Periodic Reporting for period 4 - RAMSES (Reactivity and Assembly of Multifunctional, Stimuli-responsive Encapsulation Structures) Reporting period: 2021-06-01 to 2022-11-30 Summary of the context and overall objectives of the project All matter surrounding us, including earth and wind, materials we use, food we eat as well as our own bodies consist of molecules, which themselves are composed of different atoms from the periodic table of elements. Molecules can be small or large, of simple shape or structurally complex, flat or voluminous, dense or hollow, soluble or solid. Whereas minerals are usually rather simple in composition and internal structure, biologically derived molecules, such as proteins, DNA and vitamins are more complex, both in their 3-dimensional structure as well as specific function. For example, enzymes are able to manufacture („catalyze“) the formation of other complex molecules and they possess control switches and input sites for chemical fuels to regulate their activity.Over billion years of evolution, nature has brought the production and function of its building blocks to perfection. They are capable of specific recognition, information storage, signal transduction, self-repair and replication. Acting together, they can function as molecular machines with the ability to maneuver atoms and molecules on the nanometer scale (as Richard Feynman already recognized in the 50th) and produce new molecules, thus acting as microscopic factories. Structural biologists and chemists have elucidated breathtaking details about the shape and motion of the molecules forming the living world.In the last decades, driven by an inherent curiosity, researchers started to rebuilt, mimic or in some cases even surpass natural paradigms by synthetic laboratory work. They systematically created man-made molecular structures from scratch and tested their ability to reach the structural and functional complexity of what we know from the biological world. After all, they used the same chemical elements also available to nature and built on the same physical laws.Here is where synthetic supramolecular chemistry comes into play, a dedicated branch of chemical research which aims at creating molecular assemblies with ever increasing complexity. Within the ERC project RAMSES (Reactivity and Assembly of Multifunctional, Stimuli-responsive Encapsulation Structures) the Clever Lab has specialized on the synthesis of hollow molecules ("cages") that are able to include smaller molecules in their interior. We use "self-assembly", a process comparable to a self-solving puzzle game where building blocks, organic molecules and metal ions that fit perfectly to each others, form a larger structure by "just shaking them together long enough" for the final result to emerge. We integrate functions such as switches (triggered by light), recognition sites, chiral moieties, dyes, catalytic sites (to promote chemical reactions) and many other chemical groups.Within ERC-funded project RAMSES and beyond, our mission was and is to gather fundamental knowledge about non-covalent assembly processes, develop new routes towards the rational design and straightforward synthetic realization of structural and functional complexity on the nanoscale and turn this into practical application, highly relevant for sustainable industrial processes, new medical and diagnostic developments and smart materials used in future devices.After finishing the project, the following objectives have been achieved and conclusions drawn:- several othogonal assembly strategies to achieve non-statistical formation of heteroleptic structures have been developed, broadly validated and introduced into the scientific community via high-profile publications- stimuli-responsive elements have been introduced into self-assembled nanostructures, i.w. photoswitches that allow light-triggered guest uptake & release as well as dissipative "out-of-equilibrium" behaviour- further functionalities such as endohedral recognition sites and exohedral solubility- and aggregation-controlling groups have been implemented- several combinations of functionalities within the same architecture have been established to generate emerging phenomena, e.g. chiral building blocks were combined with emissive ones to create modular circularly polarized luminescence (CPL)-active compounds via intracage chirality transfer. In addition, the created cavity can bind a guest that enhances and shifts the CPL signal.- a large number of high-rank peer-reviewed publications were disseminated, conference presentations given, students, PhDs and postdocs trained, collaborations established and international networks strengthened. Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far We developed new strategies for the self-assembly of functionalized, artificial building blocks that allow for a rational (non-statistical) integration of two or more components into a single architecture. The challenge is to design systems and assembly principles where, for example, components A, B, C and D only assemble into "heteroleptic" product ABCD, without falling into narcissistic self-sorting (A only with A, B only with B…) or a complete statistical mess (here: 55 possible “lantern-shaped”, four-component systems, from AAAA over BCCD to ABCD). Therefore, while interconnectivity between the components has to be secured, entropy – a formidable enemy favoring the formation of convoluted mixtures – has to be overcome by carefully installed molecular "nuts and bolts" or "grooves and tongues". After reliable and robust strategies towards such low-symmetric, multi-component structures have been devised, these will be used to facilitate the implementation of multiple functionalities and study their interplay in the context of photo-redox processes, materials properties and action on internalized substrates (molecular recognition, reactions under confinement).For further news, see our Twitter channel: https://twitter.com/guido_clever and website: www.clever-lab.de Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far) We enhanced the repertoire of assembly strategies to obtain multifunctional, heteroleptic structures, as we see the contribution of novel assembly principles as a fundamental enabling technique to allow a multitude of future downstream developments and applications.The worked-out assembly strategies were exploited to implement multiple functionalities within a single product, with a focus on donor-acceptor combinations to realize directed excitation or charge transfer (with relevance for molecular diagnostics, electronics and photovoltaics research), the pairing of catalytic sites with control elements (e.g. chiral groups) as well as the anisotropic outside decoration to realize higher-order structures with application in the synthesis of new nano-structured materials.In conclusion, we not only enhanced fundamental knowledge about adjusting enthalpic, entropic and geometric factors within non-covalently assembled nano-architectures, but furthermore paved the way to application of the worked-out principles. We envision several future areas of application of the project-derived findings, all of which share significance with respect to environmental aspects, sustainable process development and new smart molecular systems and materials, thus showing the potential to contribute technological advances with economic benefits on the long term. Major assembly strategies compared Collection of team pictures Examples: amphiphilic and fullerene-binding cages Lab scene Illustration Logo Concept: evolution of cage assembly strategies
