Neutral Porphyrin Research Articles

Toxicological assessment of photoactivated tetra-cationic porphyrin molecules under white light exposure in a Caenorhabditis elegans model

Photodynamic therapy (PDT) utilizes the potential of photosensitizing substances to absorb light energy and produce reactive oxygen species. Tetra-cationic porphyrins, which have organic or coordination compounds attached to their periphery, are heterocyclic derivatives with well-described antimicrobial and antitumoral properties. This is due to their ability to produce reactive oxygen species and their photobiological properties in solution. Consequently, these molecules are promising candidates as new and more effective photosensitizers with biomedical, environmental, and other biomedical applications. Prior to human exposure, it is essential to establish the toxicological profile of these molecules using in vivo models. In this study, we used Caenorhabditis elegans, a small free-living nematode, as a model for assessing toxic effects and predicting toxicity in preclinical research. We evaluated the toxic effects of porphyrins (neutral and tetra-cationic) on nematodes under dark/light conditions. Our findings demonstrate that tetra-methylated porphyrins (3TMeP and 4TMeP) at a concentration of 3.3 µg/mL (1.36 and 0.93 µM) exhibit high toxicity (as evidenced by reduced survival, development, and locomotion) under dark conditions. Moreover, photoactivated tetra-methylated porphyrins induce higher ROS levels compared to neutral (3TPyP and 4TPyP), tetra-palladated (3PdTPyP and 4PdTPyP), and tetra-platinated (3PtTPyP and 4PtTPyP) porphyrins, which may be responsible for the observed toxic effects.

Construction of Aluminum‐Porphyrin‐Based Hypercrosslinked Ionic Polymers (HIPs) by Direct Knitting Approach for CO2 Capture and In‐Situ Conversion to Cyclic Carbonates

AbstractHypercrosslinked polymers (HCPs) constructed by Friedel‐Crafts reaction have drawn increasing attention in recent decades, but their multifunctionalization remains a huge challenge. Herein, a series of aluminum‐porphyrin‐based hypercrosslinked ionic polymers have been successfully synthesized by direct knitting approach without additional electrophilic comonomers, which involves the copolymerization of neutral porphyrin monomers and ionic building. By increasing the connected nodes numbers of ionic monomers, the introduction of abundant tetraphenylmethane fragements into the porphyrin backbones endows them with high‐density ionic active sites. Accordingly, the well‐matched molar ratios of aluminum sites to nucleophilic chloride anions that work synergistically for CO2/epoxide coupling can be achieved. Al‐HIP‐2 with flexible ionic pendants and a high Al/Cl ratio allows CO2 cycloaddition to be performed at ambient conditions or with diluted CO2; while Al‐HIP‐3 with rigid ionic moieties and a relatively low Al/Cl ratio exhibits higher specific surface area and stronger CO2 capture ability. Therefore, this co‐condensation strategy provides a simple and feasible pathway for adjusting the reactivity ratios of comonomers via simple structural changes in the knitting process, thus achieving the rational construction of multifunctionalized HCPs for CO2 capture and in‐situ conversion to cyclic carbonates.

The first evidence of antibiofilm action of Proteus mirabilis with tetra-cationic porphyrins containing cisplatin by antimicrobial photodynamic therapy.

Biofilms are responsible for up to 80% of antimicrobial-resistant nosocomial infections. Most of these infections are associated with medical devices such as urinary catheters, and in this context, it is estimated that 90-100% of patients who undergo long-term catheterization develop infections. Proteus mirabilis, the most prevalent microorganism, is responsible for 20-45% of these infections. Thus, this study aimed to evaluate, for the first time, the antimicrobial and antibiofilm effects of cationic porphyrins on P. mirabilis. Neutral porphyrins 3-H2TPyP and 4-H2TpyP and tetra-cationic derivatives 3-cis-PtTPyP and 4-cis-PtTPyP were evaluated in broth microdilution tests to determine the minimum inhibitory and bactericidal concentrations. Time-kill curves, checkerboard test, reactive oxygen species (ROS) scavenger assays, conventional biofilm formation, and biofilm assay with catheters were also performed. The microdilution tests showed greater efficacy against P. mirabilis when 3-cis-PtTPyP was exposed to white-light conditions; this also occurred when the microbial time-kill curve was performed at 0, 2, 6, and 12h. The radical superoxide species was possibly responsible for photoinactivation in the ROS scavenger assays. In biofilm assays (conventional and catheter), 3-cis-PtTPyP obtained better results when irradiated with a white-light source. In the checkerboard assay, the same compound showed no differences when tested in association with ciprofloxacin hydrochloride. Our findings lead us to conclude that antimicrobial photodynamic therapy and cationic porphyrins obtained positive results and are promising alternatives to treat P. mirabilis biofilms.

