Flavin away: Dodecin binds oxidized flavins, whereas reduction of the bound flavin induces dissociation of the holoprotein into apododecin and free flavins. The stepwise reconstitution of dodecin on flavin‐terminated ds‐DNA monolayers showed that although electrochemical flavin reduction (i.e. electron transfer through DNA) was not possible, apododecin (gray circles) could be released by chemical reduction (see scheme).

DNA hydrogels are of great interest for a variety of biomedical applications owing to their biocompatibility and biodegradability but the advantages of DNA hydrogels have not been exploited yet because of their limited availability. Thus far, DNA hydrogels have been prepared from synthetically derived building blocks, and their production on large scale would be far too expensive. As an alternative, here the generation of DNA hydrogels from plasmid DNA is reported. Plasmid DNA can be prepared on large scale at reasonable costs by a fermentation process. The desired linear DNA building blocks are then obtained from the plasmid DNA by enzymatic digestion. Gel formation is carried out by covalent bond formation between individual building blocks via enzymatic ligation. The generation of pristine DNA hydrogels from plasmid DNA is thus presented for the first time. The viscoelastic properties of the hydrogels were studied by rheology, which confirmed that the gels have storage moduli G' of >100 Pa.

Diffusion‐ordered NMR spectroscopy was used to monitor the diffusion of guest molecules in DNA hydrogels and related DNA matrices. As guest molecule the highly symmetric hollow‐spherical flavoprotein dodecin was studied. Thermoresponsive hydrogels were formed by self‐assembly via hybridization of linear double‐stranded DNA building blocks of 30 base pairs equipped with sticky ends, i. e. additional overhangs of 15 bases on both ends, which were complementary to each other. This resulted in hydrogels, in which dodecin was freely diffusing. When in contrast self‐assembly was performed with rather short building blocks (9 base pairs + sticky ends of 6 bases), the diffusion of the guest molecule was hampered, but as hybridization was reversible within the timescale of the experiment, the resulting DNA matrix did not behave as a true gel. Apparently true DNA hydrogels with small mesh size can be obtained only, when self‐assembly of short DNA building blocks via hybridization is combined with enzymatic ligation leading to a covalently linked network. In that case, the minimum achievable mesh size should be limited by the diameter of the ligase. While DNA hydrogels are an ideal matrix to host rather large molecules or even living cells, it is a challenge to design pristine DNA hydrogels with mesh sizes sufficiently small to capture guest molecules such as drugs or enzymes in the size of only a few nm.