Metal complexes for catalytic and photocatalytic reactions in living cells and organisms

Madec, Hugo; Figueiredo, Francisca; Cariou, Kevin; Roland, Sylvain; Sollogoub, Matthieu; Gasser, Gilles

doi:10.1039/d2sc05672k

Cited by 36 publications

(31 citation statements)

References 111 publications

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“…The phototherapy indexes under 450 (PI-1) and 808 nm (PI-2) for Ru1 reached as high as >275 and > 390, respectively, indicating that it is an IR-excitable PS for antitumor PDT. Both PI-1 and PI-2 of HPRCs are significantly high among metal-containing PSs summarized in recent reviews (typically <100). ,,,− The phototoxicity of HPRCs [Ru(dppz-X 2 ) 3 ] 2+ have been reported to decrease as their lipophilicity increases . Quite the contrary, for HPRCs in this work, a decrease in lipophilicity leads to an apparent reduction in phototoxicity.…”

Section: Resultsmentioning

confidence: 53%

“…Many Ru(II) complexes have been successfully developed as PSs in PDT and photochemotherapy (PCT) for their long 3 ES lifetimes and high 1 O 2 quantum yields (Φ Δ ). 7,8 Although some good Ru(II)-PSs like TLD1433, which entered a clinical trial in 2018, can be excited by red light (better than traditional blue light), even longer excitation wavelength, especially the infrared (IR) light, will be more practical for a deeper (typically >1 cm) and safer PDT.…”

Section: Introductionmentioning

confidence: 99%

“…The PS in 3 ESs can produce ROS by ES electron transfer/hydrogen atom abstraction (Type I) or generate highly active singlet oxygen ( 1 O 2 ) by ES energy transfer (Type II). The light-generated ROS, notably 1 O 2 , can react with biological targets such as lipids, proteins, and nucleic acids, destroy the targeted cells, damage the vasculature associated with the tumor, and stimulate antitumor immunity. − Consequently, the characteristic of 3 ES and the ROS quantum yield are two crucial aspects of a PS.…”

Section: Introductionmentioning

confidence: 99%

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More-Is-Better Strategy for Constructing Homoligand Polypyridyl Ruthenium Complexes as Photosensitizers for Infrared Two-Photon Photodynamic Therapy

Tang,

Wang,

Yang

et al. 2023

Inorg. Chem.

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Photodynamic therapy (PDT) uses a combination of photosensitizers (PSs), light sources, and reactive oxygen species (ROS) to damage only the desired target and keep normal tissues from being hurt. The dark cytotoxicity (chemotoxicity) of PSs, leading to whole-body damage in the absence of irradiation, is a major limiting factor in PDT. How to simultaneously increase ROS generation and decrease dark cytotoxicity is an essential challenge that must be resolved in PS research. In this study, a series of homoligand polypyridyl ruthenium complexes (HPRCs) containing three singlet oxygen ( 1 O 2 )-generating ligands (L) in a single molecule ([Ru(L) 3 ] 2+ ) have been constructed. Compared to the heteroligand complexes [Ru(bpy) 2 (L)] 2+ where bpy is 2,2′-bipyridine, the 1 O 2 quantum yield under infrared two-photon irradiation and the DNA photocleavage effect of the HPRCs are significantly enhanced with two more ligands L. The intraligand triplet excited states transition played an important role in the activation of oxygen. The HPRCs target the mitochondria but not the nuclei, generating 1 O 2 intracellularly under irradiation of visible or infrared light. Ru1 exhibits high phototoxicity and low dark cytotoxicity toward human malignant melanoma cells in vitro. Moreover, HPRCs have minimal cytotoxicity to human normal liver cells, suggesting their potential as antitumor PDT reagents with more security. This study may provide inspiration for the structural design of potent PS for PDT.

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Section: Resultsmentioning

confidence: 53%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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More-Is-Better Strategy for Constructing Homoligand Polypyridyl Ruthenium Complexes as Photosensitizers for Infrared Two-Photon Photodynamic Therapy

Tang,

Wang,

Yang

et al. 2023

Inorg. Chem.

