Near‐IR Phosphorescent Ruthenium(II) and Iridium(III) Perylene Bisimide Metal Complexes

The phosphorescence emission of perylene bisimide derivatives has been rarely reported. Two novel ruthenium(II) and iridium(III) complexes of an azabenz‐annulated perylene bisimide (ab‐PBI), [Ru(bpy)₂(ab‐PBI)][PF₆]₂ 1 and [Cp*Ir(ab‐PBI)Cl]PF₆ 2 are now presented that both show NIR phosphorescence between 750–1000 nm in solution at room temperature. For an NIR emitter, the ruthenium complex 1 displays an unusually high quantum yield (Φ_p) of 11 % with a lifetime (τ_p) of 4.2 μs, while iridium complex 2 exhibits Φ_p<1 % and τ_p=33 μs. 1 and 2 are the first PBI‐metal complexes in which the spin–orbit coupling is strong enough to facilitate not only the S_n→T_n intersystem crossing of the PBI dye, but also the radiative T₁→S₀ transition, that is, phosphorescence.     

Ruthenium Complexes with Hydrophobic Ligands That Are Key Factors for the Optical Imaging of Physiological Hypoxia

The phosphorescence emission of ruthenium complexes was applied to the optical imaging of physiological hypoxia. We prepared three complexes with hydrophobic substituents on the phenanthroline ligand and characterized their emission, which was quenched by molecular oxygen. Among the complexes synthesized in this study, a pyrene chromophore‐linked ruthenium complex, Ru‐Py, exhibited optimal properties for the imaging of hypoxia; the prolonged lifetime of the triplet excited state of the ruthenium chromophore, which was induced by efficient energy distribution and transfer from the pyrene unit, provided the highest sensitivity towards molecular oxygen. The introduction of hydrophobic pyrene increased the lipophilicity of the complex, leading to enhanced cellular uptake. Consequently, the bright phosphorescence of Ru‐Py was seen in the cytoplasm of viable hypoxic cells, whereas the signal from aerobic cells was markedly weaker. Thus, we could clearly discriminate between hypoxic and aerobic cells by monitoring the phosphorescence emission. Furthermore, Ru‐Py was applied to optical imaging in live mice. An intramuscular injection of Ru‐Py successfully visualized ischemia‐based hypoxia, which was constructed by leg banding.     

Bioorthogonal Labeling,Bioimaging, and Photocytotoxicity Studies of Phosphorescent Ruthenium(II) Polypyridine Dibenzocyclooctyne Complexes

The synthesis, characterization, photophysics, lipophilicity, and cellular properties of new phosphorescent ruthenium(II) polypyridine complexes functionalized with a dibenzocyclooctyne (DIBO) or amine moiety [Ru(N^N)₂(L)](PF₆)₂ are reported (L=4‐(13‐N‐(3,4:7,8‐dibenzocyclooctyne‐5‐oxycarbonyl) amino‐4,7,10‐trioxa‐tridecanyl‐aminocarbonyl‐oxy‐methyl)‐4′‐methyl‐2,2′‐bipyridine bpy‐DIBO, N^N=2,2′‐bipyridine bpy ( 1 a ), 1,10‐phenanthroline phen ( 2 a ); L=4‐(13‐amino‐4,7,10‐trioxa‐tridecanylaminocarbonyl‐oxy‐methyl)‐4′‐methyl‐2,2′‐bipyridine bpy‐NH₂, N^N=bpy ( 1 b ), phen ( 2 b )). The strain‐promoted alkyne–azide cycloaddition (SPAAC) reaction of the DIBO complexes 1 a and 2 a with benzyl azide were studied. Also, the DIBO complexes 1 a and 2 a can selectively label N‐azidoglycans located on the surface of CHO‐K1 and A549 cells that were pretreated with 1,3,4,6‐tetra‐O‐acetyl‐N‐azidoacetyl‐D ‐mannosamine (Ac₄ManNAz). Additionally, the intracellular trafficking and localization of these biomolecules were monitored using laser‐scanning confocal microscopy. Interestingly, the biolabeling and cellular uptake efficiency of the DIBO complexes 1 a and 2 a were cell‐line dependent, as revealed by flow cytometry and ICP‐MS. Furthermore, the complexes showed good biocompatibility toward the Ac₄ManNAz‐pretreated cells in the dark, but exhibited photoinduced cytotoxicity due to the generation of singlet oxygen.     

