Ruthenium Center Research Articles

Tetratellura[36]octaphyrin(1.1.1.1.1.1.1.1) Metalation: From Dynamic Behavior to Rigid Chiral Figure-of-Eight Molecule; Activation of the C-Te Bond by Ruthenium.

The large expanded telluraporphyrin, tetratellura[36]octaphyrin(1.1.1.1.1.1.1.1), was synthesized in 7% yield by acid-catalyzed condensation of pyrrole with 2,5-bis(phenylhydroxymethyl)tellurophene and subsequent oxidation. The macrocycle acquires the chiral figure-eight conformation with two alternative spatial arrangements of the heterocyclic rings. The molecule exhibits dynamic behavior in solution, which was studied by means of 1H NMR spectroscopy. The reaction with chlorine led to a reversible oxidative addition at two distant tellurium atoms, which altered the preferred conformations. Metalation of the tetratellura[36]octaphyrin with triruthenium dodecacarbonyl selectively activated two of the eight Te-C bonds, resulting in the formation of an organometallic diruthenium compound. During the reaction, two tellurophene rings were converted to 1-ruthena-2-telluracyclohexadiene units containing octahedral ruthenium(II) centers. The rigid structure of this chiral complex allowed the separation of enantiomers.

Highly Enantiomerically Enriched Secondary Alcohols via Epoxide Hydrogenolysis.

In this article, we report the development of ruthenium-catalyzed hydrogenolysis of epoxides to selectively give the branched (Markovnikov) alcohol products. In contrast to previously reported catalysts, the use of Milstein's PNN-pincer-ruthenium complex at room temperature allows the conversion of enantiomerically enriched epoxides to secondary alcohols without racemization of the product. The catalyst is effective for a range of aryl epoxides, alkyl epoxides, and glycidyl ethers and is the first homogeneous system to selectively promote hydrogenolysis of glycidol to 1,2-propanediol, without loss of enantiomeric purity. A detailed mechanistic study was conducted, including experimental observations of catalyst speciation under catalytically relevant conditions, comprehensive kinetic characterization of the catalytic reaction, and computational analysis via density functional theory. Heterolytic hydrogen cleavage is mediated by the ruthenium center and exogenous alkoxide base. Epoxide ring opening occurs through an opposite-side attack of the ruthenium hydride on the less-hindered epoxide carbon, giving the branched alcohol product selectively.

Coumarin-modified ruthenium complexes: Synthesis, characterization, and antiproliferative activity against human cancer cells.

Among ruthenium complexes studied as anticancer metallodrugs, NKP-1339, NAMI-A, RM175, and RAPTA-C have already entered clinical trials due to their potent antitumor activity demonstrated in preclinical studies and reduced toxicity in comparison with platinum drugs. Considering the advantages of ruthenium-based anticancer drugs and the cytostatic activity of organometallic complexes with triazole- and coumarin-derived ligands, we set out to synthesize Ru(II) complexes of coumarin-1,2,3,-triazole hybrids (L) with the general formula [Ru(L)(p-cymene)(Cl)]ClO4. The molecular structure of the complex [Ru(2a)(p-cymene)(Cl)]ClO4 (2aRu) was determined by single-crystal X-ray diffraction, which confirmed the coordination of the ligand to the central ruthenium(II) cation by bidentate mode of coordination. Coordination with Ru(II) resulted in the enhancement of cytostatic activity in HepG2 hepatocellular carcinoma cells and PANC-1 pancreatic cancer cells. Coumarin derivative 2a positively regulated the expression and activity of c-Myc and NPM1 in RKO colon carcinoma cells, while the Ru(II) half-sandwich complex 2cRu induced downregulation of AKT and ERK signaling in PANC-1 cells concomitant with reduced intracellular levels of reactive oxygen species. Altogether, our findings indicated that coumarin-modified half-sandwich Ru(II) complexes held potential as anticancer agents against gastrointestinal malignancies.

Grubbs-Hoveyda catalysts conjugated to a β-barrel protein: Effect of halide substitution on aqueous olefin metathesis activity

The effect of halide substitution in Grubbs-Hoveyda II catalysts (GHII catalysts) embedded in the engineered β-barrel protein nitrobindin (NB4exp) on metathesis activity in aqueous media was studied. Maleimide tagged dibromido and diiodido derivates of the GHII catalyst were synthesized and covalently conjugated to NB4exp. The biohybrid catalysts were characterized spectroscopically confirming the structural integrity. When the two chloride substituents at ruthenium center were exchanged against bromide and iodide, the diiodo derivative was found to show significantly higher catalytic activity in ring-closing metathesis of α,ω-diolefins, whereas the dibromido derivative was less efficient when compared with the parent dichlorido catalyst. Using the diiodido catalyst, high turnover numbers of up to 75 were observed for ring-closing metathesis (RCM) yielding unsaturated six- and seven-membered N-heterocycles.

