Cellular Mechanistic Considerations on Cytotoxic Mode of Action of Phosphino Ru(II) and Ir(III) Complexes

Two piano-stool ruthenium(II) complexes Ru(η⁶-p-cymene)Cl₂PPh₂CH₂OH ( RuPOH ) and Ru(η⁶-p-cymene)Cl₂P(p-OCH₃Ph)₂CH₂OH ( RuMPOH ) and two half-sandwich iridium(III) complexes Ir(η ⁵-Cp*)Cl₂PPh₂CH₂OH ( IrPOH ) and Ir(η ⁵-Cp*)Cl₂P(p-OCH₃Ph)₂CH₂OH ( IrMPOH ) have been studied in terms of potential anticancer activity on previously selected cell line (human lung adenocarcinoma). Based on experimental results obtained in monoculture in vitro model mechanistic considerations on the possible cellular modes of action have been carried out. ICP-MS analysis revealed the higher cellular uptake for less hydrophobic Ir(III) complexes in comparison to the corresponding Ru(II) compounds. Cytometric analysis showed a predominance of apoptosis over the other types of cell death for all complexes. The apoptotic pathway was confirmed by a decrease in mitochondrial membrane potential and the activation of caspases-3/9 for both Ru(II) and Ir(III) complexes. It was concluded that in the case of Ru(II) complexes the intense ROS generation is mainly responsible for the resulting cytotoxicity. The corresponding Ir(III) complexes trigger simultaneously at least three different cytotoxic pathways i. e., depletion of mitochondrial potential, activation of caspases-dependent apoptosis, and ROS-associated oxidation. Thus, it can be assumed that the final accumulation of toxic effects over time via parallel activation of different pathways results in the highest cytotoxicity in vitro exhibited by Ir(III) complexes when compared with Ru(II) complexes.     

Synthesis and Characterization of Ru(II) Complexes with π-Expansive Imidazophen Ligands for the Photokilling of Human Melanoma Cells

Ru(II) complexes were synthesized with π-expanding (phenyl, fluorenyl, phenanthrenyl, naphthalen-1-yl, naphthalene-2-yl, anthryl and pyrenyl groups) attached at a 1H-imidazo[4,5-f][1,10]phenanthroline ligand and 4,4′-dimethyl-2,2′-bipyridine (4,4′-dmb) coligands. These Ru(II) complexes were characterized by 1D and 2D NMR, and mass spectroscopy, and studied for visible light and dark toxicity to human malignant melanoma SK-MEL-28 cells. In the SK-MEL-28 cells, the Ru(II) complexes are highly phototoxic (EC₅₀ = 0.2–0.5 µm ) and have low dark toxicity (EC₅₀ = 58–230 µm ). The highest phototherapeutic index (PI) of the series was found with the Ru(II) complex bearing the 2-(pyren-1-yl)-1H-imidazo[4,5-f][1,10]phenanthroline ligand. This high PI is in part attributed to the π-rich character added by the pyrenyl group, and a possible low-lying and longer-lived ³IL state due to equilibration with the ³MLCT state. While this pyrenyl Ru(II) complex possessed a relatively high quantum yield for singlet oxygen formation (Φ_∆ = 0.84), contributions from type-I processes (oxygen radicals and radical ions) are competitive with the type-II (¹O₂) process based on effects of added sodium azide and solvent deuteration.     

Synthesis of polypyridyl ruthenium complexes with 2-(1-aryl)-1H-imidazo[4,5-f]-1,10-phenanthroline ligand and its application for luminescent oxygen sensing

