-
Molecules (Basel, Switzerland) Mar 2021Porphyrinic compounds are widespread in nature and play key roles in biological processes such as oxygen transport in blood, enzymatic redox reactions or photosynthesis.... (Review)
Review
Porphyrinic compounds are widespread in nature and play key roles in biological processes such as oxygen transport in blood, enzymatic redox reactions or photosynthesis. In addition, both naturally derived as well as synthetic porphyrinic compounds are extensively explored for biomedical and technical applications such as photodynamic therapy (PDT) or photovoltaic systems, respectively. Their unique electronic structures and photophysical properties make this class of compounds so interesting for the multiple functions encountered. It is therefore not surprising that optical methods are typically the prevalent analytical tool applied in characterization and processes involving porphyrinic compounds. However, a wealth of complementary information can be obtained from NMR spectroscopic techniques. Based on the advantage of providing structural and dynamic information with atomic resolution simultaneously, NMR spectroscopy is a powerful method for studying molecular interactions between porphyrinic compounds and macromolecules. Such interactions are of special interest in medical applications of porphyrinic photosensitizers that are mostly combined with macromolecular carrier systems. The macromolecular surrounding typically stabilizes the encapsulated drug and may also modify its physical properties. Moreover, the interaction with macromolecular physiological components needs to be explored to understand and control mechanisms of action and therapeutic efficacy. This review focuses on such non-covalent interactions of porphyrinic drugs with synthetic polymers as well as with biomolecules such as phospholipids or proteins. A brief introduction into various NMR spectroscopic techniques is given including chemical shift perturbation methods, NOE enhancement spectroscopy, relaxation time measurements and diffusion-ordered spectroscopy. How these NMR tools are used to address porphyrin-macromolecule interactions with respect to their function in biomedical applications is the central point of the current review.
Topics: Humans; Magnetic Resonance Spectroscopy; Micelles; Nucleic Acids; Phospholipids; Photosensitizing Agents; Polymers; Porphyrins; Proteins
PubMed: 33808335
DOI: 10.3390/molecules26071942 -
Biomacromolecules Dec 2022Porphyrins and their derivatives, representing the second-generation photosensitizers, can generate reactive oxygen species (ROS) and kill tumors upon light irradiation....
Porphyrins and their derivatives, representing the second-generation photosensitizers, can generate reactive oxygen species (ROS) and kill tumors upon light irradiation. To compensate for the fluorescence quenching and reduced ROS production caused by aggregation and rigid inherent hydrophobicity of porphyrins, a series of comparable random and block glycopolymers bearing betulin and porphyrin were prepared via RAFT polymerization. Betulin was introduced into the copolymers to decrease aggregation-induced quenching of porphyrins and to improve the photodynamic therapy (PDT) efficiency of copolymers. The characteristics, self-assembly, and photophysical chemistry properties of these copolymers were systemically studied. The effect of polymer structure on photophysical chemistry properties and cellular interaction was investigated as well to demonstrate their potential targeting for PDT applications.
Topics: Porphyrins; Photochemotherapy; Photosensitizing Agents; Triterpenes; Polymers
PubMed: 36350056
DOI: 10.1021/acs.biomac.2c00922 -
Angewandte Chemie (International Ed. in... Sep 2021Electrochemical sensors are indispensable in clinical diagnosis, biochemical detection and environmental monitoring, thanks to their ability to detect analytes in...
Electrochemical sensors are indispensable in clinical diagnosis, biochemical detection and environmental monitoring, thanks to their ability to detect analytes in real-time with direct electronic readout. However, electrochemical sensors are challenged by sensitivity-the need to detect low concentrations, and selectivity-to detect specific analytes in multicomponent systems. Herein, a porphyrinic metal-organic framework (PP-MOF), Mn-PCN-222 is deposited on a conductive indium tin oxide (ITO) surface. It affords Mn-PCN-222/ITO, a versatile voltammetric sensor able to detect redox-active analytes such as inorganic ions, organic hazardous substances and pollutants, including nitroaromatics, phenolic and quinone-hydroquinone toxins, heavy metal ions, biological species, as well as azo dyes. As a working electrode, the high surface area of Mn-PCN-222/ITO enables high currents, and therefore leverages highly sensitive analysis. The metalloporphyrin centre facilitates analyte-specific redox catalysis to simultaneously detect more than one analyte in binary and ternary systems allowing for detection of a wide array of trace pollutants under real-world conditions, most with high sensitivity.
Topics: Biosensing Techniques; Electrochemical Techniques; Environmental Pollutants; Manganese; Metal-Organic Frameworks; Particle Size; Porphyrins; Surface Properties; Trace Elements
PubMed: 34260128
DOI: 10.1002/anie.202107860 -
Journal of Inorganic Biochemistry Oct 2021Electronic charge near the active site is an important factor for controlling the reactivity of metalloenzymes. Here, to investigate the effect of the cationic charge...
