Lithium Phthalocyanine Research Articles

Modulating Single-Molecule Magnetic Behavior of a Dinuclear Erbium(III) Complex by Solvent Exchange.

[Er2(thd)4Pc]·2C6H6 (1) (Hthd = 2,2,6,6-tetramethylheptanedione), obtained as green crystals from the reaction of [Er(thd)3]·2H2O with lithium phthalocyanine, Li2Pc, is a stable dinuclear complex with two ErIII centers. Its lattice benzene solvent can be exchanged by soaking the crystals in dichloromethane to give [Er2(thd)4Pc]·2CH2Cl2 (2). The magnetic susceptibility data suggest different coupling interactions for the two complexes. While 1 exhibits fast relaxation and an estimated energy barrier of Ea = 2.6 cm-1 under 600 Oe dc field, the single-molecule magnet behavior of 2 is field-induced and the energy barrier is higher at 34.3 cm-1. Ab initio calculations were performed to understand the nature of the coupling interaction between two ErIII ions bridged by the phthalocyanine and the origin of different magnetic behavior. Importantly, the single-molecule magnetic properties can be reversibly tuned through the exchange of solvent molecules, confirmed by further measurements on the reverse solvated complexes 1-re and 2-re. This subtle control of relaxation by lattice solvents is rarely observed in single-molecule magnets, especially for ErIII-based complexes.

The generation of superoxide radicals by complex III in heart mitochondria and the antioxidant effect of dinitrosyl iron complexes at different partial pressures of oxygen

The EPR spin-trapping technique and EPR-oximetry were used to study generation of superoxide radicals in heart mitochondria isolated from Wistar rats under conditions of variable oxygen concentration. Lithium phthalocyanine and TEMPONE-15N-D16 were chosen to determine oxygen content in a gas-permeable capillary tube containing mitochondria. TIRON was used as a spin trap. We investigated the influence of different oxygen concentrations in incubation mixture and demonstrated that heart mitochondria can generate superoxide in complex III at different partial pressure of oxygen as well as under the conditions of deep hypoxia (< 5% O2). Dinitrosyl iron complexes with glutathione (the pharmaceutical drug "Oxacom") exerted an antioxidant effect, regardless of the value of the partial pressure of oxygen, but the magnitude and kinetic characteristics of the effect depended on the concentration of the drug.

Direct Measurements of Oxygen Gradients in Spheroid Culture System Using Electron Parametric Resonance Oximetry.

Advanced in vitro culture from tissues of different origin includes three-dimensional (3D) organoid micro structures that may mimic conditions in vivo. One example of simple 3D culture is spheroids; ball shaped structures typically used as liver and tumour models. Oxygen is critically important in physiological processes, but is difficult to quantify in 3D culture: and the question arises, how small does a spheroid have to be to have minimal micro-environment formation? This question is of particular importance in the growing field of 3D based models for toxicological assessment. Here, we describe a simple non-invasive approach modified for the quantitative measurement and subsequent evaluation of oxygen gradients in spheroids developed from a non-malignant fish cell line (i.e. RTG-2 cells) using Electron Paramagnetic Resonance (EPR) oximetry. Sonication of the paramagnetic probe Lithium phthalocyanine (LiPc) allows for incorporation of probe particulates into spheroid during its formation. Spectra signal strength after incorporation of probe into spheroid indicated that a volume of 20 μl of probe (stock solution: 0.10 mg/mL) is sufficient to provide a strong spectra across a range of spheroid sizes. The addition of non-toxic probes (that do not produce or consume oxygen) report on oxygen diffusion throughout the spheroid as a function of size. We provide evidence supporting the use of this model over a range of initial cell seeding densities and spheroid sizes with the production of oxygen distribution as a function of these parameters. In our spheroid model, lower cell seeding densities (∼2,500 cells/spheroid) and absolute size (118±32 μm) allow control of factors such as pre-existing stresses (e.g. ∼ 2% normoxic/hypoxic interface) for more accurate measurement of treatment response. The applied methodology provides an elegant, widely applicable approach to directly characterize spheroid (and other organoid) cultures in biomedical and toxicological research.

Temporal variation in the response of tumors to hyperoxia with breathing carbogen and oxygen.