含席夫碱桥联配体的双核金属钌配合物的合成及其性能研究

合成了3种双核钌配合物[Ru(bpy)2]2{[(PyCHN)-Ph-O-C6H4-]2R}(ClO4)4,bpy=2,2′-联吡啶,PyCHN=N-2-吡啶亚甲基,R=无(1),-C(CH3)2(2),-SO2(3)并进行了有关表征。电化学研究表明:配合物3的ΔE和Kc值最大,说明苯环和硫原子之间存在着较强的(p(π)-d)π相互作用,有助于获得较强的金属-金属相互作用。配合物1,2,3都有混合价,通过Hush方程可以得到Vab的值大概为320~420 cm-1。这些结果表明:Schiff碱作为桥配体对于调配金属-金属相互作用并将其作为分子导线起着特殊的作用。     

Theoretical Modelling of Photoswitching of Hyperpolarisabilities in Ruthenium Complexes

Static excited‐state polarisabilities and hyperpolarisabilities of three Ru^II ammine complexes are computed at the density functional theory (DFT) and several correlated ab initio levels. Most accurate modelling of the low energy electronic absorption spectrum is obtained with the hybrid functionals B3LYP, B3P86 or M06 for the complex [Ru^II(NH₃)₅(MeQ⁺)]³⁺ (MeQ⁺=N‐methyl‐4,4′‐bipyridinium, 3 ) in acetonitrile. The match with experimental data is less good for [Ru^II(NH₃)₅L]³⁺ (L=N‐methylpyrazinium, 2 ; N‐methyl‐4‐{E,E‐4‐(4‐pyridyl)buta‐1,3‐dienyl}pyridinium, 4 ). These calculations confirm that the first dipole‐ allowed excited state (FDAES) has metal‐to‐ligand charge‐transfer (MLCT) character. Both the solution and gas‐phase results obtained for 3 by using B3LYP, B3P86 or M06 are very similar to those from restricted active‐space SCF second‐order perturbation theory (RASPT2) with a very large basis set and large active space. However, the time‐dependent DFT λ_max predictions from the long‐range corrected functionals CAM‐B3LYP, LC‐ωPBE and wB97XB and also the fully ab initio resolution of identity approximate coupled‐cluster method (gas‐phase only) are less accurate for all three complexes. The ground state (GS) two‐state approximation first hyperpolarisability β_2SA for 3 from RASPT2 is very close to that derived experimentally via hyper‐Rayleigh scattering, whereas the corresponding DFT‐based values are considerably larger. The β responses calculated by using B3LYP, B3P86 or M06 increase markedly as the π‐conjugation extends on moving along the series 2 → 4 , for both the GS and FDAES species. All three functionals predict substantial FDAES β enhancements for each complex, increasing with the π‐conjugation, up to about sevenfold for 4 . Also, the computed second hyperpolarisabilities γ generally increase in the FDAES, but the results vary between the different functionals.     

