Lithium Naphthalocyanine Research Articles

Oxygen-Sensing Paramagnetic Probes for Clinical Oximetry.

Electron paramagnetic resonance (EPR) oximetry based on lithium naphthalocyanine paramagnetic crystals as oxygen sensors enables direct measurement of the partial pressure of oxygen (pO2) in tissues. The method uses topical or implantable forms of these oxygen-sensing crystals embedded in a biocompatible siloxane elastomer. This article presents a summary of these sensors for EPR oximetry and their applicability for tissue oxygen measurement in the clinic.

A New Tetragonal Crystalline Polymorph of Lithium Octa-n-Butoxy-Naphthalocyanine (LiNc-BuO) Radical: Structural, Magnetic and Oxygen-Sensing Properties

The single-crystal structure, paramagnetic, and oxygen-sensing characteristics of a new tetragonal polymorph of lithium octa-n-butoxynaphthalocyanine, LiNc-BuO (Tg), is reported. The compound was synthesized as fine, diamond-shaped, neutral radicalcrystalsby reacting octa-n-butoxynaphthalocyanine (Nc-BuO) with lithium metal in n-butanol. Single-crystal X-ray diffraction analysis revealed a saddle-shaped conformation of the molecule with a crystallographic 2-fold rotation axis in a tetragonal unit cell. This represents the first single-crystal, structurally characterized, lithium naphthalocyanine complex. Unlike the triclinic polymorph of LiNc-BuO (Pandian, et al. J. Mater. Chem.2006,16,3609),the tetragonal(Tg)formof LiNc-BuOdid notshowthepresence oflargeopen channels in the crystalline packing. The magnetic susceptibility and EPR spectroscopic properties were in agreement with the X-ray crystal structure showing the existence of a high degree of spin exchange in the crystalline system. The effective magnetic moment calculated for the LiNc-BuO (Tg) was 1.56 μB per formula unit, which was smaller than the expected value of 1.73 μB for a spin system with S = 1/2. The crystals showed a single, sharp EPR spectrum with an unusually low line width of 20(5mGunderanoxicconditions.TheEPRlinewidthwaslinearlydependentonpartialpressureof oxygen(pO2)intherange0-760mmHg,withasensitivityof4.54(0.50mG/mmHg.TheLiNc-BuO (Tg) crystals possess several desirable properties for use as a probe for EPR oximetry.

A paramagnetic implant containing lithium naphthalocyanine microcrystals for high-resolution biological oximetry

Lithium naphthalocyanine (LiNc) is a microcrystalline EPR oximetry probe with high sensitivity to oxygen [R.P. Pandian, M. Dolgos, C. Marginean, P.M. Woodward, P.C. Hammel, P.T. Manoharan, P. Kuppusamy, Molecular packing and magnetic properties of lithium naphthalocyanine crystal: hollow channels enabling permeability and paramagnetic sensitivity to molecular oxygen J. Mater. Chem. 19 (2009) 4138–4147]. However, direct implantation of the crystals in the tissue for in vivo oxygen measurements may be hindered by concerns associated with their direct contact with the tissue/cells and loss of EPR signal due to particle migration in the tissue. In order to address these concerns, we have developed encapsulations (chips) of LiNc microcrystals in polydimethyl siloxane (PDMS), an oxygen-permeable, bioinert polymer. Oximetry evaluation of the fabricated chips revealed that the oxygen sensitivity of the crystals was unaffected by encapsulation in PDMS. Chips were stable against sterilization procedures or treatment with common biological oxidoreductants. In vivo oxygen measurements established the ability of the chips to provide reliable and repeated measurements of tissue oxygenation. This study establishes PDMS-encapsulated LiNc as a potential probe for long-term and repeated measurements of tissue oxygenation.