Polypyridyl ruthenium (Ru) complexes 1–3 were prepared. Their photophysical properties were investigated by UV-Vis absorption and luminescence emission spectra. The luminescent lifetimes of these Ruthenium complex were prolonged by more than 5 folds (τ = 2.50 μs for complex 3) when compared with the parent Ru complex 1 (τ = 0.45 μs). We propose that the extended luminescent lifetime of complex 3 is due to the equilibrium between ³MLCT state and the pyrene localized ³π-π* triplet state (³IL). The luminescent O₂-sensing property of the complexes in solution and the IMPEK-C polymer film were studied, and the O₂ sensing was quantified with the two-site model. The oxygen-sensing property of the Ru complexes can be improved by 104-fold with extension of the luminescent lifetimes. For example, the quenching constant K _SV was improved from 0.0023 Torr⁻¹ of 1 to 0.2393 Torr⁻¹ for 3. Our results demonstrated a versatile approach for the preparation of Ru (II) polypyridine complexes with extended luminescent lifetimes as functional materials, for example, for luminescent oxygen-sensing applications.     

DNA Interaction,DNA Photocleavage,Photocytotoxicity In Vitro,and Molecular Docking of Naphthyl-Appended Ruthenium Complexes

With the development of metal-based drugs, Ru(II) compounds present potential applications of PDT (photodynamic therapy) and anticancer reagents. We herein synthesized two naphthyl-appended ruthenium complexes by the combination of the ligand with naphthyl and bipyridyl. The DNA affinities, photocleavage abilities, and photocytotoxicity were studied by various spectral methods, viscosity measurement, theoretical computation method, gel electrophoresis, and MTT method. Two complexes exhibited strong interaction with calf thymus DNA by intercalation. Production of singlet oxygen (¹O₂) led to obvious DNA photocleavage activities of two complexes under 365 nm light. Furthermore, two complexes displayed obvious photocytotoxicity and low dark cytotoxicity towards Hela, A549, and A375 cells.     

Asymmetric transfer hydrogenation of ketones using Ru(0) nanoparticles modified by Chiral Thiones

The catalytic asymmetric transfer hydrogenation (ATH) of acetophenone in isopropanol by Ru(0) nanoparticles (NPs) obtained by the in‐situ reduction of Ru (II) half‐sandwich complexes of chiral 2‐oxazolidinethiones and 2‐thiozolidinethiones was examined and compared with the catalytic activity of Ru(0) NPs formed in‐situ by the reduction of [Ru(p‐cymene)(Cl)₂]₂ in presence of optically active ligands such as (S)‐4‐isobutylthiazolidine‐2‐thione, (S)‐4‐Isopropyl‐2(?2‐pyridinyl)‐2‐oxazoline, (8S, 9R)‐(?)‐cinchonidine, (S)‐leucinol, (S)‐phenylalaninol, and (S)‐leucine. Three of the best catalytic systems were then examined for ATH of thirteen aromatic ketones with different electronic and steric properties. A maximum of 24% ee was obtained using NPs generated from the Ru (II) half‐sandwich complex with (S)‐4‐isobutylthiazolidine‐2‐thione in the TH of acetophenone. The NPs were characterized by TEM and DLS measurements. Kinetic studies and poisoning experiments confirmed that the reaction is catalyzed by the chiral NPs formed in‐situ. Complete characterization of the complexes, including the X‐ray crystallographic characterization of two complexes, was also carried out.     

Half-sandwich ruthenium(II)-arene complexes: synthesis,spectroscopic studies,biological properties,and molecular modeling

