The solvothermal synthesis, TD-DFT calculations, and spectroscopic/electrochemical characterization of new ruthenium naphthalimide complexes, namely [Ru(bpy)2(py-NI-Br)Cl]Cl (1), [Ru(bpy)2(py-NI-NO2)Cl]Cl (2), and [Ru(bpy)2(py-NI-NH2)Cl]Cl (3) (where py-NI-Br, py-NI-NO2, and py-NI-NH2 = 4-bromo-N-(4-pyridyl)-1,8-naphthalimide, 4-nitro-N-(4-pyridyl)-1,8-naphthalimide, and 4-amino-N-(4-pyridyl)-1,8-naphthalimide, respectively) are presented. Complexes 1-3 lose the chlorido ligand when a positive potential is applied, to yield the solvate complex in solution. The Ru-bpy chromophore dominates the photoluminescence profile because the MLCT (metal-to-ligand charge transfer) levels have lower energy than the NI (naphthalimide) IL (intraligand) levels. In aqueous solutions, the chlorido ligand in the ground state is slightly labile. On the other hand, photosubstitution reactions can be tuned by choosing the appropriate solvent. In coordinating solvents with relatively high dielectric constants, the chlorido ligand is substituted, and a charged photoproduct arises. In non-polar solvents, the NI ligand is photolabile, and neutral products emerge. All the complexes investigated herein are solvatochromic. Although the NI IL transitions have charge-transfer character, which is due to the substituent groups, the MLCT transitions of complexes 1-3 feature higher solvatochromic responses. The exception is free py-NI-NH2, in which the amino group inductive effect produces Δv∼ = 1574 cm-1. Complexes 1-3 intercalate into DNA better than the corresponding free NI ligands and display moderate Ksv constants (∼104 M-1). Complex 3 increases the DNA melting temperature by 10 oC and has the highest intercalation ability in the series.

This work reports the synthesis, characterization and verification of synergistic properties of a nitrite ruthenium(II) compound [Ru(tpy)(dppz)(NO2)](PF6) (tpy = 2,2':6',2″-terpyridine; dppz = dipyrido[3,2-a:2',3'-c]phenazine), which is compared to its chlorine precursor [Ru(tpy)(dppz)(Cl)](PF6). 1H-NMR and IR analyses show the absence of any isomers other than the N-bonded nitrite species. Electronic spectroscopy analysis reveals the influence of the π-acceptor NO2- ligand on the structure of the complex, shifting the MLCT bands to higher energies and increasing the lifetime of its excited state, measured by fs-TA and TCSPC spectroscopy. The nitrosyl species [Ru(tpy)(dppz)(NO)]3+ is highly unstable due to the low electronic density on the Ru center, as shown by pKa measurements and DFT calculations. The nitrite compound proved to be able to interact strongly with DNA, generate 1O2 and release NO upon light stimulation, making it an interesting example of a synergetic compound possessing these properties simultaneously. Improving these results by adjusting the tridentate ligand provides a strategy to develop new Ru metallopharmaceutical candidates as anticancer drugs.

Four different fully water soluble triruthenium acetate complexes with general formula [Ru3O(CH3COO)6(L)3]Cl where L = imidazole (1), 1-(2-hydroxyethyl)imidazole (2), 1-methylimidazole (3) and 1-vinylimidazole (4) ligands were synthesized and characterized. Single crystal X-ray diffraction experiments were done for complexes 1 and 3, both presenting a highly organized supramolecular structure held by conventional and non-conventional hydrogen bonds. Spectroscopic and voltammetric data showed the strong π-donation of electronic density from the imidazole ligands to the polynuclear metallic core. Physical-chemical data from 1H nuclear magnetic resonance and crystallography corroborates to this observation, with more shielded bridging acetates, and the shortening of the RuN bond. Partition coefficient was calculated and, for all complexes, the obtained values were near -1, which relates directly with the high water-solubility characteristic of the complexes. All complexes were also evaluated for their biological properties as bactericidal activity against 19 Gram-positive and Gram-negative strains and, for its trypanocide activity, against the parasite T. cruzi in the amastigote form.

