Water-soluble Cationic Porphyrins Research Articles

Antimicrobial activity of cationic water-soluble porphyrin against multidrug-resistant bacteria in biofilms and canine skin samples.

Multidrug-resistant (MDR) microorganisms pose a threat to animal health, particularly in integumentary diseases, which can be caused by multiple organisms and often manifest as biofilms, hindering treatment effectiveness. We evaluated the antimicrobial activity of antimicrobial photodynamic therapy (aPDT) using a water-soluble tetra-cationic porphyrin (4-H2TMeP) against MDR bacteria cultured in biofilm and in mono and polyculture grown on canine skin samples. We utilized 4-H2TMeP porphyrin against MDR Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus pseudintermedius. A non-cytotoxic concentration of 4-H2TMeP (40 µM), previously shown to be effective in vitro against these bacteria cultured in solution, was employed. Biofilms were treated with 4-H2TMeP and subjected to light irradiation for 30, 60, and 90min. Monocultures on canine skin samples were treated with 4-H2TMeP and irradiated for 30 (S. pseudintermedius), 60 (E. coli), or 60 and 90min (P. aeruginosa). Polycultures of S. pseudintermedius and E. coli were treated with light for 60 and 90min. The efficacy of aPDT was evaluated by plating light-exposed biofilms, mono and polycultures of bacteria obtained from skin samples exposed to light and kept in the dark. Colony-forming units were counted after 24h of incubation at 37°C. aPDT using 4-H2TMeP reduced bacterial concentrations of S. pseudintermedius and E. coli biofilms. Additionally, it significantly reduced bacterial concentrations cultivated on skin samples, with a particular emphasis on S. pseudintermedius. These findings indicate that aPDT with 4-H2TMeP is a promising alternative treatment against MDR bacteria in animal skin infections and should be further explored through in vivo research.

An effective visible-light driven fumarate production from gaseous CO2 and pyruvate by the cationic zinc porphyrin-based photocatalytic system with dual biocatalysts.

Fumaric acid is a useful unsaturated dicarboxylic acid that serves as a precursor for the biodegradable plastics poly(butylene succinate) and poly(propylene fumarate). Currently, fumaric acid is mainly synthesised from petroleum resources such as benzene. It is therefore desirable to develop methods to produce fumaric acid from renewable resources such as those derived from biomass. In this work, an effective visible-light driven fumarate production from gaseous CO2 and pyruvate with the system consisting of triethanolamine, cationic water-soluble zinc porphyrin, zinc tetrakis(4-N,N,N-trimethylaminophenyl)porphyrin, pentamethylcyclopentadienyl coordinated rhodium(III) 2,2'-bipyridyl complex, NAD+, malate dehydrogenase (NAD+-dependent oxaloacetate-decarboxylating) and fumarase was developed.

Phototreatment with water-soluble cationic gallium porphyrin impacts Staphylococcus aureus viability and staphyloxanthanin level

Phototreatment with water-soluble cationic gallium porphyrin impacts Staphylococcus aureus viability and staphyloxanthanin level

Thermosensitive phosphorus(V) porphyrin: Toward subcellular ratiometric optical temperature sensing

Luminescence thermometry has attracted a lot of attention due to its ability to provide temperature sensing with high spatial, temporal, and thermal resolution. This technique is the most promising for probing changes in local temperature in living cells to monitor thermogenesis and to study cellular activity. Despite rapid progress in this field, there is still a lack of optical thermometers capable of thermal sensing at the subcellular level, especially owning additional functionality. Here, cationic ( meso -mono(4-pyridyl)-triphenylporphyrinato)phosphorus(V) bromide MPyPP(OH) 2 was used as subcellular ratiometric thermal sensor in CHO-K1 and HeLa cells within the biological temperature range (30–44 o C). Introduction of porphyrin into cells resulted in its dephosphorylation and change of luminescence properties. Ratiometric sensing was performed using peak-to-peak and peak-to-valley ratios. Thermometric performance was evaluated in terms of absolute and relative sensitivities, temperature resolution. Relative thermal sensitivity and temperature resolution reached 0.61% K -1 and 0.1 o C, respectively in the case of CHO-K1 cells. • Water-soluble cationic porphyrin was successfully applied subcellular thermometry. • Introduction of porphyrin into cells leads to its dephosphorylation and change of luminescence properties. • Ratiometric sensing was realized through peak-to-peak and peak-to-valley approaches. • Thermometric performance was evaluated using relative thermal sensitivity and temperature resolution.

