Begoña García

On the properties of 1-butyl-3-methylimidazolium octylsulfate ionic liquid

This work reports on a theoretical and experimental study on the ionic liquid 1-butyl-3-methylimidazolium octylsulfate ([BMIM]OS). The halogen-free ionic liquid [BMIM]OS is a stable solvent regarding hydrolysis, whose availability, toxicologically favourable features and well documented biodegradability turns it into a suitable candidate for different multiton-scale industrial applications. The pressure–volume–temperature behaviour of this fluid has been evaluated accurately over wide ranges of temperature and pressure, and correlated successfully with the empirical TRIDEN equation. From the measured data the relevant derived coefficients, isothermal compressibility, isobaric expansibility and internal pressure have been calculated. Other valuable properties such as isobaric heat capacity, speed of sound and refractive index were measured at several temperatures and atmospheric pressure. The molecular structure was looked into by quantum computations at the B3LYP/6-31 + g(d) level and classical molecular dynamics simulations in the NPT ensemble with the OPLS–AA forcefield. Both macroscopic and microscopic studies concur in a complex structure involving microheterogenous polar and non-polar domains, brought about by the aggregation of the non-polar anionic chains.

Anticancer activity and DNA binding of a bifunctional Ru(II) arene aqua-complex with the 2,4-diamino-6-(2-pyridyl)-1,3,5-triazine ligand.

The synthesis and full characterization of the new aqua-complex [(η(6)-p-cymene)Ru(OH2)(κ(2)-N,N-2-pydaT)](BF4)2, [2](BF4)2, and the nucleobase derivative [(η(6)-p-cymene)Ru(9-MeG)(κ(2)-N,N-2-pydaT)](BF4)2, [4](PF6)2, where 2-pydaT = 2,4-diamino-6-(2-pyridyl)-1,3,5-triazine and 9-MeG = 9-methylguanine, are reported here. The crystal structures of both [4](PF6)2 and the chloro complex [(η(6)-p-cymene)RuCl(κ(2)-N,N-2-pydaT)](PF6), [1](PF6), have been elucidated by X-ray diffraction. The former provided relevant information regarding the interaction of the metallic fragment [(η(6)-p-cymene)Ru(κ(2)-N,N-2-pydaT)](2+) and a simple model of DNA. NMR and kinetic absorbance studies have proven that the aqua-complex [2](BF4)2 binds to the N7 site of guanine in nucleobases, nucleotides, or DNA. A stable bifunctional interaction (covalent and partially intercalated) between the [(η(6)-p-cymene)Ru(κ(2)-N,N-2-pydaT)](2+) fragment and CT-DNA has been corroborated by kinetic, circular dichroism, viscometry, and thermal denaturation experiments. The reaction mechanism entails the very fast formation of the Ru-O-(PO3) linkage prior to the fast intercalation of the 2-pydaT fragment. Then, a Ru-N7-(G) covalent bond is formed at the expense of the Ru-O-(PO3) bond, yielding a bifunctional complex. The dissociation rate of the intercalated fragment is slow, and this confers additional interest to [2](BF4)2 in view of the likely correlation between slow dissociation and biological activity, on the assumption that DNA is the only biotarget. Furthermore, [2](BF4)2 displays notable pH-dependent cytotoxic activity in human ovarian carcinoma cells (A2780, IC50 = 11.0 μM at pH = 7.4; IC50 = 6.58 μM at pH = 6.5). What is more, complex [2](BF4)2 is not cross-resistant with cisplatin, exhibiting a resistance factor, RF(A2780cis), of 0.28, and it shows moderate selectivity toward the cancer cell lines, in particular, A2780cis (IC50 = 3.0 5 ± 0.08 μM), relative to human lung fibroblast cells (MRC-5; IC50 = 24 μM), the model for healthy cells.

Outer-sphere hexacyanoferrate(III) oxidation of organic substrates

Abstract This review surveys the kinetics of the oxidation of organic substrates by hexacyanoferrate(III). Although a relatively poor oxidant, hexacyanoferrate(III) is a selective outer-sphere reactant applicable to the most easily oxidizable substrates, and frequently it is used as an interceptor of free radicals; this converts this species into an efficient one-electron oxidant particularly interesting in the comparative study of octahedral complexes. The major developments for each family of substrates are emphasized, comparing the mechanistic details for the various reaction types.

