Amplifying Free Radical Generation of AIE Photosensitizer with Small Singlet-Triplet Splitting for Hypoxia-Overcoming Photodynamic Therapy.

Type-I photodynamic therapy (PDT) with less oxygen consumption shows great potential for overcoming the vicious hypoxia typically observed in solid tumors. However, the development of type-I PDT is hindered by insufficient radical generation and the ambiguous design strategy of type-I photosensitizers (PSs). Therefore, developing highly efficient type-I PSs and unveiling their structure-function relationship are still urgent and challenging. Herein, we develop two phenanthro[9,10-d]imidazole derivatives (AQPO and AQPI) with aggregation-induced emission (AIE) characteristics and boost their reactive oxygen species (ROS) generation efficiency by reducing singlet-triplet splitting (ΔEST). Both AQPO and AQPI show ultrasmall ΔEST values of 0.09 and 0.12 eV, respectively. By incorporating electron-rich anisole, the categories of generated ROS by AIE PSs are changed from type-II (singlet oxygen, 1O2) to type-I (superoxide anion radical, O2•- and hydroxyl radical, •OH). We demonstrate that the assembled AQPO nanoparticles (NPs) achieve a 3.2- and 2.9-fold increase in the O2•- and •OH generation efficiencies, respectively, compared to those of AQPI NPs (without anisole) in water, whereas the 1O2 generation efficiency of AQPO NPs is lower (0.4-fold) than that of AQPI NPs. The small ΔEST and anisole group endow AQPO with an excellent capacity for type-I ROS generation. In vitro and in vivo experiments show that AQPO NPs achieve an excellent hypoxia-overcoming PDT effect by efficiently eliminating tumor cells upon white light irradiation with good biosafety.

Biological activity and photocatalytic properties of a naphthyl-imidazo phenanthroline (HNAIP) ligand and its [Ir(ppy)2(HNAIP)]Cl and [Rh(ppy)2(HNAIP)]Cl complexes.

The synthesized 2-(hydroxy-1-naphtyl)imidazo-[4,5-f][1,10]phenanthroline (HNAIP) ligand and its new iridium ([Ir(ppy)2(HNAIP)]Cl) and rhodium ([Rh(ppy)2(HNAIP)]Cl) complexes, being ppy = 2-phenylpiridinate, show cytotoxic effects in SW480 (colon adenocarcinoma) and A549 (epithelial lung adenocarcinoma) cells. They all are cytotoxic in the tested cell lines. HNAIP and [Rh(ppy)2(HNAIP)]+ are the most cytotoxic, whereas [Ir(ppy)2(HNAIP)]+ displays negligible cytotoxicity towards A549 cells and moderate activity towards SW480. The interaction of all three compounds with Bovine Serum Albumin (BSA), l-glutathione reduced (GSH), nicotinamide adenine dinucleotide (NADH) and DNA was studied to explain the differences found in terms of cytotoxicity. None of them are able to interact with BSA, thus excluding bioavailability due to plasma protein interaction as the possible differentiating factor in their biological activity. By contrast, small differences have been observed regarding DNA interaction. In addition, taking advantage of the emission properties of these molecules, they have been visualized in the cytoplasmic region of A549 cells. Inductively coupled plasma mass spectrometry (ICP-MS) experiments show, in turn, that the internalization ability follow the sequence [Rh(ppy)2(HNAIP)]+ > [Ir(ppy)2(HNAIP)]+ > cisplatin. Therefore, it seems clear that the cellular uptake by tumour cells is the key factor affecting the different cytotoxicity of the metal complexes and that this cellular uptake is influenced by the hydrophobicity of the studied complexes. On the other hand, preliminary catalytic experiments performed on the photo-oxidation of GSH and some amino acids such as l-methionine (Met), l-cysteine (Cys) and l-tryptophan (Trp) provide evidence for the photocatalytic activity of the Ir(III) complex in this type of reactions.

Ru(TAP)32+ uses multivalent binding to accelerate and constrain photo-adduct formation on DNA.

