Luminescent mono(pentafluorophenyl) cycloplatinated complexes [Pt(C^N-κC,N)(HC^N-κN)(C6F5)] [HC^N = Hthpy (2-(2-thienyl)pyridine) 2a, Hbt (2-phenylbenzothiazole) 2b, Hpq (2-phenylquinoline) 2c] have been prepared by C–H activation of a HC^N ligand in the corresponding [Pt(HC^N-κN)2(C6F5)2] (1a, 1b, 1c) complexes. Complexes 2 evolve in DMSO solution into solvate complexes and we present here successful routes for the synthesis of [Pt(C^N)(C6F5)(DMSO)] (C^N = thpy 3a, bt 3b). They have been fully characterized (X-ray for 1a, 1c, 2b, 3a and 3b), their electronic absorption and emission properties have been investigated and DFT and TD-DFT calculations for 1a, 1c, 2b and 3a have been carried out. Complexes 3a, 3b and [Pt(ppy)(C6F5)(DMSO)] 4 (Hppy = 2-phenylpyridine) show remarkable stability in a mixed DMSO-cellular medium and their cytotoxicity towards the human lung tumor (A549) and bronchial epithelial non-tumorigenic (NL20) cell lines has been evaluated by MTS assays. Their cellular localization in A549 and NL20 human cells and in mouse embryonic fibroblasts obtained from lungs (LMEFs) has also been investigated by fluorescence microscopy.

Two series of neutral luminescent pentafluorophenyl cycloplatinated­(II) complexes [Pt­(C^N)­(C6F5)­L] [C^N = C-deprotonated 2-phenylpyridine (ppy; a), 2-(2,4-difluorophenylpyridine (dfppy; b)] incorporating dimethyl sulfoxide [L = DMSO for 1 (1a reported by us in ref )] or biocompatible phosphine [L = PPh2C6H4COOH (dpbH; 2), PPh2C6H4CONHCH2COOMe (dpbGlyOMe; 3), P­(C6H4SO3Na)3 (TPPTS; 4)] ligands have been prepared and characterized and their optical properties studied. Their cytotoxic activities against tumor A549 (lung carcinoma), HeLa (cervix carcinoma), and nontumor NL-20 (lung epithelium) cell lines, as well as the ability to interact with DNA (plasmid pBR322), were evaluated. Complexes 2 exhibit higher cytotoxicity (IC50 3.89–20.29 μM) than compounds 1 (9.03–20.50 μM), whereas the activities of complexes 3 and 4 are negligible. All cytotoxic complexes show low selective toxicities toward cancer cells. Interestingly, except 1a, these complexes do not show evidence of DNA intercalation. Along the same lines, fluorescence costaining with Hoechst (2,5′-bi-1H-benzimidazole, 2′-(4-ethoxyphenyl)-5-(4-methyl-1-piperazinyl), a nuclear DNA stain) reveals that all complexes easily internalize, being mainly localized in the cytoplasm. In order to deepen the mechanism of biological action, the effect of the most cytotoxic complex 2b toward the dynamics of tubulin was explored. This complex displays tubulin depolymerization activity, exhibiting more potent inhibition of microtubule formation in A549 than in HeLa cells, in accordance with its higher antiproliferative activity (IC50 6.98 vs 12.45 μM), placing this complex as a potential antitubulin agent.

A convenient and general strategy for the synthesis of stable bis(cyclometalated) pentafluorophenyl Pt complexes fac-[Pt(C^N) (C F )Cl] (3 a-f) and mer-[Pt(C^N) (C F )(CN)] (4 c,d) has been developed. Complexes 3 were selectively generated by low-temperature oxidation of the cyclometalated Pt complexes [Pt(C^N)(HC^N)(C F )] 2 [prepared from cis-[Pt(C F ) (HC^N) ] (1) intermediates] with PhICl and subsequent metalation of the pendant HC^N ligand. Complexes 3 a,b were also alternatively generated by irradiation (Hg lamp, 400 W) of complexes 2 a,b, respectively, in CH Cl . This latter reaction proceeds via the hydride Pt species cis-[Pt(C^N) (C F )H], detected as the only intermediate species. The molecular structures of 1 a,d, 2 a, and 3 a,b,d,e were confirmed by X-ray diffraction. The substitution of Cl by CN in fac-[Pt(C^N) (C F )Cl] [C^N=2-phenylbenzothiazole (3 c), 2-(4-bromophenyl)benzothiazole (3 d)] evolved with isomerization to give rise to the isomers (OC-6-42)-[Pt(C^N) (C F )(CN)] (4 c, 4 d) having a mer disposition of the cyclometalated and C F groups (X-ray, 4 c). All the complexes are luminescent and their electronic spectra have been compared and interpreted with the aid of time-dependent DFT calculations.

