Ruthenium Pyrazole Complexes: A Family of Highly Active Metallodrugs for Photoactivated Chemotherapy.

Ruthenium complexes bearing bis pyrazole (pzH) ligands, cis-[Ru(bpy)2(R-pzH)2]2+ (bpy = 2,2'-bipyridine, R = -H, -Cl), were examined as photoactivated anticancer prodrugs. A dicationic pyrazole complex deprotonated to give monocationic pyrazole-pyrazolate complexes, cis-[Ru(bpy)2(R-pz-)(R-pzH)]+, in an aqueous solution with pKa values of 9.5 and 7.2 for R = H and R = Cl, respectively. Upon deprotonation, relative quantum yields of photosubstitution decreased while lipophilicity of the complexes increased according to the measurements of water-octanol coefficients. The ruthenium complex with 4-chloropyrazole ligands displayed high cytotoxicity upon light irradiation (IC50 = 0.060 ± 0.016 µM) toward lung cancer cells, which was 7 times higher than that in the dark (IC50 = 0.44 ± 0.07 µM). Additional experiments for the ruthenium R-pyrazole complexes indicated that (1) selective photodissociation of the 4-chloropyrazole ligand occurs from cis-[Ru(bpy)2(4-Clpz-)(4-ClpzH)]+, (2) photoinduced ligand dissociation is dominant rather than photoinduced generation of singlet oxygen (1O2), and (3) induction of cell death occurs via the intrinsic pathway of apoptosis.

A Synthetic Route to a Ruthenium Complex via Successive Photosubstitution Reactions.

Photosubstitution reactions of cis-[Ru(bpy)2(MeCN)2]2+ with a pyrazole ligand (pzH) were studied under various conditions toward the development of a photochemical synthetic route to polypyridyl ruthenium complexes (bpy = 2,2'-bipyridine). In the absence of a base, light irradiation of an acetonitrile solution of pyrazole and cis-[Ru(bpy)2(MeCN)2]2+ gave a mixture of the reactant and cis-[Ru(bpy)2(pzH)(MeCN)]2+. In the presence of a mild base such as N,N-dimethylaminopyridine, a second photosubstitution from cis-[Ru(bpy)2(pzH)(MeCN)]2+ to cis-[Ru(bpy)2(pz)(pzH)]+ (1b) was greatly enhanced, as confirmed by UV-vis and 1H nuclear magnetic resonance spectroscopy. The yields of 1b were increased in solvents with moderate coordinating properties, such as acetone. The successive photosubstitution reaction was observed using a stoichiometric amount of pyrazole.

A multi-stimuli responsive ruthenium complex for catalytic water oxidation.

A ruthenium complex showing multi-stimuli-responsive isomerization was synthesized. The catalytic activity of this complex toward water oxidation showed responses to visible-light irradiation and heat due to photoisomerization and thermal back-isomerization, respectively. DFT calculations suggested that a pendant moiety in the complex was key to controlling the catalytic activity.

Intramolecular Hydrogen Bonding: A Key Factor Controlling the Photosubstitution of Ruthenium Complexes.

Photosubstitution reactions of ruthenium complexes with pyrazole ligands, cis-[Ru(bpy)2(pzH)2]2+ (1a), cis-[Ru(bpy)2(pz)(pzH)]+ (1b), and cis-[Ru(bpy)2(pz)2]0 (1c) (pzH = pyrazole, bpy = 2,2'-bipyridine), were investigated. Dicationic complex 1a was deprotonated to 1b using moderate base (pKa = 15.2, MeCN), while the second deprotonation to give 1c required more severe conditions (pKa = 26.9). Monocationic complex 1b possessed an N-H···N-type intramolecular hydrogen bond between the pyrazole and pyrazolate ligands, as corroborated by the solid-state crystal structure. The photosubstitution quantum yield of 1a (Φ = 0.26) was comparable to that of cis-[Ru(bpy)2(pyridine)2]2+ (Φ = 0.24) in acetonitrile solution. In contrast, the photodissociation of a pzH ligand was strongly suppressed by the deprotonation of a pyrazole ligand N-H group. In the presence of 10 000 equiv of 4,4'-dimethylaminopyridine, the quantum yield dropped to ∼2 × 10-6 in acetonitrile. The photosubstitution quantum yield of 1b was even smaller than that of neutral complex 1c, although 1c had a smaller HOMO-LUMO energy gap than monocationic complex 1b. The small quantum yield of 1b was attributed to intramolecular hydrogen bonding between pyrazole and pyrazolate ligands. The apparent rate constants for the photosubstitution of 1b were highly solvent-dependent. The photosubstitution of 1b was suppressed in aprotic solvents, while the reaction was accelerated by 2 orders of magnitude in protic solvents with strong proton donor abilities.