Complexes of the μ-oxo-bis(μ-acetate)diruthenium class exhibit ligand lability at the positions trans to the μ-oxo bridge. Lability is an important property for numerous drugs, such as cis-[Pt(NH3)2Cl2], given that its biological activity is related to an aquation reaction taking place in the biological environment. Inspired by that, we have synthesized, characterized, and explored the lability of the new complex [Ru2(μ-O)(μ-CH3COO)2(py)4(thiq)2](PF6)2 (1, py = pyridine; thiq = 5,6,7,8-tetrahydroisoquinoline). The aquation rates in water, phosphate, and tris-HCl buffered solutions were in the 10-4 s-1 range. Complex 1 quenched HSA fluorescence predominantly through a dynamic mechanism (kq = 1.74 to 2.50 × 1012 M-1 s-1, at 298 to 322 K, pH 7.2 tris-HCl buffer), and the HSA excited state lifetime changed markedly. Circular dichroism data showed that the HSA secondary structure did not change in the presence of complex 1. We rationalized these observations in terms of its hydrophilicity (logP = -0.42 ± 0.04), which probably prevented it from accessing the HSA inner hydrophobic pockets. On the basis of our data, lability in complex 1 did not favor any sort of interaction. Compared to the chemically inert [Ru3(μ-O)(μ-CH3COO)6(thiq)3]PF6 compound, complex 1 presented lower cytotoxicity against B16F10 and MCF7 cells. We assigned the small cytotoxic effect to complex 1 releasing the thiq organic ligand during its aquation. Despite not being a good metallodrug, complex 1 is a chemically useful scaffold for exploring ligand-release strategies in biological medium while yielding a non-cytotoxic aqua-complex.

This work reports on two novel bis-naphthalimide ReI complexes of general formula fac-[Re(CO)3(py-NI-R)2Cl] (NI-py = N-(4-pyridyl)-1,8-naphthalimide; R = H (1) or Br (2)). IL (intraligand) and MLCT (metal-to-ligand charge transfer) transitions dominate their absorption spectra. Photoluminescence data revealed that the lower energy state, responsible for their photoluminescence, has an IL character, matching the photoluminescence behavior of the free ligands. The solvatochromic profile, employed to help understand the intermolecular interaction of the complexes in solution, showed that hydrogen bonding and it-stacking are the principal factors that keep the solute-solvent interactions. The DNA interaction showed that there is a competition between the complexes intercalation (Kb(1) = 4.87 +/- 0.03 & sdot;104 M-1; Kb(2) = 3.95 +/- 0.05 & sdot;104 M-1) and minor groove binding (Kb(1) = 7.25 +/- 0.01 & sdot;104 M-1; Kb(2) = 5.15 +/- 0.05 & sdot;104 M-1), probably due to the relative positioning of the two coordinated naphthalimide ligand, as indicated by in silico calculations. As the complexes retain the electronic characteristics of the ligands, with short-lived and relative high-energy 1IL excited states, no DNA photocleavage was observed. With the HSA, we have obtained higher association constants for both complexes (Ka(1) = 0.26 +/- 0.01 & sdot;105 M-1; Ka(2) = 0.45 +/- 0.05 & sdot;105 M-1) due to hydrophobic interactions and hydrogen bonds between the complex and the protein.

Hydrogen peroxide promoted the release of carbon monoxide through the oxidation of the [Ru3O (CH3COO)6(L)2CO]0 complexes (L = pyridine (1a), dimethylpyrazine (2a) and 4-tert-butylpyridine (3a)). For 1a, a two-step reaction was observed in acetonitrile, with pseudo-first order rate constants kobs1 = (10.9 +/- 2.9) x 10-3 s-1 and k2 = (11.8 +/- 0.8) x 10-4 s-1, assigned to the oxidation reaction RuIII,III,II/RuIII,III,III followed by the substitution of the coordinated CO by a solvent molecule. In acetate buffer, only one-step was observable. Comparison of the reaction rate of three related clusters suggested a dependence of the rate constants with the basicity of the ligands. The 4-tert-butylpyridine ligand increases the oxidative-induced CO release, since sigma-donation of electronic density by the more basic ligand facilitates the oxidation of the Ru(II) ion to Ru(III). We also addressed the possibility of interaction with a relevant biological target, using 1a as example. It is suggested that 1a interacts with human serum albumin (HSA) by the static mechanism, while the interaction of [Ru3O (CH3COO)6(pyridine)2H2O]+ (1b), the reaction product of 1a oxidation, also has a contribution from the dynamic mechanism. This implies that weak interactions play a major role, since the labile point does not seem to favour adduct formation by coordinative bonding.

