root biomass production of Scots pine, when calculated by the ingrowth core method, was similar to that calculated by the soil core method. Both techniques have sources of error. In this research the sampling interval in the soil core method was 6–8 weeks, and thus root growth and death between sampling dates could not be accurately estimated. In the ingrowth core method, fine roots were still growing into the mesh bags. In Finnish conditions, after more than three growing seasons, roots in the ingrowth cores can be compared with those in the surrounding soil. The soil core method can be used for studying both the annual and seasonal biomass variations. For estimation of production, sampling should be done at short intervals. The ingrowth core method is more suitable for estimating the potential of annual fine-root production between different site types.     

Design of compound libraries based on natural product scaffolds and protein structure similarity clustering (PSSC)

Recent advances in structural biology, bioinformatics and combinatorial chemistry have significantly impacted the discovery of small molecules that modulate protein functions. Natural products which have evolved to bind to proteins may serve as biologically validated starting points for the design of focused libraries that might provide protein ligands with enhanced quality and probability. The combined application of natural product derived scaffolds with a new approach that clusters proteins according to structural similarity of their ligand sensing cores provides a new principle for the design and synthesis of such libraries. This article discusses recent advances in the synthesis of natural product inspired compound collections and the application of protein structure similarity clustering for the development of such libraries.     

A polyethylene-glycol-functionalized ring-like isopolymolybdate cluster

A new organic-inorganic hybrid compound, Na₆[HO(CH₂CH₂O)₄H]₃{Mo₃₆O₁₀₈(H₂O)₁₄(OH)₆[HO(CH₂CH₂O)₃H]₂} · ∼75H₂O (1) has been obtained in polyethylene glycol (PEG)/H₂O system with a good yield, and characterized by element analysis, IR, UV, TG, ¹³C NMR spectroscopy, electrochemistry and X-ray single crystal diffraction analysis. Compound 1 consists of the {Mo₃₆} clusters as the structural motif covalently decorated by PEG fragments. Such hybrid polyoxoanions are linked by Na⁺ counter-cations, leading to one-dimensional chains. The adjacent chains are closely packed together into a three-dimensional supramolecular framework via extensive H-bonding interactions among polyoxoanions and the isolated water molecules.     

Polycyclic dinitriles: a novel class of potent GABAergic insecticides provides a new radioligand, [3H]BIDN

The polycyclic dinitriles are a potent class of insecticides which are non-competitive GABA (γ-aminobutyric a acid) antagonists acting at the convulsant site. Comparison with other classes of GABA convulsant site ligands using molecular modelling has shown significant structural similarities. We have developed a pharmacophore model which unifies this class and some previous classes of GABA convulsants. Key pharmacophore elements are a polarizable functionality separated by a fixed distance from two H-bond accepting elements. This model is based on information from X-ray crystal structures and Sybyl using the Tripos force field. Using this pharmacophore model, numerous structural modifications were explored to enhance understanding of structure-activity relationships at the GABA receptor convulsant site of insects and mammals. A radiolabelled bicyclic dinitrile, [³H]BIDN ([³H]3,3-bis-trifluoromethyl-bicyclo[2,2,1] heptane-2,2-dicarbonitrile), was prepared from this area of chemistry and was used as a probe for the interaction of polycyclic dinitriles at the target site.     

Cycloaddition and electron transfer: On a synthetically useful aspect of pnictogen(I) reactivity

The behavior of several bi- or tri-dentate sp²-nitrogen-containing ligands with phosphorus(I) and arsenic(I) centers is investigated using computational and, in some cases, experimental methods. Whereas the chelation of putative Pn^I cations (Pn = P, As) by 1,4-diazabutadienes (DAB) generate stable, isolable phosphenium or arsenium cations that contain Pn^III centers, the corresponding reactions of Pn^I cations with β-diketiminate (NACNAC) ligands do not yield similar planar heterocycles. The behaviors of the ligands 2,6-diiminopyridine and 2,2′-bipyridine fall between the extremes delimited by the DAB and NACNAC ligands. The results of computational investigations of potential products provide a framework to rationalize the chemistry observed.     

