A GENERAL SCHEME BASED ON EMPIRICAL INCREMENTS FOR THE PREDICTION OF HYDROGEN-BOND ASSOCIATIONS OF NUCLEOBASES AND OF SYNTHETIC HOST-GUEST COMPLEXES

Association energies Delta G(t) in chloroform, in part also in carbon tetrachloride, were determined by NMR titrations of suitably substitut ed nucleosides and several synthetic analogues. Based on these and on many literature data, two simple free energy increments were derived d escribing the Delta G(t) values of 58 complexes within 1.8 kJ mol(-1). With chloroform as solvent the increment for the primary interaction between donor and acceptor is 7.9 kJ mol(-1), for the secondary one 2. 9 kJ mol(-1), irrespective of whether the latter is attractive or repu lsive. Addition of only 1% methanol to CCl4 led to a decrease in assoc iation constants by a factor of 25. Calorimetric titrations of G-C nuc leoside derivatives in CCl4 showed substantial contributions from G di mers, in line with NMR titrations, and surprisingly small decreases in entropy. Preliminary NOE measurements allowed us to single out some o f the possible association modes; they are also in line with expected self- and triple-association modes of the nucleobases. These modes are generally in accord with nucleobase associations predicted by MM calc ulations in the literature, which in turn agree with predictions based solely on the increments derived in the present work.