The synthesis and characterization of photonic materials composed of substituted fluorene donors and a porphyrin acceptor

Three novel porphyrin derivatives namely 5,10,15,20-tetra-[7-cyanophenyl-9,9’-bis-(2-ethylhexyl)fluoren-2-yl]-porphyrin, 5,10,15,20-tetra-[7-(4-acetylphenyl)-9,9’-bis-(2-ethylhexyl)fluoren-2-yl]-porphyrin and 5,10,15,20-tetra-[7-pyrenyl-9,9’-bis-(2-ethylhexyl)fluoren-2-yl]-porphyrin were synthesized. Substitution of the aryl groups on the meso-fluorene using Suzuki-Miyaura coupling enabled a study to be undertaken of the energy transfer from the meso fluorenyl to the porphyrin core. To calculate the extent of energy transfer, the corresponding model fluorene compounds 7-cyanophenyl-9,9’-bis-(2-ethylhexyl)fluorene, 7-acetylphenyl-9,9’-bis-(2-ethylhexyl)fluorene and 7-pyrenyl-9,9’-bis-(2-ethylhexyl)fluorene were also synthesized. Fluorescence studies of both the porphyrin derivatives and model compounds showed efficient energy transfer occured from the aryl-fluorene donor to the porphyrin acceptor. Upon excitation, due to energy transfer, a characteristic porphyrin emission was observed at ∼656 nm; ∼99% energy transfer in solution was observed in these donor–acceptor systems. Thin-film emission results indicate a low degree of aggregation in the donor–acceptor systems.     

The synthesis and characterization of photonic materials composed of substituted fluorene donors and a porphyrin acceptor

Three novel porphyrin derivatives namely 5,10,15,20-tetra-[7-cyanophenyl-9,9’-bis-(2-ethylhexyl)fluoren-2-yl]-porphyrin, 5,10,15,20-tetra-[7-(4-acetylphenyl)-9,9’-bis-(2-ethylhexyl)fluoren-2-yl]-porphyrin and 5,10,15,20-tetra-[7-pyrenyl-9,9’-bis-(2-ethylhexyl)fluoren-2-yl]-porphyrin were synthesized. Substitution of the aryl groups on the meso-fluorene using Suzuki-Miyaura coupling enabled a study to be undertaken of the energy transfer from the meso fluorenyl to the porphyrin core. To calculate the extent of energy transfer, the corresponding model fluorene compounds 7-cyanophenyl-9,9’-bis-(2-ethylhexyl)fluorene, 7-acetylphenyl-9,9’-bis-(2-ethylhexyl)fluorene and 7-pyrenyl-9,9’-bis-(2-ethylhexyl)fluorene were also synthesized. Fluorescence studies of both the porphyrin derivatives and model compounds showed efficient energy transfer occured from the aryl-fluorene donor to the porphyrin acceptor. Upon excitation, due to energy transfer, a characteristic porphyrin emission was observed at 656 nm; 99% energy transfer in solution was observed in these donor–acceptor systems. Thin-film emission results indicate a low degree of aggregation in the donor–acceptor systems.     

Novel meso-substituted porphyrins: Synthesis, characterization and photocatalytic activity of their TiO2-based composites

Two series of novel meso-substituted porphyrins, namely 5,10,15,20-tetra[4-(3-phenoxy)-propoxy]phenyl porphyrin, the structural analogue 5,10,15,20-tetra[2-(3-phenoxy)-propoxy]phenyl porphyrin and their Co(II) Cu(II) and Zn(II) complexes were synthesized. The compounds were characterized using various spectroscopic techniques and their molecular structure was proposed based on density functional theory calculations. The diverse properties of the porphyrin derivatives result from the different stereochemistry of the particular substituents at the meso site on the macrocycle and are controlled also by the coordinated metal. The ¹H NMR spectrum of the free-base porphyrin showed a complicated spin-splitting. The photocatalytic activities in degradation of 4-nitrophenol were investigated using polycrystalline TiO₂ impregnated with the porphyrins and metalloporphyrins. The Cu(II) porphyrin was a more effective sensitizer than other metal containing compounds (M = Co, Zn) as well as the free-base. Photocatalytic activity was also influenced by spatial positions of the substitutions on the porphyrin molecules.     