Biogeochemical controls on aluminum chemistry in the O horizon of a red spruce (Picea rubens Sarg.) stand in central Maine,USA

This study examined the biotic and abiotic processes controlling solution chemistry and cycling of aluminum (Al) in the organic horizons of a northern coniferous forest ecosystem. A mass balance budget indicated that aboveground inputs of Al to the O horizon averaged 0.9 kg ha^–1 1 yr^–1, with major inputs accounted for by litterfall (69%), followed by precipitation (21%), and net canopy throughfall plus stemflow (10%). Estimated leaching losses of Al from the O horizon averaged 2.1 kg Al ha^-1 yr1. We hypothesize that the difference between measured Al inputs and outputs can be accounted for by Al release from weathering of soil minerals admixed into the O horizon. Variations in O horizon solution Al chemistry were influenced by a number of factors, including pH, Al equilibria with different solid-phase organic exchange sites, and Al complexation with humic ligands in soil solution.     

Environmental changes in Lake Taihu during the past century as recorded in sediment cores

The Lake Taihu drainage basin is an economically developed area with some of the highest population densities in China. The lake has deteriorated due to ecological destruction and eutrophication. Three short sediment cores from eastern, northeastern and southwestern Lake Taihu were collected. Total organic carbon (TOC), total nitrogen (TN), pigments, elements and particle size were analyzed for the purpose of understanding past trophic status and pollution levels. Sedimentation rates were based on ¹³⁷Cs or ²¹⁰Pb methods. Results indicated that sediment particle size became coarser since the 1920s, and the lake was contaminated by heavy metals, such as Cu and Zn, since the 1970s. A remarkable increase in eutrophication since the 1980s due to increased loading of untreated effluents from industry, agriculture and urbanization is reflected by total organic carbon, total nitrogen and pigments in the studied cores. However the onset times of eutrophication in different parts of Lake Taihu were not synchronous.     

Release of sedimentary nitrogen and phosphorus in polder ditches of a low-moor peat area

The release of N and P from the sediment of two ditches, one (A) dominated by filamentous algae and the other (B) by water-lilies, was estimated by core and enclosure experiments. The release rates for ditch A tended to be higher than those for ditch B. Sediment cores covered by a filamentous algae layer released about 1.5 times more N and P than those from which the layer had been removed. During the incubation of the cores in the dark at 20°C for 2–3 weeks, about 10% of the N in the filamentous algae layer was mineralized. The mineralization could be described as a first-order reaction with a rate constant of about 0.2 d^–1. On average the cores of ditches A and B released about 40 mg mineral N and 3 mg.m^–2.d^–1 soluble reactive phosphorus. Defining the release from the sediment in the enclosures as the net increase of N and P in the water phase and in the vegetation minus the input, a negative net release,i.e. net accumulation of N and P in the sediment, was found over the summer half of the year. The negative values were due to the significant N and P input, resulting from pumping ditch water into the enclosures in order to compensate for downward seepage. From the enclosure experiments a downward seepage rate of 14 mm.d^–1 and an external load of about 6 g.m^–2 total N and 0.6 g.m^–2 total P during the summer half of the year —i.e. 33 mg.m^–2.d^–1 N and 3 mg.m^–2.d^–1 P. respectively — was calculated for the ditches. Tentative gross release rates — based on the sum of the positive net release of N and P into the water phase over 1–2 weeks intervals and the net increase of N and P in the vegetation — converted to 20°C and allowing for underestimation of the primary production by a factor of 5, amounted to 58 mg mineral N and 7 mg.m^–2.d^–1 soluble reactive phosphorus during the summer half of the year. Combining the rates estimated by cores and enclosures and converting them to rates at the mean water temperature during the summer half of the year, the release of mineral N and soluble reactive phosphorus roughly amounted to 40 and 4 mg.m^–2.d^–1, respectively. The release rates as well as the external load indicated a relatively low eutrophication of the ditches.     

