DNA interaction and cytotoxicity studies of new ruthenium(II) cyclopentadienyl derivative complexes containing heteroaromatic ligands

Four ruthenium(II) complexes with the formula [Ru(η⁵-C₅H₅)(PP)L][CF₃SO₃], being (PP = two triphenylphosphine molecules), L = 1-benzylimidazole, ; (PP = two triphenylphosphine molecules), L = 2,2′bipyridine, ; (PP = two triphenylphosphine molecules), L = 4-Methylpyridine, ; (PP = 1,2-bis(diphenylphosphine)ethane), L = 4-Methylpyridine, , were prepared, in view to evaluate their potentialities as antitumor agents. The compounds were completely characterized by NMR spectroscopy and their crystal and molecular structures were determined by X-ray diffraction. Electrochemical studies were carried out giving for all the compounds quasi-reversible processes. The images obtained by atomic force microscopy (AFM) suggest interaction with pBR322 plasmid DNA. Measurements of the viscosity of solutions of free DNA and DNA incubated with different concentrations of the compounds confirmed this interaction. The cytotoxicity of compounds 1234 was much higher than that of cisplatin against human leukemia cancer cells (HL-60 cells). IC₅₀ values for all the compounds are in the range of submicromolar amounts. Apoptotic death percentage was also studied resulting similar than that of cisplatin.     

The crystallographic study of left-handed Z-DNA d(CGCGCG)2 and thermine complexes crystallized at various temperatures and at various concentration of cations

In crystals of complexes of thermine and d(CGCGCG)₂ molecules grown at 4, 10, and 20 °C, the numbers of thermine molecules connected to the DNA molecule were dependent on the temperature of the crystallization. Two molecules of thermine and one Mg²⁺ ion were connected to DNA molecule when thermine and d(CGCGCG)₂ were co-crystallized at 4 and at 20 °C. When an increased concentration of magnesium and thermine molecules were co-crystallized with d(CGCGCG)₂ molecules at 10 °C, three Mg²⁺ ions and only one thermine molecule were bound with a d(CGCGCG)₂ molecule. The number of polyamines and of Mg²⁺ ions connected to DNA was dependent on the atomic values of the polyamine and of the metal ion. The binding of more Mg²⁺ ions occurred when the atomic value of Mg²⁺ exceeded that of the corresponding mono- or polyamine, and when the Mg²⁺ ion concentration was elevated. Furthermore, this study is the first documentation of a naturally occurring polyamine bound to the minor groove of DNA in a crystal structure.     

[Ru(phen)2(dppz)] as an efficient optical probe for staining nuclear components

The ‘molecular light switch’ complexes [Ru(bpy)₂(dppz)]²⁺ (1) and [Ru(phen)₂(dppz)]²⁺ (2), where bpy = 2,2′-bipyridine, phen = 1,10-phenanthroline and dppz = dipyrido[3,2-a:2′,3′-c]phenazine, have been explored as probes for diagnosing and staining nuclear components. The phen complex acts as a better staining agent for nonviable cells than for viable cells and exhibits a staining efficiency in tail region of comet more specific and stronger than the already known dye Hoechst 33258.     

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).     

Characterization of DNA-Hv1 histone interactions; discrimination of DNA size and shape

We have studied the formation of histone Hv1-DNA complexes using an acoustic biosensor and AFM imaging. Our results show that DNA and histone molecules aggregate into amorphous accumulations which form a compact rigid layer on the sensor’s surface. By measuring changes in the acoustic wave amplitude, it was possible to titrate surface bound DNA with Hv1 and discriminate between DNA molecules of different size and shape. From the kinetic analysis of real time data, K_eq was found equal to 3 × 10⁵ M⁻¹.     

Thermal preference,tolerance and oxygen consumption of adult white shrimp Litopenaeus vannamei (Boone) exposed to different acclimation temperatures

Final temperature preferendum of white shrimp adults were determined with acute and gravitation methods. The final preferendum was similar, independent of method (26.2–25.6 °C). A direct relationship was determined between the critical thermal maxima values and the acclimation temperatures (P<0.05). The end point of Critical Thermal Maxima (CTMax) for adults was defined as the loss of righting response (LRR). The acclimation response ratio (ARR) for adults of white shrimp had an interval of 0.36–0.76, values that agreed with others obtained for crustaceans from tropical and subtropical climates. The oxygen consumption rates increased significantly (P<0.05) from 39.6 up to 90.0 mg O₂ kg⁻¹ h⁻¹ wet weight (w.w.) as the acclimation temperature increased from 20 to 32 °C. The range of temperature coefficient (Q₁₀) of the white shrimp between 23 and 26 °C was the lower 1.60. The results obtained in this work are discussed in relation to the species importance in the reproductive scope and maintenance of breeders.     

