Highly Selective Recognition of Thymidine Mono- and Diphosphate Nucleotides in Aqueous Solution by Ditopic Receptors Zinc(II)−Bis(cyclen) Complexes (Cyclen = 1,4,7,10-Tetraazacyclododecane)

Highly selective and efficient recognition of thymidine and uridine nucleotides such as 3‘-dTMP (thymidine 3‘-monophosphate), 5‘-dTMP (thymidine 5‘-monophosphate), 2‘-UMP (uridine 2‘-monophosphate), 3‘-UMP (uridine 3‘-monophosphate), 5‘-UMP (uridine 5‘-monophosphate), 5‘-dTDP (thymidine 5‘-diphosphate), 5‘-dTTP (thymidine 5‘-triphosphate), AZTMP (3‘-azido-3‘-deoxythymidine 5‘-monophosphate), and AZTDP (3‘-azido-3‘-deoxythymidine 5‘-diphosphate) with ditopic dimeric zinc(II) complexes of macrocyclic 12-membered tetramines, meta - and para -xylyl-bis(Zn 2+ -cyclen)s (Zn 2 L 4 and Zn 2 L 5 ) (cyclen = 1,4,7,10-tetraazacyclododecane) has been studied by potentiometric pH titration, isothermal titration calorimetry, UV spectrophotometric titration, and NMR titration. The apparent 1:1 complexation constants for 5‘-dTMP, K app (= [(Zn 2 L)−(S - −OPO 3 2 - )]/[Zn 2 L] free [S−OPO 3 2 - ] free (M - 1 )), where S - denotes the imide-deprotonated thymine part), with Zn 2 L 4 or Zn 2 L 5 determined by potentiometric pH titration showed a more stable complex with Zn 2 L 5 (log K app = 6.4) than with Zn 2 L 4 (log K app = 5.5) at pH 7.6 with I = 0.1 (NaNO 3 ) and 25 °C. These values are much greater than log K app ( K app = [ZnL 3 −dT - ]/[ZnL 3 ] free [dT] free (M - 1 )) of 3.2 for a nucleoside thymidine (dT) complex with a monomeric Zn 2+ -benzylcyclen (ZnL 3 ). The 1:1 complexation was confirmed by the FAB mass spectroscopic data for Zn 2 L with 3‘- and 5‘-dTMP. The combined data from the spectrophotometric UV titration and 1 H NMR measurements of 5‘-dTMP and 5‘-dTDP with Zn 2 L 5 in D 2 O at pD 7.8 and 35 °C indicated that the terminal phosphate dianion interacted with one of the (Zn 2+ -cyclen)s and the imide anion of dT bound to the other Zn 2+ -cyclen.