pH effects on optical and DNA binding properties of a thiophene-containing ruthenium(II) complex

A new ruthenium(II) complex, [Ru(bpy)₂(Htip)]Cl₂ {where bpy = 2,2′-bipyridine and Htip = 2-(thiophen-2-yl)-1H-imidazo[4,5-f][1,10]phenanthroline}, has been synthesized and characterized by ¹H NMR spectroscopy, elemental analysis, and mass spectrometry. The pH effects on UV-Vis absorption and emission spectra of the complex have been studied, and the ground- and excited-state acidity ionization constant values have been derived. The calf thymus (ct) DNA binding properties of the complex have been investigated with UV-Vis absorption and luminescence titrations, steady-state emission quenching by [Fe(CN)₆]⁴⁻, DNA competitive binding with ethidium bromide, DNA melting experiments, and viscosity measurements. The molecular structures and electronic properties of [Ru(bpy)₂(Htip)]²⁺ and deprotonated form [Ru(bpy)₂(tip)]⁺ have also been investigated by means of density functional theory calculations in an effort to understand the DNA binding properties. The results suggest that the complex undergo three-step successive protonation/deprotonation reactions with one of which occurring over physiological pH region, and act as a ct-DNA intercalator with an intrinsic DNA binding constant value on 10⁵ M⁻¹ order of magnitude that is insensitive to pH.     

Enhanced DNA photocleavage properties of Ru(II) terpyridine complexes upon incorporation of methylphenyl substituted terpyridine and/or the polyazine bridging ligand dpp (2,3-bis(2-pyridyl)pyrazine)

The heteroleptic complexes, [(MePhtpy)RuCl(dpp)](PF₆) and [(tpy)RuCl(dpp)](PF₆), have been synthesized, characterized, and investigated with respect to their photophysical, redox, and DNA photocleavage properties (where MePhtpy = 4′-(4-methylphenyl)-2,2′:6′,2′′-terpyridine and dpp = 2,3-bis(2-pyridyl)pyrazine, tpy = 2,2′:6′,2′′-terpyridine). The X-ray crystal structure confirms the identity of the new [(MePhtpy)RuCl(dpp)](PF₆) complex. These heteroleptic complexes were found to photocleave DNA in the presence of oxygen, unlike the previously studied complex, [Ru(tpy)₂](PF₆)₂. The photophysical, redox, and DNA photocleavage properties of the heteroleptic complexes were compared with those of the homoleptic complexes, [Ru(MePhtpy)₂](PF₆)₂ and [Ru(tpy)₂](PF₆)₂. The heteroleptic complexes showed intense metal to ligand charge transfer (MLCT) transition at lower energy ([(MePhtpy)RuCl(dpp)](PF₆), 522 nm; [(tpy)RuCl(dpp)](PF₆), 516 nm) and longer excited state lifetimes as compared to the homoleptic complexes. The [Ru(MePhtpy)₂]²⁺ complex was found to photocleave DNA in contrast to [Ru(tpy)₂]²⁺. The introduction of a methylphenyl group on the tepyridine ligand not only enhances the ³MLCT excited state lifetime but also increases the lipophilicity and thereby the DNA binding ability of the molecule. An increase in lipophilicity upon addition of a methylphenyl group on the 2,2′:6′,2′′-terpyridine ligand was confirmed by determination of the partition coefficient ([(MePhtpy)RuCl(dpp)](PF₆), log P = +1.16; [(tpy)RuCl(dpp)](PF₆), log P = −1.27). The heteroleptic complexes photocleave DNA more efficiently than the homoleptic complexes, with the greatest activity being observed for the newly prepared [(MePhtpy)RuCl(dpp)](PF₆) complex.     