In search for antitumor metal-based drugs that would mitigate the severe side-effects of cisplatin, Ru(II) complexes are gaining increasing recent interest. In this work, we report on the synthesis, characterization (¹H- and ¹³C-NMR, FT-IR), and cytotoxicity studies of two new half-sandwich organometallic Ru(II) complexes of the general formula [Ru(η⁶-arene)(XY)Cl](PF₆) where arene?=?benzene or toluene and XY?=?bidentates: dipyrido[3,2-a:2′,3′-c]phenazine (dppz) or 2-(9-anthryl)-1H-imidazo[4,5-f][1,10]phenanthroline (aip), which are bound to Ru(II) via two phenanthroline-N atoms in a characteristic “piano-stool” configuration of Ru(II)-arene complexes—as confirmed by vibrational and NMR spectra. In addition, cytotoxic studies were performed for similar half-sandwich organometallic [Ru(η⁶-p-cymene)(Me₂dppz)Cl]PF₆ complex (Me₂dppz = 11,12-dimethyl-dipyrido[3,2-a:2′,3′-c]phenazine). This study is complemented with elaborate modeling with density functional theory (DFT) calculations, which provided insight into reactive sites of Ru(II) structures, further detailed by molecular docking on the B-DNA dodecamer, which identified binding sites and affinities: most pronounced for the [Ru(η⁶-benzene)(aip)Cl](PF₆) in both A-T and G-C regions of the DNA minor groove. Cytotoxic activity was probed versus tumor cell lines B16, C6, and U251 (B16 mouse melanoma, C6 rat glioma, U251 human glioblastoma) and non-tumor cell line HACAT (HACAT normal human keratinocytes).     

Application of new Ru (II) pyridine-based complexes in the partial oxidation of n-octane

Tridentate and bidentate Ru (II) complexes were prepared through reaction of four pyridine-based ligands: pyCH₂N(R)CH₂py {R = propyl, tert-butyl, cyclohexyl and phenyl; py = pyridine} with the [(η⁶-C₆H₆)Ru(μ-Cl)Cl]₂ dimer. Crystal structures of the new terdentate Ru (II) complexes [Ru{pyCH₂N(R)CH₂py}C₆H₆](PF₆)₂ (R = C₃H₇ ( 1 ), C (CH₃)₃ ( 2 ), C₆H₁₁ ( 3 ) and the bidentate Ru (II) complex [Ru{pyCH₂N(R)}C₆H₆]PF₆ (R = C₆H₅ ( 4 )) are reported. It was found that complexes 1, 2 , 3 and 4 crystallised as mono-metallic species, with a piano stool geometry around each Ru centre. All complexes were active in the selective oxidation of n-octane using t-BuOOH and H₂O₂ as oxidants. Complexes 2 and 4 reached a product yield of 12% with t-BuOOH as oxidant, however, superior yields (23–32%) were achieved using H₂O₂ over all systems. The selectivity was predominantly towards alcohols (particularly 2-octanol) over all complexes using t-BuOOH and H₂O₂ after reduction of the formed alkylhydroperoxides in solution by PPh₃. High TONs of up to 2400 were achieved over the Ru/H₂O₂ systems.     

Heteroleptic ruthenium bioflavonoid complexes: from synthesis to in vitro biological activity

Heteroleptic ruthenium(II) bioflavonoid complexes of quercetin, morin, chrysin, and 3-hydroxyflavone were prepared and their interaction with CT DNA and BSA along with antioxidant and in vitro anticancer and antimicrobial activities was investigated. The formulation and characterization of complexes were achieved through elemental and thermal analysis, mass spectrometry, ¹H NMR spectroscopy along with infrared, electronic absorption, and emission spectroscopy as well as square-wave voltammetry, and magnetic and conductivity measurements. Ruthenium(II) is octahedrally coordinated in cationic complex species to two bidentate diimine ligands (2,2′-bipyridine or 1,10-phenanthroline) and one bidentate monobasic flavonoid ligand through 3,4-site of quercetin, morin, and 3-hydroxyflavone or 4,5-site of chrysin. Complexes bind CT DNA by intercalation and binding constants comparable to ethidium bromide or 10 times higher. Binding constants of complexes to BSA were several times higher compared to ibuprofen and diazepam, and suggest that the complexes have a strong affinity to BSA. Antioxidant activity tests showed that the complexes are more potent in terms of radical inhibition compared to the parent flavonoids. Cytotoxic testing revealed that the Ru(II) complex of quercetin with 2,2′-bipyridine co-ligand has good selectivity to breast adenocarcinoma, while the complex of 3-hydroxyflavone with 2,2′-bipyridine co-ligand showed strong cytotoxicity toward all tested cell lines with IC₅₀ ～ 1 μM. All complexes showed moderate activity toward Acinetobacter baumannii, while the Ru(II) complex of 3-hydroxyflavone with 2,2′-bipyridine showed excellent activity toward MRSA and Candida albicans.     