Screening of ligands for redox-active europium using magnetic resonance imaging

We report a screening procedure to predict ligand coordination to Eu^II and Eu^III using magnetic resonance imaging in which bright images indicate complexation and dark images indicate no complexation. Here, paramagnetic Gd^III is used as a surrogate for Eu^III in the screening procedure to enable detection with magnetic resonance imaging. The screening procedure was tested using a set of eight ligands with known coordination to Eu^II and Eu^III, and results were found to be consistent with expected binding. Validation of the screening procedure with known coordination chemistry enables use with new ligands in the future.     

Latent soil effects of grazing and ammonium deposition on Deschampsia flexuosa tillers inserted and grown in heather moorland soil

Upland heather moorlands support a range of increasingly rare and threatened biota, making them a priority habitat for conservation and restoration. Over-grazing and nitrogen deposition are two of the most important threats to maintaining these heather moorlands, yet there remains a paucity of research into their combined long-term effects. During the summer of 2008, we established an experiment within an existing research site at Pwllpeiran, mid-Wales. The original site, established in 1996, investigated long-term grazing and N deposition treatments (ammonium and nitrate) on heather moorland. Previous findings from the site, following a decade of treatment, suggested no significant, detectable impacts of treatments on soil C:N ratio and the foliar nitrogen of vegetation.The aim of our study was to investigate short- (2008) and long-term (1996–2008) N deposition treatment impacts, in combination with past grazing (1990–2007), on soil nutrient bioavailability. Soil cores were harvested and aboveground vegetation removed. Tillers of the grass Deschampsia flexuosa were planted into these cores which were then reciprocally transplanted back into the field experiment. The N deposition treatment was continued but grazing was excluded. D. flexuosa biomass changes were next assessed and leaf chemistry investigated using the metabolic fingerprinting method Fourier-transform infrared spectroscopy (FTIR) following three months of growth in the field (May–August 2008).Grazing treatment (on its own) had significant negative impacts on aboveground biomass and significant changes in plant chemistry were also revealed through the metabolic fingerprinting method Fourier transform infrared spectroscopy (FTIR). Short-term N deposition treatments during 2008 had no impacts on D. flexuosa growth or chemistry. There were also no detectable latent effects of long-term nitrate treatments on either growth or chemistry of D. flexuosa. However, plants grown in plots that had received long-term treatments of ammonium (NH₄⁺) had significantly lower poly-phenolic contents (revealed by FTIR) than plants grown in either nitrate (NO₃⁻) or control plots, suggesting detectable latent effects of N application in its reduced form. Further work needs to be undertaken to assess the relevance of residual soil nitrogen pools post N deposition and grazing.     

Glycerol dehydrogenase. structure, specificity, and mechanism of a family III polyol dehydrogenase

BACKGROUND: Bacillus stearothermophilus glycerol dehydrogenase (GlyDH) (glycerol:NAD(+) 2-oxidoreductase, EC 1.1.1.6) catalyzes the oxidation of glycerol to dihydroxyacetone (1,3-dihydroxypropanone) with concomitant reduction of NAD(+) to NADH. Analysis of the sequence of this enzyme indicates that it is a member of the so-called iron-containing alcohol dehydrogenase family. Despite this sequence similarity, GlyDH shows a strict dependence on zinc for activity. On the basis of this, we propose to rename this group the family III metal-dependent polyol dehydrogenases. To date, no structural data have been reported for any enzyme in this group. RESULTS: The crystal structure of B. stearothermophilus glycerol dehydrogenase has been determined at 1.7 A resolution to provide structural insights into the mechanistic features of this family. The enzyme has 370 amino acid residues, has a molecular mass of 39.5 kDa, and is a homooctamer in solution. CONCLUSIONS: Analysis of the crystal structures of the free enzyme and of the binary complexes with NAD(+) and glycerol show that the active site of GlyDH lies in the cleft between the enzyme's two domains, with the catalytic zinc ion playing a role in stabilizing an alkoxide intermediate. In addition, the specificity of this enzyme for a range of diols can be understood, as both hydroxyls of the glycerol form ligands to the enzyme-bound Zn(2+) ion at the active site. The structure further reveals a previously unsuspected similarity to dehydroquinate synthase, an enzyme whose more complex chemistry shares a common chemical step with that catalyzed by glycerol dehydrogenase, providing a striking example of divergent evolution. Finally, the structure suggests that the NAD(+) binding domain of GlyDH may be related to that of the classical Rossmann fold by switching the sequence order of the two mononucleotide binding folds that make up this domain.     