Cation Radicals of Covalently Linked Porphyrin Dimers and their Monomeric Constituents: An ESR and ENDOR Study

The spin density distributions in the cation radicals of various covalently linked porphyrin dimers have been studied by liquid phase ESR and ENDOR methods to find out whether these systems show intramolecular electron delocalization. Such a delocalization is known to occur in the bacteriochlorophyll dimer (“special pair”) in the photosynthetic reaction center. The dimers that were studied in this work were derived from zinc mesotetratolylporphyrin (ZnTTP) and linked at the ortho or para positions of one phenyl ring with varying bridge lengths. ¹H and ^I4N hyperfine coupling constants could be measured for the dimer cation radicals and compared with those of monomeric ZnTTP as well as ZnTTP derivatives that carry alkoxy or hydroxy substituents to mimic the bridges of the dimers. By comparing the hyperfine data of the monomer and dimer cation radicals it is concluded that in the present dimers the unpaired electron is localized on one porphyrin unit.     

Flexible Etherified and Esterified Triphenylethylene Derivatives and Their Evaluation on ER-positive and Triple-Negative Breast Cancer Cell Lines

Tamoxifen (TAM) is a selective estrogen receptor modulator (SERM) with potential clinical benefits for all stages of breast cancer. TAM is primarily metabolized to more potent metabolites via polymorphic CYP2D6. This affects the clinical outcome of TAM treatment. Herein we report novel TAM analogues that can avoid metabolism via CYP2D6. The novel analogues bear a flexible skeleton. Compounds have either an ester group on ring C or homodiaminoalkoxy groups on rings B and C . Compound 6 (E/Z-4-[1-[4-(2-diethylaminoethoxy)phenyl]-3-(4-methoxyphenyl)-2-methyl[propenyl]phenol) was found to be ten-fold more potent than TAM on MCF-7 cells (GI₅₀=0.15 μM). It showed fivefold greater inhibitory activity on MDA-MB-231 cells than TAM (GI₅₀=1.71 μM). Compound 13 (4-{3,3-bis-[4-(3-dimethylaminopropoxy)phenyl]-2-methylallyl}methoxybenzene) was the most potent among the homodiaminoalkoxy derivatives (GI₅₀=0.44) on both MCF-7 and MDA-MB-231 cell lines, respectively. Furthermore, the COMPARE algorithm suggested that it has different molecular targets from those of some other reported anticancer drugs.     

A Mild Catalytic Oxidation System: Ruthenium Porphyrin and 2,6‐Dichloropyridine N‐Oxide Applied for Alkene Dihydroxylation

A new method was developed to transform alkenes into three types of functional molecules, including epoxides, aldehydes and 1,2‐diols by using dichlororuthenium(IV) meso‐tetrakis(2,6‐dichlorophenyl)porphyrin [Ru(IV)(TDCPP)Cl₂] as catalyst and 2,6‐dichloropyridine N‐oxide (Cl₂pyNO) as the oxidant, in which the 1,2‐diols were afforded via “one‐pot” reactions in moderate yields.     

An Amphiphilic BODIPY‐Porphyrin Conjugate: Intense Two‐Photon Absorption and Rapid Cellular Uptake for Two‐Photon‐Induced Imaging and Photodynamic Therapy

