Metallation of pentaphyrin with Lu(III) dramatically increases reactive-oxygen species production and cell phototoxicity

Ballico, Maurizio; Rapozzi, Valentina; Xodo, Luigi E.; Comuzzi, Clara

doi:10.1016/j.ejmech.2010.12.007

Cited by 24 publications

(33 citation statements)

References 61 publications

(8 reference statements)

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“…In a previous theoretical investigation [36], the conformational preferences of [22]-and [24]pentaphyrins and of their meso substituted derivatives, were investigated in detail using DFT calculations showing as these macrocycles can adopt a variety of intriguing structures which can be interconverted under certain conditions. [36], Actually, pentaphyrins [1.1.1.1.1], which bear five pyrroles regularly connected through meso-carbons, should contain structural frustration because of the addition of a pyrrole and a meso-carbon to the planar porphyrin skeleton.…”

Section: Ground State Propertiesmentioning

confidence: 99%

“…A slightly modified non-aromatic iso-pentaphyrin, obtained replacing the diethyl-pyrrole with an unsubstituted pyrrole and by introducing a carboxylic group on the phenyl substituent (3), and its lutetium(III) complexes has been reported and also tested for potential application in PDT. [24] Both compounds were found not able to produce singlet oxygen by irradiation, from both experimental and theoretical point of views.…”

Section: Introductionmentioning

confidence: 99%

“…[ [24][25] Herein we report a joint experimental and theoretical investigation of the new 20-(4'carboxyphenyl)-2,13-dimethyl-3,12-diethyl- [22] pentaphyrin complex PCCox (4). The photoactivation properties of the novel expanded porphyrin were recently tested in water disinfection, using S. Aureus as a Gram-positive bacteria model and data showed that 4 was effective against these bacteria at nanomolar concentration [26][27].…”

Section: Introductionmentioning

confidence: 99%

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22π-Electrons [1.1.1.1.1] pentaphyrin as a new photosensitizing agent for water disinfection: experimental and theoretical characterization

et al. 2016

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In view of their promising photosensitizing features, expanded porphyrins are gaining wide attention for their potential use in both photodynamic therapy (PDT) of cancer or as likely photoactivated agent for water disinfection. Herein, we report a joint experimental and theoretical investigation on the 20-(4'-carboxyphenyl)-2,13-dimethyl-3,12-diethyl-[22]pentaphyrin complex 4. The synthesis, NMR, UV-Vis and mass characterization of the new Author's Pre-Print Version 2 compound together with a detailed theoretical investigation of the photophysical properties are presented. In particular, type I-and type II-photoreactions have been explored by means of DFT and its TDDFT formulation characterizing the electronic absorption spectra, providing singlettriplet energy gap, vertical ionization potential and electron affinity. Results show that title compound is able to generate the cytotoxic singlet oxygen species supporting the application of the proposed molecule as a photoactivated agent for water disinfection. Supplementary Material. ESI-MS of PCCox, computed main Bond lengths (Å) and main dihedral angles (degrees) for PCCox, main vertical singlet electronic energies for several conformations of PCCox obtained with different XC functionals in methanol, computed UV-Vis Spectra, NMR computations.

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Section: Ground State Propertiesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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22π-Electrons [1.1.1.1.1] pentaphyrin as a new photosensitizing agent for water disinfection: experimental and theoretical characterization

et al. 2016

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“…In particular, the experimental spectrum of 1 recorded in dichloromethane solution (CH 2 Cl 2 ) has a Soret-like band centered at 485 nm (2.56 eV, log ε = 4.39) and a broad Q-band absorption wavelength maximum (λ max ) at 814 nm (1.52 eV, log ε = 3.71). 20 The computed five lowest excitation energies, oscillator strengths, and main orbital contributions of compound 1 in CH 2 Cl 2 are reported in Table 3. Since the first excitation energy (Q-band) is predicted at very low energy for both B3LYP and PBE0 exchange-correlation functionals (λ max = 1340 and 1501 nm, respectively), the reported data refer to the ωB97X and ωB97XD functionals.…”

Section: Computational Detailsmentioning

confidence: 99%

A Time-Dependent Density Functional Study of a Non-Aromatic [1.1.1.1.1]-Pentaphyrin and Its Lutetium Complex

et al. 2012

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The molecular structures and absorption electronic spectra of two novel phototoxic pentapyrrolic expanded porphyrins (a isopentaphyrin derivative and its lutetium complex) have been studied at the density functional level and its time-dependent extension (TDDFT). The geometries were optimized with three different exchange-correlation functionals (PBE0, B3LYP, and ωB97XD) and the SV(P) basis set plus the pseudopotential method for the complex. With respect to the porphyrin, the structure of [1.1.1.1.1]-pentaphyrin and its lutetium complex are predicted much distorted due to the lack of conjugation. The lowest excitation energy band (experimental at 814 nm) for the free-base isopentaphyrin is well predicted by the ωB97XD at 772 nm. The possible photodynamic reaction mechanisms (types I and II) were studied through the calculation of the electron affinity and ionization potentials in solvent, using the COSMO model.

