title: Hetero-tripodal hydroxypyridonate gadolinium complexes: syntheses, relaxometric properties, water exchange dynamics, and human serum albumin binding.
abstract: The synthesis and relaxometric properties of hetero-tripodal hydroxypyridonate-terephthalamide gadolinium (Gd(3+)) chelates with differing structural features for probing human serum albumin (HSA) interactions are reported. The Gd(3+) complexes are divided into two series. The first series (3-5) features a benzyl derivative connected to the hydroxypyridonate (HOPO) moiety. The second series of complexes (6-10) has the common feature of a poly(ethylene glycol) (PEG) attached to the terephthalamide (TAM) moiety and is nonbenzylated. The water exchange of the complexes is in the fast exchange regime with rates (k(ex)) in the range 0.45-1.11 x 10(8) s(-1). The complexes have a moderate interaction with HSA with association constants (K(A)'s) in the range 0.7-8.6 x 10(3) M(-1). Protein binding results in an enhancement in proton relaxivity from 7.7-10.4 mM(-1) s(-1) (r(1p)) to 15-29 mM(-1) s(-1) (r(1p)(b)). It is concluded that the interaction of the complexes with HSA (i) is enhanced by the presence of benzyl groups, (ii) is entropically driven, and (iii) results in a lower hydration number (q).
authors.affiliation: Department of Chemistry, University of California, Berkeley, California 94720, USA.
authors.forename: Marlon K
authors.initials: MK
authors.lastname: Thompson
authors.forename: Dan M J
authors.initials: DM
authors.lastname: Doble
authors.forename: Luke S
authors.initials: LS
authors.lastname: Tso
authors.forename: Serena
authors.initials: S
authors.lastname: Barra
authors.forename: Mauro
authors.initials: M
authors.lastname: Botta
authors.forename: Silvio
authors.initials: S
authors.lastname: Aime
authors.forename: Kenneth N
authors.initials: KN
authors.lastname: Raymond
mesh_terms: D003287:Contrast Media; D005682:Gadolinium / Q000737:chemistry*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D012709:Serum Albumin / Q000737:chemistry*; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
chemical_list: D003287:Contrast Media; D009942:Organometallic Compounds; D012709:Serum Albumin; D014867:Water; D005682:Gadolinium