Biocompatible Ir(III) Complexes as Oxygen Sensors for Phosphorescence Lifetime Imaging

Synthesis of biocompatible near infrared phosphorescent complexes and their application in bioimaging as triplet oxygen sensors in live systems are still challenging areas of organometallic chemistry. We have designed and synthetized four novel iridium [Ir(N^C)₂(N^N)]⁺ complexes (N^C–benzothienyl-phenanthridine based cyclometalated ligand; N^N–pyridin-phenanthroimidazol diimine chelate), decorated with oligo(ethylene glycol) groups to impart these emitters’ solubility in aqueous media, biocompatibility, and to shield them from interaction with bio-environment. These substances were fully characterized using NMR spectroscopy and ESI mass-spectrometry. The complexes exhibited excitation close to the biological “window of transparency”, NIR emission at 730 nm, and quantum yields up to 12% in water. The compounds with higher degree of the chromophore shielding possess low toxicity, bleaching stability, absence of sensitivity to variations of pH, serum, and complex concentrations. The properties of these probes as oxygen sensors for biological systems have been studied by using phosphorescence lifetime imaging experiments in different cell cultures. The results showed essential lifetime response onto variations in oxygen concentration (2.0–2.3 μs under normoxia and 2.8–3.0 μs under hypoxia conditions) in complete agreement with the calibration curves obtained “in cuvette”. The data obtained indicate that these emitters can be used as semi-quantitative oxygen sensors in biological systems.     

Cyclometalated Ruthenium(II) Anthraquinone Complexes Exhibit Strong Anticancer Activity in Hypoxic Tumor Cells

Hypoxia is the critical feature of the tumor microenvironment that is known to lead to resistance to many chemotherapeutic drugs. Six novel ruthenium(II) anthraquinone complexes were designed and synthesized; they exhibit similar or superior cytotoxicity compared to cisplatin in hypoxic HeLa, A549, and multidrug‐resistant (A549R) tumor cell lines. Their anticancer activities are related to their lipophilicity and cellular uptake; therefore, these physicochemical properties of the complexes can be changed by modifying the ligands to obtain better anticancer candidates. Complex 1 , the most potent member of the series, is highly active against hypoxic HeLa cancer cells (IC₅₀=0.53 μM ). This complex likely has 46‐fold better activity than cisplatin (IC₅₀=24.62 μM ) in HeLa cells. This complex tends to accumulate in the mitochondria and the nucleus of hypoxic HeLa cells. Further mechanistic studies show that complex 1 induced cell apoptosis during hypoxia through multiple pathways, including those of DNA damage, mitochondrial dysfunction, and the inhibition of DNA replication and HIF‐1α expression, making it an outstanding candidate for further in vivo studies.     

Catalysis of Mononuclear Aquaruthenium Complexes in Oxygen Evolution from Water: A New Radical Coupling Path using Hydroxocerium(IV) Species

The mechanism of O₂ evolution from water catalyzed by a series of mononuclear aquaruthenium complexes, [Ru(terpy)(bpy)(OH₂)]²⁺, [Ru(tmtacn)(R₂bpy)(OH₂)]²⁺ (R=H, Me, and OMe; R₂bpy=4,4′‐disubstituted‐2,2′‐bipyridines), and [Ru(tpzm)(R₂bpy)(OH₂)]²⁺ (R=H, Me, and OMe), is investigated, where terpy=2,2′:6′,2′′‐terpyridine, bpy=2,2′‐bipyridine, tmtacn=1,4,7‐trimethyl‐1,4,7‐triazacyclononane, and tpzm=tris(1‐pyrazolyl)methane. The kinetics of O₂ evolution is investigated as a function of either the catalyst concentration or the oxidant concentration by employing Ce(NH₄)₂(NO₃)₆ as an oxidant; these catalysts can be classified into two groups that have different rate laws for O₂ evolution. In one class, the rate of O₂ evolution is linear to both the catalyst and Ce⁴⁺ concentrations, as briefly reported for [Ru(terpy)(bpy)(OH₂)]²⁺ (S. Masaoka, K. Sakai, Chem. Lett. 2009 , 38, 182). For the other class, [Ru(tmtacn)(R₂bpy)(OH₂)]²⁺, the rate of O₂ evolution is quadratic to the catalyst concentration and independent of the Ce⁴⁺ concentration. Moreover, the singlet biradical character of the hydroxocerium(IV) ion was realized by experimental and DFT investigations. These results indicate that the radical coupling between the oxygen atoms of a Ru^V?O species and a hydroxocerium(IV) ion is the key step for the catalysis of [Ru(terpy)(bpy)(OH₂)]²⁺ and [Ru(tpzm)(R₂bpy)(OH₂)]²⁺, while the well‐known oxo‐oxo radical coupling among two Ru^V?O species proceeds in the catalysis of [Ru(tmtacn)(R₂bpy)(OH₂)]²⁺. This is the first report demonstrating that the radical character provided by the hydroxocerium(IV) ion plays a crucial role in the catalysis of such ruthenium complexes in the evolution of O₂ from water.     