Ru(ii)-complexes with polyazaaromatic ligands can undergo direct electron transfer with guanine nucleobases on blue light excitation that results in DNA lesions with phototherapeutic potential. Here we use single molecule approaches to demonstrate DNA binding mode heterogeneity and evaluate how multivalent binding governs the photochemistry of [Ru(TAP)3]2+ (TAP = 1,4,5,8-tetraazaphenanthrene).

Ruthenium(II) Polypyridyl Complexes as Photosensitizers for Antibacterial Photodynamic Therapy: A Structure-Activity Study on Clinical Bacterial Strains.

As a growing public health concern, the worldwide spread of antimicrobial resistance urges the development of new therapies. Antibacterial photodynamic therapy (a-PDT) may be an alternative to conventional antibiotic therapy. Herein we report the synthesis and characterization of seven original reactive oxygen species (ROS)-producing ruthenium(II) polypyridyl complexes. These are part of a collection of 17 derivatives varying in terms of the nature of the substituent(s), molecular symmetry, electrical charge, and counterions. They were characterized by considering 1) their physical properties (absorption coefficient at irradiation wavelength, 1 O2 generation quantum yield, luminescence) and 2) their antibacterial activity in a series of photodynamic assays using Gram-positive and Gram-negative bacteria of clinical relevance. The results unveiled some structure-activity relationships: one derivative that combines multiple beneficial features for a-PDT was effective against all the bacteria considered, regardless of their Gram status, species, or antibiotic resistance profile. This systematic study could guide the design of next-generation ruthenium-based complexes for enhanced antibacterial photodynamic strategies.

Infrared studies of lead(II) halide-1,10-phenanthroline photosensitive materials.

Infrared spectroscopic studies of 1:1 and 1:2 complexes of lead(II) bromide and lead(II) iodide with 1,10-phenanthroline were reported. Vibrational assignments are made by comparison to reported spectra of the uncomplexed 1,10-phenanthroline molecule. Small shifts of the ligand vibrational bands are characteristic of the complexes.

Treatment of 1,10-phenanthroline laboratory wastewater using the solar photo-Fenton process.

The red Fe(2+)-phenanthroline complex is the basis of a classical spectrophotometric method for determination of iron. Due to the toxicity of this complexing agent, direct disposal of the wastewaters generated in analytical laboratories is not environmentally safe. This work evaluates the use of the solar photo-Fenton process for the treatment of laboratory wastewaters containing phenanthroline. Firstly, the degradation of phenanthroline in water was evaluated at two concentration levels (0.1 and 0.01%, w/v) and the efficiencies of degradation using ferrioxalate (FeOx) and ferric nitrate were compared. The 0.01% w/v solution presented much higher mineralization, achieving 82% after 30min of solar irradiation with both iron sources. The solar photo-Fenton treatment of laboratory wastewater containing, in addition to phenanthroline, other organic compounds such as herbicides and 4-chlorophenol, equivalent to 4,500mgL(-1) total organic carbon (TOC) resulted in total degradation of phenanthroline and 25% TOC removal after 150min, in the presence of either FeOx or ferric nitrate. A ratio of 1:10 dilution of the residue increased mineralization in the presence of ferrioxalate, achieving 38% TOC removal after 120min, while use of ferric nitrate resulted in only 6% mineralization over the same period.

Synthesis and photochemistry of a two-position Ru(terpy)(phen)(L)2+ scorpionate complex.

A dissymmetric 1,10-phenanthroline chelate (N-phen-S) bearing two polyether chains terminated by two monodentate ligands of the benzonitrile (N) and dialkylesulfoxide (S) types was synthesized, characterized, and coordinated to ruthenium. The corresponding Ru(terpy)(N-phen-S)2+ complexes (terpy = 4'-(3,5-ditertiobutylphenyl)-2,2';6',2' '-terpyridine) were fully characterized as being two coordination isomers of the scorpionate type with one of the two tails occupying the sixth position on the coordination sphere. Photoexpulsion of the coordinated tail led to opening of the ruthena-macrocycle and subsequent rearrangement of the bidentate chelate. This rearrangement consisted of a 90 degrees rotation of the phenanthroline around the ruthenium atom. Selective irradiation of one isomer in a mixture of the two was undertaken using band-pass filters; this resulted in an enrichment of the nonirradiated isomer in the mixture. Thermal back-coordination of the tail was investigated in the dark. It took place quantitatively from the corresponding ruthenium chloride complex by trapping of the anion with silver salts.