The effect of hyperoxygenation with carbogen (95% O2 + 5% CO2) and 100% oxygen inhalation on partial pressure of oxygen (pO2) of radiation-induced fibrosarcoma (RIF-1) tumor was investigated. RIF-1 tumors were innoculated in C3H mice, and aggregates of oximetry probe, lithium phthalocyanine (LiPc), was implanted in each tumor. A baseline tumor pO2 was measured by electron paramagnetic resonance (EPR) oximetry for 20 minutes in anesthetized mice breathing 30% O2 and then the gas was switched to carbogen or 100 % oxygen for 60 minutes. These experiments were repeated for 10 days. RIF-1 tumors were hypoxic with a baseline tissue pO2 of 6.2–8.3 mmHg in mice breathing 30% O2. Carbogen and 100% oxygen significantly increased tumor pO2 on days 1 to 5, with a maximal increase at approximately 32–45 minutes on each day. However, the extent of increase in pO2 from the baseline declined significantly on day 5 and day 10. The results provide quantitative information on the effect of hyperoxic gas inhalation on tumor pO2 over the course of 10 days. EPR oximetry can be effectively used to repeatedly monitor tumor pO2 and test hyperoxic methods for potential clinical applications.

Application of Electron Paramagnetic Resonance (EPR) Oximetry to Monitor Oxygen in Wounds in Diabetic Models

A lack of oxygen is classically described as a major cause of impaired wound healing in diabetic patients. Even if the role of oxygen in the wound healing process is well recognized, measurement of oxygen levels in a wound remains challenging. The purpose of the present study was to assess the value of electron paramagnetic resonance (EPR) oximetry to monitor pO2 in wounds during the healing process in diabetic mouse models. Kinetics of wound closure were carried out in streptozotocin (STZ)-treated and db/db mice. The pO2 was followed repeatedly during the healing process by 1 GHz EPR spectroscopy with lithium phthalocyanine (LiPc) crystals used as oxygen sensor in two different wound models: a full-thickness excisional skin wound and a pedicled skin flap. Wound closure kinetics were dramatically slower in 12-week-old db/db compared to control (db/+) mice, whereas kinetics were not statistically different in STZ-treated compared to control mice. At the center of excisional wounds, measurements were highly influenced by atmospheric oxygen early in the healing process. In pedicled flaps, hypoxia was observed early after wounding. While reoxygenation occurred over time in db/+ mice, hypoxia was prolonged in the diabetic db/db model. This observation was consistent with impaired healing and microangiopathies observed using intravital microscopy. In conclusion, EPR oximetry using LiPc crystals as the oxygen sensor is an appropriate technique to follow wound oxygenation in acute and chronic wounds, in normal and diabetic animals. Nevertheless, the technique is limited for measurements in pedicled skin flaps and cannot be applied to excisional wounds in which diffusion of atmospheric oxygen significantly affects the measurements.

Field-stepped direct detection electron paramagnetic resonance

The widest scan that had been demonstrated previously for rapid scan EPR was a 155G sinusoidal scan. As the scan width increases, the voltage requirement across the resonating capacitor and scan coils increases dramatically and the background signal induced by the rapidly changing field increases. An alternate approach is needed to achieve wider scans. A field-stepped direct detection EPR method that is based on rapid-scan technology is now reported, and scan widths up to 6200G have been demonstrated. A linear scan frequency of 5.12kHz was generated with the scan driver described previously. The field was stepped at intervals of 0.01 to 1G, depending on the linewidths in the spectra. At each field data for triangular scans with widths up to 11.5G were acquired. Data from the triangular scans were combined by matching DC offsets for overlapping regions of successive scans. This approach has the following advantages relative to CW, several of which are similar to the advantages of rapid scan. (i) In CW if the modulation amplitude is too large, the signal is broadened. In direct detection field modulation is not used. (ii) In CW the small modulation amplitude detects only a small fraction of the signal amplitude. In direct detection each scan detects a larger fraction of the signal, which improves the signal-to-noise ratio. (iii) If the scan rate is fast enough to cause rapid scan oscillations, the slow scan spectrum can be recovered by deconvolution after the combination of segments. (iv) The data are acquired with quadrature detection, which permits phase correction in the post processing. (v) In the direct detection method the signal typically is oversampled in the field direction. The number of points to be averaged, thereby improving the signal-to-noise ratio, is determined in post processing based on the desired field resolution. A degased lithium phthalocyanine sample was used to demonstrate that the linear deconvolution procedure can be employed with field-stepped direct detection EPR signals. Field-stepped direct detection EPR spectra were obtained for Cu2+ doped in Ni(diethyldithiocarbamate)2, Cu2+ doped in Zn tetratolylporphyrin, perdeuterated tempone in sucrose octaacetate, vanadyl ion doped in a parasubstituted Zn tetratolylporphyrin, Mn2+ impurity in CaO, and an oriented crystal of Mn2+ doped in Mg(acetylacetonate)2(H2O)2.