The new amphiphilic BODPY‐porphyrin conjugate BZnPP and its precursor BZnPH were synthesised, and their linear and two‐photon photophysical properties, together with their cellular uptake and photo‐cytotoxicity, were studied. This amphiphilic conjugate consists of a hydrophobic BODIPY moiety and a hydrophilic tetra(ethylene glycol) chain bridging a cationic triphenylphosphonium group to an amphiphilic porphyrin ZnP through acetylide linkers at its meso positions. A large two‐photon absorption cross‐section (σ=1725 GM) and a high singlet oxygen quantum yield (0.52) were recorded. Intense linear‐ and two‐photon‐induced red emissions were also observed for both BZnPP and BZnPH. Further in vitro studies showed that BZnPP exhibited very efficient cellular uptake and strong photocytotoxic but weak dark cytotoxic properties towards human breast carcinoma MCF‐7 cells. In summary, the two‐photon‐induced emission and the potent photo‐cytotoxicity of BZnPP make it an efficacious dual‐purpose tumour‐imaging and photodynamic therapeutic agent in the tissue‐transparent spectral windows.     

Metal-Induced Structural Switching of a Folded Quinone-Sandwiched Porphyrin

We report the synthesis of a novel quinone-sandwiched porphyrin in which two benzoquinones are connected oppositely at the meso positions of a porphyrin through rigid 3-amido 2,2′-bipyridine linkers. ¹H-NMR and single crystal X-ray analyses revealed that the quinone-sandwiched porphyrin has a folded structure in which the porphyrin unit was inserted into the two quinone moieties via π-stacking. Insertion of a Zn(II) ion into the porphyrin center induced a drastic conformational change which is resulted in coordination of the oxygen atoms of both benzoquinone moieties to the Zn-porphyrin to afford a 6-coordinated structure.     

Novel D-π-A system based on zinc porphyrin dyes for dye-sensitized solar cells: Synthesis, electrochemical, and photovoltaic properties

We have designed and synthesized novel zinc porphyrin dyes which have a D-π-A system based on porphyrin derivatives containing a triphenylamine (TPA) electron-donating group and a phenyl carboxyl anchoring group substituted at the meso position of the porphyrin ring, yielding the push-pull porphyrins as the most efficient green dye for dye-sensitized solar cell (DSSC) applications. The synthesis and characterization of a novel D-π-A system based on zinc-porphyrin derivatives have been investigated through their photophysical and photoelectrochemical studies. A large red-shift of the absorption maxima due to introduction of the TPA moiety at the meso position of the porphyrin ring was expected in the D-π-A porphyrins, but the absorption maxima of HKK-Por dyes were a little red-shifted in contrast to Zn[5,-10,15-triphenyl-20-(4-carboxylphenyl)-porphyrin], due to the tilted structure between TPA and the porphyrin unit. Under the photovoltaic performance measurement, the maximum incident photon-to-current conversion efficiency (IPCE) value of the DSSC based on HKK-Por 5 was slightly higher than the efficiencies of the DSSCs based on other HKK-Por dyes due to the introduction of the alkoxy group into the TPA moiety at the meso position of the porphyrin ring. A maximum photon-to-electron conversion efficiency of 3.36% was achieved with the DSSC based on HKK-Por 5 dye (J_SC = 9.04 mA/cm², V_OC = 0.57 V, FF = 0.66) under AM1.5 irradiation (100 m Wcm⁻²).     

Ruthenium‐Catalyzed Oxidation of the Porphyrin β,β′‐Pyrrolic Ring: A General and Efficient Approach to Porpholactones

We describe an efficient ruthenium‐catalyzed oxidation of the β,β′‐pyrrolic ring on the porphyrin periphery. Through the conversion of a β,β′‐double bond to a lactone moiety, the direct preparation of porpholactones from porphyrins is achieved, which previously suffered from needing toxic reagents, multiple synthetic steps and low yields. The generality of this method has been investigated with various porphyrins with different electronic and steric effects, even some metalloporphyrins, and so represents a general and efficient approach for the synthesis of the intriguing porpholactone derivatives.     