Spectroscopic investigation of the electronic and excited state properties of para-substituted tetraphenyl porphyrins and their electrochemically generated ions

Porphyrins play pivotal roles in many crucial biological processes including photosynthesis. However, there is still a knowledge gap in understanding electronic and excited state implications associated with functionalization of the porphyrin ring system. These effects can have electrochemical and spectroscopic signatures that reveal the complex nature of these somewhat minor substitutions, beyond simple inductive or electronic effect correlations. To obtain a deeper insight into the influences of porphyrin functionalization, four free-base, meso-substituted porphyrins: tetraphenyl porphyrin (TPP), tetra(4-hydroxyphenyl) porphyrin (THPP), tetra(4-carboxyphenyl) porphyrin (TCPP), and tetra(4-nitrophenyl) porphyrin (TNPP), were synthesized, characterized, and investigated. The influence of various substituents, (-hydroxy,-carboxy, and -nitro) in the para position of the meso-substituted phenyl moieties were evaluated by spectroelectrochemical techniques (absorption and fluorescence), femtosecond transient absorption spectroscopy, cyclic and differential pulse voltammetry, ultraviolet photoelectron spectroscopy (UPS), and time-dependent density functional theory (TD-DFT). Spectral features were evaluated for the neutral porphyrins and differences observed among the various porphyrins were further explained using rendered frontier molecular orbitals pertaining to the relevant transitions. Electrochemically generated anionic and cationic porphyrin species indicate similar absorbance spectroscopic signatures attributed to a red-shift in the Soret band. Emissive behavior reveals the emergence of one new fluorescence decay pathway for the ionic porphyrin, distinct from the neutral macrocycle. Femtosecond transient absorption spectroscopy analysis provided further analysis of the implications on the excited-state as a function of the para substituent of the free-base meso-substituted tetraphenyl porphyrins. Herein, we provide an in-depth and comprehensive analysis of the electronic and excited state effects associated with systematically varying the induced dipole at the methine bridge of the free-base porphyrin macrocycle and the spectroscopic signatures related to the neutral, anionic, and cationic species of these porphyrins.

Crystalline paramagnetic supramolecular 2D-polymer of the tetra(4-pyridyl)porphyrin and terbium(III) complex.

A new promising method for the preparation of crystalline 2D polymers based on tetra(4-pyridyl)porphyrin has been developed. Radical anion {H2T(4-Py)P˙-} species are used as the starting material. A new solid-state supramolecular array [{H2T(4-Py)P}·{TbIII(TMHD)3}2]·2.84C6H14 (1) in which porphyrin units are bridged with TbIII ions to form a self-assembled 2D polymer has been obtained. The complex contains neutral porphyrin macrocycles, which is supported by optical and magnetic data. High-spin paramagnetic TbIII ions are weakly antiferromagnetically coupled in accordance with rather long distances between them.

Structural and spectral transformation of cationic porphyrin TMPyP4 at adsorption on graphene

Hybrids of graphene nanomaterials with porphyrins possess distinct photo and electronic properties that enable a wide spectrum of applications involving interaction with light. In this work we analyze structural and spectral transformations of cationic meso-5,10,15,20-tetra-(N-methyl-4-pyridyl) porphyrin (ТМРyР4) at adsorption on graphene. It is shown that the binding of TMPyP4 with graphene is stronger as compared to the neutral porphyrin (TPP) with a similar structure (-111.0 vs -22.6 kcal/mol). This is due to a large contribution from the cation-π-electrons interaction. The interaction of TMPyP4 with graphene is accompanied with a distortion of the flat structure of the porphyrin core and twisting of the side rings. As a result, the porphyrin molecule flattens. The cationic porphyrin adsorbed to graphene induces a stronger molecule flattening in comparison with the neutral porphyrin. A comparison of the experimental and calculated (DFT) UV spectra allows estimating the contribution of the π-π stacking and the twisting of the side rings to the observed red-shifting. The TMPyP4 molecule creates an area of negative potential in graphene close to the porphyrin adsorption site. The adsorption of TMPyP4 on graphene is also investigated with DFT calculations and with molecular dynamics simulations in water environment and in vacuum.