Graphene Oxide-Gold Nanorods Nanocomposite-Porphyrin Conjugate as Promising Tool for Cancer Phototherapy Performance.

The cancer mortality rate has increased, and conventional cancer treatments are known for having many side effects. Therefore, it is imperative to find a new therapeutic agent or modify the existing therapeutic agents for better performance and efficiency. Herein, a synergetic phototherapeutic agent based on a combination of photothermal and photodynamic therapy is proposed. The phototherapeutic agent consists of water-soluble cationic porphyrin (5,10,15,20-tetrakis(N-methylpyridinium-3-yl)porphyrin, TMePyP), and gold nanorods (AuNRs) anchored on graphene-oxide (GO) sheet. The TMePyP was initially synthesized by Adler method, followed by methylation, while GO and AuNRs were synthesized using Hummer’s and seed-mediated methods, respectively. The structural and optical properties of TMePyP were confirmed using UV-Vis, zeta analyzer, PL, FTIR and NMR. The formation of both GO and AuNRs was confirmed by UV-Vis-NIR, FTIR, TEM and zeta analyzer. TMePyP and AuNRs were anchored on GO to form GO@AuNRs-TMePyP nanocomposite. The as-synthesized nanocomposite was stable in RPMI and PBS medium, and, on irradiation, produced high heat than the bare AuNRs, with high photothermal efficiency. In addition, the nanocomposite produced higher singlet oxygen than TMePyP with high biocompatibility in the absence of light. These results indicated that the as-synthesized nanocomposite is a promising dual photodynamic and photothermal agent for cancer therapy.

Cellular and mitochondrial dual-targeted nanoprobe with near-infrared emission for activatable tumor imaging and photodynamic therapy

A nanotheranostic system integrating activatable photoactivity and dual targeting modalities is significant for bioimaging and biomedicine. In this study, a dual-targeting and tumor microenvironment responsive nanoassembly for imaging of HAase and PDT of tumor was developed. The synthesized water-soluble cationic porphyrin act as both the mitochondrion targeting photosensitizer and crosslinking agent to trigger the formation of HA-Mito TPP nanoparticle via the electrostatic interaction with hyaluronic acid. The nanoassembly could be efficiently endocytosed into targeted tumor cells and activated both fluorescence signal and enhanced PDT effect by highly expressed HAase. In vitro experiments suggested that the reported assay had desirable selectivity and excellent anti-interference for HAase quantitative analysis. The live cell studies showed the HA-Mito TPP had obviously enhanced PDT efficiency and caused mitochondria damage. Therefore, the developed dual-targeting nanotheranostic system provide a promising platform for bioanalysis and imaging guided photodynamic therapy.

Metal center ion effects on photoinactivating rapidly growing mycobacteria using water-soluble tetra-cationic porphyrins.

Rapidly growing mycobacteria (RGM) are pathogens that belong to the mycobacteriaceae family and responsible for causing mycobacterioses, which are infections of opportunistic nature and with increasing incidence rates in the world population. This work evaluated the use of six water-soluble cationic porphyrins as photosensitizers for the antimicrobial photodynamic therapy (aPDT) of four RGM strains: Mycolicibacterium fortuitum, Mycolicibacterium smeagmatis, Mycobacteroides abscessus subs. Abscessus, and Mycobacteroides abscessus subsp. massiliense. Experiments were conducted with an adequate concentration of photosensitizer under white-light irradiation conditions over 90min and the results showed that porphyrins 1 and 2 (M = 2H or ZnII ion) were the most effective and significantly reduced the concentration of viable mycobacteria. The present work shows the result is dependent on the metal-center ion coordinated in the cationic porphyrin core. Moreover, we showed by atomic force microscopy (AFM) the possible membrane photodamage caused by reactive oxygen species and analyzed the morphology and adhesive force properties. Tetra-positively charged and water-soluble metalloporphyrins may be promising antimycobacterial aPDT agents with potential applications in medical clinical cases and bioremediation.

