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Mass spectrometric identification and characterization of antimony complexes with ribose-containing biomolecules and an RNA oligomer

Abstract

Mass spectrometric techniques have been used to study the interaction of inorganic Sb(V) with biomolecules containing a ribose or deoxyribose moiety. Electrospray (ES) mass spectra of reaction mixtures containing inorganic Sb(V) and one of several biomolecules (adenosine, cytidine, guanosine, uridine, adenosine-5′-monophosphate, adenosine-3′,5′-cyclic monophosphate, ribose, or 2′-deoxyadenosine) afforded high-mass antimony-containing ions corresponding to Sb(V)–biomolecule complexes of stoichiometry 1:1, 1:2, or 1:3. The complexes were characterized by collision-induced dissociation (CID) tandem mass spectrometry (MS) using ion-trap multistage MS. The CID results revealed that Sb(V) binds to the ribose or deoxyribose moiety. Structures are proposed for the Sb–biomolecule complexes. Analysis of the reaction mixtures by reversed-phase chromatography coupled on-line to either inductively coupled plasma (ICP) MS or ES–MS showed that in solution Sb(V) forms complexes with all the analyzed biomolecules with vicinal cis hydroxyl groups. Evidence (from size-exclusion chromatography ICP–MS and direct infusion ES–MS) of complexation of Sb(V) with an RNA oligomer, but not with a DNA oligomer, supports the suggestion that the presence of vicinal cis hydroxyl groups is critical for complexation to occur. This is the first direct evidence of complexation of Sb(V) with RNA. Results obtained by studying the effect of changing reaction conditions, i.e. pH, reaction time, and Sb/biomolecule molar ratio, on the extent of Sb–biomolecule formation suggest the reaction may be of physiological importance. Selected reaction monitoring (SRM) and precursor-ion-scanning tandem MS were investigated to determine their potential to detect trace levels of the Sb–biomolecule complexes in biological samples. Application of SRM MS–MS in combination with high-performance liquid chromatography enabled successful detection of an Sb–adenosine complex that had been spiked into a complex biological matrix (liver homogenate).

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Acknowledgements

The authors thank the European Commission for the funding of a Marie Curie Excellence Grant (Project name: ACE-METALS, Contract No. MEXT-CT-2003-002788) and Dr Mina Tsagri (Institute of Molecular Biology and Biotechnology, Crete, Greece) for donating the DEPC used in the work with RNA/DNA and for her valuable advice on the handling of RNA.

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Correspondence to Spiros A. Pergantis.

Electronic supplementary materials

CID breakdown curves for major Sb(X) n complexes presented in manuscript Table 1. The precursor and product ions correspond to the most abundant Sb isotope (i.e. 121Sb). Analysis was performed on 1:2 molar ratio Sb–biomolecule reaction mixtures containing a total of 10 mg Sb L−1 in 1:1 methanol–water.

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Hansen, H.R., Pergantis, S.A. Mass spectrometric identification and characterization of antimony complexes with ribose-containing biomolecules and an RNA oligomer. Anal Bioanal Chem 385, 821–833 (2006). https://doi.org/10.1007/s00216-006-0456-8

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  • DOI: https://doi.org/10.1007/s00216-006-0456-8

Keywords

  • Antimony
  • RNA
  • Ribonucleoside
  • Chromatography
  • Electrospray
  • ICP–MS