Primary hemocyte culture of Penaeus monodon as an in vitro model for white spot syndrome virus titration, viral and immune related gene expression and cytotoxicity assays

Immortal cell lines have not yet been reported from Penaeus monodon, which delimits the prospects of investigating the associated viral pathogens especially white spot syndrome virus (WSSV). In this context, a method of developing primary hemocyte culture from this crustacean has been standardized by employing modified double strength Leibovitz-15 (L-15) growth medium supplemented with 2% glucose, MEM vitamins (1×), tryptose phosphate broth (2.95 g l⁻¹), 20% FBS, N-phenylthiourea (0.2 mM), 0.06 μg ml⁻¹ chloramphenicol, 100 μg ml⁻¹ streptomycin and 100 IU ml⁻¹ penicillin and hemolymph drawn from shrimp grown under a bio-secured recirculating aquaculture system (RAS). In this medium the hemocytes remained viable up to 8 days. 5-Bromo-2′-deoxyuridine (BrdU) labeling assay revealed its incorporation in 22 ± 7% of cells at 24 h. Susceptibility of the cells to WSSV was confirmed by immunofluoresence assay using a monoclonal antibody against 28 kDa envelope protein of WSSV. A convenient method for determining virus titer as MTT₅₀/ml was standardized employing the primary hemocyte culture. Expression of viral genes and cellular immune genes were also investigated. The cell culture could be demonstrated for determining toxicity of a management chemical (benzalkonium chloride) by determining its IC₅₀. The primary hemocyte culture could serve as a model for WSSV titration and viral and cellular immune related gene expression and also for investigations on cytotoxicity of aquaculture drugs and chemicals.     

A synthetic dinuclear copper(II) hydrolase and its potential as antitumoral: Cytotoxicity, cellular uptake, and DNA cleavage

We have studied the protonation equilibria of a dicopper(II) complex [Cu₂(μ-OH)(C₂₁H₃₃ON₆)](ClO₄)₂·H₂O, (1), in aqueous solution, its interactions with DNA, its cytotoxic activity, and its uptake in tumoral cells. C₂₁H₃₃ON₆ corresponds to the ligand 4-methyl-2,6-bis[(6-methyl-1,4-diazepan-6-yl)iminomethyl]phenol. From spectrophotometric data the following pKa values were calculated 3.27, 4.80 and 6.10. Complex 1 effectively promotes the hydrolytic cleavage of double-strand plasmid DNA under anaerobic and aerobic conditions. The following kinetic parameters were calculated k_cat of 2.73 × 10⁻⁴ s⁻¹, K_M of 1.36 × 10⁻⁴ M and catalytic efficiency of 2.01 s⁻¹ M⁻¹, a 2.73 × 10⁷ fold increase in the rate of the reaction compared to the uncatalyzed hydrolysis rate of DNA. Competition assays with distamycin reveal minor groove binding. Complex 1 inhibited the growth of two tumoral cell lines, GLC4 and K562, with the IC₅₀ values of 14.83 μM and 34.21 μM, respectively. There is a good correlation between cell growth inhibition and intracellular copper content. When treated with 1, cells accumulate approximately twice as much copper as with CuCl₂. Copper-DNA adducts are formed inside cells when they are exposed to the complex. In addition, at concentrations that compound 1 inhibits tumoral cell growth it does not affect macrophage viability. These results show that complex 1 has a good therapeutic prospect.     

