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 Cu²⁺ ions complexation capability. Several synthetic approaches were tested to achieve the target compound. The optimal approach involved stepwise modifications of purine <i>N</i>9, <i>C</i>8, and <i>C</i>6 positions that, in nine consecutive steps, provided purine-cyclen conjugate. The synthetic sequence involved Mitsunobu-type alkylation at <i>N</i>9 and iodination at <i>C</i>8, followed by Stille, S_NAr, CuAAC, and alkylation reactions. The designed purine-cyclen conjugate is able to complex Cu²⁺ ions in both the cyclen part and between the purine <i>N</i>7 and triazole <i>N</i>2 positions. The complexation pattern and equilibrium were studied using the NMR titration technique in MeCN-d₃ and absorption spectra.