Showing papers on "Aquation published in 2012"

The contrasting chemical reactivity of potent isoelectronic iminopyridine and azopyridine osmium(II) arene anticancer complexes

Abstract: A wide variety of steric and electronic features can be incorporated into transition metal coordination complexes, offering the prospect of rationally-designed therapeutic agents with novel mechanisms of action. Here we compare the chemical reactivity and anticancer activity of organometallic OsII complexes [Os(η6-arene)(XY)Z]PF6 where arene = p-cymene or biphenyl, XY = N,N′-chelated phenyliminopyridine or phenylazopyridine derivatives, and Z = Cl or I. The X-ray crystal structure of [Os(η6-p-cym)(Impy-OH)I]PF6·0.5CH2Cl2·H2O (Impy-OH = 4-[(2-pyridinylmethylene)amino]-phenol) is reported. Like the azopyridine complexes we reported recently (Dalton Trans., 2011, 40, 10553–10562), some iminopyridine complexes are also potently active towards cancer cells (nanomolar IC50 values). However we show that, unlike the azopyridine complexes, the iminopyridine complexes can undergo aquation, bind to the nucleobase guanine, and oxidize coenzyme nicotine adenine dinucleotide (NADH). We report the first detection of an Os-hydride adduct in aqueous solution by 1H NMR (−4.2 ppm). Active iminopyridine complexes induced a dramatic increase in the levels of reactive oxygen species (ROS) in A549 lung cancer cells. The anticancer activity may therefore involve interference in the redox signalling pathways in cancer cells by a novel mechanism.

Photochemical versus Thermal Synthesis of Cobalt Oxyhydroxide Nanocrystals

Abstract: Photochemical methods facilitate the generation, isolation, and study of metastable nanomaterials having unusual size, composition, and morphology. These harder-to-isolate and highly reactive phases, inaccessible using conventional high-temperature pyrolysis, are likely to possess enhanced and unprecedented chemical, electromagnetic, and catalytic properties. We report a fast, low-temperature and scalable photochemical route to synthesize very small (∼3 nm) monodisperse cobalt oxyhydroxide (Co(O)OH) nanocrystals. This method uses readily and commercially available pentaamminechlorocobalt(III) chloride, [Co(NH3)5Cl]Cl2, under acidic or neutral pH and proceeds under either near-UV (350 nm) or Vis (575 nm) illumination. Control experiments showed that the reaction proceeds at competent rates only in the presence of light, does not involve a free radical mechanism, is insensitive to O2, and proceeds in two steps: (1) Aquation of [Co(NH3)5Cl]2+ to yield [Co(NH3)5(H2O)]3+, followed by (2) slow photoinduced rele...

Redox processes in photochemistry of Pt(IV) hexahaloid complexes

Abstract: Ultrafast pump–probe spectroscopy (λpump = 405 nm) was applied to study the primary photochemical processes for PtCl62− and PtBr62− complexes in aqueous and alcohol solutions. For PtCl62−, an intermediate with a lifetime of ca. 200 ps was registered and identified as an Adamson radical pair [PtIIICl52−⋯Cl˙]. The transformations of the primary intermediate give rise to successive formation of different Pt(III) species. The reactions of Pt(III) results in chain photoaquation in aqueous solutions and reduction of Pt(IV) to Pt(II) in alcohol solutions. For PtBr62− complex, the previously reported (I. L. Zheldakov, M. N. Ryazantsev and A. N. Tarnovsky, J. Phys. Chem. Lett., 2011, 2, 1540; I. L. Zheldakov, PhD thesis, Bowling Green State University, 2010) formation of active 3PtBr5− intermediate is followed by very fast (15 ps) aquation of Pt(IV) in aqueous solutions and parallel reactions of solvation and reduction of Pt(IV) to Pt(II) in alcohol solutions. All the processes in alcohols are finished within 0.5 ns. The data of ultrafast experiments are supported by nanosecond laser flash photolysis and stationary photolysis.

Chimeric platinum-polyamines and DNA binding. Kinetics of DNA interstrand cross-link formation by dinuclear platinum complexes with polyamine linkers.

