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(Zn2+-cyclen)s (Zn2L4 and Zn2L5) (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 ( = [(Zn2L)-(S--OPO32-)]/[Zn2L](free)[S-OPO32-](free) (M-1)), where S- denotes the imide-deprotonated thymine part), with Zn2L4 or Zn2L5 determined by potentiometric pH titration showed a more stable complex with Zn2L5 (log K-app = 6.4) than with Zn2L4 (log K-app = 5.5) at pH 7.6 with I = 0.1 (NaNO3) and 25 degrees C. These values are mu ch greater than log K-app (K-app = [ZnL3 - dT(-)]/[ZnL3](free)[dT](free) (M-1)) Of 3.2 for a nucleoside thymidine (dT) complex with a monomeric Zn2+-benzylcyclen (ZnL3). The 1:1 complexation was confirmed by the FAB mass spectroscopic data for Zn2L with 3'- and 5'-dTMP. The combined data from the spectrophotometric UV titration and H-1 NMR measurements of 5'-dThlP and 5'-dTDP with Zn2L5 in D2O at pD 7.8 and 35 degrees C indicated that the terminal phosphate dianion interacted with one of the (Zn2+-cyclen)s and the imide anion of dT bound to the other Zn2+-cyclen.