An Atomically Dispersed Mn-Photocatalyst for Generating Hydrogen Peroxide from Seawater via the Water Oxidation Reaction (WOR).

In this work, we have fabricated an aryl amino-substituted graphitic carbon nitride (g-C3N4) catalyst with atomically dispersed Mn capable of generating hydrogen peroxide (H2O2) directly from seawater. This new catalyst exhibited excellent reactivity, obtaining up to 2230 µM H2O2 in 7 h from alkaline water and up to 1800 µM from seawater under identical conditions. More importantly, the catalyst was quickly recovered for subsequent reuse without appreciable loss in performance. Interestingly, unlike the usual two-electron oxygen reduction reaction pathway, the generation of H2O2 was through a less common two-electron water oxidation reaction (WOR) process in which both the direct and indirect WOR processes occurred; namely, photoinduced h+ directly oxidized H2O to H2O2 via a one-step 2e- WOR, and photoinduced h+ first oxidized a hydroxide (OH-) ion to generate a hydroxy radical (•OH), and H2O2 was formed indirectly by the combination of two •OH. We have characterized the material, at the catalytic sites, at the atomic level using electron paramagnetic resonance, X-ray absorption near edge structure, extended X-ray absorption fine structure, high-resolution transmission electron microscopy, X-ray photoelectron spectroscopy, magic-angle spinning solid-state NMR spectroscopy, and multiscale molecular modeling, combining classical reactive molecular dynamics simulations and quantum chemistry calculations.

GLB-3: A resilient, cysteine-rich, membrane-tethered globin expressed in the reproductive and nervous system of Caenorhabditis elegans.

The popular genetic model organism Caenorhabditis elegans (C. elegans) encodes 34 globins, whereby the few that are well-characterized show divergent properties besides the typical oxygen carrier function. Here, we present a biophysical characterization and expression analysis of C. elegans globin-3 (GLB-3). GLB-3 is predicted to exist in two isoforms and is expressed in the reproductive and nervous system. Knockout of this globin causes a 99% reduction in fertility and reduced motility. Spectroscopic analysis reveals that GLB-3 exists as a bis-histidyl-ligated low-spin form in both the ferrous and ferric heme form. A function in binding of diatomic gases is excluded on the basis of the slow CO-binding kinetics. Unlike other globins, GLB-3 is also not capable of reacting with H2O2, H2S, and nitrite. Intriguingly, not only does GLB-3 contain a high number of cysteine residues, it is also highly stable under harsh conditions (pH = 2 and high concentrations of H2O2). The resilience diminishes when the N- and C-terminal extensions are removed. Redox potentiometric measurements reveal a slightly positive redox potential (+8 ± 19 mV vs. SHE), suggesting that the heme iron may be able to oxidize cysteines. Electron paramagnetic resonance shows that formation of an intramolecular disulphide bridge, involving Cys70, affects the heme-pocket region. The results suggest an involvement of the globin in (cysteine) redox chemistry.

Correlation between the Fluorination Degree of Perfluorinated Zinc Phthalocyanines, Their Singlet Oxygen Generation Ability, and Their Photoelectrochemical Response for Phenol Sensing.

Electron-withdrawing perfluoroalkyl peripheral groups grafted on phthalocyanine (Pc) macrocycles improve their single-site isolation, solubility, and resistance to self-oxidation, all beneficial features for catalytic applications. A high degree of fluorination also enhances the reducibility of Pcs and could alter their singlet oxygen (1O2) photoproduction. The ethanol/toluene 20:80 vol % solvent mixture was found to dissolve perfluorinated FnPcZn complexes, n = 16, 52, and 64, and minimize the aggregation of the sterically unencumbered F16PcZn. The 1O2 production ability of FnPcZn complexes was examined using 9,10-dimethylanthracene (DMA) and 2,2,6,6-tetramethylpiperidine (TEMP) in combination with UV-vis and electron paramagnetic resonance (EPR) spectroscopy, respectively. While the photoreduction of F52PcZn and F64PcZn in the presence of redox-active TEMP lowered 1O2 production, DMA was a suitable 1O2 trap for ranking the complexes. The solution reactivity was complemented by solid-state studies via the construction of photoelectrochemical sensors based on TiO2-supported FnPcZn, FnPcZn|TiO2. Phenol photo-oxidation by 1O2, followed by its electrochemical reduction, defines a redox cycle, the 1O2 production having been found to depend on the value of n and structural features of the supported complexes. Consistent with solution studies, F52PcZn was found to be the most efficient 1O2 generator. The insights on reactivity testing and structural-activity relationships obtained may be useful for designing efficient and robust sensors and for other 1O2-related applications of FnPcZn.

