A comprehensive evaluation of 2,6,8-triphenyl-BODIPY-3,5-dicarboxylates was carried out to reveal the effect of substitution at 1,7-positions on properties of this structural type of BODIPY. For this purpose, a series of different 1,7-substituted ethyl 2,6,8-triphenyl-BODIPY-3,5-dicarboxylates (unsubstituted 3a, difluoro- 3b, dimethyl- 3c and dichloro- 3d) was synthesized. The resulting BODIPYs were characterized by UV-visible and fluorescence spectroscopies, cyclic voltammetry and DFT calculations. In addition, their ability to generate singlet oxygen and photostability were evaluated. The data from this investigation are summarized, compared, analyzed and discussed herein. It was found that 1,7- dimethyl derivative 3c is the most promising photosensitizer for further application in the context of balance between photophysical properties and photostability.

To investigate the influence of phthalocyanine aggregation on their photodynamic activity, a series of six cationic water-soluble zinc(II) phthalocyanines bearing from four to sixteen 4-((diethylmethylammonium)methyl)phenoxy substituents was synthesized. Depending on their structure, the phthalocyanines have different aggregation behaviors in phosphate buffer solutions ranging from fully assembled to monomeric states. Remarkably, independent of aggregation in buffer, very high photodynamic efficiencies against the tumor cell lines MCF-7 and MDA-MB-231 in the nanomolar range were found for all investigated phthalocyanine, and the IC50(light) varied from 27 to 358 nM (3.5 J/cm2, 660 nm) with IC50(dark)/IC50(light) ratios up to ∼3700. This is due to the intracellular disassembly of aggregated phthalocyanines with the formation of monomeric photoactive forms, as demonstrated by fluorescence microscopy. Indeed, the interaction of aggregated phthalocyanines with serum proteins in a buffer resulted in the disassembly of nonluminescent aggregate species with the release of photoactive monomers bound to protein macromolecules.

A modular synthesis of novel series of 1,7-difluorinated BODIPYs has been elaborated. First, the acid-catalyzed condensation of ethyl 3-aryl-4-fluoro-1H-pyrrole-2-carboxylates with aromatic aldehydes gives the corresponding dipyrromethane-1,9-dicarboxylates. The latter are subjected to the exhaustive reduction with lithium aluminum hydride to transform the ester moieties into methyl groups. The subsequent oxidation of the resulting 1,9-dimethylated dipyrromethanes followed by the boron difluoride complexation afforded a family of novel core-fluorinated BODIPYs in up to 74 % yield. Photophysical properties of the resulting BODIPYs were tuned by varying of the starting fluoropyrroles and aromatic aldehydes and were studied by UV-visible and fluorescence spectroscopy. As a result, the fluorescence quantum yields of the obtained compounds reached up to 99 %. In addition, their ability to generate singlet oxygen and electrochemical properties were also evaluated. As a result, a new promising family of fluorophores with a good combination of the fluorescence and photosensitizing properties was obtained. It was found that conversion of ester groups into methyl ones at the 3,5-positions of the BODIPY core is a crucial step toward fluorescence enhancement. In addition, DFT calculations were performed to elucidate a relationship between electronic structure, geometry and photophysical properties of these BODIPYs. This paper describes a synthetic approach to obtain novel core-fluorinated BODIPYs. The starting 4-fluoropyrroles is transformed into 3,7-difluorinated dipyrromethane-1,9-dicarboxylates. The subsequent exhaustive reduction with LAH, followed by oxidation and boron difluoride complexation, affords 3,5-dimethylated 1,7-difluoro-BODIPYs. As a result, a new promising family of fluorophores with a good combination of the fluorescence and photosensitizing properties has been obtained. image

We report the first synthesis of a polyhedral boron derivative of gadolinium(III) phthalocyaninate. Initially, reaction of 4-nitrophthalonitrile with 4-formylphenol in the presence of base was carried out to give 4-(4-formylphenoxy)phthalonitrile. This compound was then converted to 4-(4-hydroxymethylphenoxy)phthalonitrile using sodium tris-acetoxy borohydride in THF. Sequential cyclotetramerisation of this semiproduct in the presence of magnesium acetate, treatment of the resulting complex with trifluoroacetic acid, and complexation with gadolinium(III) acetate afforded gadolinium(III) phthalocyanine containing four hydroxymethylphenoxy groups at the peripheral (beta) positions. Then, a nucleophilic addition reaction of this complex with acetonitrilium derivative of [B10H10](2-) anion afforded gadolinium(III) phthalocyaninate decorated with four closo-decaborate units in good/satisfactory yield. The new product was characterised by various techniques (CHN analysis, MALDI-TOF mass spectrometry and UV-Vis spectroscopy). The boron content in this product is 21.5 wt% (40 atoms), and the r1 relaxivity of the conjugate 6.1 +/- 0.7 mM(-1)s(-1) (at 3.0 T, 20 degrees C in water), which makes it a promising prototype for theranostic agents for MRI-guided BNC therapy in future investigations.

