Parameterization of Water Electrooxidation Catalyzed by Metal Oxides Using Fourier Transformed Alternating Current Voltammetry

Detection and quantification of redox transformations involved in water oxidation electrocatalysis is often not possible using conventional techniques. Herein, use of large amplitude Fourier transformed ac voltammetry and comprehensive analysis of the higher harmonics has enabled us to access the redox processes responsible for catalysis. An examination of the voltammetric data for water oxidation in borate buffered solutions (pH 9.2) at electrodes functionalized with systematically varied low loadings of cobalt (CoO_<i>x</i>), manganese (MnO_<i>x</i>), and nickel oxides (NiO_<i>x</i>) has been undertaken, and extensive experiment-simulation comparisons have been introduced for the first time. Analysis shows that a single redox process controls the rate of catalysis for Co and Mn oxides, while two electron transfer events contribute in the Ni case. We apply a “molecular catalysis” model that couples a redox transformation of a surface-confined species (effective reversible potential, <i>E</i>_eff⁰) to a catalytic reaction with a substrate in solution (pseudo-first-order rate constant, <i>k</i>₁^f), accounts for the important role of a Brønsted base, and mimics the experimental behavior. The analysis revealed that <i>E</i>_eff⁰ values for CoO_<i>x</i>, MnO_<i>x</i>, and NiO_<i>x</i> lie within the range 1.9–2.1 V vs reversible hydrogen electrode, and <i>k</i>₁^f varies from 2 × 10³ to 4 × 10⁴ s^–1. The <i>k</i>₁^f values are much higher than reported for any water electrooxidation catalyst before. The <i>E</i>_eff⁰ values provide a guide for in situ spectroscopic characterization of the active states involved in catalysis by metal oxides

Synthesis, Spectroscopic Properties, and Photoinduced CO-Release Studies of Functionalized Ruthenium(II) Polypyridyl Complexes: Versatile Building Blocks for Development of CORM–Peptide Nucleic Acid Bioconjugates

A series of ruthenium­(II) dicarbonyl complexes of formula [RuCl₂(L)­(CO)₂] (L = bpy^CH3,CH3 = 4,4′-dimethyl-2,2′-bipyridine, bpy^CH3,CHO = 4′-methyl-2,2′-bipyridine-4-carboxyaldehyde, bpy^CH3,COOH = 4′-methyl-2,2′-bipyridine-4-carboxylic acid, CppH = 2-(pyridin-2-yl)­pyrimidine-4-carboxylic acid, dppzcH = dipyrido­[3,2-a:2′,3′-c]­phenazine-11-carboxylic acid), and [RuCl­(L)­(CO)₂]⁺ (L = tpy^COOH = 6-(2,2′:6′,2″-terpyridine-4′-yloxy)­hexanoic acid) has been synthesized. In addition, a high-yield synthesis of a peptide nucleic acid (PNA) monomer containing the 2-(pyridin-2-yl)­pyrimidine ligand was also developed, and this compound was used to prepare the first Ru­(II) dicarbonyl complex, [RuCl₂(Cpp-L-PNA)­(CO)₂],(Cpp-L-PNA = <i>tert</i>-butyl-<i>N</i>-[2-(<i>N</i>-9-fluorenylmethoxycarbonyl)­aminoethyl]-<i>N</i>-[6-(2-(pyridin-2-yl)­pyrimidine-4-carboxamido)­hexanoyl]­glycinate) attached to a PNA monomer backbone. Such metal-complex PNA–bioconjugates are attracting profound interest for biosensing and biomedical applications. Characterization of all complexes has been undertaken by IR and NMR spectroscopy, mass spectrometry, elemental analysis, and UV–vis spectroscopy. Investigation of the CO-release properties of the Ru­(II) complexes in water/dimethyl sulfoxide (49:1) using the myoglobin assay showed that they are stable under physiological conditions in the dark for at least 60 min and most of them even for up to 15 h. In contrast, photoinduced CO release was observed upon illumination at 365 nm, the low-energy shoulder of the main absorption maximum centered around 300 nm, establishing these compounds as a new class of PhotoCORMs. While the two 2,2′-bipyridine complexes release 1 equiv of CO per mole of complex, the terpyridine, 2-(2′-pyridyl)­pyrimidine, and dipyrido­[3,2-a:2′,3′-c]­phenazine complexes are less effective CO releasers. Attachment of the 2-(2′-pyridyl)­pyrimidine complex to a PNA backbone as in [RuCl₂(Cpp-L-PNA)­CO₂] did not significantly change the spectroscopic or CO-release properties compared to the parent complex. Thus, a novel class of Ru­(II)-based PhotoCORMs has been established which can be coupled to carrier delivery vectors such as PNA to facilitate cellular uptake without loss of the inherent CORM properties of the parent compound

