Metal‐Cation Recognition in Water by a Tetrapyrazinoporphyrazine‐Based Tweezer Receptor

A series of zinc azaphthalocyanines with two azacrowns in a rigid tweezer arrangement were prepared and the fluorescence sensing properties were investigated. The size‐driven recognition of alkali and alkaline earth metal cations was significantly enhanced by the close cooperation of the two azacrown units, in which both donor nitrogen atoms need to be involved in analyte binding to switch the sensor on. The mono‐ or biphasic character of the binding isotherms, together with the binding stoichiometry and magnitude of association constants (KA), indicated specific complexation of particular analytes. Water solvation was shown to play an important role and resulted in a strong quenching of sensor fluorescence in the ON state. The lead compound was embedded into silica nanoparticles and advantageous sensing properties towards K+ were demonstrated in water (λF=671 nm, apparent KA=82 m−1, increase of 17×), even in the presence of (supra)physiological concentrations of Na+ and Ca2+.In a pinch: Close cooperation of azacrowns in fluorescence sensors derived from tetrapyrazinoporphyrazines is responsible for high sensitivity and selectivity towards particular cations. Water solvation, however, quenches the fluorescence strongly. Interestingly, embedding the sensor into silica nanoparticles overcomes this problem and result in an excellent red‐emitting fluorescence sensor (see figure).Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137532/1/chem201504268.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137532/2/chem201504268-sup-0001-misc_information.pd

Peripherally crowded cationic phthalocyanines as efficient photosensitizers for photodynamic therapy

Photodynamic therapy is a treatment modality of cancer based on the production of cytotoxic species upon the light activation of photosensitizers. Zinc phthalocyanine photosensitizers bearing four or eight bulky 2,6-di(pyridin-3-yl)phenoxy substituents were synthesized, and pyridyl moieties were methylated. The quaternized derivatives did not aggregate at all in water and retained their good photophysical properties. High photodynamic activity of these phthalocyanines was demonstrated on HeLa, MCF-7, and EA.hy926 cells with a very low EC50 of 50 nM (for the MCF-7 cell line) upon light activation while maintaining low toxicity in the dark (TC50 ≈ 600 μM), giving thus good phototherapeutic indexes (TC50/EC50) above 1400. The compounds localized primarily in the lysosomes, leading to their rupture after light activation. This induced an apoptotic cell death pathway with secondary necrosis because of extensive and swift damage to the cells. This work demonstrates the importance of a bulky and rigid arrangement of peripheral substituents in the development of photosensitizersThe work was supported by the Czech Science Foundation (19-14758Y), Charles University (PRIMUS/20/SCI/013, GAUK 1620219, SVV 260 550), and by the project EFSACDN (No. CZ.02.1.01/0.0/0.0/16_019/0000841) cofunded by the ERDF. For affiliations ‡, ∥, and ⊥, the work was supported by MINECO-Feder funds (CTQ2017-85393-P (T.T.), CTQ-2014-53673-P and CTQ-2017-89539-P (A.d.l.E.), PCIN-2017-042/EuroNanoMed2017-191, TEMPEAT (T.T.)). Affiliation ⊥ (IMDEA Nanociencia) also acknowledges support from the ‘Severo Ochoa’ Programme for Centres of Excellence in R&D (MINECO, Grant SEV2016-0686

Dusikate analogy ftalocyaninu jako fotosensitizery ve fotodynamicke terapii.

The first measurements of the photodynamic activity made with azaphthalocyanines (AzaPc) substituted with diethylamine and 6-aminohexanoic acid have confirmed the prediction of the singlet oxygen production. In the beginning negative results from the in vitro tests on cells have been made account of a found increased ability of aggregation only. Later there was found that the singlet oxygen production is also negatively influenced by the chosen substitution. This may be the main reason for zero photodynamic activity of this AzaPc on cells; however, the aggregation takes place in this effect, too. Results from observations of heteroatom influence on the singlet oxygen production have brought some light into the above mentioned negative results on cells. There was found that AzaPc containing the alkylamino substitution on the periphery of the macrocycle are very low active in the singlet oxygen production. This activity is almost negligible in comparison with alkoxy or the most active alkylsulfonyl substitutions. The last mentioned peripheral modifications are the most suitable for the next research because of other advantageous properties (the longest red shift of the Q band among the studied heteroatoms and a sufficient stability during synthesis in comparison with alkoxy derivatives).Parts of the text in English.Available from STL Prague, CZ / NTK - National Technical LibrarySIGLECZCzech Republi

Tetrapyrazinoporphyrazines and their metal derivatives. Part II: Electronic structure, electrochemical, spectral, photophysical and other application related properties

Tetrapyrazinoporphyrazines (TPyzPzs), the heterocyclic azaanalogs of the phthalocyanine macrocycle, known since the 1930 s, but became an object of intensive studies in the last decades. In Part I (Coord. Chem. Rev. 2016, 309, 107–179) the synthesis of variously substituted TPyzPzs and their metal complexes as well as of their precursors was presented. In the present Part II, we consider the peculiarities of their electronic structure, electrochemical, spectral, acid–base and photophysical properties. The focus is made on the related perspectives of practical applications in the fields of nonlinear optical properties, liquid crystals, catalysis, sensors, dark quenchers of fluorescence, photodynamic therapy (PDT, including the specific aspects of water-soluble and targeting TPyzPzs, in vitro PDT results, bi- and multimodal therapy) and light harvesting

Tetrapyrazinoporphyrazines and their metal derivatives. Part I: synthesis and basic structural information