Photoisomerization and thermal isomerization of ruthenium aqua complexes with chloro-substituted asymmetric bidentate ligands.

A series of ruthenium complexes with chloro-substituted bidentate ligands, proximal-[Ru(tpy)(Cl-pyqu)L] n+ [n = 1 for L = Cl, and n = 2 for L = OH2, tpy = 2,2';6',2''-terpyridine, pyqu = 2-(2'-pyridyl)quinoline] were synthesized and their reversible photoisomerizations and thermal isomerizations were investigated experimentally. The crystal structures of the complexes indicated that introduction of a chloro substituent at the 4- or 4'-position of the pyqu ligand did not change the structure around the metal center from that of the non-substituted complex, proximal-[Ru(tpy)(pyqu)L] n+. In contrast, the 6'-substituted complexes had sterically hindered environments around the metal center. The ruthenium aqua complexes showed reversible photoisomerization between the proximal and distal isomers. The quantum yield for photoisomerization of the 6'-substituted ruthenium aqua complex was almost twice as large as those of the other derivatives. This is explained by weakening of the ligand field on the ruthenium center by introduction of a chloro substituent at the 6'-position. Thermal back isomerization from the distal isomer to the proximal one was observed for the 6'-substituted complex, but such reactions were not observed for the other derivatives. The steric hindrance in the 6'-substituted aqua complex enhanced both thermal isomerization and photoisomerization.

Mechanistic Insight into Reversible Core Structural Changes of Dinuclear µ-Hydroxoruthenium(II) Complexes with a 2,8-Di-2-pyridyl-1,9,10-anthyridine Backbone Prior to Water Oxidation Catalysis.

proximal,proximal-(p,p)-[RuII2(tpy)2LXY]n+ (tpy = 2,2';6',2″-terpyridine, L = 5-phenyl-2,8-di-2-pyridyl-1,9,10-anthyridine, and X and Y = other coordination sites) yields the structurally and functionally unusual RuII(µ-OH)RuII core, which is capable of catalyzing water oxidation with key water insertion to the core (Inorg. Chem. 2015, 54, 7627). Herein, we studied a sequence of bridging-ligand substitution among p,p-[Ru2(tpy)2L(µ-Cl)]3+ (Ru2(µ-Cl)), p,p-[Ru2(tpy)2L(µ-OH)]3+ (Ru2(µ-OH)), p,p-[Ru2(tpy)2L(OH)(OH2)]3+ (Ru2(OH)(OH2)), and p,p-[Ru2(tpy)2L(OH)2]2+ (Ru2(OH)2) in aqueous solution. Ru2(µ-Cl) converted slowly (10-4 s-1) to Ru2(µ-OH), and further Ru2(µ-OH) converted very slowly (10-6 s-1) to Ru2(OH)(OH2) by the insertion of water to reach equilibrium at pH 8.5-12.3. On the basis of density functional theory (DFT) calculations, Ru2(OH)(OH2) was predicted to be thermodynamically stable by 13.3 kJ mol-1 in water compared to Ru2(µ-OH) because of the specially stabilized core structure by multiple hydrogen-bonding interactions involving aquo, hydroxo, and L backbone ligands. The observed rate from Ru2(µ-OH) to Ru2(OH)2 by the insertion of an OH- ion increased linearly with an increase in the OH- concentration from 10 to 100 mM. The water insertion to the core is very slow (∼10-6 s-1) in aqueous solution at pH 8.5-12.3, whereas the insertion of OH- ions is accelerated (10-5-10-4 s-1) above pH 13.4 by 2 orders of magnitude. The kinetic data including activation parameters suggest that the associative mechanism for the insertion of water to the RuII(µ-OH)RuII core of Ru2(µ-OH) at pH 8.5-12.3 alters the interchange mechanism for the insertion of an OH- ion to the core above pH 13.4 because of relatively stronger nucleophilic attack of OH- ions. The hypothesized p,p-[Ru2(tpy)2L(µ-OH2)]4+ and p,p-[Ru2(tpy)2L(OH2)2]4+ formed by protonation from Ru2(µ-OH) and Ru2(OH)(OH2) were predicted to be unstable by 71.3 and 112.4 kJ mol-1 compared to Ru2(µ-OH) and Ru2(OH)(OH2), respectively. The reverse reactions of Ru2(µ-OH), Ru2(OH)(OH2), and Ru2(OH)2 to Ru2(µ-Cl) below pH 5 could be caused by lowering the core charge by protonation of the µ-OH- or OH- ligand.