Interaction of the DNA bases and their mononucleotides with pyridine-2-carbaldehyde thiosemicarbazonecopper(II) complexes. Structure of the cytosine derivative

Experimental studies of the binding interactions of [CuL(NO(3))] and [{CuL(NO(3))}(2)] (HL=pyridine-2-carbaldehyde thiosemicarbazone, and HL=pyridine-2-carbaldehyde 4N-methylthiosemicarbazone) with adenine, guanine, cytosine, thymine and their mononucleotides (dNMP), 2-deoxyadenosine-5-monophosphate, (dAMP), 2-deoxyguanosine-5-monophosphate, (dGMP), 2-deoxycytidine-5-monophosphate (dCMP), and thymidine-5-monophosphate (dTMP) have been carried out in aqueous solution at pH 6.0, I=0.1M (NaClO(4)) and T=25 degrees C. The complexation constants of these compounds, calculated by Hildebrand-Benesi plots for the dye binding, D, ([CuL] or [CuL]) to the nucleobases or nucleotides (P), have shown two linear stretches in adenine, guanine, dAMP and dGMP. The data were analyzed in terms of formation of 1:1 DP and 1:2 DP(2) complexes with increasing purine base or nucleotide content. For cytosine and dCMP only 1:1 complexes have been observed, whereas for thymine and dTMP such complex structures were not observed. The [CuL(Hcyt)](ClO(4)) cytosine derivative has been isolated and characterized. The crystal structure consists of perchlorate ions and [CuL(Hcyt)](+) monomers attached by hydrogen bond, chelate pi-ring and anion-pi interactions. The Cu(2+) ions bind to the NNS chelating moiety of the thiosemicarbazone ligand and the cytosine N13 site (N3, most common notation) yielding a square-planar geometry. A pseudocoordination to the cytosine O12 site (=O2) can also be considered.

Volumetric properties, viscosities and refractive indices of binary mixed solvents containing methyl benzoate

Densities, dynamic viscosities, and refractive indices of the binary mixed solvents of methylbenzoate with a set of eleven organic solvents provided with six carbon atoms but different structure and functional groups were measured over the whole composition range. Thermodynamic, transport, solubility, and electrical properties were analyzed for all systems; from the experimental quantities, excess and mixing properties were deduced and interpreted in terms of intermolecular interactions and structural changes upon mixing. Mixing viscosities and excess Gibbs energies of activation for viscous flow support the role played by the size of the cosolvent on the mixture behaviour. Analysis in terms of solvent solubility parameters was in convincing good agreement with experimental results. The Soave and Peng–Robinson equations of state and the Wong–Sandler mixing rule are used to correlate volumetric properties. The predictive ability of several one-parameter and two-parameter viscosity models was also tested.

Ag2 and Ag3 clusters: synthesis, characterization, and interaction with DNA.

Subnanometric samples, containing exclusively Ag2 and Ag3 clusters, were synthesized for the first time by kinetic control using an electrochemical technique without the use of surfactants or capping agents. By combination of thermodynamic and kinetic measurements and theoretical calculations, we show herein that Ag3 clusters interact with DNA through intercalation, inducing significant structural distortion to the DNA. The lifetime of Ag3 clusters in the intercalated position is two to three orders of magnitude longer than for classical organic intercalators, such as ethidium bromide or proflavine.

Biological assays and noncovalent interactions of pyridine-2-carbaldehyde thiosemicarbazonecopper(II) drugs with [poly(dA-dT)]2, [poly(dG-dC)]2, and calf thymus DNA