Borate ligand derived from CS2 unveiling ruthenium dithioformate and trithia-borinane complexes

The reactivity of κ2-N,S-chelated ruthenium borate complexes, [Ph3P(κ2-N,S-L)Ru{κ3-H,S,S′-H2B(L)2}], (L = C5H4NS, C7H4NS2) 1 and 3 with borate ligand derived from CS2 has been investigated. The thermolysis of [Ph3P(κ2-N,S-C5H4NS)Ru{κ3-H,S,S′-H2B(C5H4NS)2}], 1 with Na[BH3(SCHS)] led to the formation of ruthenium dithioformate complexes, [PPh3(κ3-H,S,S′-H2B(C5H4NS)}Ru{(η2-SCHS)}], trans-2 and [PPh3(κ3-H,S,S′-H2B(C5H4NS)}Ru{(η2-SCHS)}], cis-2. Further, to study the reactivity of the same borate ligand derived from CS2, we have performed the reaction of [Ph3P(κ2-N,S-C7H4NS2)Ru{κ3-H,S,S′-H2B(C7H4NS2)2}], 3 with Na[BH3(SCHS)] that yielded ruthenium dithioformate, [Ph3P(κ2-N,S-C5H4NS)Ru{(η2-SCHS)}], cis-4 and 1,3,5-trithia-2-borinane, [PPh3Ru{κ3-H,S,S′-H2B(NC7H4S2)2}]{(SCH2)2SBH}], 5 complexes. All these studies show that cis-4 is analogous to trans-2 and cis-2. The solid-state X-ray structure of 5 shows that the ruthenium center is stabilized by diborate, phosphine and six-membered ruthenacycle [RuSBNCS] ring that is fused with a {C2S3B} ring. The synthesized complexes have been thoroughly characterized by various spectroscopic techniques and single-crystal X-ray diffraction analysis of trans-2, cis-2 and 5. Density functional theory (DFT) calculations further provided an insight into the electronic structures of the complexes.

Air-Stable Coordinatively Unsaturated Ruthenium(II) Complex for Ligand Binding and Catalytic Transfer Hydrogenation of Ketones from Ethanol.

Coordinatively unsaturated complexes are interesting from a fundamental level for their formally empty coordination site and, in particular, from a catalytic perspective as they provide opportunities for substrate binding and transformation. Here, we describe the synthesis of a novel underligated ruthenium complex [Ru(cym)(N,N')]+, 3, featuring an amide-functionalized pyridylidene amide (PYA) as the N,N'-bidentate coordinating ligand. In contrast to previously investigated underligated complexes, complex 3 offers potential for dynamic modifications, thanks to the flexible donor properties of the PYA ligand. Specifically, they allow both for stabilizing the formally underligated metal center in complex 3 through nitrogen π-donation and for facilitating through π-acidic bonding properties the coordination of a further ligand L to the ruthenium center to yield the formal 18 e- complexes [Ru(cym)(N,N')(L)]+ (4: L = P(OMe)3; 5: L = PPh3; 6: L = N-methylimidazole; 7: L = pyridine) and neutral complex [RuCl(cym)(N,N')] 8. Analysis by 1H NMR and UV-vis spectroscopies reveals an increasing Ru-L bond strength along the sequence pyridine <1-methylimidazole < PPh3 < P(OMe)3 with binding constants varying over 3 orders of magnitude with log(Keq) values between 2.8 and 5.7. The flexibility of the Ru(PYA) unit and the ensuing accessibility of saturated and unsaturated species with one and the same ligand are attractive from a fundamental point of view and also for catalytic applications, as catalytic transformations rely on the availability of transiently vacant coordination sites. Thus, while complex 3 does not form stable adducts with O-donors such as ketones or alcohols, it transiently binds these species, as evidenced by the considerable catalytic activity in the transfer hydrogenation of ketones. Notably, and as one of only a few catalysts, complex 3 is compatible with EtOH as a hydrogen source. Complex 3 shows excellent performance in the transfer hydrogenation of pyridyl-containing substrates, in agreement with the poor coordination strength of this functional group to the ruthenium center in 3.

