Lanthanide complexes of triethylenetetramine tetra-, penta-, and hexaacetamide ligands as paramagnetic chemical exchange-dependent saturation transfer contrast agents for magnetic resonance imaging: nona- versus decadentate coordination.
The solid state and solution structure of a series of lanthanide complexes of the decadentate ligand triethylenetetramine-N,N,N',N'',N''',N'''-hexaacetamide, (ttham), its two decadentate derivatives di-tert-butyl N,N,N''',N'''-tetra(carbamoylmethyl)-triethylenetetramine-N',N''-diacetate (Bu(2)ttha-tm) and N,N,N''',N'''-tetra(carbamoylmethyl)-triethylenetetramine-N',N''-diacetic acid (H(2)ttha-tm), and its two nonadentate derivatives N-benzyl-triethylenetetramine-N,N',N'',N''',N'''-pentaacetamide (1bttpam) and N'-benzyl-triethylenetetramine-N,N,N'',N''',N'''-pentaacetamide (4bttpam) have been investigated by infrared and Raman spectroscopy, X-ray crystallography, cyclovoltammetry, and NMR spectroscopy. In these mononuclear lanthanide complexes, the first coordination sphere is generally saturated by four amine nitrogens of the triethylenetetramine ligand backbone and five or six carbonyl oxygen atoms of the pendent amide or acetate donor groups. In the [Ln(ttham)](3+) complex series, a switch from a decadentate to a nonadentate coordination occurs between [Er(ttham)](3+) and [Tm(ttham)](3+). This switch in coordination mode, which is caused by decreasing metal ion radii going from lanthanum to lutetium (lanthanide contraction), has no significant effect on the T(1)-relaxivity of these complexes. It is shown that the T(1)-relaxivity is dominated by second coordination sphere interactions, with an ascendant contribution of the classical dipolar relaxation mechanism for the earlier (Ce-Sm) and very late (Tm, Yb) lanthanides, and a prevailing Curie relaxation mechanism for most of the remaining paramagnetic lanthanide ions. In chemical exchange-dependent saturation transfer (CEST) (1)H NMR experiments, most of the above complexes exhibit multiple strong CEST peaks of the paramagnetically shifted amide protons spread over a >100 ppm chemical shift range. The effective CEST effect of the studied thulium complexes strongly depends on temperature and pH. The pH at which the CEST effect maximizes (generally between pH 7 and 8) is determined by the overall charge of the complex. Depending on the used saturation frequency offset, the temperature-dependence varies between the extremes of strongly linearly dependent and fully independent in the case of [Tm(ttham)](3+). In combination with the strong pH-dependence of the CEST effect at the latter frequency offset, this complex is highly suitable for simultaneous temperature and pH mapping using magnetic resonance imaging.
Burdinski
Dirk
D
Department of Biomolecular Engineering, Philips Research Europe, High Tech Campus 11, 5656 AE Eindhoven, The Netherlands. dirk.burdinski@philips.com
Pikkemaat
Jeroen A
JA
Lub
Johan
J
de Peinder
Peter
P
Nieto Garrido
Lidia
L
Weyhermüller
Thomas
T
D003287:Contrast Media / Q000138:chemical synthesis / Q000737:chemistry*; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004563:Electrochemistry; D028581:Lanthanoid Series Elements / Q000138:chemical synthesis / Q000737:chemistry*; D008024:Ligands; D008279:Magnetic Resonance Imaging / Q000379:methods; D008958:Models, Molecular; D013055:Spectrophotometry, Infrared; D013059:Spectrum Analysis, Raman; D014266:Trientine / Q000031:analogs & derivatives* / Q000138:chemical synthesis
D003287:Contrast Media; D056831:Coordination Complexes; D028581:Lanthanoid Series Elements; D008024:Ligands; D014266:Trientine