Visible-Light-Induced Morphological Changes of Giant Vesicles by Photoisomerization of a Ruthenium Aqua Complex.

Visible- and red-light responsive vesicles were prepared by incorporating a ruthenium aqua complex having two alkyl chains on tridentate and asymmetrical bidentate ligands (proximal-2: [Ru(C10 tpy)(C10 pyqu)OH2 ](2+) , C10 tpy=4'-decyloxy-2,2';6',2"-terpyridine, C10 pyqu=2-[2'-(6'-decyloxy)-pyridyl]quinoline). The ruthenium complex of proximal-2 with closed alkyl chain geometry and a cylinder-like molecular shape exhibited photoisomerization to distal-2 with an open alkyl chain geometry and a cone-like shape, both in an aqueous solution and in vesicle dispersions. We observed that light irradiation of giant vesicles containing proximal-2 induced diverse morphological changes.

Fabrication of Three-Layer-Component Organoclay Hybrid Films with Reverse Deposition Orders by a Modified Langmuir-Schaefer Technique and Their Pyroelectric Currents Measured by a Noncontact Method.

In an aqueous clay mineral (montmorillonite) dispersion at a low concentration, isolated clay nanosheets with negative charges were suspended. When a solution of amphiphilic octadecylammonium chloride (ODAH(+)Cl(-)) was spread on an air-dispersion interface, the clay nanosheets were adsorbed on the ODAH(+) cations at the interface to form a stable ultrathin floating film. The floating film was transferred onto a substrate by the Schaefer method, and then the film was immersed in a [Ru(dpp)3]Cl2 (dpp = 4,7-diphenyl-1,10-phenanthroline) solution. The Ru(II) complex cations were adsorbed on the film surface because the film surface possessed a cation-exchange ability. The layers of ODAH(+), clay nanosheets, and [Ru(dpp)3](2+) were deposited in this order. By repeating these procedures, three-layer-component films were fabricated (OCR films). In a similar way, three-layer-component films in which the layers of [Ru(dpp)3](2+), clay nanosheets, and ODAH(+) were deposited in the reverse order (RCO films) were prepared by spreading a [Ru(dpp)3](ClO4)2 solution and immersing the films in an ODAH(+)Cl(-) solution. Both OCR and RCO films were characterized by surface pressure-molecular area (π-A) curve measurements, IR and visible spectroscopy, and the XRD method. The OCR and RCO film systems possessed nearly the same properties in the densities of ODAH(+) and [Ru(dpp)3](2+) and the tilt angle of the Ru(II) complex cation, although the layer distance for the RCO film was a little longer than that for the OCR film and the layered structure for the RCO film was less ordered than that for the OCR film. Pyroelectric currents for the films were measured by a noncontact method using an (241)Am radioactive electrode. When the films were heated, the pyroelectric currents were observed and the current directions for the OCR and RCO films were different. This was clear evidence that the layer order in the OCR film was reverse of that in the RCO film.

Structure-distortion-induced photomagnetic effect in azobenzene/polyoxometalate Langmuir-Blodgett films.

We have prepared photomagnetic Langmuir-Blodgett films composed of an amphiphilic azobenzene and a magnetic polyoxometalate. The obtained film possesses a well-organized layered structure where polyoxometalate anions are sandwiched by azobenzene cations in a single-layered manner. Reversible photoisomerization of azobenzene was achieved even at low temperature, accompanying intensity changes in the d-d transition of polyoxometalate anions. The photomagnetic effect was observed reversibly upon alternate UV and visible light irradiation. Based on polarized spectroscopy, the observed photomagnetic effect is ascribed to the structure-distortion of polyoxometalate layers.

