Reversible Oxygen Binding Research Articles

Colorimetric Oxygen Sensing by Analyzing Chromaticity Points for Polymer Cobalt Schiff Base in CIELAB

AbstractPolymer membranes of a copolymer ligand (L) coordinated to tetra‐coordinated N,N'‐ethylene bis(salicylideneiminato) cobalt(II) at the fifth coordinating site of the center cobalt(II), Co(II)S‐L, are prepared to measure colorimetrically the color changes in response to rapid reversible oxygen binding simultaneously with slow oxidation under moist conditions to yield Co(III)S‐L. The chromaticity point observed in CIELAB is the endpoint of the vector sum of the unit vectors for Co(II)S‐L, O2‐Co(II)S‐L, and Co(III)S‐L, scaled by their respective abundance ratios: (1 − m)(1 − n), m(1 − n), and n, where m is the ratio of O2‐Co(II)S‐L to the sum of Co(II)S‐L and O2‐Co(II)S‐L and n is the ratio of Co(III)S‐L to the total of the three cobalt complexes. The observed limited area in CIELAB as a stoichiometric Euclidean space is supported by the following two different reaction processes of the polymer membranes: an oxygen‐binding reaction under several different partial pressures of oxygen supplied to the membranes in a short period, during which oxidation of the cobalt(II) complexes is negligible, and an oxidation reaction over a long period at a constant partial pressure of oxygen. The chromaticity points in both processes progress linearly in three different two‐dimensional coordinates: a*b*, a*L*, and b*L*.

Oxygen Gas-Filled Metal-Organic Frameworks (MOFs) Delivery System: A Hypothetical Design for Injectable Oxygen

Oxygen delivery systems are crucial in critical care medicine, particularly for managing acute respiratory distress. This study presents a novel approach, exploring the potential of Metal-Organic Frameworks (MOFs) as oxygen delivery systems. We highlight their unique properties and potential for enhancing oxygenation in medical settings. Understanding their biocompatibility, oxygen-carrying capacity, and controlled release mechanisms is pivotal for successful implementation in clinical practice. Thanks to their exceptional porosity, structural diversity, lower crystal density, and tunability, MOFs offer a fresh perspective on developing innovative oxygen carriers. We propose that MOFs will demonstrate biocompatibility, stability, and the ability to deliver oxygen in a controlled and sustained manner when administered intravenously in living organisms. Gas adsorption and molecular simulation techniques will demonstrate reversible oxygen binding within MOFs and predict controlled release kinetics. The findings of the simulations and experiments should indicate the feasibility of utilising MOFs as intravenous oxygen carriers with controlled and reversible oxygen release behaviour.

Elucidating the binding properties of methemoglobin in red blood cell to cyanide, hydrosulfide, and azide ions using artificial red blood cell

Methemoglobin (metHb), the oxidized form of hemoglobin, lacks the ability of reversible oxygen binding; however, it has a high binding affinity to toxic substances such as cyanide, hydrosulfide, and azide. This innate property of metHb offers the clinical option to treat patients poisoned with these toxins, by oxidizing the endogenous hemoglobin in the red blood cells (RBCs). The binding properties of naked metHb (isolated from RBC) with these toxins has been studied; however, the binding behaviors of metHb under the intracellular conditions of RBC are unclear because of the difficulty in detecting metHb status changes in RBC. This study aimed to elucidate the binding properties of metHb in RBC under physiological and poisoned conditions using artificial RBC, which was hemoglobin encapsulated in a liposome. The mimic-circumstances of metHb in RBC (metHb-V) was prepared by oxidizing the hemoglobin in artificial RBC. Spectroscopic analysis indicated that the metHb in metHb-V exhibited a binding behavior different from that of naked metHb, depending on the toxic substance: When the pH decreased, (i) the cyanide binding affinity of metHb-V remained unchanged, but that of naked metHb decreased (ii) the hydrosulfide binding affinity was increased in metHb-V but was decreased in naked metHb. (iii) Azide binding was increased in metHb-V, which was similar to that in naked metHb, irrespective of the pH change. Thus, the binding behavior of intracellular metHb in the RBC with cyanide, hydrosulfide, and azide under physiological and pathological conditions were partly elucidated using the oxidized artificial RBC.