Electronic charge near the active site is an important factor for controlling the reactivity of metalloenzymes. Here, to investigate the effect of the cationic charge near the heme in heme proteins, we synthesized new iron porphyrin complexes (1 and 2) having cationic 3-methyl-N-methyl-2-pyrdinium group and N-methyl-2-pyridinium group at one of the four meso-positions, respectively. The N-methyl-2-pyridinium groups could be introduced by Stille coupling used palladium catalysts. Oxoiron(IV) porphyrin π-cation radical complexes (Compound I) of 1 (1-CompI) and 2 (2-CompI) are soluble in most organic solvents, allowing direct comparison of their electronic structure and reactivity with Compound I of tetramesitylporphyrin (3-CompI) and tetrakis-(2,6-dichlorophenyl)porphyrin (4-CompI) under the same conditions. Spectroscopic data for 1-CompI are close to those for 3-CompI, but the redox potential for 1-CompI is close to that of 4-CompI. Kinetic analysis of the epoxidation reactions shows that 1-CompI and 2-CompI are (~250-fold) more reactive than 3-CompI, and comparable to 4-CompI. DFT calculations allow to propose that the positive shift of the redox potential and the enhanced reactivity of 1-CompI and 2-CompI is induced by the intramolecular electric field effect of N-methyl-2-pyridinium cation, not by the electron-withdrawing effect.
Topics: Coordination Complexes; Density Functional Theory; Iron; Metalloporphyrins; Models, Chemical; Oxidation-Reduction; Porphyrins; Pyridinium Compounds; Static Electricity
PubMed: 34293682
DOI: 10.1016/j.jinorgbio.2021.111542 -
Chemosphere Nov 2022The diverse applications of porphyrin-based nano-sized metal-organic frameworks (NMOFs) lead to great exposure risks to human and environment. Understanding the cellular...
The diverse applications of porphyrin-based nano-sized metal-organic frameworks (NMOFs) lead to great exposure risks to human and environment. Understanding the cellular biological effects (such as toxicity, distribution, and localization) of porphyrinic NMOFs is a prerequisite to the assessment of their health risk. However, the characteristics of distribution, localization, and immune response induced by porphyrinic NMOFs have not been studied yet. Here, we report the size-dependent biological effects of porphyrinic NMOFs under sublethal dose. Various sizes of PCN-224 (30, 90, and 180 nm) were taken as model porphyrinic NMOFs. We found that 30 nm PCN-224 gave the highest uptake content, followed by 90 and 180 nm PCN-224. The mechanism for uptake was clathrin-mediated for 30 and 90 nm PCN-224, but clathrin- and glycosylphosphatidylinositol-mediated for 180 nm PCN-224. All PCN-224 were localized in lysosome with size-dependent velocity of colocalization transport. 30 nm PCN-224 induced the highest released cytokines than 90 and 180 nm PCN-224 accompanied with the activation of NF-κB pathway. This work reveals the mechanisms for the endocytosis of PCN-224 and the release of cytokine induced by PCN-224, which is helpful for the health risk assessment of NMOFs.
Topics: Humans; Clathrin; Cytokines; Glycosylphosphatidylinositols; Immunity; Metal-Organic Frameworks; NF-kappa B; Porphyrins
PubMed: 35850215
DOI: 10.1016/j.chemosphere.2022.135680 -
Bioorganic & Medicinal Chemistry Letters Apr 2022Bacterial heme uptake pathways offer a novel target for antimicrobial drug discovery. Recently, gallium (Ga) porphyrin complexes were found to be effective against...
Bacterial heme uptake pathways offer a novel target for antimicrobial drug discovery. Recently, gallium (Ga) porphyrin complexes were found to be effective against mycobacterial heme uptake pathways. The goal of the current study is to build on this foundation and develop a new Ga(III) porphyrin and its nanoparticles, formulated by a single emulsion-evaporation technique to inhibit the growth of Mycobacterium avium complex (MAC) with enhanced properties. Gallium 5,10,15,20-tetrakis(4-methoxyphenyl)porphyrin chloride (GaMeOTP) was synthesized from 5,10,15,20-tetrakis(4-methoxyphenyl)porphyrin and GaCl. GaMeOTP showed enhanced antimicrobial activity against MAC104 and some clinical M. avium isolates. The synthesized Ga(III) porphyrin antimicrobial activity resulted in the overproduction of reactive oxygen species. Our study also demonstrated that F127 nanoparticles encapsulating GaMeOTP exhibited a smaller size than GaTP nanoparticles and a better duration of activity in MAC-infected macrophages compared to the free GaMeOTP. The nanoparticles were trafficked to endosomal compartments within MAC-infected macrophages, likely contributing to the antimicrobial activity of the drug.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Gallium; Heme; Mycobacterium avium Complex; Nanoparticles; Porphyrins
PubMed: 35219822
DOI: 10.1016/j.bmcl.2022.128645 -
Current Medicinal Chemistry 2015This review presents an in-depth overview of the modification of porphyrins with bioconjugates and their applications in medicine today. Porphyrin bioconjugates ranging... (Review)
Review
This review presents an in-depth overview of the modification of porphyrins with bioconjugates and their applications in medicine today. Porphyrin bioconjugates ranging from nucleotides to steroids are under active scrutiny. However, carbohydrates have been at the forefront of such research in recent years and offer significant potential. This is attributed to their own selectivity to lectins on the surface of cancer cells and their influence on the amphiphilicity of the porphyrin macrocycle. These characteristics and the tendency of porphyrin photosensitizers to accumulate in tumor tissues make glycoporphyrins promising candidates for use as photosensitizers. Thus, a detailed overview of the synthesis and biological evaluation of glycoporphyrins is given with a particular focus on their applications in photodynamic therapy and their future prospects as drug candidates have been reported.
