The Role of Intraligand Charge Transfer Processes in Iridium(III) Complexes with Morpholine-Decorated 4'-Phenyl-2,2':6',2″-terpyridine.

To investigate the impact of the electron-donating morpholinyl (morph) group on the ground- and excited-state properties of two different types of Ir(III) complexes, [IrCl3(R-C6H4-terpy-κ3N)] and [Ir(R-C6H4-terpy-κ3N)2](PF6)3, the compounds [IrCl3(morph-C6H4-terpy-κ3N)] (1A), 4[Ir(morph-C6H4-terpy-κ3N)2](PF6)3 (2A), [IrCl3(Ph-terpy-κ3N)] (1B) and [Ir(Ph-terpy-κ3N)2](PF6)3 (2B) were obtained. Their photophysical properties were comprehensively investigated with the aid of static and time-resolved spectroscopic methods accompanied by theoretical DFT/TD-DFT calculations. In the case of bis-terpyridyl iridium(III) complexes, the attachment of the morpholinyl group induced dramatic changes in the absorption and emission characteristics, manifested by the appearance of a new, very strong visible absorption tailing up to 600 nm, and a significant bathochromic shift in the emission of 2A relative to the model chromophore. The emission features of 2A and 2B were found to originate from the triplet excited states of different natures: intraligand charge transfer (3ILCT) for 2A and intraligand with a small admixture of metal-to-ligand charge transfer (3IL-3MLCT) for 2B. The optical properties of the mono-terpyridyl iridium(III) complexes were less significantly impacted by the morpholinyl substituent. Based on UV-Vis absorption spectra, emission wavelengths and lifetimes in different environments, transient absorption studies, and theoretical calculations, it was demonstrated that the visible absorption and emission features of 1A are governed by singlet and triplet excited states of a mixed MLLCT-ILCT nature, with a dominant contribution of the first component, that is, metal-ligand-to-ligand charge transfer (MLLCT). The involvement of ILCT transitions was reflected by an enhancement of the molar extinction coefficients of the absorption bands of 1A in the range of 350-550 nm, and a small red shift in its emission relative to the model chromophore.

Structural and Photophysical Trends in Rhenium(I) Carbonyl Complexes with 2,2':6',2″-Terpyridines.

This is the first comprehensive review of rhenium(I) carbonyl complexes with 2,2':6',2″-terpyridine-based ligands (R-terpy)-encompassing their synthesis, molecular features, photophysical behavior, and potential applications. Particular attention has been devoted to demonstrating how the coordination mode of 2,2':6',2″-terpyridine (terpy-κ2N and terpy-κ3N), structural modifications of terpy framework (R), and the nature of ancillary ligands (X-mono-negative anion, L-neutral ligand) may tune the photophysical behavior of Re(I) complexes [Re(X/L)(CO)3(R-terpy-κ2N)]0/+ and [Re(X/L)(CO)2(R-terpy-κ3N)]0/+. Our discussion also includes homo- and heteronuclear multicomponent systems with {Re(CO)3(R-terpy-κ2N)} and {Re(CO)2(R-terpy-κ3N)} motifs. The presented structure-property relationships are of high importance for controlling the photoinduced processes in these systems and making further progress in the development of more efficient Re-based luminophores, photosensitizers, and photocatalysts for modern technologies.

Copper(II) Complexes with 2,2':6',2″-Terpyridine Derivatives Displaying Dimeric Dichloro-µ-Bridged Crystal Structure: Biological Activities from 2D and 3D Tumor Spheroids to In Vivo Models.