Synthesis, Spectroscopic Properties, and Photoinduced CO-Release Studies of Functionalized Ruthenium(II) Polypyridyl Complexes: Versatile Building Blocks for Development of CORM–Peptide Nucleic Acid Bioconjugates

A series of ruthenium­(II) dicarbonyl complexes of formula [RuCl₂(L)­(CO)₂] (L = bpy^CH3,CH3 = 4,4′-dimethyl-2,2′-bipyridine, bpy^CH3,CHO = 4′-methyl-2,2′-bipyridine-4-carboxyaldehyde, bpy^CH3,COOH = 4′-methyl-2,2′-bipyridine-4-carboxylic acid, CppH = 2-(pyridin-2-yl)­pyrimidine-4-carboxylic acid, dppzcH = dipyrido­[3,2-a:2′,3′-c]­phenazine-11-carboxylic acid), and [RuCl­(L)­(CO)₂]⁺ (L = tpy^COOH = 6-(2,2′:6′,2″-terpyridine-4′-yloxy)­hexanoic acid) has been synthesized. In addition, a high-yield synthesis of a peptide nucleic acid (PNA) monomer containing the 2-(pyridin-2-yl)­pyrimidine ligand was also developed, and this compound was used to prepare the first Ru­(II) dicarbonyl complex, [RuCl₂(Cpp-L-PNA)­(CO)₂],(Cpp-L-PNA = <i>tert</i>-butyl-<i>N</i>-[2-(<i>N</i>-9-fluorenylmethoxycarbonyl)­aminoethyl]-<i>N</i>-[6-(2-(pyridin-2-yl)­pyrimidine-4-carboxamido)­hexanoyl]­glycinate) attached to a PNA monomer backbone. Such metal-complex PNA–bioconjugates are attracting profound interest for biosensing and biomedical applications. Characterization of all complexes has been undertaken by IR and NMR spectroscopy, mass spectrometry, elemental analysis, and UV–vis spectroscopy. Investigation of the CO-release properties of the Ru­(II) complexes in water/dimethyl sulfoxide (49:1) using the myoglobin assay showed that they are stable under physiological conditions in the dark for at least 60 min and most of them even for up to 15 h. In contrast, photoinduced CO release was observed upon illumination at 365 nm, the low-energy shoulder of the main absorption maximum centered around 300 nm, establishing these compounds as a new class of PhotoCORMs. While the two 2,2′-bipyridine complexes release 1 equiv of CO per mole of complex, the terpyridine, 2-(2′-pyridyl)­pyrimidine, and dipyrido­[3,2-a:2′,3′-c]­phenazine complexes are less effective CO releasers. Attachment of the 2-(2′-pyridyl)­pyrimidine complex to a PNA backbone as in [RuCl₂(Cpp-L-PNA)­CO₂] did not significantly change the spectroscopic or CO-release properties compared to the parent complex. Thus, a novel class of Ru­(II)-based PhotoCORMs has been established which can be coupled to carrier delivery vectors such as PNA to facilitate cellular uptake without loss of the inherent CORM properties of the parent compound

