Ruthenium(<scp>ii</scp>) polypyridyl complexes with π-expansive ligands: synthesis and cubosome encapsulation for photodynamic therapy of non-melanoma skin cancer

Giacomazzo, Gina Elena; Schlich, Michele; Casula, Luca; Galantini, Luciano; Giudice, Alessandra Del; Pietraperzia, Giangiacomo; Sinico, Chiara; Cencetti, Francesca; Pecchioli, Sara; Valtancoli, Barbara; Conti, Luca; Murgia, Sergio; Giorgi, Claudia

doi:10.1039/d2qi02678c

Cited by 9 publications

(9 citation statements)

References 76 publications

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“…Moreover, for 4 , this transition gives a double-humped absorption at 389 and 410 nm. A broad 1 MLCT band is centered at 435 nm …”

Section: Results and Discussionmentioning

confidence: 99%

“…1 – 3 are also characterized by an emission band after excitation at 450 nm in CH 3 CN, while 4 does not emit in these conditions, according to that reported by Giorgi et al for similar compounds (Table and Figure SI20). …”

Section: Results and Discussionmentioning

confidence: 99%

“…The synthesis of the compounds from the precursor [Ru(LL)Cl 2 ] with the dppz or dppn ligands reported in the literature was giving low yield and the purification was quite tedious . Giorgi and collaborators recently reported a different synthetic strategy for a compound similar to 4 , namely, [Ru(dppn) 2 (dmbpy)](PF 6 ) 2 (dmbpy = 4,4′-dimethyl-2,2-bipyridine), where the solubility issues related to the [Ru(LL)Cl 2 ] intermediate were overcome by a different synthesis . In this article, we propose a different synthetic strategy, starting from the precursor [Ru(phendione) 2 Cl 2 ] (phendione = 1,10-phenanthroline-5,6-dione), inspired by the work of Leveque et al With the described synthetic route, the solubility issues were overcome as well, the synthesis was straightforward, and the purification by column chromatography was remarkably not needed.…”

Section: Introductionmentioning

confidence: 99%

“…24 1−3 are also characterized by an emission band after excitation at 450 nm in CH 3 CN, while 4 does not emit in these conditions, according to that reported by Giorgi et al for similar compounds (Table 1 and Figure SI20). 24 Distribution Coefficient (Log P Values). The octanol− water partition coefficient (Log P) is an important parameter for drugs, as it highly affects the cellular uptake by passive diffusion.…”

Section: ■ Introductionmentioning

confidence: 99%

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Increasing the π-Expansive Ligands in Ruthenium(II) Polypyridyl Complexes: Synthesis, Characterization, and Biological Evaluation for Photodynamic Therapy Applications

Pozza,

Mesdom,

Abdullrahman

et al. 2023

Inorg. Chem.

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Lack of selectivity is one of the main issues with currently used chemotherapies, causing damage not only to altered cells but also to healthy cells. Over the last decades, photodynamic therapy (PDT) has increased as a promising therapeutic tool due to its potential to treat diseases like cancer or bacterial infections with a high spatiotemporal control. Ruthenium(II) polypyridyl compounds are gaining attention for their application as photosensitizers (PSs) since they are generally nontoxic in dark conditions, while they show remarkable toxicity after light irradiation. In this work, four Ru(II) polypyridyl compounds with sterically expansive ligands were studied as PDT agents. The Ru(II) complexes were synthesized using an alternative route to those described in the literature, which resulted in an improvement of the synthesis yields. Solid-state structures of compounds [Ru(DIP) 2 phen]Cl 2 and [Ru(dppz) 2 phen](PF 6 ) 2 have also been obtained. It is well-known that compound [Ru(dppz)(phen) 2 ]Cl 2 binds to DNA by intercalation. Therefore, we used [Ru(dppz) 2 phen]Cl 2 as a model for DNA interaction studies, showing that it stabilized two different sequences of duplex DNA. Most of the synthesized Ru(II) derivatives showed very promising singlet oxygen quantum yields, together with noteworthy photocytotoxic properties against two different cancer cell lines, with IC 50 in the micro-or even nanomolar range (0.06−7 μM). Confocal microscopy studies showed that [Ru(DIP) 2 phen]Cl 2 and [Ru(DIP) 2 TAP]Cl 2 accumulate preferentially in mitochondria, while no mitochondrial internalization was observed for the other compounds. Although [Ru(dppn) 2 phen](PF 6 ) 2 did not accumulate in mitochondria, it interestingly triggered an impairment in mitochondrial respiration after light irradiation. Among others, [Ru(dppn) 2 phen](PF 6 ) 2 stands out for its very good IC 50 values, correlated with a very high singlet oxygen quantum yield and mitochondrial respiration disruption.

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“…Moreover, for 4 , this transition gives a double-humped absorption at 389 and 410 nm. A broad 1 MLCT band is centered at 435 nm …”

Section: Results and Discussionmentioning

confidence: 99%

Section: Results and Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Increasing the π-Expansive Ligands in Ruthenium(II) Polypyridyl Complexes: Synthesis, Characterization, and Biological Evaluation for Photodynamic Therapy Applications

Pozza,

Mesdom,

Abdullrahman

et al. 2023

Inorg. Chem.