Surface potential studies on adsorption processes of clay nanosheets onto a floating molecular film of an amphiphilic alkylammonium cation.

A floating molecular film was formed when a chloroform solution of dimethyldioctadecylammonium bromide (DMDOA(+)Br(-)) was spread on an aqueous dispersion of a clay mineral (sodium montmorillonite). At a low concentration (<50 ppm: ppm = mg dm(-3)), a clay mineral was exfoliated into negatively charged layers (denoted by clay nanosheets). Clay nanosheets in a dispersion were adsorbed onto a floating film because of electrostatic interactions. At various clay concentrations (0-50 ppm), surface potential was measured as a function of time to obtain the quantitative information about the adsorption of clay nanosheets on a condensed floating film of DMDOA(+) ions. It was concluded that the adsorption equilibrium obeyed the Langmuir adsorption isotherm, which was supported by the atomic force microscopy (AFM) observation. The rate constants of adsorption and desorption processes were determined by the fitting analyses based on the Langmuir type kinetics. Interestingly, the delay of the adsorption was observed in the early stage indicating that clay nanosheets were removed from the surface region through the repulsion by a counteranion (Br(-)). This explanation was supported by the model simulation using the forward difference method.

Surface nano-architecture of a metal-organic framework.

The rational assembly of ultrathin films of metal-organic frameworks (MOFs)--highly ordered microporous materials--with well-controlled growth direction and film thickness is a critical and as yet unrealized issue for enabling the use of MOFs in nanotechnological devices, such as sensors, catalysts and electrodes for fuel cells. Here we report the facile bottom-up fabrication at ambient temperature of such a perfect preferentially oriented MOF nanofilm on a solid surface (NAFS-1), consisting of metalloporphyrin building units. The construction of NAFS-1 was achieved by the unconventional integration in a modular fashion of a layer-by-layer growth technique coupled with the Langmuir-Blodgett method. NAFS-1 is endowed with highly crystalline order both in the out-of-plane and in-plane orientations to the substrate, as demonstrated by synchrotron X-ray surface crystallography. The proposed structural model incorporates metal-coordinated pyridine molecules projected from the two-dimensional sheets that allow each further layer to dock in a highly ordered interdigitated manner in the growth of NAFS-1. We expect that the versatility of the solution-based growth strategy presented here will allow the fabrication of various well-ordered MOF nanofilms, opening the way for their use in a range of important applications.

Preparation of Langmuir-Blodgett films of aligned sepiolite fibers and orientation of methylene blue molecules adsorbed on the film.

Sepiolite is a clay mineral with a fibrous morphology; the fibers possess rectangular channels along the fiber direction, and have cation-exchange ability. Amphiphilic octadecylammonium cations (ODAH(+)) spread at an interface between the air and a dispersion of sepiolite fibers have hybridized with the fibers to form a floating monolayer. Surface pressure-molecular area isotherms did not indicate clear collapse points of the hybrid monolayers. Observation of the hybrid films on glass plates by atomic force microscopy revealed that the sepiolite fibers preferred to be aligned perpendicularly to the compression direction, and that some fibers overlapped upon compression or even before compression. Out-of-plane and in-plane X-ray diffraction patterns of the hybrid film showed that the fibers were not only aligned by the compression but oriented around the fiber direction. Electronic spectra of methylene blue cations (MB(+)) adsorbed on the hybrid film indicated the presence of monomers and dimers of MB(+). The absorption intensity due to the monomer was dependent on the polarization direction of the incident beam; interestingly, the monomers were spontaneously oriented along the sepiolite fiber direction but the dimers were not oriented. By comparison with the results of rhodamine 6G adsorbed on the film, the monomers of MB(+) would probably be present in the channels of sepiolite fibers, while the dimers would be adsorbed on the external surface of the fibers.

Photoreduction of Prussian Blue intercalated into titania nanosheet ultrathin films.

Ultrathin films composed of titania nanosheets and Prussian Blue were prepared by using the modified Langmuir-Blodgett technique. The ultrathin films could be deposited in a layer-by-layer manner with lamellar structure. Upon band gap excitation of titania nanosheets, the generated electrons were injected into ferromagnetic Prussian Blue, resulting in reduction to paramagnetic Prussian White. It was revealed that the reaction could proceed only in the presence of hole-scavenging interlayer water molecules.