Radical Formation in Sugar-Derived Acetals under Solvent-Free Conditions.

The degradation of acetal derivatives of the diethylester of galactarate (GalX) was investigated by electron paramagnetic resonance (EPR) spectroscopy in the context of solvent-free, high-temperature reactions like polycondensations. It was demonstrated that less substituted cyclic acetals are prone to undergo radical degradation at higher temperatures as a result of hydrogen abstraction. The EPR observations were supported by the synthesis of GalX based polyamides via ester-amide exchange-type polycondensations in solvent-free conditions at high temperatures in the presence and in the absence of radical inhibitors. The radical degradation can be offset by the addition of a radical inhibitor. The radical is probably formed on the methylene unit between the oxygen atoms and subsequently undergoes a rearrangement.

Copper(II) Complexes of Sulfonated Salan Ligands: Thermodynamic and Spectroscopic Features and Applications for Catalysis of the Henry Reaction.

Copper(II) complexes formed with sulfonated salan ligands (HSS) have been synthesized, and their coordination chemistry has been characterized using pH-potentiometry and spectroscopic methods [UV-vis, electron paramagnetic resonance (EPR), and electron-electron double resonance (ELDOR)-detected NMR (EDNMR)] in aqueous solution. Several bridging moieties between the two salicylamine functions were introduced, e.g., ethyl (HSS), propyl (PrHSS), butyl (BuHSS), cyclohexyl (cis-CyHSS, trans-CyHSS), and diphenyl (dPhHSS). All of the investigated ligands feature excellent copper(II) binding ability via the formation of a (O-,N,N,O-) chelate system. The results indicated that the cyclohexyl moiety significantly enhances the stability of the copper(II) complexes. EPR studies revealed that the arrangement of the coordinated donor atoms is more symmetrical around the copper(II) center and similar for HSS, BuHSS, CyHSS, and dPhHSS, respectively, and a higher rhombicity of the g tensor was detected for PrHSS. The copper(II) complexes of the sulfosalan ligands were isolated in solid form also and showed moderate catalytic activity in the Henry (nitroaldol) reaction of aldehydes and nitromethane. The best yield for nitroaldol production was obtained for copper(II) complexes of PrHSS and BuHSS, although their metal binding ability is moderate compared to that of the cyclohexyl counterparts. However, these complexes possess larger spin density on the nitrogen nuclei than that for the other cases, which alters their catalytic activity.

Crystal structures of zinc(II) complexes with ß-hydroxypyridinecarboxylate ligands: examples of structure-directing effects used in inorganic crystal engineering.

The coordination properties of four hydroxypyridinecarboxylates, designed for the treatment of iron-overloading conditions as bidentate O,O'-donor ligands, have been studied with ZnII in the solid state. The coordination compounds [Zn(A1)2(H2O)2] (1), [Zn(A2)2(H2O)] (2), [Zn(A3)2(H2O)]·2H2O (3) and [Zn2(B1)4(H2O)2]·4H2O (4), where the ligands are 1-methyl-4-oxidopyridinium-3-carboxylate (A1, C7H6NO3), 1,6-dimethyl-4-oxidopyridinium-3-carboxylate (A2, C8H8NO3), 1,5-dimethyl-4-oxido-pyridinium-3-carboxylate (A3, C8H8NO3) and 1-methyl-3-oxidopyridinium-4-carboxylate (B1, C7H6NO3), have been synthesized and analysed by single-crystal X-ray diffraction. The ligands were chosen to probe (i) the electronic effects of inverting the positions of the O-atom donor groups (i.e. A1 versus B1) and (ii) the electronic and steric effects of the addition of a second methyl group in different positions on the pyridine ring. Two axially coordinated water molecules resulting in a six-coordinated symmetrical octahedron complement the bis-ligand complex of A1. Ligands A2 and A3 form five-coordinated trigonal bipyramidal complexes with one additional water molecule in the coordination sphere, which is a rarely reported geometry for ZnII complexes. Ligand B1 shows a dimeric structure, where the two Zn2+ dications have slightly distorted octahedral geometry and the pyridinolate O atom of the neighbouring complex bridges them. The coordination spheres of the Zn2+ dications and the supramolecular structures are discussed in detail. The packing arrangements of 1-3 are similar, having alternating hydrophilic and hydrophobic layers, however the similarity is broken in 4. The obtained coordination geometries are compared with their previously determined CuII analogues. The study of the individual complexes is complemented with a comprehensive analysis of ZnII complexes with oxygen donor ligands with data from the Cambridge Structural Database.