Cancer phototheranostics is a new mode of precise treatment based on fluorescent and photothermal imaging (PTI), combined with photodynamic (PDT) and photothermal therapy (PTT). Herein, we designed a photoactive Pt(IV) prodrug Pt-1 with BODIPY-based triplet photosensitizer as an axial ligand that exhibits cytotoxic effects through both PDT and photoactivated chemotherapy (PACT). Based on the Pt-1 prodrug, we developed a multifunctional theranostic nanoplatform Pt-NPs with combined PDT/PTT activity, capable of light-induced cisplatin release and suitable for photothermal and fluorescent tumor imaging. Upon 660 nm laser irradiation, Pt-NPs efficiently causes regional hyperpyrexia, with a photothermal conversion efficiency of 42.1%. Synergistically, Pt-NPs acts as a PDT type I agent. In vivo PTI studies have shown bright fluorescence of the CT-26 tumor after intravenous injection of Pt-NPs, indicating accumulation and retention of Pt-NPs in the tumor. This is the first example of PTT/PDT-active NPs based on Pt(IV) prodrug capable of photoinduced release of cisplatin. This strategy of the synergistic light-induced PDT/PTT/PACT action of Pt-NPs provides a new platform for the future design of phototheranostic agents for enhanced tumor treatment and imaging.

A series of mononuclear ruthenium(II) tetra-tert-butyl-phthalocyaninates bearing axial N-donor ligands [tBu(4)PcRu]L-2 (L = trimethylamine, pyrazine, 4,4 '-bipyridine and N-methyl-4,4 '-bipyridinium iodide) as well as the binuclear complex [tBu4PcRu](2)(BiPy)(3) were synthesized starting from the complex with axially coordinated carbonyl group [tBu(4)PcRu](CO). All compounds have been characterized by NMR, UV-Vis and cyclic voltammetry. The latter allowed the determination of oxidation and reduction potentials, HOMO-LUMO gaps and revealed the possibility of electropolymerization of BiPy-containing complexes in clear contrast to complexes containing another bidentate ligand - pyrazine. Comparative electrochemical studies of the mono- and binuclear complexes [tBu(4)PcRu](BiPy)(2) and [tBu(4)PcRu](2)(BiPy)(3) revealed that the phthalocyanine rings are not conjugated in the binuclear species. The remarkable dependence of singlet oxygen generation from axial ligands in ruthenium phthalocyaninates was observed: the complexes with carbonyl group [tBu(4)PcRu](CO) and with pyrazine molecules [tBu(4)PcRu](Pyz)(2) show higher O-1(2) quantum yields, whereas the complex with axially coordinated molecules of trimethylamine [tBu(4)PcRu](NMe3)(2) and quaternized BiPy ligands [tBu(4)PcRu](BiPy-Me+)(2) have the lowest ability to generate singlet oxygen. The revealed influence of axial ligands on key physicochemical properties paves the way for the design of new ruthenium phthalocyaninates with potential optoelectronic and biomedical applications.

Light-induced release of cisplatin from Pt(IV) prodrugs represents a promising approach for precise control over the antiproliferative activity of Pt-based chemotherapeutic drugs. This method has the potential to overcome crucial drawbacks of conventional cisplatin therapy, such as high general toxicity toward healthy organs and tissues. Herein, we report two Pt(IV) prodrugs with BODIPY-based photoactive ligands Pt-1 and Pt-2, which were designed using carbamate and triazole linkers, respectively. Both prodrugs demonstrated the ability to release cisplatin under blue light irradiation without the requirement of an external reducing agent. Dicarboxylated Pt-2 prodrug turned out to be more stable in the dark and more sensitive to light than its monocarbamate Pt-1 counterpart; these observations were explained using DFT calculations. The investigation of the photoreduction mechanism of Pt-1 and Pt-2 prodrugs using DFT modeling and ΔG0 PET estimation suggests that the photoinduced electron transfer from the singlet excited state of the BODIPY axial ligand to the Pt(IV) center is the key step in the light-induced release of cisplatin from the complexes. Cytotoxicity studies demonstrated that both prodrugs were nontoxic in the dark and toxic to MCF-7 cells under low-dose irradiation with blue light, and the observed effect was solely due to the cisplatin release from the Pt(IV) prodrugs. Our research presents an elegant synthetic approach to light-activated Pt(IV) prodrugs and presents findings that may contribute to the future rational design of photoactivatable Pt(IV) prodrugs.