Comparative study of the binding and activation of 2,4-dichlorophenol by dehaloperoxidase A and B

The dehaloperoxidase-hemoglobin (DHP), first isolated from the coelom of a marine terebellid polychaete, Amphitrite ornata, is an example of a multi-functional heme enzyme. Long known for its reversible oxygen (O2) binding, further studies have established DHP activity as a peroxidase, oxidase, oxygenase, and peroxygenase. The specific reactivity depends on substrate binding at various internal and external binding sites. This study focuses on comparison of the binding and reactivity of the substrate 2,4-dichlorophenol (DCP) in the isoforms DHPA and B. There is strong interest in the degradation of DCP because of its wide use in the chemical industry, presence in waste streams, and particular reactivity to form dioxins, some of the most toxic compounds known. The catalytic efficiency is 3.5 times higher for DCP oxidation in DHPB than DHPA by a peroxidase mechanism. However, DHPA and B both show self-inhibition even at modest concentrations of DCP. This phenomenon is analogous to the self-inhibition of 2,4,6-trichlorophenol (TCP) at higher concentration. The activation energies of the electron transfer steps in DCP in DHPA and DHPB are 19.3 ± 2.5 and 24.3 ± 3.2 kJ/mol, respectively, compared to 37.2 ± 6.5 kJ/mol in horseradish peroxidase (HRP), which may be a result of the more facile electron transfer of an internally bound substrate in DHPA. The x-ray crystal structure of DHPA bound with DCP determined at 1.48 Å resolution, shows tight substrate binding inside the heme pocket of DHPA (PDB 8EJN). This research contributes to the studies of DHP as a naturally occurring bioremediation enzyme capable of oxidizing a wide range of environmental pollutants.

Reactivity of 2,4-dichlorophenol in hemoglobin-dehaloperoxidase A & B.

The multi-functional protein dehaloperoxidase-hemoglobin (DHP), from the coelom of a marine terebellid polychaete Amphitrite ornata, has diverse functions, which depend on the heme Fe oxidation state (ferric or ferrous) and on substrate binding at various internal and external binding sites. Long known for its reversible oxygen (O2) binding, further studies have established DHP as the first example of hemoglobin to have activity as a peroxidase (halophenols and guaiacols), oxidase (5-bromo-3-oxindole), oxygenase (2,3-dimethylindole and 2,3-dimethylpyrrole), and peroxygenase (nitrophenol, pyrroles and indoles). We focused on 2,4-dichlorophenol (DCP) because it is an example of a substrate that is apparently oxidized by two separate reactions, peroxidase and peroxygenase. The related molecule, 2,4-dibromophenol is a naturally occurring xenobiotic that is significantly more prevalent in marine ecosystems than 2,4,6-tribromophenol. Thus, it is a mechanistic example of novel structure/function relationships that further expands the versatility of DHP for a biological protective function in its host organism. The catalytic efficiency is 2 times higher for DCP oxidation in DHPB than DHPA. DCP shows self-inhibition even at modest concentration analogous to 2,4,6-trichlorophenol at higher concentration. The rate of DCP oxidation by DHPA of approximately 19.3 kJ/mol compared to 37.2 kJ/mol in HRP. The product 2-chloro-1,4-benzoquinone (2-CLQ) can also be hydroxylated to 2-chloro-3-hydroxy-1,4-benzoquinone (2-ClQOH) at a 10 times slower rate than the primary oxidation process. Hydroxylation of 2-ClQ in the presence DHP is not catalyzed by DHP since only H2O2 is required. The x-ray crystal structure of DHPA bound with DCP (1.48 Å) shows tight substrate binding inside the heme pocket of DHPA. Based on the electron density, we proposed two different conformations, DCPA and DCPB. This research suggests that DHP can be used as bioremediation to neutralize/oxidize a wide range of environmental pollutants.

