Water-soluble Porphyrin Derivative Research Articles

Apoptosis-Amplified Assembly of Porphyrin Nanofiber Enhances Photodynamic Therapy of Oral Tumor.

Oral squamous cell carcinoma (OSCC) is the most common oral cancer, having high recurrence and metastasis features. In addition to surgery, photodynamic therapy (PDT) is considered as another effective approach for OSCC treatment. The water solubility of currently available PDT photosensitizers (PSs) is poor, lowering their singlet oxygen (1O2) yield and consequent PDT efficiency. Strategies of PS assembly have been reported to increase 1O2 yield, but it is still possible to further enhance PDT efficiency. In this work, we utilized apoptosis to amplify the assembly of porphyrin nanofibers for enhanced PDT of OSCC. A water-soluble porphyrin derivative, Ac-Asp-Glu-Val-Asp-Asp-TPP (Ac-DEVDD-TPP), was designed for this purpose. Upon caspase-3 (Casp3, an activated enzyme during apoptosis) cleavage and laser irradiation, Ac-DEVDD-TPP was converted to D-TPP, which spontaneously self-assembled into porphyrin nanofibers, accompanied by 1.4-fold and 2.1-fold 1O2 generations in vitro and in cells, respectively. The as-formed porphyrin nanofiber induced efficient cell apoptosis and pyroptosis. In vivo experiments demonstrated that, compared with the scrambled control compound Ac-DEDVD-TPP, Ac-DEVDD-TPP led to 6.2-fold and 1.3-fold expressions of Casp3 in subcutaneous and orthotopic oral tumor models, respectively, and significantly suppressed the tumors. We envision that our strategy of apoptosis-amplified porphyrin assembly might be applied for OSCC treatment in the clinic in the near future.

Photon Upconversion with a Low Threshold Excitation Intensity in Plain Water.

A triplet-triplet annihilation-based photon upconversion (TTA-UC) system with a low threshold excitation intensity (Ith) in plain water was developed. Water-soluble anionic porphyrin (PdTPPS4-) and diphenylanthracene (DCDPA2-) derivatives were used as light absorbers and emitter molecules, respectively, and no additives such as surfactants were required. The phosphorescence emission from PdTPPS4- under an excitation wavelength of 528 nm was quenched by DCDPA2-, resulting in triplet energy transfer, whereas fluorescence from DCDPA2- was observed in a short wavelength region (400-500 nm). Three independent emission studies utilizing different excitation light sources validated the TTA-UC process in a simple aqueous solution. TTA occurred after the triplet energy transfer, according to the time profiles of phosphorescence and fluorescence detected following pulse laser excitation. The Ith for TTA-UC was estimated to be lower than 6 mW cm-2, although it could not be exactly determined due to the sensitivity limit of the experimental setup. The upper limit of Ith for the aqueous solution of DCDPA2- and PdTPPS4- is the smallest value obtained to date for aqueous systems and comparable to that of high-performance TTA-UC systems in organic solutions.

Charge effect of water-soluble porphyrin derivatives as a prototype to fight infections caused by Acinetobacter baumannii by aPDT approaches

In the last decade, Acinetobacter baumannii has emerged as a pathogen associated with infections in intensive care units worldwide, especially due to its ability to resist an extensive list of antibiotics. In this context, porphyrins have emerged as an important strategy in photodynamic therapy, since they are a group of tetrapyrrolic compounds with important photochemical and photobiological activities. In this study, the antimicrobial photodynamic activity of meso-tetra(4-N-methyl-pyridyl)porphyrin (H2TMePyP+ ) and meso-tetra(4-sulfonatophenyl)porphyrin (H2TPPS‒ ) was evaluated against A. baumannii by minimum inhibitory concentration (MIC), anti-biofilm activity, and the interaction with antibiotics after exposure to white-light LED irradiation. The cationic derivative H2TMePyP+ was more potent (MIC = 0.61 µM) than H2TPPS‒ , with anti-biofilm activity and increased the antimicrobial activity of ciprofloxacin and amikacin. Given these findings, the tetra-cationic porphyrins can be assumed as prototypes to optimize and develop new agents by promoting oxidative stress and inducing free radical production.