In Vitro Photodynamic Inactivation Effects of Ru(II) Complexes on Clinical Methicillin‐resistant Staphylococcus aureus Planktonic and Biofilm Cultures

Photosensitizers (PSs) combined with light are able to generate antimicrobial effects. Ru(II) complexes have been recognized as a novel class of PSs. In this study, we investigated the effectiveness of photodynamic inactivation (PDI) mediated by three Ru(II) polypyridine complexes, 1–3, against four isolates of clinical methicillin‐resistant Staphylococcus aureus (MRSA‐1, MRSA‐2, MRSA‐3 and MRSA‐4). In PDI of a planktonic culture of MRSA‐1, compound 3 showed the highest efficacy, likely owing to its advantageous light absorption, ¹O₂ quantum yield and bacterial cellular binding. The PDI efficacy of 3 was further evaluated against all other strains and MRSA‐1 biofilms. At appropriate PS concentrations, viability reduction of 100% or 96.83% was observed in planktonic or biofilm forms of MRSA, respectively. The mechanisms of action were investigated using negative staining transmission electron microscopy (TEM), confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM). It was demonstrated that PDI of planktonic bacteria was achieved primarily through damage to the cell envelope. Biofilms were eliminated through both the destruction of their structure and inactivation of the individual bacterial cells. In conclusion, Ru(II) complexes, especially 3, are potential candidates for the effective photodynamic control of MRSA infections.     

Anticancer Activity of Hydrogen‐Bond‐Stabilized Half‐Sandwich RuII Complexes with Heterocycles

Neutral half‐sandwich organometallic ruthenium(II) complexes of the type [(η⁶‐cymene)RuCl₂(L)] ( H1 – H10 ), where L represents a heterocyclic ligand, have been synthesized and characterized spectroscopically. The structures of five complexes were also established by single‐crystal X‐ray diffraction confirming a piano‐stool geometry with η⁶ coordination of the arene ligand. Hydrogen bonding between the N? H group of the heterocycle and a chlorine atom attached to Ru stabilizes the metal–ligand interaction. Complexes coordinated to a mercaptobenzothiazole framework ( H1 ) or mercaptobenzoxazole ( H6 ) showed high cytotoxicity against several cancer cells but not against normal cells. In vitro studies have shown that the inhibition of cancer cell growth involves primarily G1‐phase arrest as well as the generation of reactive oxygen species (ROS). The complexes are found to bind DNA in a non‐intercalative fashion and cause unwinding of plasmid DNA in a cell‐free medium. Surprisingly, the cytotoxic complexes H1 and H6 differ in their interaction with DNA, as observed by biophysical studies, they either cause a biphasic melting of the DNA or the inhibition of topoisomerase IIα activity, respectively. Substitution of the aromatic ring of the heterocycle or adding a second hydrogen‐bond donor on the heterocycle reduces the cytotoxicity.     

Ruthenium(II) complexes of pyrrol-azo ligands: cytotoxicity,interaction with calf thymus DNA and bovine serum albumin

