Self-assembling molecular drugs combine the easy preparation typical of small-molecule chemotherapy and the tumour-targeting properties of drug-nanoparticle conjugates. However, they require a... Show moreSelf-assembling molecular drugs combine the easy preparation typical of small-molecule chemotherapy and the tumour-targeting properties of drug-nanoparticle conjugates. However, they require a supramolecular interaction that survives the complex environment of a living animal. Here we report that the metallophilic interaction between cyclometalated palladium complexes generates supramolecular nanostructures in living mice that have a long circulation time (over 12 h) and efficient tumour accumulation rate (up to 10.2% of the injected dose per gram) in a skin melanoma tumour model. Green light activation leads to efficient tumour destruction due to the type I photodynamic effect generated by the self-assembled palladium complexes, as demonstrated in vitro by an up to 96-fold cytotoxicity increase upon irradiation. This work demonstrates that metallophilic interactions are well suited to generating stable supramolecular nanotherapeutics in vivo with exceptional tumour-targeting properties. Show less
Vibronic coupling is key to efficient energy flow in molecular systems and a critical component of most mechanisms invoking quantum effects in biological processes. Despite increasing evidence for... Show moreVibronic coupling is key to efficient energy flow in molecular systems and a critical component of most mechanisms invoking quantum effects in biological processes. Despite increasing evidence for coherent coupling of electronic states being mediated by vibrational motion, it is not clear how and to what degree properties associated with vibrational coherence such as phase and coupling of atomic motion can impact the efficiency of light-induced processes under natural, incoherent illumination. Here, we show that deuteration of the H11–C11=C12–H12 double-bond of the 11-cis retinal chromophore in the visual pigment rhodopsin significantly and unexpectedly alters the photoisomerization yield while inducing smaller changes in the ultrafast isomerization dynamics assignable to known isotope effects. Combination of these results with non-adiabatic molecular dynamics simulations reveals a vibrational phase-dependent isotope effect that we suggest is an intrinsic attribute of vibronically coherent photochemical processes. Show less
