Ligand O2 Research Articles

An osmium-peroxo complex for photoactive therapy of hypoxic tumors

The limited therapeutic effect on hypoxic and refractory solid tumors has hindered the practical application of photodynamic therapy. Herein, we report our investigation of an osmium-peroxo complex (Os2), which is inactive in the dark, but can release a peroxo ligand O2•− upon light irradiation even in the absence of oxygen, and is transformed into a cytotoxic osmium complex (Os1). Os1 is cytotoxic in the presence or absence of irradiation in hypoxic tumors, behaving as a chemotherapeutic drug. At the same time, the light-activated Os2 induces photocatalytic oxidation of endogenous 1,4-dihydronicotinamide adenine dinucleotide in living cancer cells, leading to ferroptosis, which is mediated by glutathione degradation, lipid peroxide accumulation and down-regulation of glutathione peroxidase 4. In vivo studies have confirmed that the Os2 can effectively inhibit the growth of solid hypoxic tumors in mice. A promising strategy is proposed for the treatment of hypoxic tumors with metal-based drugs.

Identification of a Stable Ozonide Ion Bound to a Single Cadmium Site within the Zeolite Cavity

Molecular metal oxides are invoked as the key intermediate in a variety of oxidative reactions. Although an atomic oxygen ligand and molecular O2 ligands are well known, the triatomic oxygen ligand (ozonide) is very limited due to its instability. Here, we report a successful preparation and characterization of stable cadmium ozonide species. Our approach used the negatively charged local environments within the zeolite pore, which allowed us to isolate the single cadmium ozonide species as the counter cation even at room temperature. Its state was characterized by vibronic progressions closely similar to those observed in the cryogenic inert-element matrix system. Density functional theory calculations determined the lowest-energy geometry as the side-on [CdII(O3–•)]+ having C2v symmetry. This model was stable within the ab initio molecular dynamics simulation at 300 K, rationalizing the abnormal stability of [CdII(O3–•)]+observed experimentally. The O3-a1 → Cd-5s-donation orbital interaction was the driving force for the formation of the stable CdII–(O3–•) bond. The zeolite lattice plays a pivotal role in the enhancement of the acidity of the cadmium ion and stabilizes the donation interaction but constrains the O3 adduct as a pseudo-free ozonide ion. The findings in the present work will be applicable for designing new metal ozonide compounds.

Determination of charge-compensated C 3υ (II) centers for Er3+ ions in CdF2 and CaF2 crystals* *Project supported by the National Natural Science Foundation of China (Grant No. 1170513), the Natural Science Foundation of Shaanxi Province, China (Grant No. Z20200051), the Foundation of the Education Department of Shaanxi Provincial Government, China (Grant No. 16JK1461), and the Scientific Research Foundation of Xi’an

A unified theoretical method is established to determine the charge-compensated C 3v (II) centers of Er3+ ions in CdF2 and CaF2 crystals by simulating the electron paramagnetic resonance (EPR) parameters and Stark energy levels. The potential (Er3+–F−–) and (Er3+––O2–) structures for the C 3v (II) centers of Er3+ ions in CdF2 and CaF2 crystals are checked by diagonalizing 364 × 364 complete energy matrices in the scheme of superposition model. Our studies indicate that the C 3v (II) centers of Er3+ ions in CdF2 and CaF2 may be ascribed to the local (Er3+–F−–) structure, where the upper ligand ion F− undergoes an off-center displacement by ΔZ ≈ 0.3 Å for CdF2 and ΔZ ≈ 0.29 Å for the CaF2 along the C 3 axis. Meanwhile, a local compressed distortion of the cluster is expected to be ΔR ≈ 0.07 Å for CdF2:Er3+ and ΔR ≈ 0.079 Å for CaF2:Er3+. The considerable g-factor anisotropy for Er3+ ions in each of both crystals is explained reasonably by the obtained local parameters. Furthermore, our studies show that a stronger covalent effect exists in the C 3v (II) center for Er3+ in CaF2 or CaF2, which may be due to the stronger electrostatic interaction and closer distance between the central Er3+ ion and ligand O2– with the (Er3+–F−–) structure.

