Macrocyclic bifunctional chelators

Moi, M.K., Meares, C.F., McCall, M.J., Cole, W.C., and DeNardo, S.J. (1985) Copper chelates as probes of biological systems stable copper complexes with a macrocyclic bifunctional chelating agent. Anal. Biochem. 148, 249-253. 

In analysis of the hver metabolism in rats treated with anti-colorectal carcinoma mAh 1A3 radiolabeled with Cu through three different macrocyclic bifunctional chelates, it was apparent that the radiocopper was transchelated and bound to proteins such as superoxide dismutase (SOD see Copper Proteins with Type Sites). Transchelation of the copper radiolabel appears to be a major factor for liver accumulation ofthe Cu-labeledBFC-lA3 conjugates After extensive evaluation, experimental results are consistent with in vivo transchelation of Cu from TETA-octreotide to superoxide dismutase (SOD) in rat liver. ... 

McCall M J, Diril H, Meares C F (1990). Simplified method for conjugating macrocyclic bifunctional chelating agents to antibodies via 2-iminothiolane. Bioconjug. Chem. 1 222-226. 

DPPB)(tricine)] interconvert at elevated temperatures, suggesting that the presence of these isomers might be due to conformational changes in the macro-cyclic technetium chelate. The LC-MS data for these two macrocyclic 99mTc complexes are completely consistent with the proposed composition. These phosphine-containing HYNIC chelators may have the potential to act as bifunctional chelators for 99mTc labeling of small BMs [56]. 

Compounds with enato 1,3-diaza chelate rings, e.g., (138) (cf. (37) and (38)), are oxidized to radical species which form 6,6 -C—C (139), and 6,6 -C=C linked bismacrocycles, which can be reduced to form 6,6 -biscyclams (140) (Scheme 33).177 [Ni(cyclam)]2+ and [Fe(cyclam)(MeCN)2]3+ are aerially oxidized to the 6-6 -ethylidene linked cations (141) which reduce to the 6,6 -biscyclam cations. Reaction of (138) with bifunctional o-phthaloyl dichloride gave bisacyl-linked macrocycles (142).178... 

Based on malonic ester synthesis, a bifunctional derivative of 1,4,7,10-tetraazacyclotridecane-N,N, N",N" -tetraacetic acid (TRITA) has been developed as well (Ruser et aL 1990). Again, an intermolecular reaction between a diamine and a diester leads to the macrocycle forming peptide bonds (O Fig. 45.11). The final BFCs have been studied as complexation agents for in and have shown fast chelate formation, high radiochemical yield, and high stability. 

As mentioned before, Copper prefers macrocyclic chelators like cyclam-14 and its derivatives. Cyclam-14 forms thermodynamically stable complexes and its X-ray structure shows a square-plane configuration with four equal Cu-N bonds (Tasker and Sklar 1975). This complex with coordination number four lose less than 0.5% metal when incubated for 24 h in human serum. Open chain chelators do not reach this stability. Its bifunctional derivative CPTA (O Fig. 45.17) coupled to an antibody and labeled with Cu shows a half-life for copper exchange in phosphate buffer >1,000 days (Smith-Jones et al. 1991). 

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