Complexation of Nucleotide Bases by Molecular Tweezers with Active Site Carboxylic Acids: Effects of Microenvironment

In chloroform-d molecular tweezer 1 forms a 1:1 complex (Job plot) with 9-propyladenine (4). Changes in the UV-visible absorption spectrum of 1 upon addition of 4 and the changes 1 and 4 induce in each other’s ¹H NMR spectrum are consistent with those of a complex comprised of hydrogen bonds and π-stacking interactions. The microenvironment around the carboxylic acid group in 1 markedly alters its complexation behavior relative to a simple carboxylic acid such as butyric acid (Lancelot, G. J. Am. Chem. Soc. 1977, 99, 7037–7042). The association constants for the 1–4 and butyric acid-5 complexes are 25 000 M⁻¹ (298 K) and 160 M⁻¹ (303 K), respectively. Butyric acid prefers a type 1 hydrogen bonding pattern while 1 adopts a type 7 pattern. The nucleotide base selectivities follow the order G > C > A > U for butyric acid and A > G ≫ C> U for 1. The presence of protic solvents markedly decreases the strength of the complex between 1 and 4. Two analogues of 1 have also been studied, molecular tweezer 2 and 3. Both lack the dimethylamino substituent found in 1, while 3 has a spacer unit that is fully oxidized. The association constants for the 2–4 and 3–4 complexes are 14000 and 120000 M⁻¹, respectively.