Acid-Responsive Nanoporphyrin Evolution for Near-Infrared Fluorescence-Guided Photo-Ablation of Biofilm.

Combating biofilm infections remains a challenge due to the shield and acidic conditions. Herein, an acid-responsive nanoporphyrin (PN3-NP) based on the self-assembly of a water-soluble porphyrin derivative (PN3) is constructed. Additional kinetic control sites formed by the conjugation of the spermine molecules to a porphyrin macrocycle make PN3 self-assemble into stable nanoparticles (PN3-NP) in the physiological environment. Noteworthily, near-infrared (NIR) fluorescence monitoring and synergistic photodynamic therapy (PDT) and photothermal therapy (PTT) effects of PN3-NP can be triggered by the acidity in biofilms, accompanied by intelligent transformation into dot-like nanospheres. Thus, damage to normal tissue is effectively avoided and accurate diagnosis and treatment of biofilms is achieved successfully. The good results of fluorescence imaging-guided photo-ablation of antibiotic-resistant strains methicillin-resistant Staphylococcus aureus (MRSA) biofilms verify that PN3-NP is a promising alternative to antibiotics. Meanwhile, this strategy also opens new horizons to engineer smart nano-photosensitizer for accurate diagnosis and treatment of biofilms.

Synthesis, Characterization, and Biological Evaluation of a Porphyrin-Based Photosensitizer and Its Isomer for Effective Photodynamic Therapy against Breast Cancer.

A photosensitizer with high phototoxicity, low dark toxicity, and good water solubility is crucial for effective photodynamic therapy (PDT). In this study, a novel class of porphyrin-based water-soluble derivative and its isomers, named photohexer-1 (P-1) and photohexer-2 (P-2), were synthesized and investigated for anticancer activity. Both of the isomers, P-1 and P-2, could be utilized as potential sensitizers for PDT not only owing to their definite constituents but predominantly due to their good absorption in the phototherapeutic window and high generation of intracellular ROS. Therein, P-2 exhibited stronger phototoxicity against breast cancer cells with weaker dark toxicity than P-1; however, both P-1 and P-2 were highly phototoxic as compared to their homologous compound, hematoporphyrin monomethyl ether (HMME). These findings were consistent with the antitumor efficacy in vivo. Moreover, P-1 and P-2 could both effectively localize in multiple subcellular organelles, triggering increased cellular apoptosis or necrosis under laser irradiation as compared to HMME. In conclusion, the findings of the study suggest that the two highly water-soluble porphyrin derivatives may serve as promising putative photosensitizers for improving the therapeutic efficiency of PDT.

A selective distance-based paper analytical device for copper(II) determination using a porphyrin derivative

Meso-tetrakis(1,2-dimethylpyrazolium-4-yl)porphyrin sulfonate (TDMPzP), a water-soluble porphyrin derivative, was synthesized and used as a colorimetric reagent for Cu2+ detection on a microfluidic paper-based analytical device (µPAD) using distance-based quantification. TDMPzP showed a high selectivity for Cu2+ detection in aqueous solutions. When Cu2+ was added to the TDMPzP under acidic conditions, a color change from green to a pink was observed by the naked eye. Under optimized conditions, the application of this system to a distance-based μPAD exhibited good analytical response. The presence of common metal ions (Al3+, Fe3+, Mg2+, Co2+, Mn2+, Zn2+, Pb2+, Cd2+, Sn2+, and Ni2+) did not interfere with Cu2+ detection within reasonable tolerance ratios. The lowest concentration of copper that could be measured was 1mgL−1 (1ppm) which meets the requirements for drinking water contamination regulations from the US Environmental Protection Agency (EPA) and World Health Organization (WHO) guidelines for drinking water. Real drinking water samples were analyzed to confirm the practical application of this system and the results showed good agreement with ICP-MS data. This distance-based µPAD based on TDMPzP for Cu2+ detection is convenient and effective for real-time drinking water analysis.