[Cu4(H2O)4(dmapox)2(btc)]n · 10nH2O: The first two-dimensional polymeric copper(II) complex with bridging μ-trans-oxamidate and μ4-1,2,4,5-benzentetracarboxylato ligands: Synthesis, crystal structure and DNA binding studies

A two-dimensional copper(II) polymer with formula of [Cu₄(H₂O)₄(dmapox)₂(btc)]_n · 10nH₂O, where dmapox is the dianion of N,N′-bis[3-(dimethylamino)propyl]oxamide and btc is the tetra-anion of 1,2,4,5-benzenetetracarboxylic acid, was synthesized and characterized by elemental analysis, conductivity measurement, IR and electronic spectral studies. The crystal structure of the complex has been determined by X-ray single-crystal diffraction. The structure consists of crystallized water molecules and neutral two-dimensional copper(II) coordination polymeric networks constructed both by the bis-tridentate μ-trans-dmapox and tetra-monodentate μ₄-btc bridging ligands. Each btc ligand links four trans-dmapox-bridged binuclear copper(II) building blocks [Cu₂(H₂O)₂(trans-dmapox)]²⁺ and each binuclear copper(II) building block attaches to two btc ligands forming an infinite 2D layer which consists of 4+4 grids with dimensions of 13.563(5) × 15.616(5) Å. The environment around the copper(II) atom can be described as a distorted square-pyramid and the Cu?Cu separations through μ-trans-dmapox and μ₄-btc bridging ligands are 5.225 Å (Cu1-Cu1ⁱ), 5.270 Å (Cu2-Cu2ⁱⁱ), 6.115 Å (Cu1-Cu2), 9.047 Å (Cu1-Cu2ⁱⁱⁱ) and 10.968 Å (Cu1-Cu1ⁱⁱⁱ), respectively. Abundant hydrogen bonds among the crystallized, the coordinated water molecules, and the uncoordinated carboxyl oxygen atoms cross-link the two-dimensional layers into an overall three-dimensional channel-like framework. The interaction of the copper(II) polymer with calf thymus DNA (CT-DNA) has been investigated by using absorption, emission spectral and electrochemical techniques. The results indicate that the copper(II) polymer interacts with DNA strongly (K_b = 4.8 × 10⁵ M⁻¹ and K_sv = 1.1 × 10⁴) and the interaction mode between the copper(II) polymer and DNA may be the groove binding. To the best of our knowledge, this is the first report about the crystal structure and DNA-binding studies of a two-dimensional copper(II) polymer bridged both by the trans-oxamidate and btc ligands.     

Structural diversity of neutral bis-(β-iminoaldehyde) complexes of nickel(II)

Series of Ni^II and Cu^II complexes with dianionic [N₂O₂] ligands were synthesized and characterised applying spectroscopic and X-ray diffraction techniques. The ligands were obtained by 1:2 condensation of ethylene- and propylenediamine with malonic aldehyde derivatives (R² = H, R¹ = H or OCH₃). Although the molecular formulae of the complexes are quite similar, the X-ray investigations have proved a significant structural diversity in the solid state. Among others, we found some simple nearly planar molecules stacked in the crystal lattice with electron density of six-membered rings delocalised over the chelate rings as well as some very complex polymeric or nickel acetate bridged trinuclear complexes. The coordination of the nickel ion by surrounding oxygen and nitrogen atoms is square-planar in the simplest case and octahedral in the most complex one. Small topological differences in similar molecules generate completely different crystal structures.From magnetic studies, a small, negative value of J obtained confirms the occurrence of weak antiferromagnetic interactions between the Ni^II ions in polymeric chain of the propylenediamine dialdehyde substituted derivative.     

Passage through vertebrate gap junctions of 17/18 kDa molecules is primarily dependent upon molecular configuration

In fish, amphibians and mammals, gap junctions of some cells allow passage of elongate molecules as large as 18 kDa, while excluding smaller, less elongate molecules. Fluorescently labeled Calmodulin (17 kDa) and fluorescently labeled Troponin-C (18 kDa), when microinjected into oocytes of Danio rerio, Xenopus laevis or Mus domestica, were able to transit the gap junctions between these oocytes and the granulosa cells which surrounded them. Co-microinjected with these Ca²⁺-binding proteins, Texas-red-labeled dextran (10 kDa) remained in the microinjected cell. Osteocalcin (6 kDa), also a Ca²⁺-binding protein, but with a wide “V” shape proved unable to transit these gap junctions. Calmodulin, but not Troponin-C, was able to transit gap junctions of gonadotropin treated WB cells in culture. We show evidence that molecules as large as 18 kDa can pass through some vertebrate gap junctions, both homologous and heterologous, and that it is primarily molecular configuration which governs gap junctional permeability.     