Novel Self-assembled Isonicotinic Acid Derivative and Zinc Porphyrin Dyads and Applications in Dye Sensitized Solar Cells

A new self-assemblies based on double-deck dyes ZnTPP-Wi (i?=?1–3) were synthesized and applied in dye-sensitized solar cells (DSSCs). Anchoring molecules (Wi i?=?1–3) consisting of phenyl carboxyl acid and cyanoacetic acid group. Capping layer dyes zinc meso-tetraphenylporphine (ZnTPP) with anchoring molecules Wi through axially coordination bonds of Zn-to-ligand self-assemblies solar cells devices. We herein report a consisting acylamide and cyanoacetic acid group W3 as an anchoring molecule for the axial coordination with upper zinc porphyrin ZnTPP. W3 was synthesized by introducing acylamide and cyanoacetic acid groups may inhibit adverse dye aggregation and improving electrons are effectively injected into the TiO₂ semiconductor surface. Thus, W3 anchoring molecules can be used to fabricate efficient solar cells with ZnTPP porohyrin dye, achieving good photoelectric performance, indicative of their general applicability in fabricating good-performance DSSCs. The assembled modes were also verified by transmission electron microscopy (TEM). The photoelectrochemical efficiencies for dye ZnTPP-W3 are best than those of self-assembly dyes prevailingly ascribed to larger J_sc and V_oc.

     

Photovoltaic Study of Photoelectrochemical Biofuel Cells Sensitized by Porphyrin Derivatives with Different Substituents

Two porphyrin derivatives with different substituents were investigated as dyes for the titanium dioxide (TiO₂) film electrode to construct new two-compartment photoelectrochemical biofuel cells (PEBFCs). The two porphyrin derivatives were tetrakis(4-carboxyphenyl)porphyrin (TCPP) and meso-tetra(p-hydroxyphenyl)porphine (THPP). To determine how cell performance was affected by the dye with different substituents, we analyzed the photochemical and photoelectrochemical properties of the two dyes by physical characterization and photoelectrochemical experiments. The UV–Vis absorption spectra and X-ray photoelectron spectra indicated that the interactions between the dye and TiO₂ decreased in the order of TCPP > THPP, which was also in accord with the results of Fourier transform infrared. In addition, TCPP and THPP were calculated using the density functional theory and the time-dependent density functional theory, and the calculation result exhibited that the radiative lifetime decreased in the order of TCPP > THPP. Compared with THPP, TCPP with longer excited-state was expected to enhance the performance of a PEBFC. We measured and compared the incident photon-to-collected electron conversion efficiency and the light-to-electrical conversion efficiency (η) of the porphyrin-sensitized photoelectrochemical biofuel cell. The photovoltaic characteristics showed the TCPP was more effective compared to the THPP, which obviously showed that the experimental results were consistent with theoretical expectation. These results revealed that the kind of the substituent for the porphyrin influenced the photovoltaic properties of the PEBFC.     

Templated self-assembly of porphyrin cages

The development of self-assembling catalysts, although an often-tried approach, has achieved little success so far. Toward the construction of substrate selective catalysts, we have self-assembled a porphyrin cage based upon the recognition of the templates meso-dipyridyl ( DPyP ) or meso-tetrapyridyl porphyrin ( TPyP ) by glycoluril-based receptors that are functionalized with two pendant zinc porphyrins.     

Comparison of the Effects of Resveratrol and Its Derivatives on the Radiation Response of MCF-7 Breast Cancer Cells

Radiotherapy is among the most important methods for breast cancer treatment. However, this method’s effectiveness is limited by radioresistance. The aim of this study was to investigate whether the stilbene derivatives piceid, resveratrol, and piceatannol have a radiosensitising effect on breast cancer cells (MCF-7). The conducted research enabled us to determine which of the tested compounds has the greatest potential in sensitising cells to ionising radiation (IR). Among the stilbene derivatives, resveratrol significantly increased the effect of IR. Resveratrol and IR used in combination had a higher cytotoxic effect on MCF-7 cells than using piceatannol, piceid, or radiation alone. This was due to a significant decrease in the activity of antioxidant enzymes, which resulted in the accumulation of formed reactive oxygen species (ROS). The effect of resveratrol and IR enhanced the expression of apoptotic genes, such as Bax, p53, and caspase 8, leading to apoptosis.     

