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PIDAZTA: Structurally Constrained Chelators for the Efficient Formation of Stable Gallium‐68 Complexes at Physiological pH
Author(s) -
Farkas Edit,
Vágner Adrienn,
Negri Roberto,
Lattuada Luciano,
Tóth Imre,
Colombo Valentina,
EstebanGómez David,
PlatasIglesias Carlos,
Notni Johannes,
Baranyai Zsolt,
Giovenzana Giovanni B.
Publication year - 2019
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201901512
Subject(s) - chemistry , chelation , gallium , ligand (biochemistry) , combinatorial chemistry , bicyclic molecule , scaffold , stereochemistry , amino acid , computational chemistry , organic chemistry , biochemistry , receptor , medicine , biomedical engineering
Abstract Two structurally constrained chelators based on a fused bicyclic scaffold, 4‐amino‐4‐methylperhydro‐pyrido[1,2‐ a ][1,4]diazepin‐ N , N ′, N ′‐triacetic acids [(4 R* ,10a S* )‐PIDAZTA ( L1 ) and (4 R* ,10a R* )‐PIDAZTA ( L2 )], were designed for the preparation of Ga III ‐based radiopharmaceuticals. The stereochemistry of the ligand scaffold has a deep impact on the properties of the complexes, with unexpected [Ga( L2 )OH] species being superior in terms of both thermodynamic stability and inertness. This peculiar behavior was rationalized on the basis of molecular modeling and appears to be related to a better fit in size of Ga III into the cavity of L2 . Fast and efficient formation of the Ga III chelates at room temperature was observed at pH values between 7 and 8, which enables 68 Ga radiolabeling under truly physiological conditions (pH 7.4).