Cyclometalated iridium(III) luminescent complexes in therapy and phototherapy

The chemo‐anti‐inflammatory strategy is attracting ever more attention for the treatment of cancer. Here, two cyclometalated IrIII complexes Ir2 and Ir3 formed by conjugation of Ir1 with two antiphlogistics (aspirin and salicylic acid) have been designed. Ir2 and Ir3 exhibit higher antitumor and anti‐inflammatory potencies than a mixture of Ir1 and aspirin/salicylic acid. We show that they can be hydrolyzed, accumulate in mitochondria, and induce mitochondrial dysfunction. Due to their intense long‐lived phosphorescence, Ir2 and Ir3 can track mitochondrial morphological changes. Phosphorescence lifetime imaging shows that Ir2 and Ir3 can aggregate during mitochondrial dysfunction. As expected, Ir2 and Ir3 exhibit immunomodulatory properties by regulating the activity of immune factors. Both Ir2 and Ir3 can induce caspase‐dependent apoptosis and caspase‐independent paraptosis and inhibit several events related to metastasis. Moreover, Ir2 and Ir3 show potent tumor growth inhibition in vivo. Our study demonstrates that the combination of mitochondrial‐targeting and immunomodulatory activities is feasible to develop multifunctional metal‐based anticancer agents.

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Anticancer Ir^III–Aspirin Conjugates for Enhanced Metabolic Immuno‐Modulation and Mitochondrial Lifetime Imaging

Zheng

Wang

et al. 2019

“…In general, phosphorescent biscyclometalatedi ridium(III) complexes display very interesting emission properties, for example,h igh quantum yields, large Stokes shifts, long-lived phosphorescence, modular color-tuningp ossibilities, and good photostability.A saresult, they are being studied in the development of solid-state lighting devices,s uch as organic lightemitting diodes( OLEDs) [14] and light-emitting electrochemical cells (LECs), [15,16] as biological imaging agents, [17] and as analytical probes. [18] In addition, they work as efficient PSsi ns inglet oxygen production and can be used as O 2 probes, [19,20] as photodynamic anticancer agents, [21][22][23][24][25][26][27][28][29][30][31][32][33][34] and as catalysts in photooxidation reactions. [35] Previous reports have shown that biscyclometalated Ir III complexes with 2-(2-hydroxyphenyl)oxazolebased N^O ancillary ligands, similart ot hose used in this work, exhibit highly efficient phosphorescence.…”

Section: Introductionmentioning

confidence: 99%

Strong Influence of the Ancillary Ligand over the Photodynamic Anticancer Properties of Neutral Biscyclometalated Ir^III Complexes Bearing 2‐Benzoazole‐Phenolates

Martı́nez-Alonso

Busto

Aguirre

et al. 2018

In this paper, the synthesis, comprehensive characterization and biological and photocatalytic properties of two series of neutral Ir biscyclometalated complexes of general formula [Ir(C^N) (N^O)], where the N^O ligands are 2-(benzimidazolyl)phenolate-N,O (L1, series a) and 2-(benzothiazolyl)phenolate-N,O (L2, series b), and the C^N ligands are 2-(phenyl)pyridinate or its derivatives, are described,. Complexes of types a and b exhibit dissimilar photophysical and biological properties. In vitro cytotoxicity tests conclusively prove that derivatives of series a are harmless in the dark against SW480 cancer cells (colon adenocarcinoma), but express enhanced cytotoxicity versus the same cells after stimulation with UV or blue light. In contrast, complexes of type b show a very high cytotoxic activity in the dark, but low photosensitizing ability. Thus, the ancillary N^O ligand is the main factor in terms of cytotoxic activity both in the dark and upon irradiation. However, the C^N ligands play a key role regarding cellular uptake. In particular, the complex of formula [Ir(dfppy) (L1)] (dfppy=2-(4,6-difluorophenyl)pyridinate) [3 a] has been identified as both an efficient photosensitizer for O generation and a potential agent for photodynamic therapy. These capabilities are probably related to a combination of its notable cellular internalization, remarkable photostability, high photoluminescence quantum yield, and long triplet excited-state lifetime. Both types of complexes exhibit notable catalytic activity in the photooxidation of thioanisole and S-containing aminoacids with full selectivity.

“…The latter in particular possess an additional coordination site and can easily bind DNA with a great potential for in vivo applications . such as light‐assisted chemotherapy …”

Section: Introductionmentioning

confidence: 99%

Absorption Spectroscopy and Photophysics of a Re^I‐dppz Probe for DNA‐Mediated Charge Transport

Fumanal

Vela

Gattuso

et al. 2018

Optical properties of [Re(CO) (dppz)(py)] (dppz=dipyrido[3,2-a:2',3'-c]phenazine; py=pyridine) in acetonitrile, water and DNA have been investigated based on DFT, time-dependent-DFT (TD-DFT)/ conductor-like screening model, with and without explicit solvent molecules, and molecular dynamics. Whereas implicit solvent model is not appropriate to model optical properties of dppz-substituted metal complexes, adding explicit solvent molecules in interaction with dppz stabilizes the metal-to-ligand-charge-transfer (MLCT) transitions. Classical molecular dynamics simulations point to an important conformational flexibility, as evidenced by the coexistence of two conformers A and B. When considering the conformational sampling, the lowest band of the absorption spectrum is red-shifted and broadened up to 500 nm in agreement with the experimental spectra supporting important dynamical effects. The absorption spectra of [Re(CO) (dppz)(py-R)] GC-DNA and [Re(CO) (dppz)(py-R)] /AT-DNA (R=CH -CH -COO ) intercalated in both major or minor grooves exhibit a lowest energy charge separated (CS) band at about 600 nm and 500 nm, respectively, corresponding mainly to excitations from guanine and adenine to dppz. These states may play a central role into DNA-mediated charge transport processes. The over stabilization of the lowest IL state of [Re(CO) (dppz)(py)] in water as compared to acetonitrile could be responsible for the quenching of emission in water.