Efficient modulation of hydrogen-bonding interactions by remote substituents.
[structure: see text] A series of tetralactam macrocycles having different substituents were prepared, and their binding affinities for an adipamide guest were investigated in CDCl3 by 1H NMR titrations. The association constants strongly depend on the substituents, varying up to DeltaDeltaG = 3.4 kcal/mol; electron-donating substituents (OMe, NMe2) decrease the binding affinity, while electron-withdrawing groups (Cl, NO2) increase it. These large substituent effects have been rationalized by secondary repulsions and partial perturbations of intramolecular hydrogen bonds.
Chang
Sung-Youn
SY
Center for Bioactive Molecular Hybrids and Department of Chemistry, Yonsei University, Seoul 120-749, South Korea.
Kim
Hung Sop
HS
Chang
Kyoung-Jin
KJ
Jeong
Kyu-Sung
KS