Molecular recognition of amines and amino esters by zinc porphyrin receptors: Binding mechanisms and solvent effects

Zinc porphyrin receptors bearing 12 ester groups in the meso phenyl groups (1-3) were prepared, and binding of amines and cr-amino esters was studied with emphasis on the binding mechanisms. The X-ray crystallographic analysi s of 5,10,15,20-tetrakis(2,6-bis(carbomethoxymethoxy)-4-carbomethoxyphenyl) porphyrin (free base of 1) showed that the receptor has a binding pocket ab ove the porphyrin plane. UV-visible titration experiments revealed that the zinc porphyrin receptors bound amines and alpha-amino esters with binding constants (K-a) ranging from 0.5 to 52 700 M-1 in CH2Cl2 at 25 degrees C. T he ester functional groups of 1 assisted the binding of aromatic cr-amino e aters (K-a = 8 000-23 000 M-1 in CH2Cl2 at 25 degrees C) and inhibited the binding of bulky aliphatic alpha-amino esters (K-a = 460 M-1 for Leu-OMe in CH2Cl2 at 25 degrees C), indicating that CH-pi type interactions and steri c repulsions control the selectivity. The binding of amines and a-amino est ers was tight both in a nonpolar solvent (CH2Cl2) and in a polar solvent (w ater) but loose in a solvent of intermediate polarity (H2O-MeOH (1.1)), dem onstrating that two competitive driving forces are operating: (1) attractiv e electrostatic forces between host and guest such as coordination of the a mino group to the zinc atom, and (2) entropic forces stemming from desolvat ion as well as enthalpic forces due to the host-guest dispersion forces. Th e former forces drive the binding in CH2Cl2 while the latter forces drive t he binding in water. The enthalpy changes in the binding in CH2Cl2 and thos e in water range from -50 to -30 kJ mol(-1) and from -35 to 0 kJ mol(-1), r espectively. The entropy changes in CH2Cl2 and those in water range from -1 20 to -60 J K-1 mol(-1) and from -50 to +60 J K-1 mol(-1), respectively. Th us the binding in CH2Cl2 is characterized by large negative enthalpy change s, while that in water by less negative entropy changes. These thermodynami c parameters also indicate that host-guest polar interactions (enthalpic fo rces) drive the binding in CH2Cl2 while both host-guest dispersion interact ions (an enthalpic force) and desolvation (an entropic force) drive the bin ding in water. Enthalpy-entropy compensation observed for the binding in wa ter indicates that the binding of amines and amino esters in water by zinc porphyrins is associated with conformational changes as well as a high degr ee of dehydration. In CH2Cl2, no clear compensation was observed, consisten t with the mechanism that neither desolvation processes nor conformational changes contribute significantly to the binding energetics.