Investigation on the EPR Parameters for Tetragonal VO2+ Centers in LiHSO4 Single Crystals

In this work, the electron paramagnetic resonance (EPR) parameters (g-factors and A-constants) of the tetragonal VO2+ centers in LiHSO4 single crystals are theoretically investigated by the high-order perturbation formulae for these parameters based on two-spin–orbit-parameter model. Since the spin–orbit coupling coefficient of the ligand O2− is close to that of the central ion V4+ for the present system with strong covalence, the contributions to the EPR parameters from the ligand p- and s-orbitals as well as the spin–orbit coupling coefficient of the O2− ligand should be considered. The requirements of the crystal-field parameters are determined from the optical spectrum. The calculated results show good agreement with the experimental values. The signs of A-constants are ascertained in the discussion.

New Ru(II) complexes for dual photoreactivity: ligand exchange and (1)O2 generation.

Uncovering the factors that govern the electronic structure of Ru(II)-polypyridyl complexes is critical in designing new compounds for desired photochemical reactions, and strategies to tune excited states for ligand dissociation and (1)O2 production are discussed herein. The generally accepted mechanism for photoinduced ligand dissociation proposes that population of the dissociative triplet ligand field ((3)LF) state proceeds through thermal population from the vibrationally cooled triplet metal-to-ligand charge transfer ((3)MLCT) state; however, temperature-dependent emission spectroscopy provides varied activation energies using the emission and ligand exchange quantum yields for [Ru(bpy)2(L)2](2+) (bpy = 2,2'-bipyridine; L = CH3CN or py). This suggests that population of the (3)LF state proceeds from the vibrationally excited (3)MLCT state. Because the quantum yield of ligand dissociation for nitriles is much more efficient than that for py, steric bulk was introduced into the ligand set to distort the pseudo-octahedral geometry and lower the energy of the (3)LF state. The py dissociation quantum yield with 500 nm irradiation in a series of [Ru(tpy)(NN)(py)](2+) complexes (tpy = 2,2':6',2″-terpyridine; NN = bpy, 6,6'-dimethyl-2,2'-bipyridine (Me2bpy), 2,2'-biquinoline (biq)) increases by 2-3 orders of magnitude with the sterically bulky Me2bpy and biq ligands relative to bpy. Ultrafast transient absorption spectroscopy reveals population of the (3)LF state within 3-7 ps when NN is bulky, and density functional theory calculations support stabilized (3)LF states. Dual activity via ligand dissociation and (1)O2 production can be achieved by careful selection of the ligand set to tune the excited-state dynamics. Incorporation of an extended π system in Ru(II) complexes such as [Ru(bpy)(dppn)(CH3CN)2](2+) (dppn = benzo[i]dipyrido[3,2-a:2',3'-c]phenazine) and [Ru(tpy)(Me2dppn)(py)](2+) (Me2dppn = 3,6-dimethylbenzo[i]dipyrido[3,2-a:2',3'-c]phenazine) introduces low-lying, long-lived dppn/Me2dppn (3)ππ* excited states that generate (1)O2. Similar to [Ru(bpy)2(CH3CN)2](2+), photodissociation of CH3CN occurs upon irradiation of [Ru(bpy)(dppn)(CH3CN)2](2+), although with lower efficiency because of the presence of the (3)ππ* state. The steric bulk in [Ru(tpy)(Me2dppn)(py)](2+) is critical in facilitating the photoinduced py dissociation, as the analogous complex [Ru(tpy)(dppn)(py)](2+) produces (1)O2 with near-unit efficiency. The ability to tune the relative energies of the excited states provides a means to design potentially more active drugs for photochemotherapy because the photorelease of drugs can be coupled to the therapeutic action of reactive oxygen species, effecting cell death via two different mechanisms. The lessons learned about tuning of the excited-state properties can be applied to the use of Ru(II)-polypyridyl compounds in a variety of applications, such as solar energy conversion, sensors and switches, and molecular machines.