Locations of radical species in black pepper seeds investigated by CW EPR and 9 GHz EPR imaging

In this study, noninvasive 9GHz electron paramagnetic resonance (EPR)-imaging and continuous wave (CW) EPR were used to investigate the locations of paramagnetic species in black pepper seeds without further irradiation. First, lithium phthalocyanine (LiPC) phantom was used to examine 9GHz EPR imaging capabilities. The 9GHz EPR-imager easily resolved the LiPC samples at a distance of ∼2mm. Then, commercially available black pepper seeds were measured. We observed signatures from three different radical species, which were assigned to stable organic radicals, Fe3+, and Mn2+ complexes. In addition, no EPR spectral change in the seed was observed after it was submerged in distilled H2O for 1h. The EPR and spectral–spatial EPR imaging results suggested that the three paramagnetic species were mostly located at the seed surface. Fewer radicals were found inside the seed. We demonstrated that the CW EPR and 9GHz EPR imaging were useful for the determination of the spatial distribution of paramagnetic species in various seeds.

EPR oximetry as a method for repetitive measurements of in vivo kidney tissue oxygenation (890.2)

Kidney tissue oxygenation is heterogeneous with oxygen levels normally being greater in the superficial cortex and lowest in the inner medulla. Decreased oxygenation in the kidney has been implied in the pathology of several diseases. However, there is currently no method available to repetitively monitor kidney oxygenation regionally using minimally invasive procedures. Therefore, we evaluated implantable lithium phthalocyanine (LiPc) probes, which closely correlate between EPR peak‐to‐peak line width and oxygen availability. LiPc probes were implanted in the cortex (left kidney) and medulla (right kidney) in the same mouse and EPR spectra were acquired using an L band scanner (1 GHz). Mice were measured repetitively over 45 days and during inhalation of air (21% oxygen) or an acute measurement of air and nitrogen mixture (10% oxygen). A 1 G/cm gradient was applied in order to separate the signals from the two probes. The signals were derived from 40 consecutive sweeps and a peak‐to‐peak line width comparison of the EPR spectra was used to convert the signal to an applicable oxygen tension in MATLAB. Cortical and medullary oxygenation was stable over the 45 day period (56±7 mmHg and 43±6 mmHg respectively). However, acute 10% oxygen inhalation significantly reduced oxygenation in both tissues (cortex 56±6 to 34±2 mmHg n=15 p&lt;0.05 and medulla 42±5 to 29±3 mmHg n=7 p&lt;0.05). In conclusion, EPR oximetry using LiPc probes implanted in discrete kidney structures can be used to repetitively measure regional tissue oxygenation. This minimally invasive method is particularly well suited for conditions of reduced tissue oxygenation since this increases the signal intensity which enables the quantification of the EPR signal to absolute oxygenation values.