Reactions of Pd and Pt Complexes with Molecular Oxygen

Knowledge of exactly how metal complexes react with molecular oxygen is still limited and this has hampered efforts to develop catalysts for oxidation reactions using O₂ as the oxidant and/or oxygen‐atom source. A better understanding of the reactions of different types of metal complexes with O₂ will be of great utility in rational catalyst development. Reactions between molecular oxygen and Pd^0–II and Pt^0–IV complexes are reviewed here.     

反式阿魏酸钌配合物的合成、表征、荧光光谱及其与DNA/蛋白作用

对天然产物反式阿魏酸进行化学修饰,设计、合成了2种单核钌配合物[Ru(cym)(L)Cl]Cl (Ru-1)与[Ru(bpy)2(L)]Cl2(Ru-2)(cym=对伞花烃,bpy=2,2′-联吡啶,L=(E)-3-(4-hydroxy-3-methoxyphenyl)-N-((4′-methyl-(2,2′-bipyridin)-4-yl)methyl)acrylamide),通过核磁共振氢谱和碳谱、电喷雾质谱对配合物进行了结构表征。利用荧光、紫外-可见光谱等方法研究了配合物的溶解性和光学性质。配合物均具有良好的亲水性。Ru-2有良好的荧光性能,其发射波长达到近红外的631 nm,且可以在pH值为8～10之间实现响应。Ru-2还具有较高的单线态氧量子产率(Φ=0.70),有望成为一类高效的光敏剂。2种配合物都与CT-DNA发生嵌入作用(Kb分别为1.210×104和1.233×103L·mol-1);均与BSA有一个结合位点,使其荧光发生静态淬灭(Ka值分别为1.94×104,2.45×104)。     

Bistable Molecular Switches Based on Linkage Isomerization in Ruthenium Polypyridyl Complexes with a Ligand-Bound Ambidentate Motif

Electron-transfer-induced linkage isomerization was investigated in a series of bis-tridentate Ru polypyridyl complexes [Ru(L-X-OH)(Y-tpy)]²⁺ with ambidentate ligand L-X-OH=bpy-C(R)(OH)-py (bpy=2,2′-bipyridine; py=pyridine; R=H, Me, Ph, or tBu) and spectator ligand Y-tpy (tpy=2,2′:6′,2′′-terpyridine; Y=p-tolyl, p-PhCO₂Me, Cl, OEt, N-pyrrolidine). The ligand-bound ambidentate motif switches reversibly between N and O coordination in the Ru^II and Ru^III state, respectively. The potentials of the Ru^III/II couple differ by about 0.5 V between the isomers, and this results in a bistable electrochemical response of the molecular switches. The effects of structural modifications in form of substituents on the linking carbon atom of the ambidentate ligand and on the central pyridine moiety of the spectator ligand were investigated by electrochemical and computational methods. Differences in isomerization behavior span six orders of magnitude in rate constants and two orders of magnitude in equilibrium constants. The results can be interpreted in terms of steric and electronic substituent effects and their influence on rotational barriers, ligation geometry, and electron deficiency of the metal center.     