Ultrathin hybrid films of clay minerals.

Smectites or swelling clay minerals are naturally occurring nanomaterials that can be fully delaminated to elementary clay mineral platelets in dilute aqueous dispersion. This review article gives an overview of the recent progress on how the elementary clay mineral platelets can be reorganized in monolayered or multilayered hybrid nanofilms by layer-by-layer assembly or the Langmuir-Blodgett technique. In the latter case one hybrid layer consists of one layer of elementary clay mineral platelets with a theoretical thickness of 0.96 nm, covered on one side by amphiphilic cations. The organization of the elementary clay mineral platelets and that of the adsorbed amphiphilic cations in the nanofilms has been studied in great detail by ATR-FTIR, UV-Vis and fluorescence spectroscopy, XRD and AFM. The nanofilms carry functional properties, such as chirality, optical nonlinearity and magnetism, which are due to the nature of the amphiphilic cations and to the organization of both the amphiphilic molecules and the elementary clay mineral platelets.

Photocatalytic decomposition of an alkylammonium cation in a Langmuir-Blodgett film of a titania nanosheet.

The formation of inorganic-organic hybrid films of a titania nanosheet and an amphiphilic alkylammonium cation has been investigated, and the photocatalytic decomposition of the alkylammonium cation in the film has been pursued. When a solution of the amphiphilic alkylammonium salt (octadecylammonium chloride: ODAH+ Cl-) was spread on an interface between the air and a titania nanosheet suspension, the negatively charged nanosheets were adsorbed onto the floating monolayer of ODAH+ to form a hybrid monolayer. The hybridization was confirmed by pi-A isotherm measurements, atomic force microscopy, and X-ray photoelectron spectroscopy. Multilayered films were fabricated in a layer-by-layer way by transferring the hybrid monolayers onto glass plates. Areas per ODAH+ cation in the films were estimated from the infrared (IR) spectra of the films, but these areas were smaller than those estimated from the pi-A isotherm curves. The orientation of the alkyl chain of ODAH+ in the hybrid film was determined by means of polarized IR spectroscopy. The alkyl chains were tilted 41 +/- 1 degrees and 47 +/- 1 degrees from the surface normal for the films prepared from the 8 and 20 ppm (ppm = mg dm(-3)) suspensions, respectively. Together with X-ray diffraction data of the films, the structure of the hybrid film was discussed. When the films were illuminated with a UV light, the absorption intensities due to the alkyl chain of ODAH+ decreased exponentially, indicating the photocatalytic decomposition of ODAH+ by the titania nanosheets in the films. Deviation from the exponential trend in the decomposition rate was observed in the initial period for the hybrid films prepared from the suspensions at low concentrations. Interestingly, the layered structure of the hybrid film was disturbed significantly after the ODAH+ cations were decomposed.

Observation of the anisotropic photoinduced magnetization effect in Co-Fe Prussian blue thin films fabricated by using clay Langmuir-Blodgett films as a template.

Thin films of cobalt-iron cyanide (Co-Fe Prussian blue) have been fabricated by means of the modified Langmuir-Blodgett (LB) method using a smectite clay mineral (montmorillonite). In this combined method, clay LB films play a template role in the formation of the Co-Fe Prussian blue thin layer. The films were revealed to possess a well-organized structure not only in perpendicular directions to the film surface but also in parallel directions to the film surface. The photoinduced electron transfer from the iron ion to the cobalt through the bridging cyanide in the films occurred at low temperature (8 K), similar to that in the bulk Co-Fe Prussian blue. The films clearly exhibited magnetic anisotropy with regards to the direction of the applied magnetic field. Moreover, the photoinduced magnetization effect in the films was also found to be anisotropic.

Formation of Langmuir-Blodgett films of a clay and a water-soluble alkylammonium cation.