The structure of DNA-DOPC aggregates formed in presence of calcium and magnesium ions: A small-angle synchrotron X-ray diffraction study

The structure of aggregates formed due to DNA interaction with dioleoylphosphatidylcholine (DOPC) vesicles in presence of Ca²⁺ and Mg²⁺ cations was investigated using synchrotron small-angle X-ray diffraction. For DOPC/DNA = 1:1 mol/base and in the range of concentration of the cation²⁺ 0-76.5 mM, the diffractograms show the coexistence of two lamellar phases: L^x phase with repeat distance d_Lx ∼ 8.26-7.39 nm identified as a phase where the DNA strands are intercalated in water layers between adjacent lipid bilayers, and L_DOPC phase with repeat distance d_DOPC ∼ 6.45-5.65 nm identified as a phase of partially dehydrated DOPC bilayers without any divalent cations and DNA strands. The coexistence of these phases was investigated as a function of DOPC/DNA molar ratio, length of DNA fragments and temperature. If the amount of lipid increases, the fraction of partially dehydrated L_DOPC phase is limited, depends on the portion of DNA in the sample and also on the length of DNA fragments. Thermal behaviour of DOPC + DNA + Ca²⁺ aggregates was investigated in the range 20-80 °C. The transversal thermal expansivities of both phases were evaluated.     

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.     

Single-strand DNA translation initiation step analyzed by Isothermal Titration Calorimetry

Is single-strand DNA translatable? Since the 60s, the question still remains whether or not DNA could be directly translated into protein. Some discrepancies in the results were reported about functional translation of single-strand DNA but all results converged on a similar behavior of RNA and ssDNA in the initiation step. Isothermal Titration Calorimetry method was used to determine thermodynamic constants of interaction between single-strand DNA and S30 extract of Escherichia coli. Our results showed that the binding was not affected by the nature of the template tested and the dissociation constants were in the same range when ssDNA (K_d = 3.62 ± 2.1 × 10⁻⁸ M) or the RNA corresponding sequence (K_d = 2.7 ± 0.82 × 10⁻⁸ M) bearing SD/ATG sequences were used. The binding specificity was confirmed by antibiotic interferences which block the initiation complex formation. These results suggest that the limiting step in translation of ssDNA is the elongation process.     

Formation of a wrapped DNA-protein interface: experimental characterization and analysis of the large contributions of ions and water to the thermodynamics of binding IHF to H' DNA

To characterize driving forces and driven processes in formation of a large-interface, wrapped protein-DNA complex analogous to the nucleosome, we have investigated the thermodynamics of binding the 34-base pair (bp) H′ DNA sequence to the Escherichia coli DNA-remodeling protein integration host factor (IHF). Isothermal titration calorimetry and fluorescence resonance energy transfer are applied to determine effects of salt concentration [KCl, KF, K glutamate (KGlu)] and of the excluded solute glycine betaine (GB) on the binding thermodynamics at 20 °C. Both the binding constant K_obs and enthalpy ΔH°_obs depend strongly on [salt] and anion identity. Formation of the wrapped complex is enthalpy driven, especially at low [salt] (e.g., ΔH^o_obs = − 20.2 kcal·mol^− 1 in 0.04 M KCl). ΔH°_obs increases linearly with [salt] with a slope (dΔH°_obs/d[salt]), which is much larger in KCl (38 ± 3 kcal·mol^− 1 M^− 1) than in KF or KGlu (11 ± 2 kcal·mol^− 1 M^− 1). At 0.33 M [salt], K_obs is approximately 30-fold larger in KGlu or KF than in KCl, and the [salt] derivative SK_obs = dlnK_obs/dln[salt] is almost twice as large in magnitude in KCl (− 8.8 ± 0.7) as in KF or KGlu (− 4.7 ± 0.6).A novel analysis of the large effects of anion identity on K_obs, SK_obs and on ΔH°_obs dissects coulombic, Hofmeister, and osmotic contributions to these quantities. This analysis attributes anion-specific differences in K_obs, SK_obs, and ΔH°_obs to (i) displacement of a large number of water molecules of hydration [estimated to be 1.0(± 0.2) × 10³] from the 5340 Å² of IHF and H′ DNA surface buried in complex formation, and (ii) significant local exclusion of F⁻ and Glu⁻ from this hydration water, relative to the situation with Cl⁻, which we propose is randomly distributed. To quantify net water release from anionic surface (22% of the surface buried in complexation, mostly from DNA phosphates), we determined the stabilizing effect of GB on K_obs: dlnK_obs/d[GB]  = 2.7 ± 0.4 at constant KCl activity, indicating the net release of ca. 150 H₂O molecules from anionic surface.     

