Ru(II) Oligothienyl Complexes with Fluorinated Ligands: Photophysical, Electrochemical, and Photobiological Properties.

A series of Ru(II) complexes incorporating two 4,4'-bis(trifluoromethyl)-2,2'-bipyridine (4,4'-btfmb) coligands and thienyl-appended imidazo[4,5-][1,10]phenanthroline (IP-T) ligands was characterized and assessed for phototherapy effects toward cancer cells. The [Ru(4,4'-btfmb)(IP-T)] scaffold has greater overall redox activity compared to Ru(II) polypyridyl complexes such as [Ru(bpy)]. - have additional oxidations due to the T group and additional reductions due to the 4,4'-btfmb ligands.

Ru(II) Phenanthroline-Based Oligothienyl Complexes as Phototherapy Agents.

Ru(II) polypyridyl complexes have gained widespread attention as photosensitizers for photodynamic therapy (PDT). Herein, we systematically investigate a series of the type [Ru(phen)(IP-T)], featuring 1,10-phenanthroline (phen) coligands and imidazo[4,5-][1,10]phenanthroline ligands tethered to 0-4 thiophene rings (IP-T). The complexes were characterized and investigated for their electrochemical, spectroscopic, and (photo)biological properties.

Establishing a Robust and Reliable Response from a Potent Osmium-Based Photosensitizer Via Lipid Nanoformulation.

Osmium (Os) based photosensitizers (PSs) are a unique class of nontetrapyrrolic metal-containing PSs that absorb red light. We recently reported a highly potent Os(II) PS, rac-[Os(phen) (IP-4T)](Cl) , referred to as ML18J03 herein, with light EC values as low as 20 pm. ML18J03 also exhibits low dark toxicity and submicromolar light EC values in hypoxia in some cell lines.

Anticancer Agent with Inexplicable Potency in Extreme Hypoxia: Characterizing a Light-Triggered Ruthenium Ubertoxin.

Tumor hypoxia renders treatments ineffective that are directly (e.g., radiotherapy and photodynamic therapy) or indirectly (e.

String-Attached Oligothiophene Substituents Determine the Fate of Excited States in Ruthenium Complexes for Photodynamic Therapy.

We explore the photophysical properties of a family of Ru(II) complexes, , designed as photosensitizers (PSs) for photodynamic therapy (PDT). The complexes incorporate a 1-imidazo[4,5-][1,10]-phenanthroline (ip) ligand appended to one or more thiophene rings. One of the complexes studied herein, (known as TLD1433), is currently in phase II human clinical trials for treating bladder cancer by PDT.

It Takes Three to Tango - the length of the oligothiophene determines the nature of the long-lived excited state and the resulting photocytotoxicity of a Ru(II) photodrug.

Unlabelled: TLD1433 is the first Ru(II) complex to be tested as a photodynamic therapy agent in a clinical trial. In this contribution we study TLD1433 in the context of structurally-related Ru(II)-imidozo[4,5-f][1,10]phenanthroline (ip) complexes appended with thiophene rings to decipher the unique photophysical properties which are associated with increasing oligothiophene chain length. Substitution of the ip ligand with ter- or quaterthiophene changes the nature of the long-lived triplet state from metal-to-ligand charge-transfer to ππ* character.

Fine-Feature Modifications to Strained Ruthenium Complexes Radically Alter Their Hypoxic Anticancer Activity.

In an earlier study of π-expansive ruthenium complexes for photodynamic and photochemo-therapies, it was shown that a pair of structural isomers differing only in the connection point of a naphthalene residue exhibited vastly different biological activity. These isomers are further explored in this paper through the activity of their functionalized derivatives. In normoxia, the inactive 2-NIP isomer (5) can be made as photocytotoxic as the active 1-NIP isomer (1) by functionalizing with methyl or methoxy groups, while methoxy variants of the 1-NIP isomer became inactive.

Singlet Oxygen Formation vs Photodissociation for Light-Responsive Protic Ruthenium Anticancer Compounds: The Oxygenated Substituent Determines Which Pathway Dominates.

Ruthenium complexes bearing protic diimine ligands are cytotoxic to certain cancer cells upon irradiation with blue light. Previously reported complexes of the type [(,)Ru(6,6'-dhbp)]Cl with 6,6'-dhbp = 6,6'-dihydroxybipyridine and , = 2,2'-bipyridine (bipy) (), 1,10-phenanthroline (phen) (), and 2,3-dihydro-[1,4]dioxino[2,3-][1,10]phenanthroline (dop) () show EC values as low as 4 μM (for ) vs breast cancer cells upon blue light irradiation ( 2017, 56, 7519). Herein, subscript denotes the acidic form of the complex bearing OH groups, and denotes the basic form bearing O groups.

Discovery of immunogenic cell death-inducing ruthenium-based photosensitizers for anticancer photodynamic therapy.

We report a new class of ruthenium (Ru)-based photosensitizers that induce potent cytotoxicity in melanoma cells following activation with NIR light. In addition to the direct cytotoxic effect, this Ru-based photodynamic therapy induces immunogenic cell death in melanoma cells that can be therapeutically exploited to establish protective antitumor immunity.

Os(II) Oligothienyl Complexes as a Hypoxia-Active Photosensitizer Class for Photodynamic Therapy.

Hypoxia presents a challenge to anticancer therapy, reducing the efficacy of many available treatments. Photodynamic therapy is particularly susceptible to hypoxia, given that its mechanism relies on oxygen. Herein, we introduce two new osmium-based polypyridyl photosensitizers that are active in hypoxia.

NIR-Absorbing Ru Complexes Containing α-Oligothiophenes for Applications in Photodynamic Therapy.

The design of near-infrared (NIR)-active photosensitizers (PSs) for light-based cancer treatments such as photodynamic therapy (PDT) has been a challenge. While several NIR-Ru scaffolds have been reported, this approach has not been proven in cells. This is the first report of NIR-Ru PSs that are phototoxic to cancer cells, including highly pigmented B16F10 melanoma cells.

Intracellular Photophysics of an Osmium Complex bearing an Oligothiophene Extended Ligand.

This contribution describes the excited-state properties of an Osmium-complex when taken up into human cells. The complex 1 [Os(bpy) (IP-4T)](PF ) with bpy=2,2'-bipyridine and IP-4T=2-{5'-[3',4'-diethyl-(2,2'-bithien-5-yl)]-3,4-diethyl-2,2'-bithiophene}imidazo[4,5-f][1,10]phenanthroline) can be discussed as a candidate for photodynamic therapy in the biological red/NIR window. The complex is taken up by MCF7 cells and localizes rather homogeneously within in the cytoplasm.

TLD1433-Mediated Photodynamic Therapy with an Optical Surface Applicator in the Treatment of Lung Cancer Cells In Vitro.

Intra-operative photodynamic therapy (IO-PDT) in combination with surgery for the treatment of non-small cell lung cancer and malignant pleural mesothelioma has shown promise in improving overall survival in patients. Here, we developed a PDT platform consisting of a ruthenium-based photosensitizer (TLD1433) activated by an optical surface applicator (OSA) for the management of residual disease. Human lung adenocarcinoma (A549) cell viability was assessed after treatment with TLD1433-mediated PDT illuminated with either 532- or 630-nm light with a micro-lens laser fiber.