Towards the rational design of MRI contrast agents: a practical approach to the synthesis of gadolinium complexes that exhibit optimal water exchange.
The gadolinium(iii) complex of S-SSSS-NO(2)BnDOTMA exhibits water exchange kinetics that are optimal for use in high relaxivity or targeted contrast agents. However, the synthesis of this ligand is hampered by the steric encumbrance imparted upon the cyclen ring by the nitrobenzyl substituent. A relatively simple modification has been used to enable the synthesis of larger quantities of a bifunctional ligand that retains similar fast water exchange properties. The gadolinium complex of S-SSS-NO(2)BnDO3MA-1A is shown to retain the rapid water exchange kinetics characteristic of a twisted square antiprismatic (TSAP) coordination geometry (tau(M)= 6 +/- 0.4 ns).
Woods
Mark
M
Macrocyclics, 2110 Research Row, Suite 425, Dallas, Texas 75235, USA. mark@macrocyclics.com
Botta
Mauro
M
Avedano
Stefano
S
Wang
Jing
J
Sherry
A Dean
AD
D000477:Alkylating Agents / Q000737:chemistry; D003287:Contrast Media / Q000737:chemistry*; D000080027:Cyclams; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D007700:Kinetics; D008024:Ligands; D008279:Magnetic Resonance Imaging / Q000379:methods*; D015394:Molecular Structure; D009578:Nitrobenzenes / Q000737:chemistry; D009942:Organometallic Compounds / Q000138:chemical synthesis*; D013237:Stereoisomerism; D013696:Temperature; D014867:Water / Q000737:chemistry*
D000477:Alkylating Agents; D003287:Contrast Media; D000080027:Cyclams; D006571:Heterocyclic Compounds; D008024:Ligands; D009578:Nitrobenzenes; D009942:Organometallic Compounds; D014867:Water; C078688:2-(4-nitrobenzyl)-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid; C038072:cyclen; C050823:gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate