Establishing the binding affinity of organic carboxylates to 15-metallacrown-5 complexes

The reaction of L-phenylalanine hydroxamic acid (H(2)L-pheHA) with copper(II) and lanthanide(III) salts yields 15-Metallacrown-5 structures of the general composition Ln(X)n[Cu(II)(L-pheHA)](5)((3-n)+) where X can represent a wide variety of anions. With five copper ions and one central lanthanide ion, the Ln[15-MC-5] complexes have multiple positions where these anionic guests may bind to the metallacrown host. In addition, these metallacrowns are amphiphilic, containing one face that is primarily hydrophobic (due to the five benzyl side chains which are oriented upon the same face of the molecule) and a face that is hydrophilic which has no impediment to solvent access. While it has been known that aromatic carboxylates bind preferentially to the hydrophobic face and short chain aliphatic carboxylates bind preferentially to the hydrophilic face, there have been no quantitative assessments of the stability of these host-guest complexes. Using Isothermal Calorimetry (ITC) we have determined the binding constants for several carboxylate anions to a variety of metallacrown complexes. The affinities of anions that coordinate to the lanthanide ion on the hydrophobic face are related to the hydrophobicities of the guests, with higher binding strength observed for the more hydrophobic carboxylates. Central metal such as La(III) or Nd(III) which are nine coordinate are able to accommodate two guests on the hydrophobic side; however, central metals such as Gd(III) or Dy(III) which are eight coordinate are limited to encapsulating one guest into the hydrophobic pocket. A second guest, bound to the hydrophilic face is often observed with these 8-coordinate lanthanides. The significantly weaker second binding constant between benzoate and Gd(III)[15-MC-5] supports the model that the second benzoate binds to the central metal through the hydrophilic side. Unlike the Gd(III)[15-MC-5], the higher binding constant of the second benzoate with La(III)[15-MC-5] is consistent with the crystallographic model which shows that the second guest binds to the hydrophobic side.