Cyclic peptide marine metabolites and CuII

Cyclic pseudo-peptides derived from marine metabolites of the genus Lissoclinum bistratum and Lissoclinum patella have attracted scientific interest in the last two decades. Their structural properties and solution dynamics have been analyzed in detail, elaborate synthetic procedures for the natural products and synthetic derivatives developed, the biosynthetic pathways studied and it now is possible to produce them biosynthetically. Initially, these macrocyclic ligands were studied due to their medicinal and pharmaceutical potential-some of the isolated cyclic pseudo-peptides show high cytotoxic and antiviral activity. A major focus in the last decade has been on their Cu coordination chemistry, as a number of studies have indicated that dinuclear Cu complexes of cyclic peptides may be involved in the ascidians' metabolism, and this is the focus of the present review

Confirmation of the classic tris(2,2̒-bipyridyl)ruthenium(II) and oxalate electrochemiluminescence mechanism using EPR spectroscopy

A chemically initiated adaptation of the classic [Ru(bipy) ]/oxalate electrochemiluminescence coreactant system has revealed the elusive radical intermediates of the light-producing pathway. Oxalyl (HCO) and hydroxyformyl (HCO) radicals have been captured on a quartz surface and characterised using EPR spectroscopy

The highly resolved electronic spectrum of the square planar CuCl₄²⁻ ion

The low temperature magnetic circular dichroism(MCD) and electron paramagnetic resonance(EPR)spectra of Cu(II) dopedCs₂ZrCl₆ are reported. The Cu(II) ion is incorporated as the square planar copper tetrachloride ion, CuCl₄²⁻, which substitutes at the Zr(IV) site in the Cs₂ZrCl₆ lattice, with a complete absence of axial coordination. Both the EPR and MCD show highly resolved spectra from which it is possible to determine the superhyperfine coupling constants and excited state geometries respectively. The Franck–Condon intensity patterns suggest that there is a substantial relaxation of the host lattice about the impurity ion. For the lowest energy ²B1g(x²-y²)→²B2g(xy) transition, both the magnetic dipole allowed electronic origin as well as vibronic false origins are observed. The high resolution of the spectra allowed the accurate determination of the odd parity vibrations that are active in the spectra. The opposite sign of the MCD of the two components of the ²Eg(xz,yz)excited state allows this splitting to be determined for the first time. Accurate and unambiguous spectral parameters for the CuCl₄²⁻ ion are important as it has become a benchmark transition metal complex for theoretical electronic structure calculations

Insights into the Electronic Structure of CuII Bound to an Imidazole Analogue of Westiellamide.

Three synthetic analogues of westiallamide, HL, have previously been synthesized (HL) that have a common backbone (derived from l-valine) with HL but differ in their heterocyclic rings (imidazole, oxazole, thiazole, and oxazoline). Herein we explore in detail through high-resolution pulsed electron paramagnetic resonance (EPR) and magnetic circular dichroism (MCD) spectroscopy in conjunction with density functional theory (DFT) the geometric and electronic structures of the mono- and dinuclear Cu complexes of these cyclic pseudo hexapeptides. Orientation-selective hyperfine sublevel correlation, electron nuclear double resonance, and three-pulse electron spin echo envelope modulation spectroscopy of [Cu(HL)(MeOH)] reveal delocalization of the unpaired electron spin onto the ligating and distal nitrogens of the coordinated heterocyclic rings and that they are magnetically inequivalent. DFT calculations confirm this and show similar spin densities on the distal heteroatoms in the heterocyclic rings coordinated to the Cu ion in the other cyclic pseudo hexapeptide [Cu(HL)(MeOH)] complexes. The magnetic inequivalencies in [Cu(HL)(MeOH)] arise from different orientations of the heterocyclic rings coordinated to the Cu ion, and the delocalization of the unpaired electron onto the distal heteroatoms within these N-methylimidazole rings depends upon their location with respect to the Cu dx-y orbital. A systematic study of DFT functionals and basis sets was undertaken to examine the ability to reproduce the experimentally determined spin Hamiltonian parameters. Inclusion of spin-orbit coupling (SOC) using MAG-ReSpect or ORCA with a BHLYP/IGLO-II Wachters setup with SOC corrections and ∼38% Hartree-Fock exchange gave the best predictions of the g and A(Cu) matrices. DFT calculations of the N hyperfine and quadrupole parameters for the distal nitrogens of the coordinated heterocyclic rings in [Cu(HL)(MeOH)] with the B1LYP functional and the SVP basis set were in excellent agreement with the experimental data, though other choices of functional and basis set also provided reasonable values. MCD, EPR, mass spectrometry, and DFT showed that preparation of the dinuclear Cu complex in a 1:1 MeOH/glycerol mixture (necessary for MCD) resulted in the exchange of the bridging methoxide ligand for glycerol with a corresponding decrease in the magnitude of the exchange coupling

