title: Ln[DO3A-N-α-(pyrenebutanamido)propionate] complexes: optimized relaxivity and NIR optical properties.
abstract: We have proposed recently that the DO3A-N-α-(amino)propionate chelator and its amide conjugates are leads to targeted, high relaxivity, safe contrast agents for magnetic resonance imaging. In this work we illustrate further the expeditious nature and robustness of the synthetic methodologies developed by preparing the DO3A-N-(α-pyrenebutanamido)propionate chelator. Its Gd(3+) chelate retains the optimized water exchange, high stability and inertness of the parent complex. The pyrene moiety imparts concentration-dependent self-assembly properties and aggregation-sensitive fluorescence emission to the Gd(3+) complex. The Gd(3+) complex displays pyrene-centred fluorescence whilst the Yb(3+) and Nd(3+) complexes exhibit sensitized lanthanide-centred near-infrared luminescence. The aggregated form of the complex displays high relaxivity (32 mM(-1) s(-1), 20 MHz, 25 °C) thanks to simultaneous optimization of the rotational correlation time and of the water exchange rate. The relaxivity is however still limited by chelate flexibility. This report demonstrates that the DO3A-N-(α-amino)propionate chelator is a valuable platform for constructing high relaxivity CA using simple design principles and robust chemistries accessible to most chemistry labs.
authors.affiliation: Centro de Química, Campus de Gualtar. and Universidade do Minho, 4710-057 Braga, Portugal. jmartins@quimica.uminho.pt jarm20@bath.ac.uk.
authors.forename: M F
authors.initials: MF
authors.lastname: Ferreira
authors.forename: G
authors.initials: G
authors.lastname: Pereira
authors.forename: A F
authors.initials: AF
authors.lastname: Martins
authors.forename: C I O
authors.initials: CI
authors.lastname: Martins
authors.forename: M I M
authors.initials: MI
authors.lastname: Prata
authors.forename: S
authors.initials: S
authors.lastname: Petoud
authors.forename: E
authors.initials: E
authors.lastname: Toth
authors.forename: P M T
authors.initials: PM
authors.lastname: Ferreira
authors.forename: J A
authors.initials: JA
authors.lastname: Martins
authors.forename: C F G C
authors.initials: CF
authors.lastname: Geraldes
mesh_terms: D000818:Animals; D002614:Chelating Agents / Q000138:chemical synthesis / Q000737:chemistry; D003287:Contrast Media / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D005682:Gadolinium / Q000737:chemistry; D006801:Humans; D007700:Kinetics; D028581:Lanthanoid Series Elements / Q000737:chemistry*; D011485:Protein Binding; D011721:Pyrenes / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism; D019265:Spectroscopy, Near-Infrared; D013696:Temperature; D014018:Tissue Distribution; D014867:Water / Q000737:chemistry
chemical_list: D002614:Chelating Agents; D003287:Contrast Media; D056831:Coordination Complexes; D028581:Lanthanoid Series Elements; D011721:Pyrenes; D012709:Serum Albumin; D014867:Water; C030984:pyrene; D005682:Gadolinium