Ln(iii)-complexes of a DOTA analogue with an ethylenediamine pendant arm as pH-responsive PARACEST contrast agents

Dalton Trans. 2016 Feb 28;45(8):3486-96. doi: 10.1039/c5dt04443j.

Abstract

A novel macrocyclic DO3A derivative containing a linear diamine pendant arm, H3do3aNN, was prepared and its protonation and complexation properties were studied by means of potentiometry. It determined ligand consecutive protonation constants log K(An) = 12.62, 10.28, 9.67, 8.30, 3.30 and 1.58 and stability constants of selected lanthanide (Eu(iii), Yb(iii)) complexes log K(EuL) = 23.16 and log KYbL = 22.76. The complexes could be protonated on the pendant amino group(s) with log K(HLM) ≈ 5.6 and log K(H2LM) ≈ 4.8. Solution structures of both complexes were studied by NMR spectroscopy. The study revealed that the complex species exist exclusively in the form of twisted-square-antiprismatic (TSA) isomers. The complexes show significant pH dependence of the Chemical Exchange Saturation Transfer (CEST) between their amino groups and the bulk water molecules in the pH range of 5-8. Thus, the pH dependence of the magnetization transfer ratio of CEST signals can be used for pH determination using magnetic resonance imaging techniques in a pH range relevant for in vivo conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Contrast Media / chemistry*
  • Ethylenediamines / chemistry*
  • Heterocyclic Compounds, 1-Ring / chemistry*
  • Hydrogen-Ion Concentration
  • Lanthanoid Series Elements / chemistry*
  • Ligands
  • Organometallic Compounds / chemistry*
  • Thermodynamics

Substances

  • Contrast Media
  • Ethylenediamines
  • Heterocyclic Compounds, 1-Ring
  • Lanthanoid Series Elements
  • Ligands
  • Organometallic Compounds
  • 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid
  • ethylenediamine