A zinc(II) complex of acridine-pendant cyclen, 4.2ClO(4) (cyclen = 1,4,7,10-tetraazacyclododecane, 1), has been designed and synthesized as a new "multipoint" nucleobase receptor molecule in aqueous solution at physiological pH and compared with a Zn-II pendantless cyclen complex 2 recently discovered (ref 9) as a highly selective host for dT (deoxythymidine) and U (uridine). The strong acidity of Zn-II in 2 is retained in 4; the water at the fifth coordination site has a pK(a) value of 7.46 +/- 0.02, L-Zn-OH2 reversible arrow L-Zn-OH-. Interaction of 4 with a variety of nucleosides has been studied by potentiometric pH titration, H-1 and C-13 NMR, IR, UV-vis, and fluorescence spectroscopy. The effects of the acridine functionality in 4 are (i) an enhanced 1:1 association with N(3)-deprotonated dT (log K = 7.2 +/- 0.1 at 25 degrees C and I = 0.10 (NaNO3)) and its congeners, implying an additional acridine-thymine aromatic stacking interaction; (ii) a different interaction mode with dG (2’-deoxyguanosine) (log K = 5.0 +/- 0.1 for the N(1)-deprotonated form and 4.1 +/- 0.1 for the free form) while no interaction was observed with 2, but 4 does not interact at all with the nucleosides dA (2’-deoxyadenosine) and dC (2’-deoxycytidine); and (iii) high selectivity for dT among all of the DNA nucleosides in aqueous solution. The strong "multipoint" recognition of 4 with dT is proven by IR, NMR, and the X-ray analyses of an isolated 1:1 ternary complex of 4 with N(3)-deprotonated 1-methylthymine, 10.ClO4.2H(2)O. The X-ray crystal analysis of 10.ClO4.2H(2)O shows a distorted square-pyramidal N-5-coordinate structure with a strong interaction between the Zn-II and the N(3")-deprotonated anion of the pyrimidine ring (Zn(1)-N(3") = 1.987(4) Angstrom). The carbonyl oxygen O(2") of the pyrimidine ring forms a hydrogen bond directly with a cyclen N(10)-H group (O(2")-N(10) = 2.881(5) Angstrom), while the other O(4") binds indirectly with a diagonal N(4)-H group via a water molecule. As postulated from the enhanced stability for the 4-dT complex, a strong cofacial stacking interaction is found between the acridine (at C(1’), C(2’), C(4’), C(4a’), and C(9a’)) and the pyrimidine ring with the plane-to-plane separation ranging from 3.285 to 3.419 Angstrom.