Begoña García

Universidad de Burgos | UBU · Department of Chemistry

Cancers are driven by multiple genetic mutations but evolve to evade treatments targeting specific mutations. Nonetheless, cancers cannot evade a treatment that targets mitochondria, which are essential for tumor progression. Iridium complexes have shown anticancer properties, but they lack specificity for their intracellular targets, leading to un...

A new series of perylene and hemicoronene diimides, obtained by visible light photocyclization, are presented, between them some remarkable examples that are soluble in only water, and give nanoparticles by self-association. Those compounds work as new fluorescent materials in water by complexation with cucurbit[7]uril, as well as selective G-quadr...

Three neutral Pt(II) complexes containing 1-Methylimidazole and the antifungal imidazolyl drugs Clotrimazole and Bifonazole have been prepared. The general formula of the new derivatives is [Pt(κ²-(C^N)Cl(L)], where C^N stands for ppy = 2-phenylpyridinate, and L = 1-Methylimidazole (MeIm) for [Pt-MeIm]; L = Clotrimazole (CTZ) for [Pt-CTZ] and L = B...

We report a screening study aimed to assess for the first time the air- and water-stability and the biological potential of simple metal-carbamates. These molecular metallic species are based on elements belonging to the groups 4–5, 7–9 and 11, and tin, and are easily available from inexpensive reagents. Complexes [Ag(O2CNEt2)] (13-Ag) and [Au(O2CN...

An important challenge in the field of anticancer chemotherapy is the search for new species to overcome the resistance of standard drugs. An interesting approach is to link bioactive ligands to metal fragments. In this work, we have synthesized a set of p-cymene-Ru or cyclopentadienyl-M (M = Rh, Ir) complexes with four chrysin-derived pro-ligands...

Cancer and antibiotic resistance are two global health threats that usually hamper clinical chemotherapeutic efficacy. Particularly for lung cancer, bacterial infections frequently arise thereby complicating the course of cancer treatment. In this sense, three new neutral luminescent cycloplatinated(II) photosensitizers of the type [Pt(dmba)(L)] (d...

We present here a combined spectroscopic and theoretical analysis of the binding of N,N’-bis(2-(1-piperazino)ethyl)-3,4,9,10-perylenetetracarboxylic acid diimide dichloride (PZPERY) to different biosubstrates. Absorbance titrations and circular dichroism experiments, melting studies and isothermal calorimetry (ITC) titrations reveal a picture where...

Several complexes of general formula [Ru(halide)(η6-p-cymene)(α-diimine)]+, in the form of nitrate, triflate and hexafluorophosphate salts, including a newly synthesized iodide compound, were investigated as potential anticancer drugs and bactericides. NMR and UV-Vis studies evidenced remarkable stability of the complexes in water and cell culture...

A structure-activity relationship (SAR) study in terms of G-quadruplex binding ability and antiproliferative activity of six fluorescent perylenemonoimide (PMIs) derivatives is reported. A positive charge seems to be the key to target G4. This study also reveals the importance of the element substitution in the potential biological activity of PMIs...

A series of diiron complexes with two cyclopentadienyls, two carbonyls, and one bridging vinyl‐aminoalkylidene as ligands, [3a–h]CF3SO3 and [4a–d]CF3SO3, was synthesized in 66–94% yields from diiron μ‐aminocarbyne precursors. The subsequent reactions with pyrrolidine led to selective fragmentation to aminoalkylidene‐ferracyclopentenone derivatives...

The synthesis and characterization of two half-sandwich complexes of Ru(II) and Ir(III) with thiabendazole as ancillary ligand and their DNA binding ability were investigated using experimental and computational methods. 1H NMR and acid-base studies have shown that aquo-complexes are the reactive species. Kinetic studies show that both complexes bi...

Based on the ability of terpyridines to react with G-quadruplex DNA (G4) structures along with the interest aroused by Zn as an essential metal centre in many biological processes, we have synthesized and characterized six Zn chloride or nitrate complexes containing terpyridine ligands with different 4´-substituents. In addition, we have studied th...

