Effect of organic matter on the in vitro photoeradication of Pseudomonas aeruginosa by means of a cationic tetraaryl-porphyrin

Photodynamic therapy is emerging as an antimicrobial alternative approach; the concomitant presence of a photosensitizer (PS), O(2) and visible light induces lethal oxidative damages to bacterial cells. Among Gram-negative bacteria, Pseudomonas aeruginosa seems to be one of the least susceptible to photodynamic treatment. In this study, we evaluated the influence of several experimental conditions on photoeradication of a planktonic culture of P. aeruginosa PAO1 by means of a tetracationic meso-arylsubstituted porphyrin (RM24). Our findings suggest that the photo-oxidative stress induced by RM24 is strictly correlated to the amount of PS bound to the cells that in turn decreases with the increasing concentrations of organic compounds in the medium. The photoeradication is dependent on PS concentrations, cellular density and light dose. RM24 was able to induce oxidative stress by means of singlet oxygen formation, although ROS formation cannot be ruled out. The standardized experimental conditions of the photospot test allowed us to evidence intraspecific PDT sensitivity differences among three strains of P. aeruginosa.     

Porphyrins and related compounds as photoactivatable insecticides. 3. Laboratory and field studies

The exposure of populations of Ceratitis capitata (fruit fly), Bactrocera oleae (olive fly) and Stomoxis calcitrans (house fly) to a bait containing mumolar concentrations of porphyrin-type photosensitizers resulted in a significant accumulation of the porphyrin by the insects and a consequent development of photosensitivity upon exposure to visible light. The photoinsecticidal activity appeared to increase with increasing hydrophobicity of the porphyrin molecule: thus, the amphiphilic dicationic meso-di(cis-4N-methyl-pyridyl)-cis-diphenyl-porphine (n-octanol/water partition coefficient = 20) was markedly more efficient than its tricationic analogue or the dianionic hematoporphyrin (n-octanol/water partition coefficient = 12). The observed large decrease in the acetylcholinesterase activity of the photosensitized flies suggests that the damage of the nervous system gives an important contribution to the phototoxic action of porphyrins. Studies with C. capitata indicate that the photoinsecticidal action of porphyrins can be utilized to control the population of noxious insects also in open field conditions.     

Light-activated antibacterial surfaces comprise photosensitizers

Antibacterial surfaces were prepared using a base polyethylene sheet topped with a layer containing a mixed powder of poly (vinylidene fluoride) and photosensitizers (PSs). A crimpled stamp was placed on the mixed powder, and then it was passed through a heating and pressing device. The three chosen PSs were rose bengal, toluidine blue O and methylene blue. Scanning electron microscope analysis showed that the PS surface texture was coarse and highly developed. Measurement of the apparent contact angles of the droplets deposited on the PS surfaces using goniometry showed that all three surfaces were hydrophobic. Photodynamic analysis of the surfaces into which the PSs were incorporated indicated significant reactive oxygen species formation after illumination with light fluency rate of 1.46 mW cm(-2) for 30 min. Photodynamic inactivation assays performed in nutrient broth demonstrated more than 4 log reduction of the attached Escherichia coli after illumination (1.46 mW cm(-2)) for 24 h when the inoculum was 10(3) CFU mL(-1). However, more than 4 log reduction of Staphylococcus aureus occurred even when the cultures were illuminated for only 6 h. Our results provide an inexpensive, simple, state-of-the-art method for preparing antibacterial surfaces that may help prevent infections in hospital surroundings and in some medical devices.     

Synthesis of novel azo Schiff bases and their antibacterial and antifungal activities

Ten new azo Schiff bases 5a-h and 7a-b were prepared in excellent yields via the condensation of different aromatic amines and a new azoaldehyde, 2-hydroxy-3- methoxy-5-(4-methoxyphenylazo)benzaldehyde (4) by two different methods. All new compounds were tested against five microorganisms: Staphylococcus aureus (Gram positive and methicillin resistant), Bacillus subtilis (Gram positive), Kelebsiella pneumonia, Pseudomonas aeruginosa and Escherichia coli (all Gram negative). Compounds 4, 5a, 5c, 5d and 5g were moderately active against Staphylococcus aureus and Bacillus subtilis. Compound 7b was highly active against Bacillus subtilis and moderately active against Staphylococcus aureus. Other compounds were inactive against these strains of bacteria. The antifungal activities of these compounds were also tested against eight different fungal species. None of them were active against the fungi species tested.     