We have studied the formation of ultrathin hybrid films composed of a water-soluble alkylammonium cation (trimethyloctadecylammonium caiton: TMODAH+) and clay nanosheets at an air-water interface. When a chloroform solution of the ammonium salt of TMODAH+Cl- was spread onto a surface of an aqueous clay suspension in a Langmuir trough, a stable monolayer of the water-soluble ammonium cation was formed by hybridization with the clay nanosheets at the air-water interface. Surface pressure--molecular area (pi-A) isotherm curve of the hybrid monolayer shifted to the smaller molecular area side with the increase in the concentration of the ammonium salt in the solution or with the decrease in that of the clay in the suspension. In some cases, the lift-off areas in the pi-A isotherm curves were less than the cross-sectional area of an alkyl chain (ca. 0.19 nm2). These results indicated that some ammonium cations spread onto the clay suspension were dissolved into the aqueous subphase before the hybridization with the clay nanosheets. The hybrid monolayers were transferred onto a glass plate in a layer-by-layer way by horizontal dipping to form a hybrid multilayerd film. Interestingly, the densities of TMODAH+ determined by the infrared spectral analysis were constant in the hybrid multilayers prepared from the clay suspensions at the same concentration, regardless of the concentrations of the ammonium salt solutions. XRD patterns of the films showed that the cations of TMODAH+ would lie down on the clay layer in the hybrid film.

Sensing of molecular chirality on an electrode modified with a clay-metal complex hybrid film.

A chiral sensing electrode has been prepared by coating an indium tin oxide (ITO) substrate with a hybrid film of metal complexes and a clay layer (montmorillonite). By applying the combined method of the Langmuir-Blodgett and self-assembly techniques, a monolayer of a water-soluble chiral metal complex (Lambda-[Os(phen)(3)](2+)), which acted as a mediator of oxidizing a target molecule, was fixed electrostatically onto a single-layered clay film. Chiral sensing was demonstrated by monitoring a photocurrent when the electrode was in contact with an aqueous NaClO(4) solution of 1,1'-2-binaphthol. As a result, the S-1,1'-2-binaphthol gave a photocurrent 1.8 times higher than the R-isomer at the applied potential of 700 mV (vs Ag|AgCl|KCl(sat)). Detection limit was determined to be 40 microM from the concentration dependence of a response current. Mechanisms for chiral sensing effect were explained in terms of the stereoselective binding of 1,1'-2-binaphthol with adsorbed Lambda-[Os(phen)(3)](2+) on a clay surface.

Two-dimensional molecular ordering of Os(II) complexes in organo-clay hybrid ultrathin films.

An ordered structure of [OsL(3)](2+)(L = 2, 2'-bipyridine or 1, 10-phenanthroline) layer in an ultrathin film composed of the complex cations, clay nanosheets and alkylammonium cations is reported on the basis of its in-plane X-ray diffraction and polarized electronic spectral data.

Langmuir-Blodgett films of a clay mineral and ruthenium(II) complexes with a noncentrosymmetric structure.

Mono- and multilayers of amphiphilic [Ru(phen)(2)(dcC12bpy)](2+) (phen = 1,10-phenanthroline, dcC12bpy = 4,4'-caboxyl-2,2'-bipyridyl didodecyl ester) hybridized with a clay mineral have been prepared by a modified Langmuir-Blodgett method, and their structures and properties have been investigated. Formation of a hybrid monolayer of the Ru(II) complex cations and the clay platelets at an air-clay suspension interface was confirmed by surface pressure-molecular area (pi-A) isotherm measurement and atomic force microscopic (AFM) observation. Multilayers were fabricated by depositing the hybrid monolayers onto glass substrates. The absorbance at 492 nm due to the Ru(II) complex cation in the multilayer increased linearly with the increase in the layer number, indicating layer-by-layer deposition of the hybrid monolayers. Because no increase in the second-harmonic generation (SHG) signal from the multilayers against the layer number was observed, the orientation of the Ru(II) complex cations in the layer would be disturbed. The hydrophilic surface of the transferred hybrid monolayer can be converted to a hydrophobic surface by dipping it in an aqueous solution of octadecylammonium chloride (ODAH(+)Cl(-)). The multilayers modified with ODAH(+) showed a quadratic relation between the SHG intensity and the layer number. This means that the Ru(II) complex cations in the multilayer are successfully oriented in a noncentrosymmetric way by the conversion of the surface property. Both a racemic mixture and an enantiomer of the Ru(II) complex cations were employed to examine the chiral effect on the film properties. The chiral contribution to the SHG signal was enhanced in the multilayer modified with ODAH(+).