The conformational behaviour in aqueous solution of the EgadMe complex, a gadolinium-based contrast agent sensitive to beta-Galactosidase enzymatic activity, is investigated by means of ab initio calculations and classical Molecular Dynamics simulations. Furthermore, force field parameterization of gadolinium-ligand interactions is performed, and its reliability is tested on the bench mark [Gd(DOTA)]‾ system by MD simulations. Both computational methods highlight the presence in EgadMe of two main conformational isomers. The lowest energy conformation is a “close” form, corresponding to a state of low-relaxivity (MRI “inactive”), in which the ninth coordination site of the gadolinium ion is occupied by one oxygen atom of the galactopyranose residue. The second isomer, which is 2.9 (at ab initio level) and 4.2 (at MD level) kcal mol-1 above the global minimum, presents an “open” form, corresponding to a state of high-relaxivity (MRI “active”) in which one water molecule coordinates the ion. These results are consistent with experimental findings reported for EgadMe, and show that competition at the ninth coordination site of gadolinium ion, between the intra (the galactopyranose residue) and inter (water molecules) molecular interactions, affects the relaxivity of this system.

Cosentino, U., Pitea, D., Moro, G., Saracino, G., Villa, A. (2009). Conformational behaviour determines the low-relaxivity state of a conditional MRI contrast agent. PHYSICAL CHEMISTRY CHEMICAL PHYSICS, 11, 3943-3950 [10.1039/b902049g].

Conformational behaviour determines the low-relaxivity state of a conditional MRI contrast agent

COSENTINO, UGO RENATO;PITEA, DEMETRIO;MORO, GIORGIO;
2009

Abstract

The conformational behaviour in aqueous solution of the EgadMe complex, a gadolinium-based contrast agent sensitive to beta-Galactosidase enzymatic activity, is investigated by means of ab initio calculations and classical Molecular Dynamics simulations. Furthermore, force field parameterization of gadolinium-ligand interactions is performed, and its reliability is tested on the bench mark [Gd(DOTA)]‾ system by MD simulations. Both computational methods highlight the presence in EgadMe of two main conformational isomers. The lowest energy conformation is a “close” form, corresponding to a state of low-relaxivity (MRI “inactive”), in which the ninth coordination site of the gadolinium ion is occupied by one oxygen atom of the galactopyranose residue. The second isomer, which is 2.9 (at ab initio level) and 4.2 (at MD level) kcal mol-1 above the global minimum, presents an “open” form, corresponding to a state of high-relaxivity (MRI “active”) in which one water molecule coordinates the ion. These results are consistent with experimental findings reported for EgadMe, and show that competition at the ninth coordination site of gadolinium ion, between the intra (the galactopyranose residue) and inter (water molecules) molecular interactions, affects the relaxivity of this system.
Articolo in rivista - Articolo scientifico
MRI contast agents; computational chemistry; molecular dynamics
English
2009
11
3943
3950
none
Cosentino, U., Pitea, D., Moro, G., Saracino, G., Villa, A. (2009). Conformational behaviour determines the low-relaxivity state of a conditional MRI contrast agent. PHYSICAL CHEMISTRY CHEMICAL PHYSICS, 11, 3943-3950 [10.1039/b902049g].
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/9305
Citazioni
  • Scopus 15
  • ???jsp.display-item.citation.isi??? 14
Social impact