The mu -Oxo-trinuclear ruthenium acetates are promising metallodrug candidates and have been evaluated for their cytotoxicity against certain cancer cell lines, as well as for their anti-parasitic activity against T. cruzi and vasodilator profile. Therefore, the interaction between fish sperm deoxyribonucleic acid (fs-DNA) and the clusters [Ru3O(CH3COO)6(pic)3]PF6 (1), [Ru3O(CH3COO)6(pic)2(H2O)]PF6 (2), [Ru3O(CH3COO)6(pic)2(CO)] (3), [Ru3O(CH3COO)6(py)2(H2O)]PF6 (4), and [Ru3O(CH3COO)6(H2O)3]PF6 (5) (pic 3-picoline; py pyridine) was evaluated by steady-state fluorescence and viscosity measurements and molecular docking calculations. The capacity of compounds 1-5 to displace the probes ethidium was moderate to weak, with Stern-Volmer quenching constant (Ksv) values in the order of 103 to 104 M-1. The highest constants consistently occurred for the DAPI probe, indicating that all compounds are minor groove binders, agreeing with the molecular docking trend, which also showed that van der Waals forces were mostly responsible for the interaction. Compounds 2, 4, and 5, containing a labile water molecule in their structure, moderately changed the fs-DNA viscosity, signaling the possibility of coordinative binding. Finally, variation in hydrophobicity (presence or absence of a methyl group in the structure of the ligands) and charge did not lead to significant differences in the interaction profile.

Six fac-[Re-(NN)-(CO)3Cl] complexes, where NN is a 2,2'-bipyridine ligand with systematically varied electron-donating or -withdrawing groups at the 4,4' positions, were explored as photocatalysts for CO2 reduction to CO. The light absorption, redox potentials, and excited-state dynamics of the complexes, as well as the reactivity and stability of key catalysis intermediates, were correlated with the Hammett constants (σp) of the substituents, revealing their impact on the photocatalytic activity. Electron-donating substituents, such as -OCH3 and -CH3, resulted in slower excited-state quenching by sacrificial electron donors in comparison to the unsubstituted complex, but their corresponding one-electron-reduced species (OERS) reacted quickly with CO2. On the other hand, electron-withdrawing substituents, such as -Br, -COOH, and -CO2CH3, resulted in more favorable and faster reductive quenching, but at the cost of slower reactivity of the OERS. A comparison of the catalytic activity of the complexes employing two different sacrificial electron donors displayed how the interplay of these factors affects the CO2 reduction performance and how photocatalysis can be controlled by strategic manipulation of both the ligand environment and the reaction conditions.