Electrochemistry and Spectroscopy of Tri- and Tetracationic Porphyrins

Water-soluble cationic porphyrins have been shown to possess promising therapeutic potential, through biochemical processes. which depend on solubility as well as the extent of aggregation. under biological conditions. These properties are influenced by a multitude of factors the most important of which are the number of positively charged meso-substituents, the type of counteranion, the central metal ion and the solvent. We have previously investigated mono- di- and tetra-methylpyridyl porphyrins with mainly Cl- counterions and we now turn our attention to trisubstituted derivatives of the type shown at the bottom of the figure. These six new tricationic porphyrins represented as [(TriMPyP)M]3+X- 3 (where M = 2H, ZnII or PdII and X- = Cl- or Tosyl-) containing three N-methyl-4-pyridyl groups and chloride or tosylate counteranions were electrochemically and spectroscopically characterized for the first time. The physicochemical properties of the [(TriMPyP)M]3+X- 3 complexes were compared, under the same solution conditions, to several free base and metal tetracationic porphyrins shown at the top of the figure and represented as [(TMPyP)M]4+X- 4 (where M = 2H, MnIII, FeIII, CoII, ZnII or PdII). Figure 1

Adenosine Triphosphate Templated Self-Assembly of Cationic Porphyrin into Chiral Double Superhelices and Enzyme-Mediated Disassembly.

Self-assembly of small molecules through noncovalent interactions into nanoscale architectures has been extensively studied in supramolecular chemistry. However, it is still challenging to develop a biologically inspired self-assembly system that functions in water with complex structure and dynamics by analogy with those found in nature. Here, we report a new water-soluble cationic porphyrin that undergoes adenosine triphosphate (ATP)-templated self-assembly into right-handed double-helical supramolecular structures. Direct observation of the porphyrin-ATP assembly by transmission electron microscopy has been accomplished. The assemblies consist of superhelical fibers with length greater than 1 μm and width ∼46 nm. The chiral superhelical fibers show reversible disassembly to monomers upon hydrolysis of ATP catalyzed by alkaline phosphatase (ALP), and the nanofibers can be re-formed with subsequent addition of ATP. Moreover, transient self-assembly of a chiral double helix is formed when ALP is present to consume ATP.

Cationic porphyrins with large side arm substituents as resonance light scattering ratiometric probes for specific recognition of nucleic acid G-quadruplexes.

Specific G-quadruplex-probing is crucial for both biological sciences and biosensing applications. Most reported probes are focused on fluorescent or colorimetric recognition of G-quadruplexes. Herein, for the first time, we reported a new specific G-quadruplex-probing technique—resonance light scattering (RLS)-based ratiometric recognition. To achieve the RLS probing of G-quadruplexes in the important physiological pH range of 7.4-6.0, four water soluble cationic porphyrin derivatives, including an unreported octa-cationic porphyrin, with large side arm substituents were synthesized and developed as RLS probes. These RLS probes were demonstrated to work well for ratiometric recognition of G-quadruplexes with high specificity against single- and double-stranded DNAs, including long double-stranded ones. The working mechanism was speculated to be based on the RLS signal changes caused by porphyrin protonation that was promoted by the end-stacking of porphyrins on G-quadruplexes. This work adds an important member in G-quadruplex probe family, thus providing a useful tool for studies on G-quadruplex-related events concerning G-quadruplex formation, destruction and changes in size, shape and aggregation. As a proof-of-concept example of applications, the RLS probes were demonstrated to work well for label-free and sequence-specific sensing of microRNA. This work also provides a simple and useful way for the preparation of cationic porphyrins with high charges.