Highly Efficient Singlet Oxygen Generators Based on Ruthenium Phthalocyanines: Synthesis,Characterization and in vitro Evaluation for Photodynamic Therapy

The synthesis of ruthenium(II) phthalocyanines (RuPcs) endowed with one carbohydrate unit—that is, glucose, galactose and mannose—and a dimethylsulfoxide (DMSO) ligand at the two axial coordination sites, respectively, is described. Two series of compounds, one unsubstituted at the periphery, and the other one bearing eight PEG chains at the isoindole meta-positions, have been prepared. The presence of the axial DMSO unit significantly increases the phthalocyanine singlet oxygen quantum yields, related to other comparable RuPcs. The compounds have been evaluated for PDT treatment in bladder cancer cells. In vitro studies have revealed high phototoxicity for RuPcs unsubstituted at their periphery. The phototoxicity of PEG-substituted RuPcs has been considerably improved by repeated light irradiation. The choice of the axial carbohydrate introduced little differences in the cellular uptake for both series of photosensitizers, but the phototoxic effects were considerably higher for compounds bearing mannose units.     

Three‐Dimensional Branched and Faceted Gold–Ruthenium Nanoparticles: Using Nanostructure to Improve Stability in Oxygen Evolution Electrocatalysis

Achieving stability with highly active Ru nanoparticles for electrocatalysis is a major challenge for the oxygen evolution reaction. As improved stability of Ru catalysts has been shown for bulk surfaces with low‐index facets, there is an opportunity to incorporate these stable facets into Ru nanoparticles. Now, a new solution synthesis is presented in which hexagonal close‐packed structured Ru is grown on Au to form nanoparticles with 3D branches. Exposing low‐index facets on these 3D branches creates stable reaction kinetics to achieve high activity and the highest stability observed for Ru nanoparticle oxygen evolution reaction catalysts. These design principles provide a synthetic strategy to achieve stable and active electrocatalysts.     

Metallomacrocycles with a Difference: Macrocyclic Complexes with Exocyclic Ruthenium(II)‐Containing Domains

The templated synthesis of organic macrocycles containing rings of up to 96 atoms and three 2,2′‐bipyridine (bpy) units is described. Starting with the bpy‐centred ligands 5,5′‐bis[3‐(1,4‐dioxahept‐6‐enylphenyl)]‐2,2′‐bipyridine and 5,5′‐bis[3‐(1,4,7‐trioxadec‐9‐enylphenyl)]‐2,2′‐bipyridine, we have applied Grubbs’ methodology to couple the terminal alkene units of the coordinated ligands in [FeL₃]²⁺ complexes. Hydrogenation and demetallation of the iron(II)‐containing macrocyclic complexes results in the isolation of large organic macrocycles. The latter bind {Ru(bpy)₂} units to give macrocyclic complexes with exocyclic ruthenium(II)‐containing domains. The complex [Ru(bpy)₂(L)]²⁺ (isolated as the hexafluorophosphate salt), in which L=5,5′‐bis[3‐(1,4,7,10‐tetraoxatridec‐12‐enylphenyl)]‐2,2′‐bipyridine, undergoes intramolecular ring‐closing metathesis to yield a macrocycle which retains the exocyclic {Ru(bpy)₂} unit. The poly(ethyleneoxy) domains in the latter macrocycle readily scavenge sodium ions, as proven by single‐crystal X‐ray diffraction and atomic absorption spectroscopy data for the bulk sample. In addition to the new compounds, a series of model complexes have been fully characterized, and representative single‐crystal X‐ray structural data are presented for iron(II) and ruthenium(II) acyclic and macrocyclic species.     

