Structural effects on the stability of some hydrogen-bonded complexes withnucleobases

The effect that additional groups flanking the hydrogen bond donor/acceptor arrays have on the association constants (K-a) of complexes of chloroform- soluble thymine and adenine derivatives has been investigated by NMR shift titration. Constants for thymine and 2,6-diaminoacyl pyridine derivatives, in which the acyl group bears either (CH2)(n)R or some other substituent, v ary greatly. The peak value of K-a = 1130 M-1 occurs for n = 2 and R = phen yl. Computer modeling with CHARMm suggests that this is due to a weak addit ional stabilization by a C-H-pi interaction; in Line with this the complex shows small upfield NMR shifts for the terminal methyl groups. Four other r eceptors were prepared which could, in principle, form hydrogen bonds with all donor/acceptor sites of adenine; NMR titrations, however, showed very l ow complexation energies, probably due to deviations from the ideal hydroge n bond geometry necessary to form stronger complexes.