Selenosalicylate; a little-studied heavy-element analogue of the versatile thiosalicylate ligand.

Selenosalicylic acid (ortho-HSeC6H4CO2H), the heavy element congener of the widely studied thiosalicylic acid, was prepared by reaction of 2-carboxybenzenediazonium chloride (HO2CC6H4N2+Cl-) with Na2Se2, followed by reduction of the resulting diselenide (SeC6H4CO2H)2 with zinc and acetic acid. The coordination chemistry of the selenosalicylate ligand towards a variety of platinum(ii), palladium(ii), nickel(ii), gold(iii), gold(i), rhodium(iii), iridium(iii) and ruthenium(ii) centres was explored. X-ray crystal structure determinations were carried out on the complexes [Pt(SeC6H4CO2)(PPh3)2], [{(p-cym)Ru(SeC6H4CO2)}2] (p-cym = η6-p-cymene, CH3C6H4CH(CH3)2), [{Cp*Rh(SeC6H4CO2)}2] (Cp* = η5-C5Me5) and [Cp*Ir(SeC6H4CO2)(PPh3)], and comparisons are made with corresponding thiosalicylate complexes. The complexes were characterised by NMR spectroscopy as well as ESI mass spectrometry, which indicated a greater propensity for fragmentation including by selenium loss, compared to the thiosalicylate analogues. Hirshfeld surface analysis to visualise and quantify intermolecular interactions revealed the dominance of H⋯H contacts in [{(p-cym)Ru(SeC6H4CO2)}2] and [Cp*Ir(SeC6H4CO2)(PPh3)].

Binding modes of a flexible ruthenium polypyridyl complex to DNA.

Ruthenium(II) polypyridyl complexes are attractive binders to DNA. Modifying the hydrophobicity, shape, or size of the ancillary ligands around the central ruthenium atom can induce changes in the binding mode to the DNA double helix. In this paper, we investigate the binding modes of [Ru(2,2'-bipyridine)2 (5-{4-[(pyren-1-yl)methyl]-1H-1,2,3-triazol-4-yl}-1,10-phenanthroline)]2+ (RuPy for short), a metal complex featuring a flexible pyrene moiety known for its intercalative properties. Classical molecular dynamics simulations are employed to gain insight into the non-covalent binding interactions of RuPy with two different 20 base pair DNA sequences, poly(dA)poly(dT) (AT) and poly(dC)poly(dG) (CG). In addition to examining the intercalation of the pyrene moiety from the major groove, the stability of RuPy-DNA adducts is investigated when the metal complex interacts externally with the DNA and with the major and minor groove pockets. The results indicate that external interaction and major groove binding are not stable, whereas intercalation consistently forms stable adducts. Minor groove binding showed less stability than intercalation and more variability, with some trajectories transitioning to intercalation, involving either the pyrene moiety or a bipyridine ligand. Pyrene intercalation, especially from the minor groove, was the most stable, while bipyridine intercalation was less favorable and associated with higher binding free energies.

Binding of Stimuli-Responsive Ruthenium Aqua Complexes with 9-Ethylguanine.

Stimuli-responsive ruthenium complexes proximal- and distal-[Ru(C10tpy)(C10pyqu) OH2]2+ (proximal-1 and distal-1; C10tpy = 4'-decyloxy-2,2':6',2″-terpyridine and C10pyqu = 2-[2'-(6'-decyloxy)-pyridyl]quinoline) were experimentally studied for adduct formation with a model DNA base. At 303 K, proximal-1 exhibited 1:1 adduct formation with 9-ethylguanine (9-EtG) to yield proximal-[Ru(C10tpy)(C10pyqu)(9-EtG)]2+ (proximal-RuEtG). Rotation of the guanine ligand on the ruthenium center was sterically hindered by the presence of an adjacent quinoline moiety at 303 K. Results from 1H NMR measurements indicated that photoirradiation of a proximal-RuEtG solution caused photoisomerization to distal-RuEtG, whereas heating of proximal-RuEtG caused ligand substitution to proximal-1. The distal isomer of the aqua complex, distal-1, was observed to slowly revert to proximal-1 at 303 K. In the presence of 9-EtG, distal-1 underwent thermal back-isomerization to proximal-1 and adduct formation to distal-RuEtG. Kinetic analysis of 1H NMR measurements showed that adduct formation between proximal-1 and 9-EtG was 8-fold faster than that between distal-1 and 9-EtG. This difference may be attributed to intramolecular hydrogen bonding and steric repulsion between the aqua ligand and the pendant moiety of the bidentate ligand..