Real-time monitoring of ischemic and contralateral brain pO2 during stroke by variable length multisite resonators

PurposeElectron paramagnetic resonance (EPR) oximetry using variable length multi-probe implantable resonator (IR), was used to investigate the temporal changes in the ischemic and contralateral brain pO2 during stroke in rats. Material and methodsThe EPR signal to noise ratio (S/N) of the IR with four sensor loops at a depth of up to 11 mm were compared with direct implantation of lithium phthalocyanine (LiPc, oximetry probe) deposits in vitro. These IRs were used to follow the temporal changes in pO2 at two sites in each hemisphere during ischemia induced by left middle cerebral artery occlusion (MCAO) in rats breathing 30% O2 or 100% O2. ResultsThe S/N ratios of the IRs were significantly greater than the LiPc deposits. A similar pO2 at two sites in each hemisphere prior to the onset of ischemia was observed in rats breathing 30% O2. However, a significant decline in the pO2 of the left cortex and striatum occurred during ischemia, but no change in the pO2 of the contralateral brain was observed. A significant increase in the pO2 of only the contralateral non-ischemic brain was observed in the rats breathing 100% O2. No significant difference in the infarct volume was evident between the animals breathing 30% O2 or 100% O2 during ischemia. ConclusionsEPR oximetry with IRs can repeatedly assess temporal changes in the brain pO2 at four sites simultaneously during stroke. This oximetry approach can be used to test and develop interventions to rescue ischemic tissue by modulating cerebral pO2 during stroke.

Skeletal muscle and glioma oxygenation by carbogen inhalation in rats: a longitudinal study by EPR oximetry using single-probe implantable oxygen sensors.

The feasibility of EPR oximetry using a single-probe implantable oxygen sensor (ImOS) was tested for repeated measurement of pO₂ in skeletal muscle and ectopic 9L tumors in rats. The ImOS (50 mm length) were constructed using nickel-chromium alloy wires, with lithium phthalocyanine (LiPc, oximetry probe) crystals loaded in the sensor loop and coated with AF 2400(®) Teflon. These ImOS were implanted into the skeletal muscle in the thigh and subcutaneous 9L tumors. Dynamic changes in tissue pO₂ were assessed by EPR oximetry at baseline, during tumor growth, and repeated hyperoxygenation with carbogen breathing. The mean skeletal muscle pO₂ of normal rats was stable and significantly increased during carbogen inhalation in experiments repeated for 12 weeks. The 9L tumors were hypoxic with a tissue pO₂ of 12.8 ± 6.4 mmHg on day 1; however, the response to carbogen inhalation varied among the animals. A significant increase in the glioma pO₂ was observed during carbogen inhalation on day 9 and day 14 only. In summary, EPR oximetry with ImOS allowed direct and longitudinal oxygen measurements in deep muscle tissue and tumors. The heterogeneity of 9L tumors in response to carbogen highlights the need to repeatedly monitor pO₂ to confirm tumor oxygenation so that such changes can be taken into account in planning therapies and interpreting results.

Recurrent low-dose chemotherapy to inhibit and oxygenate head and neck tumors.

A lack of strategy to counteract hypoxia (pO₂ < 10-15 mmHg) and technique to repeatedly measure tumor pO₂ has restricted therapeutic optimization. We report the results obtained with an innovative anti-angiogenic strategy of recurrent low-dose (metronomic) chemotherapy to modulate hypoxia and growth of the Head and Neck tumor xenografts.The FaDu tumors were established in the flank of immune deficient mice and EPR oximetry with lithium phthalocyanine crystals was used to follow the temporal changes in tumor pO₂ on treatment with gemcitabine including controls for three weeks. The FaDu tumors were hypoxic with a baseline (pre-treatment) pO₂ of 2-8 mmHg. A transient increase in the tumor pO₂ was evident on day 3 on treatment with a conventional schedule of gemcitabine (150 mg/kg, d1, d8, d15). No significant change in the tumor pO₂ on treatment with metronomic gemcitabine (25 mg/kg on d1, d3, d5 for 3 weeks) was observed. However, tumor pO₂ increased significantly on d15-d18 during treatment with a metronomic schedule of 15 mg/kg gemcitabine (d1, d3, d5 for 3 weeks). A modest decrease in the tumor growth was evident on treatment with conventional gemcitabine. Notably, tumor growth was significantly inhibited by metronomic (25 and 15 mg/kg) gemcitabine treatment. The immunohistochemistry (IHC) analyses of the tumor samples indicate a decrease in HIF-1α and TSP-1 on treatment with metronomic gemcitabine.In conclusion, a significant inhibition of tumor growth on treatment with metronomic gemcitabine was observed; however, the increase in pO₂ was dose dependent. EPR oximetry can be used to follow the temporal changes in tumor pO₂ to identify a therapeutic window on treatment with metronomic chemotherapy for potential combination with radiotherapy.

