[GdPCP2A(H(2)O)(2)](-): a paramagnetic contrast agent designed for improved applications in magnetic resonance imaging.
A novel ligand based on a pyridine-containing macrocycle bearing two acetic and one methylenephosphonic arms (PCP2A) has been synthesized. An efficient synthesis of PCP2A is based on the macrocyclization reaction between 2,6-bis(chloromethyl)pyridine and a 1,4, 7-triazaheptane derivative bearing a methylenephosphonate group on N-4. The Gd(III) complex of PCP2A displays characteristic properties which make it a very promising contrast agent for improved applications in magnetic resonance imaging. In fact it shows (i) a very high stability constant (log K(GdPCP2A) = 23.4) which should guarantee against the in vivo release of toxic free Gd(III) ions and free ligand molecules and (ii) a relaxivity that is about 2 times higher than the values reported for contrast agents currently used in the clinical practice. Its high relaxivity is the result of the presence of two water molecules in the inner coordination sphere and a significant contribution from water molecule(s) hydrogen bonded to the phosphonate group. Moreover, the inner sphere water molecules are involved in an exchange with the bulk water which is relatively fast. This property is important for the attainment of an even higher relaxivity once the molecular reorientation rate of the [GdPCP2A(H(2)O)(2)](-) moiety is lengthened by means of conjugation to a macromolecular substrate.
Aime
S
S
Dipartimento di Chimica I.F.M., Università di Torino, via P. Giuria 7, I-10125 Torino, Italy. aime@ch.unito.it
Botta
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M
Frullano
L
L
Geninatti Crich
S
S
Giovenzana
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G
Pagliarin
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R
Palmisano
G
G
Sirtori
F R
FR
Sisti
M
M
D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000737:chemistry; D002614:Chelating Agents / Q000138:chemical synthesis* / Q000737:chemistry; D003287:Contrast Media / Q000138:chemical synthesis* / Q000737:chemistry; D005682:Gadolinium; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D013816:Thermodynamics
D019086:Bridged Bicyclo Compounds, Heterocyclic; D002614:Chelating Agents; D003287:Contrast Media; D009942:Organometallic Compounds; C415577:diaqua(3,9-bis(carboxymethyl)-6-dihydroxyphosphorylmethyl-3,6,9,15-tetraazabicyclo(9.3.1)pentadeca-1(15),11,13-triene)gadolinate(I); D005682:Gadolinium