Meso-tetra(dioxanyl)porphyrins: Neutral, low molecular weight, and chiral porphyrins with solubility in aqueous solutions

The synthesis of the low-molecular weight, meso-tetra(dioxan-2-yl)porphyrin with considerable solubility in aqueous solution is described. The key intermediate dioxan-2-carbaldehyde is accessible in either racemic or in stereo-pure forms from commercially available starting materials in three steps. Using 4 × 1 or 2 + 2-type syntheses provide the porphyrin in modest yields. While the racemic aldehyde created an intractable mixture of diastereomers, the enantiopure aldehyde created a single enantiomer of the target porphyrin. The porphyrin was spectroscopically characterized. As its free base or zinc complex, it showed excellent solubility properties in organic and aqueous solvents, though free water-solubility was not achieved. The work expands on the availability of chiral porphyrins and neutral porphyrins with considerable solubility in aqueous solution.

Structural Investigations, Cellular Imaging, and Radiolabeling of Neutral, Polycationic, and Polyanionic Functional Metalloporphyrin Conjugates.

Over the past decade, porphyrin derivatives have emerged as invaluable synthetic building blocks and theranostic kits for the delivery of cellular fluorescence imaging and photodynamic therapy. Tetraphenylporphyrin (TPP), its metal complexes, and related derivatives have been investigated for their use as dyes in histology and as components of multimodal imaging probes. The photophysical properties of porphyrin–metal complexes featuring radiometals have been a focus of our attention for the realization of fluorescence imaging probes coupled with radioimaging capabilities and therapeutic potential having “true” theranostic promise. We report hereby on the synthesis, radiochemistry, structural investigations, and preliminary in vitro and in vivo uptake studies on a range of functionalized porphyrin-based derivatives. In pursuit of developing new porphyrin-based probes for multimodality imaging applications, we report new functionalized neutral, polycationic, and polyanionic porphyrins incorporating nitroimidazole and sulfonamide moieties, which were used as targeting groups to improve the notoriously poor pharmacokinetics of porphyrin tags. The resulting functional metalloporphyrin species were stable under serum challenges and the nitroimidazole and sulfonamide derivatives remained fluorescent, allowing in vitro confocal studies and visualization of the lysosomal uptake in a gallium(III) sulfonamide derivative. The molecular structures of selected porphyrin derivatives were determined by single crystal X-ray diffraction using synchrotron radiation. We also investigated the nature of the emission/excitation behavior of model functional porphyrins using in silico approaches such as TD DFT in simple solvation models. The conjugation of porphyrins with the [7-13] and [7-14] fragments of bombesin was also achieved, to provide targeting of the gastrin releasing peptide receptor (GRPR). Depending on the metal, probe conjugates of relevance for single photon emission computed tomography (SPECT) or positron emission tomography (PET) probes have been designed and tested hereby, using TPP and related functional free base porphyrins as the bifunctional chelator synthetic scaffold and 111In[In] or 68Ga[Ga], respectively, as the central metal ions. Interestingly, for simple porphyrin conjugates good radiochemical incorporation was obtained for both radiometals, but the presence of peptides significantly diminished the radio-incorporation yields. Although the gallium-68 radiochemistry of the bombesin conjugates did not show radiochemical incorporation suitable for in vivo studies, likely because the presence of the peptide changed the behavior of the TPP-NH2 synthon taken alone, the optical imaging assays indicated that the conjugated peptide tags do mediate uptake of the porphyrin units into cells.

Efficient photodynamic inactivation of Candida albicans by porphyrin and potassium iodide co-encapsulation in micelles.

Photodynamic inactivation of bacterial and fungal pathogens is a promising alternative to the extensive use of conventional single-target antibiotics and antifungal agents. The combination of photosensitizers and adjuvants can improve the photodynamic inactivation efficiency. In this regard, it has been shown that the use of potassium iodide (KI) as adjuvant increases pathogen killing. Following our interest in this topic, we performed the co-encapsulation of a neutral porphyrin photosensitizer (designated as P1) and KI into micelles and tested the obtained nanoformulations against the human pathogenic fungus Candida albicans. The results of this study showed that the micelles containing P1 and KI displayed a better photodynamic performance towards C. albicans than P1 and KI in solution. It is noteworthy that higher concentrations of KI within the micelles resulted in increased killing of C. albicans. Subcellular localization studies by confocal fluorescence microscopy revealed that P1 was localized in the cell cytoplasm, but not in the nuclei or mitochondria. Overall, our results show that a nanoformulation containing a photosensitizer plus an adjuvant is a promising approach for increasing the efficiency of photodynamic treatment. Actually, the use of this strategy allows a considerable decrease in the amount of both photosensitizer and adjuvant required to achieve pathogen killing.

Photosensitizers for H2 Evolution Based on Charged or Neutral Zn and Sn Porphyrins.

We report a comparison between a series of zinc and tin porphyrins as photosensitizers for photochemical hydrogen evolution using cobaloxime complexes as molecular catalysts. Among all the chromophores tested, only the positively charged zinc porphyrin, [ZnTMePyP4+]Cl4, and the neutral tin porphyrin derivatives, Sn(OH)2TPyP, Sn(Cl2)TPP-[COOMe]4, and Sn(Cl2)TPP-[PO(OEt)2]4, were photocatalytically active. Hydrogen evolution was strongly affected by the pH value as well as the different concentrations of both the sensitizer and the catalyst. A comprehensive photophysical and electrochemical investigation was conducted in order to examine the mechanism of photocatalysis. The results derived from this study establish fundamental criteria with respect to the design and synthesis of porphyrin derivatives for their application as photosensitizers in photoinduced hydrogen evolution.

Robust Mn(III) N-pyridylporphyrin-based biomimetic catalysts for hydrocarbon oxidations: heterogenization on non-functionalized silica gel versus chloropropyl-functionalized silica gel.

Two classes of heterogenized biomimetic catalysts were prepared and characterized for hydrocarbon oxidations: (1) by covalent anchorage of the three Mn(iii) meso-tetrakis(2-, 3-, or 4-pyridyl)porphyrin isomers by in situ alkylation with chloropropyl-functionalized silica gel (Sil-Cl) to yield Sil-Cl/MnPY (Y = 1, 2, 3) materials, and (2) by electrostatic immobilization of the three Mn(iii) meso-tetrakis(N-methylpyridinium-2, 3, or 4-yl)porphyrin isomers (MnPY, Y = 4, 5, 6) on non-modified silica gel (SiO2) to yield SiO2/MnPY (Y = 4, 5, 6) materials. Silica gel used was of column chromatography grade and Mn porphyrin loadings were deliberately kept at a low level (0.3% w/w). These resulting materials were explored as catalysts for iodosylbenzene (PhIO) oxidation of cyclohexane, n-heptane, and adamantane to yield the corresponding alcohols and ketones; the oxidation of cyclohexanol to cyclohexanone was also investigated. The heterogenized catalysts exhibited higher efficiency and selectivity than the corresponding Mn porphyrins under homogeneous conditions. Recycling studies were consistent with low leaching/destruction of the supported Mn porphyrins. The Sil-Cl/MnPY catalysts were more efficient and more selective than SiO2/MnPY ones; alcohol selectivity may be associated with hydrophobic silica surface modification reminiscent of biological cytochrome P450 oxidations. The use of widespread, column chromatography, amorphous silica yielded Sil-Cl/MnPY or SiO2/MnPY catalysts considerably more efficient than the corresponding, previously reported materials with mesoporous Santa Barbara Amorphous No 15 (SBA-15) silica. Among the materials studied, in situ derivatization of Mn(iii) 2-N-pyridylporphyrin by covalent immobilization on Sil-Cl to yield Sil-Cl/MnP1 showed the best catalytic performance with high stability against oxidative destruction and reusability/recyclability.

Ethynylphenyl-Derivatized Free Base Porphyrins: Anodic Oxidation Processes and Covalent Grafting onto Glassy Carbon Electrodes.

In six of seven cases, direct anodic oxidation of the ethynyl group of an ethynylphenyl-derivatized free-base porphyrin gave modified glassy carbon electrodes in which the porphyrin was strongly surface-bound, most likely in a perpendicular geometry through covalent attachment of the ethynyl group to a surface carbon atom. The porphyrins each contained an ethynylphenyl group in one meso position and varied in the groups present in the other three meso positions. Electrografted 5,10,15,20-tetrakis(ethynylphenyl)porphyrin, H21, which has ethynyl moieties in all four meso positions, has well-defined surface voltammetry and grows to multilayer levels upon repeated cyclic voltammetry (CV) deposition scans. Multilayering was not observed to the same degree for monoethynylphenyl-substituted porphyrins and became progressively less for porphyrins having groups in the 15-meso position that were more protective against ethynyl radical attack. Clean molecular monolayer-level coverage was observed for 5-ethynylphenyl-10,20-bis(3-methoxyphenyl)-15-hexylporphyrin, H25. Owing to the fact that the ethynyl oxidation potential (1.1 to 1.5 V vs ferrocene) is more positive than that of the second macrocycle oxidation, the longevities and follow-up reactions of the porphyrin dications were also studied by CV, chemical oxidation, and optical spectroscopy in homogeneous solution. The primary follow-up products of the doubly oxidized porphyrins, whether surface-bound or in solution, were pyrrole-protonated species that were easily reduced back to the neutral porphyrin.

The Insertion of Ruthenium into Porphyrins Revisited and Improved: Proof of Concept Results with a Ruthenium(II) Monocarbonyl Compound, and the Spectacular Effect of Propionic Acid

This contribution, that readdresses the insertion of the RuII–CO fragment into model porphyrins (i.e. ruthenation), has a Janus character, with one speculative and one practical side. As a proof of concept we demonstrate that ruthenation of a porphyrin can be performed under relatively mild conditions using the RuII monocarbonyl complex [Ru(CO)(dmso)5][PF6]2 that – besides CO – features exclusively labile dmso ligands. Even though this finding might seem trivial, it is only the second example that uses a RuII carbonyl for porphyrin ruthenation, the first one having been reported almost 50 years ago and then neglected. From a practical point of view, we show the spectacular effect of propionic acid as solvent for performing the ruthenation of neutral and anionic model porphyrins with Ru3(CO)12 (1). This process turned out to be extremely efficient and advantageous in terms of both reaction rates and yields (e.g. 100 % ruthenation of TPP in 30 min at 140 °C) compared to the procedures described in the literature.

β-Functionalized Dibenzoporphyrins with Mixed Substituents Pattern: Facile Synthesis, Structural, Spectral, and Electrochemical Redox Properties.

A new series of mixed β-substituted dibenzoporphyrins were synthesized, and the effect of β-substitution on the spectral and electrochemical redox properties of the macrocycle was elucidated. The synthetic route to β-tetrasubstituted dibenzoporphyrins begins with the regioselective bromination of NiTPP(Benzo)2 to afford NiTPP(Benzo)2Br4, followed by Pd catalyzed coupling reaction to access NiTPP(Benzo)2(R)4 (R = phenyl (Ph) and phenylethynyl (PE)). Synthesized benzoporphyrins exhibited red-shifted absorption spectral features with tunable redox properties. These benzoporphyrins displayed pronounced electronic effects of β-substituents on the macrocyclic skeleton. NiTPP(Benzo)2(PE)4 exhibited the lowest HOMO-LUMO gap among the series due to extended π-conjugation. Intrestingly, metal-centered oxidation of Ni(II)/Ni(III) was observed for NiOPP(Benzo)2 and NiOPP(Benzo)Br2 after an initial conversion of the neutral porphyrin to its dicationic form under electrochemical conditions.

Visible light-induced biocidal activities and mechanistic study of neutral porphyrin derivatives against S. aureus and E. coli

Positive charged porphyrins have long been regarded as effective biocidal agents, however neutral porphyrins have rarely been studied in their ability photoinactivating microbials, and the structure-activity relationship such as correlation of electronic effect and biocidal activity of porphyrins still remains unclear. Herein, four neutral porphyrins with various electronic effects were selected to undergo light-induced biocidal processes. It turned out that the TPPOH and TPPNH2 with electron-donating groups NH2 and OH, respectively, exhibited much more powerful light-induced biocidal activities against E. coli and S. aureus than TPP and TPPNO2 with electron-withdrawing group NO2. This phenomenon suggested that neutral porphyrins may be treated as a new class of biocidal agents and functional groups with various electronic effects on porphyrins can dramatically affect porphyrins' light-induced biocidal activities. Mechanistic studies demonstrate that despite a better light-induced antibacterial ability of TPPOH, its singlet oxygen generation efficacy is a little lower than that of TPPNH2, together with charge characteristics and lipophilicity, it is clear that (1) the oxidative species singlet oxygen and ROS played the key role in the photo-activated antimicrobial processes of porphyrins, and (2) higher singlet oxygen or ROS yields of TPPOH and TPPNH2 may originate from their structural characteristics, namely electron-donating groups OH or NH2, and (3) a synergistic effect of all other factors including the electrostatic and hydrophobic effects must involve in the process and cooperatively determine their biocidal activities.