Synthesis, double stranded DNA-binding and photocleavage studies of a functionalized ruthenium(II) complex with 7,7′-methylenedioxyphenyldipyrido[3,2-a:2′,3′-c]-phenazine

A new Ru(II) complex [Ru(phen)₂(mdpz)]²⁺ (phen = 1,10-phenanthroline, mdpz = 7,7′-methylenedioxyphenyl-dipyrido-[3,2-a:2′,3′-c]phenazine) has been synthesized and characterized in detail by elemental analysis, mass spectrometry and ¹H NMR spectroscopy. The interaction of the complex with calf thymus DNA was investigated by spectroscopic and viscosity measurements. The results suggest that the complex binds to DNA via an intercalative mode and serves as a molecular “light switch” for DNA. Moreover, the complex has been found to promote the photocleavage of plasmid DNA pBR322 under irradiation at 365 nm. The mechanism studies reveal that singlet oxygen (¹O₂) plays a significant role in the photocleavage.     

The relationship between the structures of periphery ligands and the DNA binding mode of [Ru(II)(1,10-phenanthroline)(L1L2)dipyrido[3,2-a:2',3'-c]phenazine](n+) (L1=Cl or pyridine and L2=pyridine, n=1,2)

The binding modes of the [Ru(II)(1,10-phenanthroline)(L₁L₂) dipyrido[3,2-a:2′,3′-c]phenazine]²⁺ {[Ru(phen)(py) Cl dppz]⁺ (L₁ = Cl, L₂ = pyridine) and ([Ru(phen)(py)₂dppz]²⁺ (L₁ = L₂ = pyridine)} to native DNA is compared to that of the [Ru(II)(1,10-phenanthroline)₂dipyrido[3,2-a:2′,3′-c]phenazine]²⁺ complex ([Ru(phen)₂dppz]²⁺) by various spectroscopic and hydrodynamic methods including electric absorption, linear dichroism (LD), fluorescence spectroscopy, and viscometric titration. All measured properties, including red-shift and hypochromism in the dppz absorption band, nearly perpendicular molecular plane of the dppz ligand with respect to the local DNA helix axis, prohibition of the ethidium binding, the light switch effect and binding stoichiometry, increase in the viscosity upon binding to DNA, increase in the melting temperature are in agreement with classical intercalation of dppz ligand of the [Ru(phen)₂dppz]²⁺ complex, in which both phenanthroline ligand anchored to the DNA phosphate groups by electrostatic interaction. [Ru(phen)(py)₂ dppz]²⁺ and [Ru(phen)(py) Cl dppz]⁺ complexes had one of the phenanthroline ligand replaced by either two pyridine ligands or one pyridine plus a chlorine ion. They exhibited similar protection from water molecules, interaction with DNA bases, and occupying site that is common with ethidium. The dppz ligand of these two Ru(II) complex were greatly tilted relative to the DNA helix axis, suggesting that the dppz ligand resides inside the DNA and is not perpendicular relative to the DNA helix axis. These observation suggest that anchoring the [Ru(phen)₂dppz]²⁺complex by both phenanthroline is essential for the dppz ligand to be classically intercalated between DNA base-pairs.     

pH- and DNA-induced dual molecular light switches based on a novel ruthenium(II) complex

A novel Ru(II) complex, [Ru(bpy)₂(btppz)]Cl₂, where bpy = 2,2′-bipyridine and btppz = benzo[h]tripyrido[3,2-a:2′,3′-c:2″,3″-j]phenazine, has been synthesized and characterized. The pH effects on UV-visible (UV-vis) absorption and emission spectra of the complex have been studied and ground- and excited-state ionization constants of the complex have been derived. The calf thymus DNA (ct-DNA) binding properties of the complex were investigated with UV-vis absorption and luminescence spectrophotometric titrations, steady-state emission quenching by [Fe(CN)₆]⁴⁻, DNA competitive binding with ethidium bromide, DNA melting experiments, reverse salt titrations and viscosity measurements. The complex was demonstrated to act as dual molecular switches: pH-induced “on-off” emission switch with an on-off intensity ratio of ∼54 which is favorably compared with those reported for structurally analogous Ru(II) complexes, and a DNA molecular light switch with a luminescence enhancement factor of 22 as it intercalatively bound to the DNA.     