Two ruthenium(II) complexes of newly designed pyrrol-azo ligands(L) and bipyridine(bpy) formulated as [Ru(L)(bpy)₂]ClO₄, where HL^1?=?(4-chloro-phenyl)-(1H-pyrrol-2-yl)-diazene (1) complex 1 and HL^2?=?(4-nitro-phenyl)-(1H-pyrrol-2-yl)-diazene for 2, were isolated in pure form. The complexes were characterized by physicochemical and spectroscopic methods. The electrochemical behavior of the complexes showed the Ru(III)/Ru(II) couple at different potentials with quasi-reversible voltammograms. The study of cytotoxicity effects of 1 and 2 on human breast cancer cells (MCF 7, MDA-MB 231) and cervical cancer cell (HeLa) taking Cisplatin as a positive reference showed that 1 exhibited higher cytotoxicity against cancer cell lines than 2, but less activity than Cisplatin. The interaction of 1 with calf thymus DNA (CT-DNA) using absorption, emission spectral studies, viscosity-measurement, and electrochemical techniques has been used to determine the binding constant K _b and the linear Stern–Volmer quenching constant K _SV. The results indicate that 1 strongly interacts with CT-DNA in groove binding mode. The interaction of bovine serum albumin (BSA) with 1 was also investigated with the help of spectroscopic tools. Absorption spectroscopy proved the formation of a BSA-[Ru(L¹)(bpy)₂]ClO₄ complex.     

Piano‐stool Ru (II) arene complexes that contain ethylenediamine and application in alpha‐alkylation reaction of ketones with alcohols

A series of piano‐stool Ru (II) complexes ( Ru _1–7 ) bearing ethylenediamine with aryl and aliphatic groups were prepared and fully characterized by ¹H, ¹³C, ¹⁹F and ³¹P NMR spectroscopy, FT‐IR and elemental analysis. The crystal structures of Ru _2–4 and Ru ₇ were determined by X‐ray crystallography. They were successfully applied to the alpha(α)‐alkylation of aliphatic and aromatic ketones with alcohols via the borrowing hydrogen strategy in mild reaction conditions within a short time. The catalytic system has a broad substrate scope, which allows the synthesis of alpha alkylated ketones with excellent yields. The electronic and steric effects of complexes on catalytic activity were analysed. The influence of the carbon chain length of the ligand on the alpha‐alkylation reaction of ketones was also investigated. The catalytic cycle was also examined by ¹H‐NMR spectroscopy in d₈‐toluene.     

A Red‐Light‐Activated Ruthenium‐Caged NAMPT Inhibitor Remains Phototoxic in Hypoxic Cancer Cells

We describe two water‐soluble ruthenium complexes, [ 1 ]Cl₂ and [ 2 ]Cl₂, that photodissociate to release a cytotoxic nicotinamide phosphoribosyltransferase (NAMPT) inhibitor with a low dose (21 J cm⁻²) of red light in an oxygen‐independent manner. Using a specific NAMPT activity assay, up to an 18‐fold increase in inhibition potency was measured upon red‐light activation of [ 2 ]Cl₂, while [ 1 ]Cl₂ was thermally unstable. For the first time, the dark and red‐light‐induced cytotoxicity of these photocaged compounds could be tested under hypoxia (1 % O₂). In skin (A431) and lung (A549) cancer cells, a 3‐ to 4‐fold increase in cytotoxicity was found upon red‐light irradiation for [ 2 ]Cl₂, whether the cells were cultured and irradiated with 1 % or 21 % O₂. These results demonstrate the potential of photoactivated chemotherapy for hypoxic cancer cells, in which classical photodynamic therapy, which relies on oxygen activation, is poorly efficient.     

Simple Synthesis of Ruthenium π Complexes of Aromatic Amino Acids and Small Peptides

The interaction of [Ru(η⁶‐C₁₀H₈)(Cp)]⁺ (Cp=C₅H₅) with aromatic amino acids (L ‐phenylalanine, L ‐tyrosine, L ‐tryptophane, D ‐phenylglycine, and L ‐threo‐3‐phenylserine) under visible‐light irradiation gives the corresponding [Ru(η⁶‐amino acid)(Cp)]⁺ complexes in near‐quantitative yield. The reaction proceeds in air at room temperature in water and tolerates the presence of non‐aromatic amino acids (except those which are sulfur containing), monosaccharides, and nucleotides. The complex [Ru(η⁶‐C₁₀H₈)(Cp)]⁺ was also used for selective labeling of Tyr and Phe residues of small peptides, namely, angiotensin I and II derivatives.     

