A Synthetic Creatinine Receptor: Imprinting of a Lewis-Acidic Zinc(II)cyclen Binding Site to Shape its Molecular Recognition Selectivity

Abstract

Molecularly imprinted polymers (MIPs) from polymerizable Lewis acidic zinc(II)cyclen complexes
and ethylene glycol dimethyl acrylate have been prepared. For the imprinting process the template molecule
creatinine is reversibly coordinated to the zinc atom. The high strength of this interaction allows analyte
binding to the MIP from aqueous solution with high affinity. Its pH dependence is used for controlled guest
release with nearly quantitative analyte recovery rate. The binding capacity and selectivity profile of the
MIP remains constant through several pH controlled binding and release cycles. MIPs missing a suitable
metal binding site showed no significant affinity for thymine or creatinine. Flavin adsorbs nonspecifically to
all polymers. The imprinting process reverses the binding selectivity of zinc(II)cyclen for creatinine and
thymine from 1:34 in homogeneous solution to 3.5:1 in the MIP. Scatchard plot analysis of creatinine binding
isotherms reveals uniform binding of the imprint, with fits indicating a one-site model; however, similar
analysis for thymine indicate high and low affinity sites. This corresponds to unrestricted coordination sites
freely accessible for thymine, e.g., at the polymer surface, and misshaped imprinted sites, which still can
accommodate thymine. More than 50% of all binding sites exclusively bind creatinine and are not accessible
to thymine. The binding properties of a copolymer of polymerizable zinc(II)cyclen and ethylene glycol dimethyl
acrylate missing the creatinine template, which match the binding selectivity of the complex in solution,
confirm that the origin of altered selectivities is the imprinting process. With binding ability at physiological
pH, the MIPs are applicable for tasks in medicinal diagnostics or biotechnology. Imprinted zinc(II)cyclen
complexes provide, like a metalloenzyme binding motif, high binding affinity by reversible coordination
while the surrounding macromolecule determines binding selectivity.