In an international cooperation, researchers at the Universities of Amsterdam and Zurich have developed a molecular system for controlled release of iron. They integrated ferrocene, a molecular sandwich that encloses an iron atom, with a carbon ‘nanohoop’. As a result, the system allows for the release of Fe2+ ions upon activation with benign green light. It has recently been presented in a paper in the Journal of the American Chemical Society (JACS) and is now featured on the front cover of the latest JACS issue.

The research was carried out by the groups of Dr Tomáš Šolomek at the University of Amsterdam’s Van ‘t Hoff Institute for Molecular Sciences and Dr Peter Štacko at the University of Zurich (Department of Chemistry). Their expertise is in photocages, molecular photochemical tools that offer precise control over substrate activity in time and space using light as a bio-orthogonal stimulus. Photocages permit activation of biologically significant molecules such as proteins, nucleotides, or drugs. Not only are they a great tool to study mechanisms and dynamics of biochemical processes, they also have potential for therapeutic applications such as photoactivated chemotherapy.

In the research now published in JACS, the researchers shifted their focus from controlling the activity of organic molecules to another crucial component in many biological systems: iron. Renowned for its role in oxygen transport in the human body, it also has a pivotal role in the energy-providing redox processes in mitochondria, in the synthesis of deoxyribonucleotides, or in protecting cells from oxidative stress.

Strain-induced photorelease

Nature has developed a protein-based system to tightly regulate iron’s uptake and balance. In their paper, the researchers present a less sophisticated yet fully functional synthetic equivalent that stores iron and releases it ‘on demand’.

The system is based upon the use of ferrocene as the iron carrier, and enables controlling its function by integrating it into a carbon nanohoop. Ferrocene is an organometallic ‘sandwich complex’ that tightly holds an iron atom between two cyclopentadienyl rings. On itself, it is chemically rock stable and resistant to light. Incorporating it into a molecular nanohoop, however, changes this. When the two cyclopentadienyl rings are connected by means of six coupled benzene rings (a cycloparaphenylene nanohoop), a system emerges that enables control over the iron containment. Although conformationally stable, the integration twists the entire nanohoop structure and exerts a large mechanical stress on the ferrocene. As a result, the system becomes susceptible to irradiation with green light, which results in release of the iron.

In their paper, the researchers describe how the iron can be released with high efficiency upon irradiation. They expect this strategy of introducing mechanical stress in molecules to offer great promise also beyond the realm of photocages. For instance, it can potentially enable the development of new responsive materials in supramolecular, organometallic, or polymer chemistry.

Abstract, as published with the paper

We present the synthesis, structural analysis and remarkable reactivity of the first carbon nanohoop that fully incorporates ferrocene in the macrocyclic backbone. The high strain imposed on the ferrocene by the curved nanohoop structure enables unprecedent photochemical reactivity of this otherwise photochemically inert metallocene complex. Visible light activation triggers a ring-opening of the nanohoop structure fully dissociating the Fe–cyclopentadienyl bonds in the presence of 1,10-phenanthroline. This process uncages Fe²⁺ ions captured in the form of [Fe(phen)₃]²⁺ complex in high chemical yield and can operate efficiently in a water-rich solvent with green light excitation. The measured quantum yields of [Fe(phen)₃]²⁺ formation show that embedding ferrocene into a strained nanohoop boosts its photoreactivity by three orders of magnitude compared to an unstrained ferrocene macrocycle or ferrocene itself. Our data suggest that the dissociation occurs by intercepting the photoexcited triplet state of the nanohoop by the nucleophilic solvent or external ligand. The strategy portrayed in this work proposes that new, tunable reactivity of analogous metallamacrocycles can be achieved with spatial and temporal control, which will aid and abet development of responsive materials for metal ions delivery and supramolecular, organometallic, or polymer chemistry.