Does the coordination geometry of CuII bispidine complexes influence the radiopharmacological properties?


Does the coordination geometry of CuII bispidine complexes influence the radiopharmacological properties?

Fähnemann, S.; Stephan, H.; Walther, M.; Steinbach, J.; Haaf, C.; Comba, P.

3,7-Diazabicyclo[3.3.1]nonane derivatives (bispidines) represent a versatile platform for the development of new copper radiopharmaceuticals.[1] An extensive research effort has shown that bispidines with additional donor substituents form very stable complexes with copper(II) (L1, logK = 16.3). The CuII complexes of these so-called 1st generation hexadentate bispidine ligands (L1-Cu) enforce a distorted octahedral geometry which is well preorganized for CuII.

Recently, the 2nd generation of bispidine derivatives has been reported (L2 – L3).[2, 3] These ligands yield very high complex stabilities with CuII (logK from 19.5 to 26.4) similar to [CuII(cyclam)]2+ (logK = 27.2). In contrast to the 1st generation bispidines they provide exclusively aliphatic nitrogen atoms in the backbone, combined with one (L2) or two (L3) rigid diazacycloheptane rings for tetra- or hexadentate coordination, leading to distorted trigonal bipyramidal or distorted trigonal prismatic coordination geometries.

Ligands L1 – L3 have been labeled with 64Cu, and their radiopharmacological data, e.g. labeling efficiency and kinetics, lipophilicity and in vitro stability will be discussed.

Literature:

[1] S. Juran, M. Walther, H. Stephan, R. Bergmann, L. Steinbach, W. Kraus, F. Emmerling, P.Comba; Bioconjugate Chem. 2009, 20, 347-59.
[2] P. Comba, C. Haaf, H. Wadephol; Inorg. Chem. 2009, 48, 6604-6614.
[3] P. Comba, C. Haaf, A. Lienke, A. Muruganantham, H. Wadepohl: Chem.-Eur. J., 2009, 41, 10880-10887.

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