Effect of albumin on the photodynamic inactivation of microorganisms by a cationic porphyrin

BACKGROUND: Photodynamic inactivation (PDI) employs visible light and a photosensitizer to inactivate cells. The technique is currently clinically used for the treatment of several malignancies. However, the PDI of microorganisms still remains in the research phase. PURPOSE: To study the effect of human blood plasma and human serum albumin (HSA) on the PDI of Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans. METHODS: PDI experiments were performed using white light (30 mW cm-2) and the cationic 5-phenyl-10,15,20-tris(N-methyl-4-pyridyl)porphyrin chloride (TriP[4]) as photosensitizer. RESULTS: The microorganisms could be successfully photoinactivated by TriP[4] when suspended in phosphate buffered saline (PBS). In this medium, P. aeruginosa was the most resistant microorganism. Changing the suspending medium from PBS to human blood plasma reduced the PDI of all three microorganisms. In human blood plasma C. albicans was the most resistant microorganism. The same results were obtained with 4.5% and 7% HSA/PBS suspensions. CONCLUSIONS: Albumin inhibits the PDI of S. aureus, P. aeruginosa and C. albicans in a dose dependent manner. However, our results are encouraging towards the potential future application of PDI for the treatment of superficial wound infections caused by S. aureus, P. aeruginosa and C. albicans.     

A nonionic porphyrin as a noninterfering DNA antibacterial agent

The increasing interest in clinical bacterial photodynamic inactivation has led to the search for photosensitizers with higher bactericidal efficiency and less side effects on the surrounding tissues. We present a novel nonionic porphyrin, the 5,10,15-tris(2,6-dichlorophenyl)-20-[4-N-(6-amino-hexyl)sulfonamido)phenyl]-porphyrin (ACS769F4) with substantial improvements in the efficiency of nonionic sensitizers. This porphyrin causes eradication of both Escherichia coli and Staphylococcus aureus by the photodynamic effect but in higher concentrations compared with 5,10,15,20-tetrakis (4-N,N,N-trimethylammoniumphenyl)-porphyrin p-tosylate (TTAP(4+)), a known bactericidal tetracationic porphyrin. More important, under such conditions, ACS769F4 proved to be harmless to two mammalian cells lines (human embryonic and baby hamster kidney), causing no reduction in their viability or negative impact on their cytoskeleton, despite its accumulation in cellular structures. On the contrary, TTAP(4+) is shown to accumulate in the nucleus of mammalian cells, in association to DNA, causing chromatin condensation after exposure to light. Furthermore, dark incubation with TTAP(4+) was shown to have a deleterious effect on the microtubule network. Based on its bactericidal efficiency, also observed without exposure to light, and on the low tendency to be harmful or genotoxic to mammalian cells, ACS769F4 should be looked at as an interesting photosensitizer to be evaluated for clinical purposes.     

Membrane‐Anchoring Photosensitizer with Aggregation‐Induced Emission Characteristics for Combating Multidrug‐Resistant Bacteria

Traditional photosensitizers (PSs) show reduced singlet oxygen (¹O₂) production and quenched fluorescence upon aggregation in aqueous media, which greatly affect their efficiency in photodynamic therapy (PDT). Meanwhile, non‐targeting PSs generally yield low efficiency in antibacterial performance due to their short lifetimes and small effective working radii. Herein, a water‐dispersible membrane anchor (TBD‐anchor) PS with aggregation‐induced emission is designed and synthesized to generate ¹O₂ on the bacterial membrane. TBD‐anchor showed efficient antibacterial performance towards both Gram‐negative (Escherichia coli) and Gram‐positive bacteria (Staphylococcus aureus). Over 99.8 % killing efficiency was obtained for methicillin‐resistant S. aureus (MRSA) when they were exposed to 0.8 μm of TBD‐anchor at a low white light dose (25 mW cm^?2) for 10 minutes. TBD‐anchor thus shows great promise as an effective antimicrobial agent to combat the menace of multidrug‐resistant bacteria.     

