Wanhua Lei

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.

Greatly enhanced binding of a cationic porphyrin towards bovine serum albumin by cucurbit[8]uril

Binding affinity towards serum albumin and intracellular proteins is of importance for a photodynamic therapy (PDT) sensitizer to selectively localize in tumours and efficiently induce cell death. In this paper, it was found that cucurbit[8]uril (CB8) can greatly improve the binding affinity of 5,10,15,20-tetrakis(1-methyl-4-pyridinio)porphyrin tetra(p-toluenesulfonate) (TMPyP), a promising PDT photosensitizer, towards bovine serum albumin (BSA). Absorption, fluorescence emission, (1)H NMR, dynamic light scattering, atomic force microscope, as well as protein photocleavage measurements suggest that the binding enhancement originates from the formation of a ternary complex of CB8·TMPyP·tryptophan residues. This finding opens up a new approach for the development of more efficient PDT agents.

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.

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.

Self-Assembly of Anionic Porphyrins and Alkaline or Alkaline Earth Metal Ions Mediated by Cucurbit[7,8]uril

Nanoscaled coordination polymers based on biologically prevalent ions have potential applications in drug delivery and biomedical imaging. Herein, coordination polymer nanoparticles of anionic porphyrins, including meso-tetra(4-carboxyphenyl)-porphyrin (H2 TCPP(4-)) and meso-tetra(4-sulfonatophenyl)-porphyrin (H2 TPPS(4-)), and alkaline or alkaline earth metal cations, such as K(+) and Ca(2+), were constructed in aqueous solution in the presence of cucurbit[7]uril (CB7) or cucurbit[8]uril (CB8). UV/Vis absorption and fluorescence spectroscopy, dynamic light scattering (DLS), scanning electron spectroscopy (SEM), and atomic force microscopy (AFM) were applied to explore the assembly and particle formation of porphyrin anions and metal cations mediated by CBn. The particle size depends on the kinds of CBn and metal cations and their concentrations. The uptake of H2 TPPS(4-) particles by tumor cells (A549 cells) was found to be more efficient than H2 TPPS(4-) at 37 °C, showing the application potential of such assembled particles in biology and medicine.

Photodynamic inactivation of Escherichia coli by porphyrin cytochrome c

The positively charged porphyrin cytochrome c (porphyrin Cyt c) was found to be able to bind to Escherichia coli, and showed efficient antimicrobial activity upon visible light irradiation, opening avenues for the development of protein-loaded photoinactivation agents against Gram-negative bacteria.

Interband and intraband photocurrent of self-assembled InAs/InAlAs/InP nanostructures

The interband and intraband photocurrent properties of InAs/InAlAs/InP nanostructures have been studied. The doping effect on the photoluminescence properties of the quantum dots and the anisotropy of the quantum wire interband photocurrent properties are presented and discussed. With the help of interband excitation, an intraband photocurrent signal of the InAs nanostructures is observed. With the increase of the interband excitation power, the intraband photocurrent signal first increases and then decreases, which can be explained by the variance of the ground state occupation of the InAs nanostructures and the change of the mobility and lifetime of the electrons. The temperature dependence of the intraband photocurrent signal of the InAs nanostructures is also investigated.

Supramolecular assembly of a new squaraine and β-cyclodextrin for detection of thiol-containing amino acids in water

A new unsymmetrical aniline-based squaraine (SQ2) bearing binding unit of Hg2+ ion was designed and synthesised. SQ2 can form 1:2 inclusion complex with β-cyclodextrin, and the resulting complex, which undergoes absorption and fluorescence bleaching upon binding Hg2+, can serve as a turn-on colorimetric or fluorescent chemosensor in organic solvent-free aqueous solution for thiol-containing amino acids with high selectivity and tunable measuring range.