Polyoxoanion-supported organometallic complexes

Synthetic, spectroscopic and x-ray crystallographic research directed at assessing the steric and electronic factors which influence the chemical reactivity of polyoxoanions toward electrophiles is reviewed. Emphasis is placed on studies of hexametalate- and trimetaphosphate-supported organometallic complexes of octahedra d⁶ and square-planar d⁸ transition metals as well as actinide metals. The effects of metal-and-terminal-ligand substitution within the hexametalate cage are demonstrated through protonation and complexation studies.     

随机单链DNA文库SELEX筛选寡核苷酸适配子方法的建立

指数富集配基的系统进化(SELEX)技术是一种新的组合化学技术.体外构建了一个长度为81 nt、含有35个随机序列的单链DNA(ssDNA)文库,优化了ssDNA文库扩增为双链DNA (dsDNA)文库的PCR反应条件.通过对比不对称PCR和生物素-链亲和素磁珠分离方法制备ssDNA文库的效果,确定了以生物素-链亲和素磁珠分离方法制备ssDNA.由于脱氧核糖核酸的疏水性导致ssDNA文库与硝酸纤维素滤膜的结合背景过高,因此选择以微孔板为介质,分离与靶蛋白结合的适配子.经过9轮循环筛选,随机ssDNA文库与丙型肝炎病毒(HCV)核心蛋白(C蛋白)的结合率从0.5%上升到32.5%.     

N-methyl-bis(2-bromo 6-pyridylmethyl)amine: high yield synthesis, and spectroscopic properties of the dichloroferrous complex with trigonal bipyramidal geometry

The new tridentate title ligand has been synthesized by a very convenient and high yield method. The dichloroferrous derivative was prepared in order to provide spectroscopic bases for solution studies of trigonal bipyramidal derivatives with aminomethylpyridyl containing ligands. Its crystal structure is reported, together with UV-Vis, ¹H NMR and molecular conductivity data. The absence of any MLCT in UV-Vis, significant broadening of the β and β′ resonances in ¹H NMR and neutral electrolytic behavior are reported and taken together, these parameters can now unequivocally serve as criteria to detect any tridentate coordination mode of the tripod in the chemistry of dichloroferrous complexes with tris-(2-pyridylmethyl)amine type ligands.     

Ecological risk and contamination history of heavy metals in the Andong tidal flat,Hangzhou Bay,China

In this study, we collected two sediment cores (C1 and C2) from the Andong tidal flat, Hangzhou Bay, and studied the temporal variations of heavy metals in the cores. Vertical distributions of heavy metals were almost unchanged in both the cores before 2000. After 2000, however, the heavy metal concentrations increased dramatically, suggesting that the sediments have been affected by enhanced human pollution in the recent decade. In the core C1, the sediments were severely polluted by Pb, moderately to considerably polluted by Cr and Zn, and low to moderately polluted by other heavy metals. The core C2 was relatively unpolluted before 2000 and low to moderately polluted after 2000. Multi-statistical analyses indicated that the core C1 was additionally contaminated by local human activities such as wastewater discharge and the Hangzhou Bay Bridge. The heavy metals in the core C2, however, were largely contributed by the Yangtze River and controlled by sedimentation process. The calculated sedimentary flux (4–8 g m^?2 a^?1) of heavy metals generally increased with time. It was closely related to the wastewater discharge in adjacent areas. This study reconstructed the local heavy metal pollution history and provides important information for environmental protection and policy making.     

