Hydrogen bonding of adenine derivatives to tyrosine side chain

High resolution proton magnetic resonance measurements provide evidence for the formation of hydrogen-bonded complexes between 9-ethyladenine and p-cresol used as a model of tyrosine side chain in CDCl3. We have calculated the sum of the association constants corresponding to the three existing 1:1 complexes: K=6.3+/-0.15. By methylation of the amino group of adenine, we were able to calculate the ratio of the two strongest equilibrium constants K7/K1=1.6+/-0.3. Theoretical computations by the complete neglect of differential overlap (CNDO/2) method indicate that several hydrogen-bonded planar complexes can form between 9-methyladenine and phenol. The computed energy of the complexes with 6-dimethylamino adenine removes some ambiguity concerning the computed ratio of the association constants. Comparison of the calculated energies with free energies experimentally determined in organic solvent shows that despite the competition with CDCl3, which associates with both solute molecules, the preferential order of association is conserved. The small variations of charge density of adenine carbon atoms when complexed with phenol are in agreement with very small chemical shifts observed by 13C-nuclear magnetic resonance.