Eight 2,2':6',2″-terpyridines, substituted at the 4'-position with aromatic groups featuring variations in π-conjugation, ring size, heteroatoms, and methoxy groups, were employed to enhance the antiproliferative potential of [Cu2Cl2(R-terpy)2](PF6)2. Assessing the cytotoxicity in A2780 (ovarian carcinoma), HCT116 (colorectal carcinoma), and HCT116DoxR (colorectal carcinoma resistant to doxorubicin) and normal primary fibroblasts revealed that Cu(II) complexes with 4-quinolinyl, 4-methoxy-1-naphthyl, 2-furanyl, and 2-pyridynyl substituents showed superior therapeutic potential in HCT116DoxR cells with significantly reduced cytotoxicity in normal fibroblasts (42-129× lower). Besides their cytotoxicity, the Cu(II) complexes are able to increase intracellular ROS and interfere with cell cycle progression, leading to cell death by apoptosis and autophagy. Importantly, they demonstrated antimetastatic and antiangiogenic properties without in vivo toxicity. In accordance with their nuclear accumulation, the Cu(II) complexes are able to cleave pDNA and interact with bovine serum albumin, which is a good indication of their ability for internalization and transport toward tumor cells.

Large Magnetic Anisotropy in Mono- and Binuclear cobalt(II) Complexes: The Role of the Distortion of the Coordination Sphere in Validity of the Spin-Hamiltonian Formalism.

To get a better insight into understanding the factors affecting the enhancement of the magnetic anisotropy in single molecule (single ion) magnets, two cobalt(II) complexes based on a tridentate ligand 2,6-di(thiazol-2-yl)pyridine substituted at the 4-position with N-methyl-pyrrol-2-yl have been synthesized and studied by X-ray crystallography, AC and DC magnetic data, FIRMS and HFEPR spectra, and theoretical calculations. The change of the counteranion in starting Co(II) salts results in the formation of pentacoordinated mononuclear [Co(mpyr-dtpy)Cl2]·2MeCN (1) complex and binuclear [Co(mpyr-dtpy)2][Co(NCS)4] (2) compound. The observed marked distortion of trigonal bipyramid geometry in 1 and cationic octahedral and anionic tetrahedral units in 2 brings up a question about the validity of the spin-Hamiltonian formalism and the possibility of determining the value and sign of the zero-field splitting D parameter. Both complexes exhibit field-induced slow magnetic relaxation with two or three relaxation channels at BDC = 0.3 T. The high-frequency relaxation time in the reciprocal form τ(HF)-1 = CTn develops according to the Raman relaxation mechanism (for 2, n = 8.8) and the phonon-bottleneck-like mechanism (for 1, n = 2.3). The high-frequency relaxation time at T = 2.0 K and BDC = 0.30 T is τ(HF) = 96 and 47 µs for 1 and 2, respectively.

Further Insights into the Impact of Ligand-Localized Excited States on the Photophysics of Phenanthroline-Based Rhenium(I) Tricarbonyl Complexes.

The present work shows the pivotal role of N-donor substituents attached to 1,10-phenanthroline at the 4,7-positions in perturbation of ground- and excited-state properties of fac-[ReCl(CO)3(R2phen)]. Excited-state processes occurring upon photoexcitation in the designed systems were thoroughly explored with a wide range of steady-state and time-resolved spectroscopic techniques, including transient absorption, as well as experimental results were complemented by theoretical studies based on the density functional theory (DFT). It was demonstrated that the attachment of six-membered heterocyclic amines (piperidine─ppr, morpholine─mor, and thiomorpholine─tmor) is a very effective tool for extending absorptivity and excited-state lifetimes of resulting fac-[ReCl(CO)3(R2phen)] due to the contribution of the excited state localized on the phenanthroline-based ligand. Both absorption and emission properties of these systems were attributed to configurationally mixed MLCT/IL excited states. Re(I) complexes with phenoxazine (pxz) and phenothiazine (ptz) substituents were shown to possess charge-separated excited states, clearly evidenced by the simultaneous presence of signals typical of phen-* and pxz+* or ptz+* in transient absorption spectra. Both complexes are rare examples of NIR light-emitting coordination compounds. The decoration of the phen framework with less polar 9,9-dimethyl-9,10-dihydroacridine (dmac) groups resulted in the formation of [ReCl(CO)3(R2phen)] with mixed 3MLCT/3ILCT triplet excited state.

Pyrenyl-Substituted Imidazo[4,5-f][1,10]phenanthroline Rhenium(I) Complexes with Record-High Triplet Excited-State Lifetimes at Room Temperature: Steric Control of Photoinduced Processes in Bichromophoric Systems.

