A synthetic approach to the first hybride triazolyl-pyridyl-imidazolone ligands with redox-active auxiliary groups was developed. These tridentate ligands may be used to obtain copper coordination compounds of two structural types, differing in the oxidation state of the copper ion and the geometry of its environment. These complexes were successifully synthesised and characterized by NMR, CV, RDE, HRMS, EPR, and XRD data. All coordination compounds exhibited cytotoxic activity against the MCF-7 and A549 tumor cell lines, exceeding significantly the IC50 of the free ligands. The two most promising complexes, 11c and 15c, demonstrated cytotoxicity at low micromolar concentrations, in vitro selectivity better than cisplatin, and inhibition of tumor growth in vivo. The mechanism of cytotoxic action of these complexes is most likely associated with oxidative cleavage of DNA under redox reactions involving metal ions in coordination compounds.

Copper-organic compounds are being investigated as antitumor candidates. Besides their efficacy as cytotoxic agents alone, the oxidative potential of electrochemical Cu2+-to-Cu1+ transition emerges as an attractive approach for elimination of tumor cells otherwise resistant to chemotherapy. To minimize side effects of the potent oxidative burst upon Cu(II) reduction, the metal cations should be delivered to the tumor site. Taking advantage of the ability of bisphosphonates to accumulate in the bone, we synthesized a Cu(II) complex of zoledronic acid (ZA), an FDA-approved drug for prevention of bone destruction. The CuZA complex obtained upon precipitation of ZA and different copper salts (sulfate, chloride or perchlorate) were structurally identical, consisting of two organic moieties coordinated by three metal cations. Combined treatment with water-soluble formulations of CuZA and cysteine triggered rapid death in human cell lines. This effect was achievable with non-toxic concentrations of CuZA and cysteine alone. Importantly, the K562 chronic myelogenous leukemia cells that demonstrated an attenuated response to the 3d generation Bcr-Abl tyrosine kinase inhibitor in the medium conditioned by bone marrow-derived fibroblasts, were readily killed by CuZA-cysteine combination. Thus, oxidative burst upon metal reduction in CuZA complexes emerges as a promising method of eradication of tumor cells in the bone microenvironment.

A new hybrid organic ligand with 2-(2-pyridyl)benzothiazoles and catechol fragments was synthesized and studied in the complexation reaction with copper(II) chloride. Synthesis conditions that allow for obtaining a complex in which copper coordination is carried out by the pyridylbenzothiazole fragment, and the catechol fragment does not participate in the coordination, have been determined. To find the possibility and optimal conditions for a complex without coordination of catechol formation, DFT calculation data were used. The structure of the obtained coordination compound with LCuCl2 composition was established using as elemental analysis, UV-Vis spectroscopy, cyclic voltammetry and total X-ray scattering with pair distribution function analysis. Measurement of cytotoxicity and the ability to reactive oxygen species (ROS) generation for synthesized complex on MCF-7 cell lines demonstrated reasonable cytotoxicity of 5 µМ, not associated with ROS formation.

New vitamin E hydrazone analogues bearing (2-hydroxyaryl) methylene moieties were obtained from Trolox hydrazide and the corresponding 2-hydroxyarenecarbaldehydes. The compounds demonstrated effective antioxidant activity and selective action against cancer cells, suggesting their potential as supportive pharmacological agents in oncology.

A modular synthesis of a new family of core-fluorinated BODIPYs was elaborated. β-Fluoro-β-nitrostyrenes were used as starting materials to prepare a set of mono-fluorinated pyrrole-2-amides using the Barton-Zard reaction with 2-isocyanoacetamides. The prepared monofluorinated building blocks were successively transformed into the corresponding dipyrromethanes and 1,7-difluoro-BODIPY-3,5-diamides. As a result, a new family of luminophores with a combination of fluorescence and photosensitizing properties was obtained. The photophysical properties of novel BODIPYs were studied by UV-vis and fluorescence spectroscopy, cyclic voltammetry and DFT calculations. In addition, their ability to generate singlet oxygen was assessed. The properties of 1,7-difluoro-BODIPY-3,5-diamides were compared with their analogues to reveal the substituent effect at the 3,5-positions. The fluorescent properties of the obtained dyes were significantly improved in comparison to their 3,5-diester analogous.