P-orbital nanomagnetism in an organic chain magnet

A long-standing challenge in spintronics is the development of a stable, processable and tunable organic magnetic semiconductor. We reveal, through first-principles calculations, that a $p$-electron organic molecular magnet, lithium phthalocyanine (LiPc), can display surprisingly strong antiferromagnetic coupling. The strong coupling, far exceeding that observed in the widely studied transition-metal phthalocyanines, is found to be due to the delocalized spin orbital of the ligand which facilitates intermolecular interactions. The enhanced hopping between the $\ensuremath{\pi}$-conjugated orbitals is also responsible for the wide bandwidth required for high spin mobility. The interactions are a strong function of the intermolecular arrangement and increase when approaching a face-on geometry resulting in a crossover to an itinerant spin density wave ground state, which we propose as an explanation for the unusual spin susceptibility in the related $x$-LiPc phase [M. Brinkmann et al., J. Mater. Chem. 8, 675 (1998)]. This strong coupling, in conjunction with the structural flexibility of the metal phthalocyanine organic semiconductors, suggests a promising route for the fabrication of transition-metal-free, room-temperature, chain magnets for spintronic applications.

Influences of dispersion and long‐range corrections on molecular structures of three types of lithium phthalocyanine dimer

AbstractWe report here the results from theoretical calculations of the potential energy curves for three dimers of lithium phthalocyanine (LiPc) using nine types of functionals: the M06‐2x, M06L, B97D, ωB97, ωB97X, ωB97XD, CAM‐B3LYP, LC‐ωPBE, and LC‐BLYP. The results were discussed in comparison with those obtained for the dimers of magnesium phthalocyanine (MgPc). The dispersive and long‐range interactions were considered in part by using these functionals. The mechanism whereby the dispersive and long‐range interactions affect the geometric structures of the LiPc and MgPc dimers is discussed. The calculated results provide insight into the computational methods for both open‐ and closed‐shell metal phthalocyanine (MPc) dimers: Although it is difficult for the CAM‐B3LYP, LC‐ωPBE, and LC‐BLYP functionals only with the long‐range corrections to evaluate weak dispersion interactions appropriately, the M06‐families, ωB97‐families, and B97D functionals can estimate a weak dispersion interaction well in both open‐ and closed‐shell MPc dimers. However, the results should be used with caution against overestimation of the relative stabilities for the results of functionals considering despersion correction. © 2012 Wiley Periodicals, Inc.

Theoretical and experimental study on the excited states of the X-, α- and β-forms of lithium phthalocyanine

The electronic structures and absorption spectra for three different types (X, α and β) of model dimers of lithium phthalocyanine (LiPc) were investigated by the density functional theory (DFT) and compared with a LiPc monomer. We quantitatively investigated the excited states of the three LiPc dimers using time-dependent DFT calculations. The differences and similarities of the observed absorption spectra in the solution and the polymorphic solids of LiPc were clearly interpreted by the calculated excited states of the monomer and dimers. The calculated results for the dimers presumed that the X-form showed a different electronic spectral pattern from the monomer and the other two forms, whereas the α- and β-forms presented similar electronic absorption profiles to each other and to the monomer. The calculated excited states also explained the differences in absorption profiles between LiPc and typical phthalocyanine compounds. These characteristic features of LiPc would be closely related to its molecular orbitals, especially those which originated from the singly occupied molecular orbital (SOMO) of the LiPc monomer. It was shown that the next highest occupied π-type orbital to the SOMO of the monomer reduced the energy of the low-lying excited states, which corresponded to the Q- and B-bands of the dimers.

ESR Microscopy for Biological and Biomedical Applications

We report on electron-spin resonance microscopy (ESRM) providing sub-micron resolution (~700nm) with a high spin concentration sample, i.e. lithium phthalocyanine (LiPc) crystal. For biomedical applications of our ESRM, we have imaged samples containing rat basophilic leukemia (RBL) cells as well as cancerous tissue samples with a resolution of several microns using a water soluble spin probe, Trityl_OX063_d24. Phantom samples with the nitroxide spin label, (15)N PDT, were also imaged to demonstrate that nitroxides, which are commonly used as spin labels, may also be used for ESRM applications. ESRM tissue imaging would therefore be valuable for diagnostic or therapeutic purposes. Also, ESRM can be used to study the motility or the metabolism of cells in various environments. With further modification and/or improvement of imaging probe and spectrometer instrumentation sub-micron biological images should be obtainable, thereby providing a useful tool for various biomedical applications.