Vertically Aligned Interlayer Expanded MoS₂ Nanosheets on a Carbon Support for Hydrogen Evolution Electrocatalysis

This work describes the facile microwave synthesis of interlayer expanded, nanosized MoS₂ sheets that are vertically aligned on a well-conducting reduced graphene (rGO) support, as confirmed by X-ray diffraction, Raman and X-ray photoelectron spectroscopy, scanning electron microscopy with energy dispersive X-ray analysis, and high-resolution transmission electron microscopy. Such structure has been predicted to be highly favorable for efficient electrocatalysis of hydrogen evolution by MoS₂ but could not be achieved until now. Films deposited from the microwave-synthesized MoS₂-rGO composites demonstrate outstanding and stable hydrogen evolution performance in acidic solution. These catalysts exhibit an exchange current density as high as 1.0 ± 0.2 A g^–1_MoS2‑rGO, sustain a current density of 10 mA cm^–2 (36 A g^–1_MoS2‑rGO) at an overvoltage of 0.104 ± 0.002 V, and maintain steady performance for many hours. Importantly, our simple synthesis affords several advantages over more sophisticated methods used previously to prepare MoS₂ catalysts

Studies of Carbon Monoxide Release from Ruthenium(II) Bipyridine Carbonyl Complexes upon UV-Light Exposure

The UV-light-induced CO release characteristics of a series of ruthenium­(II) carbonyl complexes of the form <i>trans</i>-Cl­[RuLCl₂(CO)₂] (L = 4,4′-dimethyl-2,2′-bipyridine, 4′-methyl-2,2′-bipyridine-4-carboxylic acid, or 2,2′-bipyridine-4,4′-dicarboxylic acid) have been elucidated using a combination of UV–vis absorbance and Fourier transform infrared spectroscopies, multivariate curve resolution alternating least-squares analysis, and density functional theory calculations. In acetonitrile, photolysis appears to proceed via a serial three-step mechanism involving the sequential formation of [RuL­(CO)­(CH₃CN)­Cl₂], [RuL­(CH₃CN)₂Cl₂], and [RuL­(CH₃CN)₃Cl]⁺. Release of the first CO molecule occurs quickly (<i>k</i>₁ ≫ 3 min^–1), while release of the second CO molecule proceeds at a much more modest rate (<i>k</i>₂ = 0.099–0.17 min^–1) and is slowed by the presence of electron-withdrawing carboxyl substituents on the bipyridine ligand. In aqueous media (1% dimethyl sulfoxide in H₂O), the two photodecarbonylation steps proceed much more slowly (<i>k</i>₁ = 0.46–1.3 min^–1 and <i>k</i>₂ = 0.026–0.035 min^–1, respectively) and the influence of the carboxyl groups is less pronounced. These results have implications for the design of new light-responsive CO-releasing molecules (“photoCORMs”) intended for future medical use

Electrochemiluminescent Monomers for Solid Support Syntheses of Ru(II)-PNA Bioconjugates: Multimodal Biosensing Tools with Enhanced Duplex Stability