Synthesis, structures, electrochemistry and properties of dioxo-molybdenum(VI) and -tungsten(VI) complexes with novel asymmetric N2OS, and partially symmetric N2S2, NOS2N-capped tripodal ligands

A new class of asymmetric N-capped (dianionic/trianionic) tripodal proligands [H_x(Lⁿ)] (x = 2, n = 1-6; x = 3, n = 7, 8) which possess pendant arms with N₂OS, N₂S₂ or NOS₂ donor groups and with different chelate ring sizes {5,5,5} or {5,6,5} has been prepared. Treatment of these ligands with [WO₂Cl₂(dme)] (dme = 1,2-dimethoxyethane) in the presence of base (triethylamine or KOH) leads to the formation of cis-dioxotungsten(VI) complexes of the types [WO₂(Lⁿ)] (n = 1-6) and K[WO₂(Lⁿ)] (n = 7, 8). Reaction of these tetradentate ligands with [MoO₂(acac)₂] (acac = acetylacetonate) gives the corresponding Mo(VI) analogues [MoO₂(Lⁿ)] (n = 1-6) and K[MoO₂(Lⁿ)] (n = 7, 8). Moreover, a new five coordinate dioxomolybdenum(VI) complex with an NS₂ tridentate ligand [MoO₂(L⁹)] has been synthesised using similar procedure. All these compounds have been spectroscopically characterised and the molecular structures of [MoO₂(Lⁿ)] (n = 2, 6) and [WO₂(L⁶)] have been established by X-ray diffraction analysis. The electrochemistry and the catalytic activity for oxidation of allylic and benzylic alcohols of these dioxo complexes have also been investigated.     

Effect of the central metal ion on the cleavage of DNA by [M(TPA)Cl]ClO4 complexes (M = Co, Cu and Zn, TPA = tris(2-pyridylmethyl)amine): An efficient artificial nuclease for DNA cleavage

[M(TPA)Cl]ClO₄·nH₂O complexes (1: M = Co^II, n = 0; 2: M = Cu^II, n = ½; 3: M = Zn^II, n = 0) where TPA = tris(2-pyridylmethyl)amine, were synthesized and structurally characterized. The molecular structure of [Cu(TPA)Cl]ClO₄·½H₂O was determined by single crystal X-ray crystallography. In aqueous solution, the complex ions [M(TPA)Cl]⁺ (M = Co^II or Cu^II) are hydrolyzed to the corresponding aqua species [M(TPA)(H₂O)]²⁺. In contrast to the TBP [Cu(TPA)(H₂O)]²⁺, the corresponding TBP cobalt(II) species showed severe distortion towards tetrahedral geometry. The interactions of the three complexes with DNA have been investigated at pH 7.0 (1.0 mM Tris-Cl buffer) and 37 °C. Significant DNA cleavages were obtained for complexes 1 and 2, whereas complex 3 did not show any detectable cleavage for DNA. Under pseudo Michaelis-Menten kinetic conditions, the kinetic parameters k_cat and K_M were determined as k_cat = 6.59 h⁻¹ and K_M = 2.20 × 10⁻⁴ M for 1 and the corresponding parameters for 2 are k_cat = 5.7 × 10⁻² h⁻¹ and K_M = 6.9 × 10⁻⁵ M, and the reactivity of the complexes in promoting the cleavage of DNA decreases in the order 1 > 2 ? 3. The rate enhancements for the DNA cleavage by 1 and 2 correspond to 1.8 × 10⁸ and 1.6 × 10⁶, respectively, over the non-catalyzed DNA. The reactivity of the two complexes was discussed in relation to other related artificial nucleases.     

