Porphyrin Iron(Ill) Mixed Function Oxidases: An Evolutionary Endpoint for Transition Metal(III) Reactions with Oxygen Donors

Peroxidases, catalases, and cytochrome P-450 enzymes have in common iron(III) protoporphyrin-IX as a cofactor. The reactions catalyzed by these enzymes can be, for the most part, duplicated by use of transition metal(III) porphyrins. Porphyrins serve admirably well as conjugated and rigidly planar ligands that prevent other than transformations of the ligated metal moiety at axial positions. The adjacent and distal axial positions serve to separate the enzyme-bound (distal) ligand from the reactive face (adjacent) of the iron(III). These features are not required, however, to mimic the chemical conversions that are catalyzed by peroxidases, catalases, and cytochrome P-450 enzymes. Indeed, other simple ligands may be used with a number of transition metals (cf. In the oxidation reactions catalyzed by peroxidases, catalases, and cytochrome P-450, an oxidant is initially formed that might be described as a "porphyrin-ironoxene" compound. The formation of the porphyriniron-oxene compound occurs by reaction of the iron(III) porphyrin with a reagent that may be symbolically represented as Z-OH. With horseradish (HR) peroxidase (distal axial ligand a histidine imidazole) and catalase (distal axial ligand a tyrosine hydroxyl function), Z-OH represents HO-OH (for both enzymes) and, in addition, alkyl-O-OH (for the peroxidase). The porphyrin-iron-oxene compound formed in these reactions is known as compound I. Much evidence exists to support the structure of compound I as being an iron(IV)-oxo porphyrin ~r-cation radical (Eq. 1, where X is imidazole or tyrosine-O , cf. Aside from the structures of the porphyrin-ironoxene species of HR peroxidase, catalase, and cytochrome P-450, a complete description of these systems requires a knowledge of the mechanisms of formation of the porphyrin-iron-oxene species and a description of their reactions with substrates. The electrochemical stepwise oxidation of iron(III)-hydroxy porphyrins to iron(IV)-oxo porphyrins (compound II oxidation level) and iron(IV)-oxo porphyrin ~r-cation radicals (compound I oxidation level) have been investigated The slopes of plots (/3lg) of log kyooH versus pK a of YOH were found to be markedly negative (-0.35 to -1.25), which is expected for such a polar reaction. When kvooH values for alkyl hydroperoxides were determined and included in the plots of log kyoon versus pKa of YOH for percarboxylic acids, it was found that a single linear free-energy line was obtained with 9 1987 Cold Spring Harbor Laboratory 0-87969-054-2/87 $1.00 567 Cold Spring Harbor Laboratory Press on October 7, 2016 -Published by symposium.cshlp.org Downloaded fro

Application of Quadratic Constitutive Relation to One- Equation k-kL Turbulence Model

This paper analyzes the accuracy of the recently developed one-equation k-kL turbulence model with Quadratic Constitutive Relation (QCR) compared to the linear Boussinesq relation and Algebraic Reynolds Stress Model (ARSM). The computational results in several benchmark cases from NASA TMR are compared to other widely used one equation turbulence models with QCR, such as Spalart-Allmaras model (SA), Wray-Agarwal model (WA) and SST k-ω model. In particular, one-equation k-kL-QCR model shows good accuracy with experimental data for supersonic flow in a square duct where the effect of QCR is clearly visible in capturing the secondary flow vortices which is not feasible with the any standard model without QCR. In addition, both one-equation k-kL and one-equation k- kL-QCR models show better accuracy for subsonic separated flow in 3D NASA Glenn S- duct compared to other one-equation models. Other test cases show little difference in the results obtained without and with QCR

Advanced flavin catalysts elaborated with polymers

A variety of biological redox reactions are mediated by flavoenzymes due to the unique redox activity of isoalloxazine ring systems, which are found in flavin cofactors. In the field of synthetic organic chemistry, the term “flavin” is generally used for not only isoalloxazines but also related molecules including their isomers and some analogues, and those having catalytic activity are called flavin catalyst. Flavin catalysts are typically metal-free, and their catalytic activity can be readily accessed using mild terminal oxidants such as H2O2 and O2; therefore, redox reactions with these compounds have great promise as alternatives to reactions with conventional metal catalysts for the sustainable production of important chemicals. We recently became interested in using polymers for the development of flavin catalysts, especially to improve their practicality and advance the field of catalysis. Here, we summarize our recent research on such flavin-polymer collaborations including the development of facile preparation methods for flavin catalysts using polymers, readily reusable polymer-supported flavin catalysts, and flavin-peptide-polymer hybrids that can catalyze the first flavoenzyme-mimetic aerobic oxygenation reactions

Polyamide-Scorpion Cyclam Lexitropsins Selectively Bind AT-Rich DNA Independently of the Nature of the Coordinated Metal

Cyclam was attached to 1-, 2- and 3-pyrrole lexitropsins for the first time through a synthetically facile copper-catalyzed “click” reaction. The corresponding copper and zinc complexes were synthesized and characterized. The ligand and its complexes bound AT-rich DNA selectively over GC-rich DNA, and the thermodynamic profile of the binding was evaluated by isothermal titration calorimetry. The metal, encapsulated in a scorpion azamacrocyclic complex, did not affect the binding, which was dominated by the organic tail

Insights into the Mechanism of Bovine CD38/NAD+Glycohydrolase from the X-Ray Structures of Its Michaelis Complex and Covalently-Trapped Intermediates

Bovine CD38/NAD+glycohydrolase (bCD38) catalyses the hydrolysis of NAD+ into nicotinamide and ADP-ribose and the formation of cyclic ADP-ribose (cADPR). We solved the crystal structures of the mono N-glycosylated forms of the ecto-domain of bCD38 or the catalytic residue mutant Glu218Gln in their apo state or bound to aFNAD or rFNAD, two 2′-fluorinated analogs of NAD+. Both compounds behave as mechanism-based inhibitors, allowing the trapping of a reaction intermediate covalently linked to Glu218. Compared to the non-covalent (Michaelis) complex, the ligands adopt a more folded conformation in the covalent complexes. Altogether these crystallographic snapshots along the reaction pathway reveal the drastic conformational rearrangements undergone by the ligand during catalysis with the repositioning of its adenine ring from a solvent-exposed position stacked against Trp168 to a more buried position stacked against Trp181. This adenine flipping between conserved tryptophans is a prerequisite for the proper positioning of the N1 of the adenine ring to perform the nucleophilic attack on the C1′ of the ribofuranoside ring ultimately yielding cADPR. In all structures, however, the adenine ring adopts the most thermodynamically favorable anti conformation, explaining why cyclization, which requires a syn conformation, remains a rare alternate event in the reactions catalyzed by bCD38 (cADPR represents only 1% of the reaction products). In the Michaelis complex, the substrate is bound in a constrained conformation; the enzyme uses this ground-state destabilization, in addition to a hydrophobic environment and desolvation of the nicotinamide-ribosyl bond, to destabilize the scissile bond leading to the formation of a ribooxocarbenium ion intermediate. The Glu218 side chain stabilizes this reaction intermediate and plays another important role during catalysis by polarizing the 2′-OH of the substrate NAD+. Based on our structural analysis and data on active site mutants, we propose a detailed analysis of the catalytic mechanism