The feasibility of devising a solid support mediated approach to multimodal Ru­(II)-peptide nucleic acid (PNA) oligomers is explored. Three Ru­(II)-PNA-like monomers, [Ru­(bpy)₂(Cpp-L-PNA-OH)]²⁺ (<b>M1</b>), [Ru­(phen)₂(Cpp-L-PNA-OH)]²⁺ (<b>M2</b>), and [Ru­(dppz)₂(Cpp-L-PNA-OH)]²⁺ (<b>M3</b>) (bpy = 2,2′-bipyridine, phen = 1,10-phenanthroline, dppz = dipyrido­[3,2-<i>a</i>:2′,3′-<i>c</i>]­phenazine, Cpp-L-PNA-OH = [2-(<i>N</i>-9-fluorenylmethoxycarbonyl)­aminoethyl]-<i>N</i>-[6-(2-(pyridin-2yl)­pyrimidine-4-carboxamido)hexanoyl]-glycine), have been synthesized as building blocks for Ru­(II)-PNA oligomers and characterized by IR and ¹H NMR spectroscopy, mass spectrometry, electrochemistry and elemental analysis. As a proof of principle, <b>M1</b> was incorporated on the solid phase within the PNA sequences H-g-c-a-a-t-a-a-a-a-Lys-NH₂ (<b>PNA1</b>) and H-P-K-K-K-R-K-V-g-c-a-a-t-a-a-a-a-lys-NH₂ (<b>PNA4</b>) to give <b>PNA2</b> (H-g-c-a-a-t-a-a-a-a-<i><b>M1</b></i>-lys-NH₂) and <b>PNA3</b> (H-P-K-K-K-R-K-V-g-c-a-a-t-a-a-a-a-<i><b>M1</b></i>-lys-NH₂), respectively. The two Ru­(II)-PNA oligomers, <b>PNA2</b> and <b>PNA3</b>, displayed a metal to ligand charge transfer (MLCT) transition band centered around 445 nm and an emission maximum at about 680 nm following 450 nm excitation in aqueous solutions (10 mM PBS, pH 7.4). The absorption and emission response of the duplexes formed with the cDNA strand (<b>DNA</b>: 5′-T-T-T-<b>T-T-T-T-A-T-T-G-C</b>-T-T-T-3′) showed no major variations, suggesting that the electronic properties of the Ru­(II) complexes are largely unaffected by hybridization. The thermal stability of the <b>PNA·DNA</b> duplexes, as evaluated from UV melting experiments, is enhanced compared to the corresponding nonmetalated duplexes. The melting temperature (<i>T</i>_m) was almost 8 °C higher for <b>PNA2·DNA</b> duplex, and 4 °C for <b>PNA3·DNA</b> duplex, with the stabilization attributed to the electrostatic interaction between the cationic residues (Ru­(II) unit and positively charged lysine/arginine) and the polyanionic DNA backbone. In presence of tripropylamine (TPA) as co-reactant, <b>PNA2</b>, <b>PNA3</b>, <b>PNA2·DNA</b> and <b>PNA3·DNA</b> displayed strong electrochemiluminescence (ECL) signals even at submicromolar concentrations. Importantly, the combination of spectrochemical, thermal and ECL properties possessed by the Ru­(II)-PNA sequences offer an elegant approach for the design of highly sensitive multimodal biosensing tools

Phosphodiester Cleavage Properties of Copper(II) Complexes of 1,4,7-Triazacyclononane Ligands Bearing Single Alkyl Guanidine Pendants