Homogeneous photocatalytic hydrogen production using π-conjugated platinum(II) arylacetylide sensitizers

Three platinum(II) terpyridylacetylide charge-transfer complexes possessing a lone ancillary ligand systematically varied in phenylacetylide π-conjugation length, [Pt((t)Bu(3)tpy)([C≡CC(6)H(4)](n)H)]ClO(4) (n = 1-3), are evaluated as photosensitizers (PSs) for visible-light-driven (λ > 420 nm) hydrogen production in the presence of a cobaloxime catalyst and the sacrificial electron donor triethanolamine (TEOA). Excited-state reductive quenching of the PS by TEOA produces PS(-) (k(q) scales with the driving force as 1 > 2 > 3), enabling thermal electron transfer to the cobalt catalyst. The initial H(2) evolution is directly proportional to the incident photon flux and visible-light harvesting capacity of the sensitizer, 3 > 2 > 1. The combined data suggest that PSs exhibiting attenuated bimolecular reductive quenching constants with respect to the diffusion limit can overcome this deficiency through improved light absorption in homogeneous H(2)-evolving compositions.     

Altholactone displays promising antimicrobial activity

The antimicrobial activity of altholactone, a naturally extracted styryllactone isolated from Goniothalamus malayanus, was determined against Gram positive (S. aureus ATTC 25923, S. aureus ATTC 25392, and E. faecalis ATTC 29212) and Gram negative (E. coli ATTC 35218, S. typhi ATTC 14023 and P. aeruginosa ATCC 27853) reference bacteria and against the fungus C. albicans ATTC 10231. Different concentrations of altholactone (0, 12, 25, and 50 μg/mL) were used. Results revealed that altholactone inhibited the growth of all tested microbes except P. aeruginosa ATCC 27853 in a dose-dependent manner, with the highest cytotoxic effects occurring at 50 μg/mL. The average of the inhibition zones of the different concentrations was between 0-30 mm. Furthermore, altholactone-induced antimicrobial activity against the more sensitive microbes was assessed by measuring the minimal inhibitory concentration (MIC). Results indicated that Gram positive (S. aureus ATTC 25923, S. aureus ATTC 25392, and E. faecalis ATTC 29212) cells were more sensitive to altholactone than Gram negative ones (E. coli ATTC 35218, S. typhi ATTC 14023). C. albicans showed moderate sensitivity. These results indicate that altholactone might be a potential antimicrobial agent, particularly in ciprofloxacin-refractory S. aureus and E. faecalis infections. Further investigations are required to illustrate the mechanism(s) by which altholactone produces its antimicrobial effects.     

Establishing a Robust and Reliable Response from a Potent Osmium-Based Photosensitizer Via Lipid Nanoformulation†

Osmium (Os) based photosensitizers (PSs) are a unique class of nontetrapyrrolic metal-containing PSs that absorb red light. We recently reported a highly potent Os(II) PS, rac-[Os(phen)₂(IP-4T)](Cl)₂, referred to as ML18J03 herein, with light EC₅₀ values as low as 20 pm . ML18J03 also exhibits low dark toxicity and submicromolar light EC₅₀ values in hypoxia in some cell lines. However, owing to its longer oligothiophene chain, ML18J03 is not completely water soluble and forms 1–2 μm sized aggregates in PBS containing 1% DMSO. This aggregation causes variability in PDT efficacy between assays and thus unreliable and irreproducible reports of in vitro activity. To that end, we utilized PEG-modified DPPC liposomes (138 nm diameter) and DSPE-mPEG₂₀₀₀ micelles (10.2 nm diameter) as lipid nanoformulation vehicles to mitigate aggregation of ML18J03 and found that the spectroscopic properties important to biological activity were maintained or improved. Importantly, the lipid formulations decreased the interassay variance between the EC₅₀ values by almost 20-fold, with respect to the unformulated ML18J03 when using broadband visible light excitation (P = 0.0276). Herein, lipid formulations are presented as reliable platforms for more accurate in vitro photocytotoxicity quantification for PSs prone to aggregation (such as ML18J03) and will be useful for assessing their in vivo PDT effects.     