Photocatalytic hydrogen production based on a water-soluble porphyrin derivative as sensitizer and a series of Wilkinson type complexes as catalysts

Herein, we report photochemical hydrogen evolution systems consisting of various rhodium based catalysts with Wilkinson type structures, Zn metalated porphyrins and fluorescein as photosensitizers and triethanolamine as a sacrificial electron donor in acetonitrile/H2O (1:1) solution. Since rhodium complexes 1 and 2 are used for the first time as catalysts in this type of systems, a systematic study was performed in order to elucidate the best conditions for H2 production. Upon visible irradiation hydrogen production was detected and the best results were obtained at pH 7 when dye P3 and catalyst 1 were used with a TON of 61, after 48 h and in the presence of dye P1 and catalyst 2 with a TON of 69, after the 48 h.

Colorimetric and Fluorescent Bimodal Ratiometric Probes for pH Sensing of Living Cells.

pH measurement is widely used in many fields. Ratiometric pH sensing is an important way to improve the detection accuracy. Herein, five water-soluble cationic porphyrin derivatives were synthesized and their optical property changes with pH value were investigated. Their pH-dependent assembly/disassembly behaviors caused significant changes in both absorption and fluorescence spectra, thus making them promising bimodal ratiometric probes for both colorimetric and fluorescent pH sensing. Different substituent identity and position confer these probes with different sensitive pH-sensing ranges, and the substituent position gives a larger effect. By selecting different porphyrins, different signal intensity ratios and different fluorescence excitation wavelengths, sensitive pH sensing can be achieved in the range of 2.1-8.0. Having demonstrated the excellent reversibility, good accuracy and low cytotoxicity of the probes, they were successfully applied in pH sensing inside living cells.

Effect of DNA microenvironment on photosensitized reaction of watersoluble cationic porphyrins.

Endogenous and exogenous photosensitizers induce DNA damage, leading to carcinogenesis. Further, DNA is an important target biomacromolecule of photodynamic therapy (PDT) for cancer. Since the solar-induced DNA damage and PDT reaction occur in a complex biological environment, the interaction between biomolecule and photosensitizer is important. In this study, we examined the effect of a DNA microenvironment on the photosensitized reaction by watersoluble porphyrin derivatives, tetrakis(N-methyl-p-pyridinio)porphyrin (H(2)TMPyP) and its zinc complex (ZnTMPyP). In the presence of a sufficient concentration of DNA, H(2)TMPyP mainly intercalates to calf thymus DNA, whereas ZnTMPyP binds into a DNA groove. An electrostatic interaction with DNA raises the redox potential of the binding porphyrins. This effect suppressed the photoinduced electron transfer from an electron donor to the DNA-binding porphyrins, whereas the electron transfer from the porphyrins to the electron acceptor was enhanced. In the case of hydrophobic electron acceptors, static complexes with porphyrins were formed, making rapid electron transfer possible. Since the interaction with DNA cleaved this complex, the electron transfer rate was decreased in the presence of DNA. The microenvironment of a DNA strand may assist or inhibit its oxidative damage by photoinduced electron transfer through an electrostatic interaction with binding photosensitizers and the steric effect.

Photocatalytic hydrogen production from a noble metal free system based on a water soluble porphyrin derivative and a cobaloxime catalyst

A combination of noble-metal free components, a water soluble porphyrin photosensitizer zinc meso-tetrakis(1-methylpyridinium-4-yl)porphyrin chloride [ZnTMPyP(4+)]Cl4 (1) with cobaloxime complex [Co(III)(dmgH)2(py)Cl] (2) as a catalyst, creates an efficient system for photochemical hydrogen production acting under visible light with 280 TONs. This is the first example of a water soluble porphyrin acting as a photosensitizer for cobaloxime catalysed H2 production.