Studies on synthesis, characterization, and G-quadruplex binding of Ru(II) complexes containing two dppz ligands

In this work, the interaction between the guanine-rich single-strand oligomer AG₃(T₂AG₃)₃ quadruplex and two Ru(II) complexes, [Ru(L¹)(dppz)₂](PF₆)₄ (1) and [Ru(L²)(dppz)₂](PF₆)₄ (2) (L¹ = 5,5′-di(1-(trimethylammonio)methyl)-2,2′-dipyridyl cation, L² = 5,5′-di(1-(triethylammonio)methyl)-2,2′-dipyridyl cation, dppz = dipyrido[3,2-a:2′,3′-c] phenazine), has been studied by UV-Visible, fluorescence, DNA melting, and circular dichroism in K⁺ buffer. The two complexes after binding to G-quadruplex have shown different DNA stability and fluorescence enhancement. The results show that both complexes can induce the stabilization of quadruplex DNA. ΔT_m values of complexes 1 and 2 at [Ru]/[DNA] ratio of 1:1 were 9.4 and 7.0, respectively. Binding stoichiometry along with the quadruplex was investigated through a luminescence-based Job plot. The major inflection points for complexes 1 and 2 were 0.49 and 0.46, respectively. The data were consistent with the binding mode at a [quadruplex]/[complex] ratio of 1:1. In addition, the conformation of G-quadruplex was not changed by the complexes at the high ionic strength of K⁺ buffer.     

New insights in the DNA-[Cr(phen)2(dppz)] binding and photocleavage properties by the complex with an intercalating ligand

Due to the key role of DNA in cell life and pathological processes, the design of specific chemical nucleases, DNA probes and alkylating agents is an important research area for the development of new therapeutic agents and tools in Biochemistry. Hence, the interaction of small molecules with DNA has attracted in particular a great deal of attention.The aim of this study was to investigate the ability of [Cr(phen)₂(dppz)]³⁺ to associate with DNA and to characterize it as photocleavage reagent for Photodynamic Therapy (PDT).Chromium(III) complex [Cr(phen)₂(dppz)]³⁺, (dppz = dipyridophenazine, phen = 1,10-phenanthroline), where dppz is a planar bidentate ligand with an extended π system, has been found to bind strongly to double strand oligonucleotides (ds-oligo) and plasmid DNA with intrinsic DNA binding constants, K_b, of (3.9 ± 0.3) × 10⁵ M⁻¹ and (1.1 ± 0.1) × 10⁵ M⁻¹, respectively. The binding properties to DNA were investigated by UV-visible (UV-Vis) absorption spectroscopy and electrophoretic studies. UV-Vis absorption data provide clearly that the chromium(III) complex interacts with DNA intercalatively. Competitive binding experiments show that the enhancement in the emission intensity of ethidium bromide (EthBr) in the presence of DNA was quenched by [Cr(phen)₂(dppz)]³⁺, indicating that the Cr(III) complex displaces EthBr from its binding site in plasmid DNA. Moreover, [Cr(phen)₂(dppz)]³⁺, non-covalently bound to DNA, promotes the photocleavage of plasmid DNA under 457 nm irradiation. We also found that the irradiated Cr(III)-plasmid DNA association is able to impair the transforming capacity of bacteria. These results provide evidence confirming the responsible and essential role of the excited state of [Cr(phen)₂(dppz)]³⁺ for damaging the DNA structure. The combination of DNA, [Cr(phen)₂(dppz)]³⁺ and light, is necessary to induce damage. In addition, assays of the photosensitization of transformed bacterial suspensions suggest that Escherichia coli may be photoinactivated by irradiation in the presence of [Cr(phen)₂(dppz)]³⁺. In sum, our results allow us to postulate the [Cr(phen)₂(dppz)]³⁺ complex as a very attractive candidate for DNA photocleavage with potential applications in Photodynamic Therapy (PDT).     