Protoporphyrin-IX conjugated cellulose nanofibers that exhibit high antibacterial photodynamic inactivation efficacy

Towards the development of anti-infective nanoscale materials employing a photodynamic mechanism of action, we report the synthesis, physical properties (SEM, mechanical strength, water contact angle), spectroscopic characterization (infrared, Raman, DRUV), and evaluation of antibacterial efficacy of porphyrin-conjugated regenerated cellulose nanofibers, termed RC-TETA-PPIX-Zn. Cellulose acetate was electrospun to produce nanofibers, thermally treated to enhance mechanical strength, and finally hydrolyzed to produce regenerated cellulose (RC) nanofibers that possessed a high surface area and nanofibrous structure. Covalent grafting of a protoporphyrin IX (PPIX) photosensitizer using epichlorohydrin/triethylenetetramine (TETA), followed by zinc chelation, afforded RC-TETA-PPIX-Zn. The high surface area afforded by the nanofibers and efficient photosensitizer conjugation led to a very high loading of 412 nmol PPIX/mg material, corresponding to a degree of substitution of 0.1. Antibacterial efficacy was evaluated against Staphylococcus aureus (ATCC-6538) and Escherichia coli (ATCC-8099), with our best results achieving detection limit inactivation (99.999+%) of both bacteria after only 20 min illumination (Xe lamp, λ ≥ 420 nm). No statistically significant loss in antibacterial activity was observed when using nanofibers that had been ‘photo-aged’ with 5 h of pre-illumination to simulate the effects of photobleaching. Post aPDI, scanning electron microscopy revealed that the bacteria had undergone cell membrane leakage, consistent with oxidative damage caused by photo-generated reactive oxygen species. Taken together, the conjugation strategy employed here provides a scalable, facile and efficient route to creating nanofibrous materials from natural polymers with a high photosensitizer loading, enabling the use of commercially-available neutral porphyrin photosensitizers, such as PPIX, in the design and synthesis of potent anti-infective nanomaterials.

Synthesis and in vitro PDT evaluation of new porphyrins containing meso-epoxymethylaryl cationic groups.

Photodynamic therapy (PDT) is an effective cancer treatment that uses photosensitizers, light, and oxygen to destroy malignant cells. Porphyrins, and in particular the cationic derivatives, are the most investigated photosensitizers for PDT. In this context, it is important to study new methodologies to develop efficient cationic photosensitizers for use in PDT. New porphyrins bearing cationic epoxymethylaryl groups were synthesized and characterized. Their cellular uptake, intracellular localization, and phototoxicity were evaluated in human HEp2 cells, and compared with their methylated analogs. All cationic porphyrins were efficient generators of singlet oxygen, with quantum yields in the range 0.35-0.61. The two methylated derivatives (3 and 4) accumulated the most within cells at all times investigated, up to 24 hours. Of these two porphyrins, 4 was the most phototoxic to the cells (LD50 = 2.4 μM at 1.5 J/cm2 ); however, porphyrin 3 also showed high phototoxicity (LD50 = 7.4 μM at 1.5 J/cm2 ). The epoxymethyl-containing porphyrins were found to be less phototoxic than the methylated derivatives, with LD50 > 38 μM. The neutral porphyrins showed no phototoxicity up to the 100 μM concentrations investigated, and had the lowest singlet oxygen quantum yields. All cationic porphyrins localized mainly in the cell ER, Golgi apparatus, and lysosomes. Our results suggest that cationic methylated porphyrin derivatives are promising PDT photosensitizing agents. The epoxymethyl-containing derivatives showed increased efficacy relative to the neutral analogs, and are good candidates for further investigation. Lasers Surg. Med. 50:566-575, 2018. © 2018 Wiley Periodicals, Inc.