Solvophobic versus Electrostatic Interactions Drive Spontaneous Adsorption of Porphyrins onto Inorganic Surfaces: A Full Noncovalent Approach

The successful transferring of a porphyrin complex assembly from a solution to a solid surface is important for an economical development of functional materials, biomaterials, and sensing devices. The understanding of the mechanisms and factors that drive spontaneous and stable deposition, in water, of porphyrins (and their complex species) onto inorganic surfaces paves the way for a straightforward and environmentally friendly noncovalent functionalization of solid surfaces. Here, we show that surface charge considerations need to be carefully considered if water-soluble porphyrin derivatives have to be successfully immobilized onto zinc oxide (ZnO) layers deposited on glass. In particular, it will be demonstrated that the electrostatics of the glass support has a central role in driving the layering of charged (anionic and cationic) porphyrin derivatives. Finally, our results underline the robustness and versatility of the noncovalently driven deposition—in terms of both reproducibility and stability o...

Femtosecond to Second Studies of a Water-Soluble Porphyrin Derivative in Chemical and Biological Nanocavities

The interactions of 5,10,15,20-tetrakis(4-sulfonatophenyl)-porphyrin (TSPP) with a quaternary ammonium modified β-cyclodextrin (QA-β-CD) and human serum albumin (HSA) protein in aqueous solutions at pH 7 were studied using steady-state, stopped-flow, and femtosecond to millisecond spectroscopy. TSPP forms 1:1 and 1:2 complexes with QA-β-CD (K(1) = 1.9 × 10(5) M(-1) and K(2) = 7 × 10(3) M(-1)) at 293 K, whereas with the HSA protein only 1:1 complex (K(1) = 1.7 × 10(6) M(-1)) has been found. The chemical and biological nanocavities have notable effects on the fluorescence lifetimes of the Q(x) state (from 9.3 to 11.1 ns in QA-β-CD and 11.6 ns in HSA). Furthermore, the rotational times (400 ps for the free TSPP, 1.6 and 19 ns for QA-β-CD and HSA protein complexes, respectively) clearly indicate the robustness of the formed entities. The confined environment does not affect much the fs dynamics (0.1-0.2 ps) of the encapsulated molecule. However, it clearly affect the ps one (1-2 ps (H(2)O) and 5-10 ps (QA-β-CD and HSA)). The effect of O(2) on the relaxation of the triplet state of the free and encapsulated TSPP is also studied and the obtained results are discussed in light of the shielding effect provided by the chemical and biological cavities. The observed difference, longer triplet lifetime upon encapsulation, might be relevant to the efficiency of this porphyrin in photodynamic therapy. The presteady-state kinetics of the TSPP:HSA has been studied by the stopped-flow spectrometer, and a two-step model was proposed for the complexation processes. The results show the importance of the initial association step for the overall ligand recognition process. This first step occurs with rate constant of ~4 × 10(5) M(-1) s(-1), which is about 5 orders of magnitude larger than the rate constant of the consecutive relaxation processes. We believe that our observations of molecular interaction between TSPP, QA-β-CD, and HSA protein from femtosecond to second at both ground and electronically first excited state give detailed information to improve our understanding of this kind of system and thus for a better design of drug delivery nanocarriers.

Porphyrin and phthalocyanine glycodendritic conjugates: synthesis, photophysical and photochemical properties

Synthesis of water soluble porphyrin and phthalocyanine derivatives with, respectively, eight and sixteen galactose units has been carried out. The combined preliminary photophysical and photochemical features of the new products suggest that they might be promising photodynamic therapeutic agents.

