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Angewandte Chemie (International Ed. in... Mar 2021Porphyrins and porphyrin derivatives have been widely explored for various applications owing to their excellent photophysical and electrochemical properties. However,... (Review)
Review
Porphyrins and porphyrin derivatives have been widely explored for various applications owing to their excellent photophysical and electrochemical properties. However, inherent shortcomings, such as instability and self-quenching under physiological conditions, limit their biomedical applications. In recent years, metal-organic frameworks (MOFs) have received increasing attention. The construction of porphyrin-based MOFs by introducing porphyrin molecules into MOFs or using porphyrins as organic linkers to form MOFs can combine the unique features of porphyrins and MOFs as well as overcome the limitations of porphyrins. This Review summarizes important synthesis strategies for porphyrin-based MOFs including porphyrin@MOFs, porphyrinic MOFs, and composite porphyrinic MOFs, and highlights recent achievements and progress in the development of porphyrin-based MOFs for biomedical applications in tumor therapy and biosensing. Finally, the challenges and prospects presented by this class of emerging materials for biomedical applications are discussed.
Topics: Animals; Biosensing Techniques; Drug Carriers; Humans; Immunotherapy; Metal-Organic Frameworks; Neoplasms; Photochemotherapy; Photosensitizing Agents; Photothermal Therapy; Porphyrins
PubMed: 31989749
DOI: 10.1002/anie.201909880 -
Anais Da Academia Brasileira de Ciencias 2018This review has two parts. The first one gives an approach to interdisciplinary studies against cancer carried out by many scientists using porphyrin-type substrates as... (Review)
Review
This review has two parts. The first one gives an approach to interdisciplinary studies against cancer carried out by many scientists using porphyrin-type substrates as photosensitizers in PDT. Intensive studies were performed for almost six decades. The successes really started in 1993 with the first formulation patented under the trade name Photofrin, which was immediately approved in several countries to treat certain types of cancer. Photofrin is still used although certain negative features soon became well known. That has motivated the search for better new photosensitizers. Several ones were developed, evaluated and a few of them had clinical approval. This group includes porphyrin derivatives and pro-drugs (aminolevulinic acid and its alkyl esters). Oncological, dermatological and ophthalmic applications are now taking place for the benefit of mankind. The second part of this review is related with the work carried out in Aveiro at the authors University on the synthesis and biological evaluation of several potential PDT photosensitizers. Not only new synthetic methodologies mainly for porphyrins and chlorins were developed but also other related macrocycles of the phthalocyanine and corrole types have entered in the same "pipeline". In vivo and in vitro biological evaluations also took place under interdisciplinary studies.
Topics: Humans; Neoplasms; Photochemotherapy; Photosensitizing Agents; Porphyrins
PubMed: 29873666
DOI: 10.1590/0001-3765201820170811 -
Genome Biology Dec 2022G-quadruplexes (G4s) are unique noncanonical nucleic acid secondary structures, which have been proposed to physically interact with transcription factors and chromatin...
BACKGROUND
G-quadruplexes (G4s) are unique noncanonical nucleic acid secondary structures, which have been proposed to physically interact with transcription factors and chromatin remodelers to regulate cell type-specific transcriptome and shape chromatin landscapes.
RESULTS
Based on the direct interaction between G4 and natural porphyrins, we establish genome-wide approaches to profile where the iron-liganded porphyrin hemin can bind in the chromatin. Hemin promotes genome-wide G4 formation, impairs transcription initiation, and alters chromatin landscapes, including decreased H3K27ac and H3K4me3 modifications at promoters. Interestingly, G4 status is not involved in the canonical hemin-BACH1-NRF2-mediated enhancer activation process, highlighting an unprecedented G4-dependent mechanism for metabolic regulation of transcription. Furthermore, hemin treatment induces specific gene expression profiles in hepatocytes, underscoring the in vivo potential for metabolic control of gene transcription by porphyrins.
CONCLUSIONS
These studies demonstrate that G4 functions as a sensor for natural porphyrin metabolites in cells, revealing a G4-dependent mechanism for metabolic regulation of gene transcription and chromatin landscapes, which will deepen our knowledge of G4 biology and the contribution of cellular metabolites to gene regulation.
Topics: G-Quadruplexes; Chromatin; Hemin; Porphyrins; Transcription, Genetic
PubMed: 36522639
DOI: 10.1186/s13059-022-02830-8 -
Canadian Medical Association Journal Apr 1949
Topics: Animals; Porifera; Porphyrias; Porphyrins
PubMed: 18113865
DOI: No ID Found -
Journal of Liposome Research 2015Porphyrin-lipid nanovesicles (PLN) have been developed with intrinsic capabilities as activatable multimodal photonic contrast agents. Radiolabeling of PLN encapsulating...
