Two diastereomeric P,P*-phosphine-diamidophosphites featuring a 1,3,2-diazaphospholidine ring and an oxalamide scaffold were synthesized. These C1-symmetric ligands are far more convenient for probing coordination by NMR than their C2-symmetric bisdiamidophosphite or bisphosphine analogs, because the chemical nonequivalence of their phosphorus nuclei gives rise to well-resolved spin-spin couplings in the NMR spectra of the resulting complexes. The NMR spectral data, in combination with DFT calculations, demonstrate the bridging, rather than chelating, mode of the "unnatural" diastereomer in Pd(ii) and Rh(i) complexes. Both ligands were evaluated for Pd-catalyzed asymmetric allylic substitution and Rh-catalyzed asymmetric hydrogenation. The influence of the ligands' chiral constituents on enantioselectivity was assessed, and the effects of the ligand-to-metal ratio on complexation and catalytic performance were investigated.

Background/Objectives: Transition metal complexes of imidazoles exhibit a variety of biological activities. This makes them promising metal-based drugs for use in medicine. The aim of this research is to investigate the complexes of zinc(II) with N-vinyl, N-allyl, and N-propargylimidazoles, represented by the formula [ZnL2Cl2], as potential drug candidates. Methods: Structural studies of the obtained complexes were performed using single-crystal X-ray diffraction analysis, IR and NMR spectroscopy. DFT calculations were used to determine structural, electronic and thermochemical parameters of the complexes. QSAR analysis was performed using PASS. The wound-healing and antihypoxic activities were studied in vivo using models of wounds and acute hypoxia of various origins. The antimicrobial activity of the complexes was evaluated against Staphylococcus aureus Wood 46, Escherichia coli M-17, and the yeast fungus Candida albicans 927. The cytotoxic activity was tested using several cell lines, including monkey kidney (Vero) cells, human cervical cancer cells (Hep2C and HeLa), human lung carcinoma (A549), and human embryonal rhabdomyosarcoma (RD). Results: New complexes of N-allylimidazole and N-allyl-2-methylimidazole with ZnCl2 were synthesized and characterized. All the studied complexes possess diverse biological activities. While the antimicrobial activity was modest, a distinct antifungal activity was observed. The cytotoxicity of the complexes was found to be mainly in relation to Hep2c and RD cell lines. Conclusions: Based on the results of QSAR analysis and experimental findings, the diverse biological activities of the compounds indicate that they are promising lead structures for further optimization in drug development.

New dyads consisting of 5,15-diphenylporphyrin and pyrene chromophores were synthesized through the Suzuki coupling of halogenated porphyrins with pyreneboronic acid. Two different types of dyads were obtained: one with a direct connection between the macrocycles, and the other with an ethene bridge in between them. The free bases as well as the nickel and zinc complexes of these dyads were investigated using electron absorption and emission spectroscopy. A weak interaction was observed between the components in the ground state in the directly linked dyads, while a stronger interaction was found in the ethene-bridged ones. In the excited state, energy flows from pyrene to porphyrin chromophore in both types of dyad, but with different efficiencies depending on the metal complex or free base porphyrin used as a component of the dyad. DFT calculations provide insights into the structural features and interactions in these dyads. The obtained dyads may be of interest as potential photosensitizers and ratiometric luminescent sensors based on their dual blue and red luminescence.

The bromination of a carbon–carbon double bond is a classic reaction, the mechanism of which has been thoroughly studied for a long time. However, it has been found that the behavior of certain porphyrin substrates does not follow generally accepted concepts. Instead of bromine addition to the double bond, these substrates undergo substitution of a hydrogen atom by a bromine atom. Using the methods of low-temperature NMR spectroscopy and quantum chemical calculations, the mechanism of the bromination reaction of vinylporphyrins has been established. It has been demonstrated that the influence of a porphyrin substituent on the double bond leads to a change in the mechanism from electrophilic addition AdE, which is typical for alkenes, to electrophilic substitution SE, which is characteristic of aromatic compounds but not alkenes. This fact significantly challenges the well-established classical concept that alkenes do not undergo electrophilic substitution reactions. The obtained results of mechanistic studies have not only fundamental scientific value, but also practical application: using the bromination reaction studied, it is possible to perform the CH-functionalization of vinyl substrates in a single step with high efficiency. As a result of this functionalization, corresponding bromovinyl (2-bromovinyl) derivatives are obtained, which are valuable electrophilic synthons— building blocks for catalytic reactions of carbon–carbon (cross-coupling) and carbon–heteroatom (substitution) bond formation.