A new family of neutral chiral cyclometalated platinum(II) complexes with formula [Pt(κ2-(C^N))Cl(κ1-(L))], where (C^N) = 2-phenylpyridinate and (L) = 2-(2-pyridyl)benzimidazole (L1) or (N-(CH2)-Ar-(2-(2-pyridyl)benzimidazole) ligands; (Ar = phenyl (L2), naphthyl (L3), pyrenyl (L4)), have been synthesized and completely characterized. The unexpecte...

The synthesized 2-(hydroxy-1-naphtyl)imidazo-[4,5-f][1,10]phenanthroline (HNAIP) ligand and its new iridium ([Ir(ppy)2(HNAIP)]Cl) and rhodium ([Rh(ppy)2(HNAIP)]Cl) complexes, being ppy = 2-phenylpiridinate, show cytotoxic effects in SW480 (colon adenocarcinoma) and A549 (epithelial lung adenocarcinoma) cells. They all are cytotoxic in the tested ce...

A new family of neutral ruthenium(II) arene complexes of the type [Ru(η6-arene)X(κ2- O, N-L)] (η6-arene = p-cym, bz; X = Cl-, SCN-; HL1 = 2-(2'-hydroxyphenyl)benzimidazole, HL2 = 2-(2'-hydroxyphenyl)benzothiazole) has been synthesized and characterized. The cytotoxic activity of the Ru(II) complexes was evaluated in several tumor cell lines (A549,...

We describe the synthesis, characterization and biological and photocatalytic properties of two series of neutral Ir(III) biscyclometalated complexes of formula [Ir(C^N)2(N^O)], where the N^O ligands are 2‐(benzimidazolyl)phenolate‐N,O (L1, series a) and 2‐(benzothiazolyl)phenolate‐N,O (L2, series b), and the C^N ligands are 2‐(phenyl)pyridinate or...

Evidence of the significance of targeting chromatin compaction to increase the therapeutic index of chemotherapy is provided by Arturo López‐Quintela, Fernando Domínguez, and co‐workers in article number 1801317. Co‐administration of silver quantum clusters of three atoms, which increases chromatin accessibility, raises the efficacy of DNA‐binding...

Nanomaterials with very low atomicity deserve consideration as potential pharmacological agents owing to their very small size and to their properties that can be precisely tuned with minor modifications to their size. Here, it is shown that silver clusters of three atoms (Ag3‐AQCs)—developed by an ad hoc method—augment chromatin accessibility. Thi...

The proposed in vivo formation of G‐quadruplex DNA (G4 DNA) in promoter regions of oncogenes and in telomeres has prompted the development of small molecules with high affinity and selectivity for these structures. Herein we report the synthesis of a new di‐substituted bipyridine ligand and the corresponding complexes with Ni2+ and VO2+. Both these...

Given the potent anticancer properties of cis-diamminedichloroplatinum(II) and knowing its mode of action, we synthesized four new cis-[PtCl2(N^N)] organoplatinum complexes, two with N-substituted pbi ligands (pbiR = 1-R-2-(2-pyridyl)benzimidazole) (namely, 1 and 2) and two more with 4,4'-disubstituted bpy ligands (bpy = 2,2'-bipyridine) (namely, 3...

A new fluorescent, non‐cytotoxic perylene diimide derivative with two biotins at the peri position, PDI2B, has been synthesized. This molecule is able to interact selectively with G‐quadruplexes with scarce or no affinity towards single‐ or double‐stranded DNA. These features have enabled us to design a simple, effective, safe, cheap, and selective...

The interaction of RNA and DNA with two aluminum-containing complexes has been studied at 25°C by 1H-NMR, UV and CD spectroscopies, viscosity measurements and DFT simulations. The complex identified at pH = 7, Al13Cacx, can interact with the polynucleotides by external binding. Even though the affinity degree of the aluminum complex with RNA is ess...

Over the last years, focused interest in aluminum has been heightened by recent studies regarding its health effects. The possible relation with chronic diseases makes it convenient to address more in depth the reactivity of aluminum with biologically relevant molecules. The present work investigates the interaction of aluminum ion with two synthet...

Background: Stabilization of G-quadruplex helices by small ligands has attracted growing attention because they inhibit the activity of the enzyme telomerase, which is overexpressed in >80% cancer cells. TMPyP4, one of the most studied G-quadruplex ligands, is used as a model to show that the ligands can exhibit different binding features with dif...