Photochemical applications based on intermolecular photoinduced energy triplet state transfer require photosensitizers with strong visible absorptivity and extended triplet excited-state lifetimes. Using a bichromophore approach, two Re(I) tricarbonyl complexes with 2-(1-pyrenyl)-1H-imidazo[4,5-f][1,10]phenanthroline (pyr-imphen) and 1-(4-(methyl)phenyl)-2-(1-pyrenyl)-imidazo[4,5-f][1,10]phenanthroline (pyr-tol-imphen) showing extraordinary long triplet excited states at room temperature (>1000 µs) were obtained, and their ground- and excited-state properties were thoroughly investigated by a wide range of spectroscopic methods, including femtosecond transient absorption (fs-TA). It is worth noting that the designed [ReCl(CO)3(pyr-imphen)] (1) and [ReCl(CO)3(pyr-tol-imphen)] (2) complexes form a unique pair differing in the mutual chromophore arrangement due to introduction of a 4-(methyl)phenyl substituent into the imidazole ring at the H1-position, imposing an increase in the dihedral angle between the pyrene and {ReCl(CO)3(imphen)} chromophores. The magnitude of the electronic coupling between the pyrene and {ReCl(CO)3(imphen)} chromophores was found to be an efficient tool to tune the photophysical properties of 1 and 2. The usefulness of designed Re(I) compounds as triplet photosensitizers was successfully verified by examination of their abilities for 1O2 generation and triplet-triplet annihilation upconversion. The phosphorescence lifetimes, ∼1800 µs for 1 and ∼1500 µs for 2, are the longest lifetimes reported for Re(I) diimine carbonyl complexes in solution at room temperature.

In Vitro and In Vivo Biological Activities of Dipicolinate Oxovanadium(IV) Complexes.

The work is focused on anticancer properties of dipicolinate (dipic)-based vanadium(IV) complexes [VO(dipic)(N∩N)] bearing different diimines (2-(1H-imidazol-2-yl)pyridine, 2-(2-pyridyl)benzimidazole, 1,10-phenanthroline-5,6-dione, 1,10-phenanthroline, and 2,2'-bipyridine), as well as differently 4,7-substituted 1,10-phenanthrolines. The antiproliferative effect of V(IV) systems was analyzed in different tumors (A2780, HCT116, and HCT116-DoxR) and normal (primary human dermal fibroblasts) cell lines, revealing a high cytotoxic effect of [VO(dipic)(N∩N)] with 4,7-dimethoxy-phen (5), 4,7-diphenyl-phen (6), and 1,10-phenanthroline (8) against HCT116-DoxR cells. The cytotoxicity differences between these complexes can be correlated with their different internalization by HCT116-DoxR cells. Worthy of note, these three complexes were found to (i) induce cell death through apoptosis and autophagy pathways, namely, through ROS production; (ii) not to be cytostatic; (iii) to interact with the BSA protein; (iv) do not promote tumor cell migration or a pro-angiogenic capability; (v) show a slight in vivo anti-angiogenic capability, and (vi) do not show in vivo toxicity in a chicken embryo.

Vanadium(IV) Complexes with Methyl-Substituted 8-Hydroxyquinolines: Catalytic Potential in the Oxidation of Hydrocarbons and Alcohols with Peroxides and Biological Activity.