Combined viral and photodynamic therapy for oncological diseases has great potential to treat aggressive tumors such as glioblastomas. A conjugate of vesicular stomatitis virus (VSV) with protoporphyrin IX was prepared, and its oncolytic effects were studied and compared to the effects of the individual components. The VSV showed an oncolytic effect on glioblastoma cell lines T98G and LN229 at a virus titer of 105 TCID50/mL. A VSV titer of 104 TCID50/mL was sufficient for neuroblastoma cell death. A study of the effect of VSV in tumor 3D cell modeling found that VSV had a clear viral cytopathic effect on spheroids of T98G and LN229 cells. Conjugation with the porphyrin significantly reduced the viral titer, but when irradiated, lysis of cells was observed. Photodynamic treatment of T98G and LN229 cells and spheroids with protoporphyrin IX as a photosensitizer also had a cytotoxic effect on cells and, to a lesser extent, on the tumoroids, as complete cell death was not achieved for the tumoroids. The combination therapy, which involved sequential photodynamic therapy using protoporphyrin IX as a photosensitizer and treatment with VSV, was shown to significantly enhance efficacy, resulting in complete cell death of both T98G and LN229 cells and tumoroids. The combination treatment allowed for the use of a lower viral titer (103–104 TCID50/mL) and a lower porphyrin concentration (0.5 μg/mL) to achieve a significant cytotoxic effect. As a result, the implementation of this combination therapy would likely lead to fewer side effects from the treatment. This study clearly demonstrated the excellent perspectives of combination therapy for the treatment of highly aggressive tumors such as glioblastomas.

An unusual neutral dinuclear palladium(II) complex with two head-to-head orientated μ-P,S-bridging ligands was obtained by the reaction of Pd(MeCN)2 Cl2 with (1R,5R)-3-(4-phenylthiobutoxy)-2,4-diphenyl-2,4-diaza-3-phospha-bicyclo[3.4.0]nonane. The dimeric structure of the complex in the solid state and in solution was thoroughly confirmed using appropriate analytical techniques: single crystal X-ray diffraction analysis, HRMS, FTIR and NMR spectroscopy.

Conjugated porphyrin dyads have valuable electron-optical properties that make them useful for a variety of applications. Two dyads of palladium(ii) beta-octaethylporphyrin linked with a butenyne bridge to nickel(ii) meso-diphenylporphyrin and methyl pyropheophorbide-a were synthesized using the Sonogashira cross-coupling reaction. Both dyads exhibited optical properties considerably different from their corresponding components, which indicated strong electronic interaction between the units in the dyads in both the ground and excited states, providing fast energy flow between the chromophores. DFT calculations revealed the structural features of the dyads in interconnection with their electronic properties. Conjugation energy gain forced a decrease in the dihedral angle between the porphyrin plane and the linking carbon-carbon double bond, although at the expense of distortion of the diphenylporphyrin ring. Electron transitions upon excitation comprise molecular orbitals centered on both chromophores, and their interaction led to an emerging new bathochromically shifted Soret band component at 460 nm. The palladium porphyrinate-chlorin dyad exhibits luminescence properties in the red visible range at room temperature and phosphorescence in the near-infrared (NIR) range at 77 K. In contrast, the palladium-nickel porphyrinate dyad does not emit light but absorbs light more efficiently across the entire visible spectrum. Both dyads feature broad and strong absorption representing panchromatic-like dyes. These dyads could be useful as potential photosensitizers for solar light conversion devices.

A series of easy-to-prepare and modular chiral P,S-bidentate phosphoramidites were synthesized. With respect to Pd(II), these ligands showed the ability to form stable P,S-chelate allylic complexes. The structures of the ligands and their complexes were confirmed by 2D NMR spectroscopy and single-crystal X-ray diffraction. These chiral inducers provided up to 99% ee in the Pd-catalyzed asymmetric allylic substitution of (E)-1,3-diphenylallyl acetate with C- and N-nucleophiles and up to 94% ee in the Pd-mediated allylic alkylation of cinnamyl esters with beta-ketoesters and 2,5-dimethylpyrrole. Furthermore, up to 92% ee with quantitative conversion and chemo- and regioselectivity was achieved in the rare reaction between 2-(diethoxyphosphoryl)-1-phenylallyl acetate and aniline. The effects of the structural parameters, reaction conditions and ligand-to-metal ratio on the catalytic results are discussed. It was shown that the ligands surpass their analogues with different denticity.