The interesting DNA-binding properties of three novel dinuclear Ru(II) complexes with varied lengths of flexible bridges

Three binuclear Ru(II) complexes with two [Ru(bpy)₂(pip)]²⁺-based subunits {where bpy = 2,2′-bipyridine and pip = 2-phenylimidazo[4,5-f][1,10]phenanthroline} being linked by varied lengths of flexible bridges, were synthesized and characterized by ¹H NMR, elemental analysis, UV-visible (UV-vis) and photoluminescence spectroscopy. The structures of the three complexes were optimized by density functional theory calculations. The interaction of the complexes with calf thymus DNA was investigated by UV-vis and luminescence titrations, steady-state emission quenching by [Fe(CN)₆]⁴⁻, DNA competitive binding with ethidium bromide, DNA melting experiments, and viscosity measurements. The experimental results indicated that the three complexes bound to the DNA most probably in a threading intercalation binding mode with high DNA binding constant values three orders of magnitude greater than the DNA binding constant value reported for proven DNA intercalator, mononuclear counterpart [Ru(bpy)₂(p-mopip)]²⁺ {p-mopip = 2-(4-methoxylphenyl)imidazo[4,5-f][1,10]phenanthroline}.     

A novel 1,2,4-triazole-based copper(II) complex: Synthesis, characterization, magnetic property and nuclease activity

A novel binuclear copper(II) complex [Cu₂L(μ-SO₄)](PF₆)₂ (1) (L = 3,5-bis (bis(pyridine-2-ylmethyl)amino)methyl)-4H-1,2,4-triazol-4-amine) has been synthesized and structurally characterized. X-ray structure shows that the two copper(II) atoms are bridged by one bidentate sulfate ion and the 1,2,4-triazole ring of L with Cu1?Cu2 distance of 4.404 Å. Each copper(II) center has a distorted trigonal-bipyramidal configuration. Variable-temperature magnetic susceptibility studies (2-300 K) indicate the existence of weak antiferromagnetic coupling between the copper(II) ions in complex 1. The interaction of complex 1 with calf thymus DNA (CT-DNA) has been studied by UV absorption, fluorescence spectroscopy, circular dichroism spectroscopy, viscosity and cyclic voltammetry. Furthermore, complex 1 was able to promote single and double strand DNA cleavage in both aerobic and anaerobic conditions, the pseudo-Michaelis-Menten kinetic parameters k_cat = 2.58 h⁻¹ and K_m = 1.2 × 10⁻⁴ M were obtained for 1. The hydrolytic cleavage of DNA by the complex was supported by the evidence from free radical quenching, anaerobic experiment, thiobarbituric acid-reactive substances (TBARS) assay.     

Influence of DNA end structure on the mechanism of initiation of DNA unwinding by the Escherichia coli RecBCD and RecBC helicases

Escherichiacoli RecBCD is a bipolar DNA helicase possessing two motor subunits (RecB, a 3′-to-5′ translocase, and RecD, a 5′-to-3′ translocase) that is involved in the major pathway of recombinational repair. Previous studies indicated that the minimal kinetic mechanism needed to describe the ATP-dependent unwinding of blunt-ended DNA by RecBCD in vitro is a sequential n-step mechanism with two to three additional kinetic steps prior to initiating DNA unwinding. Since RecBCD can “melt out” ∼ 6 bp upon binding to the end of a blunt-ended DNA duplex in a Mg²⁺-dependent but ATP-independent reaction, we investigated the effects of noncomplementary single-stranded (ss) DNA tails [3′-(dT)₆ and 5′-(dT)₆ or 5′-(dT)₁₀] on the mechanism of RecBCD and RecBC unwinding of duplex DNA using rapid kinetic methods. As with blunt-ended DNA, RecBCD unwinding of DNA possessing 3′-(dT)₆ and 5′-(dT)₆ noncomplementary ssDNA tails is well described by a sequential n-step mechanism with the same unwinding rate (mk_U = 774 ± 16 bp s^− 1) and kinetic step size (m = 3.3 ± 1.3 bp), yet two to three additional kinetic steps are still required prior to initiation of DNA unwinding (k_C = 45 ± 2 s^− 1). However, when the noncomplementary 5′ ssDNA tail is extended to 10 nt [5′-(dT)₁₀ and 3′-(dT)₆], the DNA end structure for which RecBCD displays optimal binding affinity, the additional kinetic steps are no longer needed, although a slightly slower unwinding rate (mk_U = 538 ± 24 bp s^− 1) is observed with a similar kinetic step size (m = 3.9 ± 0.5 bp). The RecBC DNA helicase (without the RecD subunit) does not initiate unwinding efficiently from a blunt DNA end. However, RecBC does initiate well from a DNA end possessing noncomplementary twin 5′-(dT)₆ and 3′-(dT)₆ tails, and unwinding can be described by a simple uniform n-step sequential scheme, without the need for the additional k_C initiation steps, with a similar kinetic step size (m = 4.4 ± 1.7 bp) and unwinding rate (mk_obs = 396 ± 15 bp s^− 1). These results suggest that the additional kinetic steps with rate constant k_C required for RecBCD to initiate unwinding of blunt-ended and twin (dT)₆-tailed DNA reflect processes needed to engage the RecD motor with the 5′ ssDNA.     

