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
Many drug delivery systems end up in the lysosome because they are built from covalent or kinetically inert supramolecular bonds. To reach other organelles, nanoparticles hence need to either be... Show moreMany drug delivery systems end up in the lysosome because they are built from covalent or kinetically inert supramolecular bonds. To reach other organelles, nanoparticles hence need to either be made from a kinetically labile interaction that allows re-assembly of the nanoparticles inside the cell following endocytic uptake, or, be taken up by a mechanism that short-circuits the classical endocytosis pathway. In this work, the intracellular fate of nanorods that self-assemble via the Pt horizontal ellipsis Pt interaction of cyclometalated platinum(II) compounds, is studied. These deep-red emissive nanostructures (638 nm excitation, approximate to 700 nm emission) are stabilized by proteins in cell medium. Once in contact with cancer cells, they cross the cell membrane via dynamin- and clathrin-dependent endocytosis. However, time-dependent confocal colocalization and cellular electron microscopy demonstrate that they directly move to mitochondria without passing by the lysosomes. Altogether, this study suggests that Pt horizontal ellipsis Pt interaction is strong enough to generate emissive, aggregated nanoparticles inside cells, but labile enough to allow these nanostructures to reach the mitochondria without being trapped in the lysosomes. These findings open new venues to the development of bioimaging nanoplatforms based on the Pt horizontal ellipsis Pt interaction. Show less
To improve the performance of dye-sensitized photoelectrochemical cell (DS-PEC) devices for splitting water, the tailoring of the photocatalytic four-photon water oxidation half-reaction represents... Show moreTo improve the performance of dye-sensitized photoelectrochemical cell (DS-PEC) devices for splitting water, the tailoring of the photocatalytic four-photon water oxidation half-reaction represents a principle challenge of fundamental significance. In this study, a Ru-based water oxidation catalyst (WOC) covalently bound to two 2,6-diethoxy-1,4,5,8-diimide-naphthalene (NDI) dye functionalities provides comparable driving forces and channels for electron transfer. Constrained ab initio molecular dynamics simulations are performed to investigate the photocatalytic cycle of this two-channel model for photocatalytic water splitting. The introduction of a second light-harvesting dye in the Ru-based dye-WOC-dye supramolecular complex enables two separate parallel electron-transfer channels, leading to a five-step catalytic cycle with three intermediates and two doubly oxidized states. The total spin S=1 is conserved during the catalytic process and the system with opposite spin on the oxidized NDI proceeds from the Ru=O intermediate to the final Ru-O-2 intermediate with a triplet molecular O-3(2) ligand that is eventually released into the environment. The in-depth insight into the proposed photocatalytic cycle of the two-channel model provides a strategy for the development of novel high-efficiency supramolecular complexes for DS-PEC devices with buildup and conservation of spin multiplicity along the reaction coordinate as a design principle. Show less
As a virtually inexhaustible source, solar energy plays a major role in future global energy scenarios. Solar-driven water splitting via dye-sensitized photoelectrochemical (DS-PEC) devices is a... Show moreAs a virtually inexhaustible source, solar energy plays a major role in future global energy scenarios. Solar-driven water splitting via dye-sensitized photoelectrochemical (DS-PEC) devices is a scalable, affordable and sustainable technology of great potential for direct conversion of solar energy into storable chemical fuels to produce clean, cost-efficient and environmentally friendly H2 or CO2-derived fuels and thus to contribute to the transformation of a sustainable society from the blueprint to reality. Proton-coupled electron transfer (PCET) plays a crucial role in a wide range of biological and chemical reactions concerning energy conversion processes, such as natural and artificial photosynthesis. Given that the overall catalytic water oxidation consists of four consecutive PCET steps, sequential or concerted, it is therefore of fundamental significance to unveil the intrinsic catalytic mechanism as well as the factors determining the PCET rate and thus to find strategies to facilitate the catalytic water oxidation. Computational tools provide a powerful and essential technique for the understanding and engineering of efficient DS-PEC devices for water splitting. This thesis provides an in-depth understanding of the catalytic mechanisms for the water oxidation half-reaction in catalyst-dye supramolecular complexes and rational strategies to facilitate the involved catalytic reactions. Show less
