A NEW TERNARY ZINC(II) COMPLEX WITH [12]ANEN(4) (=1,4,7,10-TETRAAZACYCLODODECANE) AND AZT (=3'-AZIDO-3'-DEOXYTHYMIDINE) - HIGHLY SELECTIVE RECOGNITION OF THYMIDINE AND ITS RELATED NUCLEOSIDES BY A ZINC(II) MACROCYCLIC TETRAAMINE COMPLEX WITH NOVEL COMPLEMENTARY ASSOCIATIONS

Novel complementary associations have been found in a newly synthesized ternary Zn(II) complex of a macrocyclic tetraamine, [12]aneN4 (= 1,4,7,10-tetraazacyclododecane, cyclen, L), and N(3)-deprotonated AZT (= 3'-azido-3'-deoxythymidine), 8. The X-ray crystal analysis of 8 revealed a distorted square-pyramidal N5-coordinate structure where a strong interaction occurs between Zn(II) and the N(3)-deprotonated anion of the pyrimidine ring (Zn(II)-N(3) = 2.053(8) angstrom. Although the distances between the two pyrimidine carbonyls and the symmetrical cyclen NH groups (O(2)-N(17) = 3.22(1) angstrom; O(2)-N(20) = 3.34(1) angstrom; O(4)-N(11) = 3.34(1) angstrom; O(4)-N(14) = 3.33(1) angstrom) appear long in the solid state, a little wagging of the cyclen ring along the Zn(II)-N(3) axis in solution may allow the formation of the two (direct or indirect) hydrogen bonds between them to contribute to the stability of 8. Crystals of 8.ClO4.2H2O (C18H36N9O10ClZn) are monoclinic, space group P2(1) with a = 8.950(4) angstrom, b = 34.966(4) angstrom, c = 8.843(3) angstrom, beta = 93.13(3)degrees; V = 2763(2) angstrom3, and Z = 4. Full-matrix least-squares refinement converged at R = 0.078 and R(w) = 0.105 for 3290 independent reflections. Potentiometric titrations of deoxyribonucleosides, dA (= 2'-deoxyadenosine), dG (= 2'-deoxyguanosine), dC (= 2'-deoxycytidine), and dT (= thymidine), and related compounds in the presence of Zn(II)-[12]aneN4 complex 4 disclosed extremely selective binding of 4 to dT and its derivatives, AZT, U (= uridine), Ff (= ftorafur, 5-fluoro-1-(tetrahydro-2-furyl)uracil), and riboflavin. The UV absorption spectral measurement of dT in the presence of 4 has confirmed that 4 binds to dT only in the N(3)-deprotonated form. By these two analytical methods, the anion affinity constants, K(ZnL-S) (= [ZnL-S]/[ZnL][S], where S represents ''imide'' N-deprotonated substrate), were determined at 25-degrees-C and I = 0.10 (NaClO4) for dT (log K = 5.6), AZT (5.6), U (5.2), Ff (4.6), and riboflavin (5.6). Other nucleosides containing an amino group in place of the carbonyl oxygen of dT (i.e., dG) or containing no 'imide'' hydrogen (i.e., dA and dC) did not bind to 4 at all, presumably due to the nonbonding steric interaction between their amino groups or to the lack of N- anion formation. Ino (=inosine) that lacks one carbonyl group at C(2) from dT showed a weaker affinity (log K = 4.2). We conclude that the two possible hydrogen bonds between the carbonyl oxygens of dT and the cyclen amino groups appreciably contribute to the stability of the ternary complexes. Thus, the present study provides a novel type of complementary nucleoside recognition by the Zn(II) macrocyclic tetraamine complex with high selectivity in aqueous solution.