Methyl-substituted 8-hydroxyquinolines (Hquin) were successfully used to synthetize five-coordinated oxovanadium(IV) complexes: [VO(2,6-(Me)2-quin)2] (1), [VO(2,5-(Me)2-quin)2] (2) and [VO(2-Me-quin)2] (3). Complexes 1-3 demonstrated high catalytic activity in the oxidation of hydrocarbons with H2O2 in acetonitrile at 50 °C, in the presence of 2-pyrazinecarboxylic acid (PCA) as a cocatalyst. The maximum yield of cyclohexane oxidation products attained was 48%, which is high in the case of the oxidation of saturated hydrocarbons. The reaction leads to the formation of a mixture of cyclohexyl hydroperoxide, cyclohexanol and cyclohexanone. When triphenylphosphine is added, cyclohexyl hydroperoxide is completely converted to cyclohexanol. Consideration of the regio- and bond-selectivity in the oxidation of n-heptane and methylcyclohexane, respectively, indicates that the oxidation proceeds with the participation of free hydroxyl radicals. The complexes show moderate activity in the oxidation of alcohols. Complexes 1 and 2 reduce the viability of colorectal (HCT116) and ovarian (A2780) carcinoma cell lines and of normal dermal fibroblasts without showing a specific selectivity for cancer cell lines. Complex 3 on the other hand, shows a higher cytotoxicity in a colorectal carcinoma cell line (HCT116), a lower cytotoxicity towards normal dermal fibroblasts and no effect in an ovarian carcinoma cell line (order of magnitude HCT116 > fibroblasts > A2780).

Square planar Au(III), Pt(II) and Cu(II) complexes with quinoline-substituted 2,2':6',2″-terpyridine ligands: From in vitro to in vivo biological properties.

Cancer is the second leading cause of death worldwide. Cisplatin has challenged cancer treatment; however, resistance and side effects hamper its use. New agents displaying improved activity and more reduced side effects relative to cisplatin are needed. In this work we present the synthesis, characterization and biological activities of three complexes with quinoline-substituted 2,2':6',2″-terpyridine ligand: [Pt(4'-(2-quin)-terpy)Cl](SO3CF3) (1), [Au(4'-(2-quin)-terpy)Cl](PF6)2·CH3CN (2) and [Cu(4'-(2-quin)-terpy)Cl](PF6) (3). The three complexes displayed a high antiproliferative activity in ovarian carcinoma cell line (A2780) and even more noticeable in a colorectal carcinoma cell line (HCT116) following the order 3 > 2 > 1. The complexes IC50 are at least 20 × lower than the IC50 displayed by cisplatin (15.4 µM) in HCT116 cell line while displaying at the same time, much reduced cytotoxicity in a normal dermal fibroblast culture. These cytotoxic activities seem to be correlated with the inclination angles of 2-quin unit to the central pyridine. Interestingly, all complexes can interact with calf-thymus DNA (CT-DNA) in vitro via different mechanisms, although intercalation seems to be the preferred mechanism at least for 2 and 3 at higher concentrations of DNA. Moreover, circular dichroism (CD) data seems to indicate that complex 3, more planar, induces a high destabilization of the DNA double helix (shift from B-form to Z-form). Higher the deviation from planar, the lower the cytotoxicity displayed by the complexes. Cellular uptake may be also responsible for the different cytotoxicity exhibited by complexes with 3 > 2 >1. Complex 2 seems to enter cells more passively while complex 1 and 3 might enter cells via energy-dependent and -independent mechanisms. Complexes 1-3 were shown to induce ROS are associated with the increased apoptosis and autophagy. Moreover, all complexes dissipate the mitochondrial membrane potential leading to an increased BAX/BCL-2 ratio that triggered apoptosis. Complexes 2 and 3 were also shown to exhibit an anti-angiogenic effect by significantly reduce the number of newly formed blood vessel in a CAM model with no toxicity in this in vivo model. Our results seem to suggest that the increased cytotoxicity of complex 3 in HCT116 cells and its potential interest for further translation to pre-clinical mice xenografts might be associated with: 1) higher % of internalization of HCT116 cells via energy-dependent and -independent mechanisms; 2) ability to intercalate DNA and due to its planarity induced higher destabilization of DNA; 3) induce intracellular ROS that trigger apoptosis and autophagy; 4) low toxicity in an in vivo model of CAM; 5) potential anti-angiogenic effect.

Carbazole effect on ground- and excited-state properties of rhenium(i) carbonyl complexes with extended terpy-like ligands.

