Rhenium and technetium tricarbonyl, {M(CO3}+ (M = Tc, Re), binding to mammalian metallothioneins: New insights into chemical and radiopharmaceutical implications

Joan Lecina, Òscar Palacios, Sílvia Atrian, Mercè Capdevila, Joan Suades

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11 Citations (Scopus)

Abstract

© 2014 SBIC. Abstract This paper deals with the binding of the four mammalian metallothioneins (MTs) to the organometallic metal fragment {fac-M(CO)3}+ (M = 99Tc, Re), which is highly promising for the preparation of second-generation radiopharmaceuticals. The study of the transmetallation reaction between zinc and rhenium in Zn7-MT1 by means of UV-vis and CD spectroscopy demonstrated the incorporation of the {fac-Re(CO)3}+ fragment to the MTs. This reaction should be performed at 70 C to accelerate the reaction rate, a result that is consistent with the reported reactivity of the rhenium fragment. ESI-TOF MS demonstrated the formation of mixed-metal species as Zn6,{Re(CO)3}-MT, Zn6,{Re(CO)3}2-MT, and Zn5,{Re(CO)3}3-MT, as well as the different reactivity of the four MT isoforms. Hence, Zn-MT3 showed the highest reactivity, in agreement with its high Cu-thionein character, whereas Zn-MT2 exhibited the lowest reactivity, in line with its high Zn-thionein character. The reactivity of the Zn-loaded forms of MT1 and MT4 is intermediate between those of MT3 and MT2. The study of the binding of the {fac-99Tc(CO)3}+ fragment to MTs showed a significant and very interesting different reactivity in relation to rhenium. The transmetallation reaction is much more effective with technetium than with rhenium and significant amounts of mixed Zn x,{99Tc(CO)3} y -MT species were formed with the four MT isoforms whereas only MT3 rendered similar amounts of rhenium derivatives. The results obtained in this study support the possible use of technetium for labelling mammalian metallothioneins and also for possible radiopharmaceutical applications.
Original languageEnglish
Pages (from-to)465-474
JournalJournal of Biological Inorganic Chemistry
Volume20
Issue number3
DOIs
Publication statusPublished - 1 Apr 2015

Keywords

  • Mass spectrometry
  • Metal carbonyl
  • Metallothionein
  • Rhenium
  • Technetium

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