The chemical reactivity of nitrosyl- and nitrite-coordinated compounds in an aqueous environment is a vital part of understanding the action of these compounds as potential nitric oxide-releasing molecules (NORMs). This work reports the behaviour of the [Ru3O(CH3COO)6(py)2NO2] (1) complex, which is an isomeric mixture of nitrite-N and nitrite-O, and the nitrosyl complex [Ru3O(CH3COO)6(py)2NO]PF6 (2) in aqueous medium with and without light irradiation. NO release under light irradiation was detected through chronoamperometry, which showed that nitrite complex 1 produces NO but is less effective than nitrosyl complex 2. This difference is due to the mechanism of NO production by complex 1, which depends on the nitrite-O isomer, present in minor proportion in the synthetic sample, as shown by computational and NMR data. The reactivity of these compounds in the dark was investigated under various pH values. The nitrite complex 1 had the coordinated nitrite converted to NO+, with a pK = 4.2. NO+ was readily released, yielding the solvate species [Ru3O(CH3COO)6(py)2S]+. For the nitrosyl complex 2, two successive nucleophilic attacks by hydroxide ions were observed producing the [Ru3O(CH3COO)6(py)2HNO2] (3) and [Ru3O(CH3COO)6(py)2NO2]- (4) compounds, with pK values of 9.8 and 12.3, respectively. In buffered solutions (TRIS.HCl and PBS), the kinetic trace for the conversion of 2 to 3 suggested an induction period followed by the complete conversion to [Ru3O(CH3COO)6(py)2HNO2] at pH values where the nitrosyl [Ru3O(CH3COO)6(py)2NO]+ should be the major species. Based on these observations, our data suggest a sequence of steps in which compound 3 accumulates and then, with the aid of the buffer components, increases the rate of its own formation.

The understanding of the Ru-NO bond in Ru nitrosyl systems is of great interest due to the non-innocent nature of the NO ligand, and because of the ability of such compounds to release nitric oxide, an essential physiological regulator. The Ru-NO bond description can be even more complicated when it comes to polynuclear systems such as the mu-oxo clusters of general formula [Ru3O(CH3COO)6(L)3]n, which can be electronically localized or delocalized themselves depending on the nature of the L ligands, or present unpaired electrons depending on the Ru ions oxidation state. Herein, we present a detailed electronic- and molecular-structure description of the [Ru3O (CH3COO)6(py)2NO]PF6 (py = pyridine) cluster using multiconfigurational approaches and X-ray diffraction analysis. The X-ray data unveil a linear Ru-NO moiety with a Ru-NO angle of 180 degrees. Although most linear {RuNO}6 complexes have been largely described as RuII-NO+, our valence bond-type analysis based on a CASSCF ground state wavefunction, with an active space comprised of 18 electrons and 16 orbitals, showed a predominance of the RuIII-NO degrees configuration, with minor contributions from RuIV-NO- and RuII-NO+. These findings provide a more precise framework to rationalize the electronic properties of trinuclear ruthenium nitrosyls, aiding the planning of new NO releasers based on those clusters.

The triruthenium ortho-metallated phenazine [Ru3O(CH3COO)5(py)2(dppzCl)]PF6 (1, py = pyridine; dppz-Cl = 7-chlorodipyrido[3,2-a:2’,3’-c]phenazine) is a potential metallo-drug candidate with in vitro anticancer and trypanosomicidal activities. It also showed strong interactions with deoxyribonucleic acid (DNA) and human serum albumin due to the presence of the planar and π-conjugated phenazine in its structure. Pursuing our interest in compound 1 behavior in a biological environment, we described its interaction with the cytochrome P450 (CYP450) enzymes present in human liver microsomes through a preliminary in vitro metabolism assay. This study showed that the human liver microsomes metabolized compound 1 in a concentration dependent manner. A phenotyping study suggests that CYP3A is the primary enzyme involved in the interaction, even though other isoforms metabolized 1 in a minor extent. It is worth mentioning that the results of phenotyping using supersomes should be interpreted cautiously, taking into account the inhibitory effect of the surfactant employed. Blind molecular docking results agreed with the experimental trend, showing the highest interactive profile with the isoforms CYP3A4 and 3A5, and suggested hydrophobic, π-stacking, and hydrogen bonds as the primary intermolecular forces responsible for the protein-compound interaction.