New Halogenated Water‐Soluble Chlorin and Bacteriochlorin as Photostable PDT Sensitizers: Synthesis,Spectroscopy, Photophysics,and in vitro Photosensitizing Efficacy

Chlorin and bacteriochlorin derivatives of 5,10,15,20‐tetrakis(2‐chloro‐5‐sulfophenyl)porphyrin have intense absorptions in the phototherapeutic window, high water solubility, high photostability, low fluorescence quantum yield, long triplet lifetimes, and high singlet oxygen quantum yields. Biological studies revealed their negligible dark cytotoxicity, yet significant photodynamic effect against A549 (human lung adenocarcinoma), MCF7 (human breast carcinoma) and SK‐MEL‐188 (human melanoma) cell lines upon red light irradiation (cutoff λ<600 nm) at low light doses. Time‐dependent cellular accumulation of the chlorinated sulfonated chlorin reached a plateau at 2 h, as previously observed for the related porphyrin. However, the optimal incubation time for the bacteriochlorin derivative was significantly longer (12 h). The spectroscopic, photophysical, and biological properties of the compounds are discussed in relevance to their PDT activity, leading to the conclusion that the bacteriochlorin derivative is a promising candidate for future in vivo experiments.     

Synthesis and Anticancer Evaluation of 1,4-Naphthoquinone Derivatives Containing a Phenylaminosulfanyl Moiety

1,4-Naphthoquinones are exceptional building blocks in organic synthesis and have been used to synthesize several well-known pharmaceutically active agents. Herein we report the synthesis, structural characterization, and biological evaluation of new phenylaminosulfanyl-1,4-naphthoquinone derivatives. We evaluated the cytotoxic activity of the synthesized compounds against three human cancer cell lines: A549, HeLa, and MCF-7. Most of the synthesized compounds displayed potent cytotoxic activity. Specifically, compounds 5 e [3,5-dichloro-N-(4-((4-((1,4-dioxo-3-(phenylthio)-1,4-dihydronaphthalen-2-yl)amino)phenyl)sulfonyl)phenyl)benzamide], 5 f [N-(4-((4-((1,4-dioxo-3-(phenylthio)-1,4-dihydronaphthalen-2-yl)amino)phenyl)sulfonyl)phenyl)-3,5-dinitrobenzamide], and 5 p [N-(4-((4-((1,4-dioxo-3-(phenylthio)-1,4-dihydronaphthalen-2-yl)amino)phenyl)sulfonyl)phenyl)thiophene-2-carboxamide] showed remarkable cytotoxic activity. The synthesized compounds showed low toxicity in normal human kidney HEK293 cells. The cytotoxic mechanism of compounds 5 e , 5 f , and 5 p was explored in MCF-7 cells. The results confirmed that these three compounds induce apoptosis and arrest the cell cycle at the G₁ phase. In addition, compounds 5 e , 5 f , and 5 p were found to induce apoptosis via upregulation of caspase-3 and caspase-7 proteins as well as by upregulation of the gene expression levels of caspases-3 and -7. Our findings demonstrate that compounds 5 e , 5 f , and 5 p could be potent agents against a number of cancer types.     

β-Diketonate versus β-Ketoiminate: The Importance of a Ferrocenyl Moiety in Improving the Anticancer Potency

