TY - JOUR
T1 - Optimising the relaxivities of Mn2+ complexes by targeting human serum albumin (HSA)
AU - Forgács, Attila
AU - Tei, Lorenzo
AU - Baranyai, Zsolt
AU - Esteban-Gómez, David
AU - Platas-Iglesias, Carlos
AU - Botta, Mauro
N1 - Publisher Copyright:
© 2017 The Royal Society of Chemistry.
PY - 2017
Y1 - 2017
N2 - We report two novel macrocyclic ligands based on the 1,4-DO2AM platform (1,4-DO2AM = 2,2′-(1,4,7,10-tetraazacyclododecane-1,4-diyl)diacetamide) and containing two benzyl groups attached either to the nitrogen atoms of the macrocyclic unit (1,4-BzDO2AM) or to the amide pendant arms (1,4-DO2AMBz). The protonation constants of the ligands and the stability constants of their Mn2+ complexes were determined using pH potentiometry. The introduction of benzyl groups results in a slight decrease of the stability constants of the Mn2+ complexes and a slight increase of their acid-catalysed dissociation reactions. A detailed relaxometric characterisation of the complexes using nuclear magnetic dispersion relaxation (NMRD) and 17O NMR studies indicated that the increase in molecular weight associated with the presence of benzyl groups results in a remarkable increase of proton relaxivities r1p, which take values of 3.8, 3.5 and 2.5 mM-1 s-1 for [Mn(1,4-BzDO2AM)]2+, [Mn(1,4-DO2AMBz)]2+ and [Mn(1,4-DO2AM)]2+ (at 25 °C and 20 MHz). The [Mn(1,4-BzDO2AM)]2+ and [Mn(1,4-DO2AMBz)]2+ complexes form relatively strong adducts with Human Serum Albumin (HSA) with association constants of (3.9 ± 0.6) × 103 and (2.0 ± 0.3) × 103 M-1, respectively. The interaction with the protein slows down the rotational tumbling of the complex in solution, which results in adducts endowed with remarkably high proton relaxivities (r1p b = 18.5 ± 0.7 and 27.4 ± 1.4 mM-1 s-1 for [Mn(1,4-BzDO2AM)]2+ and [Mn(1,4-DO2AMBz)]2+, respectively).
AB - We report two novel macrocyclic ligands based on the 1,4-DO2AM platform (1,4-DO2AM = 2,2′-(1,4,7,10-tetraazacyclododecane-1,4-diyl)diacetamide) and containing two benzyl groups attached either to the nitrogen atoms of the macrocyclic unit (1,4-BzDO2AM) or to the amide pendant arms (1,4-DO2AMBz). The protonation constants of the ligands and the stability constants of their Mn2+ complexes were determined using pH potentiometry. The introduction of benzyl groups results in a slight decrease of the stability constants of the Mn2+ complexes and a slight increase of their acid-catalysed dissociation reactions. A detailed relaxometric characterisation of the complexes using nuclear magnetic dispersion relaxation (NMRD) and 17O NMR studies indicated that the increase in molecular weight associated with the presence of benzyl groups results in a remarkable increase of proton relaxivities r1p, which take values of 3.8, 3.5 and 2.5 mM-1 s-1 for [Mn(1,4-BzDO2AM)]2+, [Mn(1,4-DO2AMBz)]2+ and [Mn(1,4-DO2AM)]2+ (at 25 °C and 20 MHz). The [Mn(1,4-BzDO2AM)]2+ and [Mn(1,4-DO2AMBz)]2+ complexes form relatively strong adducts with Human Serum Albumin (HSA) with association constants of (3.9 ± 0.6) × 103 and (2.0 ± 0.3) × 103 M-1, respectively. The interaction with the protein slows down the rotational tumbling of the complex in solution, which results in adducts endowed with remarkably high proton relaxivities (r1p b = 18.5 ± 0.7 and 27.4 ± 1.4 mM-1 s-1 for [Mn(1,4-BzDO2AM)]2+ and [Mn(1,4-DO2AMBz)]2+, respectively).
UR - http://www.scopus.com/inward/record.url?scp=85021996032&partnerID=8YFLogxK
U2 - 10.1039/c7dt01508a
DO - 10.1039/c7dt01508a
M3 - Article
SN - 1477-9226
VL - 46
SP - 8494
EP - 8504
JO - Dalton Transactions
JF - Dalton Transactions
IS - 26
ER -