Theoretical study on the molecular structures of X‐, α‐, and β‐types of lithium phthalocyanine dimer

We report here the results from theoretical calculations of the potential energy curves, the geometry optimizations, and the electronic structures for three dimers of lithium phthalocyanine (LiPc) by using three types of functional systems: PBE1PBE, B3LYP, and M06. The results were discussed in comparison with those obtained for the dimers of magnesium phthalocyanine (MgPc). The long-range dispersive interactions were considered in part using these functional systems in the increasing order of PBE1PBE, B3LYP, and M06. The mechanism whereby the dispersive interactions affect the geometric and electronic structures of the LiPc and MgPc dimers is discussed. The calculated results provide insight into the computational methods for both open- and closed-shell metal phthalocyanine (MPc) dimers: Although the PBE1PBE and B3LYP functional systems cannot evaluate a weak dispersion interaction appropriately, the M06 functional can estimate a weak dispersion interaction well in both open- and closed-shell MPc dimers. Basis set superposition error (BSSE) corrections play an important role for the quantitative analysis; however, the calculation results without BSSE corrections may be sufficient for the qualitative discussion on the properties of these dimers such as geometries, stabilities, electronic structures, and so on.

Synthesis of composite microgel capsules by ultrasonic spray combined with in situ crosslinking

Composite microgel capsules were fabricated through an ultrasonic spray accompanied by in situ surface crosslinking between glycol chitosan (GC) and benzaldehyde capped poly(ethylene glycol) (OHC–PEG–CHO) in the nebulized droplets. The methodology enables a selective one-pot encapsulation for different functional species inside the interior cavity or within the shell. Herein lithium phthalocyanine (LiPc) microcrystals and citrate stabilized iron oxide (Fe3O4) nanoparticles were selected as model materials for the functionalization, which led to the electron paramagnetic resonance (EPR) and superparamagnetic dual performance of the composite microgel capsules. This shows the potential of the microgel capsules in diagnosis and targeting delivery applications.

Improvement of power conversion efficiency of phthalocyanine/C60 heterojunction solar cells by inserting a lithium phthalocyanine layer at the indium-tin oxide/phthalocyanine interface

Improvement of power conversion efficiency of a zinc phthalocyanine (ZnPc)/C60 heterojunction solar cell was achieved by inserting a lithium phthalocyanine (LiPc) layer at the indium-tin oxide (ITO)/ZnPc interface. The results of photoelectron spectroscopy suggest that the barrier height for the hole transport at the ITO/ZnPc interface is reduced by the LiPc layer. A similar improvement of the power conversion efficiency by the insertion of a LiPc layer was also observed in M-phthalocyanine (M=H2, Cu, and TiO)/C60 cells.

Deconvolution of sinusoidal rapid EPR scans

In rapid scan EPR the magnetic field is scanned through the signal in a time that is short relative to electron spin relaxation times. Previously it was shown that the slow-scan lineshape could be recovered from triangular rapid scans by Fourier deconvolution. In this paper a general Fourier deconvolution method is described and demonstrated to recover the slow-scan lineshape from sinusoidal rapid scans. Since an analytical expression for the Fourier transform of the driving function for a sinusoidal scan was not readily apparent, a numerical method was developed to do the deconvolution. The slow scan EPR lineshapes recovered from rapid triangular and sinusoidal scans are in excellent agreement for lithium phthalocyanine, a trityl radical, and the nitroxyl radical, tempone. The availability of a method to deconvolute sinusoidal rapid scans makes it possible to scan faster than is feasible for triangular scans because of hardware limitations on triangular scans.

ChemInform Abstract: Effect of Oxygen on Phthalocyanine Radicals. Part 1. ESR Study of Lithium Phthalocyanine Spin Species at Different Oxygen Concentrations

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