Rational design of iridium–porphyrin conjugates for novel synergistic photodynamic and photothermal therapy anticancer agents

Near-infrared (NIR) emitters are important probes for biomedical applications. Nanoparticles (NPs) incorporating mono- and tetranuclear iridium(iii) complexes attached to a porphyrin core have been synthesized. They possess deep-red absorbance, long-wavelength excitation (635 nm) and NIR emission (720 nm). TD-DFT calculations demonstrate that the iridium–porphyrin conjugates herein combine the respective advantages of small organic molecules and transition metal complexes as photosensitizers (PSs): (i) the conjugates retain the long-wavelength excitation and NIR emission of porphyrin itself; (ii) the conjugates possess highly effective intersystem crossing (ISC) to obtain a considerably more long-lived triplet photoexcited state. These photoexcited states do not have the usual radiative behavior of phosphorescent Ir(iii) complexes, and they play a very important role in promoting the singlet oxygen (¹O₂) and heat generation required for photodynamic therapy (PDT) and photothermal therapy (PTT). The tetranuclear 4-Ir NPs exhibit high ¹O₂ generation ability, outstanding photothermal conversion efficiency (49.5%), good biocompatibility, low half-maximal inhibitory concentration (IC₅₀) (0.057 μM), excellent photothermal imaging and synergistic PDT and PTT under 635 nm laser irradiation. To our knowledge this is the first example of iridium–porphyrin conjugates as PSs for photothermal imaging-guided synergistic PDT and PTT treatment in vivo.

Iridium–porphyrin conjugates assembled in nanoparticles are photosensitizers that exhibit excellent photothermal imaging and synergistic PDT and PTT in vivo.     

Chlorination-Mediated π–π Stacking Enhances the Photodynamic Properties of a NIR-II Emitting Photosensitizer with Extended Conjugation

NIR-II-emitting photosensitizers (PSs) have attracted great research interest due to their promising clinical applications in imaging-guided photodynamic therapy (PDT). However, it is still challenging to realize highly efficient PDT on NIR-II PSs. In this work, we develop a chlorination-mediated π–π organizing strategy to improve the PDT of a PS with conjugation-extended A-D-A architecture. The significant dipole moment of the carbon-chlorine bond and the strong intermolecular interactions of chlorine atoms bring on compact π–π stacking in the chlorine-substituted PS, which facilitates energy/charge transfer and promotes the photochemical reactions of PDT. Consequently, the resultant NIR-II emitting PS exhibits a leading PDT performance with a yield of reactive oxygen species higher than that of previously reported long-wavelength PSs. These findings will enlighten the future design of NIR-II emitting PSs with enhanced PDT efficiency.     

The antimicrobial activity of inert oligonuclear polypyridylruthenium(II) complexes against pathogenic bacteria, including MRSA