Cyclization, Decyclization, and Metallacyclization of Pyridine-Substituted Homopropargylic Alcohols on Ruthenium(II) and Osmium(II) Centers.

Systematic investigations on the reactions between cis-[M(dppm)2 Cl2 ] (M=Ru/Os; dppm=1,1-bis(diphenylphosphino)methane) and pyridine/quinoline substituted homopropargylic alcohols uncovered the diverse Ru(II)/Os(II)-induced alkyne activation pathways. The alkynes underwent cyclization on M via a "non-vinylidene" pathway at lower temperatures, resulting in alkenyl intermediates which might further metallacyclize to give metallapyrroloindolizines. Conversely, reactions at higher temperatures induced alkyne cyclization on M via a "vinylidene" pathway, affording cyclic oxacarbene complexes. Additionally, a rare decyclization mechanism was observed during the transformation of a metallacyclization-resistant alkenyl complex into a cyclic oxacarbene complex. DFT calculations were employed to validate the experimental findings. Overall, these results not only provide insights into controlling alkyne activation pathways, but also offer new strategies for preparing metalated heterocyclic and metallacyclic complexes.

Molecular structure of Ru(II)/diphosphine/4,6-dimethyl-2-pyrimidinethiol complexes: A combined experimental and density functional theory study

Reactions of cis-[RuCl2(P-P)(bipy)] precursors with the SpymMe2 ligand (4,6-dimethyl-2-pyrimidinethiol) yielded complexes of the [Ru(SpymMe2)(P-P)(bipy)]PF6 type, where P-P = 1,2-bis(diphenylphosphino)ethane (dppe - for complex 1), 1,3-bis(diphenylphosphino)propane (dppp - for complex 2) and 1,1’-bis(diphenylphosphino)ferrocene (dppf - for complex 3) and bipy = 2,2’-bipyridine. The new compounds were obtained by displacing the chlorido ligands from the precursors and coordination of one monoanionic 4,6-dimethyl-2-pyrimidinethiol ligand. All complexes were characterized by spectroscopic, electrochemical and elemental analysis techniques, as well as single-crystal X-ray diffraction, where the structures of complexes 1, 2 and 3 showed that the SpymMe2 ligand coordinates to the ruthenium(II) center as bidentated, yielding complexes with the sulfur atom trans positioned to the nitrogen atom from the bipy ligand. A theoretical study of the structures of the complexes was performed using the DFT/B3LYP method. Distances and angles of optimized structures agree with X-ray experimental data. Furthermore, the calculated IR and UV-Vis spectra are compatible with experimental data. Charge decomposition analysis (CDA) and NBO (natural bond orbitals) charges showed that there was an overall charge transfer from bipy and P-P ligands to the ruthenium centers. Higher electrochemical stability and 1H and 31P{1H} NMR shifts of 1, 2 and 3 compared with precursors could be explained by the lower values of calculated molecular orbital energies, NBO charge on atoms and CDA data. Finally, the structure of the isomers of complexes 1, 2 and 3, considering the sulfur atom trans positioned to the phosphorus atom, were optimized, showing that they are slightly less stable, presenting total energy higher, 10.4, 31.5 and 60.5 kJ/mol than 1, 2 and 3, where nitrogen is trans to the phosphorus atom.

Plugging the 3MC Sink in RuII‐Based Photocatalysts

AbstractQuantum chemical methods have been utilised to explore the kinetics and thermodynamics of a prominent charge recombination pathway in a series of RuII based molecular photocatalysts. Selective tuning of the RuII coordination sphere, replacing the tbbpy ligands of the hydrogen evolving parent photocatalyst with electron rich, biimidazole based ligands, promotes unidirectional charge transfer towards the bridging ligand during initial photoexcitation. These electronic effects are also significant in the triplet manifold, where the predicted rate of the undesired deactivation process from the 3MLCT state on the bridging ligand to a 3MC state on the ruthenium centre, is decreased relative to the parent complex, by 1–2 orders of magnitude, alongside a decrease in electronic coupling. This design methodology could be utilised to promote targeted (light‐driven) electron transfer pathways, as well as to potentially reduce 3MC deactivation pathways in commonly used polypyridyl‐based RuII photocentres, thus enhancing the quantum efficiency of light driven catalysis.

Sequestration of Ruthenium Residues via Efficient Fluorous-enyne Termination.

