ИСТИНА

Macrocyclic polyaminopolycarboxylates are intensively studied as chelators in radiopharmaceuticals for target delivery of alpha- and betaemitters to tumor cells. Water soluble azacrown-ethers demonstrate affinity to heavy cations. They could be synthesized with high yields and purity. This kind of crown ethers have not been studied for trivalent cations complexation earlier. Earlier complexes of one analogous compound with rare earth elements have been studied and demonstrated moderate stability constants. We supposed that aryl fragment will preorganize cavity for cations and provide fast formation of strong complex. Potentiometric titration shows that ligand releases two protons from two macrocyclic nitrogens and complete deprotonation achieves at pH>9. To characterize complexing ability of L competitive extraction technique with chromatographic cellulose and di-2-ethylhexyl phosphoric acid was used. It was shown that 1:1 complexes are formed with Bi3+, Ac3+, Y3+ and Eu3+. The calculated stability constants of ML for actinium (logK=7.04(1)), yttrium (logK=7.10(3)) and europium (logK=7.71(1)) are similar and 50% complex formation occurs at pH>6.5. Such similar behavior of Ac3+ to rare earth elements is not surprising since Ac3+ is chemical analog for La3+. The obtained values are 1-1,5 orders lower in comparison with earlier described complexes of REE with aryl-free ligand. This fact indicates that aryl fragment adds rigidity to macrocycle and weakens the strength of formed complex. At the same time Bi3+ is bound by L even at pH 3 and variation of pH leads to monotonous change in BiL stability constants that could be associated with formation of two types of complexes: BiL+ (logK=18.48) and BiLOH (logK=13.03). Bi3+ as easily hydrolysable cation possesses affinity to different ligands as OH- and different polyaminopolycarboxylates, so constants of respective complexes are usually higher than analogous complexes with REE. Furthermore smaller radius of Bi3+ provides its deeper location in cavities formed by carboxylate and macrocyclic oxygens and nitrogens of the ligand while rare earths usually have capping water molecule to complete coordination sphere. This suggestion is confirmed by quantum chemical modeling of complexes’ geometry: Eu3+ is much farther from the macrocyclic ring than Bi3+. Addition of M3+ to aqueous solution of ligand leads to blue shift of band in UV-vis absorbance spectrum. This also proves crown moiety’s participation in complexation process. Duration of complex formation was studied by UV-vis absorption spectroscopy using Arsenazo III as indicator. It was demonstrated that complexation by L takes 1 minute as well as “gold standard” DTPA and in the same conditions DOTA requires 1,5 hours for complexation. The work was supported by RFBR project 13-03-01304