Spectroscopic, thermodynamic and molecular docking studies on the interaction of two water-soluble asymmetric cationic porphyrins with calf thymus DNA

The water-soluble cationic porphyrin, 5-(1-dodecyl pyridinium-4-yl)-10,15,20-tris(1-methylpyridinium-4-yl)-21H,23H-porphyrin tetrachloride (MDTMPyP), and its Cu(II) complex (CuMDTMPyP) have been prepared and characterized by 1H NMR, UV–visible spectroscopy and elemental analyses. The binding properties of the porphyrins with calf thymus DNA (CT-DNA) have been investigated by electrochemical, spectroscopic and molecular docking methods. These observations were further confirmed by monitoring DNA viscosity and also circular dichroism studies in the Soret region. The absorption spectrum changes of both porphyrins in Soret band region showed that they could intercalate in DNA structure. The obtained results showed that MDTMPyP has a higher affinity to CT-DNA than CuMDTMPyP. The porphyrin solutions were titrated with DNA and the UV–visible titration spectra were analyzed with multivariate curve resolution-alternating least squares (MCR-ALS) technique to obtain spectrum of porphyrin–DNA complex, and concentration profiles of free and DNA-bonded porphyrin. Then the binding constant was calculated by the combination of MCR-ALS and McGhee–von Hippel equation. Also, the thermodynamic parameters of the DNA binding process were acquired from the van’t Hoff equation at various temperatures. The positive and large values of the entropy, and enthalpy revealed that the interaction is endothermic, and the entropically driven process. Two water soluble cationic asymmetric porphyrins have been synthesized and structurally characterized with various techniques. Their binding properties with CT-DNA have been explored by electrochemical and spectroscopic methods. The DNA binding studies offered that these porphyrins can intercalate into CT-DNA.

Photosensitized enzyme deactivation and protein oxidation by axial-substituted phosphorus(V) tetraphenylporphyrins

The activity for photodynamic therapy of water-soluble cationic porphyrins, tetraphenylporphyrin P(V) complexes, was investigated. Bis(cyclohexylmethoxy)P(V)tetraphenylporphyrin (DCHMP(V)TPP), dichloroP(V)tetraphenylporphyrin (Cl2P(V)TPP), and dimethoxyP(V)tetraphenylporphyrin (DMP(V)TPP) could cause the photosensitized deactivation of tyrosinase. The tryptophan residue of human serum albumin (HSA) and several kinds of amino acids could be damaged by these P(V)porphyrins under visible light irradiation. The photosensitized damage of these biomolecules was inhibited by sodium azide, a singlet oxygen (1O2) quencher, and enhanced in deuterium oxide, suggesting the contribution of 1O2. However, an excess amount of sodium azide did not completely inhibit the photosensitized damage. In addition, the redox potential measurements demonstrated the possibility of electron transfer from tryptophan and tyrosine to photoexcited P(V)porphyrins. These results suggest that electron transfer-mediated oxidation of amino acids contributes to the photosensitized protein and amino acid damage by these P(V)porphyrins. Specifically, Cl2P(V)TPP showed the highest photodamaging activity in the P(V)porphyrins used in this study. Oxidized products of amino acids by photoexcited P(V)porphyrins were analyzed with a liquid chromatography-mass spectrometer. Because of the hypoxic condition of a tumor, photodynamic therapy through a 1O2-mediated mechanism should be restricted, and the electron transfer-mediated mechanism may improve the photodynamic effect. In the cases of these P(V)porphyrins, redox potential is the most important factor for photosensitized protein and amino acid oxidation through photoinduced electron transfer.