Tetrapyrazinoporphyrazines (TPyzPzs), the heterocyclic azaanalogs of the phthalocyanine macrocycle, are known since 1937 and were intensively studied especially in the last fifteen years. Due to advances in the synthesis, peripherally substituted TPyzPzs and their innumerable metal derivatives have become one of the most easily accessible phthalocyanine analogues. External substituents endow these species with solubility in organic solvents or water, influence aggregation behavior, determine spectral, electrochemical, coordination, acid-base, catalytic and photochemical properties. Moreover, by the building of new exocyclic coordination sites, they enable formation of multimetallic porphyrazines. Aspects concerning the synthesis of precursors, TPyzPz macrocycles and their metal derivatives and the related available structural information are illustrated and discussed in detail in this review including also low symmetry species, oligomeric and polymeric TPyzPzs and higher TPyzPz homologues with fused benzene and heteroaromatic rings. (C) 2015 Elsevier B.V. All rights reserved

Tuning Electron-Accepting Properties of Phthalocyanines for Charge Transfer Processes

Phthalocyanines play fundamental roles as electron-acceptors in many different fields; thus, the study of structural features affecting electron-accepting properties of these macrocycles is highly desirable. A series of low-symmetry zinc(II) phthalocyanines, in which one, three, or four benzene rings were replaced for pyrazines, was prepared and decorated with electron-neutral (alkylsulfanyl) or strongly electron-withdrawing (alkylsulfonyl) groups to study the role of the macrocyclic core as well as the effect of peripheral substituents. Electrochemical studies revealed that the first reduction potential (Ered1) is directly proportional to the number of pyrazine units in the macrocycle. Introduction of alkylsulfonyl groups had a very strong effect and resulted in a strongly electron-deficient macrocycle with Ered1 = −0.48 V vs SCE (in THF). The efficiency of intramolecular-charge transfer (ICT) from the peripheral bis(2-methoxyethyl)amine group to the macrocycle was monitored as a decrease in the sum of ΦΔ + ΦF and correlated well with the determined Ered1 values. The strongest quenching by ICT was observed for the most electron-deficient macrocycle. Importantly, an obvious threshold at −1.0 V vs SCE was observed over which no ICT occurs. Disclosed results may substantially help to improve the design of electron-donor systems based on phthalocyanines

Role of Steric Hindrance in the Newman-Kwart Rearrangement and in the Synthesis and Photophysical Properties of Arylsulfanyl Tetrapyrazinoporphyrazines

Conditions for the Newman-Kwart rearrangement of phenols into thiophenols were investigated in relation to the bulkiness of substituents at the 2 and 6 positions of the starting phenol derivative with an emphasis on eliminating side reactions. Thiophenols with different 2,6-disubstitution patterns (including hydrogen, methyl, isopropyl or <i>tert</i>-butyl groups) were used for the synthesis of 5,6-bis­(arylsulfanyl)­pyrazine-2,3-dicarbonitriles that underwent cyclotetramerization leading to the corresponding zinc tetrapyrazinoporphyrazines (TPyzPz), aza-analogues of phthalocyanines. Several methods for the cyclotetramerization were attempted to eliminate problematic side reactions. Magnesium butoxide was found as the most suitable cyclotetramerization agent and afforded TPyzPzs in reasonable yields of approximately 30% under mild conditions. The varying arrangements of the peripheral substitutions resulting from the different bulkiness of the substituents were demonstrated by the X-ray structures of the pyrazine-2,3-dicarbonitriles. The prepared zinc arylsulfanyl TPyzPzs showed an absorption maximum at a Q-band over 650 nm, fluorescence quantum yields between 0.078 and 0.20, and singlet oxygen quantum yields ranging 0.58–0.69. TPyzPzs with isopropyl groups were found to be the best derivatives in this series as they combined facile cyclotetramerization, no aggregation, and good photophysical properties, which makes them potentially suitable for photodynamic therapy

Role of Steric Hindrance in the Newman-Kwart Rearrangement and in the Synthesis and Photophysical Properties of Arylsulfanyl Tetrapyrazinoporphyrazines

Conditions for the Newman-Kwart rearrangement of phenols into thiophenols were investigated in relation to the bulkiness of substituents at the 2 and 6 positions of the starting phenol derivative with an emphasis on eliminating side reactions. Thiophenols with different 2,6-disubstitution patterns (including hydrogen, methyl, isopropyl or <i>tert</i>-butyl groups) were used for the synthesis of 5,6-bis­(arylsulfanyl)­pyrazine-2,3-dicarbonitriles that underwent cyclotetramerization leading to the corresponding zinc tetrapyrazinoporphyrazines (TPyzPz), aza-analogues of phthalocyanines. Several methods for the cyclotetramerization were attempted to eliminate problematic side reactions. Magnesium butoxide was found as the most suitable cyclotetramerization agent and afforded TPyzPzs in reasonable yields of approximately 30% under mild conditions. The varying arrangements of the peripheral substitutions resulting from the different bulkiness of the substituents were demonstrated by the X-ray structures of the pyrazine-2,3-dicarbonitriles. The prepared zinc arylsulfanyl TPyzPzs showed an absorption maximum at a Q-band over 650 nm, fluorescence quantum yields between 0.078 and 0.20, and singlet oxygen quantum yields ranging 0.58–0.69. TPyzPzs with isopropyl groups were found to be the best derivatives in this series as they combined facile cyclotetramerization, no aggregation, and good photophysical properties, which makes them potentially suitable for photodynamic therapy