Reactivity of Inorganic Mn and Mn Desferrioxamine B with O2, O2–, and H2O2 in Seawater

Manganese (Mn) is a required element for oceanic phytoplankton as it plays a critical role in photosynthesis, through its unique redox chemistry, as the active site in photosystem II, and in enzymes that act as defenses against reactive oxygen species (ROS), most notably for protection against superoxide (O2?), through the action of superoxide dismutase (SOD), and against hydrogen peroxide (H2O2) via peroxidases and catalases. The distribution and redox speciation of Mn in the ocean is also apparently controlled by reactions with ROS. Here we examine the connections between ROS and dissolved Mn species in the upper ocean using field and laboratory experimental data. Our results suggest it is unlikely that significant concentrations of Mn(III) are produced in the euphotic zone, as in the absence of evidence for the existence of strong Mn(III) ligands, Mn(II) reacts with O2? to form the short-lived transient manganous superoxide, MnO2+, which may react rapidly with other redox species in a manner similar to O2?. Experiments with the strong Mn(III) chelator, desferrioxamine B (DFB), in seawater indicated that the Mn(III) species are unlikely to form, as formation of the precursor Mn(II) complex is hindered due to the stability of the Ca complex with DFB.

A Quantitative Investigation of Selected Reactions in the Fibrinolytic Cascade

Previous work has shown that thrombin activatable fibrinolysis inhibitor (TAFI) was unable to prolong lysis of purified clots in the presence of Lys-plasminogen (Lys-Pg), indicating a possible mechanism for fibrinolysis to circumvent prolongation mediated by activated TAFI (TAFIa). Therefore, the effects of TAFIa on Lys-Pg activation and Lys-plasmin (Lys-Pn) inhibition by antiplasmin (AP) were quantitatively investigated using a fluorescently labeled recombinant Pg mutant which does not produce active Pn. High molecular weight fibrin degradation products (HMW-FDPs), a soluble fibrin surrogate that models Pn modified fibrin, treated with TAFIa decreased the catalytic efficiency (kcat/Km) of 5IAF-Glu-Pg cleavage by 417-fold and of 5IAF-Lys-Pg cleavage by 55-fold. A previously devised intact clot system was used to measure the apparent second order rate constant (k2) for Pn inhibition by AP over time. While TAFIa was able to abolish the protection associated with Pn modified fibrin in clots formed with Glu-Pg, it was not able to abolish the protection in clots formed with Lys-Pg. However, TAFIa was still able to prolong the lysis of clots formed with Lys-Pg. TAFIa prolongs clot lysis by removing the positive feedback loop for Pn generation. The effect of TAFIa modification of the HMW-FDPs on the rate of tissue type plasminogen activator (tPA) inhibition by plasminogen activator inhibitor type 1 (PAI-1) was investigated using a previously devised end point assay. HMW-FDPs decreased the k2 for tPA inhibition rate by 3-fold. Thus, HMW-FDPs protect tPA from PAI-1. TAFIa treatment of the HMW-FDPs resulted in no change in protection. Vitronectin also did not appreciably affect tPA inhibition by PAI-1. Pg, in conjunction with HMW-FDPs, decreased the k2 for tPA inhibition by 30-fold. Hence, Pg, when bound to HMW-FDPs, protects tPA by an additional 10-fold. TAFIa treatment of the HMW-FDPs completely removed this additional protection provided by Pg. In conclusion, an additional mechanism was identified whereby TAFIa can prolong clot lysis by increasing the rate of tPA inhibition by PAI-1 by eliminating the protective effects of Pn-modified fibrin and Pg. Because TAFIa can suppress Lys-Pg activation but cannot attenuate Lys-Pn inhibition by AP, the Glu- to Lys-Pg/Pn conversion is able to act as a fibrinolytic switch to ultimately lyse the clot.

