Phosphate esters are essential to any living organism and their specific hydrolysis plays an important role in many metabolic processes. As phosphodiester bonds can be extraordinary stable, as in DNA, great effort has been put into mimicking the active sites of hydrolytic enzymes which can easily cleave these linkages and were often found to contain one or more coordinated metal ions. With this in mind, we report micellar and vesicular Zn(II)-cyclen complexes which considerably promote the hydrolytic cleavage of native DNA and the activated model substrate bis(4-nitrophenyl)phosphate (BNPP). They are formed by self-assembly from amphiphilic derivatives of previously employed complexes in aqueous solution and therefore allow a simple and rapid connection of multiple active metal sites without great synthetic effort. Considering the hydrolytic cleavage of BNPP at 25 °C and pH 8, the micellar and vesicular metal catalysts show an increase of second-order rate constants (k(2)) by 4-7 orders of magnitude compared to the unimolecular complexes under identical conditions. At neutral pH, they produce the highest k(2) values reported so far. For pBR322 plasmid DNA, both a conversion of the supercoiled to the relaxed and linear form, and also a further degradation into smaller fragments by double strand cleavages could be observed after incubation with the vesicular Zn(II)-complexes. Finally, even the cleavage of nonactivated single-stranded oligonucleotides could be considerably promoted compared to background reaction.

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Biological membranes play a key role for the function of living organisms. Thus, many artificial systems have been designed to mimic natural cell membranes and their functions. A useful concept for the preparation of functional membranes is the embedding of synthetic amphiphiles into vesicular bilayers. The dynamic nature of such noncovalent assemblies allows the rapid and simple development of bio-inspired responsive nanomaterials, which find applications in molecular recognition, sensing or catalysis. However, the complexity that can be achieved in artificial functionalized membranes is still rather limited and the control of their dynamic properties and the analysis of membrane structures down to the molecular level remain challenging.

Come together: Dynamic molecular recognition events at biological membrane receptors play a key role in cell signaling. Artificial membranes have been prepared with embedded synthetic receptors which dynamically arrange and selectively respond to external stimuli, such as, small peptide ligands.

The anion binding ability of bis-zinc cyclen complexes in buffered aqueous solution was investigated using indicator displacement assays (IDA) as well as luminescent labelled complexes. A high affinity to phosphate anions, such as UTP or pyrophosphate was observed in IDA while there was no observable binding of other anions. The binding affinity, and as a result the selectivity, between different phosphate anions correlates with their overall negative charge and steric demand. Complexes bearing luminescent labels did not respond to the presence of phosphate anions in homogeneous solution, but did if embedded as amphiphiles in small unilamellar vesicle (SUV) membranes. The scope of possible anionic analytes was extended to phosphorylated protein surfaces by using such metal complex-functionalized vesicles bearing oligoethylene glycol residues in an optimized amount on their surface to suppress non-specific interactions. Under physiological conditions these surface-modified vesicles show a selective response and nanomolar affinity for alpha-S1-Casein, which is multiple phosphorylated, while not responding to the corresponding dephosphorylated Casein or BSA. The vesicular luminescent metal complexes do not currently reach the sensitivity and selectivity of reported enzymatic assays or some chemosensors for phosphate anions, but they present a novel type of artificial receptor for molecular recognition. Membrane-embedding of multiple, different receptors and their possible structuring on the vesicular surface is expected to improve affinities and selectivities and may allow the design of artificial antibodies.