The minimum inhibitory concentrations (MIC) of a series of synthetic inert polypyridylruthenium(II) complexes against four strains of bacteria--Gram positive Staphylococcus aureus (S. aureus) and methicillin-resistant S. aureus (MRSA), and Gram negative Escherichia coli (E. coli) and Pseudomonas aeruginosa (P. aeruginosa)--have been determined. The results demonstrate that for the dinuclear ruthenium(II) complexes ΔΔ/ΛΛ-[{Ru(phen)(2)}(2){μ-bb(n)}](4+) {where phen = 1,10-phenanthroline; bb(n) = bis[4(4'-methyl-2,2'-bipyridyl)]-1,n-alkane (n = 2, 5, 7, 10, 12 or 16)} the complexes linked by the bb(12), bb(14) and bb(16) ligands are highly active, with MIC values of 1 μg mL(-1) against both S. aureus and MRSA, and 2-4 and 8-16 μg mL(-1) against E. coli and P. aeruginosa, respectively. The mononuclear complex [Ru(Me(4)phen)(3)](2+) showed equal activity (on a mole basis) against S. aureus compared with the Rubb(12), Rubb(14) and Rubb(16), but was considerably less active against MRSA and the two Gram negative bacteria. For the dinuclear Rubb(n) family of complexes, the antimicrobial activity was related to the octanol-water partition coefficient (logP). However, the highly lipophilic mononuclear complex Δ-[Ru(phen)(2)(bb(16))](2+) was significantly less active than Rubb(16), highlighting the importance of the dinuclear structure. Preliminary toxicity assays were also carried out for the ΔΔ isomers of Rubb(7), Rubb(10), Rubb(12) and Rubb(16) against two human cells lines, fresh red blood cells and THP-1 cells. The results showed that the dinuclear ruthenium complexes are significantly less toxic to human cells compared to bacterial cells, with the HC(50) and IC(50) values 100-fold higher than the MIC for the complex that showed the best potential--ΔΔ-Rubb(12).     

Effect of monovalent and divalent cations on the photoinactivation of bacteria with meso-substituted cationic porphyrins

It is well established that for successful photoinactivation (PI) of gram-negative bacteria a cationic photosensitizer is required. This requirement suggests a charge-dependent interaction between the photosensitizer and the gram-negative bacterium, which may be influenced by the presence of ions in the suspending medium. The aim of the present study was to investigate the effect of cations Na+ and Ca2+ on the efficacy of the PI of the gram-negative Pseudomonas aeruginosa and the gram-positive Staphylococcus aureus. The bacteria were suspended in buffer containing either meso-tetra(N-methyl-4-pyridyl)-porphyrin or meso-mono-phenyl-tri(N-methyl-4-pyridyl)-porphyrin as photosensitizer and various concentrations of Na+ or Ca2+. The cell suspensions were exposed to a broadband light dose of 9 J/cm2. In buffer without added cations, P. aeruginosa and S. aureus were equally sensitive to PI. Addition of cations strongly decreased the sensitivity of both bacteria to PI, with the PI of P. aeruginosa being much more decreased than that of S. aureus, and Ca2+ being more effective than Na+. The decreased sensitivity was accompanied by a reduced binding of the photosensitizers to the bacteria.     

Photodynamic antifungal chemotherapy

The growing resistance against antifungal drugs has renewed the search for alternative treatment modalities, and antimicrobial photodynamic therapy (PDT) seems to be a potential candidate. Preliminary findings have demonstrated that dermatophytes and yeasts can be effectively sensitized in vitro and in vivo by administering photosensitizers (PSs) belonging to four chemical groups: phenothiazine dyes, porphyrins and phthalocyanines, as well as aminolevulinic acid, which, while not a PS in itself, is effectively metabolized into protoporphyrin IX. Besides efficacy, PDT has shown other benefits. First, the sensitizers used are highly selective, i.e., fungi can be killed at combinations of drug and light doses much lower than that needed for a similar effect on keratinocytes. Second, all investigated PSs lack genotoxic and mutagenic activity. Finally, the hazard of selection of drug resistant fungal strains has been rarely reported. We review the studies published to date on antifungal applications of PDT, with special focus on yeast, and aim to raise awareness of this area of research, which has the potential to make a significant impact in future treatment of fungal infections.     

Highly-efficient photosensitizer based on AIEgen-decorated porphyrin for protein photocleaving

An AIEgen decorated porphyrin (TPETPyP) with ¹O₂ quantun yield as high as 0.85 in PBS was facilely prepared through a simple one-step reaction for efficient photocleavage of proteins in PDT.     