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“…However, this is highly challenging because metal-catalyzed nitroreduction normally requires high temperature and substrate concentrations, inert atmosphere, and/or highly nucleophilic hydride sources which are incompatible with biological systems . It remains a formidable challenge to uncover efficacious organometallic catalysts that can efficiently carry out nitroreduction within a complex intracellular milieu using endogenous cofactors, in keeping with native NTRs. , …”

Section: Introductionmentioning

confidence: 99%

“…26 It remains a formidable challenge to uncover efficacious organometallic catalysts that can efficiently carry out nitroreduction within a complex intracellular milieu using endogenous cofactors, in keeping with native NTRs. 27,28 Formate is an essential cell metabolite for anaerobic respiration and folate biosynthesis in certain classes of bacterial microorganisms. It is maintained at high intracellular concentrations (mM) through multiple biosynthetic pathways, and its level is regulated by different formate-dependent enzymes.…”

Section: ■ Introductionmentioning

confidence: 99%

Targeting Pathogenic Formate-Dependent Bacteria with a Bioinspired Metallo–Nitroreductase Complex

et al. 2023

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Nitroreductases (NTRs) constitute an important class of oxidoreductase enzymes that have evolved to metabolize nitro-containing compounds. Their unique characteristics have spurred an array of potential uses in medicinal chemistry, chemical biology, and bioengineering toward harnessing nitro caging groups and constructing NTR variants for niche applications. Inspired by how they carry out enzymatic reduction via a cascade of hydride transfer reactions, we sought to develop a synthetic small-molecule NTR system based on transfer hydrogenation mediated by transition metal complexes harnessing native cofactors. We report the first water-stable Ru−arene complex capable of selectively and fully reducing nitroaromatics into anilines in a biocompatible buffered aqueous environment using formate as the hydride source. We further demonstrated its application to activate nitro-caged sulfanilamide prodrug in formate-abundant bacteria, specifically pathogenic methicillin-resistant Staphylococcus aureus. This proof of concept paves the way for a new targeted antibacterial chemotherapeutic approach leveraging on redox−active metal complexes for prodrug activation via bioinspired nitroreduction.

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Bleeding the Excited State Energy to the Utmost: Single‐Molecule Iridium Complexes for In Vivo Dual Photodynamic and Photothermal Therapy by an Infrared Low‐Power Laser

Tang

Wang

et al. 2023

Adv Healthcare Materials

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A series of cyclometalated Ir(III) complexes with morpholine and piperazine groups are designed as dual photosensitizers and photothermal agents for more efficient antitumor phototherapy via infrared low‐power laser. Their ground and excited state properties, as well as the structural effect on their photophysical and biological properties, are investigated by spectroscopic, electrochemical, and quantum chemical theoretical calculations. They target mitochondria in human melanoma tumor cells and trigger apoptosis related to mitochondrial dysfunction upon irradiation. The Ir(III) complexes, particularly Ir6, demonstrate high phototherapy indexes to melanoma tumor cells and a manifest photothermal effect. Ir6, with minimal hepato‐/nephrotoxicity in vitro, significantly inhibits the growth of melanoma tumors in vivo under 808 nm laser irradiation by dual photodynamic therapy and photothermal therapy and can be efficiently eliminated from the body. These results may contribute to the development of highly efficient phototherapeutic drugs for large, deeply buried solid tumors.

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Metal complexes for catalytic and photocatalytic reactions in living cells and organisms

Abstract: TThe development of organometallic catalysis has greatly expanded the synthetic chemist toolbox compared to that only exploiting "classical" organic chemistry. Although more widely used in organic solvents, metal-based catalysts have...

Cited by 36 publications

References 111 publications

More-Is-Better Strategy for Constructing Homoligand Polypyridyl Ruthenium Complexes as Photosensitizers for Infrared Two-Photon Photodynamic Therapy

More-Is-Better Strategy for Constructing Homoligand Polypyridyl Ruthenium Complexes as Photosensitizers for Infrared Two-Photon Photodynamic Therapy

Targeting Pathogenic Formate-Dependent Bacteria with a Bioinspired Metallo–Nitroreductase Complex

Bleeding the Excited State Energy to the Utmost: Single‐Molecule Iridium Complexes for In Vivo Dual Photodynamic and Photothermal Therapy by an Infrared Low‐Power Laser

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