Topics: Cell Death; Humans; Molecular Structure; Neoplasms; Photochemotherapy; Photosensitizing Agents; Porphyrins
PubMed: 25921642
DOI: 10.2174/0929867322666150429113104 -
ACS Nano Jan 2024Porphyrins and their derivatives are widely used as photosensitizers and sonosensitizers in tumor treatment. Nevertheless, their poor water solubility and low chemical...
Near-Infrared-II-Activatable Self-Assembled Manganese Porphyrin-Gold Heterostructures for Photoacoustic Imaging-Guided Sonodynamic-Augmented Photothermal/Photodynamic Therapy.
Porphyrins and their derivatives are widely used as photosensitizers and sonosensitizers in tumor treatment. Nevertheless, their poor water solubility and low chemical stability reduce their singlet oxygen (O) yield and, consequently, their photodynamic therapy (PDT) and sonodynamic therapy (SDT) efficiency. Although strategies for porphyrin molecule assembly have been developed to augment O generation, there is scope for further improving PDT and SDT efficiencies. Herein, we synthesized ordered manganese porphyrin (SM) nanoparticles with well-defined self-assembled metalloporphyrin networks that enabled efficient energy transfer for enhanced photocatalytic and sonocatalytic activity in O production. Subsequently, Au nanoparticles were grown on the SM surface by anchoring the terminal alkynyl of porphyrin to form plasmonic SMA heterostructures, which showed the excellent near-infrared-II (NIR-II) region absorption and photothermal properties, and facilitated electron-hole pair separation and transfer. With the modification of hyaluronic acid (HA), SMAH heterostructure nanocomposites exhibited good water solubility and were actively targeted to cancer cells. Under NIR-II light and ultrasound (US) irradiation, the SMAH generates hyperthermia, and a large amount of O, inducing cancer cell damage. Both and studies confirmed that the SMAH nanocomposites effectively suppressed tumor growth by decreasing GSH levels in SDT-augmented PDT/PTT. Moreover, by utilizing the strong absorption in the NIR-II window, SMAH nanocomposites can achieve NIR-II photoacoustic imaging-guided combined cancer treatment. This work provides a paradigm for enhancing the O yield of metalloporphyrins to improve the synergistic therapeutic effect of SDT/PDT/PTT.
Topics: Humans; Photochemotherapy; Manganese; Porphyrins; Gold; Photoacoustic Techniques; Metal Nanoparticles; Phototherapy; Nanoparticles; Neoplasms; Water; Cell Line, Tumor
PubMed: 38117769
DOI: 10.1021/acsnano.3c09011 -
Chemical Reviews Feb 2017Compared to porphyrin, its isomeric, expanded, and contracted analogues are less well explored. This contrast is found to be even more drastic in the case of their... (Review)
Review
Compared to porphyrin, its isomeric, expanded, and contracted analogues are less well explored. This contrast is found to be even more drastic in the case of their peripherally annulated counterparts. Nevertheless, the chemistry of annulated isomeric, expanded, and contracted porphyrins started flourishing recently with considerable efforts over the past few years, as evidenced by an increasing number of publications. While keeping the essence of porphyrins, these annulated versions exhibit quite unique properties that have no precedence in their nonannulated counterparts. An in-depth update of research carried out so far in this emerging area will be presented in this review.
Topics: Crystallography, X-Ray; Isomerism; Porphyrins; Spectrophotometry, Ultraviolet; Spectroscopy, Near-Infrared
PubMed: 28005351
DOI: 10.1021/acs.chemrev.6b00411 -
Organic & Biomolecular Chemistry Jun 2023Porphyrin-fullerene composite systems are attracting great attention as photodynamic agents; however, water-soluble derivatives are still scarce. Herein, we prepared...
Porphyrin-fullerene composite systems are attracting great attention as photodynamic agents; however, water-soluble derivatives are still scarce. Herein, we prepared noncovalently a lipid membrane-incorporated porphyrin-fullerene composite system with relative stability in aqueous solution. As in the case of porphyrin-fullerene composite systems in nonpolar solvents, efficient formation of singlet oxygen occurred photoinduced energy transfer between porphyrin and fullerene as the predominant pathway in the photodynamic activity under the hydrophobic conditions of the lipid membranes, resulting in enhanced photodynamic activity toward Colon26 and HeLa cells compared with the individual porphyrin and fullerene components. Furthermore, the porphyrin-fullerene composite system exhibited high selectivity toward HeLa cells over normal mouse fibroblast L929 cells.
Topics: Animals; Mice; Humans; Porphyrins; Fullerenes; HeLa Cells; Energy Transfer; Lipids
PubMed: 37248815
DOI: 10.1039/d3ob00027c