Copper(ii)-mediated base pairing involving the artificial nucleobase 3H-imidazo[4,5-f]quinolin-5-ol

Different N3-substituted derivatives of the new ligand 3H-imidazo[4,5-f]quinolin-5-ol were synthesized. The three pKa values of its nucleoside derivative 1 were determined as 2.72 ± 0.09, 5.2 ± 0.2 and 9.7 ± 0.2. Sophisticated computational methods were used to explain these experimental acidity constants. The artificial nucleoside analogue 1 containing the new ligand was introduced into various DNA duplexes. Upon the addition of Cu(ii) ions to the DNA, highly stabilizing 1-Cu(ii)-1 base pairs were formed, with an increase in the DNA melting temperature upon Cu(ii) insertion of up to 38 °C. The ligand represents the largest artificial nucleobase used for Cu(ii)-mediated base pairing. It was also applied in Cu(ii)-mediated base pairing with the smallest Cu(ii)-binding nucleoside 2, involving the ligand 4-carboxyimidazole. The thermal duplex stabilization upon 2-Cu(ii)-1 base pair formation is smaller than that of 1-Cu(ii)-1 and comes close to that of the previously reported 2-Cu(ii)-2. Important design principles for Cu(ii)-mediated base pairs can be derived by comparing the homoleptic complexes of the largest and the smallest Cu(ii)-binding nucleosides with the heteroleptic complexes comprising both nucleosides.