Chemical and Photochemical Water Oxidation Catalyzed by Mononuclear Ruthenium Complexes with a Negatively Charged Tridentate Ligand

Two mononuclear ruthenium complexes [RuL(pic)₃] ( 1 ) and [RuL(bpy)(pic)] ( 2 ) (H₂L=2,6‐pyridinedicarboxylic acid, pic=4‐picoline, bpy=2,2′‐bipyridine) have been synthesized and fully characterized. Both complexes could promote water oxidation chemically and photochemically. Compared with other known ruthenium‐based water oxidation catalysts using [Ce(NH₄)₂(NO₃)₆] (Ce^IV) as the oxidant in solution at pH 1.0, complex 1 is one of the most active catalysts yet reported with an initial rate of 0.23 turnover s^?1. Under acidic conditions, the equatorial 4‐picoline in complex 1 dissociates first. In addition, ligand exchange in 1 occurs when the Ru^III state is reached. Based on the above observations and MS measurements of the intermediates during water oxidation by 1 using Ce^IV as oxidant, [RuL(pic)₂(H₂O)]⁺ is proposed as the real water oxidation catalyst.     

(OXO)(Phosphine)Ruthenium(IV) Complexes: Oxygen Atom Transfer in the Oxidation of Olefins,Sulfides, Sulfoxides,and Free Phosphines

Kinetic and mechanistic studies of the oxidation of olefins, sulfides, and sulfoxides by [Ru^IV(bpy)₂(O)- (PR₃)](ClO₄)₂ (bpy = 2,2′-bipyridine; R = ethyl or phenyl) complexes have been conducted in both methylene chloride and acetonitrile. In all cases, the rate law shows a first-order dependence on both the concentration of (oxo)ruthenium(IV) species and the target substrate. In addition, product distributions of substrate oxidation exhibit a strong dependence on both the particular phosphine ligand and the solvent utilized in the experiment. On the basis of labelling experimcnts and kinetic evidence, a mechanism is proposed involving a two-electron, oxygen atom insertion into the target substrate. Notably, an (oxidized substrate)ruthenium(II) complex has been isolated and characterized for the oxidation of styrene by the (oxo)(triethylphosphine)ruthenium(IV) complex, where a cyclic voltammogram of this complex displays one quasi-reversible Ru(III)/Ru(II) couple with an E_1/2 = 1.24 V vs SSCE. Kinetic analysis of styrene oxidation indicates that the formation of benzaldehyde from styrene does not occur simply by two sequential two-electron steps. In this regard, alternative mechanisms are discussed.     

Oxygen‐Sensing Methods in Biomedicine from the Macroscale to the Microscale

Oxygen monitoring has been a topic of exhaustive study given its central role in the biochemistry of life. The ability to quantify the physiological distribution and real‐time dynamics of oxygen from sub‐cellular to macroscopic levels is required to fully understand the mechanisms associated with both normal physiology and disease states. This Review will present the most significant recent advances in the development of oxygen‐sensing materials and techniques, including polarographic, nuclear medicine, magnetic resonance, and optical approaches, that can be applied specifically for the real‐time monitoring of oxygen dynamics in cellular and tissue environments. As some of the most exciting recent advances in synthetic methods and biomedical applications have been in the field of optical oxygen sensors, a major focus will be on the development of these toolkits.     

Structure–Reactivity Relationships in the Hydrogenation of Carbon Dioxide with Ruthenium Complexes Bearing Pyridinylazolato Ligands

Pyridinylazolato (N–N′) ruthenium(II) complexes of the type [(N–N′)RuCl(PMe₃)₃] have been obtained in high yields by treating the corresponding functionalised azolylpyridines with [RuCl₂(PMe₃)₄] in the presence of a base. ¹⁵N NMR spectroscopy was used to elucidate the electronic influence of the substituents attached to the azolyl ring. The findings are in agreement with slight differences in the bond lengths of the ruthenium complexes. Furthermore, the electronic nature of the azolate moiety modulates the catalytic activity of the ruthenium complexes in the hydrogenation of carbon dioxide under supercritical conditions and in the transfer hydrogenation of acetophenone. DFT calculations were performed to shed light on the mechanism of the hydrogenation of carbon dioxide and to clarify the impact of the electronic nature of the pyridinylazolate ligands.