Breathe and burn: Novel roles for myoglobin in thermogenesis

Breathe and burn: Novel roles for myoglobin in thermogenesis

Synthesis, spectroscopic characterization, DFT, oxygen binding, antioxidant activity on Fe(III), Co(II) and Ni(II) complexes with a tetradentate ONNO donor Schiff base ligand

The Schiff base ligand, namely (7E)-N-benzylidene-2-styrylbenzenamine- 1,2-diamine-2,4-dihydroxy-phenol (L), was synthesized by condensation of 2,4-dihydroxybenzaldehyde with o-phenylenediamine. The reaction of the ligand with Fe(III), Co(II) and Ni(II) salts in an 1:1 ratio yielded three complexes (1?3). Different analytical tools, like elemental analysis, ESI-MS, UV?Vis, FT-IR, NMR and EPR spectroscopy, then molar conductivity and magnetic susceptibility spectra, were used to elucidate the structure of the ligand and complexes. Density functional theory calculation at the B3LYP/3- -211G++/LANL2DZ level of the theory has been carried out to optimize the geometry of the ligand and complexes. The tetradentate ligand has coordinated to metals through ONNO donors affording octahedral geometry. Complexes were studied for their oxygen-binding activity and free radical scavenging activities. Complexes 1 and 2, which contain Fe(IIl) and Co(II), displayed reversible oxygen binding activity. On the other hand, complex 3 fails to show oxygen binding. The order of antioxidant activity is: 3 > 1 > 2 > L.

Atomic force microscope observation of athletes' hemoglobin imaging

Hemoglobin (Hb) is a protein and its functional form has a tetrameric structure. This structure is the result of a combination of four sub-units called globin and indicates the dynamic interaction between them. Each subunit has a ring-shaped organic molecule called a heme that contains an iron atom; Heme is a group that mediates the reversible binding of oxygen by hemoglobin. This research was performed to observe the image of Hb by an atomic force microscope (AFM) and measure the physical function of athletes. For this purpose, based on the principle of AFM imaging, the hemoglobin crosslinking method was used to measure the morphology and size of cross-linked Hb, glutaraldehyde and Hb diameter were detected to prepare cross-linked Hb samples with different molar ratio, the activity of peroxidase was detected by Trinder reaction. The AFM was used to detect the influence of physiological environment changes such as pH, temperature, oxygen partial pressure and osmotic pressure on the absorption spectrum of Hb imaging. Results showed that the size of the uncrosslinked Hb was 6.64 nm. With the increase of the molar ratio of glutaraldehyde to Hb, the number of Hb molecules involved in the crosslinking increased, and the molecular size increased. During the crosslinking process, the aggregation of the cross-linked molecules would make the particle size of some Hb molecules reach 80-100 nm. The peak height, peak position and peak shape of the characteristic absorption peaks of pH to hemoglobin at 550 and 589 nm occurred. When the temperature changes continuously in the range of 30-55℃, the peak height of Hb absorption spectrum of normal red blood cells at 550 nm and 589 nm decreases gradually with the increase of temperature, and the peak shape at 610 nm changes obviously at 42℃, which indicates that the molecular structure of Hb changes; the absorption spectrum curve of deoxygenation disappears at 500 nm, the oxygen-binding capacity of Hb is very low, and the oxygen affinity and oxygenated hemoglobin are low (The concentration of HbO2) decreased, the osmotic pressure increased, the RBC dehydrated, the volume decreased, and the concentration of Hb increased. Conclusion: It is more accurate and comprehensive to use AFM to observe athletes' hemoglobin.

Takashi Yonetani: A stellar biochemist, a man with dignity. The Roman connection

Takashi Yonetani: A stellar biochemist, a man with dignity. The Roman connection

Black Phosphorus-Loaded Separable Microneedles as Responsive Oxygen Delivery Carriers for Wound Healing.

Oxygen carriers are attracting extensive interest in biomedical research and clinical applications such as wound healing, alternative blood transfusion, and acute trauma treatment. Great efforts have been devoted to the generation of oxygen carriers with special functions and properties to meet specific demands. Here, we present black phosphorus (BP)-loaded separable responsive microneedles (MNs) with oxygen carrying and controllable oxygen delivering ability for wound healing. Such MNs are composed of a polyvinyl acetate (PVA) backing layer and gelatin methacryloyl (GelMA) tips that are loaded with BP quantum dots (BP QDs) and hemoglobin (Hb). Taking advantage of the fast dissolvability of PVA, the backing layer soon disappears after the MNs are applied to skin and the noncytotoxic, biocompatible GelMA tips are left inside the skin. Due to the excellent photothermal effect of BP QDs and the reversible oxygen binding property of Hb, the local temperature of the skin will increase after near-infrared ray irradiation, resulting in the responsive oxygen release. Notably, the practical performance of such MNs has been demonstrated by treating the full-thickness cutaneous wounds of a type I diabetes rat model, indicating their potential value in wound healing and other related biomedical fields.

