Mechanical Tuning of Molecular Recognition To Discriminate the Single-Methyl-Group Difference between Thymine and Uracil

Construction of enzyme-like artificial cavities is a complex and challenging subject. Rather than synthesizing complicated host molecules, we have proposed mechanical adaptation of relatively simple hosts within dynamic media to determine the optimum conformation for molecular recognition. Here we have applied this concept to one of the most challenging biomolecular recognition problems, i.e., that of discriminating thymine from uracil. We synthesized the novel cholesterol-armed triazacyclononane as a host molecule and subjected it to structural tuning by compression of its Langmuir monolayers in the absence and in the presence of Li(+) cations in the subphase. Experimental results confirm that the monolayer of triazacyclononane host selectively recognizes uracil over adenine (ca. 7 times based on the binding constant) and thymine (ca. 64 times) under optimized conditions ([LiCl] = 10 mM at surface pressure of 35 mN m(-1)). The concept of mechanical tuning of a host structure for optimization of molecular recognition offers a novel methodology in host-guest chemistry as an alternative to the more traditional molecular design strategies.