The creation of polymers without metal contamination remains a significant challenge for metathesis-based polymerization techniques and has complicated applications in biomedical and electronic applications. This communication reports a new approach for the removal of ruthenium byproducts through the design of an enyne terminator for metathesis polymerization that contains a fluorous tag. Upon reaction of a living polymer chain with the enyne, the ruthenium center is captured as a stable sulfur-chelated complex that can be efficiently removed after a single filtration through a fluorous cartridge. Levels of ruthenium residues as determined by ICP-MS were found to depend on the monomer structure, eluting solvent, and the degree of polymerization targeted. Ruthenium residues were minimized to low ppm levels (4-75 ppm) for most samples examined and also led to the improved thermal stability of the final materials. This represents the most efficient single method for removal of ruthenium residues from metathesis polymerization products.

Synthesis and characterization of CIS-[Ru(DPPM)2(BTA)]PF6 (BTA– = 4,4,4-trifluoro-1-phenyl-1,3-butanedionate)

The title complex cis-[Ru(dppm)2(bta)]PF6, dppm = 1,1-bis(diphenylphosphino)methane; bta– = 4,4,4-trifluoro-1-phenyl-1,3-butanedionate, was prepared from the cis-[RuCl2(dppm)2] precursor in mild conditions. Elemental analysis, spectroscopy (FTIR, 1H, 31P{1H} and 19F{1H} NMR) as well as single-crystal X-ray diffraction were used to characterize the new complex. Electronic structure of the complex was described utilizing TD-DFT analysis. All data indicate a good degree of purity, a cis arrangement for the diphosphines and a distorted geometry for the ruthenium center.

A Lock-and-Kill Anticancer Photoactivated Chemotherapy Agent†.

Photosubstitutionally active ruthenium complexes show high potential as prodrugs for the photoactivated chemotherapy (PACT) treatment of tumors. One of the problems in PACT is that the localization of the ruthenium compound is hard to trace. Here, a ruthenium PACT prodrug, [Ru(3)(biq)(STF-31)](PF6 )2 (where 3=3-(([2,2':6',2″-ter- pyridin]-4'-yloxy)propyl-4-(pyren-1-yl)butanoate) and biq=2,2'-biquinoline), has been prepared, in which a pyrene tracker is attached via an ester bond. The proximity between the fluorophore and the ruthenium center leads to fluorescence quenching. Upon intracellular hydrolysis of the ester linkage, however, the fluorescence of the pyrene moiety is recovered, thus demonstrating prodrug cellular uptake. Further light irradiation of this molecule liberates by photosubstitution STF-31, a known cytotoxic nicotinamide phosphoribosyltransferase (NAMPT) inhibitor, as well as singlet oxygen via excitation of the free pyrene chromophore. The dark and light cytotoxicity of the prodrug, embedded in liposomes, as well as the appearance of blue emission upon uptake, were evaluated in A375 human skin melanoma cells. The cytotoxicity of the liposome-embedded prodrug was indeed increased by light irradiation. This work realizes an invitro proof-of-concept of the lock-and-kill principle, which may ultimately be used to design strategies aimed at knowing where and when light irradiation should be realized invivo.

Self‐assembled Ru(bda) Coordination Oligomers as Efficient Catalysts for Visible Light‐Driven Water Oxidation in Pure Water

AbstractWater‐soluble multinuclear complexes based on ruthenium 2,2′‐bipyridine‐6,6′‐dicarboxylate (bda) and ditopic bipyridine linker units are investigated in three‐component visible light‐driven water oxidation catalysis. Systematic studies revealed a strong enhancement of the catalytic efficiency in the absence of organic co‐solvents and with increasing oligomer length. In‐depth kinetic and morphological investigations suggest that the enhanced performance is induced by the self‐assembly of linear Ru(bda) oligomers into aggregated superstructures. The obtained turnover frequencies (up to 14.9 s−1) and turnover numbers (more than 1000) per ruthenium center are the highest reported so far for Ru(bda)‐based photocatalytic water oxidation systems.

Self-assembled Ru(bda) Coordination Oligomers as Efficient Catalysts for Visible Light-Driven Water Oxidation in Pure Water.