The ground- and excited-state properties of three novel complexes [ReCl(CO)3(Ln-κ2N)] bearing 2,2':6',2''-terpyridine, 2,6-di(thiazol-2-yl)pyridine and 2,6-di(pyrazin-2-yl)pyridine functionalized with 9-carbazole attached to the central pyridine ring of the triimine core via phenylene linkage were investigated by spectroscopic and electrochemical methods and were simulated using density functional theory (DFT) and time-dependent DFT. To get a deeper and broader understanding of structure-property relationships, the designed Re(i) carbonyl complexes were compared with previously reported analogous systems - without any groups attached to the phenyl ring and bearing pyrrolidine instead of 9-carbazole. The results indicated that attachment of the N-carbazolyl substituent to the triimine core has less influence on the nature of the triplet excited state of [ReCl(CO)3(Ln-κ2N)] than the pyrrolidine group. Additionally, the impact of the ligand structural modifications on the light emission of the Re(i) complexes under external voltage was preliminarily examined with electroluminescence spectra of diodes containing the synthesized new molecules in an active layer.

Towards better understanding of the photophysics of platinum(II) coordination compounds with anthracene- and pyrene-substituted 2,6-bis(thiazol-2-yl)pyridines.

The photophysical properties of platinum(ii) compounds with 4-(9-anthryl)-2,6-bis(thiazol-2-yl)pyridine (1) and 4-(1-pyrenyl)-2,6-bis(thiazol-2-yl)pyridine (2) were widely investigated. In DMSO and MeCN, the triplet emission of (1) and (2) most probably experiences the solvent-induced exciplex quenching and both complexes exhibit ligand-based fluorescence with maxima in the range of 468-570 nm. In non-coordinating dichloromethane, the emission of (1) and (2) shifts to longer wavelengths, and the lifetimes in microseconds are indicative of phosphorescence. The formation of the triplet excited state was further supported by the observation of singlet oxygen photoluminescence in the near-IR at 1270 nm. To explore the nature of the triplet excited state, the emission properties of (1) and (2) in low temperature glasses were analysed in comparison with those for free ligands and appropriate hydrocarbons, as well as transient absorption spectra were recorded in femtosecond and nanosecond regimes. The studies revealed that the lowest energy triplet state of both complexes is an admixture of 3ILCT and 3(π-π*)aryl character, but the contribution of the 3ILCT state in (1) originating from anthracene to 2,6-bis(thiazol-2-yl)pyridine can be determined as rather negligible.

In vitro antiproliferative effect of vanadium complexes bearing 8-hydroxyquinoline-based ligands - the substituent effect.

This is the first comprehensive study demonstrating the antiproliferative effect of vanadium complexes bearing 8-hydroxyquinoline (quinH) ligands, including the parent and -CH3 (Me), -NO2, -Cl and -I substituted ligands, on HCT116 and A2780 cancer cell lines. To determine the structure-cytotoxicity relationships seven six-coordinate oxovanadium(v) complexes [VO(OMe)(5,7-(Me)2-quin)2] (1), [VO(OMe)(5,7-Cl2-quin)2] (2), [VO(OMe)(5,7-Cl,I-quin)2] (3), [VO(OMe)(5,7-I2-quin)2] (4), [VO(OMe)(5-NO2-quin)2] (5), [VO(OMe)(5-Cl-quin)2] (6), and [VO(OMe)(quin)2] (7) were investigated. The cytotoxicity of 8-hydroxyquinoline oxovanadium(v) complexes is higher in the A2780 cell line (lower IC50) than that observed for the widely used chemotherapeutic agent, cisplatin, while displaying low cytotoxicity for normal human primary fibroblasts. Substituents introduced into the 8-hydroxyquinoline backbone reduced the antiproliferative effect of the vanadium complexes, and the complexes with the ligand substituted only in the 5 position (5 and 6) were more cytotoxic than those with substituents in the 5,7 positions of the quin backbone (1-4). Depending on the substituent type, the cytotoxicity of 1-4 followed the trend: -Cl > -CH3 > -I. Incubation of A2780 cancer cells with IC50 concentrations of complexes 5, 6 and 7 promoted cellular detachment, possibly through membrane destabilization, and triggered apoptosis and necrosis. ROS production might be responsible for the cell death mechanism observed particularly in the A2780 cells exposed to complexes 5 and 6.