Understanding the g-tensors of perchlorotriphenylmethyl and Finland-type trityl radicals.

The 285 GHz EPR spectra of perchlorotriphenylmethyl and tetrathiatriarylmethyl radicals in frozen solution have been accurately measured. The relationship between their molecular structures and their g-tensors has been investigated with the aid of DFT calculations, revealing that the degree of spin density delocalization away from the central methylene carbon is an important determining factor of the g-anisotropy. In particular, the small amount of spin densities on the Cl or S heteroatoms at the 2 and 6 positions with respect to the central carbon have the strongest influence. Furthermore, the amount of spin densities on these heteroatoms and thus the anisotropy can be modulated by the protonation (esterification) state of the carboxylate groups at the 4 position. These results provide unique insights into the g-anisotropy of persistent trityl radicals and how it can be tuned.

Anti-inflammatory activity of superoxide dismutase mimics functionalized with cell-penetrating peptides.

A superoxide dismutase mimic (Mn1) was functionalized with three positively charged-peptides: RRRRRRRRR (Mn1-R9), RRWWWRRWRR (Mn1-RW9) or Fx-r-Fx-K (Mn1-MPP). Characterization of the physico-chemical properties of the complexes show that they share similar binding affinity for Mn2+, apparent reduction potential and intrinsic superoxide dismutase activity. However, their accumulation in cells is different (Mn1-R9 < Mn1-MPP < Mn1-RW9 < Mn1), as well as their subcellular distribution. In addition, the three functionalized-complexes display a better anti-inflammatory activity than Mn1 when assayed at 10 µM. This improvement is due to a combination of an anti-inflammatory effect of the peptidyl moiety itself, and of the SOD mimic for Mn1-RW9 and Mn1-MPP. In contrast, the enhanced anti-inflammatory activity of Mn1-R9 is solely due to the SOD mimic.

Rhenium Complexes Based on 2-Pyridyl-1,2,3-triazole Ligands: A New Class of CO2 Reduction Catalysts.

A series of [Re(N^N)(CO)3(X)] (N^N = diimine and X = halide) complexes based on 4-(2-pyridyl)-1,2,3-triazole (pyta) and 1-(2-pyridyl)-1,2,3-triazole (tapy) diimine ligands have been prepared and electrochemically characterized. The first ligand-based reduction process is shown to be highly sensitive to the nature of the isomer as well as to the substituents on the pyridyl ring, with the peak potential changing by up to 700 mV. The abilities of this class of complexes to catalyze the electroreduction and photoreduction of CO2 were assessed for the first time. It is found that only Re pyta complexes that have a first reduction wave with a peak potential at ca. -1.7 V vs SCE are active, producing CO as the major product, together with small amounts of H2 and formic acid. The catalytic wave that is observed in the CVs is enhanced by the addition of water or trifluoroethanol as a proton source. Long-term controlled potential electrolysis experiments gave total Faradaic yield close to 100%. In particular, functionalization of the triazolyl ring with a 2,4,6-tri-tert-butylphenyl group provided the catalyst with a remarkable stability.

Using Genetically Encodable Self-Assembling Gd(III) Spin Labels To Make In-Cell Nanometric Distance Measurements.