Synthesis, characterization, and reversible oxygen binding of β-diketonate–Eu(III) complexes bearing anthracene

A series of β-diketonate–Eu(III) complexes with the general formula [EuX3L] {X = benzoyltrifluoroacetonate (BTA), naphthoyltrifluoroacetonate (NTA); L = N,N-dimethyl-N′-(9-methylanthracenyl)ethylenediamine (L1), 1,2-bis[(anthracen-9-ylmethyl)amino]ethane (L2)} has were newly prepared and structurally elucidated by single crystal X-ray diffraction. The complexes displayed anthracene-based absorption bands and weak red emissions which were remarkably changed upon reaction with singlet oxygen (1O2). The strong red emission of endoperoxides [EuX3L-EPO] became almost indiscernible after 1.5 h at room temperature, making oxygen binding of β-diketonate–Eu(III) complexes reversible.

Cobalt-Chelated Polyamine Brushes on Solid Microspheres for Rapid Binding and Chemical Storage of Molecular Oxygen

Methylated poly(vinyl amine) brushes generated on PS-DVB microspheres were demonstrated as excellent macroligands, forming hydrophilic Co(II) chelates capable of reversible molecular oxygen binding. The oxygenation is extremely fast when counteranions of cobalt are replaced with hydroxyl ions. The experiments carried out using oxygen sensor, FT-IR, TGA techniques, and gas volumetric measurements showed that the polymer complexes with either 4/1 or 2/1 [amine]/[Co] ratios form 1:1 molecular oxygen adducts which are stable up to 110–120 °C. In order to impart the chain extension effect, poly(vinyl amine-stat-DADMAC) brushes were also generated on the microspheres by using DADMAC as additional comonomer. Fast oxygenation, high oxygen binding capacity (ca. 80 mL/g), and long-term stability of the oxygen adducts make the polymeric complex superior to current systems. The cobalt complex system presented can be considered as a high capacity solid matrix for dissociation and chemical storage of the molecular oxyg...

Structural Transformation in Metal-Organic Frameworks for Reversible Binding of Oxygen.

Polycyclic aromatic derivatives can trap 1 O2 to form endoperoxides (EPOs) for O2 storage and as sources of reactive oxygen species. However, these materials suffer from structural amorphism, which limit both practical applications and fundamental studies on their structural optimization for O2 capture and release. Metal-organic frameworks (MOFs) offer advantages in O2 binding, such as clear structure-performance relationships and precise controllability. Herein, we report the reversible binding of O2 is realized via the chemical transformation between anthracene-based and the corresponding EPO-based MOF. It is shown that anthracene-based MOF, the framework featuring linkers with polycyclic aromatic structure, can rapidly trap 1 O2 to form EPOs and can be restored upon UV irradiation or heating to release O2 . Furthermore, we confirm that photosensitizer-incorporated anthracene-based MOF are promising candidates for reversible O2 carriers controlled by switching Vis/UV irradiation.

Structural Transformation in Metal–Organic Frameworks for Reversible Binding of Oxygen

AbstractPolycyclic aromatic derivatives can trap 1O2 to form endoperoxides (EPOs) for O2 storage and as sources of reactive oxygen species. However, these materials suffer from structural amorphism, which limit both practical applications and fundamental studies on their structural optimization for O2 capture and release. Metal–organic frameworks (MOFs) offer advantages in O2 binding, such as clear structure–performance relationships and precise controllability. Herein, we report the reversible binding of O2 is realized via the chemical transformation between anthracene‐based and the corresponding EPO‐based MOF. It is shown that anthracene‐based MOF, the framework featuring linkers with polycyclic aromatic structure, can rapidly trap 1O2 to form EPOs and can be restored upon UV irradiation or heating to release O2. Furthermore, we confirm that photosensitizer‐incorporated anthracene‐based MOF are promising candidates for reversible O2 carriers controlled by switching Vis/UV irradiation.

Potential Modulation of Vascular Function by Nitric Oxide and Reactive Oxygen Species Released From Erythrocytes.