Theoretical studies of the local structure of Cu2 + center in aluminium lead borate glasses by their EPR and optical spectra

The local structure of the Cu2+ center in aluminium lead borate glasses was theoretically studied based on the optical spectral data and high-order perturbation formulas of the electron paramagnetic resonance (EPR) parameters (g factors g||, g⊥ and the hyperfine structure constants A||, A⊥) for a 3d9 ion in a tetragonally elongated octahedron. In the calculations, the ligand orbital and spin–orbit coupling of the impurity Cu2+ are taken into account; the required crystal-field parameters are estimated from the superposition model. Based on the calculations, the defect model of the Cu2+ center was confirmed and the defect structure (i.e., the ligand O2− octahedron around Cu2+ is determined to suffer about 19.2% relative elongation along the C4 axis due to the Jahn–Teller effect) was acquired, and a negative sign for A|| and positive sign of A⊥ for the Cu2+ center were suggested in the discussion.

Co and No Binding in Inducible Nitric Oxide Synthase

Nitric oxide synthases (NOSs) are homodimeric heme enzymes that catalyze the oxidative degradation of L-arginine (L-Arg) to nitric oxide (NO). Three structurally similar isoforms have been identified in endothelial cells (eNOS), neuronal tissues (nNOS) and in macrophages (iNOS). Different from eNOS and nNOS, iNOS is not present in resting cells but is expressed upon inflammatory and immunologic stimulation. As this isoform has been implicated in the pathogenesis of various diseases, there is a growing need for potent and highly selective inhibitors.The targeted development of potent inhibitors that are highly specific for iNOS requires detailed insights into the interaction between the ligand, the heme and the surrounding protein matrix on the molecular level. Therefore, we have investigated ligand and substrate binding in iNOSoxy using Fourier transform infrared (FTIR) spectroscopy in combination with temperature derivative spectroscopy (TDS). The physiological ligand O2 was replaced by carbon monoxide (CO) and NO. Both CO and NO allow us to exploit their excellent properties as spectroscopic probes. Previous studies on CO and NO migration in myoglobin have shown distinct differences in CO and NO migration despite their similar sizes.

Investigation of the local structure of Cu2+ ions doped in alkali lead tetraborate glasses by their electron paramagnetic resonance and optical spectra

The local structure of the Cu2+ centers in alkali lead tetraborate glasses was theoretically studied based on the optical spectra data and high-order perturbation formulas of the spin Hamiltonian parameters (electron paramagnetic resonance g factors g∥, g⊥ and hyperfine structure constants A∥, A⊥) for a 3d9 ion in a tetragonally elongated octahedron. In these formulas, the relative axial elongation of the ligand O2− octahedron around the Cu2+ due to the Jahn–Teller effect is taken into account by considering the contributions to the g factors from the tetragonal distortion which is characterized by the tetragonal crystal-field parameters Ds and Dt. From the calculations, the ligand O2− octahedral around Cu2+ is determined to suffer about 19.2% relative elongation along the C4 axis of the alkali lead tetraborate glass system, and a negative sign for A∥ and a positive sign for A⊥ for these Cu2+ centers are suggested in the discussion.

Co Recombination in Human IDO and TDO - A Comparison

The heme enzymes tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO) catalyze the oxidative cleavage of the L-tryptophan (L-Trp) pyrrole ring and the insertion of molecular oxygen to produce N-formylkynurenine, the first and rate-limiting step in the kynurenine pathway.The catalytic reaction involves the formation of a ternary complex including the protein, the ligand (O2), which binds to the ferrous heme iron, and the substrate (L-Trp). For optimal turnover of the enzyme, the protein scaffold has to provide easy access for both O2 and L-Trp to the heme active site. Efficient O2 association may require transient docking sites to be accessible. As both oxygen atoms are inserted into the C2 - C3 bond of the L-Trp pyrrole ring during the reaction, efficient ligand escape is (most likely) not required. L-Trp binding calls for a rather large 'access gate'. In addition, the reaction product N-formylkynurenine must be expelled from the active site to allow the uptake of new reagents.The molecular details of the catalytic mechanisms employed by TDO and IDO have, as yet, not been elucidated. Therefore, we have investigated ligand rebinding in ferrous IDO and TDO using flash photolysis at ambient temperatures, replacing the physiological ligand O2 by CO, to disclose both similarities of and differences between the enzymes. CO allows us to exploit its excellent properties as a spectroscopic probe. Moreover, CO is not reactive towards L-Trp, so that we can focus on ligand and substrate dynamics in the absence of the ensuing enzymatic reaction.