Double electron-electron resonance (DEER) can be used to study the structure of a protein in its native cellular environment. Until now, this has required isolation, in vitro labeling, and reintroduction of the protein back into the cells. We describe a completely biosynthetic approach that avoids these steps. It exploits genetically encodable lanthanide-binding tags (LBT) to form self-assembling Gd(III) metal-based spin labels and enables direct in-cell measurements. This approach is demonstrated using a pair of LBTs encoded one at each end of a 3-helix bundle expressed in E. coli grown on Gd(III) -supplemented medium. DEER measurements directly on these cells produced readily detectable time traces from which the distance between the Gd(III) labels could be determined. This work is the first to use biosynthetically produced self-assembling metal-containing spin labels for non-disruptive in-cell structural measurements.

A Bis-Manganese(II)-DOTA Complex for Pulsed Dipolar Spectroscopy.

High-spin gadolinium(III) and manganese(II) complexes have emerged as alternatives to standard nitroxide radical spin labels for measuring nanometric distances by using pulsed electron-electron double resonance (PELDOR or DEER) at high fields/frequencies. For certain complexes, particularly those with relatively small zero-field splitting (ZFS) and short distances between the two metal centers, the pseudosecular term of the dipolar coupling Hamiltonian is non-negligible. However, in general, the contribution from this term during conventional data analysis is masked by the flexibility of the molecule of interest and/or the long tethers connecting them to the spin labels. The efficient synthesis of a model system consisting of two [Mn(dota)](2-) (MnDOTA; DOTA(4-) =1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate) directly connected to the ends of a central rodlike oligo(phenylene-ethynylene) (OPE) spacer is reported. The rigidity of the OPE is confirmed by Q-band PELDOR measurements on a bis-nitroxide analogue. The Mn(II) -Mn(II) distance distribution profile determined by W-band PELDOR is in reasonable agreement with one simulated by using a simple rotamer analysis. The small degree of flexibility arising from the linking MnDOTA arm appears to outweigh the contribution from the pseudosecular term at this interspin distance. This study illustrates the potential of MnDOTA-based spin labels for measuring fairly short nanometer distances, and also presents an interesting candidate for in-depth studies of pulsed dipolar spectroscopy methods on Mn(II) -Mn(II) systems.

The Use of Mn(II) Bound to His-tags as Genetically Encodable Spin-Label for Nanometric Distance Determination in Proteins.

A genetically encodable paramagnetic spin-label capable of self-assembly from naturally available components would offer a means for studying the in-cell structure and interactions of a protein by electron paramagnetic resonance (EPR). Here, we demonstrate pulse electron-electron double resonance (DEER) measurements on spin-labels consisting of Mn(II) ions coordinated to a sequence of histidines, so-called His-tags, that are ubiquitously added by genetic engineering to facilitate protein purification. Although the affinity of His-tags for Mn(II) was low (800 µM), Mn(II)-bound His-tags yielded readily detectable DEER time traces even at concentrations expected in cells. We were able to determine accurately the distance between two His-tag Mn(II) spin-labels at the ends of a rigid helical polyproline peptide of known structure, as well as at the ends of a completely cell-synthesized 3-helix bundle. This approach not only greatly simplifies the labeling procedure but also represents a first step towards using self-assembling metal spin-labels for in-cell distance measurements.

Bioinspired superoxide-dismutase mimics: The effects of functionalization with cationic polyarginine peptides.