A novel ionogenic water-soluble zinc complex with n-extended ligand - tetraquinoxalinoporphyrazine bearing eight benzoate groups - ZnQPz(COONa)8 was synthesized by template condensation of a new building block, dipentyl 4,4'-(6,7-dicyanoquinoxalin-2,3-diyl)dibenzoate followed by alkaline hydrolysis of ester groups. The photophysical properties of the complex were studied and a significant bathochromic shift of the Q-band by 100 nm was observed as compared to conventional phthalocyanine complexes. However, in contrast to other NIR-absorbing n-extended derivatives with similar optical properties, ZnQPz(COONa)8 showed a high degree of photostability - its photobleaching rate in DMSO was about 3 times lower than that of the zinc tetra-15-crown-5-naphthalocyanate Zn[(15C5)4Nc]. The improved photostability together with the ability to generate singlet oxygen (CYRILLIC CAPITAL LETTER EF Delta = 0.65 in aqueous DMSO) and absorb light in the near infrared region makes quinoxaline-porphyrazine a good candidate for use in photodynamic therapy.

Inverted perovskite solar cells with a p-i-n configuration have attracted considerable attention from the research community because of their simple design, insignificant hysteresis, improved operational stability, and low-temperature fabrication technology. However, this type of device is still lagging behind the classical n-i-p perovskite solar cells in terms of its power conversion efficiency. The performance of p-i-n perovskite solar cells can be increased using appropriate charge transport and buffer interlayers inserted between the main electron transport layer and top metal electrode. In this study, we addressed this challenge by designing a series of tin and germanium coordination complexes with redox-active ligands as promising interlayers for perovskite solar cells. The obtained compounds were characterized by X-ray single-crystal diffraction and/or NMR spectroscopy, and their optical and electrochemical properties were thoroughly studied. The efficiency of perovskite solar cells was improved from a reference value of 16.4% to 18.0–18.6%, using optimized interlayers of the tin complexes with salicylimine (1) or 2,3-dihydroxynaphthalene (2) ligands, and the germanium complex with the 2,3-dihydroxyphenazine ligand (4). The IR s-SNOM mapping revealed that the best-performing interlayers form uniform and pinhole-free coatings atop the PC61BM electron-transport layer, which improves the charge extraction to the top metal electrode. The obtained results feature the potential of using tin and germanium complexes as prospective materials for improving the performance of perovskite solar cells.

Photodynamic therapy (PDT), a rapidly developing method for the treatment of cancer and bacterial diseases, is based on the photosensitization of oxygen to generate reactive oxygen species (ROS) that destroy specific biological targets. Among the various photosensitizers, phthalocyanines (Pc) have attracted particular attention due to their excellent photophysical properties, most of which meet the therapeutic requirements. The statement that aggregation of Pc-based photosensitizers is undesirable because it suppresses ROS generation has become commonplace in PDT. In this review, we have collected and discussed a number of works whose results refute this well-established axiom and show that aggregated forms of phthalocyanines can still exhibit photodynamic activity, in some cases in synergy with the photothermal and optoacoustic effects. In addition, ROS generation can be induced by aggregates under the conditions of sonodynamic therapy.

