Photoactivated chemotherapy is an approach where a biologically active compound is protected against interaction with the cell environment by a light-cleavable protecting group, and unprotected by light irradiation. As such, PACT represents a major scientific opportunity for developing new bioactive inorganic compounds. However, the societal impact of this approach will only take off if the PACT field is used to address real societal challenges, i.e., therapeutic questions that make sense in a clinical context, rather than purely chemical questions. In particular, I advocate here that the field has become mature enough to switch from a compound-based approach, where a particular cancer model is chosen only to demonstrate the utility of a compound, to a disease-based approach, where the question of which disease to cure comes first: which PACT compound should I make to solve that particular clinical problem? The advantages and disadvantages of PACT vs. other phototherapeutic techniques are discussed, and a roadmap towards real clinical applications of PACT is drawn.

Photocatalysis is a versatile and rapidly developing field with applications spanning artificial photosynthesis, photo-biocatalysis, photoredox catalysis in solution or supramolecular structures, utilization of abundant metals and organocatalysts, sustainable synthesis, and plastic degradation. In this Perspective, we summarize conclusions from an interdisciplinary workshop of young principal investigators held at the Lorentz Center in Leiden in March 2023. We explore how diverse fields within photocatalysis can benefit from one another. We delve into the intricate interplay between these subdisciplines, by highlighting the unique challenges and opportunities presented by each field and how a multidisciplinary approach can drive innovation and lead to sustainable solutions for the future. Advanced collaboration and knowledge exchange across these domains can further enhance the potential of photocatalysis. Artificial photosynthesis has become a promising technology for solar fuel generation, for instance, via water splitting or CO₂ reduction, while photocatalysis has revolutionized the way we think about assembling molecular building blocks. Merging such powerful disciplines may give rise to efficient and sustainable protocols across different technologies. While photocatalysis has matured and can be applied in industrial processes, a deeper understanding of complex mechanisms is of great importance to improve reaction quantum yields and to sustain continuous development. Photocatalysis is in the perfect position to play an important role in the synthesis, deconstruction, and reuse of molecules and materials impacting a sustainable future. To exploit the full potential of photocatalysis, a fundamental understanding of underlying processes within different subfields is necessary to close the cycle of use and reuse most efficiently. Following the initial interactions at the Lorentz Center Workshop in 2023, we aim to stimulate discussions and interdisciplinary approaches to tackle these challenges in diverse future teams.

Ruthenium(II) polypyridyl complexes form a vast family of molecules characterized by their finely tuned photochemical and photophysical properties. Their ability to undergo excited-state deactivation via photosubstitution reactions makes them quite unique in inorganic photochemistry. As a consequence, they have been used, in general, for building dynamic molecular systems responsive to light but, more particularly, in the field of oncology, as prodrugs for a new cancer treatment modality called photoactivated chemotherapy (PACT). Indeed, the ability of a coordination bond to be selectively broken under visible light irradiation offers fascinating perspectives in oncology: it is possible to make poorly toxic agents in the dark that become activated toward cancer cell killing by simple visible light irradiation of the compound inside a tumor. In this Perspective, we review the most important concepts behind the PACT idea, the relationship between ruthenium compounds used for PACT and those used for a related phototherapeutic approach called photodynamic therapy (PDT), and we discuss important questions about real-life applications of PACT in the clinic. We conclude this Perspective with important challenges in the field and an outlook.

We describe two water‐soluble ruthenium complexes, [1]Cl₂ and [2]Cl₂, that photodissociate to release a cytotoxic nicotinamide phosphoribosyltransferase (NAMPT) inhibitor with a low dose (21 J cm⁻²) of red light in an oxygen‐independent manner. Using a specific NAMPT activity assay, up to an 18‐fold increase in inhibition potency was measured upon red‐light activation of [2]Cl₂, while [1]Cl₂ was thermally unstable. For the first time, the dark and red‐light‐induced cytotoxicity of these photocaged compounds could be tested under hypoxia (1 % O₂). In skin (A431) and lung (A549) cancer cells, a 3‐ to 4‐fold increase in cytotoxicity was found upon red‐light irradiation for [2]Cl₂, whether the cells were cultured and irradiated with 1 % or 21 % O₂. These results demonstrate the potential of photoactivated chemotherapy for hypoxic cancer cells, in which classical photodynamic therapy, which relies on oxygen activation, is poorly efficient.

The two-step spin crossover of a new mononuclear iron(II) complex is studied by magnetic, crystallographic and calorimetric methods revealing two successive first-order phase transitions and an ordered intermediate phase built by the repetition of the unprecedented [HS–LS–LS] motif.