Probing the role of the divalent metal ion in uteroferrin using metal ion replacement and a comparison to isostructural biomimetics

Purple acid phosphatases (PAPs) are a group of heterovalent binuclear metalloenzymes that catalyze the hydrolysis of phosphomonoesters at acidic to neutral pH. While the metal ions are essential for catalysis, their precise roles are not fully understood. Here, the Fe(III)Ni(II) derivative of pig PAP (uteroferrin) was generated and its properties were compared with those of the native Fe(III)Fe(II) enzyme. The kcat of the Fe(III)Ni(II) derivative (approximately 60 s–1) is approximately 20% of that of native uteroferrin, and the Ni(II) uptake is considerably faster than the reconstitution of full enzymatic activity, suggesting a slow conformational change is required to attain optimal reactivity. An analysis of the pH dependence of the catalytic properties of Fe(III)Ni(II) uteroferrin indicates that the l-hydroxide is the likely nucleophile. Thus, the Ni(II) derivative employs a mechanism similar to that proposed for the Ga(III)Zn(II) derivative of uteroferrin, but different from that of the native enzyme, which uses a terminal Fe(III)-bound nucleophile to initiate catalysis. Binuclear Fe(III)Ni(II) biomimetics with coordination environments similar to the coordination environment of uteroferrin were generated to provide both experimental benchmarks (structural and spectroscopic) and further insight into the catalytic mechanism of hydrolysis. The data are consistent with a reaction mechanism employing an Fe(III)-bound terminal hydroxide as a nucleophile, similar to that proposed for native uteroferrin and various related isostructural biomimetics. Thus, only in the uteroferrin- catalyzed reaction are the precise details of the catalytic mechanism sensitive to the metal ion composition, illustrating the significance of the dynamic ligand environment in the protein active site for the optimization of the catalytic efficiency

Catalase vs Peroxidase Activity of a Manganese(II) Compound: Identification of a Mn(III)-(μ-O)2-Mn(IV) Reaction Intermediate by Electrospray Ionization Mass Spectrometry and Electron Paramagnetic Resonance Spectroscopy

Herein, we report reactivity studies of the mononuclear water-soluble complex [Mn(II)(HPClNOL)(η1-NO3)(η2-NO3)] 1, where HPClNOL ) 1-(bis-pyridin-2-ylmethyl-amino)-3-chloropropan-2-ol, toward peroxides (H2O2 and tertbutylhydroperoxide). Both the catalase (in aqueous solution) and peroxidase (in CH3CN) activities of 1 were evaluated using a range of techniques including electronic absorption spectroscopy, volumetry (kinetic studies), pH monitoring during H2O2 disproportionation, electron paramagnetic resonance (EPR), electrospray ionization mass spectrometry in the positive ion mode [ESI(+)-MS], and gas chromatography (GC). Electrochemical studies showed that 1 can be oxidized to Mn(III) and Mn(IV). The catalase-like activity of 1 was evaluated with and without pH control. The results show that the pH decreases when the reaction is performed in unbuffered media. Furthermore, the activity of 1 is greater in buffered than in unbuffered media, demonstrating that pH influences the activity of 1 toward H2O2. For the reaction of 1 with H2O2, EPR and ESI(+)-MS have led to the identification of the intermediate [Mn(III)Mn(IV)(μ- O)2(PClNOL)2]+. The peroxidase activity of 1 was also evaluated by monitoring cyclohexane oxidation, using H2O2 or tert-butylhydroperoxide as the terminal oxidants. Low yields (<7%) were obtained for H2O2, probably because it competes with 1 for the catalase-like activity. In contrast, using tert-butylhydroperoxide, up to 29% of cyclohexane conversion was obtained. A mechanistic model for the catalase activity of 1 that incorporates the observed lag phase in O2 production, the pH variation, and the formation of a Mn(III)-(μ-O)2-Mn(IV) intermediate is proposed

Multi-Element Abundance Measurements from Medium-Resolution Spectra. IV. Alpha Element Distributions in Milky Way Dwarf Satellite Galaxies