A number of new azo dyes were synthesized using azo-coupling of nitrohydroxyphenols (2-nitroresorcinol and nitrophloroglicinol) with ortho-aminophenol and its nitro-and sulfonic-substituted derivatives. The dye mole-cules contain multiple hydroxy groups which can be easily deprotonated, and their ionization affects the con-jugated & pi;-electron system of the dye molecule leading to the significant spectral changes. Spectrophotometric titration of the obtained dyes with an acid and an alkali revealed their halochromic behaviour, i.e. an ability to alter color upon pH change. All the dyes absorb light with wavelength shorter 500 nm in acidic media, and with wavelength longer 500 nm in alkaline media. Variation of substituents in the dye molecules allows to tune the pH range of the color change. The obtained dye series covers the pH range from 0 to 10. DFT calculations of the dye molecules revealed their structures and preferential isomeric forms. TD-DFT calculations of the excited states allowed to clarify the acid-base equilibrium based on the spectrophotometric titration, and to determine the nature of the observed absorption bands. The dyes were adsorbed on polyamide fabrics, and the dyed fabrics reversibly changed their color upon treating with acids and alkalis. These fabrics with applied dyes showed good resistance to aggressive environments and mechanical influences. Results of tests of the dyed fabrics showed that the obtained materials can be used as flexible textile pH sensors.

New asymmetric dyads consisting of porphyrin and chlorin components connected by an azine bridge have been obtained. Nickel and palladium complexes of tetramethyl ester of coproporphyrin I were used as porphyrin components, and chlorin was represented by methyl esters of pyropheophorbide a and d. Mesohydrazones of NiII and PdII complexes of the coproporphyrin I tetraethyl ester reacted with methyl pyropheophorbide a and methyl pyropheophorbide d resulting in the formation of dyads with good yields. Photophysical studies of dyads showed that in the ground state there is a weak interaction between the components. In this case, the interaction is enhanced in the excited state. DFT calculations showed the orthogonality of the orientation of the azine bridge with respect to the porphyrin ring in the ground state and the presence of conjugation in the excited state.

A new transformation of the 152,173-dimethyl ester of chlorin e6, leading to its 131,133-lactone derivative, has been discovered. The reaction proceeded at treatment of the substrate with lead tetraacetate in presence of LiCl, during which oxidative cyclization was observed leading to the formation of a lactone cycle fused with the tetrapyrrole macrocycle at positions 13 and 15. The reaction mechanism has been suggested, and quantum chemical calculations were carried out to substantiate the mechanism.

This review presents a strategy for obtaining various functional derivatives of tetrapyrrole compounds based on transformations of unsaturated carbon-oxygen and carbon-carbon bonds of the substituents at the meso position (meso-formyl, vinyl, and ethynyl porphyrins). First, synthetic approaches to the preparation of these precursors are described. Then diverse pathways for the transformations of the multipotent synthons are discussed, revealing a variety of products of such reactions. The structures, electronic, and optical properties of the compounds obtained by the methods under consideration are analyzed. In addition, there is an overview of the applications of the products obtained. Biomedical use of the compounds is among the most important. Finally, the advantages of using the reviewed synthetic strategy to obtain dyes with targeted properties are highlighted.

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.

Cell analysis by optochemical sensing represents large and important niche in life and biomedical sciences. We present advanced multi-modal, multi-analyte sensing platform and dedicated materials for cell analysis based on the substituted phosphorescent Pt(II)- or Pd(II)-porphyrin indicator dyes bearing dual O2 and pH sensing functionality (MePor-SB). The study includes screening of the different host matrices for the sensor, synthesis and evaluation of new MePor-SB derivatives with altered protonation behaviour, development of the ratiometric version of the pH sensor, assessment of photoluminescent signal enhancement options, deposition of sensor coatings on common cell analysis substrates and their demonstration of sensor performance in Oxygen Consumption Rate (OCR) and Extracellular Acidification (ECA) measurements with relevant cell models. The main outcomes include the elaboration of the structure-function relationships for this biosensor system, development of the self-referenced tandem O2/pH and OCR/ECA sensing system which enables calibration-free operation, demonstration of the sensor operation on common plastic substrates in cell analysis, benchmarking against the existing platforms and real-life experiments with cells. This new sensing platform shows potential for wide practical use.