Three new metal-coordinating ligands, L¹·4HCl [1-(2-guanidinoethyl)-1,4,7-triazacyclononane tetrahydrochloride], L²·4HCl [1-(3-guanidinopropyl)-1,4,7-triazacyclononane tetrahydrochloride], and L³·4HCl [1-(4-guanidinobutyl)-1,4,7-triazacyclononane tetrahydrochloride], have been prepared via the selective N-functionalization of 1,4,7-triazacyclononane (tacn) with ethylguanidine, propylguanidine, and butylguanidine pendants, respectively. Reaction of L¹·4HCl with Cu­(ClO₄)₂·6H₂O in basic aqueous solution led to the crystallization of a monohydroxo-bridged binuclear copper­(II) complex, [Cu₂L¹₂(μ-OH)]­(ClO₄)₃·H₂O (<b>C1</b>), while for L² and L³, mononuclear complexes of composition [Cu­(L²H)­Cl₂]­Cl·(MeOH)_0.5·(H₂O)_0.5 (<b>C2</b>) and [Cu­(L³H)­Cl₂]­Cl·(DMF)_0.5·(H₂O)_0.5 (<b>C3</b>) were crystallized from methanol and DMF solutions, respectively. X-ray crystallography revealed that in addition to a tacn ring from L¹ ligand, each copper­(II) center in <b>C1</b> is coordinated to a neutral guanidine pendant. In contrast, the guanidinium pendants in <b>C2</b> and <b>C3</b> are protonated and extend away from the Cu­(II)–tacn units. Complex <b>C1</b> features a single μ-hydroxo bridge between the two copper­(II) centers, which mediates strong antiferromagnetic coupling between the metal centers. Complexes <b>C2</b> and <b>C3</b> cleave two model phosphodiesters, <i>bis</i>(<i>p</i>-nitrophenyl)­phosphate (BNPP) and 2-hydroxypropyl-<i>p</i>-nitrophenylphosphate (HPNPP), more rapidly than <b>C1</b>, which displays similar reactivity to [Cu­(tacn)­(OH₂)₂]²⁺. All three complexes cleave supercoiled plasmid DNA (pBR 322) at significantly faster rates than the corresponding <i>bis</i>(alkylguanidine) complexes and [Cu­(tacn)­(OH₂)₂]²⁺. The high DNA cleavage rate for <b>C1</b> {<i>k</i>_obs = 1.30 (±0.01) × 10^–4 s^–1 vs 1.23 (±0.37) × 10^–5 s^–1 for [Cu­(tacn)­(OH₂)₂]²⁺ and 1.58 (±0.05) × 10^–5 s^–1 for the corresponding <i>bis</i>(ethylguanidine) analogue} indicates that the coordinated guanidine group in <b>C1</b> may be displaced to allow for substrate binding/activation. Comparison of the phosphate ester cleavage properties of complexes <b>C1</b>–<b>C3</b> with those of related complexes suggests some degree of cooperativity between the Cu­(II) centers and the guanidinium groups

Synthesis, Characterization, and Biological Evaluation of New Ru(II) Polypyridyl Photosensitizers for Photodynamic Therapy

Two Ru­(II) polypyridyl complexes, Ru­(DIP)₂(bdt) (<b>1</b>) and [Ru­(dqpCO₂Me)­(ptpy)]²⁺ (<b>2</b>) (DIP = 4,7-diphenyl-1,10-phenanthroline, bdt = 1,2-benzenedithiolate, dqpCO₂Me = 4-methylcarboxy-2,6-di­(quinolin-8-yl)­pyridine), ptpy = 4′-phenyl-2,2′:6′,2″-terpyridine) have been investigated as photosensitizers (PSs) for photodynamic therapy (PDT). In our experimental settings, the phototoxicity and phototoxic index (PI) of <b>2</b> (IC₅₀(light): 25.3 μM, 420 nm, 6.95 J/cm²; PI >4) and particularly of <b>1</b> (IC₅₀(light): 0.62 μM, 420 nm, 6.95 J/cm²; PI: 80) are considerably superior compared to the two clinically approved PSs porfimer sodium and 5-aminolevulinic acid. Cellular uptake and distribution of these complexes was investigated by confocal microscopy (<b>1</b>) and by inductively coupled plasma mass spectrometry (<b>1</b> and <b>2</b>). Their phototoxicity was also determined against the Gram-(+) Staphylococcus aureus and Gram-(−) Escherichia coli for potential antimicrobial PDT (aPDT) applications. Both complexes showed significant aPDT activity (420 nm, 8 J/cm²) against Gram-(+) (S. aureus; >6 log₁₀ CFU reduction) and, for <b>2</b>, also against Gram-(−) E. coli (>4 log₁₀ CFU reduction)

Molecular and Cellular Characterization of the Biological Effects of Ruthenium(II) Complexes Incorporating 2‑Pyridyl-2-pyrimidine-4-carboxylic Acid