Three novel 2-thio-4H-imidazol-4-ones containing conjugated five, six- or seven-membered S,N-heterocycle and pyridin-2-ylmethylidene moiety (L) were synthesized by two-step reaction sequence starting from 2-thiohydantion. The ligand structures were confirmed by H-1 NMR, C-13 NMR and HRMS. The reactions of the ligands L with copper chloride dihydrate give the complexes of LCuCl2 composition. Copper coordination compounds with 6-(pyridin-2-ylmethylidene)-2,3-dihydroimidazo[2,1-b][1,3]thiazol-5(6H)-one (L1) and 2-(pyridin-2-ylmethylidene)-6,7-dihydro-5H-imidazo[2,1-b][1,3]thiazin-3(2H)-one (L2) were characterized by the X-ray data, demonstrating the distorted tetrahedral copper coordination environment. It was shown that the presence in the ligand L1 of a five-membered thiazolidine ring fused with imidazolone leads to a significant change in the geometric characteristics of the complex: an increase in the Cu-S distance and the flattening of copper coordination polyhedron. Both synthesized complexes were evaluated using cyclic voltammetry and demonstrated the quasi-reversible reduction of Cu(II) at similar to -0.25 V. Testing of the antibacterial activity on the reporter strains E. coli Delta tolC pDualrep2 (AmpR) and E. coli lptDmut pDualrep2 (KanR) showed a lower activity of the synthesized copper-containing complexes compared to the complexes of similar ligand that did not have an additional condensed ring in its structure.

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.

Two novel macrocyclic compounds with a crown ether moiety annulated to a tetracyclic thiophene-containing aromatic fragment were synthesized by the Mallory–Katz photocyclization reaction from a single stilbene precursor. These compounds...

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

The copper-catalyzed azide-alkyne cycloaddition of BODIPY acetylene derivative and ferrocene azides in supercritical CO2 2 at 80 degrees C and 81 bar affords the corresponding triazole-containing BODIPY-ferrocene conjugates in high yields. The fluorescent and electrochemical properties of the compounds thus obtained were explored.

The copper-catalyzed azide–alkyne cycloaddition of BODIPY acetylene derivative and ferrocene azides in supercritical CO2 at 80 °C and 81 bar affords the corresponding triazole-containing BODIPY–ferrocene conjugates in high yields. The fluorescent and electrochemical properties of the compounds thus obtained were explored.

Copper–organic compounds have gained momentum as potent antitumor drug candidates largely due to their ability to generate an oxidative burst upon the transition of Cu2+ to Cu1+ triggered by the exogenous-reducing agents. We have reported the differential potencies of a series of Cu(II)–organic complexes that produce reactive oxygen species (ROS) and cell death after incubation with N-acetylcysteine (NAC). To get insight into the structural prerequisites for optimization of the organic ligands, we herein investigated the electrochemical properties and the cytotoxicity of Cu(II) complexes with pyridylmethylenethiohydantoins, pyridylbenzothiazole, pyridylbenzimidazole, thiosemicarbazones and porphyrins. We demonstrate that the ability of the complexes to kill cells in combination with NAC is determined by the potential of the Cu+2 → Cu+1 redox transition rather than by the spatial structure of the organic ligand. For cell sensitization to the copper–organic complex, the electrochemical potential of the metal reduction should be lower than the oxidation potential of the reducing agent. Generally, the structural optimization of copper–organic complexes for combinations with the reducing agents should include uncharged organic ligands that carry hard electronegative inorganic moieties.

Two series of novel Cu (II) (4a–e) and Ni (II) (5a–e) complexes bearing 1-(N-phenylthiocarbamoyl)-pyrazoline ligands (3a–e) were synthesized and characterized. The structures of Ni (II) complexes 5a, c were confirmed by X-ray crystallography; both complexes have a distorted octahedral coordination environment of the Ni (II); metal atoms are coordinated by pyridyl and pyrazoline nitrogen atoms and thiocarbonyl sulfur of two ligand moiety, with two chloride anions in the outer sphere. The Cu (II) complex 4a derived from ligand 3a demonstrate a non-typical electrochemical behavior indicating Cu (I) complex formation which can be explained either by pyrazoline ligand ring opening in DMF solution or by a non-innocent nature of 3a. All of the synthesized complexes were cytotoxic against HCT116 and К562 cell lines; the most cytotoxic ligand was 3d, which is structurally related to combretastatin A4.

