Metallosupramolecular chemistry in aqueous solutions: applications in ribonuclease mimicry and molecular sensing

Abstract

The use of kinetically labile metal ions to template designed interactions between organic ligands in aqueous solutions is described. This strategy is employed to target small biological molecules using coordinatively unsaturated metalloreceptors, which perform specific functions as a result of their association modes. Within this framework, two distinct examples are presented. The first case involves a tridentate Zn(II) complex with guanidinium-containing auxiliary groups that are constrained within the proximity of the metal center. This defines a bifunctional tetracationic cleft, which promotes the hydrolytic cleavage of a dinucleotide with cooperativity between the guanidinium groups and the Zn(II) center. The synergistic use of guanidinium residues and a metal center is also central to the activity of staphylococcal nuclease, which is one of the most active known nuclease enzymes. The second example concerns the incorporation asymmetric metal complexes into multi-component, colorimetric enantiosensors for α-amino acids. After several unsuccessful attempts, chiral vicinal diamine-Cu(II) complexes were identified as suitable receptors, and accurate spectrophotometric enantiomeric excess determinations were made for several hydrophobic α-amino acids. This system was extended for the construction of an enantioselective differential array sensor, which segregates chemo- and enantiomeric variance when sensors of opposite enantiomeric preference are included. The modality of this analysis likely parallels that of the mammalian gustatory response to α-amino acids, as actual amino acid taste receptor proteins respond with opposing enantioselectivities.