Porphyrin-lipid nanovesicles (PLN) have been developed with intrinsic capabilities as activatable multimodal photonic contrast agents. Radiolabeling of PLN encapsulating drugs could eventually be able to provide quantitative in vivo information for diagnosing and treating diseases. In this study, we developed (99m)Tc-labeled porphyrin-lipid nanovesicles ((99m)Tc-PLN) as a cargo-encapsulated formulation without significant impact on liposome integrity and encapsulation stability. 50 mM calcein was encapsulated into PLN by probe sonication. The size of the PLN was about 150 nm. The PLN were then reacted with (99m)Tc using SnCl2 dissolved in 1 mM HCl as a reducing agent and incubated for 10 min at 22 °C. The radiolabeling efficiency and stability of (99m)Tc-PLN were evaluated by instant thin-layer chromatography and low-pressure liquid chromatography (LPLC). (99m)Tc labeling was successful with a >92% labeling efficiency. LPLC showed that the liposomal elution peaks of the porphyrin-lipid and the calcein overlapped with the radioactivity elution peak of (99m)Tc-labeled PLN. The (99m)Tc-labeling procedure did not change the size of PLN. Encapsulated calcein remained inert inside PLN. Thus, this work lays out a simple and effective radiolabeling method using SnCl2 in HCl in the preparation of (99m)Tc-PLN.
Topics: Lipids; Nanostructures; Porphyrins; Technetium
PubMed: 24963601
DOI: 10.3109/08982104.2014.932379 -
Cellular and Molecular Gastroenterology... 2019Genetic porphyrias comprise eight diseases caused by defects in the heme biosynthetic pathway that lead to accumulation of heme precursors. Consequences of porphyria... (Review)
Review
Genetic porphyrias comprise eight diseases caused by defects in the heme biosynthetic pathway that lead to accumulation of heme precursors. Consequences of porphyria include photosensitivity, liver damage and increased risk of hepatocellular carcinoma, and neurovisceral involvement, including seizures. Fluorescent porphyrins that include protoporphyrin-IX, uroporphyrin and coproporphyrin, are photo-reactive; they absorb light energy and are excited to high-energy singlet and triplet states. Decay of the porphyrin excited to ground state releases energy and generates singlet oxygen. Porphyrin-induced oxidative stress is thought to be the major mechanism of porphyrin-mediated tissue damage. Although this explains the acute photosensitivity in most porphyrias, light-induced porphyrin-mediated oxidative stress does not account for the effect of porphyrins on internal organs. Recent findings demonstrate the unique role of fluorescent porphyrins in causing subcellular compartment-selective protein aggregation. Porphyrin-mediated protein aggregation associates with nuclear deformation, cytoplasmic vacuole formation and endoplasmic reticulum dilation. Porphyrin-triggered proteotoxicity is compounded by inhibition of the proteasome due to aggregation of some of its subunits. The ensuing disruption in proteostasis also manifests in cell cycle arrest coupled with aggregation of cell proliferation-related proteins, including PCNA, cdk4 and cyclin B1. Porphyrins bind to native proteins and, in presence of light and oxygen, oxidize several amino acids, particularly methionine. Noncovalent interaction of oxidized proteins with porphyrins leads to formation of protein aggregates. In internal organs, particularly the liver, light-independent porphyrin-mediated protein aggregation occurs after secondary triggers of oxidative stress. Thus, porphyrin-induced protein aggregation provides a novel mechanism for external and internal tissue damage in porphyrias that involve fluorescent porphyrin accumulation.
Topics: Animals; Carcinoma, Hepatocellular; Dermatitis, Phototoxic; Heme; Humans; Liver; Liver Neoplasms; Mice; Oxidation-Reduction; Oxidative Stress; Photosensitivity Disorders; Porphyrias; Porphyrins; Protein Aggregates; Protoporphyrins; Uroporphyrins; Zebrafish
PubMed: 31233899
DOI: 10.1016/j.jcmgh.2019.06.006 -
Chemical Research in Toxicology Dec 2022-Methyl protoporphyrin IX (NmePPIX) is a derivative of protoporphyrin IX (PPIX) and the lattice of heme. Certain xenobiotics strongly induce NmePPIX production in the... (Review)
Review
-Methyl protoporphyrin IX (NmePPIX) is a derivative of protoporphyrin IX (PPIX) and the lattice of heme. Certain xenobiotics strongly induce NmePPIX production in the liver. The existence of endogenous NmePPIX in untreated animal liver has also been reported. The detailed mechanisms of NmePPIX biosynthesis remain unclear, but cytochrome P450 enzymes are thought to be critical in xenobiotic-induced NmePPIX production. High levels of NmePPIX cause PPIX accumulation because NmePPIX is a potent inhibitor ( = 7 nM) of ferrochelatase, the last enzyme in the heme biosynthesis pathway that converts PPIX to heme. NmePPIX is also involved in several other physiological processes, including inhibition of nitric oxide production and promotion of lamin aggregation. Compared to the two well-characterized porphyrins, PPIX and heme, NmePPIX is understudied regarding the mechanism of formation, fate, and physiological functions. This Review summarizes the current understanding of NmePPIX and provides perspectives on areas of future research on NmePPIX.