The primary role for erythrocytes is oxygen transport that requires the reversible binding of oxygen to hemoglobin. There are, however, secondary reactions whereby the erythrocyte can generate reactive oxygen species (ROS) and nitric oxide (NO). ROS such as superoxide anion and hydrogen peroxide are generated by the autoxidation of hemoglobin. NO can be generated when nitrite reacts with hemoglobin forming an HbNO+ intermediate. Both of these reactions are dramatically enhanced under hypoxic conditions. Within the erythrocyte, interactions of NO with hemoglobin and enzymatic reactions that neutralize ROS are expected to prevent the release of any generated NO or ROS. We have, however, demonstrated that partially oxygenated hemoglobin has a distinct conformation that enhances hemoglobin-membrane interactions involving Band 3 protein. Autoxidation of the membrane bound partially oxygenated hemoglobin facilitates the release of ROS from the erythrocyte. NO release is made possible when HbNO+, the hemoglobin nitrite-reduced intermediate, which is not neutralized by hemoglobin, is bound to the membrane and releases NO. Some of the released ROS has been shown to be transferred to the vasculature suggesting that some of the released NO may also be transferred to the vasculature. NO is known to have a major effect on the vasculature regulating vascular dilatation. Erythrocyte generated NO may be important when NO production by the vasculature is impaired. Furthermore, the erythrocyte NO released, may play an important role in regulating vascular function under hypoxic conditions when endothelial eNOS is less active. ROS can react with NO and, can thereby modulate the vascular effects of NO. We have also demonstrated an inflammatory response due to erythrocyte ROS. This reflects the ability of ROS to react with various cellular components affecting cellular function.

Mutagenesis of an Active-Site Loop in Tryptophan Hydroxylase Dramatically Slows the Formation of an Early Intermediate in Catalysis.

Solution studies of the aromatic amino acid hydroxylases are consistent with the FeIVO intermediate not forming until both the amino acid and tetrahydropterin substrates have bound. Structural studies have shown that the positions of active-site loops differs significantly between the free enzyme and the enzyme-amino acid-tetrahydropterin complex. In tryptophan hydroxylase (TrpH) these mobile loops contain residues 124-134 and 365-371, with a key interaction involving Ile366. The I366N mutation in TrpH results in decreases of 1-2 orders of magnitude in the kcat and kcat/ Km values. Single turnover analyses establish that the limiting rate constant for turnover is product release for the wild-type enzyme but is formation of the first detectable intermediate I in catalysis in the mutant enzyme. The mutation does not alter the kinetics of NO binding to the ternary complex nor does it uncouple FeIVO formation from amino acid hydroxylation. The effects on the kcat value of wild-type TrpH of changing viscosity are consistent with rate-limiting product release. While the effect of viscosity on the kcat/ KO2 value is small, consistent with reversible oxygen binding, the effects on the kcat/ Km values for tryptophan and the tetrahydropterin are large, with the latter value exceeding the expected limit and varying with the identity of the viscogen. In contrast, the kinetic parameters of I366N TrpH show small changes with viscosity. The results are consistent with binding of the amino acid and pterin substrate to form the ternary complex being directly coupled to closure of loops over the active site and formation of the reactive complex. The mutation destabilizes this initial event.

Coexistence of multiple globin genes conferring protection against nitrosative stress to the Antarctic bacterium Pseudoalteromonas haloplanktis TAC125