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“…This can be achieved, for example, by inserting π-expansive chelate ligands in Ru(II) scaffolds, as they can change the lowest-lying excited state from 3 MLCT to long-lived intraligand 3 IL states 9 : a classic case is the use of the popular benzo[i]dipyrido[3,2-a:2′,3′-c]phenazine (dppn) ligand/s. 10,11 Asides from that, another valid alternative is represented by the decoration of metal-coordinated ligands with distinct organic chromophores having their lowest-lying and long-lived triplet state close in energy to the 3 MLCT of the metal-based units. In these bichromophoric arrangements, the 3 IL states act as excited-state energy reservoirs that prolong the 3 MLCT emission, endowing the resulting dyads with improved sensitizing properties, beyond to augment light absorption in the vis/NIR region.…”

Section: ■ Introductionmentioning

confidence: 99%

Photosensitizers Based on Bichromophoric Dyads Combining Ru(II)-Polypyridyl Complexes and Dissymmetric Perylene Monoimide Derivatives: The Nontrivial Role of Ligand Substitution

Giacomazzo,

Doria,

Revilla-Cuesta

et al. 2024

Inorg. Chem.

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The covalent modification of Ru(II) polypyridyl complexes (RPCs) with organic chromophores is a powerful strategy to obtain metal-based photosensitizer agents (PSs) with improved performance for application in photodynamic therapy (PDT). In this respect, perylene-imides are of particular interest due to their rich chemical–physical repertoire, and it is therefore quite surprising that their combination with RPCs has been poorly considered so far. Herein, we report on the photophysical behavior of two newly synthesized RPCs bearing a perylene monoimide appendant (PMI-Ad). Differently from the majority of RPCs-perylene-imides dyads, these chromophores are dissymmetric and are tethered to the metal centers through a single C–C bond in the 3- or 5-position of 1,10-phenanthroline (Ru-3PMI-Ad and Ru-5PMI-Ad). Both compounds show excellent singlet oxygen photosensitizing activity, with quantum yields reaching >90% in the case of Ru-3PMI-Ad. A combined spectroscopic and theoretical analysis, also involving transient absorption and luminescence lifetime measurements, demonstrates that both compounds undergo intersystem crossing on a very fast time scale (tens of picoseconds) and with high efficiency. Our results further demonstrate that the increased electron delocalization between the metal center and the PMI-Ad chromophore observed for Ru-3PMI-Ad additionally contributes to increase the singlet oxygen quantum yields by prolonging the lifetime of the triplet state.

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Ruthenium(II) Polypyridyl Complexes with Benzoxazole Derivatives and Non‐Innocent Ligands as Effective Antioxidants in Human Neuroblasts

Giacomazzo,

Conti,

Paderni

et al. 2024

Chemistry A European J

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Ruthenium(II) polypyridyl complexes continue to raise increasing interest for the encouraging results in several biomedical areas. Considering their vast chemical‐physical repertoire, in particular the possibility to switch from the sensitization of reactive oxygen species (ROS) to ROS‐scavenging abilities by tuning the nature of their ligands, it is therefore surprising that their potential as antioxidants has not been largely investigated so far. Herein, we explored the antioxidant behaviour of the novel ruthenium compound [Ru(dbpy)(2,3‐DAN)Cl]PF6 (Ru1), featuring a benzoxazole derivative (dpby = 2,6‐bis(4‐methyl‐2‐ossazolyl)pyridine) and the non‐innocent 2,3‐diamminonaftalene (2,3 DAN) ligand, along with the reference tpy‐containing analogue [Ru(tpy)(2,3‐DAN)Cl]PF6 (Ru2) (tpy = 2,2’:6’,2’’‐terpyridine). Following the synthesis and the electrochemical characterization, chemical antioxidant assays highlighted the beneficial role of dpby for the ROS‐scavenging properties of Ru1. These data have been corroborated by the highest protective effect of Ru1 against the oxidative stress induced in SH‐SY5Y human neuroblastoma, which exerts pro‐survival and anti‐inflammatory actions. The results herein reported highlight the potential of Ru1 as pharmacological tool in neurodegenerative diseases and specially prove that the antioxidant properties of such compounds are likely the result of a non‐trivial synergetic action involving the bioactive ligands in their chemical architectures.

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Ruthenium(ii) polypyridyl complexes with π-expansive ligands: synthesis and cubosome encapsulation for photodynamic therapy of non-melanoma skin cancer

Abstract: In photodynamic therapy (PDT), Ru(II) polypyridyl complexes (RPCs) featuring the popular π-expansive benzo[i]dipyrido[3,2-a:2′,3′-c]phenazine (dppn) ligand have attracted much attention, mainly due to the good singlet oxygen sensitizing properties imparted by...

Cited by 9 publications

References 76 publications

Increasing the π-Expansive Ligands in Ruthenium(II) Polypyridyl Complexes: Synthesis, Characterization, and Biological Evaluation for Photodynamic Therapy Applications

Increasing the π-Expansive Ligands in Ruthenium(II) Polypyridyl Complexes: Synthesis, Characterization, and Biological Evaluation for Photodynamic Therapy Applications

Photosensitizers Based on Bichromophoric Dyads Combining Ru(II)-Polypyridyl Complexes and Dissymmetric Perylene Monoimide Derivatives: The Nontrivial Role of Ligand Substitution

Ruthenium(II) Polypyridyl Complexes with Benzoxazole Derivatives and Non‐Innocent Ligands as Effective Antioxidants in Human Neuroblasts

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