Syntheses of 3‐arm and 4‐arm star‐branched polystyrene Ru(II) complexes by the click‐to‐chelate approach

Metal template synthesis is a useful methodology to make sophisticated macromolecular architectures because of the variety of metal ion coordination. To use metal template methodology, chelating functionalities should be introduced to macromolecules before complexation. In this article, we demonstrate the click‐to‐chelate approach to install chelating functionality to polystyrene (PS) and complexation with Ru(II) ions to form 3‐arm and 4‐arm star‐branched PS Ru(II) complexes. Azide‐terminated PS (PS‐N₃) was readily prepared by atom transfer radical polymerization using 1‐bromoethylbenzene as an initiator followed by substitution of bromine by an azide group. The Cu(I)‐catalyzed 1,3‐dipolar cycloaddition of PS‐N₃ with 2‐ethynylpyridine or 2,6‐diethynylpyridine affords 2‐(1H‐1,2,3‐triazol‐4‐yl)pyridine (PS‐tapy) or 2,6‐bis(1H‐1,2,3‐triazol‐4‐yl)pyridine (PS‐bitapy) ligands bearing one or two PS chains at the first‐position of the triazole rings. Ru(II) complexes of PS‐tapy and PS‐bitapy were prepared by conventional procedure. The number‐averaged molecular weights (M_ns) of these complexes were determined to be 6740 and 10,400, respectively, by size exclusion chromatography using PS standards. These M_n values indicated the formation of 3‐arm and 4‐arm star‐branched PS Ru(II) complexes [Ru(PS‐tapy)₃](PF₆)₂ and [Ru(PS‐bitapy)₂](PF₆)₂ on the basis of the M_n values of PS‐tapy (2090) and PS‐bitapy (4970). The structures of these complexes were also confirmed by UV–vis spectroscopy and X‐ray crystallography of the Ru(II) complexes [Ru(Bn‐tapy)₃](PF₆)₂ and [Ru(Bn‐bitapy)₂](PF₆)₂, which bear a benzyl group instead of a PS chain. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Synthesis,characterization, and cytotoxic and antimicrobial activities of ruthenium(II) arene complexes with N,N-bidentate ligands

Three new complexes, [(η⁶-C₆H₆)RuCl(C₅H₄N-2-CH=N-Ar)]PF₆ (Ar = phenylmethylene (1), (4-methoxyphenyl)methylene (2), and phenylhydrazone (3)), were prepared by reacting [(η⁶-C₆H₆)Ru(μ-Cl)Cl]₂ with N,N′-bidentate ligands in a 1 : 2 ratio. Full characterization of the complexes was accomplished using ¹H and ¹³C NMR, elemental and thermal analyses, UV–vis and IR spectroscopy and single crystal X-ray structures. Single crystal structures confirmed a pseudo-octahedral three-legged, piano-stool geometry around Ru(II), with the ligand coordinated to the ruthenium(II) through two N atoms. The cytotoxicity of the mononuclear complexes was established against three human cancer cell lines and selectivity was also tested against non-cancerous human epithelial kidney (HEK 293) cells. The compounds were selective toward the tumor cells in contrast to the known anti-cancer drug 5-fluoro uracil which was not selective between the tumor cells and non-tumor cells. All the compounds showed moderate activity against MCF7 (human breast adenocarcinoma), but showed low antiproliferative activity against Caco-2 and HepG2. Also, antimicrobial activities of the complexes were tested against a panel of antimicrobial-susceptible and -resistant Gram-negative and Gram-positive bacteria. Of special interest is the anti-mycobacterial activity of all three synthesized complexes against Mycobacterium smegmatis, and bactericidal activity against resistant Enterococcus faecalis and methicillin-resistant Staphylococcus aureus ATCC 43300.     