阿糖胞苷金属卟啉衍生物的合成及光动力抗肿瘤活性

设计并合成了阿糖胞苷卟啉衍生物(AHP), 并通过金属插入反应获得了4种金属卟啉衍生物, 采用核磁共振、红外光谱、紫外-可见光谱和质谱等手段对化合物的结构进行了表征.光动力抗肿瘤活性实验结果表明, 含药浓度为25 μmol/L的ZnAHP经光照30 min后对人乳腺癌MCF-7细胞的光动力杀伤率平均达(45.86±8.20)%.     

Synthesis and biological activity of N-substituted-3-chloro-2-azetidinones

2-Aminobenzothiazole-6-carboxylic acid (1), on condensation with chloroacetyl chloride yielded 2-(2-chloroacetylamino)benzothiazole-6-carboxylic acid (2), which on amination with hydrazine hydrate yielded in turn 2-(2-hydrazinoacetylamino)benzo-thiazole-6-carboxylic acid (3). Compound 3, on condensation with various aromatic aldehydes afforded a series of 2-{2-[N'-(arylidene)hydrazino]acetylamino}benzothiazole-6-carboxylic acids 4a-h, which upon dehydrative annulation in the presence of chloroacetyl chloride and triethylamine yielded 2-{2-[3-chloro-2-(aryl)-4-oxoazetidin-1-ylamino]-acetylamino}benzothiazole-6-carboxylic acids 5a-h. The synthesized compounds 4a-h and 5a-h were screened for their antibacterial activity against four microorganisms: Staphylococcus aureus (Gram positive), Bacillus subtilis (Gram positive), Psuedomonas aeruginosa (Gram negative) and Escherichia coli (Gram negative). They were found to exhibit good to moderate antibacterial activity. The antifungal activity of these compounds were also tested against three different fungal species. None of them were active against the species tested.     

Green synthesis and characterization of spherical copper nanoparticles as organometallic antibacterial agent

A facile and green route for the synthesis of copper nanoparticles (Cu NPs) has been achieved using green tea extract as a reducing, capping and stabilizing agent. UV–visible spectra gave surface plasmon resonance at 560 nm. The Cu NPs were characterized using various techniques. The size of the Cu NPs was about 20 nm. Antibacterial activity of biogenic Cu NPs were investigated against bacterial species Staphylococcus aureus , Bacillus subtilis , Pseudomonas aeruginosa and Escherichia coli and compared based on diameter of inhibition zone in disc diffusion assay and minimum inhibitory concentration and minimum bactericidal concentration of NPs dispersed in liquid cultures. The NPs showed better inhibitory activity against Gram‐positive bacteria (S. aureus and B. subtilis ) compared to Gram‐negative bacteria. Toxicity of the NPs was evaluated against animal cell line using MTT assay.     

Strong Visible‐Light‐Absorbing Cuprous Sensitizers for Dramatically Boosting Photocatalysis

Developing strong visible‐light‐absorbing (SVLA) earth‐abundant photosensitizers (PSs) for significantly improving the utilization of solar energy is highly desirable, yet it remains a great challenge. Herein, we adopt a through‐bond energy transfer (TBET) strategy by bridging boron dipyrromethene (Bodipy) and a Cu^I complex with an electronically conjugated bridge, resulting in the first SVLA Cu^I PSs ( Cu‐2 and Cu‐3 ). Cu‐3 has an extremely high molar extinction coefficient of 162 260 m ^?1 cm^?1 at 518 nm, over 62 times higher than that of traditional Cu^I PS ( Cu‐1 ). The photooxidation activity of Cu‐3 is much greater than that of Cu‐1 and noble‐metal PSs (Ru(bpy)₃²⁺ and Ir(ppy)₃⁺) for both energy‐ and electron‐transfer reactions. Femto‐ and nanosecond transient absorption and theoretical investigations demonstrate that a “ping‐pong” energy‐transfer process in Cu‐3 involving a forward singlet TBET from Bodipy to the Cu^I complex and a backward triplet‐triplet energy transfer greatly contribute to the long‐lived and Bodipy‐localized triplet excited state.