Elaborated DNA-binding specialities, in vitro medicated apoptosis and restrained malignancy of neotype water-soluble cationic porphyrin acylhydrazone Cu-complex

Tetrad novel Cu-complex containing multifarious meso-10,15,20-Tris (N-methyl-2′-pyridyl)-5-(4′-X-acylhydrazone) porphyrin ligands, where X respectively referred to salicylaldehyde (Cu-P1), o-Vanillin (Cu-P2), pyridine-2-carboxaldehyde (Cu-P3) and acetone (Cu-P4), have been successfully isolated and well characterized. Multiple physicochemical approaches reveal the complex Cu-P4 with preferable binding affinity than its analogues due to smaller molecular dimension. Moreover, the mechanism of the anti-neoplasm action of these conjugates have been appraised via MTT assay, manifesting all of them possess superior cytotoxicity towards A549 (non-small cell lung cancer) and HepG2 (liver hepatocellular carcinoma cells) but weak cell toxicity for Hs 578Bst (human normal breast cells) which might be boiled down to porphyrin derivatives could enrich around malignant neoplasms. The flow cytometric analysis illustrates that delegate compound Cu-P4 induced cell death predominantly through late apoptosis and arrested S phase cells.

Efficient Upconversion by Highly Water-Soluble Cationic Sensitizer and Emitter in Aqueous Solutions with DNA.

Highly water-soluble cationic palladium porphyrin as a sensitizer and 9,10-bis(4-trimethylammoniumphenyl)anthracene as an emitter were newly synthesized. They were shown to be bound and immobilized in DNA double helix assembly from absorption, fluorescence, phosphorescence, and circular dichroism spectra. Upon excitation at 532 nm in deaerated aqueous solutions, they showed weak blue upconversion fluorescence, the efficiency of which increased dramatically in the presence of DNA. The threshold power density between the second-order and first-order power dependence of upconversion fluorescence decreased to less than a half upon addition of DNA. The emitter triplet lifetime estimated from time dependences of upconversion fluorescence at low power ns pulsed laser was found to considerably increase in the presence of DNA. From these results, DNA was concluded to work effectively in concentrating both sensitizer and emitter and in migrating excited triplet states, resulting in efficient upconversion.

Highly specific G-quadruplex recognition covering physiological pH range by a new water-soluble cationic porphyrin with low self-aggregation tendency

A new water-soluble cationic porphyrin derivative m-TMPyEOPP (5,10,15,20-tetrakis{4-[2-(O-(N-methylpyridyl)ethoxyl]oxyphenly}porphyrin) has been designed, synthesized, and fully characterized. This porphyrin derivative combines the advantages of two cationic porphyrins used in G-quadruplex recognition and stabilization studies, i.e., the widely investigated G-quadruplex ligand TMPyP4 and TMPipEOPP reported by us. That is to say, the presence of four bulky side-arm substituents endows the m-TMPyEOPP derivative with the capacity for colorimetric and fluorescence-based recognition of G-quadruplexes with high specificity. By virtue of almost negligible pH-dependent self-aggregation, and hence reduced single- and double-stranded DNA-templated aggregation behavior, it can also work well under acidic conditions. By combining the fluorescence signals obtained at different excitation wavelengths (690 or 260 nm), specific G-quadruplex recognition can be achieved by m-TMPyEOPP in the pH range 5.0–7.5, which almost covers the physiological pH range. Ratiometric signal output mode might confer G-quadruplex recognition with high accuracy, reliability and repeatability. This work demonstrates that the aggregation behaviours of water-soluble cationic porphyrins can be controlled by adjusting the nature of the substituents on their side arms, thus endowing them with different G-quadruplex-specific recognition abilities suitable for different pH conditions.

