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Calix[4]arenes as Molecular Platforms for Magnetic Resonance Imaging (MRI) Contrast Agents
Author(s) -
Schühle Daniel T.,
Schatz Jürgen,
Laurent Sophie,
Vander Elst Luce,
Muller Robert N.,
Stuart Marc C. A.,
Peters Joop A.
Publication year - 2009
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200802099
Subject(s) - mri contrast agent , monomer , micelle , chemistry , dota , nuclear magnetic resonance , relaxation (psychology) , rotational correlation time , dynamic light scattering , chelation , crystallography , gadolinium , materials science , molecule , nanoparticle , aqueous solution , polymer , nanotechnology , organic chemistry , psychology , social psychology , physics
The novel amphipilic conjugate of a calix[4]arene with four Gd–1,4,7,10‐ tetra(carboxymethyl)‐1,4,7,10‐tetraazacyclododecane (DOTA) chelates has potential as a magnetic resonance imaging contrast agent, both in its monomeric and in its micellar form. The system, illustrated here with its nuclear magnetic relaxation profile, shows good relaxivities, thanks to its high rigidity.An amphiphilic conjugate 1 of a calix[4]arene with four Gd–DOTA chelates (DOTA=1,4,7,10‐tetra(carboxymethyl)‐1,4,7,10‐tetraazacyclododecane) was prepared and the properties relevant to its application as a magnetic resonance imaging (MRI) contrast agent were investigated by NMR, dynamic light scattering (DLS), and cryo‐electron microscopy (cryo‐TEM). The compound aggregates in water; its critical micelle concentration (cmc) is 0.21 m M (or 0.84 m M for Gd) at 37 °C. The relaxivity of the aggregates at 37 °C and 20 MHz (18.3 s −1 per m M Gd or 73.2 s −1 per m M 1 ) is about twice that of the monomer. Nuclear magnetic relaxation dispersion (NMRD) profiles show the relaxivity of the monomer to be almost independent of the magnetic field strength up to 60 MHz. At higher concentrations, the NMRD profiles exhibit a maximum at about 20 MHz, which is typical for high molecular volumes. The average water residence lifetime is 1.20 μs at 298 K as determined by 17 O NMR. The rotational correlation time of the monomer (390 ns at 37 °C) is very close to the optimal value predicted for high‐field contrast agents. Monomer as well as micelles are very rigid systems with negligible local contributions to the overall rotational dynamics. The binding to human serum albumin (HSA) is significant ( K A =1.2×10 3 M −1 ) and the relaxivity of the HSA adduct at 20 MHz is 24.6 s −1 per m M Gd or 98.5 s −1 per m M 1 .