Living organisms rely on an efficient yet complex array of multiply interrelated molecular machines to regulate their metabolic activities. Considering metal ions, their heterogenous spatial distribution within intra- and extracellular structures implies the existence of mechanisms, which maintain this concentration gradient a long way from thermodynamic equilibrium. However, even though this requires a huge energy investment in terms of ATP, biological systems utilize concentration gradients of sodium, potassium and calcium ions in many regulatory and recognitory events. The modelling of such processes thus presents a challenge for scientists. Consequently synthetic chemists have been imitating some of the very basic functions realized in the biology. Thess activities have resulted in a number of artificial systems, such as molecular switches, sensors, ratchets, wires, artificial enzymes and self-assembled species to name only a few.

Our research in this field deals with redox-switched ferrocene crown ethers. In such compounds a macrocyclic unit (crown ether) is linked to an electrochemically active group (ferrocene) and the bonding of metal ions within the crown ether is coupled to electron-transfer reactions, i.e. upon oxidation of the ferrocene unit, the bonding of the metal ion within the crown ether is considerably weakened, due to the repulsion of equally charged metal centers.

While our previous work had concentrated on improving the efficiency of such molecular devices, we have now extended our activities in this field by designing an artificial regulatory device, which is able to indirectly control (via electron-transfer reactions) the availability of sodium ions and is based on the coupled action of two different molecular switches.

 

The basic components of our artificial regulatory system using two different molecular switches are two types of redox-active chelating ligands based upon ferrocenes. A chelating aminoferrocene (Fcdpa) forms very stable complexes with soft transition metal ions and responds to the incorporation of metal ions by a drastic change of the ferrocene redox potential (redox-responsive ligands). Complexes of oxaferrocene cryptands (Fccrypt) with hard group I and II metal ions are severly destabilzed upon oxidizing the ferrocene (redox-switching). Based on such ligands a device was assembled which can imitate a regulatory event (see diagram below).
 
 

In short the individual tasks performed by these subunits are the following: a redox-responsive ligand changes its redox properties to become an oxidizing agent upon binding of a cofactor (zinc); thus generating a redox-equivalent to act as a mediator; this mediator triggers the redox-switch and changes the binding properties of the redox-switched ligand for sodium ions, thus regulating the availability of sodium; the removal of the cofactor by an added deactivator results in the reversal of the switching event via back transfer of the mediator and the reactivation of sodium binding by the redox-switch.
In conclusion the availability of sodium can be controlled indirectly (e-transfer!) by zinc ions, which represents a simple of model of a regulatory event. However, the artificial regulatory system described here is only operative when all individual components cooperate and are well adjusted in their binding and redox behavior.

In conclusion it is obviously possible to use small abiotic molecules, to imitate  – in a primitive fashion -  some complex functions which otherwise require a highly sophisticated protein machinery and billions of years of evolution.