Manganese porphyrins immobilized on magnetic SBA-15 mesoporous silica as selective and efficient catalysts for cyclic and linear alkane oxidation

This work describes the immobilization of neutral and cationic Mn porphyrins (MnP) on magnetic SBA-15 mesoporous silica. XRD patterns, TEM images and N2 adsorption-desorption analyses showed that the prepared solids had high surface areas and homogeneous porosities, confirming the presence of magnetite (Mag), which is a key feature for fast and easy recovery and reuse of the catalysts. The cationic MnP1 and MnP2 interacted with the support by electrostatic attraction and the neutral MnP by covalent bonding (MnP3). The catalytic activity for oxidation of cis-cyclooctene, cyclohexane, adamantane, n-hexane and substrate mixture (cyclohexane/n-hexane) by iodosylbenzene (PhIO) was investigated for all prepared solids. In heterogeneous catalysis, the solids produced similar or higher yields than the corresponding free MnP catalysts with selectivity for alcohol when alkanes were used as substrate. The best yields of the supported catalysts were 30% of cyclohexanol, 28% of 1-adamantanol, 10% of 2-hexanol, and 18% of cyclohexanol, for oxidations of cyclohexane, adamantane, n-hexane, and cyclohexane/n-hexane mixture, respectively. The catalytic results and the catalyst characterization suggested that MnP2 is immobilized inside the pores of SBA-15. This conclusion was also confirmed further by the selectivity for the primary alcohol in the n-hexane oxidation observed for the catalyst solid prepared with the MnP2. The assembly resulting from the immobilization of MnP2 and the silica pores probably created an adequate environment for the approach of the linear substrate, enabling its oxidation at the terminal carbon.

Neutral Porphyrin Derivative Exerts Anticancer Activity by Targeting Cellular Topoisomerase I (Top1) and Promotes Apoptotic Cell Death without Stabilizing Top1-DNA Cleavage Complexes.

Camptothecin (CPT) selectively traps topoisomerase 1-DNA cleavable complexes (Top1cc) to promote anticancer activity. Here, we report the design and synthesis of a new class of neutral porphyrin derivative 5,10-bis(4-carboxyphenyl)-15, 20-bis(4-dimethylaminophenyl)porphyrin (compound 8) as a potent catalytic inhibitor of human Top1. In contrast to CPT, compound 8 reversibly binds with the free enzyme and inhibits the formation of Top1cc and promotes reversal of the preformed Top1cc with CPT. Compound 8 induced inhibition of Top1cc formation in live cells was substantiated by fluorescence recovery after photobleaching (FRAP) assays. We established that MCF7 cells treated with compound 8 trigger proteasome-mediated Top1 degradation, accumulate higher levels of reactive oxygen species (ROS), PARP1 cleavage, oxidative DNA fragmentation, and stimulate apoptotic cell death without stabilizing apoptotic Top1-DNA cleavage complexes. Finally, compound 8 shows anticancer activity by targeting cellular Top1 and preventing the enzyme from directly participating in the apoptotic process.

Photoconductive behavior of binary porphyrin crystalline assemblies

The mechanism of photoconductivity in a crystalline photoconductor synthesized from 1:1 ratio of meso-tetra(4-pyridyl)porphyrin (TPyP) and meso-tetra(4-sulfonatophenyl)porphyrin (TSPP) ionic tectons was examined. The rod-like crystals of TPyP:TSPP insulate in the dark but become photoconducting on illumination and a portion of the photoinduced current persists after the laser light is turned off. This persistent photoconductivity (PPC) is investigated as a function of laser illumination wavelength, laser power, and sample temperature. The primary charge carriers in the TPyP:TSPP upon photoexcitation are electrons and the charge recombination mechanism follows monomolecular kinetics. The number of electrons contributing to the photocurrent is directly proportional to the number of photons absorbed thus, the mechanisms of the photoconductivity resulting from excitations within the Soret band and the Q-band are the same. The PPC is interpreted to be the result of the formation of photoinduced metastable defects that allow for Miller–Abrahams-like hopping conductivity. The TPyP:TSPP has an incommensurately modulated crystal lattice and its proposed model structure is based on both ionic and neutral porphyrin tectons. The thermogravimetric analysis shows that the porphyrin crystals undergo dehydration on heating (˜50 ∘C) by losing water molecules located in the crystalline channels. Temperature dependent XRD indicates that dehydration causes irreversible changes to the crystal structure. The loss of crystallinity observed with heating the TPyP:TSPP crystals above 90 ∘C causes approximately 25% loss in photoconductivity but has little effect on the lifetime associated with the persistent photoconductivity.