Synthesis of Purine-1,4,7,10-Tetraazacyclododecane Conjugate and Its Complexation Modes with Copper(II).

Purine-1,4,7,10-tetraazacyclododecane (cyclen) conjugate was designed to study its Cu ions complexation capability. Several synthetic approaches were tested to achieve the target compound. The optimal approach involved stepwise modifications of purine 9, 8, and 6 positions that, in nine consecutive steps, provided purine-cyclen conjugate. The synthetic sequence involved Mitsunobu-type alkylation at 9 and iodination at 8, followed by Stille, SAr, CuAAC, and alkylation reactions. The designed purine-cyclen conjugate is able to complex Cu ions in both the cyclen part and between the purine 7 and triazole 2 positions. The complexation pattern and equilibrium were studied using the NMR titration technique in MeCN-d and absorption spectra.