Influence of the pyrazine substituent on the structure and magnetic properties of dicyanamide-bridged cobalt(ii) complexes.

Substituted pyrazines were successfully used to prepare two new coordination polymers of formulas {[Co(dca)2(NH2pyz)2]·H2O}n (1) and [Co3(dca)6(HOpyz)5(H2O)2]n (2) [dca = dicyanamide, NH2pyz = 2-aminopyrazine and HOpyz = 2-hydroxypyrazine] whose structures were determined by single-crystal X-ray crystallography. The structure of 1 consists of a two-dimensional rhombus grid of cobalt(ii) ions where the dca ligand adopts the µ1,5 bridging mode with trans-positioned monodentate NH2pyz molecules completing the six-coordination around each metal ion. Compound 2 exhibits a stair-like two-dimensional structure where the intralayer connections are performed by the dca and HOpyz groups exhibiting µ1,5 and bis-monodentate coordination modes, respectively. The values of the cobalt-cobalt separation through the dca bridges are 8.2107(3) (1) and 8.4746(4) and 8.5249(4) Å (2) whereas the value through the hydroxypyrazine is 7.2052(6) Å (2). Solid-state direct-current magnetic susceptibility analyses in the temperature range of 1.9-300 K for 1 and 2 reveal the occurrence of magnetically isolated high-spin cobalt(ii) ions with a significant contribution to the magnetic moment (1 and 2), D = +95.4 (1) and +76.5 cm-1 (2) and the antiferromagnetically coupled pairs of cobalt(ii) centres through the bis-monodentate 2-hydroxypyrazine, J = -0.3 cm-1 (2). Both compounds exhibit frequency dependence of the out-of-phase alternating current (ac) magnetic susceptibility (χ''M) under non-zero applied dc fields, a feature which is characteristic of single-ion magnet behaviour (SIM). Q-band EPR studies on the polycrystalline samples of 1 and 2 at low temperatures confirm the positive sign of D and reveal the occurrence of a strong asymmetry in the g-tensors. Theoretical calculations by CASSCF/NEVPT2 support these results. An analysis of the dynamic behaviour of 1 and 2 suggests that the relaxation of the magnetization occurs in the ground state under applied fields through two Orbach processes possibly bound to low-lying vibrational modes in the high temperature range, and to the slowing down of the fast interconversion between the two contributions of the ground Kramers doublet at lower temperatures induced by the applied dc field.

Platinum(II) coordination compounds with 4'-pyridyl functionalized 2,2':6',2″-terpyridines as an alternative to enhanced chemotherapy efficacy and reduced side-effects.

Two platinum(II) coordination compounds, [PtCl(4'-R1-terpy)](SO3CF3) (1) and [PtCl(4'-R2-terpy)](SO3CF3) (2), with 4'-(2-pyridyl)-2,2':6',2″-terpyridine (4'-R1-terpy) or 4'-(3-pyridyl)-2,2':6',2″-terpyridine (4'-R2-terpy) were synthesized and the impact of the pendant pyridyl ring on the structure and cytotoxic activity of Pt(II)-terpyridine complexes was explored. The single-crystal X-ray diffraction analysis confirmed square planar coordination of the cations [PtCl(4'-Rn-terpy)]+. The mode of binding of 1 and 2 to calf thymus DNA was examined by UV-Vis absorption titration, ethidium displacement assay and reaction with 9-ethylguanine, and the mixed covalent-intercalative mode was demonstrated. The cytotoxicity of the Pt(II) complexes against six cancer cell lines and three normal ones was determined using MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay and compared to cisplatin. The IC50 values for the compound 2 towards the cancer cell lines are in the low micromolar range. Most remarkably, 2 was over 4 times more effective than 1 and cisplatin against non-small lung adenocarcinoma (A549), and its selectivity index was ~60-80 times higher than that for 1 and cisplatin. The mechanisms underlying the loss of viability under treatment of 2 was further investigated including F-actin staining, mitotic index analysis, cytometric cell cycle analysis, Fluorescein isothiocyanate (FITC) -conjugated Annexin V antibody and propidium iodide (PI) staining, measurements of reactive oxygen species (ROS) in cells, analysis of changes in the mitochondrial mass and potential and quantitative real time polymerase chain reaction (qRT-PCR) genes analysis. The compound 2 was found to have a pro-oxidative effect by strong stimulation of cells for the production of reactive oxygen species and cytostatic effect through cell cycle arrest.