Covalent modification of DNA by cis-Rh(phen)2Cl2+ upon irradiation in the red region.

The metal complex, cis-Rh(phen)2Cl2+ (phen = 1,10-phenanthroline), absorbs in the near UV region and is apparently transparent in the red region of the electromagnetic radiation. We have previously shown that the chemical can be photosensitized by the red light absorbing dye, methylene blue, and the activated compound forms permanent bonds with DNA. In the present paper we report that despite the negligible absorption of the metal complex beyond UVA (320-400 nm) region, irradiation with red light populates a highly reactive excited state, which forms covalent linkages with DNA. The purified DNA photoadducts indicate binding as high as 105 nmol Rh, which corresponds to 1.8% metal incorporation. The quantum efficiency for covalent binding of Rh complex to DNA with the 633 nm-excitation is in the range of 0.01-0.02 under anaerobic conditions. These data reveal that one Rh atom occurs approximately every 300 DNA bases. HPLC and UV/Vis analyses of the enzymatic digest of the photoadducts support that the DNA-Rh photoadducts are stable to nucleolytic enzymes. The DNA photo-modification is inhibited by the presence of oxygen indicating that the new excited state of cis-Rh(phen)2Cl2+ to be different from that populated by UVA excitation.

Luminescence quenching by DNA-bound viologens: effect of reactant identity on efficiency and dynamics of electron transfer in DNA.

Photoinduced electron transfer from two intercalating photoactive donors, Ru(phen)2dppz2+ and ethidium, to intercalating viologen acceptors of the N,N'-dialkyl-6-(2'-pyridiniumyl)phenanthridinium family has been investigated through steady-state and time-resolved luminescence quenching measurements. Efficient quenching of the emission from these donors bound to DNA is observed at low concentrations of acceptor (1-10 eq.), and in time-resolved emission experiments it is determined that electron transfer occurs on the nanosecond time scale. Furthermore, transient absorption measurements confirm that the quenching is the result of a charge-transfer process; upon photoreaction of intercalated Ru(phen)2dppz2+ with a viologen acceptor, an intermediate with spectral properties resembling the expected charge-separated pair is observed. The quenching yields and kinetics obtained with this quencher are in marked contrast to those observed with these same donors paired with Rh(phi)2bpy3+ as an acceptor. The differing efficiencies of electron transfer for these donor/acceptor pairs bound to DNA as compared to others previously described are discussed qualitatively in terms of the structural and electronic properties of the different reactants.

Photoaquation of cis-dichlorobis-(1,10-phenanthroline)chromium(III) and the photochemical and thermal reactions of this complex with native calf-thymus DNA.

The photoaquation of the title compound [cis-Cr(phen)2CL+2] has been studied using high performance liquid chromatography. Both monoaquo [cis-Cr(phen)2Cl(OH2)2+2] and diaquo [cis-Cr(phen)2(OH2)3+2] products are formed, and the quantum efficiency for the loss of starting material in Tris buffer (pH 7) under argon and oxygen is 0.010 +/- 0.001 and 0.0026 +/- 0.0002, respectively. The presence of deoxyguanosine (dG) increases the rate of loss, as much as twofold under argon, but only the rate of diaquo product formation is enhanced by the nucleoside. The dG effect is attributed to reductive quenching of the cis-Cr(phen)2Cl+2 excited state by the base. Equilibrium dialysis studies indicate that both cis-Cr(phen)2Cl+2 and cis-Cr(phen)2(OH2)3+2 minimally associate with calf-thymus DNA. However, photolyses of cis-Cr(phen)2Cl+2 with the nucleic acid yield a mixture of unidentified covalent adducts. The diaquo complex also forms covalent adducts with DNA in the absence of light. Photolyses of the cis-Cr(phen)2Cl+2 with polyribonucleotides indicate a clear preference for covalent binding to the purines.