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001-es BibID:BIBFORM073151
035-os BibID:(WoS)000405972200021 (Scopus)85024393994
Első szerző:Vanasschen, Christian
Cím:Novel CDTA-based, Bifunctional Chelators for Stable and Inert Mn Complexation: Synthesis and Physicochemical Characterization / Christian Vanasschen, Enikő Molnár, Gyula Tircsó, Ferenc K. Kálmán, Éva Tóth, Marie Brandt, Heinz H. Coenen, Bernd Neumaier
Dátum:2017
ISSN:0020-1669
Megjegyzések:In the search for MnII MR and PET/MR imaging agentswith optimal balance between thermodynamic stability, kinetic inertness, and relaxivity, two novel bifunctional MnII chelators (BFMnCs) based on CDTA (trans-1,2-diaminocyclohexane-N,N,N·,N·-tetraacetic acid) weresynthesized. A six-step synthesis, involving the buildup of a functionalized trans-1,2-diaminocyclohexane core, provided CuAAC-reactive 6a and 6b bearing an alkyne or azide substituent on the cyclohexane ring, respectively (CuAAC = CuI-catalyzed azide?alkyne 1,3-dipolar cycloaddition).Thermodynamic, kinetic, and relaxometric studies wereperformed with 4-HET-CDTA (8a) as a "model chelator," synthesized in two steps from 6a. The protonation constants revealed that 8a is slightly less basic than CDTA and forms a MnII complex of marginally lower thermodynamic stability (log KMnL = 13.80 vs 14.32, respectively), while the conditional stability constant is almost identical for both chelates (pMn = 8.62 vs 8.68, respectively). Kinetic assessment of the CuII-mediated transmetalation of [Mn(4-HET-CDTA)]2? showed that proton-assisted complex dissociation is slightly slower than for [Mn(CDTA)]2? (k1 = 297 vs 400 M?1 s?1, respectively). Importantly, the dissociation half-life near physiological conditions (pH 7.4, 25 ?C) underlined that [Mn(4-HET-CDTA)]2? is ?35% more inert (t1/2 = 16.2 vs 12.1 h, respectively). Those findings may be accounted for by a combination of reduced basicity and increased rigidity of the ligand. Analysis of the17O NMR and 1H NMRD data attributed the high relaxivity of [Mn(4-HET-CDTA)]2? (r1 = 4.56 mM?1 s?1 vs 3.65 mM?1 s?1for [Mn(CDTA)]2?; 20 MHz, 25 ?C) to slower rotational dynamics (?R298 = 105 ps). Additionally, the fast water exchange of the complex correlates well with the value reported for [Mn(CDTA)]2? (kex298 = 17.6 ? 107 vs 14.0 ? 107 s?1, respectively). Given the exquisite compromise between thermodynamic stability, kinetic inertness, and relaxivity achieved by [Mn(4-HET-CDTA)]2?, appropriately designed CuAAC-conjugates of 6a/6b are promising precursors for the preparation of targeted, bioresponsive, or high relaxivity manganese-based PET/MR tracers (52g/55 MnII) and MR contrast agents (MnII).
Tárgyszavak:Természettudományok Kémiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Bifunctional chelators
Manganese(II) complexes
Alternative MRI contrast agents
Stability
Inertness
Megjelenés:Inorganic Chemistry. - 56 : 14 (2017), p. 7746-7760. -
További szerzők:Molnár Enikő (1991-) (vegyész) Tircsó Gyula (1977-) (vegyész, kémia tanár) Kálmán Ferenc K. (1978-) (vegyész) Tóth Éva (1967-) (koordinációs kémia) Brandt, Marie Coenen, Heinz H. Neumaier, Bernd
Pályázati támogatás:K-120224
OTKA
János Bolyai Research Scholarship of the Hungarian Academy of Sciences
Egyéb
GINOP-2.3.2-15-2016-00008
GINOP
Le Studium, Loire Valley Institute for Advanced Studies
Egyéb
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