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Eizaguirre A.,Modulo 13 | Yanez M.,Modulo 13 | Eriksson L.A.,Gothenburg University
Physical Chemistry Chemical Physics | Year: 2012

There is evidence that the interaction of the α-ketol group of the Doxorubicin and Epirubicin anti-cancer drugs with Fe(iii) generates hydroxyl radicals under aerobic conditions, causing cardiotoxicity in patients. Considering that the formation of DNA adducts is one of the main targets of Anthracycline drugs, we have in the present study characterized several [Anthracycline-DNA]Fe(iii) complexes with respect to their stability and Fe(iii) coordination, by means of MD simulations. Iron is found to coordinate well to the drugs containing an α-ketol group, this being the only group of the drug that binds to the metal. The complexes containing an α-ketol group, [Doxorubicin-DNA]Fe(iii) and [Epirubicin-DNA]Fe(iii), thus show greater stability than those not containing it, i.e., [Daunorubicin-DNA]Fe(iii), [Idarubicin-DNA]Fe(iii) and [5-Imino-Daunorubicin]Fe(iii). Metal attachment to the α-ketol group is furthermore facilitated by the phosphate groups of DNA. The coordination to iron in the [Doxorubicin-DNA]Fe(iii) system is smaller than that found for the [Epirubicin-DNA]Fe(iii) system, and the corresponding number of coordinating waters in the former is larger than in the latter. This may in turn result in higher hydroxyl radical production, thus explaining the increased cardiotoxicity noted for Doxorubicin. This journal is © the Owner Societies 2012.

Corral I.,Modulo 13 | Yanez M.,Modulo 13
Physical Chemistry Chemical Physics | Year: 2011

Doubly charged species in the gas phase have been an oddity for many years, but the possibility of generating and detecting them with the new available experimental techniques has faced the scientific community with challenging questions regarding their stability, bonding and reactivity. In this paper we analyze, mainly from a theoretical perspective, these questions for the particular subset of [ML n] 2+ dications, where M is a metal and L an organic or inorganic ligand. Special attention is devoted to the challenges associated with their theoretical description, in particular as far as their bonding and their life times are concerned. A survey of their unimolecular reactivity is also presented as well as a discussion of the information available on dication affinities, and how they correlate with proton affinities or monocation affinities in general. © 2011 The Owner Societies.

Gamez J.A.,Modulo 13 | Yanez M.,Modulo 13
Journal of Chemical Theory and Computation | Year: 2011

Up to now it has been generally assumed that the electron capture on diselenides XSeSeX produces a fragmentation of the Se-Se bond. However, our high-level ab initio calculations indicate that this is the case only when the substituents X and X attached to the diselenide bridge have low electronegativity. Also importantly, even when the two substituents are of similar electronegativity, the Se-Se bond cleavage rarely is an adiabatic process. For low-electronegative X substituents, the extra electron is placed in the θ*(Se-Se) antibonding orbital, and the cleavage of the Se-Se bond is the most favorable process. However, the mechanism of this bond breaking is more intricate than previously assumed, and for asymmetric derivatives it proceeds through a conical intersection (CI). These findings emphasize the importance of using accurate ab initio calculations, rather than the usually employed density functional theory approaches, when dealing with reactions in biochemistry and organometallic chemistry, because the characterization of a CI requires the use of multireference methods to account for the mixing of states. When X is highly electronegative, the θ*(Se-X) antibonding orbital becomes highly stabilized with respect to the θ*(Se-Se) strongly favoring the cleavage of the Se-X bond, whereas the Se-Se remains practically unperturbed. Finally, when comparing the present results on diselenides with those of the disulfide analogues, it is apparent that the activation barriers and the final products of the different unimolecular reactions are higher in energy for the diselenides, in spite of the higher antioxidant strength of diselenides. This seems to indicate that the electron detachment process, less favorable for diselenides than for disulfides, competes with the electron-capture dissociation process and therefore should also be considered to explain the different antioxidant ability of these compounds. © 2011 American Chemical Society.

Eizaguirre A.,Modulo 13 | Mo O.,Modulo 13 | Yanez M.,Modulo 13 | Tortajada J.,University of Évry Val d'Essonne | And 3 more authors.
Journal of Physical Chemistry B | Year: 2013

The interactions between urea and Sr2+ in the gas phase have been investigated by combining electrospray ionization/mass spectrometry techniques and density functional and high-level ab initio molecular orbital calculations. Our theoretical survey indicates that [Sr(urea)]2+ adducts are thermodynamically stable with respect to direct Coulomb explosions. However, after isomerization, some of the local minima of the PES are thermodynamically unstable with respect to the formation of NH4 +, but kinetically metastable. The loss of neutral fragments with the concomitant generation of lighter doubly charged fragment ions, namely, [(H3N)Sr]2+ and [(HNCO)]Sr2+, compete with the aforementioned Coulomb explosion processes yielding NH4 + + [(NCO)Sr]+ and [(H2N)Sr]+ + [H 2NCO]+, although the former processes dominate. Hence, both singly and doubly charged species are detected as dissociation products. Quite importantly, the observed eliminations of NH3 or HNCO lead to the formation of new doubly charged species, which turn out to be thermodynamically stable. © 2013 American Chemical Society.