In view of the considerably high activation energy barrier of the O-O bond formation photocatalytic step in water oxidation, it is essential to understand if and how nonadiabatic factors can... Show moreIn view of the considerably high activation energy barrier of the O-O bond formation photocatalytic step in water oxidation, it is essential to understand if and how nonadiabatic factors can accelerate the proton-coupled electron transfer (PCET) rate in this process to find rational design strategies facilitating this step. Herein we perform constrained ab initio molecular dynamics simulations to investigate this rate-limiting step in a series of catalyst-dye supramolecular complexes functionalized with different alkyl groups on the catalyst component. These structural modifications lead to tuneable thermodynamic driving forces, PCET rates, and vibronic coupling with specific resonant torsional modes. These results reveal that such resonant coupling between electronic and nuclear motions contributes to crossing catalytic barriers in PCET reactions by enabling semiclassical coherent conversion of a reactant into a product. Our results provide insight on how to engineer efficient catalyst-dye supramolecular complexes by functionalization with steric substituents for high-performance dye-sensitized photoelectrochemical cells. Show less
The O–O bond formation process via water nucleophilic attack represents a thermodynamic and kinetic bottleneck in photocatalytic water oxidation because of the considerably high activation free... Show moreThe O–O bond formation process via water nucleophilic attack represents a thermodynamic and kinetic bottleneck in photocatalytic water oxidation because of the considerably high activation free energy barrier. It is therefore of fundamental significance and yet challenging to find strategies to facilitate this reaction. The microscopic details of the photocatalytic water oxidation step involving the O–O bond formation in a catalyst–dye supramolecular complex are here elucidated by density functional theory-based Car–Parrinello molecular dynamics simulations in the presence of an extra proton acceptor. Introducing a proton acceptor group (OH–) in the hydration shell near the catalytic active site accelerates the rate-limiting O–O bond formation by inducing a cooperative event proceeding via a concerted proton-coupled electron-transfer mechanism and thus significantly lowering the activation free energy barrier. The in-depth insight provides a strategy for facilitating the photocatalytic water oxidation and for improving the efficiency of dye-sensitized photoelectrochemical cells. Show less
A dye-sensitized photoelectrochemical cell (DS-PEC) is a promising device for direct conversion of solar energy into fuel. The basic idea, inspired by natural photosynthesis, is to couple the... Show moreA dye-sensitized photoelectrochemical cell (DS-PEC) is a promising device for direct conversion of solar energy into fuel. The basic idea, inspired by natural photosynthesis, is to couple the photoinduced charge separation process to catalytic water splitting. The photo-oxidized dye coupled to a water oxidation catalyst (WOC) should exert a thermodynamic driving force for the catalytic cycle, while water provides the electrons for regenerating the oxidized dye. These conditions impose specific energetic constraints on the molecular components of the photoanode in the DS-PEC. Here, we consider a supramolecular complex integrating a mononuclear Ru-based WOC with a fully organic naphthalene-diimide (NDI) dye that is able to perform fast photoinduced electron injection into the conduction band of the titanium-dioxide semiconductor anode. By means of constrained ab initio molecular dynamics simulations in explicit water solvent, it is shown that the oxidized NDI provides enough driving force for the whole photocatalytic water splitting cycle. The results provide strong evidence for the significant role of spin alignment and solvent rearrangement in facilitating the proton-coupled electron transfer processes. The predicted activation free energy barriers confirm that the O–O bond formation is the rate-limiting step. Our results expand the current understanding of the photocatalytic water oxidation mechanism and provide guidelines for the optimization of high-performance DS-PEC devices. Show less
