HOST-GUEST SUPRAMOLECULAR CHEMISTRY .35. COMPLEXATION OF NUCLEOSIDES, NUCLEOTIDES, AND ANALOGS IN AN AZONIACYCLOPHANE - VANDERWAALS AND ELECTROSTATIC BINDING INCREMENTS AND NMR SHIELDING EFFECTS

Binding free energies (DELTA-G) and complexation-induced NMR shifts (CIS) were determined for complexes in water between 16 nucleic acid components-including some analogs-and lipophilic receptor models bearing positively charged nitrogen atoms. The CIS values with up to -1.7 ppm shielding, e.g., on adenine protons, agree with earlier shielding calculations of the corresponding azacyclophane (CP66) naphthalene complex; the shifts on the host protons exerted, for example, by adenine are only about one-fourth of those exerted by naphthalene. All CIS values demonstrate intracavity inclusion for the adenine moiety, whereas the sugar parts, and in particular the pyrimidines, stay outside the CP66 cavity, although MM simulations as well as earlier measurements with related benzene guest molecules indicate that these heterocycles would also be suitable for encapsulation in CP66. The selectivity for adenine derivatives is also seen in binding constants with, for example, 1900 M-1 for AMP2- compared to 450 M-1 for GMP2-. DELTA-G values show regular differences between nucleotides and nucleosides as well as between differently charged nucleotides which can be factorized to 5 + 1 kJ mol-1 per salt bridge. Comparison of AMP2- binding between CP66 and a structurally similar, cleftlike host with DELTA-G = 9.5 kJ mol-1 shows, numerically, the same hydrophobic cavity effect as completely different guest molecules.