Topics: Animals; Porphyrins; Protoporphyrins; Ferrochelatase; Heme
PubMed: 36459538
DOI: 10.1021/acs.chemrestox.2c00214 -
Molecules (Basel, Switzerland) Dec 2022This study presents the spectral characterization of TiO nanoparticles (NPs) functionalized with three porphyrin derivatives: 5,10,15,20-(Tetra-4-aminophenyl) porphyrin...
This study presents the spectral characterization of TiO nanoparticles (NPs) functionalized with three porphyrin derivatives: 5,10,15,20-(Tetra-4-aminophenyl) porphyrin (TAPP), 5,10,15,20-(Tetra-4-methoxyphenyl) porphyrin (TMPP), and 5,10,15,20-(Tetra-4-carboxyphenyl) porphyrin (TCPP). UV-Vis absorption and Fourier transform infrared spectroscopy-attenuated total reflection (FTIR-ATR) spectroscopic studies of these porphyrins and their complexes with TiO NPs were performed. In addition, the efficiency of singlet oxygen generation, the key species in photodynamic therapy, was investigated. UV-Vis absorption spectra of the NPs complexes showed the characteristic bands of porphyrins. These allowed us to determine the loaded porphyrins on TiO NPs functionalized with porphyrins. FTIR-ATR revealed the formation of porphyrin-TiO complexes, suggesting that porphyrin adsorption on TiO may involve the pyrroles in the porphyrin ring, or the radicals of the porphyrin derivative. The quantum yield for singlet oxygen generation by the studied porphyrin complexes with TiO was higher compared to bare porphyrins for TAPP and TMPP, while for the TCPP-TiO NPs complex, a decrease was observed, but still maintained a good efficiency. The TiO NPs conjugates can be promising candidates to be tested in photodynamic therapy in vitro assays.
Topics: Porphyrins; Singlet Oxygen; Photochemotherapy; Spectroscopy, Fourier Transform Infrared; Nanoparticles; Photosensitizing Agents
PubMed: 36615512
DOI: 10.3390/molecules28010318 -
Chemistry (Weinheim An Der Bergstrasse,... Sep 2015Silylation of peripherally lithiated porphyrins with silyl electrophiles has realized the first synthesis of a series of directly silyl-substituted porphyrins. The...
Silylation of peripherally lithiated porphyrins with silyl electrophiles has realized the first synthesis of a series of directly silyl-substituted porphyrins. The meso-silyl group underwent facile protodesilylation, whereas the β-silyl group was entirely compatible with standard work-up and purification on silica gel. The meso-silyl group caused larger substituent effects to the porphyrin compared with the β-silyl group. Silylation of β-lithiated porphyrins with 1,2-dichlorodisilane furnished β-to-β disilane-bridged porphyrin dimers. A doubly β-to-β disilane-bridged Ni(II)-porphyrin dimer was also synthesized from a β,β-dilithiated Ni(II)-porphyrin and characterized by X-ray crystallographic analysis to take a steplike structure favorable for interporphyrinic interaction. Denickelation of β-silylporphyrins was achieved upon treatment with a 4-tolylmagnesium bromide to yield the corresponding freebase porphyrins.
Topics: Crystallography, X-Ray; Metalloporphyrins; Molecular Structure; Nickel; Porphyrins; Silanes
PubMed: 26356498
DOI: 10.1002/chem.201502563 -
Molecules (Basel, Switzerland) Jul 2017Phthalocyanine and porphyrin were among the first organic compounds investigated by means of electronic spectroscopy in superfluid helium nanodroplets. Superfluid helium... (Review)
Review
Phthalocyanine and porphyrin were among the first organic compounds investigated by means of electronic spectroscopy in superfluid helium nanodroplets. Superfluid helium nanodroplets serve as a very gentle host system for preparing cold and isolated molecules. The uniqueness of helium nanodroplets is with respect to the superfluid phase which warrants the vanishing viscosity and, thus, minimal perturbation of the dopant species at a temperature as low as 0.37 K. These are ideal conditions for the study of molecular spectra in order to analyze structures as well as dynamic processes. Besides the investigation of the dopant species itself, molecular spectroscopy in helium droplets provides information on the helium droplet and in particular on microsolvation. This article, as part of a special issue on phthalocyanines and porphyrins, reviews electronic spectroscopy of phthalocyanine and porphyrin compounds in superfluid helium nanodroplets. In addition to the wide variety of medical as well as technical and synthetical aspects, this article discusses electronic spectroscopy of phthalocyanines and porphyrins in helium droplets in order to learn about both the dopant and the helium environment.
Topics: Helium; Indoles; Isoindoles; Nanoparticles; Photoelectron Spectroscopy; Porphyrins
PubMed: 28757568
DOI: 10.3390/molecules22081244