Despite the large number of globins recently discovered in bacteria, our knowledge of their physiological functions is restricted to only a few examples. In the microbial world, globins appear to perform multiple roles in addition to the reversible binding of oxygen; all these functions are attributable to the heme pocket that dominates functional properties. Resistance to nitrosative stress and involvement in oxygen chemistry seem to be the most prevalent functions for bacterial globins, although the number of globins for which functional roles have been studied via mutation and genetic complementation is very limited. The acquisition of structural information has considerably outpaced the physiological and molecular characterisation of these proteins.The genome of the Antarctic cold-adapted bacterium Pseudoalteromonas haloplanktis TAC125 (PhTAC125) contains genes encoding three distinct single-chain 2/2 globins, supporting the hypothesis of their crucial involvement in a number of functions, including protection against oxidative and nitrosative stress in the cold and O2-rich environment. In the genome of PhTAC125, the genes encoding 2/2 globins are constitutively transcribed, thus suggesting that these globins are not functionally redundant in their physiological function in PhTAC125. In the present study, the physiological role of one of the 2/2 globins, Ph-2/2HbO-2217, was investigated by integrating in vivo and in vitro results. This role includes the involvement in the detoxification of reactive nitrogen and O2 species including NO by developing two in vivo and in vitro models to highlight the protective role of Ph-2/2HbO-2217 against reactive nitrogen species. The PSHAa2217 gene was cloned and over-expressed in the flavohemoglobin-deficient mutant of Escherichia coli and the growth properties and O2 uptake in the presence of NO of the mutant carrying the PSHAa2217 gene were analysed. The ferric form of Ph-2/2HbO-2217 is able to catalyse peroxynitrite isomerisation in vitro, indicating its potential role in the scavenging of reactive nitrogen species. Here we present in vitro evidence for the detoxification of NO by Ph-2/2HbO-2217.

Heme as a Target for Therapeutic Interventions.

Heme is a complex of iron and the tetrapyrrole protoporphyrin IX with essential functions in aerobic organisms. Heme is the prosthetic group of hemoproteins such as hemoglobin and myoglobin, which are crucial for reversible oxygen binding and transport. By contrast, high levels of free heme, which may occur in various pathophysiological conditions, are toxic via pro-oxidant, pro-inflammatory and cytotoxic effects. The toxicity of heme plays a major role for the pathogenesis of prototypical hemolytic disorders including sickle cell disease and malaria. Moreover, there is increasing appreciation that detrimental effects of heme may also be critically involved in diseases, which usually are not associated with hemolysis such as severe sepsis and atherosclerosis. In mammalians homeostasis of heme and its potential toxicity are primarily controlled by two physiological systems. First, the scavenger protein hemopexin (Hx) non-covalently binds extracellular free heme with high affinity and attenuates toxicity of heme in plasma. Second, heme oxygenases (HOs), in particular the inducible HO isozyme, HO-1, can provide antioxidant cytoprotection via enzymatic degradation of intracellular heme. This review summarizes current knowledge on the pathophysiological role of heme for various diseases as demonstrated in experimental animal models and in humans. The functional significance of Hx and HOs for the regulation of heme homeostasis is highlighted. Finally, the therapeutic potential of pharmacological strategies that apply Hx and HO-1 in various clinical settings is discussed.

HemoCD as a Totally Synthetic Artificial Oxygen Carrier: Improvements in the Synthesis and O2 /CO Discrimination.

HemoCD, which is composed of an iron(II)porphyrin such as 5,10,15,20-tetrakis(4-sulfonatophenyl)porphinatoiron(II) (Fe(II)TPPS) and a cyclodextrin (CD) dimer having a pyridine linker, represents a synthetic hemoglobin (Hb) model compound that exhibits reversible oxygen (O2 ) binding ability in aqueous solution at an ambient temperature. Therefore, hemoCD has the potential to be used as a totally synthetic artificial oxygen carrier. In this article, we describe the improvements of hemoCD related to its synthesis and O2 /CO selectivity. The synthesis procedure of the CD dimer of hemoCD was re-examined, and the CD dimer was successively synthesized from inexpensive β-CD with a 38% yield (three-steps), which enabled us to obtain the CD dimer in gram-quantities. The O2 /CO selectivity of hemoCD was also markedly improved using an iron(II)porphyrin having a carboxylate group at the distal site of hemoCD.

Study of Intermediates in Iridium–(Phosphoramidite,Olefin)-Catalyzed Enantioselective Allylic Substitution

Experimental mechanistic studies of iridium-catalyzed, enantioselective allylic substitution enabled by (phosphoramidite,olefin) ligands are reported. (η2-Allylic alcohol)iridium(I) and (η3-allyl)iridium(III) complexes were synthesized and characterized by NMR spectroscopy as well as X-ray crystallography. The substrate complexes are catalytically and kinetically competent to be intermediates in allylic substitutions of branched, racemic allylic alcohols with various nucleophiles. In addition, we have identified an off-cycle pathway involving reversible binding of molecular oxygen to iridium, which contributes to the air tolerance of the catalyst system.