ABSTRACT
Four Ru(II)-centered isomeric complexes [RuCl(5cqn)(Val)(NO)] (1-4) were synthesized with 5cqn (5-chloro-8-hydroxyquinoline) and chiral Val (Val = L- or D-valine) as co-ligand, and their structures were confirmed using the X-ray diffraction method. The cytotoxicity and photodynamic activity of the isomeric complexes and their human serum albumin (HSA) complex adducts were evaluated. Both the isomeric complexes and their HSA complex adducts significantly affected HeLa cell proliferation, with an IC50 value in the range of 0.3-0.5 µM. The photo-controlled release of nitric oxide (NO) in solution was confirmed using time-resolved Fourier transform infrared and electron paramagnetic resonance spectroscopy techniques. Furthermore, photoinduced NO release in living cells was observed using a selective fluorescent probe for NO. Moreover, the binding constants (Kb) of the complexes with HSA were calculated to be 0.17-1.98 × 104 M-1 and the average number of binding sites (n) was found to be close to 1, it can serve as a crucial carrier for delivering metal complexes. The crystal structure of the HSA complex adduct revealed that one [RuCl(H2O)(NO)(Val)]+ molecule binds to a pocket in domain I. This study provides insight into possible mechanism of metabolism and potential applications for nitrosylruthenium complexes.
Subject(s)
Antineoplastic Agents , Coordination Complexes , Humans , Antineoplastic Agents/pharmacology , Nitric Oxide , Serum Albumin, Human/metabolism , HeLa Cells , Binding Sites , Coordination Complexes/pharmacology , Coordination Complexes/chemistryABSTRACT
The extension peptide (EP) is the most distinctive feature of mature plant ferritin. Some EPs have exhibited serine-like protease activity, which is associated with iron uptake and release. EP forms a helix and a long loop, followed by a conserved core helical bundle. However, whether the EP adopts a stable or uniform folding pattern in all plants remains unclear. To clarify this, we investigated the crystal structure of ferritin-1 from Setaria italica (SiFer1), a type of monocotyledon. In our structure of SiFer1, the EP is different from other EPs in other solved structures of plant ferritins and consisted of a pair of ß-sheets, a shorter helix, and two loops, which masks two hydrophobic pockets on the outer surface of every subunit. Furthermore, sequence analysis and structure comparison suggest that the EPs in ferritins from monocotyledons may adopt a novel fold pattern, and the conformations of EPs in ferritins are alterable among different plant species. Furthermore, additional eight iron atoms were first founded binding in the fourfold channels, demonstrating the vital function of fourfold channels in iron diffusion. In all, our structure provides new clues for understanding plant ferritins and the functions of the EP.
Subject(s)
Ferritins , Setaria Plant , Ferritins/chemistry , Setaria Plant/metabolism , Iron/metabolism , Plants/metabolism , Peptides/metabolismABSTRACT
A three-layer prey-predator model with two time-delays and one delay-dependent parameter is established in this paper. To begin, the paper calculates the conditions for each population in the model to maintain the quantity stable and Hopf bifurcation when τ = τ = 0, τ = 0 , τ ≠ 0, τ is in the stable interval, and τ > 0. The crossing curves, their type, and the direction of the crossing curves are then obtained using the crossing curve method, which is composed of the threshold values of the dynamic behavior change on the two time-delays plane when τ , τ > 0. The real data from the forage grass-Ochotona curzoniae-Buteo hemilasius food chain is used to conduct an empirical study of the model. When τ , τ > 0, the feasible region of the crossing curves is open-ended, and the model's crossing curves on the ( τ , τ ) plane are truncated. This indicates that the model's threshold distribution of dynamic behavior change is a regular curve made of several curves. The simulation using the time-delay value on the crossing curves shows that the model produces different dynamic behaviors such as stability, bifurcation, and chaos depending on the time-delay value on both sides of the curves. The critical values of dynamic behavior change are time-delay values on the crossing curves. The empirical study shows that increasing Ochotona curzoniae's environmental capacity can easily cause Hopf bifurcation of the system. At this time, the number of each population in the Plateau ecosystem constantly fluctuates, and Ochotona curzoniae is vulnerable to extinction.
Subject(s)
Ecosystem , Lagomorpha , Animals , Predatory Behavior , Models, Biological , Food Chain , Computer SimulationABSTRACT
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.
Subject(s)
Coordination Complexes/metabolism , Nitric Oxide/metabolism , Ruthenium Compounds/metabolism , Serum Albumin, Human/metabolism , Coordination Complexes/chemical synthesis , Coordination Complexes/chemistry , Crystallography, X-Ray , Fluorescent Dyes/chemistry , HeLa Cells , Humans , Models, Molecular , Molecular Structure , Nitric Oxide/chemistry , Optical Imaging , Photochemical Processes , Ruthenium Compounds/chemistry , Serum Albumin, Human/chemistry , Tumor Cells, CulturedABSTRACT
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.
Subject(s)
DNA Cleavage/drug effects , Iron/chemistry , Nitrogen Oxides/chemistry , Sulfur Compounds/chemistry , DNA Damage/drug effects , Density Functional Theory , Iron/pharmacology , Models, Molecular , Nitrogen Oxides/pharmacology , Photolysis/drug effects , Sulfur Compounds/pharmacologyABSTRACT
The structures and spectral properties of three ruthenium complexes with 8-hydroxyquinoline (Hhqn) and their derivatives 2-methyl-8-quinolinoline (H2mqn) and 2-chloro-8-quiolinoline (H2cqn) as ligands (QN = hqn, 2mqn, or 2cqn) were calculated with density functional theory (DFT) at the B3LYP level. The UV-Vis and IR spectra of the three [RuCl(QN)NO]- complexes were theoretically assigned via DFT calculations. The calculated spectra reasonably correspond to the experimentally measured spectra. Photoinduced NO release was confirmed through spin trapping of the electron paramagnetic resonance spectroscopy (EPR), and the dynamic process of the NO dissociation upon photoirradiation was monitored using time-resolved infrared (IR) spectroscopy. Moreover, the energy levels and related components of frontier orbitals were further analyzed to understand the electronic effects of the substituent groups at the 2nd position of the ligands on their photochemical reactivity. This study provides the basis for the design of NO donors with potential applications in photodynamic therapy.