Synthesis, structure, and magnetic properties of dinuclear nickel(II) complexes with a phenol-based dinucleating ligand with four methoxyethyl chelating arms

Dinuclear nickel(II) complexes [Ni₂(bomp)(MeCO₂)₂]BPh₄ (1) and [Ni₂(bomp)(PhCO₂)₂]BPh₄ (2) were synthesized with the dinucleating ligand 2,6-bis[bis(2-methoxyethyl)aminomethyl]-4-methylphenol [H(bomp)]. X-Ray analysis revealed that the complex 1 · 0.5CHCl₃ contains two nickel(II) ions bridged by phenolic oxygen and two acetate groups, forming a μ-phenoxo-bis(μ-acetato)dinickel(II) core. Electronic spectra were investigated for 1 and 2 in the range of 400-1800 nm, and the data were typical for the octahedral high-spin nickel(II) complexes. Obtained spectral components were well simulated based on the angular overlap model assuming the trigonally distorted octahedral geometry. Magnetic susceptibility was measured for 1 and 2 over a temperature range of 4.5-300 K. The optimized magnetic data were J = 1.75 cm⁻¹, zJ′ = −0.234 cm⁻¹, g = 2.21, D = 15.1 cm⁻¹, and TIP = 370 × 10⁻⁶ cm⁻¹ for complex 1 and J = 3.55 cm⁻¹, zJ′ = −0.238 cm⁻¹, g = 2.23, D = 21.8 cm⁻¹, and TIP = 470 × 10⁻⁶ cm⁻¹ for complex 2. The data revealed ferromagnetic interactions between the two nickel(II) ions.     

Synthesis, characterization, and aqueous chemistry of cytotoxic Au(III) polypyridyl complexes

This work reports the synthesis, characterization, and aqueous chemistry of a series of cytotoxic [Au(polypyridyl)Cl₂]PF₆ complexes {(where polypyridyl = dipyrido[3,2-f:2′,3′-h] quinoxaline (DPQ), dipyrido[3,2-a:2′,3′-c] phenazine (DPPZ) and dipyrido[3,2-a:2′,3′-c](6,7,8,9-tetrahydro) phenazine (DPQC))}. The crystal structure of [Au(DPQ)Cl₂]PF₆ was determined as example of the series and exhibits the anticipated square planar geometry common for d⁸ coordination complexes. The crystals of the complex belong to the space group P2₁/n with a = 7.624(2) Å, b = 18.274(5) Å, c = 14.411(14) Å, β = 98.03(3)°, and Z = 4. In ¹H NMR studies of these compounds in the presence of aqueous buffer, all four complexes rapidly converted to the dihydroxy species [Au(polypyridyl)(OH)₂] in a stepwise fashion. However, the [Au(polypyridyl)]³⁺ fragment believed to impart cytotoxicity in human ovarian cancer cell lines (A2780) remained intact and appeared stable for days. It was also noted that these Au(III) complexes were readily reduced in the presence of the common biological reducing agents, reduced glutathione and sodium ascorbate. How solution and redox stability may affect the biological activity of these novel Au(III) complexes is discussed.     