Toulouse, France

In this work, we report experimental and computational evidence for the intercalation into the DNA base-pairs of the free quinones quinizarin (Q) and naphthazarin (N) and the interstrand covalent binding of their p-cymene di-ruthenium(ii) complexes (Cl2Ru2X, with X = N, Q bridging ligands). The intercalation extent for the N complex was larger than...

Thiosemicarbazones and their metal derivatives have long been screened as antitumor agents, and their interactions with DNA have been analysed. Herein, we describe the synthesis and characterization of compounds containing [CuL](+) entities (HL = pyridine-2-carbaldehyde thiosemicarbazone) and adenine, cytosine or 9-methylguanine, and some of their...

The interaction of doxorubicin (DOX) with triplex, duplex and single RNA helices has been studied by fluorimetric, circular dichroism, viscometry, DSC, ITC, T-jump kinetic relaxation technique and fluorescence lifetime measurements in near physiological conditions (pH = 7, I = 0.1 M and 25 °C). DOX binds to the groove of poly(rA)·2poly(rU), while i...

This work deals with the structure and solvation ability of the binary mixtures of the essential oil 1,8-cineole with n-hexane, n-octane and n-decane. The relevant derived properties excess isobaric heat capacity, molar excess volume, mixing viscosity, excess isentropic compressibility and activation Gibbs free energy were calculated from the measu...

Photocleavage, Metal Complexes, interaction with biological molecules

For the first time, careful T-Jump relaxation kinetics experiments conducted in the microsecond timescale at pH = 7.5 and 25 °C in dilute solutions of Human Telomeric DNA, have evinced two different equilibria. The set of data recorded concurs with two G-quadruplex ↔ G-triplex equilibria coexisting in the presence of both Na+ and K+-buffering ions.

Aluminium ion is believed to cause a number of neurological and skeletal disorders in human body. The study of the biological processes and molecular mechanisms that underlie these pathological disorders is rendered a difficult task due to the wide variety of complex species that result from hydrolysis of Al3+ion. In addition, this ion displays a p...

Essential processes for living cells such as transcription and replication depend on the formation of specific protein-DNA recognition complexes. Proper formation of such complexes requires suitable fitting between the protein surface and the DNA surface. Adopting doxorubicin (DOX) as a model probe, we report here that Ag3 clusters (Ag-AQCs) inhibi...

Photoleavage DNA, Electrophoresis, Photoirradiation

Anticancer activity and mechanistic insights of new Ru(II) half-sandwich complexes with hydroxiphenylbenzoazole ligands

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 thro...

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 thro...

The ability of magnesium(II) and nickel(II) to induce dramatic conformational changes in the synthetic RNA poly(rA)poly(rU) has been investigated. Kinetic experiments, spectrofluorometric titrations, melting experiments and DSC measurements contribute in shedding light on a complex behaviour where the action of metal ions (Na(+), Mg(2+), Ni(2+)), i...

Selected new fluorogenic probes that interact in different ways with Hg2+ and MeHg+ have been prepared and used for the chemical speciation of both cations in aqueous solution as well as in HEK293 cells. The best selective speciation of Hg2+ and MeHg+ has been achieved by in vitro approaches based on fluorogenic probes supported in cultured cells,...

The functionality of the bisbenzimide Hoechst 33258 in solution has been largely exploited in the quantification of DNA. Understanding of its behavior is essential to promote its widespread application and learning of biological processes. A detailed study of the dimerization process of the fluorescent blue dye Hoechst 33258 is carried out by isoth...

The complex [(η6-p-cymene)Ru(OH2)(κ2-N,N-HL1)](OTf)2 (HL1 = 2-pyridin-2-yl-1H-benzimidazole), [2c](OTf)2, undergoes easy deprotonation of the N–H group at physiological pH, producing [(η6-p-cymene)Ru(OH2)(κ2-N,N-L1)]+, [2c′]+, prone to dimerization both in solution and in the solid state. X-ray measurements on [2c′]BF4 have shown that dimer units a...

Ethanol affects unequally the thermal stability of DNA and RNA. The slopes of the melting temperature (Tm) versus ethanol/water content (v/v) was negative for [poly(dA-dT)]2 and positive for poly(rA)•poly(rU); for ct-DNA, the sign of the slope depends on the scan rate of heating and the ethanol concentration. The increase in Tm when the ethanol con...