Development of polymer-coated paramagnetic Implants for biomedical oximetry Applications

There are a variety of methods available for measuring and mapping of oxygen concentration in biological tissues. The particulate-based, electron paramagnetic resonance (EPR) oximetry is a powerful technology that allows non-invasive and repetitive monitoring of oxygenation in tissues. Lithium naphthalocyanine (LiNc) forms highly stable paramagnetic crystals which can be used for high resolution oximetry in tissues. To show efficient biocompatibility, long-term in vivo stability and responsiveness of LiNc oximetry probes, as well as for making the probes surgically implantable/ retrievable, we coated LiNc microcrystals with Teflon AF 2400 (TAF) polymeric materials. EPR linewidths of polymer-coated LiNc probes under anoxic conditions as well as at varying partial pressures of oxygen (pO2) did not show appreciable change relative to uncoated LiNc particulates, yet the linewidth of coated LiNc crystals was linearly dependent on varying pO2. The coated implantable probes responded to changes in pO2 quickly and reproducibly, enabling dynamic measurements of oxygenation in real time. The implants were unaffected by biological oxidoreductants. The oxygen sensitivity and stability of the coated LiNc was demonstrated in vivo in mice for more than two months. Thus, new TAF polymer-coated LiNc crystals are potential candidates for future in vivo studies including clinical trials for oxygen measurements in pathophysiological tissues.

Molecular packing and magnetic properties of lithium naphthalocyanine crystals: hollow channels enabling permeability and paramagnetic sensitivity to molecular oxygen.

The synthesis, structural framework, magnetic and oxygen-sensing properties of a lithium naphthalocyanine (LiNc) radical probe are presented. LiNc was synthesized in the form of a microcrystalline powder using a chemical method and characterized by electron paramagnetic resonance (EPR) spectroscopy, magnetic susceptibility, powder X-ray diffraction analysis, and mass spectrometry. X-Ray powder diffraction studies revealed a structural framework that possesses long, hollow channels running parallel to the packing direction. The channels measured approximately 5.0 × 5.4 Å(2) in the two-dimensional plane perpendicular to the length of the channel, enabling diffusion of oxygen molecules (2.9 × 3.9 Å(2)) through the channel. The powdered LiNc exhibited a single, sharp EPR line under anoxic conditions, with a peak-to-peak linewidth of 630 mG at room temperature. The linewidth was sensitive to surrounding molecular oxygen, showing a linear increase in pO(2) with an oxygen sensitivity of 31.2 mG per mmHg. The LiNc microcrystals can be further prepared as nano-sized crystals without the loss of its high oxygen-sensing properties. The thermal variation of the magnetic properties of LiNc, such as the EPR linewidth, EPR intensity and magnetic susceptibility revealed the existence of two different temperature regimes of magnetic coupling and hence differing columnar packing, both being one-dimensional antiferromagnetic chains but with differing magnitudes of exchange coupling constants. At a temperature of ∼50 K, LiNc crystals undergo a reversible phase transition. The high degree of oxygen-sensitivity of micro- and nano-sized crystals of LiNc, combined with excellent stability, should enable precise and accurate measurements of oxygen concentration in biological systems using EPR spectroscopy.

Lutetium Monophthalocyanine and Diphthalocyanine Complexes and Lithium Naphthalocyanine as Catalysts for Electrochemical CO 2 Reduction

Phthalocyanine and naphthalocyanine complexes with redox-inactive metals adsorbed on activated carbon supports were shown to be effective catalysts for electroreduction in the form of gas diffusion electrodes, yielding carbon monoxide with current efficiencies up to ca. 75%. A mechanism for electroreduction catalyzed by these complexes has been proposed in which the key step is the coordination of a molecule to the external N-atom of the phthalocyanine or naphthalocyanine ring. © 2003 The Electrochemical Society. All rights reserved.