Anharmonic Vibrational Frequency Shifts upon Interaction of Phenol(+) with the Open Shell Ligand O2. The Performance of DFT Methods versus MP2

Anharmonic vibrational frequency shifts of the phenol(+) O-H stretching mode upon complex formation with the open-shell ligand O(2) were computed at several DFT and MP2 levels of theory, with various basis sets, up to 6-311++G(2df,2pd). It was found that all DFT levels of theory significantly outperform the MP2 method with this respect. The best agreement with the experimental frequency shift for the hydrogen-bonded minimum on the potential energy surfaces was obtained with the HCTH/407 functional (-93.7 cm(-1) theoretical vs -86 cm(-1) experimental), which is a significant improvement over other, more standard DFT functionals (such as, e.g., B3LYP, PBE1PBE), which predict too large downshifts (-139.9 and -147.7 cm(-1), respectively). Good agreement with the experiment was also obtained with the mPW1B95 functional proposed by Truhlar et al. (-109.2 cm(-1)). We have attributed this trend due to the corrected long-range behavior of the HCTH/407 and mPW1B95 functionals, despite the fact that they have been designed primarily for other purposes. MP2 method, even with the largest basis set used, manages to reproduce only less than 50% of the experimentally detected frequency downshift for the hydrogen-bonded dimer. This was attributed to the much more significant spin contamination of the reference HF wave function (compared to DFT Kohn-Sham wave functions), which was found to be strongly dependent on the O-H stretching vibrational coordinate. All DFT levels of theory outperform MP2 in the case of computed anharmonic OH stretching frequency shifts upon ionization of the neutral phenol molecule as well. Besides the hydrogen-bonded minimum, DFT levels of theory also predict existence of two other minima, corresponding to stacked arrangement of the phenol(+) and O(2) subunits. mPW1B95 and PBE1PBE functionals predict a very slight blue shift of the phenol(+) O-H stretching mode in the case of stacked dimer with the nearly perpendicular orientation of oxygen molecule with respect to the phenolic ring, which is entirely of electrostatic origin, in agreement with the experimental observations of an additional band in the IR photodissociation spectra of phenol(+)-O(2) dimer [Patzer, A.; Knorke, H.; Langer, J.; Dopfer, O. Chem. Phys. Lett. 2008, 457, 298]. The structural features of the minima on the studied PESs were discussed in details as well, on the basis of NBO and AIM analyses.

Spectroscopic Studies of Substrate and Ligand Binding in Inducible Nitric Oxide Synthase

Nitric oxide is a small molecule involved in various physiological processes. It serves for instance as a vasorelaxant or neurotransmitter. The three isoforms of nitric oxide synthase (eNOS, nNOS, iNOS) catalyze the formation of NO in a two-step reaction. In a first step arginine is converted to hydroxy-arginine. Subsequently, this intermediate is cleaved to yield citrulline and NO.In spite of the increasing interest in these proteins in medical research, little is known about the molecular details of the catalytic mechanism. We have used UV/visible and Fourier Transform Infrared / Temperature Derivative Spectroscopy (FTIR/TDS) over a wide range of temperature (4 - 300 K) to observe the interaction between protein (iNOS), ligand and substrate. In these experiments, the physiological ligand O2 has been replaced by CO to observe the ternary complex without steady turnover of arginine. In particular, we have focused on the influence of arginine, the intermediate hydroxy-arginine and cofactor H4B on ligand binding.

