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.

Enhancement of subunit vaccine delivery with zinc-carnosine coordination polymer through the addition of mannan.

Vaccines represent a pivotal health advancement for preventing infection. However, because carrier systems with repeated administration can invoke carrier-targeted immune responses that diminish subsequent immune responses (e.g.

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.

Development of a broadly active influenza intranasal vaccine adjuvanted with self-assembled particles composed of mastoparan-7 and CpG.

Currently licensed vaccine adjuvants offer limited mucosal immunity, which is needed to better combat respiratory infections such as influenza. Mast cells (MCs) are emerging as a target for a new class of mucosal vaccine adjuvants. Here, we developed and characterized a nanoparticulate adjuvant composed of an MC activator [mastoparan-7 (M7)] and a TLR ligand (CpG).

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.

Ruthenium Photosensitizers for NIR PDT Require Lowest-Lying Triplet Intraligand (IL) Excited States.

A family of complexes of the type [Ru(tpbn)(IP-R)(4-pic)]Cl (tbpn=2,2'-(4-(-butyl)pyridine-2,6-diyl)bis(1,8-napthyridine); 4-pic=4-picoline; IP-R=imidazo[4,5-][1,10]phenanthroline attached to an aromatic group R for - and H for ) were prepared as near-infrared (NIR) absorbing coordination complexes to test whether triplet intraligand excited states (IL) of higher energy than the lowest-lying triplet metal-to-ligand charge transfer excited states (MLCT) could effectively generate cytotoxic singlet oxygen (O) and elicit in vitro photodynamic therapy (PDT) effects. Aromatic groups ranged from benzene to anthracene, with corresponding triplet state energies that were all significantly higher (approximately 3.7-1.

Development of an Intranasal Gel for the Delivery of a Broadly Acting Subunit Influenza Vaccine.

Influenza virus is a major cause of death on a global scale. Seasonal vaccines have been developed to combat influenza; however, they are not always highly effective. One strategy to develop a more broadly active influenza vaccine is the use of multiple rounds of layered consensus buildings to generate recombinant antigens, termed computationally optimized broadly reactive antigen (COBRA).

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.

Bis[pyrrolyl Ru(ii)] triads: a new class of photosensitizers for metal-organic photodynamic therapy.

A new family of ten dinuclear Ru(ii) complexes based on the bis[pyrrolyl Ru(ii)] triad scaffold, where two Ru(bpy) centers are separated by a variety of organic linkers, was prepared to evaluate the influence of the organic chromophore on the spectroscopic and photodynamic therapy (PDT) properties of the compounds. The bis[pyrrolyl Ru(ii)] triads absorbed strongly throughout the visible region, with several members having molar extinction coefficients () ≥ 10 at 600-620 nm and longer. Phosphorescence quantum yields ( ) were generally less than 0.

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.

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.

A New Class of Homoleptic and Heteroleptic Bis(terpyridine) Iridium(III) Complexes with Strong Photodynamic Therapy Effects.

Six homo- or heteroleptic tricationic Ir(R-tpy)(R-tpy) complexes (-, R/R = Ph, 4'-N(CH)Ph, pyren-1-yl, or 4'-{2-[2-(2-methoxyethoxy)ethoxy]ethoxy}Ph, tpy = 2,2';6',2"-terpyridine) were synthesized and tested for photodynamic therapy (PDT) effects. The ground- and excited-state characteristics of these complexes were studied systematically spectroscopic methods and quantum chemistry calculations. All complexes possessed intraligand charge transfer (ILCT) / metal-to-ligand charge transfer (MLCT) dominated transition(s) in their low-energy absorption bands, which red-shifted with the increased electron-releasing strength of the R/R substituent.

Predictive Strength of Photophysical Measurements for in Vitro Photobiological Activity in a Series of Ru(II) Polypyridyl Complexes Derived from π-Extended Ligands.

This study investigates the correlation between photocytotoxicity and the prolonged excited-state lifetimes exhibited by certain Ru(II) polypyridyl photosensitizers comprised of π-expansive ligands. The eight metal complexes selected for this study differ markedly in their triplet state configurations and lifetimes. Human melanoma SKMEL28 and human leukemia HL60 cells were used as in vitro models to test photocytotoxicity induced by the compounds when activated by either broadband visible or monochromatic red light.

Synthesis, Characterization and Photobiological Studies of Ru(II) Dyads Derived from α-Oligothiophene Derivatives of 1,10-Phenanthroline.

Three new bis(2,2'-bipyridine)-heteroleptic Ru(II) dyads incorporating thienyl groups (n = 1-3, compounds 1, 2 and 3, respectively) appended to 1,10-phenanthroline were synthesized and characterized to investigate the impact of n on the photophysical and photobiological properties within the series. All three complexes showed unstructured emission near 618 nm from a triplet metal-to-ligand charge transfer ( MLCT) state with a lifetime (τ ) of approximately 1 μs. Transient absorption measurements revealed an additional excited state that was nonemissive and long-lived (τ  = 43 μs for 2 and 27 μs for 3), assigned as a triplet intraligand ( IL) state that was accessible only in 2 and 3.

Rapid and efficient pesticide detection via cyclodextrin-promoted energy transfer.

Cyclodextrins facilitate non-covalent fluorescence energy transfer from a variety of pesticides to high quantum-yield fluorophores, resulting in a rapid, sensitive detection scheme for these compounds with detection limits as low as two micromolar. Such a facile detection tool has significant potential applications in agriculture and public health research.