Synthesis and characterization of silver(I) derivatives containing acylpyrazolonate and phosphino ligands: X-ray crystal structures of monomeric [Ag(Q)(PPh3)2] and of dimeric [{Ag(Q)(PiBu3)}2] (Q = 1-phenyl-3-methyl-4-tert-butylacetylpyrazolon-5-ato)

New silver(I) acylpyrazolonate derivatives [Ag(Q)], [Ag(Q)(PR₃)]₂ and [Ag(Q)(PR₃)₂] (HQ = 1-R¹-3-methyl-4-R²(CO)pyrazol-5-one, HQ^Bn = R¹ = C₆H₅, R² = CH₂C₆H₅; HQ^CHPh2 = R¹ = C₆H₅, R² = CH(C₆H₅)₂; HQ^nPe = R¹ = C₆H₅, R² = CH₂C(CH₃)₃; HQ^tBu = R¹ = C₆H₅, R² = C(CH₃)₃; HQ^fMe = R¹ = C₆H₄-p-CF₃, R² = CF₃; HQ^fEt = R¹ = C₆H₅, R² = CF₂CF₃; R = Ph or iBu) have been synthesized and characterized in the solid state and solution. The crystal structure of 1-(4-trifluoromethylphenyl)-3-methyl-5-pyrazolone, the precursor of proligand HQ^fMe and of derivatives [Ag(Q^nPe)(PPh₃)₂] and [Ag(Q^nPe)(PiBu₃)]₂ have been investigated. [Ag(Q^nPe)(PPh₃)₂] is a mononuclear compound with a silver atom in a tetrahedrally distorted AgO₂P₂ environment, whereas [Ag(Q^nPe)(PiBu₃)]₂ is a dinuclear compound with two O₂N-exotridentate bridging acylpyrazolonate ligands connecting both silver atoms, their coordination environment being completed by a phosphine ligand.     

Controlled nitric oxide photo-release from nitro ruthenium complexes: The vasodilator response produced by UV light irradiation

Preliminary pharmacological studies of various nitric oxide (NO) photo-releasing agents are reported based on the flash-photolysis studies of the nitro ruthenium complexes cis-[Ru^II(NO₂)L(bpy)₂]⁺ (bpy = 2,2′-bipyridine and L = pyridine, 4-picoline and pyrazine) and [Ru^II(NO₂)(bpy)(terpy)]⁺ (terpy = terpyridine) in physiological medium. The net photoreactions under these conditions are two primary photoproducts, in (I) there is Ru^II-NO₂ photoaquation, where the photoproducts are Ru^II-H₂O plus and (II) homolytic dissociation of NO from a coordinated nitrito to derive the Ru^II-OH₂ specie and NO. Based on photochemical processes, the nitro ruthenium complexes were incorporated in water in oil (W/O) microemulsion and used in the vasorelaxation induced experiment. Denuded rat aortas were contracted with KCl and nitro ruthenium complexes in microemulsion were added. Perfusion pressures were recorded while arteries were irradiated at 355 nm The time to reach maximum relaxation was longer for [Ru^II(NO₂)(bpy)(terpy)]⁺ complex (ca. 50 min, n = 6) than for cis-[Ru(NO₂)L(bpy)₂]⁺ with L = py and 4-pic complex (ca. 28 min, n = 6) and cis-[Ru(NO₂)(bpy)₂ (pz)]²⁺ complex (ca. 24 min, n = 5).     

Synthesis, structures and in vitro cytotoxicity of some cationic cis-platinum(II) complexes containing chelating thiocarbamates

The thiocarbamates 4-RC₆H₄NHC(S)NR₂′ (R = H, Cl; R′ = Me, Et), 4-ClC₆H₄NHC(S)NR (NR = 2-pyridylpiperazine) react with cis-[PtCl₂(PTA)₂] (PTA = 1,3,5-triaza-7-phosphaadamantane) in the presence of base to afford the monocationic platinum(II) complexes cis-[Pt{SC(NR₂′) = NC₆H₄R}(PTA)₂]⁺ (R = H, Cl; R′ = Me, Et), cis-[Pt{SC(NR) = NC₆H₄Cl}(PTA)₂]⁺ (NR = 2-pyridylpiperazine), which were isolated as their PF₆ salts in high yields. The complexes were fully characterised spectroscopically and also by X-ray crystallography. Cytotoxicity of these complexes was studied in vitro in three human cancer cell lines (CH1, A549 and SW480) using the MTT assay.     