Titanocene conjugates with four different non-steroidal anti-inflammatory drugs (flurbiprofen, naproxen, ibuprofen, and diclofenac; NSAIDs) were obtained and studied for the first time.

Methods for the synthesis of new ditopic organic ligands containing coordinating fragments of two types, terpyridine and thiohydantoin, have been developed. The complex formation reactions of the synthesized ligands with copper(II) chloride were studied. As a result, two types of coordination compounds were isolated and characterized by electron spectroscopy, elemental analysis, and cyclic voltammetry: copper(I,II) bis-ligand tetranuclear mixed-valent complexes and a monoligand binuclear complex containing two copper(II) ions. The cytotoxic activity of the obtained coordination compounds with respect to the MCF7, A549, and HEK293 cell lines was studied.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

Using the [3+2] cycloaddition reaction of [HC≡C-GePh2 -]2 (1) and a number of RCH2 N3 , this work described the synthesis of a series of novel heterocyclic digermanes, bitriazoles [1,4-C2 HN3 (CH2 R)GePh2 -]2 , 2-12 (R=Ph, p-Tol, p-C6 H4 NMe2 , p-C6 H4 OMe, p-C6 H4 Br, m-C6 H4 NO2 , 2-Naphth, CH2 -p-OC6 H4 CHO, CH2 -p-OC6 H4 COOMe, CH2 P(O)(OEt)2 , COOEt), difficult to produce by other methods. The structural peculiarities of these compounds were studied in detail by NMR spectroscopy and by XRD analysis (for 6, 9 and 10). The properties of 1-12 were studied by UV/vis and luminescence emission spectroscopy, electrochemistry and DFT calculations, indicating an effective conjugation in their molecules.

The search for new anticancer drugs based on biogenic metals, which have weaker side effects compared to platinum-based drugs, remains an urgent task in medicinal chemistry. Titanocene dichloride, a coordination compound of fully biocompatible titanium, has failed in pre-clinical trials but continues to attract the attention of researchers as a structural framework for the development of new cytotoxic compounds. In this study, a series of titanocene (IV) carboxylate complexes, both new and those known from the literature, was synthesized, and their structures were confirmed by a complex of physicochemical methods and X-ray diffraction analysis (including one previously unknown structure based on perfluorinated benzoic acid). The comprehensive comparison of three approaches for the synthesis of titanocene derivatives known from the literature (the nucleophilic substitution of chloride anions of titanocene dichloride with sodium and silver salts of carboxylic acids as well as the reaction of dimethyltitanocene with carboxylic acids themselves) made it possible to optimize these methods to obtain higher yields of individual target compounds, generalize the advantages and disadvantages of these techniques, and determine the substrate frames of each method. The redox potentials of all obtained titanocene derivatives were determined by cyclic voltammetry. The relationship between the structure of ligands, the reduction potentials of titanocene (IV), and their relative stability in redox processes, as obtained in this work, can be used for the design and synthesis of new effective cytotoxic titanocene complexes. The study of the stability of the carboxylate-containing derivatives of titanocene obtained in the work in aqueous media showed that they were more resistant to hydrolysis than titanocene dichloride. Preliminary tests of the cytotoxicity of the synthesised titanocene dicarboxilates on MCF7 and MCF7-10A cell lines demonstrated an IC50 ≥ 100 μM for all the obtained compounds.

Two novel aromatic thiophene-containing annulated compounds, viz. 2-methoxy[b]naphtho[2,1-d]thiophene and 1,3-dimethoxy[b]naphtho[2,1-d]thiophene, were synthesized via the Mallory-type photocyclization. Their optical, redox and photophysical properties have been studied along with phosphorescence spectra and lifetimes at 77 K. The first compound exhibited much higher charge mobility in thin films than the second one suggesting the former being prospective for molecular electronics applications.