PET radioligands for dopamine receptors and re-uptake sites: Chemistry and biochemistry

This report, based on the past experience of European centres, offers practical guidance on the chemistry and biochemistry of PET radioligands used for the in vivo imaging of dopamine receptors and re-uptake sites. It mainly summarizes methods for the preparation of D1 and D2 receptor ligands labelled with positron-emitting radioisotopes. Some of these ligands (¹¹C-labelled SCH23390, raclopride and nomifensine, ¹⁸F-labelled butyrophenones, [⁷⁶Br]bromolisuride), which have been found useful in PET clinical investigations, have been emphasized. This report is intended as an introduction and guideline for new PET-groups who want to start research in the dopaminergic neurotransmission imaging field.     

Insights into molecular interactions between CaM and its inhibitors from molecular dynamics simulations and experimental data

In order to contribute to the structural basis for rational design of calmodulin (CaM) inhibitors, we analyzed the interaction of CaM with 14 classic antagonists and two compounds that do not affect CaM, using docking and molecular dynamics (MD) simulations, and the data were compared to available experimental data. The Ca²⁺-CaM-Ligands complexes were simulated 20 ns, with CaM starting in the “open” and “closed” conformations. The analysis of the MD simulations provided insight into the conformational changes undergone by CaM during its interaction with these ligands. These simulations were used to predict the binding free energies (ΔG) from contributions ΔH and ΔS, giving useful information about CaM ligand binding thermodynamics. The ΔG predicted for the CaM’s inhibitors correlated well with available experimental data as the r² obtained was 0.76 and 0.82 for the group of xanthones. Additionally, valuable information is presented here: I) CaM has two preferred ligand binding sites in the open conformation known as site 1 and 4, II) CaM can bind ligands of diverse structural nature, III) the flexibility of CaM is reduced by the union of its ligands, leading to a reduction in the Ca²⁺-CaM entropy, IV) enthalpy dominates the molecular recognition process in the system Ca²⁺-CaM-Ligand, and V) the ligands making more extensive contact with the protein have higher affinity for Ca²⁺-CaM. Despite their limitations, docking and MD simulations in combination with experimental data continue to be excellent tools for research in pharmacology, toward a rational design of new drugs.     

Can we rationally design promiscuous drugs?

Structure-based drug design is now used widely in modern medicinal chemistry. The application of structural biology to medicinal chemistry has heralded the "rational drug design" vision of discovering exquisitely selective ligands. However, recent advances in post-genomic biology are indicating that polypharmacology may be a necessary trait for the efficacy of many drugs, therefore questioning the "one drug, one target" assumption of current rational drug design. By combining advances in chemoinformatics and structural biology, it might be possible to rationally design the next generation of promiscuous drugs with polypharmacology.     

虎头梁遗址楔型细石核研究

本文以动态类型学和操作链思想为指导,运用数量统计分析等方法对虎头梁遗址中的444件楔型细石核进行了研究。根据台面生成方式的不同将这批楔型细石核分成Ⅰ型和Ⅱ型两个大类。Ⅰ型的台面为刃状,Ⅱ型的台面为平面状。通过对石叶疤的测量得知,从两类细石核上剥离的细石叶的宽度基本一致,都集中在3—8mm之间。Ⅰ型细石核剥离的细石叶的长度集中在15—40mm之间,Ⅱ型则集中在10—40mm之间,Ⅰ型细石核较Ⅱ型细石核有更多剥离下较长细石叶的可能性。两类细石核所采用的原料包括火山角砾岩、硅质岩、流纹岩、石英岩、碧玉、玛瑙、英安岩、黑曜岩及水晶等9种,以火山角砾岩和硅质岩为主,原料利用方面没有大的差别。将石核按剥片阶段划分为预制、剥片、中止、终极4种,处于不同阶段的石核被废弃的原因是不同的,包括毛坯中存在瑕疵、剥片失误以及用尽遗弃等。