A novel 177Lu-labeled porphyrin for possible use in targeted tumor therapy

Porphyrin and its derivatives exhibit inherent affinity for localization in tumors. Hence, porphyrin derivatives radiolabeled with suitable therapeutic radionuclides could be envisaged as potential agents for targeted tumor therapy. In this direction, a water-soluble porphyrin derivative, viz., 5,10,15,20-tetrakis[4-carboxymethyleneoxyphenyl]porphyrin was synthesized in-house and radiolabeled with (177)Lu with an aim to prepare an agent for targeted tumor therapy. (177)Lu is an attractive radionuclide for the development of targeted radiotherapeutic agents owing to its suitable decay characteristics [T(1/2)=6.73 d, E(beta(max))=0.49 MeV, Egamma=208 keV (11%)], comparatively longer half-life and ease of production with high specific activity. (177)Lu was produced by irradiation of enriched Lu(2)O(3) (64.3% (176)Lu) at a thermal neutron flux of 1x10(14) n/cm(2).s for 14 d. The porphyrin was coupled to a suitable chelator, namely, p-aminobenzyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid for complexation with (177)Lu. The radiolabeling was achieved by incubating 50 microg of the conjugate with (177)LuCl(3) (200 ng Lu) in acetate buffer (pH approximately 5) at 50 degrees C for 1 h. The radiolabeled conjugate was characterized by high-performance liquid chromatography and its biological efficacy was studied in Swiss mice bearing fibrosarcoma tumors. (177)Lu was obtained with a specific activity of approximately 550 TBq/g and radionuclidic purity of 99.98%. The (177)Lu-labeled porphyrin conjugate was obtained with 99% radiochemical purity and it exhibited good in vitro stability. Biodistribution studies revealed good tumor uptake (2.01% IA/g) within 3 h post injection (p.i.) with >94% injected activity exhibiting renal clearance. No significant accumulation of activity was observed in any of the vital organs/tissue. The tumor/blood and tumor/muscle ratios were 2.89 and 16.80, respectively, at 3 h p.i. and further increased till 2 days p.i. up to which the studies continued. Serial scintigraphic images recorded using a gamma camera exhibited significant accumulation of activity in tumor over background at 3 days p.i., and the activity was observed to be retained in the tumor till 14 d. Preliminary efficacy studies carried out in Swiss mice bearing fibrosarcoma tumors showed significant regression of the tumor growth in the treated animals. Bioevaluation and preliminary tumor regression studies provide supportive evidences toward the possible potential of the (177)Lu-labeled porphyrin for targeted tumor therapy.

Enhanced optical limiting performance of a nonlinear absorber in a solution containing scattering nanoparticles

The optical limiting performance of a water-soluble porphyrin derivative is shown to be improved when small-sized (400-nm-diameter) nonabsorbing polystyrene spheres are added to the solution. The optical limiting enhancement is attributed to absorption of diffusive photons that experience longer light pathways than ballistic photons. The effect is demonstrated for nanosecond laser excitation at 532 nm.

Singlet Oxygen Production in Water: Aggregation and Charge-Transfer Effects

Precise quantum yields for generation of singlet molecular oxygen, O2(1Δg), have been measured for tetrakis(4-sulfonatophenyl)porphyrin (TSPP), closely-related water-soluble porphyrin derivatives, and tris(2,2‘-bipyridyl)ruthenium(II) (bpy3Ru2+) in O2-saturated water. Under the experimental conditions, TSPP is present in an aggregated state, but the measured quantum yield for formation of O2(1Δg), ΦΔ = 0.51, remains on the same order as that of the corresponding monomer in methanol, ΦΔ = 0.70. Comparison with the quantum yield for formation of the triplet state indicates that quenching of the triplet by O2 gives O2(1Δg) with an efficiency of ca. 80%. There is a small but significant increase in ΦΔ when D2O is used in place of H2O. For the other porphyrin derivatives, the ability of the aggregate to sensitize formation of O2(1Δg) appears to depend on the total electronic charge resident on the molecule, decreasing with decreasing negative charge. A strong solvent dependence noted for O2(1Δg) production with (bpy3Ru2+) is explained in terms of competition between triplet energy transfer and photoinduced electron (or partial charge) transfer. Similar behavior could be responsible for the relatively low ΦΔ value observed for TSPP.

Synthesis and Some Spectroscopic Properties of Porphyrin Derivatives Connected with Nucleobases (Adenine, Thymine, Guanine and Cytosine) by Alkanamide Chains.