Continuing a bio-mimetic approach, we have prepared peptide conjugates of a superoxide dismutase (SOD) mimic [MnL](+) (where HL=N-(2-hydroxybenzyl)-N,N'-bis[2-(N-methylimidazolyl)methyl]ethane-1,2-diamine), namely [MnL'-Arg(n-1)](n+) (where n=2, 4, 7 and 10) and [MnL'-Gly1](+). [MnL'-Arg(n-1)](n+) contained cationic residue(s) that emulate the electrostatic channel of the enzyme. Physicochemical methods showed that functionalization at the secondary amine of HL did not impair coordination to Mn(II) with association constants (Kassoc) between 1.6 and 3.3×10(6)M(-1). The Mn(III)/Mn(II) redox potential of the conjugates was between 0.27 and 0.30V vs SCE, slightly higher than [MnL](+) under the same conditions, but remain at a value that facilitates O2(-) dismutation. The catalytic rate constant (kcat) of the dismutation for the series was studied using a direct stopped-flow method, which showed that for compounds with the same overall charge, the alkylation of the secondary amine of [MnL](+) (kcat=5.0±0.1×10(6)M(-1)s(-1)) led to a lower value (i.e. for [MnL'Gly](+), kcat=4.2±0.1×10(6)M(-1)s(-1)). However, under the same conditions, kcat values between 5.0±0.4×10(6)M(-1)s(-1) and 6.6±0.1×10(6)M(-1)s(-1) were determined for [MnL'-Arg(n-1)](n+) conjugates, indicating that the cationic residue(s) compensated for the loss in activity. Analysis of the effect of ionic strength on the kcat strongly suggested that not all the charges were involved, but only the closest ones electrostatically influenced the SOD active metal centre.

Supramolecular ß-cyclodextrin adducts of boron-rich DNA metallointercalators containing dicarba-closo-dodecaborane(12).

A chiral, isomeric series of novel boron-rich Pt(II) metallointercalators ([PtL2(phen)](NO3)2: L = (x)-(1,y-closo-carboran-1-yl)pyrid-z-ylmethanol: x = R, S; y = 7, 12; z = 3, 4) wre prepared and fully characterized. By means of variable-temperature NMR spectroscopy, different combinations of Δ-head-to-tail, head-to-head, and Λ-head-to-tail rotamers were identified, and the free energies of activation for Pt-N bond rotation were determined for the pyrid-4-yl complexes with ΔG(‡)307 = 16.1 ± 0.3 kcal mol(-1) and ΔG(‡)325 = 16.2 ± 0.5 kcal mol(-1) for the 1,7-carboranyl derivative and ΔG(‡)307 = 16.4 ± 0.5 kcal mol(-1) and ΔG(‡)325 = 16.2 ± 0.5 kcal mol(-1) for the 1,12-carboranyl derivative. The corresponding 2:1 host-guest ß-cyclodextrin (ß-CD) adducts ([PtL2(phen)·2ß-CD](NO3)2) were also prepared and fully characterized by high resolution electrospray ionization mass spectrometry and 2D-(1)H{(11)B} nuclear Overhauser enhancement spectroscopy and rotating-frame Overhauser effect spectroscopy NMR experiments. The interaction of the novel supramolecular adducts with calf thymus DNA was investigated by means of linear dichroism, ultraviolet-visible spectroscopy, thermal denaturation, and isothermal titration calorimetry experiments which revealed a bimodal binding regime with DNA intercalation favored at low [drug]/[DNA] ratios, while at higher drug loading, surface aggregation was observed. Furthermore, the data were also consistent with some degree of dissociation of the ß-CD host-guest adducts upon DNA binding. When we used a single binding-site model, interpreted as a weighted average of all of the possible equilibrium interactions, the compounds showed high affinity for ct-DNA with K(assoc) ranging from (1.3 ± 0.1) × 10(5) M(-1) to (5.7 ± 0.4) × 10(5) M(-1). In general, the overall DNA-binding behavior was enthalpically driven with a minor or unfavorable entropic component, which is consistent with the thermodynamics of an intercalation-dominated process. A higher degree of DNA intercalation was observed for the R-isomer in the pyrid-3-yl compounds, and the opposite trend was observed in the case of pyrid-4-yl derivatives.

Electrochemical formation of Mn(III)-peroxo complexes supported by pentadentate amino pyridine and imidazole ligands.

A novel and efficient method for preparing [Mn(III)(O2)(L)](+) complexes using electrochemically generated superoxide is reported, with the reaction probed by low temperature electronic absorption and electron paramagnetic resonance spectroscopic techniques.

Synthesis and supramolecular studies of chiral boronated platinum(II) complexes: insights into the molecular recognition of carboranes by ß-cyclodextrin.

