Structural and Photodynamic Studies on Nitrosylruthenium-Complexed Serum Albumin as a Delivery System for Controlled Nitric Oxide Release.

How to deliver nitric oxide (NO) to a physiological target and control its release quantitatively is a key issue for biomedical applications. Here, a water-soluble nitrosylruthenium complex, [(CH3)4N][RuCl3(5cqn)(NO)] (H5cqn = 5-chloro-8-quinoline), was synthesized, and its structure was confirmed with 1H NMR and X-ray crystal diffraction. Photoinduced NO release was investigated with time-resolved Fourier transform infrared and electron paramagnetic resonance (EPR) spectroscopies. The binding constant of the [RuCl3(5cqn)(NO)]- complex with human serum albumin (HSA) was determined by fluorescence spectroscopy, and the binding mode was identified by X-ray crystallography of the HSA and Ru-NO complex adduct. The crystal structure reveals that two molecules of the Ru-NO complex are located in the subdomain IB, which is one of the major drug binding regions of HSA. The chemical structures of the Ru complexes were [RuCl3(5cqn)(NO)]- and [RuCl3(Glycerin)NO]-, in which the electron densities for all ligands to Ru are unambiguously identified. EPR spin-trapping data showed that photoirradiation triggered NO radical generation from the HSA complex adduct. Moreover, the near-infrared image of exogenous NO from the nitrosylruthenium complex in living cells was observed using a NO-selective fluorescent probe. This study provides a strategy to design an appropriate delivery system to transport NO and metallodrugs in vivo for potential applications.

Synthesis, Biomacromolecular Interactions, Photodynamic NO Releasing and Cellular Imaging of Two [RuCl(qn)(Lbpy)(NO)]X Complexes.

Two light-activated NO donors [RuCl(qn)(Lbpy)(NO)]X with 8-hydroxyquinoline (qn) and 2,2'-bipyridine derivatives (Lbpy) as co-ligands were synthesized (Lbpy1 = 4,4'-dicarboxyl-2,2'-dipyridine, X = Cl- and Lbpy2 = 4,4'-dimethoxycarbonyl-2,2'-dipyridine, X = NO3-), and characterized using ultraviolet-visible (UV-vis) spectroscopy, Fourier transform infrared (FT-IR) spectroscopy, nuclear magnetic resonance (1H NMR), elemental analysis and electrospray ionization mass spectrometry (ESI-MS) spectra. The [RuCl(qn)(Lbpy2)(NO)]NO3 complex was crystallized and exhibited distorted octahedral geometry, in which the Ru-N(O) bond length was 1.752(6) Å and the Ru-N-O angle was 177.6(6)°. Time-resolved FT-IR and electron paramagnetic resonance (EPR) spectra were used to confirm the photoactivated NO release of the complexes. The binding constant (Kb) of two complexes with human serum albumin (HSA) and DNA were quantitatively evaluated using fluorescence spectroscopy, Ru-Lbpy1 (Kb~106 with HSA and ~104 with DNA) had higher affinity than Ru-Lbpy2. The interactions between the complexes and HSA were investigated using matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF-MS) and EPR spectra. HSA can be used as a carrier to facilitate the release of NO from the complexes upon photoirradiation. The confocal imaging of photo-induced NO release in living cells was successfully observed with a fluorescent NO probe. Moreover, the photocleavage of pBR322 DNA for the complexes and the effect of different Lbpy substituted groups in the complexes on their reactivity were analyzed.

Structure, photodynamic reaction and DNA photocleavage properties of a nitrosyl iron-sulfur cluster (Me4N)2[Fe2S2(NO)4]: A DFT calculation and experimental study.

Density functional theory calculations were performed on the structure of the nitrosyl iron-sulfur cluster (Me4N)2[Fe2S2(NO)4]. The IR spectra were assigned and the electronic ground-state properties in different solvents were analyzed. Dynamic conversion of [Fe2S2(NO)4]2- was analyzed quantitatively using the time-resolved IR spectra in different solvents. Photo irradiation and polarity of solvent obviously affect the reaction rates, which are faster in CH3CN and CH3OH than those in DMSO and water. The calculated orbital energies of HOMOs are higher and those of LUMO-HOMO gap are smaller in CH3CN and CH3OH than those in DMSO and water, which is consistent with the reaction rate and explains the experimental observation. Moreover, the photo-induced nitric oxide (NO) release and cluster conversion was identified using EPR spectra. The photocleavage of pBR322 DNA was observed, both NO and oxygen related free radicals play key roles in the process. The study provides an effective method to monitor the photodynamic reactions for better understanding of the physiological activity of nitrosyl iron-sulfur clusters.

The first synthesis of Bi self-doped Bi2MoO6-Bi2Mo3O12 composites and their excellent photocatalytic performance for selective oxidation of aromatic alkanes under visible light irradiation.

We report the synthesis of Bi self-doped Bi2MoO6-Bi2Mo3O12 composites with heterostructures by a one-step method using Bi3.64Mo0.36O6.55 as precursor. Among them, Bi2.1MoO6-Bi2.1Mo3O12 shows excellent selectivity as well as recyclability in the oxidation of aromatic alkanes to aldehydes under visible light irradiation.

Non-Covalent Fluorescent Labeling of Hairpin DNA Probe Coupled with Hybridization Chain Reaction for Sensitive DNA Detection.

An enzyme-free signal amplification-based assay for DNA detection was developed using fluorescent hairpin DNA probes coupled with hybridization chain reaction (HCR). The hairpin DNAs were designed to contain abasic sites in the stem moiety. Non-covalent labeling of the hairpin DNAs was achieved when a fluorescent ligand was bound to the abasic sites through hydrogen bonding with the orphan cytosine present on the complementary strand, accompanied by quench of ligand fluorescence. As a result, the resultant probes, the complex formed between the hairpin DNA and ligand, showed almost no fluorescence. Upon hybridization with target DNA, the probe underwent a dehybridization of the stem moiety containing an abasic site. The release of ligand from the abasic site to the solution resulted in an effective fluorescent enhancement, which can be used as a signal. Compared with a sensing system without HCR, a 20-fold increase in the sensitivity was achieved using the sensing system with HCR. The fluorescent intensity of the sensing system increased with the increase in target DNA concentration from 0.5 nM to 100 nM. A single mismatched target ss-DNA could be effectively discriminated from complementary target DNA. Genotyping of a G/C single-nucleotide polymorphism of polymerase chain reaction (PCR) products was successfully demonstrated with the sensing system. Therefore, integrating HCR strategy with non-covalent labeling of fluorescent hairpin DNA probes provides a sensitive and cost-effective DNA assay.