Evaluation of two chelators for labelling a PNA monomer with the fac-[99mTc(CO)3]+ moiety

A PNA monomer containing thymine as nucleobase (1) was synthesized, characterized and coupled to the pyrazolyl containing ligand 3,5-Me2pz(CH2)2N((CH2)3COOH)(CH2)2NHBoc (2) and to a modified cysteine S-(carboxymethyl-pentafluorphenyl)-N-[(trifluor)carbonyl]-l-cysteine methyl ester (3) yielding the bifunctional chelators 6 and 7, respectively. Reactions of 6 and 7 with the Re(I) tricarbonyl starting material [Re(CO)3(H2O)3]Br afforded the complexes fac-[Re(CO)3(κ3-6)]+ (8) and fac-[Re(CO)3(κ3-7)] (9), respectively. The identity of 8 and 9 has been established based on IR spectroscopy, elemental analysis, ESI-MS spectrometry and HPLC. The multinuclear NMR spectroscopy (1H, 13C, g-COSY, g-HSQC) has also been very informative in the case of complex 8, showing the presence of rotamers in solution. For 9 the NMR spectrum was too complex due to the presence of rotamers and diastereoisomers. The radioactive congeners of complexes 8 and 9, fac-[99mTc(CO)3(κ3-6)]+ (8a) and fac-[99mTc(CO)3(κ3-7)] (9a), have been prepared by reacting the precursor fac-[99mTc(CO)3(H2O)3]+ with the corresponding ligands being their identity established by comparing their HPLC chromatograms with the HPLC of the rhenium surrogates.

Two bifunctional chelators bearing a PNA monomer containing a thymine as nucleobase were synthesized and characterized. These bifunctional chelators allowed the synthesis of the tricarbonyl complexes fac-[M(CO)3(κ3-6)]+ (M = Re (8), M = 99mTc (8a)) and fac-[M(CO)3(κ3-7)] (M = Re (9), M = 99mTc (9a)). The possibility of preparing these model complexes encourages to pursue the labelling of PNAs with clinical relevance, using these bifunctional chelators.Figure optionsDownload as PowerPoint slide