Novel particulate spin probe for targeted determination of oxygen in cells and tissues

The synthesis and characterization of a new lithium octa-n-butoxy-substituted naphthalocyanine radical probe (LiNc-BuO) and its use in the determination of concentration of oxygen (oximetry) by electron paramagnetic resonance (EPR) spectroscopy are reported. The probe is synthesized as a needle-shaped microcrystalline particulate. The particulate shows a single-line EPR spectrum that is highly exchange-narrowed with a line-width of 210 mG. The EPR line-width is sensitive to molecular oxygen showing a linear relationship between the line-width and concentration of oxygen (pO(2)) with a sensitivity of 8.5 mG/mmHg. We studied a variety of physicochemical and biological properties of LiNc-BuO particulates to evaluate the suitability of the probe for in vivo oximetry. The probe is unaffected by biological oxidoreductants, stable in tissues for several months, and can be successfully internalized in cells. We used this probe to monitor changes in concentration of oxygen in the normal muscle and RIF-1 tumor tissue of mice as a function of tumor growth. The data showed a rapid decrease in the tumor pO(2) with increase of tumor volume. Human arterial smooth muscle cells, upon internalization of the LiNc-BuO probe, showed a marked oxygen gradient across the cell membrane. In summary, the newly synthesized octa-n-butoxy derivative of lithium naphthalocyanine has unique properties that are useful for determining oxygen concentration in chemical and biological systems by EPR spectroscopy and also for magnetic tagging of cells.

A naphthalocyanine-based EPR probe for localized measurements of tissue oxygenation

A new electron paramagnetic resonance (EPR) oximetry probe, based on a naphthalocyanine macrocycle, is reported to exhibit high oxygen sensitivity and favorable EPR characteristics for biological applications. The free radical probe, lithium naphthalocyanine (LiNc), is synthesized as fine microcrystalline powder with particle size less than 1 μm and high spin density. It exhibits a single sharp EPR peak, whose width varies linearly with oxygen partial pressure (pO 2). The EPR spectrum is nonsaturable at typical microwave power levels (< 25 mW at X-band). These unique characteristics make this probe ideal for measuring oxygen concentration in biological tissues, in vivo. The peak-to-peak width under anoxic conditions is 0.51 G (at X-band), and it increases linearly with increase in oxygen partial pressure and reaches 26.0 G for 100% oxygen (760 mmHg), showing an oxygen sensitivity of 34 mG/mmHg. The probe responds to changes in pO 2 quickly and reproducibly, thus enabling dynamic measurements of regional oxygenation in real time. The application of this probe for oximetry is demonstrated in an in vivo biological system. The changes in pO 2 were monitored in the leg muscle tissue of a living mouse breathing room air and carbogen (95% oxygen + 5% CO 2), alternatively. The mean pO 2 measured with this probe in muscle tissues was consistent with values reported previously using other methods. Overall, the probe shows very desirable characteristics for localized measurements of tissue oxygenation.

Lithium naphthalocyanine as a new molecular radical probe for electron paramagnetic resonance oximetry

A new lithium naphthalocyanine dye aggregate [Li 2Nc][LiNc] is reported as a potential electron paramagnetic resonance (EPR) oximetry probe for accurate measurement of oxygen concentration in biological systems. The Li 2Nc is diamagnetic; however, the LiNc molecule has an unpaired electron and hence is paramagnetic. The aggregate shows a strong and single line EPR signal that is non-saturating at normal EPR power levels. An oxygen-dependent peak-to-peak EPR spectral width ranging from 0.51 G (at pO 2: 0 mmHg) to 26.2 G (at pO 2: 760 mmHg) has been observed. The application of this probe has been demonstrated in the measurement of arterial and venous oxygen tensions in a rat.

Synthesis and Spectral Properties of Lithium Naphthalocyanine: A Novel EPR Oximetry Probe

Abstract A novel EPR oximetry probe, lithium naphthalocyanine (LiNc) dye has been sythesized successfully and has been characterized using UV–vis spectroscopy, X-ray diffraction and ESR techniques. X-ray diffraction pattern showed the crystalline nature of the synthesized powder and resembles that of typical naphthalocyanine. EPR measurements indicated a linear dynamic EPR line width ranging from 400 mG to 26 G with increasing oxygen concentration.

Electrosynthesis of a new molecular semiconductor: lithium naphthalocyanine radical

An electrochemical procedure is used to reduce 2,3-dicyanonaphthalene into the lithium naphthalocyanine radical (NPcLi·): a new material with semiconducting properties.