The ligands 2-pyridin-2-yl-1H-benzimidazole (HL(1)), 1-methyl-2-pyridin-2-ylbenzimidazole (HL(2)), and 2-(1H-imidazol-2-yl)pyridine (HL(3)) and the proligand 2-phenyl-1H-benzimidazole (HL(4)) have been used to prepare five different types of new ruthenium(II) arene compounds: (i) monocationic complexes with the general formula [(η(6)-arene)RuCl(κ(2...

Kinetic, RNA, Metal Complexes, aggregation

A kinetic, calorimetric, mass spectrometry and EPR study has been performed on the formation of the metallacrown Cu(2+)[12-MCCu(Alaha)-4] from Cu(ii) and α-alaninehydroxamic acid (H2L). The acidity range where Cu(2+)[12-MCCu(Alaha)-4] is stable lies between pH 3.5 and 6.0. For pH values below that range the complex CuHL(+) is the prevailing species...

Spectrophotometric, circular dichroism, calorimetric, displacement assay and kinetic analyses of the binding of the fluorescent dye coralyne to poly(A)2poly(U) have served to enlighten the ability of the dye to produce dramatic changes in the RNA structure. The sets of data assembled convey that coralyne is able to induce the triplex-to-duplex conv...

Doxorubicin (DOX) is an important anthracycline antibiotic whose intricate features of binding to DNAs, not yet fully understood, have been the object of intense debate. The dimerization equilibrium has been studied at pH = 7.0, I = 2.5 mM and T = 25ºC. A thermodynamic and kinetic study of the binding of doxorubicin to DNA, carried out by circular...

New cationic, half-sandwich Ru(ii) arene compounds of general formula [(η(6)-arene)RuCl(κ(2)-N,N-L)]X (where L are functionalized phenanthrolines such as 1,10-phenanthroline-5-amine (aphen); 5,6-epoxy-5,6-dihydro-[1,10]phenanthroline (ephen); or 4,7-dihydroxy-1,10-phenanthroline (dhphen)) have been prepared to study their anticancer potential. All...

The structure and dynamics of alkan-1-ol/alkylbenzoate binary mixtures have been studied by microwave dielectric relaxation spectroscopy in the 200 MHz-20 GHz frequency range. The binary mixtures of methanol, ethanol, propan-1-ol, butan-1-ol and pentan-1-ol with methyl, ethyl, propyl and butyl benzoates were studied at 298.15 K. The relaxational re...

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 b...

Kinetic, RNA, Metal Compexes, Aluminium

Metal Complexes

The interaction of thionine with triple, double and single RNA helices has been fully characterized by thermodynamic and kinetic methods. The nature of the interaction of thionine with the synthetic polynucleotides poly(rU), poly(rA)∙poly(rU) and poly(rA)∙2poly(rU) has been studied at pH=7.0 and 25ºC by UV absorbance, fluorescence, circular dichroi...

Heat capacities for the binary mixtures of methanol with (C(1)-C(4)) alkylbenzoates and methylbenzoate with (C(1)-C(11)) alkan-1-ols have been measured over the whole composition range at 298.15 K under atmospheric pressure. From the experimental measurements, the derived excess molar heat capacities and partial excess molar heat capacities at infi...

The equilibria and kinetics (stopped-flow) of the binding of Ni(II) to salicylhydroxamic acid (SHA) and phenylbenzohydroxamic acid (PBHA) have been investigated in aqueous solutions containing SDS micelles. The two ligands are fairly distributed between the two pseudophases present, so the binding reaction occurs in both phases. The contributions t...

A thermodynamic and kinetic study on the mode of binding of 9-amino-6-chloro-2-methoxi-acridine (ACMA) to poly(dA-dT)·poly(dA-dT) and poly(dG-dC)·poly(dG-dC) has been undertaken at pH = 7.0 and I = 0.1 M. The spectrophotometric, kinetic (T-jump), circular dichroism, viscometric and calorimetric information gathered point to formation of a fully int...

The reactions of two diaminotriazine ligands 2,4-diamino-6-(2-pyridyl)-1,3,5-triazine (2-pydaT) and 6-phenyl-2,4-diamino-1,3,5-triazine (PhdaT) with ruthenium-arene precursors led to a new family of ruthenium(II) compounds that were spectroscopically characterized. Four of the complexes were cationic, with the general formula [(η(6)-arene)Ru(κ(2)-N...

