Yuanjun Hou

Mitochondria-targeting properties and photodynamic activities of porphyrin derivatives bearing cationic pendant

Four meso-tetraphenylporphyrin derivatives bearing either triphenylphosphonium ion-(P1 and P2) or triethylammonium ion-(P3 and P4) terminated alkoxy group at either para-(P1 and P3) or meta-(P2 and P4) position of one meso-phenyl group were designed and synthesized. P1-P4 show similar absorption and fluorescence emission spectra and (1)O(2) quantum yields. The more lipophilic nature of triphenylphosphonium ion over triethylammonium ion renders P1 and P2 higher octanol/water partition coefficients than P3 and P4. Confocal fluorescence microscopy proved that P1-P4 are all mitochondria-targeting. MTT assay showed that P1-P4 presented significant phototoxicity at the concentrations that dark toxicity is negligible towards human breast cancer cell line MCF-7 cells, displaying their application potential in PDT.

Highly efficient charge transfer from a trans-ruthenium bipyridine complex to nanocrystalline TiO2 particles

trans-Di(isothiocyanato)-[N-bis(2,2′-bipyridyl-4,4′-dicarboxylic acid) ruthenium(II) acts as a very efficient charge-transfer sensitizer for nanocrystalline TiO2 films. The incident photon-to-electron conversion efficiency (IPCE) for the dye-coated TiO2 film exceeded 80% in the wavelength domain between 400 and 600 nm. A sandwich-type regenerative solar cell fabricated from a 10 μm thick TiO2 film sensitized with this dye generated a short-circuit photocurrent of 19.6 mA cm−2 and an open-circuit photovoltage of 720 mV in simulated AM1.5 solar light (924 W m−2) with an overall power conversion efficiency of 8.6%.

DNA photocleavage by a cationic BODIPY dye through both singlet oxygen and hydroxyl radical: new insight into the photodynamic mechanism of BODIPYs.

Two new NIR-absorbing BODIPY dyes, each bearing two pyridinium groups, are synthesized and their DNA-binding affinities and DNA photocleavage abilities examined in depth. While one BODIPY dye photocleaves DNA mainly through singlet oxygen, the other photocleaves DNA through both singlet oxygen and hydroxyl radical. To the best of our knowledge, this is the first example of a hydroxyl radical being involved in the photodynamic behavior of BODIPY-type dyes. EPR experiments confirm the ability of these and several related BODIPYs to generate superoxide anion radical and hydroxyl radical. This finding may shed light on the mechanism of BODIPY-based photodynamic therapy (PDT) and open a new avenue for development of more efficient BODIPY-type PDT agents.

Selective Photodynamic Inactivation of Bacterial Cells over Mammalian Cells by New Triarylmethanes

Three new triarylmethane dyes (TAMs), MPCV, DPCV, and AEV, were synthesized and their photodynamic inactivation abilities against E. coli and human pulmonary carcinoma A549 cells were compared to two commercial TAMs, CV and EV. The enhanced hydrophilicity of MPCV and AEV decreases their cellular uptake to A549 cells dramatically. However, their binding affinity toward E. coli cells are comparable to that of CV and EV by virtue of the improved electrostatic attraction with highly negatively charged E. coli outer membranes. MPCV and AEV were also found to generate hydroxyl radicals more efficiently upon irradiation than CV and EV. Consequently, MPCV and AEV exhibited markedly improved photodynamic inactivation of E. coli cells but remarkably diminished photodynamic inactivation of A549 cells than CV and EV. The photodynamic inactivation ability of DPCV was much lower than that of CV due to its high propensity for bleaching in neutral aqueous solution. Our work demonstrates that the introduction of protonatable groups in a proper manner into the structures of TAMs may lead to selective binding and photodynamic inactivation toward bacterial cells over mammalian cells. This strategy may be extended to other types of photodynamic antimicrobial chemotherapy (PACT) agents to improve their clinical potential.

DNA photocleavage in anaerobic conditions by a Ru(II) polypyridyl complex with long wavelength MLCT absorption

Ru(II) polypyridyl complexes possessing long wavelength absorption and an efficient DNA photocleavage activity exhibit a potential application in photodynamic therapy (PDT). In this article, we reported a Ru(II) polypyridyl complex, [Ru(bpy)2(dpb)]2+ (bpy = 2,2′-bipyridine, dpb = 2,3-bis(2-pyridyl)benzoquinoxaline), that exhibits a very long wavelength 1MLCT absorption, with a maximum at 550 nm, and DNA photocleavage activity in anaerobic conditions in the presence of suitable oxidative quenchers, showing a promising potential application in the PDT of hypoxic tumors.