Octahedral cyanohydroxo cluster complex trans-[Re6Se8(CN)4(OH)2]: Synthesis, crystal structure, and properties

A hexarhenium cyanohydroxo anionic cluster complex [Re₆Se₈(CN)₄(OH)₂]⁴⁻ was synthesized for the first time starting from [Re₆Se₈(OH)₆]⁴⁻, which was crystallized as a salt of the composition Cs_2.75K_1.25[Re₆Se₈(CN)₄(OH)₂]·H₂O (1). The reaction of the complex with Cu²⁺ in an aqueous ammonia or methylamine solutions afforded [Cu(NH₃)₅]₂[Re₆Se₈(CN)₄(OH)₂]·8H₂O (2) or [{Cu(CH₃NH₂)₄}₂Re₆Se₈(CN)₄(OH)₂] (3), respectively. All of these three compounds were characterized by a single-crystal X-ray diffraction method. Compound 1 is crystallized in the tetragonal space group I4/m with eight formula units per cell (a = b = 17.4823(14) Å, c = 19.430(2) Å, V = 5938.3(10) Å³); compound 2 is crystallized in the monoclinic space group P2₁/n with two formula units per cell (a = 12.1845(13) Å, b = 8.6554(9) Å, c = 19.2568(19) Å, β = 91.081(2)°, V = 2030.5(4) Å³); compound 3 is crystallized in the orthorhombic space group Cmcm with four formula units per cell (a = 19.816(4) Å, b = 14.611(3) Å, c = 13.751(3) Å, V = 3981.2(13) Å³). The luminescence properties of 1 were studied in both aqueous solution and solid state. In addition, the electronic structure of [Re₆Se₈(CN)₄(OH)₂]⁴⁻ was elucidated by DFT calculations.     

Kinetic studies on the first dihydrogen aquacomplex, [Ru(H2)(H2O)5]: Formation under H2 pressure and catalytic H/D isotope exchange in water

The ruthenium(II) hexaaqua complex [Ru(H₂O)₆]²⁺ reacts with dihydrogen under pressure to give the η²-dihydrogen ruthenium(II) pentaaqua complex [Ru(H₂)(H₂O)₅]²⁺.The complex was characterized by ¹H, ²H and ¹⁷O NMR: δ_H = −7.65 ppm, J_HD = 31.2 Hz, δ_O = −80.4 ppm (trans to H₂) and δ_O = −177.4 ppm (cis to H₂).The H-H distance in coordinated dihydrogen was estimated to 0.889 Å from J_HD, which is close to the value obtained from DFT calculations (0.940 Å).Kinetic studies were performed by ¹H and ²H NMR as well as by UV-Vis spectroscopy, yielding the complex formation rate and equilibrium constants: k_f = (1.7 ± 0.2) × 10⁻³ kg mol⁻¹ s⁻¹ and K_eq = 4.0 ± 0.5 mol kg⁻¹.The complex formation rate with dihydrogen is close to values reported for other ligands and thus it is assumed that the reaction with dihydrogen follows the same mechanisn (I_d).In deuterated water, one can observe that [Ru(H₂)(H₂O)₅]²⁺ catalyses the hydrogen exchange between the solvent and the dissolved dihydrogen.A hydride is proposed as the intermediate for this exchange.Using isotope labeling, the rate constant for the hydrogen exchange on the η²-dihydrogen ligand was determined as k₁ = (0.24 ± 0.04) × 10⁻³ s⁻¹.The upper and lower limits of the pK_a of the coordinated dihydrogen ligand have been estimated:3 < pK_a < 14.