[FeFe]-Hydrogenase synthetic mimics based on peri-substituted dichalcogenides

[FeFe]-hydrogenase plays an important role in the microbial energy metabolism, catalysing the reduction of protons into molecular hydrogen. Herein the synthesis and the spectroscopic analysis (NMR, IR, UV/vis) of [FeFe]-complexes based on the naphtho[1,8-cd][1,2]dithiole, naphtho[1,8-cd][1,2]diselenole and naphtho[1,8-cd][1,2]thiaselenole backbone, which incorporate substituents in position 2 of the naphthalene ring (OMe, tBu) are described. Additionally, dichalcogenide-based [FeFe]-complexes, containing the rigid aromatic phenanthrene and fluorene backbones are discussed. Cyclic voltammetry was applied in order to investigate the electrochemical properties of these new [FeFe]-hydrogenase synthetic analogues. Titration with pTsOH was monitored by cyclic voltammetry and showed that these [FeFe]-complexes are catalysts for proton reduction. After having studied these promising systems for proton reduction catalysis, the functionalization of naphthalene-1,8-dithiolate and diselenolate-based [FeFe]-complexes by insertion of aromatic and alkyl amino and imino groups is described. Spectroscopic and electrochemical techniques were applied to confirm protonation of the nitrogen, upon acid addition, and the effect on proton reduction catalysis, which was remarkably improved. Following these results, the synthesis of a molecular dyad containing zinc tetraphenylporphyrin, covalently linked to naphthalene-1,8-dithiolate-based [FeFe]-complex, via amino group, is reported. The initial investigations (UV/vis and emission spectroscopy) showed catalytic photo-induced hydrogen production, which was monitored by gas chromatography

Photo-induced anticancer activity and singlet oxygen production of prodigiosenes

© 2018 The Royal Society of Chemistry and Owner Societies. The photo-induced cytotoxicity of prodigiosenes is reported. One prodigiosene represents a synthetic analogue of the natural product prodigiosin, and two are conjugated to molecules that target the estrogen receptor (ER). A comparison of incubation and irradiation frameworks for the three prodigiosenes is reported, with activity against ER- and ER+ lines explored. Furthermore, the ability of the three prodigiosenes to photosensitise the production of singlet oxygen is demonstrated, shedding mechanistic light onto possible photodynamic therapeutic effects of this class of tripyrroles

Organic & Biomolecular Chemistry Prodigiosenes conjugated to tamoxifen and estradiol †

International audienceWe report the synthesis of the first click-appended prodigiosene conjugates. Four prodigiosene conjugates of estradiol functionalised at the 7α-position were prepared, as were three prodigiosene conjugates of tamoxifen. The coupling between a prodigiosene and an 11-hydroxy estradiol derivative via an ether linkage was investigated, as was the 11-and 7-functionalisation of the estradiol core. The robustness of estradiol protecting groups was severely challenged by reactions typically used to equip such frameworks for 11-and 7-functionalisation. Specifically, and important to synthesis involving estradiol, TBS, TMS and THP are not useful protecting groups for the functionalisation of this core. When the chemical features of the therapeutic agent limit the choice of protecting group (in this case, prodigiosenes bearing aryl, NH, alkenyl and ester groups), click chemistry becomes an attractive synthetic strategy. The anti-cancer activity of the seven click prodigiosene conjugates was evaluated

A step-wise synthetic approach is necessary to access γ-conjugates of folate: folate-conjugated prodigiosenes

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N-Derivatives of peri-Substituted Dichalcogenide [FeFe]-Hydrogenase Mimics: Towards Photocatalytic Dyads for Hydrogen Production

International audienceSynthetic strategies towards molecular dyads based on peri-substituted dichalcogenide (S,Se) [FeFe]-hydrogenase synthetic mimics covalently linked to a ZnTPP photosensitizer are described. Dithiolate and diselenolate model systems 2–5 are prepared through condensation of 2-naphthaldehydes with p-methoxyaniline, reduction of the resulting Schiff base and oxidative insertion of Fe2(CO)6 into the dichalcogen bond of the imine or amine. Diselenolate-based [FeFe] complexes (imine 3 and amine 5) are more efficient in electrocatalysis of proton reduction than their sulfur analogues 2 and 4 with increasing concentrations of pTsOH. Molecular dyad 1 containing a peri-substituted naphthalene dithiolate Fe2(CO)6 cluster covalently linked via an amine to ZnTPP is prepared through sequential zinc insertion into the porphyrin followed by iron insertion into the disulfide bond

Synthesis and anticancer activity of prodigiosenes bearing C-ring esters and amides

International audienceProdigiosenes, a class of compounds characterised by their 4-methoxypyrrolyldipyrrin framework, are known to possess anti-cancer activity. Structural modification of the C-ring of prodigiosenes presented ten new prodigiosenes bearing pendant alkyl esters and amides. These prodigiosenes were evaluated biologically and displayed notable anticancer in vitro activity, particularly when featuring a hexyl chain

Probing the hydrolytic reactivity of 2-difluoromethyl pyrroles

International audienceα-Difluoromethyl pyrroles were found to be stable while N-protected with an electron-withdrawing group. Due to the propensity of pyrroles to access azafulvenium-like intermediates, the C–F bonds of an α-difluoromethyl substituent are labile under hydrolytic conditions. The presence of certain electron-withdrawing substituents about the pyrrolic ring can accelerate this process, as determined through a kinetic comparison of the deprotection and subsequent hydrolysis reactions of N-protected β-aryl α-difluoromethyl pyrrole

Idun (Årg. 29, N:r 50)

An asymmetric meso-<i>H</i> dipyrrin featuring a conjugated terminal alkyne substituent was converted to its corresponding difluoro boron complex, and the extent of π-conjugation was extended using Sonogashira cross-coupling. Treatment of the alkyne-substituted dipyrrin with BF₃·OEt₂ and NEt₃ revealed the reactivity of the conjugated terminal alkyne toward Lewis-activated electrophilic substitution and led to the isolation of <i>F</i>-BODIPYs bearing terminal bromovinyl and enol substituents

Regioselective Substituent Effects upon the Synthesis of Dipyrrins from 2-Formyl Pyrroles

The synthesis of symmetric Îą-free meso-H-dipyrrin hydrobromides from 5-H-2-formyl pyrroles was investigated. The self-condensation produces regioisomeric dipyrrins through adoption of two mechanistic pathways. The key difference between the two pathways lies in which position of the pyrrole directs nucleophilic attack. Through a systematic study involving various substituted and/or isotopically labelled 5-H-2-formyl pyrroles, we herein provide evidence to suggest that not only do two mechanistic pathways exist, but that the steric bulk of the substituent adjacent to the 5-unsubstituted position influences which pathway dominates.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Glutathione peroxidase mimics based on conformationally-restricted, peri-like, 4,5-disubstituted fluorene dichalcogenides

International audienceGlutathione peroxidase (GPx) regulates cellular peroxide levels through glutathione oxidation. GPx-mimics based on 4,5-disubstituted fluorene diselenides, their oxides, and ditellurides show catalytic activities consistent with conformational restriction about the dichalcogen bond