Bis­(cyclometalated) diiridium complexes [Ir­(ppy)2(μ–κC α:η2-CCR)]2 (R = Tol 1, C6H4OMe-4 2, 1-Np 3, SiMe3 4, t Bu 5), stabilized by a double alkynyl bridging system, have been synthesized by alkynylation of [Ir­(ppy)2(μ-Cl)]2 with excess of the appropriate LiCCR (1:6 or 1:10 molar ratio). Complexes 1–3 were alternatively generated by treatment of [Ir­(ppy)2(MeCN)2]­(OTf) with 2.5 equiv of LiCCR. However, the related reaction with LiCC t Bu evolves with the formation of mixtures from which the unexpected dinuclear complex [Ir­(ppy)2(μ-CH2CN)]2 6 was crystallized, as confirmed by X-ray diffraction studies. Complexes 1–5 have been characterized by NMR, IR, absorption and emission spectroscopies, cyclic voltammetry, and mass spectrometric methods. Characterization indicates that 1–3 and 5 are obtained as a unique diastereoisomer (ΛΛ/ΔΔ), whereas 4 gives the two diastereoisomers (ΔΛ and ΛΛ/ΔΔ). Single crystals of [Ir­(ppy)2(μ-CCTol)]2 1 contains the inversion related ΛΛ/ΔΔ isomers, and crystals of 4 (chosen from a mixture of two different types of crystals) consist of the meso-ΔΛ isomer. Electrochemical studies showed the presence in 1–3 and 5 of two consecutive one-electron-oxidation IrIII/IrIV processes, whereas 4 displayed only one irreversible oxidation peak. In degassed fluid solutions, complexes 1–5 are emissive in the 505–515 nm region with quantum yields higher (ϕ = 0.007–0.024) than that of the dichloro bridged precursor (0.0037). The influence of the alkynyl substituent in the emissive state at room and at low temperatures has been investigated. For the naphthylacetylide derivative 3, a clear switch from a mixed charge transfer 3MLCT/3L′LCT excited state at 298 K (515 nm) to a characteristic long-lived low lying naphthalene emission at low temperature (77 K) is observed. DFT and TD-DFT calculations were performed on complexes 1 and 3 in the ground and triplet states to gain insight into the structural, electronic, and photophysical properties.

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Oxidation of [Pt(bzq-κN,κC 10 )(C 6 F 5 )(η 2 -HCCFc)] (1) with PhICl 2 and I 2 affords the unusual halideferrocenyl(vinyl)benzoquinoline Pt II derivatives [Pt{bzq-κN-η 2 -CHC(X)Fc}(C 6 F 5 )X] (X = Cl (4a), I (4b)), arising from C−X and C−C coupling processes, together with small amounts of the corresponding Pt IV products [{Pt(bzq-κN,κC 10 )(C 6 F 5 )X(μ-X)} 2 ] (X = Cl (5a), I (5b)), respectively. Complexes 4 are very stable but they undergo easy displacement reactions with PPh 3 , yielding trans-[Pt(C 6 F 5 )X(PPh 3 ) 2 ] and the corresponding new functionalized (vinyl)benzoquinoline ligands [(Z)-bzq-CHC(X)Fc] (X = Cl (6a), I (6b)). The dinuclear Pt IV derivatives 5 are alternatively obtained in high yield by oxidation of the solvate [Pt(bzq-κN,κC 10 )(C 6 F 5 )(CH 3 COCH 3 )] (2). Treatment of 5 with dmso or direct oxidation of [Pt(bzq-κN,κC 10 )(C 6 F 5 )(tht)] (3) provides mononuclear [Pt(bzq-κN,κC 10 )(C 6 F 5 )X 2 (L)] (L = dmso (7a−c), tht (8a−c)) as a mixture of cis and trans isomers.

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In the present work, a series of aryl‐cycloplatinated(II) complexes with general formula [Pt(C^N)(Ar)(κ1‐dppm)], 1, [C^N = 7,8‐benzoquinolinyl (bzq) or 2‐phenylpyridinyl (ppy); Ar = C6F5 or p‐MeC6H4, dppm = 1,1‐bis(diphenylphosphanyl)methane] was employed in the reaction with AuCl(SMe2) in order to generate heterobimetallic PtII‐AuI complexes, [Pt(C^N)(Ar)(µ‐dppm)Au(Cl)], 2, featuring a dppm bridge between the metal centers. The expectation was to induce metallophilic character into the excited state and to reduce non‐radiative deactivation pathways of the dangling auxiliary κ1‐dppm ligand through molecular motions, to improve the photophysical properties. After characterization of the new complexes by means of NMR spectroscopy and X‐ray crystallography technique, the photophysical properties of all the complexes were investigated by UV/Vis and photoluminescence spectroscopy. Both of the monometallic complexes and heterobimetallic products have shown to be luminescent in different states and temperature conditions. However, by addition of AuI, the impact on the photophysics of the heterobimetallic products in relation to the precursors with dangling dppm is minimal, a finding which can be attributed to the absence of a PtII‐AuI bond in these compounds. Indeed, the character of the excited states of the monomer PtII complexes and their corresponding bimetallic PtII‐AuI ones are similar, as confirmed by density functional theory (DFT) and time resolved DFT (TD‐DFT) calculations. The cytotoxic activities of the compounds along with that of [ClAu(µ‐dppm)AuCl] were evaluated against human breast cancer (MCF‐7), human lung cancer (A549), human ovarian cancer (SKOV3) and non‐tumorigenic epithelial breast (MCF‐10A) cell lines. The highest activity was found for the heterometallic Pt‐Au species, suggesting a cooperative effect of both metallic fragments. The most cytotoxic compound, i.e. [Pt(bzq)(p‐MeC6H4)(µ‐dppm)Au(Cl)], 2b, effectively causes cell death in MCF‐7 cancer cell line by inducing apoptosis. Fluorescence microscopy experiments for 2a were performed.