The interaction of the Cu(II) drugs CuL(NO3) and CuL′(NO3) (HL is pyridine-2-carbaldehyde thiosemicarbazone and HL′ is pyridine-2-carbaldehyde 4N-methylthiosemicarbazone, in water named [CuL]+ and [CuL′]+) with [poly(dA–dT)]2, [poly(dG–dC)]2, and calf thymus (CT) DNA has been probed in aqueous solution at pH 6.0, Ixa0=xa00.1xa0M, and Txa0=xa025xa0°C by absorbance, fluorescence, circular dichroism, and viscosity measurements. The results reveal that these drugs act as groove binders with [poly(dA–dT)]2, with a site size nxa0=xa06–7, whereas they act as external binders with [poly(dG–dC)]2 and/or CT-DNA, thus establishing overall electrostatic interaction with nxa0=xa01. The binding constants with [CuL′]+ were slightly larger than with [CuL]+. The title compounds display some cleavage activity in the presence of thiols, bringing about the rupture of the DNA strands by the reactive oxygen species formed by reoxidation of Cu(I) to Cu(II); this feature was not observed in the absence of thiols. Mutagenic assays performed both in the presence and in the absence of S9 mix, probed by the Ames test on TA 98, TA 100, and TA 102, were negative. Weak genotoxic activity was detected for [CuL]+ and [CuL′]+, with a significative dose–response effect for [CuL′]+, which was shown to be more cytotoxic in the Ames test and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cell proliferation assays. Methylation of the terminal NH2 group enhances the antiproliferative activity of the pyridine-2-carbaldehyde thiosemicarbazones.

ZWITTERIONIC PYRIDINECARBOXYLIC ACIDS

A study of the acid-base behaviour of the three isomeric pyridinecarboxylic acids (picolinic, nicotinic and isonicotinic acid) was carried out using spectrophotometric and potentiometric measurements. The cationic form of picolinic acid converts partially into the corresponding zwitterion (pK1) within a borderline acidity range where neither the pH scale nor the acidity functions work satisfactorily. Protonation of the carboxyl groups (pK33) occurred at the highest acidity levels employed. The medium effects observed on the spectral curves were corrected by factor analysis. The potentiometric measurements gave values for pK1 and pK2 only, which were in good agreement with those determined spectrophotometrically.

New aspects of the interaction of the antibiotic coralyne with RNA: coralyne induces triple helix formation in poly(rA)•poly(rU)

The interaction of coralyne with poly(A)•poly(U), poly(A)•2poly(U), poly(A) and poly(A)•poly(A) is analysed using spectrophotometric, spectrofluorometric, circular dichroism (CD), viscometric, stopped-flow and temperature-jump techniques. It is shown for the first time that coralyne induces disproportionation of poly(A)•poly(U) to triplex poly(A)•2poly(U) and single-stranded poly(A) under suitable values of the [dye]/[polymer] ratio (CD/CP). Kinetic, CD and spectrofluorometric experiments reveal that this process requires that coralyne (D) binds to duplex. The resulting complex (AUD) reacts with free duplex giving triplex (UAUD) and free poly(A); moreover, ligand exchange between duplex and triplex occurs. A reaction mechanism is proposed and the reaction parameters are evaluated. For CD/CP> 0.8 poly(A)•poly(U) does not disproportionate at 25°C and dye intercalation into AU to give AUD is the only observed process. Melting experiments as well show that coralyne induces the duplex disproportionation. Effects of temperature, ionic strength and ethanol content are investigated. One concludes that triplex formation requires coralyne be only partially intercalated into AUD. Under suitable concentration conditions, this feature favours the interaction of free AU with AUD to give the AUDAU intermediate which evolves into triplex UAUD and single-stranded poly(A). Duplex poly(A)•poly(A) undergoes aggregation as well, but only at much higher polymer concentrations compared to poly(A)•poly(U).

The N-methylpyrrolidone–(C1–C10) alkan-1-ols solvent systems

Densities, viscosities and refractive indices of the N-methylpyrrolidoneu2006+u2006alkan-1-ols (C1–C10) binary systems at 298.15 K and atmospheric pressure have been measured over the whole composition range; from these measurements the values for excess molar volumes, mixing viscosities, internal pressures, and excess Gibbs energies of activation for viscous flow were calculated. The molecular interactions in these mixtures can be interpreted on the basis of the variation of the excess and mixing functions with the mixture composition. The cubic equations of state proposed by Soave and Peng–Robinson were used to process the data on excess molar volumes and partial molar volumes using two different mixing rules. Several semiempirical methods for predicting viscosities of liquid mixtures were applied with good results; the ability of the models proposed by Cao (GC-UNIMOD) and Wu to predict viscosity data nwas also tested.