The oxido-bridged diiron(III) complex [Fe-2(mu-O)(mu-OAc)(DPEAMP)(2)](OCH3) (1), based on a new unsymmetrical ligand with an N4O donor set, viz. [2-((bis(pyridin-2-ylmethyl)amino)methyl)-6-((ethylamino)methyl)-4-meth-ylphenol (HDPEAMP)], has been prepared and characterized by spectroscopic methods and X-ray crystallog-raphy. The crystal structure of the complex reveals that each Fe(III) ion is coordinated by three nitrogen and three oxygen donors, two of which are the bridging oxido and acetate ligands. Employing H2O2 as a terminal oxidant, 1 is capable of oxidizing a number of alkanes and alkenes with high activity. The catalytic oxidation of 1,2-dimethylcyclohexane results in excellent retention of configuration. Monitoring of the reaction of 1 with H2O2 and acetic acid in the absence of substrate, using low-temperature UV-Vis spectroscopy, suggests the in situ formation of a transient Fe(III)(2)-peroxido species. While the selectivity and nature of oxidation products implicate a high-valent iron-oxido complex as a key intermediate, the low alcohol/ketone ratios suggest a simultaneous radical-based process.

Here, we disclose a new copper(i)-Schiff base complex series for selective oxidation of primary alcohols to aldehydes under benign conditions. The catalytic protocol involves 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO), N-methylimidazole (NMI), ambient air, acetonitrile, and room temperature. This system provides a straightforward and rapid pathway to a series of Schiff bases, particularly, the copper(i) complexes bearing the substituted (furan-2-yl)imine bases N-(4-fluorophenyl)-1-(furan-2-yl)methanimine (L2) and N-(2-fluoro-4-nitrophenyl)-1-(furan-2-yl)methanimine (L4) have shown excellent yields. Both benzylic and aliphatic alcohols were converted to aldehydes selectively with 99% yield (in 1-2 h) and 96% yield (in 16 h). The mechanistic studies via kinetic analysis of all components demonstrate that the ligand type plays a key role in reaction rate. The basicity of the ligand increases the electron density of the metal center, which leads to higher oxidation reactivity. The Hammett plot shows that the key step does not involve H-abstraction. Additionally, a generalized additive model (GAM, including random effect) showed that it was possible to correlate reaction composition with catalytic activity, ligand structure, and substrate behavior. This can be developed in the form of a predictive model bearing in mind numerous reactions to be performed or in order to produce a massive data-set of this type of oxidation reaction. The predictive model will act as a useful tool towards understanding the key steps in catalytic oxidation through dimensional optimization while reducing the screening of statistically poor active catalysis.

We introduce LytU, a short member of the lysostaphin family of zinc-dependent pentaglycine endopeptidases. It is a potential antimicrobial agent for S. aureus infections and its gene transcription is highly upregulated upon antibiotic treatments along with other genes involved in cell wall synthesis. We found this enzyme to be responsible for the opening of the cell wall peptidoglycan layer during cell divisions in S. aureus. LytU is anchored in the plasma membrane with the active part residing in the periplasmic space. It has a unique Ile/Lys insertion at position 151 that resides in the catalytic site-neighbouring loop and is vital for the enzymatic activity but not affecting the overall structure common to the lysostaphin family. Purified LytU lyses S. aureus cells and cleaves pentaglycine, a reaction conveniently monitored by NMR spectroscopy. Substituting the cofactor zinc ion with a copper or cobalt ion remarkably increases the rate of pentaglycine cleavage. NMR and isothermal titration calorimetry further reveal that, uniquely for its family, LytU is able to bind a second zinc ion which is coordinated by catalytic histidines and is therefore inhibitory. The pH-dependence and high affinity of binding carry further physiological implications.

Changes in prolyl oligopeptidase (PREP) expression levels, protein distribution, and activity correlate with aging and are reported in many neurodegenerative conditions. Together with decreased neuropeptide levels observed in aging and neurodegeneration, and PREP's ability to cleave only small peptides, PREP was identified as a druggable target. Known PREP non-enzymatic functions were disregarded or attributed to PREP enzymatic activity, and several potent small molecule PREP inhibitors were developed during early stages of PREP research. These showed a lot of potential but with variable results in experimental memory models, however, the initial excitement was short-lived and all of the clinical trials were discontinued in either Phase I or II clinical trials for unknown reasons. Recently, PREP's ability to form protein-protein interactions, alter cell proliferation and autophagy has gained more attention than earlier recognized catalytical activity. Of new findings, particularly the aggregation of alpha-synuclein (aSyn) that is seen in the presence of PREP is especially interesting because PREP inhibitors are capable of altering aSyn-PREP interaction in a manner that reduces the aSyn dimerization process. Therefore, it is possible that PREP inhibitors that are altering interactions could have different characteristics than those aimed for strong inhibition of catalytic activity. Moreover, PREP co-localization with aSyn, tau, and amyloid-beta hints to PREP's possible role not only in the synucleinopathies but in other neurodegenerative diseases as well. This commentary will focus on less well-acknowledged non-enzymatic functions of PREP that may provide a better approach for the development of PREP inhibitors for the treatment of neurodegenerative disorders.

We report here new copper(I)-Schiff base complexes for the selective oxidation of primary alcohols to aldehydes under ambient conditions (with 2,2,6,6-tetramethylpiperdine-N-oxyl (TEMPO), N-methylimidazole (NMI), ambient air, acetonitril and RT). Particularly, the copper(I) complex bearing N-(4-fluorophenyl)-1-(furan-2-yl)methanimine (L2) showed high activity in the series and gave near- quantitative yields in the oxidations of benzyl alcohol (99% yield in 1 h) and 1-octanol (96% yield in 24 h). Based on the X-ray structure determination, the complex has a square pyramidal coordination accomplished by two L2 ligands and bromide as a counter anion. The oxidation reactions were monitored with UV vis and in situ ATR-IR spectroscopy to study the changes in the catalytic structure and to elucidate the catalytic properties and the mechanistic details. Accordingly, detachment of one of the L2 ligands from the complexes is related to the oxidation activity.