New synthetic pathway toward water-soluble phthalocyanines (Pc) bearing cationic 4-(N,N,N-trialkylammonium-methyl)-phenoxy groups has been elaborated. It involves the convenient reductive amination of various (4-formylphenoxy)-substituted phthalonitriles with diethylamine and NaBH(OAc)(3), leading to 3-, 4- and 4,5-(p-diethylaminomethyl-phenoxy)-substituted phthalonitriles as precursors to new Zn(II), Mg(II) and metal-free phthalocyanines (4 alpha-MPc, 4 beta-MPc and 8 beta-MPc, M = 2H, Mg, Zn) containing four or eight cationic groups in non-peripheral (alpha-) or peripheral (beta-) positions. Novel compounds have been characterized by different spectroscopic techniques (H-1, C-13 NMR, FTIR, UV-Vis) and MALDI TOF mass spectrometry. All cationic Pcs exhibited strong absorption in the phototherapeutical spectral range from 670 to 700 nm (epsilon(max) > 10(5) M-1 cm(-1)) and high quantum yields of singlet oxygen generation in DMSO where all phthalocyanines existed in monomeric forms. Also, cationic complexes showed moderate solubility in water with high tendency to aggregation, however alpha-substituted Zn(II) and Mg(II) complexes existed in water in predominantly monomeric states. Further monomerization of Zn(II) complex 4 alpha-ZnPc in aqueous solution can be achieved by interaction either with nonionic surfactant Tween-80 or bovine serum albumin (BSA). The advantage of our results is not limited to new convenient synthetic approach to the cationic phthalocyanines but it also consists in preparation of new phototherapeutic agents with promising photophysical and photochemical properties.

This review presents a wide range of tetrapyrrole photosensitizers used for photodynamic therapy (PDT), antimicrobial photodynamic therapy, photoinactivation of pathogens. Methods of synthesis and design of new photosensitizers with greater selectivity of accumulation in tumor tissue and increased photoinduced antitumor activity are considered. The issues of studying the properties of new photosensitizers, their photoactivity, the ability to generate singlet oxygen, and the possibility of using targeted photodynamic therapy in clinical practice are discussed. The review examines the work on PDT by national and foreign researchers.

The synthesis and characterization of A3B-type phthalocyanines, ZnPc1–4, bearing bulky 2,6-diisopropylphenoxy-groups or chlorine atoms on isoindoline units “A” and either one or two carboxylic anchors on isoindoline unit “B” are reported. A comparison of molecular modelling with the conventional time dependent—density functional theory (TD-DFT) approach and its simplified sTD-DFT approximation provides further evidence that the latter method accurately reproduces the key trends in the spectral properties, providing colossal savings in computer time for quite large molecules. This demonstrates that it is a valuable tool for guiding the rational design of new phthalocyanines for practical applications.

Nucleic acid aptamers are generally accepted as promising elements for the specific and high-affinity binding of various biomolecules. It has been shown for a number of aptamers that the complexes with several related proteins may possess a similar affinity. An outstanding example is the G-quadruplex DNA aptamer RHA0385, which binds to the hemagglutinins of various influenza A virus strains. These hemagglutinins have homologous tertiary structures but moderate-to-low amino acid sequence identities. Here, the experiment was inverted, targeting the same protein using a set of related, parallel G-quadruplexes. The 5′- and 3′-flanking sequences of RHA0385 were truncated to yield parallel G-quadruplex with three propeller loops that were 7, 1, and 1 nucleotides in length. Next, a set of minimal, parallel G-quadruplexes with three single-nucleotide loops was tested. These G-quadruplexes were characterized both structurally and functionally. All parallel G-quadruplexes had affinities for both recombinant hemagglutinin and influenza virions. In summary, the parallel G-quadruplex represents a minimal core structure with functional activity that binds influenza A hemagglutinin. The flanking sequences and loops represent additional features that can be used to modulate the affinity. Thus, the RHA0385–hemagglutinin complex serves as an excellent example of the hypothesis of a core structure that is decorated with additional recognizing elements capable of improving the binding properties of the aptamer.

An aptamer is a synthetic oligonucleotide with a unique spatial structure that provides specific binding to a target. To date, several aptamers to hemagglutinin of the influenza A virus have been described, which vary in affinity and strain specificity. Among them, the DNA aptamer RHA0385 is able to recognize influenza hemagglutinins with highly variable sequences. In this paper, the structure of RHA0385 was studied by circular dichroism spectroscopy, nuclear magnetic resonance, and size-exclusion chromatography, demonstrating the formation of a parallel G-quadruplex structure. Three derivatives of RHA0385 were designed in order to determine the contribution of the major loop to affinity. Shortening of the major loop from seven to three nucleotides led to stabilization of the scaffold. The affinities of the derivatives were studied by surface plasmon resonance and an enzyme-linked aptamer assay on recombinant hemagglutinins and viral particles, respectively. The alterations in the loop affected the binding to influenza hemagglutinin, but did not abolish it. Contrary to aptamer RHA0385, two of the designed aptamers were shown to be conformationally homogeneous, retaining high affinities and broad binding abilities for both recombinant hemagglutinins and whole influenza A viruses.