Theoretical studies of the spin Hamiltonian parameters and the local structure for the orthorhombic V4+ in CaYAlO4

AbstractThe spin Hamiltonian parameters (g ‐factors and the hyperfine structure constants) and the local structure for the orthorhombic V4+ in CaYAlO4 are theoretically studied from the perturbation formulas of these parameters for a 3d1 ion in orthorhombically distorted octahedra. Based on the present studies, this center is explicitly assigned to V4+ occupying the Al3+ site, associated with one next‐nearest‐neighbor Mg2+ replacing the host Al3+ (i.e. MgAl) in the ab ‐plane due to the charge compensation. Since the effective charge of the compensator is negative (−e), the ligand O2− intervening in the impurity V4+ and the MgAl would undergo a small displacement (≈0.08 Å) towards the central ion because of the electrostatic repulsion. The local structure of this center can be described as elongation of the oxygen octahedron along the c‐ axis and the slight orthorhombic distortion in the perpendicular direction. The theoretical spin Hamiltonian parameters and the optical transitions based on the above local structure show reasonable agreement with the experimental data. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)

Electronic structure and optical properties of SrCu2O2

The electronic structure of SrCu2O2, a wide gap (∼3.3 eV) p-type oxide semiconductor, was examined by photoelectron and optical spectroscopy. The spectroscopy results were compared with the energy band structure calculated by the local density approximation method to clarify the origins of p-type conductivity in this material. Despite the significant difference in band gap energy, the basic electronic structure around the band gap region was found to be quite similar to that of Cu2O. Thus, the 3d−4sp orbital of Cu+ ion is hybridized with the 2p orbital of ligand O2− ions due to the covalency of Cu–O bonds, to form states near the valence band maximum; the conduction band minimum is predominantly composed of the hybridized orbital of Cu 4sp and O 2p, forming the direct band gap at Γ point. A sharp absorption band observed near the fundamental absorption edge is likely attributable to an exciton. Although the corresponding exciton emission was not observed near the absorption edge, a blue-green emission band (Stokes shift of ∼1 eV) was observed at ∼2.47 eV. The emission is presumably attributable to intra-atomic transitions of Cu+, partially allowed by p-orbital mixing into s and d orbitals.

Structural and Oxygen-Binding Properties of Divinyl-Sulfone-Reacted Bovine Hemoglobin as a Function of Protein Ligation State and Reactant Concentration

Bovine hemoglobin (HbBv) was reacted with divinyl sulfone (DVS) at 2-4 degrees C and pH 7.4 for 24 h. Two procedures were employed: (1) low concentration (conc.) of oxygenated HbBv (ligand O2) and low molar ratio of DVS/oxyHbBv (25 ml of 8% oxyHbBv, 0.01 M DVS); (2) low conc. of deoxygenated HbBv (no ligand) and low DVS/deoxyHbBv molar ratio (25 ml of 8% deoxyHbBv, 0.01 M DVS). The nonpolymerized purified products of procedures 1 and 2 were designated oxyHbBv-DVS and HbBv-DVS. Utilizing a high conc. solution of oxyHbBv-DVS and a relatively high molar ratio of DVS/oxyHbBv-DVS (25 ml of 15% oxyHbBv-DVS, 0.03 M DVS) it was possible to aerobically polymerize the modified hemoglobin (procedure 3). Similarly it was possible to anaerobically polymerize HbBv-DVS (25 ml of 15% HbBv-DVS, 0.03 M DVS)(procedure 4). The polymerized products of procedures 3 and 4 were designated oxyPoly HbBv-DVS and Poly HbBv-DVS. The four isolated products were characterized structurally using SDS-PAGE and gel-permeation HPLC and functionally employing a Hemox-analyzer at 37 degrees C, pH 7.4 and 0.15 M Cl. Both oxyPoly HbBv-DVS (P50 = 13 mm Hg, n = 1.1) and Poly HbBv-DVS (P50 = 61 mm Hg, n = 1.6) were shown to be mixtures of intermolecularly-crosslinked hemoglobin. OxyHbBv-DVS (P50 = 13 mm Hg, n = 1.3) was shown to be an intramolecularly-crosslinked 64 kDa material, whereas HbBv-DVS (P50 = 52 mm Hg, n = 1.9) was found to be an intramolecularly-modified 64 kDa derivative, but not an intramolecularly-crosslinked one.(ABSTRACT TRUNCATED AT 250 WORDS)