Reference : Positive and negative ion mode ESI-MS and MS/MS for studying drug-DNA complexes
Scientific journals : Article
Physical, chemical, mathematical & earth Sciences : Chemistry
Positive and negative ion mode ESI-MS and MS/MS for studying drug-DNA complexes
Rosu, Frédéric [Université de Liège - ULiège > > Chimie physique, spectrométrie de masse >]
Pirotte, Sophie [Université de Liège - ULiège > > Labo de recherche sur les métastases >]
De Pauw, Edwin mailto [Université de Liège - ULiège > > Chimie physique, spectrométrie de masse >]
Gabelica, Valérie mailto [Université de Liège - ULiège > > Chimie physique, spectrométrie de masse >]
International Journal of Mass Spectrometry
Elsevier Science
Yes (verified by ORBi)
The Netherlands
[en] drug-DNA complexes ; noncovalent complexes ; MS/MS ; negative ion mode ; gas-phase basicity ; mass spectrometry
[en] We report systematic investigation of duplex DNA complexes with minor groove binders (Hoechsts 33258 and 33342, netropsin and DAPI) and intercalators (daunomycin, doxorubicin, actinomycin D, ethidium, cryptolepine, neocryptolepine, m-Amsacrine, proflavine, ellipticine and mitoxantrone) by ESI-MS and ESI-MS/MS in the negative ion mode and in the positive ion mode. The apparent solution phase equilibrium binding constants can be determined by measuring relative intensities in the ESI-MS spectrum. While negative ion mode gives reliable results, positive ion mode gives a systematic underestimation of the binding constants and even a complete suppression of the complexes for intercalators lacking functional groups capable of interacting in the grooves. In the second part of the paper we systematically compare MS/MS fragmentation channels and breakdown curves in the positive and the negative modes, and discuss the possible uses and caveats of MS/MS in drug-DNA complexes. In the negative mode, the drugs can be separated in three groups: (1) those that leave the complex with no net charge; (2) those that leave the complex with a negative charge; and (3) those that remain attached on the strands upon dissociation of the duplex due to their positive charge. In the positive ion mode, all complexes fragment via the loss of protonated drug. Information on the stabilization of the complex by drug-DNA noncovalent interactions can be obtained straightforwardly only in the case of neutral drug loss. In all other cases, proton affinity (in the positive ion mode), gas-phase basicity (in the negative ion mode) and coulombic repulsion are the major factors influencing the fragmentation channel and the dissociation kinetics.
Centre Interfacultaire d'Analyse des Résidus en Traces - CART
Fonds de la Recherche Scientifique (Communauté française de Belgique) - F.R.S.-FNRS
This is a postprint version of an article published in Int J Mass Spectrom © 2006 Elsevier Science B.V.

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