Herein we present a library of fully characterized β-diketonate and β-ketoiminate compounds that are functionalized with a ferrocenyl moiety. Their cytotoxic potential has been determined by screening against human breast adenocarcinomas (MCF-7 and MDA-MB-231), human colorectal carcinoma p53 wild type (HCT116 p53^+/+) and normal human prostate (PNT2) cell lines. The ferrocenyl β-diketonate compounds are more than 18 times more cytotoxic than the ferrocenyl β-ketoiminate analogues. Against MCF-7, compounds functionalized at the meta position are up to nine times more cytotoxic than when functionalized at the para position. The ferrocenyl β-diketonate compounds have increased selectivity towards MCF-7 and MDA-MB-231, with several complexes having selectivity index (SI) values that are more than nine times (MCF-7) and more than six times (MDA-MB-231) that of carboplatin. The stability of these compounds in dimethyl sulfoxide (DMSO) and dimethylformamide (DMF) has been assessed by NMR spectroscopy and mass spectrometry studies, and the compounds show no oxidation of the iron center from Fe^II to Fe^III. Cytotoxicity screening was performed in both DMSO and DMF, with no significant differences observedin their potency.     

Selective oxidation of lupeol by iodosylbenzene catalyzed by manganese porphyrins

Manganese porphyrin-catalyzed oxidation of lupeol by iodosylbenzene was achieved under mild conditions with low isolated yields but with remarkable selectivity, depending on the catalyst of choice. Mn(III) meso-tetraphenylporphyrin and Mn(III) meso-tetrakis(4-carbomethoxyphenyl)porphyrin provided an entry for the preparation of 3β,30-dihydroxylup-20(29)-ene (6–14% yields), whereas Mn(III) β-octabromo-meso-tetrakis(4-carbomethoxyphenyl)porphyrin led to 20-oxo-3β-hydroxy-29-norlupeol (6% yield), as single products. Unreacted lupeol was recovered in quantitative yield. The oxidative transformations at lupeol C20 or C30 take place with no need for protection of C3 hydroxyl moiety.     

Amino Alcohol Acrylonitriles as Activators of the Aryl Hydrocarbon Receptor Pathway: An Unexpected MTT Phenotypic Screening Outcome

Lead (Z)-N-(4-(2-cyano-2-(3,4-dichlorophenyl)vinyl)phenyl)acetamide, 1 showed MCF-7 GI₅₀=30 nM and 400-fold selective c.f. MCF10A (normal breast tissue). Acetamide moiety modification ( 13 a - g ) to introduce additional hydrophobicity was favoured with MCF-7 breast cancer cell activity enhanced at 1.3 nM. Other analogues were potent against the HT29 colon cancer cell line at 23 nM. Textbook SAR data was observed in the MCF-7 cell line, in an MTT assay, via the ortho ( 17 a ), meta ( 17 b ) and para ( 13 f ). The amino alcohol -OH moiety was pivotal, but no stereochemical preference noted. But, these data did not fit our homology modelling expectations. Aberrant MTT ((3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) screening results and metabolic interference confirmed by sulforhodamine B (SRB) screening. Interfering analogues resulted in 120 and 80-fold CYP1A1 and CYP1A2 amplification, with no upregulation of SULT1A1. This is consistent with activation of the AhR pathway. Piperidine per-deuteration reduced metabolic inactivation. 3-OH / 4-OH piperidine analogues showed differential MTT and SRB activity supporting MTT assay metabolic inactivation. Data supports piperidine 3-OH, but not the 4-OH, as a CYP substrate. This family of β-amino alcohol substituted 3,4-dichlorophenylacetonitriles show broad activity modulated via the AhR pathway. By SRB analysis the most potent analogue was 23 b , (Z)-3-(4-(3-(4-phenylpiperidin-1-yl)-2-hydroxypropoxy)phenyl)-2-(3,4-dichlorophenyl)-acrylonitrile.     

Synthesis oftrans-substituted porphyrin building blocks containing two S-trityl or thiol groups

The synthesis of some linear structuredtrans-porphyrin bearing functional groups (S-trityl or thiol) was described. The rational synthetic pathway consisted of 6 reaction steps (up to S-trityl derivatized porphyrin, 5 steps), constituting a MacDonald-type 2+2 condensation and amine-carboxylic acid coupling. The completion of each step was confirmed by¹H-NMR, UV/Vis adsorption, and FAM-MS. The resulting porphyrins would be applicable to the study of self-assembled gold-thiol structures, due to the reactive nature of the molecules with a gold surface.