We derive the star formation histories of eight dwarf spheroidal (dSph) Milky Way satellite galaxies from their alpha element abundance patterns. Nearly 3000 stars from our previously published catalog (Paper II) comprise our data set. The average [alpha/Fe] ratios for all dSphs follow roughly the same path with increasing [Fe/H]. We do not observe the predicted knees in the [alpha/Fe] vs. [Fe/H] diagram, corresponding to the metallicity at which Type Ia supernovae begin to explode. Instead, we find that Type Ia supernova ejecta contribute to the abundances of all but the most metal-poor ([Fe/H] < -2.5) stars. We have also developed a chemical evolution model that tracks the star formation rate, Types II and Ia supernova explosions, and supernova feedback. Without metal enhancement in the supernova blowout, massive amounts of gas loss define the history of all dSphs except Fornax, the most luminous in our sample. All six of the best-fit model parameters correlate with dSph luminosity but not with velocity dispersion, half-light radius, or Galactocentric distance.Comment: 28 pages, 14 figures; accepted for publication in ApJ; very minor editorial corrections in v

Carbonic anhydrase activity of dinuclear CuII complexes with patellamide model ligands

The dicopper(ii) complexes of six pseudo-octapeptides, synthetic analogues of ascidiacyclamide and the patellamides, found in ascidians of the Pacific and Indian Oceans, are shown to be efficient carbonic anhydrase model complexes with k up to 7.3 × 10 s (uncatalyzed: 3.7 × 10 s; enzyme-catalyzed: 2 × 10 -1.4 × 10 s) and a turnover number (TON) of at least 1700, limited only by the experimental conditions used. So far, no copper-based natural carbonic anhydrases are known, no faster model systems have been described and the biological role of the patellamide macrocycles is so far unknown. The observed CO hydration rates depend on the configuration of the isopropyl side chains of the pseudo-octapeptide scaffold, and the naturally observed R*,S*, R*,S* geometry is shown to lead to more efficient catalysts than the S*,S*,S*,S* isomers. The catalytic efficiency also depends on the heterocyclic donor groups of the pseudo-octapeptides. Interestingly, the dicopper(ii) complex of the ligand with four imidazole groups is a more efficient catalyst than that of the close analogue of ascidiacyclamide with two thiazole and two oxazoline rings. The experimental observations indicate that the nucleophilic attack of a Cu- coordinated hydroxide at the CO carbon center is rate determining, i.e. formation of the catalyst-CO adduct and release of carbonate/bicarbonate are relatively fast processes

Early peri-operative hyperglycaemia and renal allograft rejection in patients without diabetes

BACKGROUND: Patients with diabetes have an increased risk for allograft rejection, possibly related to peri-operative hyperglycaemia. Hyperglycaemia is also common following transplantation in patients without diabetes. We hypothesise that exposure of allograft tissue to hyperglycaemia could influence the risk for rejection in any patient with high sugars. To investigate the relationship of peri-operative glucose control to acute rejection in renal transplant patients without diabetes, all patients receiving their first cadaveric graft in a single center were surveyed and patients without diabetes receiving cyclosporin-based immunosuppression were reviewed (n = 230). Records of the plasma blood glucose concentration following surgery and transplant variables pertaining to allograft rejection were obtained. All variables suggestive of association were entered into multivariate logistic regression analysis, their significance analysed and modeled. RESULTS: Hyperglycaemia (>8.0 mmol/L) occurs in over 73% of non-diabetic patients following surgery. Glycaemic control immediately following renal transplantation independently predicted acute rejection (Odds ratio=1.08). 42% of patients with a glucose < 8.0 mmol/L following surgery developed rejection compared to 71% of patients who had a serum glucose above this level. Hyperglycaemia was not associated with any delay of graft function. CONCLUSION: Hyperglycaemia is associated with an increased risk for allograft rejection. This is consistent with similar findings in patients with diabetes. We hypothesise a causal link concordant with epidemiological and in vitro evidence and propose further clinical research

Characterization of DorC from Rhodobacter capsulatus, a c-type Cytochrome Involved in Electron Transfer to Dimethylsulfoxide Reductase

The dorC gene of the dimethyl sulfoxide respiratory (dor) operon of Rhodobacter capsulatus encodes a pentaheme c-type cytochrome that is involved in electron transfer from ubiquinol to periplasmic dimethyl sulfoxide reductase. DorC was expressed as a C-terminal fusion to an 8-amino acid FLAG epitope and was purified from detergent-solubilized membranes by ion exchange chromatography and immunoaffinity chromatography. The DorC protein had a subunit Mr = 46,000, and pyridine hemochrome analysis indicated that it contained 5 mol heme c/mol DorC polypeptide, as predicted from the derived amino acid sequence of the dorC gene. The reduced form of DorC exhibited visible absorption maxima at 551.5 nm (alpha -band), 522 nm (beta -band), and 419 nm (Soret band). Redox potentiometry of the heme centers of DorC identified five components (n = 1) with midpoint potentials of -34, -128, -184, -185, and -276 mV. Despite the low redox potentials of the heme centers, DorC was reduced by duroquinol and was oxidized by dimethyl sulfoxide reductase