A family of easily accessible light-activated hydrazone switches has been developed having thermal half-lives of up to 2700 years! Structure-property analysis shows that replacing the rotor pyridyl group of our typical hydrazone switch with a phenyl one leads to the long-lived negative photochromic compounds. The switching properties of the hydrazones in both toluene and DMSO were assessed offering insights into the kinetics and thermodynamics of the switching process.

Over years, mathematicians, biologists and chemists have capitalised on the highly useful concept of orthogonality for developing sophisticated complex systems. The use of orthogonal pairs ensures that any modification made on one pair does not propagate any effect onto the other. While the concept equally pertains to dynamic supramolecular interactions, interference-free self-assembly built on multiple orthogonal interactions is still limited and the underlying notions are not yet firmly established. Herein, we identify, classify and evaluate dynamic interactions in various orthogonal settings in order to distill out general recommendations for reliable dynamic orthogonality. Our classification has to exclude templating, allosteric and/or cooperative effects as the latter are specific for individual cases only.

Reversible switching between two states of the triangular nanoswitch [Cu(1)](+) was accomplished by alternate addition of 2-ferrocenyl-1,10-phenanthroline (2) and copper(I) ions. The two switching states regulate the binding and release of two distinct catalysts, piperidine and [Cu(2)](+), in a fully interference-free manner and allow alternating on/off switching of two orthogonal catalytic processes. In switching state I, piperidine is released from the nanoswitch and catalyzes a Knoevenagel addition between 4-nitrobenzaldehyde and diethyl malonate (ON-1 and OFF-2), while in state II the released [Cu(2)](+) catalyzes a click reaction between 4-nitrophenylacetylene and benzylazide (OFF-1 and ON-2). Upon addition of one equivalent of 2 to the (OFF-1 and ON-2)-state, both catalytically active processes are shut down (OFF-1 and OFF-2).

Flip a switch: a nanoswitch uses chemical inputs to turn an organocatalytic Knoevenagel reaction on and off (see scheme: R=reactant, P=product). To stop catalysis the chemical input (pink and green) wraps around the inhibitory segment of the nanoswitch to effect release or unlocking of the switch. The process can run reversibly over three cycles without loss of activity.

A negative feedback loop that relies on the coordination-coupled deprotonation (CCD) of a hydrazone switch has been developed. Above a particular threshold of zinc(II), CCD releases enough protons to the environment to trigger a cascade of reactions that yield an imine. This imine sequesters the excess of zinc(II) from the hydrazone switch, hence lowering the effective amount of protons, and switching the cascade reactions "OFF", thus establishing the negative feedback loop.

A triangular framework with a terpyridine and shielded phenanthroline at its termini constitutes an open/close nanoswitch that is toggled by chemical inputs. In the presence of copper(I) ions, the open triangular framework (OPEN-I) firmly closes to a catalytically inactive heteroleptic [Cu(phen)(terpy)](+) complex (CLOSE). Reversible switching between CLOSE and OPEN-I states was demonstrated by successive addition and removal of Cu(+). In contrast, after addition of iron(II) ions to the CLOSE state a bishomoleptic dimeric [Fe(terpy)2](2+) complex is formed with the copper(I) ions placed in the phenanthroline cavities (OPEN-II). Due to its coordinatively unsaturated [Cu(Phen)](+) sites the dimeric iron complex is able to serve as a catalyst in the cyclopropanation of Z-cyclooctene using ethyl diazoacetate.

The nanoswitches 1 and 2 are interdependently linked in so-called network states (NetStates). In NetState I, defined by presence of [Cu(1)] and 2, the organocatalyst N-methylpyrrolidine catalyzes a conjugate addition. Addition of iron(II) ions as an external chemical trigger to NetState I discharges Cu from [Cu(1)]. The liberated copper(I) ion acts as a second messenger and changes the toggling state at nanoswitch 2. The resulting nanoswitch [Cu(2)] captures the catalytically active species from solution and the conjugate addition is turned OFF. Removal of the original trigger reverses the sequence and turns catalysis ON. The ON/OFF catalytic cycle was run three times in situ.

Using principles of completive and integrative self-sorting, a clean supramolecule-to-supramolecule transformation is realised that involves fusion of a 3-component rectangle and a 2-component equilateral triangle into a 5-component scalene triangle. While the spontaneous process takes 15 h at 25 °C, the catalytic transformation is completed within 1 h.