A great majority of the Ru complexes currently studied in anticancer research exert their antiproliferative activity, at least partially, through ligand exchange. In recent years, however, coordinatively saturated and substitutionally inert polypyridyl Ru­(II) compounds have emerged as potential anticancer drug candidates. In this work, we present the synthesis and detailed characterization of two novel inert Ru­(II) complexes, namely, [Ru­(bipy)₂(Cpp-NH-Hex-COOH)]²⁺ (<b>2</b>) and [Ru­(dppz)₂(CppH)]²⁺ (<b>3</b>) (bipy = 2,2′-bipyridine; CppH = 2-(2′-pyridyl)­pyrimidine-4-carboxylic acid; Cpp-NH-Hex-COOH = 6-(2-(pyridin-2-yl)­pyrimidine-4-carboxamido)­hexanoic acid; dppz = dipyrido­[3,2-<i>a</i>:2′,3′-<i>c</i>]­phenazine). <b>3</b> is of particular interest as it was found to have IC₅₀ values comparable to cisplatin, a benchmark standard in the field, on three cancer cell lines and a better activity on one cisplatin-resistant cell line than cisplatin itself. The mechanism of action of <b>3</b> was then investigated in detail and it could be demonstrated that, although <b>3</b> binds to calf-thymus DNA by intercalation, the biological effects that it induces did not involve a nuclear DNA related mode of action. On the contrary, confocal microscopy colocalization studies in HeLa cells showed that <b>3</b> specifically targeted mitochondria. This was further correlated by ruthenium quantification using High-resolution atomic absorption spectrometry. Furthermore, as determined by two independent assays, <b>3</b> induced apoptosis at a relatively late stage of treatment. The generation of reactive oxygen species could be excluded as the cause of the observed cytotoxicity. It was demonstrated that the mitochondrial membrane potential in HeLa was impaired by <b>3</b> as early as 2 h after its introduction and even more with increasing time

Molecular and Cellular Characterization of the Biological Effects of Ruthenium(II) Complexes Incorporating 2‑Pyridyl-2-pyrimidine-4-carboxylic Acid

A great majority of the Ru complexes currently studied in anticancer research exert their antiproliferative activity, at least partially, through ligand exchange. In recent years, however, coordinatively saturated and substitutionally inert polypyridyl Ru­(II) compounds have emerged as potential anticancer drug candidates. In this work, we present the synthesis and detailed characterization of two novel inert Ru­(II) complexes, namely, [Ru­(bipy)₂(Cpp-NH-Hex-COOH)]²⁺ (<b>2</b>) and [Ru­(dppz)₂(CppH)]²⁺ (<b>3</b>) (bipy = 2,2′-bipyridine; CppH = 2-(2′-pyridyl)­pyrimidine-4-carboxylic acid; Cpp-NH-Hex-COOH = 6-(2-(pyridin-2-yl)­pyrimidine-4-carboxamido)­hexanoic acid; dppz = dipyrido­[3,2-<i>a</i>:2′,3′-<i>c</i>]­phenazine). <b>3</b> is of particular interest as it was found to have IC₅₀ values comparable to cisplatin, a benchmark standard in the field, on three cancer cell lines and a better activity on one cisplatin-resistant cell line than cisplatin itself. The mechanism of action of <b>3</b> was then investigated in detail and it could be demonstrated that, although <b>3</b> binds to calf-thymus DNA by intercalation, the biological effects that it induces did not involve a nuclear DNA related mode of action. On the contrary, confocal microscopy colocalization studies in HeLa cells showed that <b>3</b> specifically targeted mitochondria. This was further correlated by ruthenium quantification using High-resolution atomic absorption spectrometry. Furthermore, as determined by two independent assays, <b>3</b> induced apoptosis at a relatively late stage of treatment. The generation of reactive oxygen species could be excluded as the cause of the observed cytotoxicity. It was demonstrated that the mitochondrial membrane potential in HeLa was impaired by <b>3</b> as early as 2 h after its introduction and even more with increasing time