Palladium(II) binding to N(7) of acyclovir: DNA interaction and herpes simplex virus (HSV-1) inhibitory activity

Cytotoxicity and herpes simplex virus (HSV-1) inhibitory activity of acyclovir (ACV), 9-[(2-hydroxyethoxy)methyl]guanine, and the palladium(II) coordination complex cis-[PdCl₂(H₂O)(N7-ACV)] · ACV · xH₂O have been tested in African green monkey kidney (Vero line) epithelial cell cultures. The N(7) position of ACV represents the preferred binding site to afford a pseudo-chelate N7/O6 Pd(II) complex involving H-bonds with the cis H₂O molecule. The Pd(II)-ACV complex has been structurally characterized by FTIR and ¹H NMR spectroscopy techniques, chemical composition was measured by elemental analysis, and the thermoanalytical study was performed by TG/DTA. The recognition of secondary ACV molecules by the Pd(II) derivative promotes cooperatively potent HSV-1 inhibitory activity which, in turn, strongly depends on concentration conditions. At the optimal concentration of 10 μM, this complex exhibits antiviral efficiency in vitro, approximately hundred-fold (ca. 1.87 log₁₀) more effective in herpes-infected cells when compared with that of the parent ACV molecules. The molecular-level observation of noticeable modifications caused by the complex on the morphology of the plasmid pBR322 DNA was monitored by AFM, whose mutual interaction evolves to eventually afford DNA condensates upon increasing the period of incubation.     

The effect of hydrostatic pressure on the thermal stability of DNA hairpins

DNA hairpins consist of two distinct structural domains: a double stranded stem and a single-stranded loop that connect the two strands of the stem. Previous studies of short DNA hairpins have revealed that loop and stem sequences can significantly affect the thermodynamic stability of short DNA hairpins. In this work we present the effect of hydrostatic pressure on the helix-coil transition temperature (T_M) for 11 16-base, hairpin-forming DNA oligonucleotides. All of the samples form a hairpin with a 6-base pair stem and a four-base loop. In addition, the four base pairs at the end of the stem distal from the loop are the same for every molecule. We have varied loop sequence and identity of the two duplex base pairs adjacent to the loop. Using the change in UV absorption to monitor the conformational state of the oligonucleotide the hairpin-coil transition temperature of these molecules was studied as a function of sodium ion concentration and pressure. From these data we calculated the volume change accompanying the transition. Model-dependent (van't Hoff) transition parameters such as ΔH_vH and transition volume (ΔV) were estimated from the analysis of conformational transitions. Experiments revealed that the ΔV for denaturation of these molecules range from − 2.35 to + 6.74 cm³ mol⁻¹. The expansibility (ΔΔV/ΔT) and the pressure dependence of cation release are also presented. The difference in the volume change for this transition is related to the differences in the hydration of these molecules.     

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.     

Synthesis, crystal structure, spectral properties and catalytic activity of hexakis(imidazole)manganese(II) bisindole-2-carboxylato bisneocuproine bisdimethyl sulfoxide solvates {[Mn(Im)6] · 2(2-IC) · 2(NC) · 2(DMSO)}

Synthesis, X-ray crystal structure and IR spectrum of {[Mn^II(Im)₆] · 2(2-IC) · 2(NC) · 2(DMSO)} (Im = imidazole, 2-HIC = indole-2-carboxylic acid, NC = 2,9-dimethyl-1,10-phenanthroline, DMSO = dimethyl sulfoxide) are reported. The manganese(II) ion has octahedral geometry with a MnN₆ core. The crystal structure is completed by two NC, two 2-IC⁻ and two DMSO solvate molecules. The individual cations are linked into chains running parallel to the a axis by four intermolecular hydrogen bonding involving two 2-IC⁻solvate. Moreover, these chains are connected by π-π stacking interactions which occur between neocuproine molecules related through inversion center. In IR spectroscopy, the compound spectrum is roughly similar to the imidazole one: (i) above 1800 cm⁻¹, the bands are broad, but when focussing on some of them a doublet structure can be found; (ii) below 1800 cm⁻¹, the bands are sharp and it is then possible to point out the modification of S-O band when this later is involved in bifurcated hydrogen bonding to a second solvate 2-IC⁻. The compound catalyses the disproportionation of H₂O₂; moreover an additional quantity of imidazole increases the reaction rate.