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“…One major objective of PDT is the search of new photosensitizers with high water solubility, low dark cytotoxycity, high capacity to penetrate the plasma membrane and generate 1 O 2 , and an ability to interact with specific cellular targets [6-8]. In previous studies from our laboratory we synthesized expanded porphyrins, composed of a macrocycle of five pyrroles, that exhibit a photodynamic activity in cancer cells at micromolar concentrations, either as free molecules or complexed to Zn or Lu [9,10]. In addition, we examined squaraines [11] and pheophorbide a [12-15], a chlorophyll derivative with a tetrapyrrolic macrocycle which is active at a nanomolar concentration range, comparable to that of verteporfin and temoporfin: two well-known photosensitizers used in clinic [16,17].…”

Section: Introductionmentioning

confidence: 99%

Anticancer activity of cationic porphyrins in melanoma tumour-bearing mice and mechanistic in vitro studies

et al. 2014

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BackgroundPorphyrin TMPyP4 (P4) and its C14H28-alkyl derivative (C14) are G-quadruplex binders and singlet oxygen (1O2) generators. In contrast, TMPyP2 (P2) produces 1O2 but it is not a G-quadruplex binder. As their photosensitizing activity is currently undefined, we report in this study their efficacy against a melanoma skin tumour and describe an in vitro mechanistic study which gives insights into their anticancer activity.MethodsUptake and antiproliferative activity of photoactivated P2, P4 and C14 have been investigated in murine melanoma B78-H1 cells by FACS, clonogenic and migration assays. Apoptosis was investigated by PARP-1 cleavage and annexin-propidium iodide assays. Biodistribution and in vivo anticancer activity were tested in melanoma tumour-bearing mice. Porphyrin binding and photocleavage of G-rich mRNA regions were investigated by electrophoresis and RT-PCR. Porphyrin effect on ERK pathway was explored by Western blots.ResultsThanks to its higher lipophylicity C14 was taken up by murine melanoma B78-H1 cells up to 30-fold more efficiently than P4. When photoactivated (7.2 J/cm2) in B78-H1 melanoma cells, P4 and C14, but not control P2, caused a strong inhibition of metabolic activity, clonogenic growth and cell migration. Biodistribution studies on melanoma tumour-bearing mice showed that P4 and C14 localize in the tumour. Upon irradiation (660 nm, 193 J/cm2), P4 and C14 retarded tumour growth and increased the median survival time of the treated mice by ~50% (P <0.01 by ANOVA), whereas porphyrin P2 did not. The light-dependent mechanism mediated by P4 and C14 is likely due to the binding to and photocleavage of G-rich quadruplex-forming sequences within the 5′-untranslated regions of the mitogenic ras genes. This causes a decrease of RAS protein and inhibition of downstream ERK pathway, which stimulates proliferation. Annexin V/propidium iodide and PARP-1 cleavage assays showed that the porphyrins arrested tumour growth by apoptosis and necrosis. C14 also showed an intrinsic light-independent anticancer activity, as recently reported for G4-RNA binders.ConclusionsPorphyrins P4 and C14 impair the clonogenic growth and migration of B78-H1 melanoma cells and inhibit melanoma tumour growth in vivo. Evidence is provided that C14 acts through light-dependent (mRNA photocleavage) and light-independent (translation inhibition) mechanisms.

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Metallation of pentaphyrin with Lu(III) dramatically increases reactive-oxygen species production and cell phototoxicity

Cited by 24 publications

References 61 publications

22π-Electrons [1.1.1.1.1] pentaphyrin as a new photosensitizing agent for water disinfection: experimental and theoretical characterization

22π-Electrons [1.1.1.1.1] pentaphyrin as a new photosensitizing agent for water disinfection: experimental and theoretical characterization

A Time-Dependent Density Functional Study of a Non-Aromatic [1.1.1.1.1]-Pentaphyrin and Its Lutetium Complex

Anticancer activity of cationic porphyrins in melanoma tumour-bearing mice and mechanistic in vitro studies

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