The synthesis and characterisation of a novel isomeric family of closo-carborane-containing Pt(II) complexes ((R/S)-(1-4)⋅2 NO(3)) are reported. Related complexes (5⋅NO(3) and 6⋅NO(3)) that contain the 7,8-nido-carborane cluster were obtained from the selective deboronation of the 1,2-closo-carborane analogues. The corresponding water-soluble supramolecular 1:1 host-guest ß-cyclodextrin (ß-CD) adducts ((R/S)-(1-4)⋅ß-CD⋅2 NO(3)) were also prepared and fully characterised. HR-ESI-MS experiments confirmed the presence of the host-guest adducts, and 2D-(1) H{(11)B} ROESY NMR studies showed that the boron clusters enter the ß-CD from the side of the wider annulus. Isothermal titration calorimetry (ITC) experiments revealed enthalpically driven 1:1 and higher-order supramolecular interactions between ß-CD and (R/S)-(1-4)⋅2 NO(3) in aqueous solution. A comparison of the predominate 1:1 binding mode established that the affinity of ß-CD for the guest molecule is mainly influenced by the pyridyl ring substitution pattern and chirality of the host, whilst the nature of the closo-carborane isomer also plays some role, with the most favourable structural features for ß-CD binding being the presence of the 4-pyridyl ring, 1,12-closo-carborane, and an S configuration. The results reported here represent the first comprehensive calorimetric study of the supramolecular interactions between closo-carborane compounds and ß-CD, and it provides fascinating insights into the structural features influencing the thermodynamics of this phenomenon.

Evaluation of the anti-oxidant properties of a SOD-mimic Mn-complex in activated macrophages.

SOD-mimics are small complexes that reproduce the activity of superoxide dismutases, natural proteins that catalytically dismutate the superoxide anion. Activated macrophages, which produce ROS and RNS fluxes, constitute a relevant model to challenge antioxidant activity in a cellular context and were used to test a Mn-complex which was shown to efficiently alter the flow of O(2)(-), ONOO(-) and H(2)O(2).

A ternary supramolecular system containing a boronated DNA-metallointercalator, ß-cyclodextrin and the hexanucleotide d(GTCGAC)2.

Solution NMR studies of the interaction between the hexanucleotide d(GTCGAC)(2), ß-cyclodextrin and a boronated 2,2':6',2''-terpyridineplatinum(II) complex containing 1,12-dicarba-closo-dodecaborane(12) (1,12-closo-carborane) reveal the formation of a remarkable ternary supramolecular system in which the terpyridine ligand is intercalated between the C(3) and G(4) bases, whilst the closo-carborane moiety is encapsulated by the cyclic sugar.

Synthesis and preliminary DNA-binding studies of diimineplatinum(II) complexes containing 3- or 4-pyridineboronic acid.

A series of platinum(II) complexes of the type [Pt(NN)(pyB)2](NO3)2 (NN = bipy, phen; pyB = 3- or 4-pyridineboronic acid) were successfully prepared and fully characterised by 1D- and 2D-multinuclear NMR spectroscopy and ESI-MS. Using VT 1H NMR spectroscopy, rotational isomers for [Pt(NN)(3-pyB)2](NO3)2 were identified and the free energies of activation for rotation of 3-pyB about the Pt-N bond were determined to be DeltaG++310) = 69.2 +/- 0.1 kJ mol(-1) and DeltaG++(305) = 66.0 +/- 0.1 kJ mol(-1) for [Pt(bipy)(3-pyB)2](NO3)2 and [Pt(phen)(3-pyB)2](NO3)2, respectively. The 3- and 4-pyB ligands readily deboronate in boiling H2O to afford [Pt(NN)(py)2](NO3)2; the structure of [Pt(phen)(py)2](2+) (as its PF6- salt) was confirmed by X-ray crystallography. Preliminary thermal denaturation studies revealed only minimal interactions between [Pt(NN)(pyB)2](NO3)2 and calf-thymus DNA and is attributed to hydroxylation of the boronic acid groups at pH 7.4 to afford the corresponding zwitterionic boronate species. This was confirmed by means of variable pH 1H and 11B{1H} NMR spectroscopy.