Protoporphyrine IX | EPFL Graph Search

Protoporphyrin IX is an organic compound, classified as a porphyrin, that plays an important role in living organisms as a precursor to other critical compounds like heme (hemoglobin) and chlorophyll. It is a deeply colored solid that is not soluble in water. The name is often abbreviated as PPIX. Protoporphyrin IX contains a porphine core, a tetrapyrrole macrocycle with a marked aromatic character. Protoporphyrin IX is essentially planar, except for the N-H bonds that are bent out of the plane of the rings, in opposite (trans) directions. The general term protoporphyrin refers to porphine derivatives that have the outer hydrogen atoms in the four pyrrole rings replaced by other functional groups. The prefix proto often means 'first' in science nomenclature (such as carbon protoxide), hence Hans Fischer is thought to have coined the name protoporphyrin as the first class of porphyrins. Fischer described iron-deprived heme becoming the "proto-" porphyrin, particularly in reference to Hugo Kammerer's porphyrin. In modern times, 'proto-' specifies a porphyrin species bearing methyl, vinyl, and carboxyethyl/propionate side groups. Fischer also generated the Roman numeral naming system which includes 15 protoporphyrin analogs, the naming system is not systematic however. An alternative name for heme is iron protoporphyrin IX (iron PPIX). PPIX contains four methyl groups (M), two vinyl groups (V), and two propionic acid groups (P). The suffix "IX" indicates that these chains occur in the circular order MV-MV-MP-PM around the outer cycle at the following respective positions: c2,c3-c7,c8-c12,c13-c17,c18. The methine bridges of PPIX are named alpha (c5), beta (c10), gamma (c15), and delta (c20). In the context of heme, metabolic biotransformation by heme oxygenase results in the selective opening of the alpha-methine bridge to form biliverdin/bilirubin. In this case, the resulting bilin carries the suffix IXα which indicates the parent molecule was protoporphyrin IX cleaved at the alpha position.

Stimulation and homogenization of the protoporphyrin IX endogenous production by photobiomodulation to increase the potency of photodynamic therapy

Georges Wagnières, Jaroslava Joniová, Emmanuel Louis Arthur Gerelli, Cyrus Kazemiraad

Protoporphyrin IX (PpIX) is produced in the mitochondria and used as fluorescent contrast agent or photosensitizer after exogenous 5-aminolevulinic acid (ALA) delivery in cancer photodynamic detection and therapy (PDT). Although routinely used in the clinics, the stimulated production of PpIX is often insufficient and/or heterogeneous within the lesions, thereby limiting the PDT performances. Since photobiomodulation, which is based on the illumination of the tissues with sub-thermal radiometric conditions in the red or near-infrared, is known to stimulate the cell metabolism, we have optimized these conditions in vitro. Some of them lead to the homogenization and strong stimulation of the PpIX endogenous production. Interestingly, combined sequentially, PBM enhanced significantly the potency of PpIX-based PDT in vitro and in vivo in tumors grown on the chicken embryo chorioallantoic membrane. These results are in excellent agreement with other assays based on measurements of the cell survival/death, the production of reactive oxygen species, including singlet oxygen, and the mitochondrial membrane potential.

ELSEVIER SCIENCE SA2021

A general framework for non-exponential delayed fluorescence and phosphorescence decay analysis, illustrated on Protoporphyrin IX

Georges Wagnières, Jaroslava Joniová, Emmanuel Louis Arthur Gerelli, Aurelien Stephen Arnaud Gregor

Delayed fluorescence (DF) is a long-lived luminescence process used in a variety of applications ranging from oxygen sensing in biological tissues to organic Light Emitting Diodes. In common cases, DF results from the deexcitation of the first excited triplet state via the first excited singlet state of the chromophore, which produces a mono-exponential light signal whose amplitude and lifetime give an insight into the probed environment. However, non-linear de-excitation reactions such as triplet-triplet annihilation, which can cause decays to lose their mono-exponential nature, are often neglected. In this work, we derive a global framework to properly interpret decays resulting from a combination of linear and non-linear de-excitation processes. We show why the standard method of using multi-exponential models when decays are not mono-exponential is not always relevant, nor accurate. First, we explain why the triplet de-excitation and light production processes should be analyzed individually: we introduce novel concepts to precisely describe these two processes, namely the deactivation pathway - the reaction which mainly contributes to the triplet state de-excitation - and the measurement pathway - the reaction which is responsible for light production. We derive explicit fitting functions which allow the experimenter to estimate the reaction rates and excited state concentrations in the system. To validate our formalism, we analyze the in vitro Transient Triplet Absorption and DF of Protoporphyrin IX, a well-known biological aromatic molecule used in photodynamic therapy, cancer photodetection and oxygen sensing, which produces DF through various mechanisms depending on concentration and excitation intensity. We also identify the precise assumptions necessary to conclude that triplet-triplet annihilation DF should follow a monoexponential decay with a lifetime of half the triplet state lifetime. Finally, we describe why the commonly used definitions of triplet / DF lifetime are ill-defined in the case where second-order reactions contribute to the deactivation process, and why the fitting of precise mixed-orders DF kinetics should be preferred in this case. This work could allow the correct interpretation of various long-lived luminescence processes and facilitate their understanding.

2020

Catechin reduces phototoxic effects induced by protoporphyrin IX-based photodynamic therapy in the chick embryo chorioallantoic membrane

Georges Wagnières, Jaroslava Joniová

Significance: Side effects of many cancer treatments are associated with the production of reactive oxygen species (ROS) in normal tissues. This explains why patients treated by photodynamic therapy (PDT) often suffer from skin photosensitization, whereas those subject to radiotherapies frequently experience damages in various organs, including the skin. Aim: Catechin, which belongs to the natural flavanols family, is well known for its antioxidant properties. Hence, our main objective was to investigate whether catechin can reduce damages induced by PDT using protoporphyrin IX (PpIX-PDT), an endogenous photosensitizer commonly used in dermatology. Approach: An in vivo model, the chick embryo chorioallantoic membrane (CAM), was used for this study. An amount of 20 mu l of a solution containing 5-aminolevulinic acid, a natural precursor of PpIX, was applied topically on the CAM 4 h before PDTs (405 nm, 2.9 mW/cm(2), 1.2 J/cm(2)). Catechin was applied at different concentrations (1 to 50 mu M) and times (0 to 240 min) before PDT. In addition, we assessed the potency of catechin to reduce the PpIX fluorescence photobleaching induced by PDT. Results: We observed that catechin significantly reduces the vascular damages generated by PpIX-PDT. Moreover, we have shown that catechin inhibits PpIX photobleaching. Conclusions: These observations suggest that catechin significantly reduces the level of ROS produced by PpIX-PDT. (C) The Authors. Published by SPIE under a Creative Commons Attribution 4.0 Unported License.

SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS2020

A general framework for non-exponential delayed fluorescence and phosphorescence decay analysis, illustrated on Protoporphyrin IX

Georges Wagnières, Jaroslava Joniová, Emmanuel Louis Arthur Gerelli, Aurelien Stephen Arnaud Gregor

2020