Abstract: The first observation of a polyamine–DNA interaction using 2D [1H, 15N] HSQC NMR spectroscopy allows study of the role of the linker in polynuclear platinum-DNA interactions and a novel “anchoring” of the polyamine by Pt–DNA bond formation allows examination of the details of conformational B → Z transitions induced by the polyamine. The kinetics and mechanism of the stepwise formation of 5′-5′ 1,4-GG interstrand cross-links (IXLs) by fully 15N-labeled [{trans-PtCl(15NH3)2}2{μ-(15NH2(CH2)615NH2(CH2)615NH2)}]3+ (1,1/t,t-6,6, 1) and [{trans-PtCl(15NH3)2}2{μ-(15NH2(CH2)615NH2(CH2)215NH2(CH2)615NH2)}]4+ (1,1/t,t–6,2,6, 1′) with the self-complementary oligonucleotide 5′-{d(ATATGTACATAT)2} (duplex I) are compared to the analogous reaction with 1,0,1/t,t,t (BBR3464) under identical conditions (pH 5.4, 298 K). Initial electrostatic interactions with the DNA are delocalized and followed by aquation to form the monoaqua monochloro species. The rate constant for monofunctional adduct formation, kMF, for 1 (0.87 M–1 ...

Factors that influence the antiproliferative activity of half sandwich RuII–[9]aneS3 coordination compounds: activation kinetics and interaction with guanine derivatives

Abstract: Half sandwich Ru(II)–[9]aneS3 complexes ([9]aneS3 = 1,4,7-trithiacyclononane) are being studied for their antiproliferative activity. We investigated here the activation kinetics of three such complexes, namely [Ru([9]aneS3)(en)Cl](PF6) (1), [Ru([9]aneS3)(bpy)Cl](PF6) (2) and [Ru([9]aneS3)(pic)Cl] (3) (en = 1,2-diaminoethane, pic = picolinate), and their interaction with DNA model bases. The aim of the study was to assess how they are affected by the nature and charge of the chelating ligand. The model reactions of 1–3 with the guanine derivatives 9-methylguanine (9MeG), guanosine (Guo), and guanosine 5′-monophosphate (5′-GMP) were studied by NMR spectroscopy. All reactions lead, although with different rates and to different extents, to the formation of monofunctional adducts with the guanine derivatives N7-bonded to the Ru center. Two products, the complexes [Ru([9]aneS3)(en)(9MeG-N7)](PF6)2 (4) and [Ru([9]aneS3)(pic)(9MeG-N7)](PF6) (10), were structurally characterized also by X-ray crystallography. The structure of 4 is stabilized by strong intramolecular H-bonding between an NH of en and the carbonyl O6 of 9MeG. The kinetics of aquation and anation of complexes 2 and 3, as well as the kinetics and the mechanism of the reaction of complexes 1–3 with the biologically more relevant 5′-GMP ligand were studied by UV-Vis spectroscopy. The rate of the reaction of 1–3 with 5′-GMP depends on the nature of the chelating ligand rather than on the charge of the complex, decreasing in the order 3 ≈ 2 > 1. The measured enthalpies and entropies of activation (ΔH≠ > 0, ΔS≠ < 0) support an associative mechanism for the substitution process.

Hydrolysis mechanism of anticancer Pd(II) complexes with coumarin derivatives: a theoretical investigation

Abstract: The hydrolysis reaction mechanisms of a new generation Pd(II) anticancer drugs containing coumarin derivatives have been investigated combining density functional theory with the conductor-like dielectric continuum model approach. The first and the second aquation processes have been explored for the cis and trans counterpart of title PdL2 complex. Two possibilities for the second hydrolysis process have been analyzed for both compounds. From our data emerge that cis and trans PdL2 compounds have a different behavior in water. cis-isomer readily undergo first hydrolysis process generating a mono-aqua complex while both the pathways investigated for the second aquation reaction are more energetically demanding, suggesting that the mono-aqua complex could act as active species. On the contrary, for trans-compound, both the investigated reactions for the second aquation process occur by overcoming activation barriers comparable with that found for the first hydrolysis reaction. According to our data, trans-oriented PdL2 drug could undergo degradation process generating non-active compounds with the consequent lack of pharmacological activity.