The water-soluble compound [Ru3O(CH3COO)(6)(4-ampy)(3)]Cl (1, 4-ampy=4-aminopyridine) was evaluated in terms of its biologically relevant properties. Compound 1 participates in a hydrogen bonding network which includes the NH2 substituents of the ancillary ligands, methanol molecules, the Cl- counter-ion, and a non-conventional hydrogen bond with the neighboring 4-ampy molecules ' pi-cloud, as determined by X-ray measurements. One protonation equilibrium was observed at pH values below 2.3. Additionally, the compound exhibited a partition coefficient value of -0.86 (+/- 0.07), indicating that it is highly hydrophilic. At 37(degrees)C and pH=7.4 (phosphate buffer), compound 1 shows moderate (K-sv=2.4 10(4) M-1) and spontaneous (Delta G=-26.4 kJ mol(-1)) binding to human serum albumin (HSA) through ground-state association, which involves formation of hydrogen bonds (Delta H=-35.7 kJ mol(-1) and, Delta S=-29.8 J mol-K-1 (-1)). Molecular docking calculations support the formation of hydrogen bonds between 1 and HSA, and suggest subdomain IIA (site I), which contains the Trp-214 residue, as the primary interactive pocket, in agreement with the experimental static fluorescence quenching mechanism. Furthermore, a preliminary assay reveals that 1 has low cytotoxicity towards human glioblastoma U87-MG cells.

We report the DNA-binding properties of three porphyrins with peripheral thienyl substituents (TThPor, PdTThPor and PtTThPor). The binding capacity of each porphyrin with DNA was determined by UV-Vis and steady-state fluorescence emission spectroscopy combined with molecular docking calculations. The results suggest that the interaction of these compounds probably occurs via secondary interactions via external grooves (minor grooves) around the DNA macromolecule. Moreover, porphyrins containing peripheral Pd(II) or Pt(II) complexes (PdTThPor and PtTThPor) were able to promote photo-damage in the DNA.

Due to the scarcity of spectroscopic studies on metal-coordinated naphthalimides, and aiming to investigate fundamental spectroscopic aspects, we have described here the aggregates of N-(4-pyridyl)-1,8-naphthalimide (NI-py) in solution as well as solvatochromism displayed by it and by the coordination compounds [Ru3O(CH3COO)6(NI-py)3]n, n = +1 or 0. Based both on theoretical calculations and luminescence spectra, we demonstrated that in aqueous media, the NI-py π-stacking is thermodynamically favored, suggesting a preferable conformation where the pyridine and naphthalene moieties of two NI-py molecules are parallel to each other, but are not co-planar within an individual molecule, due to steric hindrance. The NI-py ππ* band displayed positive solvatochromism, to which the major contribution was the Catalan's SP parameter (solvent polarizability). This observation is fully consistent with the extended π-electron cloud of the NI-py naphthalene ring. However, a secondary contribution of the SA (solvent acidity) was also observed, owing to the electron pairs available at the N-heteroatom of the pyridine rings and at the carbonyl-group oxygen atoms. Finally, the multiparametric solvent effect analysis indicated that the electronic coupling between coordinated NI-py and the metallic core is modulated by the charge of the [Ru3O(CH3COO)6] core, being higher for the reduced species [Ru3O(CH3COO)6(NI-py)]0. In addition, in this reduced species, there is no overlap between NI-py ππ* and the [Ru3O(CH3COO)6] charge transfer (CT) transitions, leading to the observation of the dependence of the CT energy with the SdP parameter (solvent dipolarity) since the CT transition implies in a charge-separation state.

The mu-oxo bridged ruthenium acetate 1 [Ru2O(CH3COO)(2)(5-CH3-1,10-phen)(2)(py)(2)](PF6)(2) (5-CH3-1,10-phen=5-methyl-1,10-phenanthroline; py=pyridine) is presented. Its electronic and infrared spectra, as well as its cyclic voltammograms are all consistent with the proposed structure. Regarding biological properties, we collected data for 1 and its analog [Ru2O(CH3COO)(2)(1,10-phen)(2)(py)(2)](PF6)(2) (2) to infer the role of phenantroline methylation. The HSA fluorescence is quenched by 1 and the presence of variable concentrations of it did not affect the tau(1/2) values for the HSA excited state lifetime (mean tau(1/2) values=3.56, 3.46, and 3.32 ns at 298, 304, and 310 K respectively). Circular dichroism showed that the HSA alpha-helix content decreased only 5 % upon interaction with 1, which formed a ground-state adduct with HSA, not changing the protein structure to a significant extent. Interaction between 1 and DNA was weak; Benesi-Hildebrand constants were in the order of 10(2) M-1. We probed the allergenic potential/antiallergic activity of 1, observing that 200 mu M inhibited mast cell degranulation by about 80 %, while cell viability remained unaltered throughout the measurement (2 h). Therefore, 1 has antiallergic potential and is not an allergen. Regarding its anticancer activity, at all the employed concentrations, 1 was more cytotoxic than 2 against B16F10 murine melanoma cancer cells. At 25 mu M, 1 reduced cell viability to less than 14 %, while 2 reduced cell viability to only 78 %.

