The synthesis and application of porphyrins has seen a huge shift towards research in porphyrin bio-molecular based systems in the past decade. The preferential localization of porphyrins in tumors, as well as their ability to generate reactive singlet oxygen and low dark toxicities has resulted in their use in therapeutic applications such as photodynamic therapy. However, their inherent lack of bio-distribution due to water insolubility has shifted research into porphyrin-nanomaterial conjugated systems to address this challenge. This has broadened their bio-applications, viz. bio-sensors, fluorescence tracking, in vivo magnetic resonance imaging (MRI), and positron emission tomography (PET)/CT imaging to photo-immuno-therapy just to highlight a few. This paper reviews the unique theranostic role of porphyrins in disease diagnosis and therapy. The review highlights porphyrin conjugated systems and their applications. The review ends by bringing current challenges and future perspectives of porphyrin based conjugated systems and their respective applications into light.

https://www.mdpi.com/1420-3049/24/14/2669/pdf

Porphyrin as Diagnostic and Therapeutic Agent.

As nanomedicine-based clinical strategies have continued to develop, the possibility of combining chemotherapy and singlet oxygen-dependent photodynamic therapy (PDT) to treat pancreatic cancer (PaC) has emerged as a viable therapeutic modality. The efficacy of such an approach, however, is likely to be constrained by the mechanisms of drug release and tumor oxygen levels. In the present study, we developed an Fe(III)-complexed porous coordination network (PCN) which we then used to encapsulate PTX (PCN-Fe(III)-PTX) nanoparticles (NPs) in order to treat PaC via a combination of chemotherapy and PDT. The resultant NPs were able to release drug in response to both laser irradiation and pH changes to promote drug accumulation within tumors. Furthermore, through a Fe(III)-based Fenton-like reaction these NPs were able to convert H2O2 in the tumor site to O2, thereby regulating local hypoxic conditions and enhancing the efficacy of PDT approaches. Also these NPs were suitable for use as a T1-MRI weighted contrast agent, making them viable for monitoring therapeutic efficacy upon treatment. Our results in both cell line and animal models of PaC suggest that these NPs represent an ideal agent for mediating effective MRI-guided chemotherapy-PDT, giving them great promise for the clinical treatment of PaC.

PCN-Fe(III)-PTX nanoparticles for MRI guided high efficiency chemo-photodynamic therapy in pancreatic cancer through alleviating tumor hypoxia

https://hal.archives-ouvertes.fr/hal-02358923/document

Metal-based redox-responsive MRI contrast agents

The preparation of covalently linked manganese(III) meso-tetrakis(2,6-dichlorophenyl)porphyrin acetate to aminopropyl functionalized silica gel and its full characterization by standard spectroscopic methods including Fourier transform infrared spectroscopy (FTIR), thermogravimetry (TG) and scanning electronic microscopy (SEM) is described. The supported metalloporphyrin was evaluated as catalyst in the degradation of trimethoprim (TMP), using hydrogen peroxide as green oxidant. Catalyst was reused for five consecutive cycles without significant loss of activity or catalyst degradation/leaching. Degradation products were identified by UHPLC-MS, allowing to propose a plausible degradation pathway. Furthermore, ecotoxicity (EC50 and EC20) of TMP-based solutions (before and after degradation) were evaluated towards the bacterium V. fischeri, the microalgae R. subcapitata and the invertebrate B. calyciflorus.

Supported metalloporphyrins as reusable catalysts for the degradation of antibiotics: Synthesis, characterization, activity and ecotoxicity studies

Sustainable and efficient electrosynthesis of naproxen using carbon dioxide and ionic liquids

For the development of redox responsive MRI probes based on the MnIII/MnII couple, stable complexation of both reduced and oxidized forms of the metal ion and appropriate tuning of the redox potential in the biologically relevant range are key elements. The water soluble fluorinated Mn-porphyrin derivative Mn-3 satisfies both requirements. In aqueous solutions, it can reversibly switch between MnIII/MnII oxidation states. In the presence of ascorbic acid or β-mercaptoethanol, the MnIII form undergoes reduction, which is slowly but fully reversed in the presence of air oxygen. A UV-Vis kinetic study of MnIII/MnII reduction under oxygen-free conditions yielded second-order rate constants, k2, of 46.1 M−1 s−1 and 13.8 M−1 s−1 for the reaction with ascorbic acid and β-mercaptoethanol, respectively. This could correspond, in the absence of oxygen, to a half-life of a few minutes in blood plasma and a few seconds in circulating immune cells where ascorbic acid reaches 20–40 μM and a few mM concentrations, respectively. In contrast to expectations based on the redox potential, reduction with glutathione or cysteine does not occur. It is prevented by the coordination of the glutathione carboxylate group(s) to MnIII in the axial position, as was evidenced by NMR data. Therefore, MnIII-3 acts as an ascorbate specific turn-on MRI probe, which in turn can be re-oxidized by oxygen. The relaxivity increase from the oxidized to the reduced form is considerably improved at medium frequencies (up to 80 MHz) with respect to the previously studied Mn-TPPS4 analogues; at 20 MHz, it amounts to 150%. No in vitro cytotoxicity is detectable for Mn-3 in the typical MRI concentration range. Finally, 19F NMR resonances of MnIII-3 are relatively sharp which could open further opportunities to exploit such complexes as paramagnetic 19F NMR probes.

/pdf/a-biocompatible-redox-mri-probe-based-on-a-mn-ii-mn-iii-xh6qsx6fsg.pdf

A biocompatible redox MRI probe based on a Mn( ii )/Mn( iii ) porphyrin

Electrochemically promoted arylation of iodoaromatics

The dianions formed by the electroreduction of Z-O2NC6H4CHCHC6H4NO2, E-O2NC6H4CHCHC6H4NO2, O2NC6H4CH2–CH2C6H4NO2 or O2NC6H4CMeH–CMeHC6H4NO2, as well as the anion radical arising from 4-nitrotoluene, are stable, in the time scale of cyclic voltammetry (DMF + 0.10 M NBu4BF4). However, in the electrolysis time scale (from minutes to hours), only the dianion O2NC6H4CMeH–CMeHC6H4NO22− remains stable, since the reduced species, Z-O2NC6H4CHCHC6H4NO22−, O2NC6H4CH2–CH2C6H4NO22− or O2NC6H4Me˙−, evolve to form the E-O2NC6H4CHCHC6H4NO22− dianion. This intermediate is recovered as the neutral species E-O2NC6H4CHCHC6H4NO2 with concomitant water reduction after the work-up with water, as demonstrated by combined electrolysis, cyclic voltammetry experiments, UV-spectroelectrochochemistry and theoretical calculations. Bulk electrolysis under optimized conditions (ACN + 0.10 M NBu4BF4) provides 40% and 67% isolated yields of E-4,4′-dinitrostilbene from 4-nitrotoluene and 4,4′-dinitrobibenzyl, respectively.

Sergio Soler

Papers

A biocompatible redox MRI probe based on a Mn( ii )/Mn( iii ) porphyrin

Electrochemically promoted arylation of iodoaromatics

From 4-nitrotoluene and 4,4′-dinitrobibenzyl to E-4,4′-dinitrostilbene: an electrochemical approach