Aquation and dimerization of osmium(II) anticancer complexes: a density functional theory study

Abstract: In this paper, the hydrolytic and aqueous solution chemistry of two half-sandwich OsII arene complexes [(η6-p-cym)Os(pic)Cl] (1) and [(η6-p-cym)Os(mal)Cl] (2) (pic = 2-picolinic acid and mal = maltolate) have been investigated using density functional theory (DFT). For aquation (substitution of chloride by H2O) of the complexes, three attacking models were explored, including two forms of side attack (A and B) and back attack C. Side attack A required the lowest free energy of activation of the three, both in the gas phase and in aqueous solution, suggesting that it best describes the hydrolysis of the complexes. Both the activation and reaction energies indicated faster aquation for 2 than 1, which was in accordance with previous experimental observations. With the side attack model of the complexes, it was found that the conformations of complexes had little effect on the aquation process. Moreover, mechanistic pathways have been obtained for the dimerization of aqua adducts. As for 1a, the ligand departure was the rate-determining step with an activation free energy of 26.1 kcal mol−1, while for 2a, the first step of ring opening and protonation is rate-determining with a free energy of activation of 24.8 kcal mol−1, suggesting that 1a was kinetically more stable toward dimerization. There were three factors presented to explain the stability of 1a: differences in HOMO/LUMO densities, the large activation energy of 1a, and stabilization of Os-pic bonding. This study assists in understanding the aqueous solution chemistry of the anticancer complexes and in the design of novel anticancer drugs.

Kinetic studies on H+-catalysed aquation of chromium(III)-oxalato-asparaginato and chromium(III)-oxalato-histidinato complexes

Abstract: Three chromium(III) complexes with asparagine (Asn) and histidine (His) of the [Cr(ox)2(Aa)]2− type, where Aa = N,O–Asn, N,O–His or N,N′–His, were obtained and characterized in solution. The complexes with N,O–Aa undergo acid-catalysed aquation to give a free amino acid and cis-[Cr(ox)2(H2O)2]−, whereas the complex with N,N′–His undergoes parallel reaction paths: (1) isomerization to the N,O–His complex and (2) liberation of an oxalate ligand. Kinetics of the N,O–Aa complexes in HClO4 media were studied spectrophotometrically under pseudo-first-order conditions. The absorbance changes were attributed to the chelate ring opening at the Cr–N bond. The linear dependence of rate constants on [H+] was established, and a mechanism for the chelate ring cleavage was postulated. The existence of a metastable intermediate with O-monodentate Aa ligand was proved experimentally. Effect of [Cr(ox)2(Aa)]2− on 3T3 fibroblasts proliferation was studied. The tests revealed low cytotoxicity of the complexes. Complexes with Ala, His and Cys are good candidates for biochromium sources.

Photodissociation of a ruthenium(II) arene complex and its subsequent interactions with biomolecules: a density functional theory study.

Abstract: The piano-stool RuII arene complex [(η6-benz)Ru(bpm)(py)]2+ (benz = benzene, bpm = 2,2′-bipyrimidine, and py = pyridine), which is conventionally nonlabile (on a timescale and under conditions relevant for biological reactivity), can be activated by visible light to selectively photodissociate the monodentate ligand (py). In the present study, the aquation and binding of the photocontrolled ruthenium(II) arene complex [(η6-benz)Ru(bpm)(py)]2+ to various biomolecules are studied by density functional theory (DFT) and time-dependent DFT (TDDFT). Potential energy curves (PECs) calculated for the Ru–N (py) bonds in [(η6-benz)Ru(bpm)(py)]2+ in the singlet and triplet state give useful insights into the photodissociation mechanism of py. The binding energies of the various biomolecules are calculated, which allows the order of binding affinities among the considered nuleic-acid- or protein-binding sites to be discerned. The kinetics for the replacement of water in the aqua complex with biomolecules is also considered, and the results demonstrate that guanine is superior to other biomolecules in terms of coordinating with the RuII aqua adduct, which is in reasonable agreement with experimental observations.