Water-soluble multinuclear complexes based on ruthenium 2,2'-bipyridine-6,6'-dicarboxylate (bda) and ditopic bipyridine linker units are investigated in three-component visible light-driven water oxidation catalysis. Systematic studies revealed a strong enhancement of the catalytic efficiency in the absence of organic co-solvents and with increasing oligomer length. In-depth kinetic and morphological investigations suggest that the enhanced performance is induced by the self-assembly of linear Ru(bda) oligomers into aggregated superstructures. The obtained turnover frequencies (up to 14.9 s-1 ) and turnover numbers (more than 1000) per ruthenium center are the highest reported so far for Ru(bda)-based photocatalytic water oxidation systems.

Synthesis, Characterization, and Cytotoxicity Studies of N-(4-Methoxybenzyl) Thiosemicarbazone Derivatives and Their Ruthenium(II)-p-cymene Complexes.

The reaction of [Ru2Cl2(μ-Cl)2(η6-p-cymene)2] with two thiosemicarbazones obtained by the condensation of N-(4-methoxybenzyl) thiosemicarbazide and 1,4-hydroxy-3-methoxyphenyl)ethan-1-one (HL1) or 2-fluoro-4-hydroxybenzaldehyde (HL2) was studied. The cationic complexes of formula [RuCl(η6-p-cymene)(HL)]+ were isolated as solid chloride and trifluoromethylsulfate (TfO) salts. A study of the solid state and NMR spectra suggests the presence in the material of two isomers that differ in the configuration in the iminic bond, C2=N3, of the coordinated thiosemicarbazone in the triflate salts and only the E isomer in the chloride. An X-ray study of single crystals of the complexes supports this hypothesis. The thiosemicarbazone ligand coordinates with the ruthenium center through the iminic and sulfur atoms to form a five-membered chelate ring. Furthermore, the isolation of single crystals containing the thiosemicarbazonate complex [Ru2(μ-L2)2(η6-p-cymene)2]2+ suggests the easy labilization of the coordinated chloride in the complex. The redox behavior of the ligands and complexes was evaluated by cyclic voltammetry. It seems to be more difficult to oxidize the complex derived from HL1 than HL2. The ability of the complexes to inhibit cell growth against the NCI-H460, A549 and MDA-MB-231 lines was evaluated. The complexes did not show greater potency than cisplatin, although they did have greater efficacy, especially for the complex derived from HL1.

Ruthenium Complexes Bearing Bis‐N‐heterocyclic Carbene Donors in TiO2 Sensitization for Dye‐Sensitized Solar Cells

AbstractThis report presents ruthenium (II) complexes featuring bis‐imidazole‐2‐ylidene donors and carboxylic acid‐functionalized terpyridine ligands (tpy−COOH or tpy4′−phenyl−COOH). We introduced the monodentate −NCS or pyridine carboxylate ligands into the coordination sphere to render sizeable changes in photo‐functional attributes. The coordination of the thiocyanate ligands to these ruthenium centers extends their absorption tails up to 800 nm. In contrast, the absorption bands of complexes featuring isonicotinic acid last only until 600 nm. Even though phenyl spacers at the acceptor end rendered a bathochromic shift in the λmax, in their absence, complexes exhibited a longer electron lifetime at the TiO2 photoanode. The complexes devoid of phenyl spacers show lower charge transfer resistance at the TiO2/electrolyte interface giving improved photon conversion efficiency (PCE) in Dye‐Sensitized Solar Cells (DSSCs). Herein, we analyze the relationship between the structure and the light‐harvesting efficiency via a combined experimental and computational approach.

Hydration of Nitriles Catalyzed by Ruthenium Complexes: Role of Dihydrogen Bonding Interactions in Promoting Base-Free Catalysis.

Ru(II) complexes of amide-phosphine-based tridentate ligands additionally containing pyridine, isoquinoline, and quinoline rings have been synthesized, and their catalytic utility for the selective hydration of nitriles to amides is explored under the base-containing as well as base-free conditions. The chloride-ligated complexes 1-3 exhibited significant catalytic activity in the presence of a base, whereas hydride-ligated complexes 4-6 carried out the hydration of nitrile without the requirement of any base. The mechanistic studies revealed the involvement of [Ru-H] species as the active catalyst in the catalytic cycle. The [Ru-H] species assisted in the polarization of an incoming water molecule through [Ru-H···H-OH] dihydrogen bonding interaction and consequently aided in the attack of a positioned water molecule to a nitrile coordinated to a ruthenium center. Substrate binding studies and kinetic experiments further supported the mechanism. A wide variety of aromatic nitriles containing both electron-withdrawing and electron-releasing groups as well as other substrates including aliphatic nitriles, base-sensitive nitriles, and a few biologically relevant nitriles were employed for the selective hydration.