Synthetic control of the photophysical and photoelectrochemical properties of ruthenium(II) polypyridyl complexes

Abstract Two classes of useful complexes of cis-Ru(bpy-X)2(NCS)2 and [Ru(bpy)2(bpy-X)]2+ have been prepared and their spectroscopic and photoelectrochemical properties investigated. All the complexes ([Ru(bpy)2(bpy-X)]2+) examined display luminescence at room temperature. The energy of the emission maximum is red shifted for both electron-withdrawing and electron-donating substituents compared to that of parent [Ru(bpy)3]2+ complex. Furthermore, the complexes bearing electron-acceptor substituents have higher luminescence quantum yield and longer excited-state lifetime than that of the compounds bearing electron-donating ones. Such behaviors demonstrate that the values of rate constants for radiationless decay from the luminescent excited state to the ground state are determined not only by the energy gap but also by the nature of the substituents, which presumably influenced the changes in the equilibrium displacement between the two levels. In addition, the photoelectrochemical results of the cis-Ru(bpy-X)2(NCS)2 clearly show that the nature of the substituents on the bpy ligands does not substantially affect the photon-to-electric energy conversion efficiency.

Synthesis and photoelectric studies of Ru(II) polypyridyl sensitizers

New cis-Ru(3,3′-dcbpy)2(NCS)2 photosensitizer (where 3,3′-dcbpy is 3,3′-dicarboxy-2,2′-bipyridine) was synthesized using Ru(DMSO)4Cl2 as a starting material and characterized. Its photophysical and redox properties were compared with those of cis-Ru(4,4′-dcbpy)2(NCS)2 and cis-Ru(5,5′-dcbpy)2(NCS)2.The photoelectrochemical properties of the three dyes adsorbed on the surface of the nanocrystalline TiO2 electrodes as well as on self-assembly monolayers (SAMs) were investigated. The photocurrents generated by sensitized TiO2 electrodes were much higher than those by SAMs. And cis-Ru(4,4′-dcbpy)2 showed a most efficient photosensitizer in both systems. The mechanism is discussed in the paper.

A new Co(III)–hypocrellin B complex with enhanced photonuclease activity

Hypocrellin B (HB), a naturally occurring photosensitizer, has been extensively and intensively studied as a promising photodynamic therapy (PDT) agent. In this work, a new Co(III) complex [Co(2)(HB)(tmp)(4)](4+) (tmp=3,4,7,8-tetramethyl-1,10-phenanthroline) was designed and synthesized with HB as bridging ligand and tmp as terminal ligand. [Co(2)HB(tmp)(4)](4+) exhibits improved water solubility, enhanced absorptivity in the phototherapeutic window, increased binding affinity and DNA photocleavage capability toward dsDNA with respect to HB. The photodynamic activity of [Co(2)(HB)(tmp)(4)](4+) stems from its (1)O(2) photosensitization ability, in sharp contrast to [Cu(2)(HB)(tmp)(2)](2+) which relies on superoxide anion radical (O(2)(-)) and hydroxyl radical (·OH) to photocleave DNA, though the both complexes possess similar electrochemical properties. The remarkable difference between the photodynamic mechanisms of [Co(2)(HB)(tmp)(4)](4+) and [Cu(2)(HB)(tmp)(2)](2+) was discussed in detail.

Host–Guest Interaction of Hoechst 34580 and Cucurbit[7]uril

To track nuclear dynamic processes by fluorescence imaging, nuclear stains should be highly fluorescent, resistant to photobleaching, and inert to nuclear processes. The nuclear stains of the Hoechst family, such as Hoechst 34580, show bright fluorescence only on groove binding to DNA, and therefore may interfere with visualization of nuclear dynamic processes induced by other stimuli. We study host-guest interactions between Hoechst 34580 and Cucurbit[7]uril (CB7) in aqueous solutions. The formation of CB7-Hoechst 34580 inclusion complexes with stoichiometry of 2:1 in water and 1:1 in phosphate-buffered saline (PBS) solution (pH 7.0) is confirmed by (1)H NMR, absorption spectra, fluorescence spectra, MALDI-TOF MS, and molecular modeling. Compared to Hoechst 34580, the inclusion complex exhibits redshifted absorption, intensified fluorescence, improved photostability, weakened DNA binding affinity, comparable ability to penetrate cell nuclei, and better nuclear-staining capability, and thus a new avenue for the application of cucurbituril in fluorescence imaging is opened.

A ferrocenyl pyridine-based Ru(II) arene complex capable of generating ·OH and 1O2 along with photoinduced ligand dissociation

Photoactivated chemotherapy (PACT) and photodynamic therapy (PDT) are two types of cancer treatment modalities that rely on photoinduced ligand dissociation and photosensitized or photocatalyzed reactive oxygen species (ROS) generation to realize anticancer activities with high selectivity, respectively. In this study, a novel Ru complex, [(p-cym)Ru(bpy)(py-Fc)]2+ (1), where p-cym = para-cymene, bpy = 2,2′-bipyridine, and py-Fc = 4-pyridyl ferrocene, was demonstrated to show dual activity from PACT and PDT. 1 has a long-wavelength absorption band extending to 600 nm and can generate both hydroxyl radicals (·OH) and singlet oxygen (1O2) along with photoinduced monodentate ligand dissociation. As a result, 1 displays DNA photocleavage activity as well as phototoxicity against human ovarian adenocarcinoma cells SKOV3 and human lung adenocarcinoma cells A549. The underlying mechanisms were discussed by comparing the photophysical, photochemical, and photobiological properties of 1 with that of [(p-cym)Ru(bpy)(py)]2+ (2, py = pyridine) and free py-Fc, providing guidelines for developing new photoactivated metallodrugs with multiple functions.