“Roof shaped” chiral diamidophosphites of various structures and denticities were obtained and tested in Pd-catalyzed asymmetric allylic substitution.

A method for obtaining porphyrin dimers bound by a 1,3-butadiene bridge through homocoupling of 2-boronylethenylporphyrins has been developed. The homocoupling reaction proceeds under mild conditions at room temperature using tetrakistriphenylphosphine palladium as a catalyst in the presence of the oxidizer silver oxide Ag2O. The corresponding dimeric product was obtained from palladium meso(2-pinacolboronylethenyl)-beta-octaethylporphyrinate. The UV-Vis absorption spectrum of the dimeric product is slightly different from that of the monomeric palladium meso-vinyl-beta-octaethylporphyrinate, which indicates the absence of pi-electronic conjugation between tetrapyrrole aromatic systems. The DFT calculation of the dimer showed that the orthogonal orientation of the butadiene bridge with respect to the plane of tetrapyrrole macrocycles is realized.

A method of direct borylation of vinyl-substituted porphyrinoids (porphyrins and chlorins) has been developed based on the copper catalyzed vinylic C-H activation. Ni(II) complexes of meso- and β-vinylporphyrinoids have been transformed to the corresponding pinacolboronated derivatives with good yields and high (E)-stereoselectivity. The method provides an easy and direct access to the valuable synthons which were shown to act as nucleophylic partners in the Suzuki cross-coupling building tetrapyrrole derivatives with π-conjugation through the carbon-carbon double bond.

In order to increase the bioavailability of water-insoluble pyropheophorbide-a (PPP-a) methyl ester, its liposomal form is prepared and the physicochemical and photochemical properties of this form are studied. The quantum yield of 1O2 is found to have a bell-shaped dependence on the concentration of PPP-a in the lipid phase of liposomes with the maximum at 31.6 µmol/g of lipids. The IR spectroscopy shows the photoinduced formation of aldehyde groups in the lipid phase of liposomes. The intracellular accumulation of PPP-a is confirmed by confocal microscopy.

A large family of P,S-bidentate diamidophosphite ligands were readily synthesized from accessible hydroxyl-thioether compounds. One type of Pd(II) cationic allylic complex with these diamidophosphites fulfilling a P-monodentate function, and three types, where the ligands act as P,S-bridging ligands (coordination polymer and head-to-head and head-to-tail dimers), were obtained. In addition, neutral Pd(II) halide complexes were generated in situ as common intermediates for both groups of cationic dimers. The structures of the ligands and complexes were elucidated by means of 2D-NMR and were confirmed by powder X-ray diffraction, as well as by DFT calculations. Asymmetric inducers of this type exhibited up to 94% ee in the Pd-mediated allylic substitution of (E)-1,3-diphenylallyl acetate with various C- and N-nucleophiles. Ee values of up to 80% were obtained in the Pd-catalyzed allylic alkylation of cinnamyl acetate with beta-ketoesters. In addition, up to 61% ee was achieved in the asymmetric amination of 2-(diethoxyphosphoryl)-1-phenylallyl acetate with aniline. The effects of the diamidophosphite and thioether moieties on the catalytic activity and enantioselectivity were investigated.

Characteristics of LiClO4/TTG and LiClO4/DMF electrolytes at different salt concentrations have been experimentally determined by conductometry, Li-7, H-1, C-13 NMR. It has been demonstrated that the influence of these parameters on the oxygen reaction is due to solvation and electrical conductivity, which, determine the transport characteristics of the reaction participants. In DMF the formation of Li2O2 proceeds predominantly through the solution bulk. In TTG the reaction proceeds predominantly on the electrode surface and does not depend on LiClO4 concentration, which is likely due to the formation of Li2O2 on the electrode surface without passing into the solution bulk with a weak concentration dependence of LiClO4 dissociation in TTG. It cannot be ruled out that the LiClO4 concentration in TTG has an effect on the oxygen reduction mechanism at higher concentrations (> 2 M) because of the complex formation. At any LiClO4 concentration in TTG, the amount of electricity in the cathodic process is lower and the reaction reversibility is higher than in DMF solutions. The key factor responsible for the change in the characteristics of the oxygen reaction in TTG is the decrease in the electrical conductivity and diffusion coefficients of O-2 and Li+ with increasing concentration, due to the viscosity of the solution and low dielectric constant. (c) 2021 Elsevier Ltd. All rights reserved.