Copper(ii) complexes with 2,2':6',2''-terpyridine, 2,6-di(thiazol-2-yl)pyridine and 2,6-di(pyrazin-2-yl)pyridine substituted with quinolines. Synthesis, structure, antiproliferative activity, and catalytic activity in the oxidation of alkanes and alcohols with peroxides.

A series of 2,2':6',2''-terpyridine (terpy), 2,6-di(thiazol-2-yl)pyridine (dtpy) and 2,6-di(pyrazin-2-yl)pyridine (dppy) derivatives with n-quinolyl substituents (n = 2 and 4) was used to synthesize five-coordinate complexes [CuCl2(n-quinolyl-terpy)] (1-2), [CuCl2(n-quinolyl-dtpy)] (3-4) and [CuCl2(n-quinolyl-dppy)] (5-6), respectively. The main emphasis of the research was to investigate the impact of the triimine skeleton (terpy, dtpy and dppy) and n-quinolyl pendant substituent on the antiproliferative and catalytic properties of 1-6. The obtained Cu(ii) compounds were studied as antiproliferative agents against human colorectal (HCT116) and ovarian (A2780) carcinoma, and they were used as catalysts for the oxidation of alkanes and alcohols with peroxides under mild conditions. The kinetic characteristics of the oxidizing species generated by the catalytic system Cu(ii) complex-H2O2 in CH3CN were obtained from the dependence of the alkane oxidation rate on its initial concentration. A model of competitive interaction of hydroxyl radicals with CH3CN and RH in the catalyst cavity has been proposed which is based on the simultaneous study of kinetics and selectivity in alkane oxidations.

Platinum(ii) complexes showing high cytotoxicity toward A2780 ovarian carcinoma cells.

2,6-Bis(thiazol-2-yl)pyridines functionalized with 9-anthryl (L1), 9-phenanthryl (L2), and 1-pyrenyl (L3) groups were used for the preparation of [Pt(Ln)Cl]CF3SO3 (1-3). The constitution of the Pt(ii) complexes was determined by 1H and 13C NMR spectroscopy, HR-MS spectrometry, elemental analysis and X-ray analysis (for (1)). The electrochemical and photophysical properties of [Pt(Ln)Cl]CF3SO3 were compared with the behaviour of the Pt(ii) complexes with aryl-substituted 2,2':6',2''-terpyridine ligands. What is noteworthy is that the coordination ability of dtpy toward the Pt(ii) centre was investigated for the first time. All complexes were tested in vitro by MTS assay on four tumor cell lines, A2780 (ovarian carcinoma), HTC116 (colon rectal carcinoma), MCF7 (breast adenocarcinoma), and PC3 (prostate carcinoma) and on normal primary fibroblasts. Compounds (1-3) showed a dose dependent antiproliferative effect in the A2780 cell line with (3) > (2) > (1) and this loss of A2780 cell viability was due to a combination of an apoptotic cell death mechanism via mitochondria and autophagic cell death. Exposure to IC50 concentration of (2) induced an increase in the number of apoptotic nuclei and a depolarization of the mitochondrial membrane which is consistent with the induction of apoptosis while exposure to IC50 concentration of (3) showed an increase in the apoptotic nuclei with a slight hyperpolarization of the mitochondrial membrane that might indicate an initial step of apoptosis induction. The complexes (2) and (3) induce an increase in the production of intracellular ROS which is associated with the trigger of the apoptotic pathways. The ROS production was augmented by the presence of oxidants and correlated with an increase of oxygen radicals. The IC50 of (2) and (3) (4.4 µM and 2.9 µM, respectively) was similar to the IC50 of cisplatin (3.4 µM) in the A2780 cell line, which together with their low cytotoxicity in normal fibroblasts, demonstrates their potential for further studies.