We report a fluorogenic probe that is able to discriminate a range of primary or secondary biogenic amines and their natural or synthetic mimics, in water or buffer, by means of the turn-on transient generation of green fluorescence, with high quantum yields and low detection limits, thus making the system suitable for the detection of abuse drugs,...

The interaction of ACMA (9-amino-6-chloro-2-methoxy acridine) (D) with DNA (P) has been studied by absorbance, fluorescence, circular dichroism, spectrophotometry, viscometry and unwinding electrophoresis. A T-jump kinetic study has also been undertaken. The experimental data show that, totally unlike other drugs, ACMA is able to form with DNA thre...

The equilibria and the kinetics of the binding of Iron(III) to salicylhydroxamic (SHA) and benzohydroxamic (BHA) acids have been investigated in aqueous solution (I = 1 M (HClO(4)/NaClO(4)), T = 298 K) using spectrophotometric and stopped-flow methods. Whereas Iron(III) forms a 1:1 complex (ML) with BHA, it forms both ML and M(2)L complexes with SH...

The binary mixtures of methanol with (C(1)-C(4)) alkylbenzoates and of (C(1), C(3), C(5), C(7), C(9), C(11)) alkan-1-ols with methylbenzoate were used as solvents to look into the preferential solvation and intermolecular interactions of the solvatochromic indicators 2-nitroanisole, 4-nitroaniline, 4-nitrophenol, and Reichardt's dye by UV-vis measu...

Ferrocyanide ion behaves as a tetravalent Brønsted base and can react with four protons, forming ferrocyanic acid. By potentiometric and spectrophotometric techniques it is shown that the first two protonation equilibria overlap, as do the third and fourth equilibria. The two techniques yield identical results when processed with the inclusion of n...

A wide study was carried out of the acid–base behaviour of ferricyanide ions in aqueous perchloric acid media in the range 0.1–11.5 M. This study shows that protonation and decomposition of the ferricyanide ions occur simultaneously. The three successive protonation equilibria were found in the acidity ranges 0.1–4.0, 3.5–8.5, and 7.0–11.5 M HClO4,...

Excess viscosities, excess volumes, and excess free energies of activation for flow of the binary mixtures containing propionic acid with aniline, o-toluidine, o-anisidine, and o-chloroaniline were determined at five different temperatures from density and viscosity measurements. Based on the Regular Solutions Theory, the empirical parameter θ was...

The excess volumes VE of the binary mixtures 2-pyrrolidinone–(C6–C10) n-alkanols have been calculated from density measurements over the whole composition range and the 298.15–318.15 K temperature range. The excess volumes were independent of temperature, but changed noticeably with the chain length of the alkanol. The VE values were only positive...

The mechanisms for the hydrolysis of organopalladium complexes [Pd(CNN)R]BF(4) (R=P(OPh)(3), PPh(3), and SC(4)H(8)) were investigated at 25 °C by using UV/Vis absorbance measurements in 10 % v/v ethanol/water mixtures containing different sulphuric acid concentrations in the 1.3-11.7 M range. In all cases, a biphasic behavior was observed with rate...

The conditions under which different structures of left-handed DNA (poly(dG-me(5)dC)·poly(dG-me(5)dC)) can exist are investigated by spectrofluorometric, spectrophotometric, circular dichroism and calorimetric measurements and the kinetics of the transformations are analysed. The effects of temperature, salt and ethanol content on the transitions a...

The decomposition reaction of the purple dye murexide in acidic media is used as a probe indicator for protons in nonionic microemulsions. The reaction kinetics primarily rely on the proton concentration and permit assessment of the proton activity in the nonionic microemulsions of water/cyclohexane/Igepal and water/heptane/Igepal. The experiments...

The equilibria and kinetics of the binding of proflavine to poly(dG-dC).poly(dG-dC) and poly(dA-dT).poly(dA-dT) were investigated in ethanol/water mixtures using spectrophotometric, circular dichroism, viscometric, and T-jump methods. All methods concur in showing that two modes of interaction are operative: intercalation and surface binding. The l...