Toward Near-Infrared Emission in Pt(II)-Cyclometallated Compounds: From Excimers' Formation to Aggregation-Induced Emission.

Two series of Pt(II)-cyclometallated compounds containing N^C^N tridentate and alkynyl-chromophore ligands have been synthesized and structurally characterized. The N^C^N ligands differ on the presence of R1 = H or F in the central aromatic ring, while six different chromophores have been introduced to the alkynyl moiety. Single-crystal X-ray structures for some of the compounds reveal the presence of weak intermolecular contacts responsible for the formation of some dimers or aggregates. The photophysical characterization shows the presence of two emission bands in solution assigned to the 3π-π* transition from the N^C^N ligands mixed with 3MLCT/3ILCT transitions (higher energy band) in deaerated samples. The formation of excimers has also been identified as a broad band at longer wavelengths [near-infrared (NIR) emission] that becomes the main emission band for compounds containing phenanthrene as the chromophore. NIR emission behavior has also been explored using acetonitrile/water mixtures, and the presence of aggregates that emit at ca. 650 nm has also been detected.

Luminescent PtII and PtIV Platinacycles with Anticancer Activity Against Multiplatinum-Resistant Metastatic CRC and CRPC Cell Models.

Platinum-based chemotherapy persists to be the only effective therapeutic option against a wide variety of tumours. Nevertheless, the acquisition of platinum resistance is utterly common, ultimately cornering conventional platinum drugs to only palliative in many patients. Thus, encountering alternatives that are both effective and non-cross-resistant is urgent. In this work, we report the synthesis, reduction studies, and luminescent properties of a series of cyclometallated (C,N,N')PtIV compounds derived from amine-imine ligands, and their remarkable efficacy at the high nanomolar range and complete lack of cross-resistance, as an intrinsic property of the platinacycle, against multiplatinum-resistant colorectal cancer (CRC) and castration-resistant prostate cancer (CRPC) metastatic cell lines generated for this work. We have also determined that the compounds are effective and selective for a broader cancer panel, including breast and lung cancer. Additionally, selected compounds have been further evaluated, finding a shift in their antiproliferative mechanism towards more cytotoxic and less cytostatic than cisplatin against cancer cells, being also able to oxidize cysteine residues and inhibit topoisomerase II, thereby holding great promise as future improved alternatives to conventional platinum drugs.

Room-Temperature Phosphorescence and Efficient Singlet Oxygen Production by Cyclometalated Pt(II) Complexes with Aromatic Alkynyl Ligands.

The synthesis of five novel cyclometalated platinum(II) compounds containing five different alkynyl-chromophores was achieved by the reaction of the previously synthesized Pt-Cl cyclometalated compound (1) with the corresponding RC≡CH by a Sonogashira reaction. It was observed that the spectral and photophysical characteristics of the cyclometalated platinum(II) complexes (Pt-Ar) are essentially associated with the platinum-cyclometalated unit. Room-temperature emission of the Pt-Ar complexes was attributed to phosphorescence in agreement with DFT calculations. Broad nanosecond (ns)-transient absorption spectra were observed with decays approximately identical to those obtained from the emission of the triplet state. From the femtosecond-transient absorption (fs-TA) data, two main excited-state decay components were identified: one in the order of a few picoseconds was assigned to fast intersystem crossing to populate the triplet excited-state and the second (hundreds of ns) was associated with the decay of the transient triplet state. In general, efficient singlet oxygen photosensitization quantum yields were observed from the triplet state of these complexes.

Exploring the effect of the axial ligands on the anticancer activity of [C,N,N'] Pt(IV) cyclometallated compounds.

The synthesis of three novel [C,N,N'] Pt(IV) cyclometallated compounds containing hydroxo, dichloroacetato or trifluoroacetato axial ligands is reported. Compound [PtCl(OH)2{(CH3)2N(CH2)2NCH(4-FC6H3)}] (3) was prepared by the oxidative addition of hydrogen peroxide to [C,N,N'] Pt(II) cyclometallated compound [PtCl{(CH3)2N(CH2)2NCH(4-FC6H3)}] (1) and further the reaction of compound 3 with dichloroacetate or trifluoroacetate anhydrides led to the formation of the corresponding compounds [PtCl(CHCl2COO)2{(CH3)2N(CH2)2NCH(4-FC6H3)}] (4) and [PtCl(CF3COO)2{(CH3)2N(CH2)2NCH(4-FC6H3)}] (5). The properties of the new compounds along with those of the compound [PtCl3{(CH3)2N(CH2)2NCH(4-FC6H3)}] (2), including stability in aqueous media, reduction potential using cyclic voltammetry, cytotoxic activity against the HCT116 CRC cell line, DNA interaction, topoisomerase I and cathepsin inhibition, and computational studies involving reduction of the Pt(IV) compounds and molecular docking studies, are presented. Interestingly, the antiproliferative activity of these compounds against the HCT116 CRC cell line, which is in all cases higher than that of cisplatin, follows the same trend as the reduction potentials so that the most easily reduced compound 2 is the most potent. In contrast, according to the electrophoretic mobility and molecular docking studies, the efficacy of these compounds in binding to DNA is not related to their cytotoxicity. The most active compound 2 does not modify the DNA electrophoretic mobility while the less potent compound 3 is the most efficient in binding to DNA. Although compounds 2 and 3 have only a slight effect on cell cycle distribution and apoptosis induction, generation of ROS to a higher extent for the most easily reduced compound 2 was observed.