Trujillo C.,Modulo 13 | Lamsabhi A.M.,Modulo 13 | Mo O.,Modulo 13 | Yanez M.,Modulo 13 | Salpin J.-Y.,CNRS Laboratory for Analysis and Modelling for Biology and Environment
International Journal of Mass Spectrometry | Year: 2011

The stability against collisional dissociation of [uracil-Ca]2+ complexes has been investigated by combining nanoelectrospray ionization/mass spectrometry techniques and B3LYP/6-311++G(3df,2p)//B3LYP/6-31+G(d,p) density functional theory (DFT) calculations. The reactivity upon collision seems to be dominated by Coulomb explosion processes, since the most intense peaks in the MS/MS spectra correspond to singly-charged species (CaOH+ and [C 4,H3,N2,O]+). Nevertheless, additional peaks corresponding to the loss of neutral species, namely [H,N,C,O] and H2O have been also detected. A systematic study of the CID spectra obtained with different labeled species, namely, 2-13C- uracil, 3-15N-uracil and 2-13C-1,3-15N 2-uracil, concludes unambiguously that the loss of [H,N,C,O] involves exclusively atoms C2 and N3. Suitable mechanisms for these fragmentation processes are proposed through a theoretical survey of the corresponding potential energy surface. A comparison between these results and those reported for two other metal dications, namely Cu2+ and Pb2+, as well as for protonated uracil and uracil-M+ (M = Li, Na, K) complexes denotes the existence of significant differences and interesting similarities, among the various systems. © 2011 Elsevier B.V. All rights reserved.

Benidar A.,Rennes Institute of Physics | Montero-Campillo M.M.,Modulo 13 | Lamsabhi A.M.,Modulo 13 | Yanez M.,Modulo 13 | And 3 more authors.
ChemPhysChem | Year: 2014

A series of six small alkylmercury hydrides of the general formula RHgH with R=methyl, ethyl, n-propyl, isopropyl, n-butyl, and 3-butenyl were obtained by reduction in vacuo of the corresponding mercury halide with tributyltin hydride in the presence of a radical inhibitor. These very reactive compounds, which have to be removed from the reaction mixture as they are formed, were characterized by 1H NMR and 13C NMR spectroscopy. The IR spectra of n-propyl-, isopropyl-, n-butyl-, and 3-butenylmercury hydride were recorded for the first time. All compounds were then studied by density functional theory calculations on the basis of a recent theoretical assessment for alkylmercury compounds performed by our group. Comparison of the experimental and theoretical results allowed the assignment of the vibrational modes in an unambiguous way, in spite of the low intrinsic stability of some of the derivatives investigated. The experimental procedure implemented for registering the IR spectra of these unstable species in the gas phase allowed us to obtain reasonable estimates of their lifetimes. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Eizaguirre A.,Modulo 13 | Mo O.,Modulo 13 | Yanez M.,Modulo 13 | Boyd R.J.,Dalhousie University
Organic and Biomolecular Chemistry | Year: 2011

The structures and relative stabilities of the complexes formed by uracil and its thio- and seleno-derivatives with the Sr2+ cation, in the gas phase, have been analyzed by means of G96LYP density functional theory (DFT) calculations. The attachment of the Sr2+ cation to the heteroatom at position 4 is preferred systematically. Although the enolic forms of uracil and its derivatives should not be observed in the gas phase, the corresponding Sr2+ complexes are the most stable. The enhanced stability of these tautomers is two-fold, on the one hand Sr2+ interacts with two basic sites simultaneously, and on the other hand an aromatization of the six-membered ring takes place upon Sr2+ association. Sr2+ attachment also has a clear catalytic effect in the tautomerization processes involving uracil and its derivatives. This catalytic effect increases when oxygen is replaced by sulfur or selenium. The Sr2+ binding energy with uracil and its derivatives is bigger than the tautomerization barriers connecting the dioxo forms with the corresponding enolic tautomers. Consequently, when associated with Sr2+, all tautomers are energetically accessible and should all be observed in the gas phase. © 2011 The Royal Society of Chemistry.

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