A Density Functional Theory Study on the Active Center of Fe-Only Hydrogenase: Characterization and Electronic Structure of the Redox States

We have carried out extensive density functional theory (DFT) calculations for possible redox states of the active center in Fe-only hydrogenases. The active center is modeled by [(H(CH(3))S)(CO)(CN(-))Fe(p)(mu-DTN)(mu-CO)Fe(d)(CO)(CN(-))(L)](z) (z is the net charge in the complex; Fe(p)= the proximal Fe, Fe(d) = the distal Fe, DTN = (-SCH(2)NHCH(2)S-), L is the ligand that bonds with the Fed at the trans position to the bridging CO). Structures of possible redox states are optimized, and CO stretching frequencies are calculated. By a detailed comparison of all the calculated structures and the vibrational frequencies with the available experimental data, we find that (i) the fully oxidized, inactive state is an Fe(II)-Fe(II) state with a hydroxyl (OH(-)) group bonded at the Fe(d), (ii) the oxidized, active state is an Fe(II)-Fe(l) complex which is consistent with the assignment of Cao and Hall (J. Am. Chem. Soc. 2001, 123, 3734), and (iii) the fully reduced state is a mixture with the major component being a protonated Fe(l)-Fe(l) complex and the other component being its self-arranged form, Fe(II)-Fe(II) hydride, Our calculations also show that the exogenous CO can strongly bond with the Fe(II)-Fe(l) species, but cannot bond with the Fe(l)-Fe(l) complex. This result is consistent with experiments that CO tends to inhibit the oxidized, active state, but not the fully reduced state. The electronic structures of all the redox states have been analyzed. It is found that a frontier orbital which is a mixing state between the e(g) of Fe and the 2pi of the bridging CO plays a key role concerning the reactivity of Fe-only hydrogenases: (1) it is unoccupied in the fully oxidized, inactive state, half-occupied in the oxidized, active state, and fully occupied in the fully reduced state; (ii) the e(g)-2pi orbital is a bonding state, and this is the key reason for stability of the low oxidation states, such as Fe(l)-Fe(l) complexes; and (iii) in the e(g)-2pi orbital more charge accumulates between the bridging CO and the Fe(d) than between the bridging CO and the Fe(p), and the occupation increase in this orbital will enhance the bonding between the bridging CO and the Fe(d), leading to the bridging-CO shift toward the Fe(d).

Heterogeneously catalysed selective hydrogenation reactions in ionic liquids

The selective hydrogenation of , unsaturated aldehydes has been performed in a range of room temperature ionic liquids. The reaction data reported show that it is possible to enhance the selectivity of supported palladium catalysts for the reduction of the conjugated CC bond by using ionic liquids as solvents compared with conventional molecular organic solvents. The catalyst system is easily recycled without the need to isolate or filter the catalyst and may be used without further treatment.

The SPHERE Study: Secondary prevention of heart disease in general practice: protocol of a randomised controlled trial of tailored practice and patient care plans with parallel qualitative, economic and policy analyses. [ISRCTN24081411]

Background: The aim of the SPHERE study is to design, implement and evaluate tailored practice and personal care plans to improve the process of care and objective clinical outcomes for patients with established coronary heart disease (CHD) in general practice across two different health systems on the island of Ireland.CHD is a common cause of death and a significant cause of morbidity in Ireland. Secondary prevention has been recommended as a key strategy for reducing levels of CHD mortality and general practice has been highlighted as an ideal setting for secondary prevention initiatives. Current indications suggest that there is considerable room for improvement in the provision of secondary prevention for patients with established heart disease on the island of Ireland. The review literature recommends structured programmes with continued support and follow-up of patients; the provision of training, tailored to practice needs of access to evidence of effectiveness of secondary prevention; structured recall programmes that also take account of individual practice needs; and patient-centred consultations accompanied by attention to disease management guidelines.

Methods: SPHERE is a cluster randomised controlled trial, with practice-level randomisation to intervention and control groups, recruiting 960 patients from 48 practices in three study centres (Belfast, Dublin and Galway). Primary outcomes are blood pressure, total cholesterol, physical and mental health status (SF-12) and hospital re-admissions. The intervention takes place over two years and data is collected at baseline, one-year and two-year follow-up. Data is obtained from medical charts, consultations with practitioners, and patient postal questionnaires. The SPHERE intervention involves the implementation of a structured systematic programme of care for patients with CHD attending general practice. It is a multi-faceted intervention that has been developed to respond to barriers and solutions to optimal secondary prevention identified in preliminary qualitative research with practitioners and patients. General practitioners and practice nurses attend training sessions in facilitating behaviour change and medication prescribing guidelines for secondary prevention of CHD. Patients are invited to attend regular four-monthly consultations over two years, during which targets and goals for secondary prevention are set and reviewed. The analysis will be strengthened by economic, policy and qualitative components.