Kinetics and mechanism of aquation of bromopentammine cobalt(III) cation assisted by ion-pairing succinate anion in ethane-2-diol-water mixtures

Abstract: The aquation kinetics of bromopentammine cobalt(III) ion has been investigated in the presence of different concentrations of succinate ion in aqueous medium and that mixed with ethane-1,2-diol (up to 50%, w/w) within the temperature range (35-65 o C). The ion-pairing succinate ion concentration (L) and the observed rate constant have been determined at different experimental conditions. The thermodynamic parameters of activation have been calculated and discussed in terms of solvent effects. Also the extrathermodynamic analyses of the obtained results have been discussed on the basis of solute-solvent and solvent-solvent interactions. An empirical correlation between the rate coefficient and the concentration of the ion-pairing succinate ligand (L) has been established and a suggested reaction mechanism is proposed.

Kinetic studies on H+-catalysed aquation of some chromium(III)-oxalato-amino acid complexes

Abstract: The following chromium(III) complexes with serine (Ser) and aspartic acid (Asp) were obtained and characterized in solution: [Cr(ox)2(Aa)]2− (where Aa = Ser or Asp), [Cr(AspH−1)2]− and [Cr(ox)(Ser)2]−. In acidic solutions, [Cr(ox)2(Aa)]2− undergoes acid-catalysed aquation to cis-[Cr(ox)2(H2O)2]− and the appropriate amino acid. [Cr(ox)(Ser)2]− undergoes consecutive acid-catalysed Ser liberation to give [Cr(ox)(H2O)4]+, and the [Cr(Asp)2]− ion is converted into [Cr(Asp)(H2O)4]2+. Kinetics of these reactions were studied under isolation conditions. The determined rate expressions for all the reactions are of the form: kobs = a + b[H+]. Reaction mechanisms are proposed, and the meaning of the determined parameters has been established. Evidence for the formation of an intermediate with O-monodentate amino acid is given. The effect of the R-substituent at the α-carbon atom of the amino acid on the complex reactivity is discussed.

Inclusion Compounds of Cucurbit[n]urils with Metal Complexes

Abstract: A new class of supramolecular compounds—inclusion compounds of metal complexes encapsulated in organic macrocyclic cavitands cucurbit[n]urils (CB[n], C6n H6n N4n O2n , n = 7−10)—has been surveyed. A unique combination of a rather rigid hydrophobic intramolecular cavity and negatively charged portals favors the formation of stable host-guest compounds. Basic methods of synthesis of inclusion compounds of CB[n] with metal complexes have been reported, and the structures of the resulting products isolated as crystals and characterized by X-ray crystallography have been considered. The effect of encapsulation on the geometric and spectral characteristics of the complexes and their redox properties has been traced. It has been shown that encapsulation in CB[n] can lead to a change in the reactivity of the complexes in thermolysis and isomerization and aquation reactions. Encapsulation of biologically active metal complexes in CB[n] is a promising strategy for designing new-generation prolonged-action pharmaceuticals.

Reactivity of the antitumor complex (H2trz)[trans-RuCl4(N2-Htrz)2] in the presence of DNA purines within a fluorinated silica matrix.

Abstract: The stability of the antitumor Ru(III) complex (H(2)trz)[trans-RuCl(4)(N(2)-Htrz)(2)] within a tailored sol-gel silica matrix was studied, combining the information from UV-vis and infrared spectroscopies. The matrix was synthesized by a one-step sol-gel process catalyzed by hydrofluoric acid, resulting extremely light, hydrophobic and fluorinated. It is shown that upon encapsulation, the complex undergoes a series of processes, starting with the increase in charge density on the metal center, followed by hydrolysis reactions. The modified complex interacts with the matrix through hydrogen bonds between the aquo/hydroxo ligands and the fluorine atoms. Its interactions with DNA purines (guanine and adenine) were probed within the confined medium defined by the same silica matrix. It is found that coencapsulated guanine does not interfere with the complex aquation processes, while coencapsulated adenine has a delaying effect. No covalent bonding between the complex and the purines is detected, but interactions between the triazole ligands and the imidazole ring of guanine and the imidazole and pyrimidine rings of adenine are observed. Hydrogen bonding is established between the carbonyl and the ammine groups of guanine and the aquo/hydroxo ligands of the complex. For adenine, those interactions involve mostly the N9H of the purine and the NH groups of the triazole ligands, in addition to π-π interactions.