Polynuclear mu-oxo complexes are commonly observed for second and third row transition metals. This review is particularly interested in the mu 3-oxo-bridged ruthenium trinuclear clusters of general formula [Ru3O (CH3COO)6(L)3]n, where typically L are coordinating solvents, N-heterocyclic ligands, phosphines or small species such as CO, NO, and CN-; and n = 0 or + 1. These molecules are very versatile coordination compounds, characterized by an absorption profile with high coverage of the ultraviolet and visible regions, depending on their formal charges, and rich multi-electron redox behavior, yielding, for example, electrochromic devices and sensors. More recently, innovative approaches allowed the community to explore previously unfathomable applications for this type of system, such as trypanocidal or anticancer agents. Besides their intrinsic characteristics, they have also been used as building blocks for extended structures, opening up a whole new range of options. This text invites the readers to a description, from a structural point of view, of monomeric and extended compounds obtained from the primary unit [Ru3O(RCOO)6]n, reported on the last 20 years. In addition, we present an overview of the compounds' applications, focusing on their use as catalysts, in the construction of

A comparative analysis of ruthenium nitrosyl spectroscopic data helps unravel the electronic character of the unit {RuNO}6[RuIIIRuIIIO].

The compound [Ru2O(keto)(2)(py)(6)](PF6)(2), keto=ketoprofen and py=pyridine, interacts with calf thymus-DNA with K-b=1.08x10(4) M-1. It efficiently quenches HSA fluorescence in different temperatures, with Ksv values in the 10(4)-10(5) M-1 range, both by dynamic and static mechanisms. The data provided by the double logarithmic and van't Hoff approximations indicated a moderate (K-b approximate to 10(4) M-1) and spontaneous (Delta G<0) interaction, being enthalpically driven (Delta H=-27.1 kJ mol(-1) and Delta S=-5.3 J mol(-1) K-1). Molecular docking calculations confirmed that the binuclear compound interacts with HSA more strongly than with DNA. The occurrence of a high contribution from electrostatic forces was observed, fully consistent with the bicationic nature of [Ru2O(keto)(2)(py)(6)](PF6)(2). The molecular docking results also revealed that the interaction occurs in an external subdomain, explaining the lack of significant conformational changes in the protein, as probed by circular dichroism spectra.

This work presents for the first time a systematic investigation on the thermal decomposition and thermal stability of ten representative triruthenium clusters of general formula [Ru-3(mu(3)-O)(mu-Ac)(6)(L)(2)L '](n) (Ac = CH3COO and L = N-heterocycles or H2O; L ' = py, Ac, H2O, CO or NO; n = 1+ or 0). Despite the variation of the N-heterocyclic L ligands, the pyridyl, nitrosyl and carbonyl species are quite similar in terms of their thermal decomposition path. The loosely bound solvent molecules are lost first, followed by the loss of the N-heterocyclic ligands, with the final collapse of the metallic core upon acetates oxidation in the range from 270 to 300 degrees C. Their thermal stability depends on the nature of the L and L ' ligands, varying up to 60 degrees depending on the presence of NO, CO or N-heterocyclic ligands. (C) 2021 Elsevier Ltd. All rights reserved.

Four metalo-intercalators ([Ru3(μ3-O)(μ2-OAc)5(L)(py)2]PF6, L = phenazines) present high DNA intercalation constants and high HSA affinity. They are active against melanoma cancer and T. Cruzi parasite.