Several kinds of porphyrin derivatives covalently connected with adenine, thymine, guanine, cytosine or adenine-thymine pair in a stacking mode between the porphyrin and nucleobase moiety have been synthesized via amide formation reaction of (2-aminophenyl)porphyrin derivatives with nucleobase-alkanoic acids, and characterized by spectroscopic methods. In the 1H-NMR spectra of these nucleobase-porphyrins the proton signals of the nucleobase moieties appear at remarkably higher fields than those of the reference compounds (the corresponding nucleobase-alkanoates) which have no porphyrin moiety. The behaviors of the high field shifts, due to the diamagnetic ring current effect of the porphyrin ring, reflect the characteristic conformational features of these compounds in which the base moieties are located at the upper zone of the porphyrin ring. The Soret bands of the porphyrin in the electronic absorption spectra were markedly weaker in intensity compared with those of the reference compound which has no nucleobase moiety. Both the high-field shifts of the base protons and the hypochromic effects on the Soret band are larger in guanine and cytosine systems than those in adenine and thymine systems, respectively.Those results indicate greater affinity of guanine and cytosine for porphyrin in comparison with adenine and cytosine, respectively, and this conclusion is compatible with the reported electronic spectral properties of mixtures of polynucleotides and water-soluble porphyrin derivatives.

Interactions of Water Soluble Porphyrin Derivatives with a Zwitterionic Polypeptide

Complex formation of water-soluble porphyrin derivatives with the β-sheet structure of zwitterionic poly(Glu-Val-Lys-Val) was studied by absorption spectra and circular dichroism measurements. Interaction of tetrakis(4-N-methylpyridyl)porphine (TMPyP) with the polypeptide is not observed, whereas tetraphenylporphinetetrasulfonic acid (TPPS) interacts when TPPS exists as a diacid species. Positive charges in porphyrin center for the diacid species may play an important role in complex formation. The monomeric TPPS diacid species aggregates by the addition of the polypeptide, and two types of aggregation species with S-chiral conformation are observed. From [P]/[D]=1 to 5, one aggregation species has absorption bands at 489 nm and 701 nm, which increases with [P]/[D] ratios or decreasing pH. Both the monomer and aggregation species can more effectively bind to the polypeptide with decreasing pH. The other aggregation species is present above [P]/[D]=10, it increases with increasing [P]/[D]. Interconversion between two types of aggregation species would take place from [P]/[D]=5 to 10. The β-sheet content of the polypeptide is kept constant above [P]/[D]=2, but increases slightly around [P]/[D]=1.

Interaction of water-soluble porphyrins with single- and double-stranded polyribonucleotides.

CD and uv-visible absorption studies with several tetracationic water-soluble porphyrin derivatives show that some of these species can serve as probes to discriminate between A- and B-conformational forms of single-stranded polynucleotides. It is also observed that these porphyrins can participate in the formation of double helices by forming transient intermediate complexes en-route to duplex formation.

PHOTOCYTOTOXICITY OF WATER‐SOLUBLE METALLOPORPHYRIN DERIVATIVES

A new water-soluble porphyrin derivative, 2,4-bis(1-decyloxyethyl)-deuteroporphyrinyl-6,7-bisaspart ic acid (C10-DP), and its metal complexes (Ga, I(n), Zn, Mn, Cu, Ni and Fe) were examined for their physicochemical properties (absorption, fluorescence, triplet lifetime and partition coefficient) and photocytotoxicity on HeLa cells. The five derivatives with longer (> 1 ms) triplet lifetimes (free base, Zn, Ga, I(n) and Sn complexes) exhibited remarkable photocytotoxicity, and the other derivatives (Mn, Cu, Ni and Fe), which had or were deduced to have fairly short (< 0.01 ms) triplet lifetimes, manifested no photocytotoxicity, indicating that the triplet lifetime of these derivatives played a significant role in their photocytotoxicity. Cellular fluorescence due to C10-DP and its gallium complex was observed mainly on the plasma membrane at the concentrations showing significant photocytotoxicity with low (< 32.6%) cytotoxicity in the dark (2-10 microM).