Efficient Synthesis of Anionic and Cationic Water-Soluble Porphyrins

Efficient Synthesis of Anionic and Cationic Water-Soluble Porphyrins

Water soluble cationic porphyrin showing pH-dependent optical responses to G-quadruplexes: Applications in pH-sensing and DNA logic gate

A water soluble cationic porphyrin derivative 5,10,15,20-tetra-{4-[3-(1-methyl-1-piperidinyl) propoxy]phenyl}porphyrin (TMPipPrOPP), which showed attractive pH-dependent optical responses to G-quadruplexes, was synthesized and characterized. Under molecular crowding conditions, a stable TMPipPrOPP/G-quadruplex complex was formed in acidic pH range. Alkalization of the system to neutral and basic pH caused destruction of the complex due to reduced electrostatic interactions. The formation and destruction of the TMPipPrOPP/G-quadruplex complex was reversibly adjusted by pH, accompanied by repeated on-off switching of the colorimetric and fluorescent responses of TMPipPrOPP to G-quadruplexes. In comparison, no optical responses were observed for single-stranded, duplex and i-motif DNAs in the tested pH range (5.0–8.5). Besides highlighting the importance of designing novel drugs targeting G-quadruplexes in specific genome regions, this work may also provide a useful tool for G-quadruplex-based biosensing and nanomachine construction. One example is the design of colorimetric and fluorescent sensors for ratiometric pH-sensing. The proposed sensing platform can be used not only for highly sensitive pH-sensing in a narrow biological pH range, but also for pH detection in a broad range. Another example is the construction of DNA-based dual-output all-optical molecular logic gates that can perform basic AND, NAND, OR, NOR, INHIBIT and IMPLICATION logic operations.

Water soluble cationic porphyrin TMPipEOPP-induced G-quadruplex and double-stranded DNA photocleavage and cell phototoxicity

A water soluble cationic porphyrin derivative TMPipEOPP can preferentially photocleave G-quadruplex in the presence of ​double-stranded DNA, thus might be used as a human telomere-targeted photosensitizer for tumor photodynamic therapy.

Development of PDT/PET Theranostics: Synthesis and Biological Evaluation of an (18)F-Radiolabeled Water-Soluble Porphyrin.

Synthesis of the first water-soluble porphyrin radiolabeled with fluorine-18 is described: a new molecular theranostic agent which integrates the therapeutic selectivity of photodynamic therapy (PDT) with the imaging efficacy of positron emission tomography (PET). Generation of the theranostic was carried out through the conjugation of a cationic water-soluble porphyrin bearing an azide functionality to a fluorine-18 radiolabeled prosthetic bearing an alkyne functionality through click conjugation, with excellent yields obtained in both cold and hot synthesis. Biological evaluation of the synthesized structures shows the first example of an (18)F-radiolabeled porphyrin retaining photocytotoxicity following radiolabeling and demonstrable conjugate uptake and potential application as a radiotracer in vivo. The promising results gained from biological evaluation demonstrate the potential of this structure as a clinically relevant theranostic agent, offering exciting possibilities for the simultaneous imaging and photodynamic treatment of tumors.

Influence of H2TOEtPyP4 porphyrin on the stability and conductivity of bilayer lipid membranes.

Many water-soluble cationic porphyrins are known to be prospective chemotherapeutics and photosensitizers for cancer treatment and diagnosis. The physicochemical properties of porphyrins, in particular their interactions with membranes, are important determining factors of their biological activity. The influence of cationic meso-tetra-[4-N-(2'-hydroxyethyl) pyridyl] porphyrin (H2TOEtPyP) on the stability and conductivity of bilayer lipid membranes (BLMs) was studied. H2TOEtPyP4 porphyrin was shown to decrease the stability of BLMs made of a mixture of DOPS and DPPE (1:1) in an electric field because of a reduction of line tension of spontaneously formed pore edges in the BLM. The presence of cationic porphyrin was found to reduce BLM surface tension. This effect was enhanced with increasing porphyrin concentration. H2TOEtPyP4 increased the probability of spontaneous pore formation. Further investigating the cyclic current-voltage characteristics of BLMs allowed determining the electrical capacity and conductivity of BLMs in the presence of H2TOEtPyP4 porphyrin. It was shown that in the presence of cationic porphyrin the electrical capacity as well as conductivity of the BLM increases.