4-Vinylbenzyl-substituted silver(I) N-heterocyclic carbene complexes and ruthenium(II) N-heterocyclic carbene complexes: synthesis and transfer hydrogenation of ketones

4-Vinylbenzyl-substituted Ag(I) N-heterocyclic carbene (NHC) complexes and Ru(II) NHC complexes have been synthesized. The Ag(I) complexes were synthesized from the imidazolium salts and Ag₂O in dichloromethane at room temperature. The Ru(II) complexes were prepared from Ag(I) NHC complexes by transmetallation. The six 4-Vinylbenzyl-substituted Ag(I) NHC complexes and six 4-Vinylbenzyl-substituted Ru(II) NHC complexes have been characterized by spectroscopic techniques and elemental analyses. The Ru(II) NHC complexes show catalytic activity for the transfer hydrogenation of ketones.     

Synthesis,characterization, and antitumor properties of ruthenium(II) anthraquinone complexes

Three new Ru(II) complexes, [Ru(dmb)₂(ipad)](ClO₄)₂ (dmb = 4,4′-dimethyl-2,2′-bipyridine, ipad = 2-(anthracene-9,10-dione-2-yl) imidazo[4,5-f][1,10]phenanthroline, 1), [Ru(dmp)₂(ipad)](ClO₄)₂ (dmp = 2,9-dimethyl-1,10-phenanthroline, 2), and [Ru(dip)₂(ipad)](ClO₄)₂ (dip = 4,7-diphenyl-1,10-phenanthroline, 3), have been synthesized and characterized. The three Ru(II) complexes intercalate with the base pairs of DNA. The in vitro antiproliferative activities and apoptosis-inducing characteristics of these complexes were investigated. The complexes exhibited cytotoxicity against various human cancer cell lines. BEL-7402 cells displayed the highest sensitivity to 1, accounted for by the greatest cellular uptake. Complex 1 was shown to accumulate preferentially in the nuclei of BEL-7402 cells and cause DNA damage and induce apoptosis, which involved cell cycle arrest and reactive oxygen species generation.     

Interpretation of the Electronic Spectra of Ruthenium Nitrosyl Complexes with Nitrogen-containing Heterocyclic Ligands

The electronic absorption spectra of ruthenium nitrosyl complexes with nitrogen-containing heterocyclic ligands were analyzed on the basis of ab initio and CINDO/CI semiempirical calculations of free ligands L and complexes trans-[Ru(NO)(NH₃)₄(L)]^{3 +} (L = pyridine, pyrazine, nicotinamide, isonicotinamide, l-histidine, imidazole). Spectral manifestations of a strong covalent Ru-NO bond were observed to conclude that the oxidation states of Ru and NO in the RuNO^{3 +} group are expedient to represent as Ru(III) and NO⁰. Introduction of a nitrosyl group into the inner coordination sphere of Ru(II) complexes with nitrogen-containing heterocyclic ligands much affects the entire spectral patterns and denudes these ligands of the capacity to exhibit chromophoric properties.     

Switching the Mechanism of NADH Photooxidation by Supramolecular Interactions

A series of three Ru(II) polypyridine complexes was investigated for the selective photocatalytic oxidation of NAD(P)H to NAD(P)⁺ in water. A combination of (time-resolved) spectroscopic studies and photocatalysis experiments revealed that ligand design can be used to control the mechanism of the photooxidation: For prototypical Ru(II) complexes a ¹O₂ pathway was found. Rudppz ([(tbbpy)₂Ru(dppz)]Cl₂, tbbpy=4,4'-di-tert-butyl-2,2'-bipyridine, dppz=dipyrido[3,2-a:2′,3′-c]phenazine), instead, initiated the cofactor oxidation by electron transfer from NAD(P)H enabled by supramolecular binding between substrate and catalyst. Expulsion of the photoproduct NAD(P)⁺ from the supramolecular binding site in Rudppz allowed very efficient turnover. Therefore, Rudppz permits repetitive selective assembly and oxidative conversion of reduced naturally occurring nicotinamides by recognizing the redox state of the cofactor under formation of H₂O₂ as additional product. This photocatalytic process can fuel discontinuous photobiocatalysis.