Mixed (Anti)Aromaticity, Unorthodox Interactions and Topologies – MixAr

Our teams have pioneered the synthesis of hexaphyrin-cyclodextrin hybrid structures which together form a new class of highly versatile compounds. Indeed, this unique design based on triple-linked units enables chiral communication, tightly associated confined space and global conformational restriction of hexaphyrin, thus stabilizing an antiaromatic state. In this proposal, we aim to maintain chiral communication and an associated cThe MixAr project aims to deepen our understanding of antiaromaticity, a key phenomenon for the development of new functional materials. The main objective is to harness this property through supramolecular concepts, exploring three under-explored areas in particular: mixed (anti)aromaticity, unorthodox interactions and Möbius [4n+2] antiaromaticity. - Mixed (anti)aromaticity: Very few studies have explored what happens when antiaromatic systems interact with each other or with aromatic systems. MixAr seeks to understand how antiaromatic character can diffuse “through space” or “through bonds”, and control conversion to so-called “3D aromatic” forms. This knowledge could pave the way for innovative devices for information storage and transfer. - Unconventional interactions: While aromatic systems (4n+2) are well known for their ability to bind other chemical entities, antiaromatic systems [4n] remain virtually unexplored in this field. MixAr aims avity, but also to achieve greater flexibility in the hybrid structures so that the antiaromatic and aromatic characters can be switched either by redox processes or by conformational adaptation (Möbius torsion) triggered by external stimuli. Very recently, we have also developed hybrid structures based on doubly-linked units, using a readily available A,D-modified cyclodextrin platform. These new hybrids offer the best compromise in terms of accessibility, conformational control and aromaticity, chirality transfer phenomena, coordination behavior and redox stability. These multifunctional molecules thus offer a cutting-edge toolbox to meet the challenges of the current MixAr project. We therefore propose to explore two complementary approaches in parallel, depending on the environment undergone by an antiaromatic cycle: (i) a first focusing on interaction across space (3D arrangement). This part will be developed in Paris (scientific leader: M. Ménand) and will concern dimeric architectures enabling hexaphyrins to be placed in immediate proximity (“face-to-face” design). This approach will address concerns identified as “mixed (anti)aromaticity” and “unorthodox interactions”; (ii) a second exploring through-link communications (“in-line” arrangement). This part will be developed at Rennes (scientific leader: S. Le Gac) and will target meso-meso-ethynyl bonded hexaphyrins. This approach will address concerns identified as “mixed (anti)aromaticity”. For both approaches, a third component identified as “[4n+2] Möbius antiaromaticity” will be explored in different arrangements.

Among the major results, a significant expansion of hybrid hexaphyrin–cyclodextrin (HCD) structures has been achieved. Totemic architectures in which the hexaphyrin adopts gable-shape, figure-of-eight, or rectangular conformations (functionalized with bisalkynyl motifs) have been synthesized, and their properties (coordination, chirality, molecular recognition, etc.) are currently being evaluated. Additionally, linear “2+1” hybrids (CD–H–CD) featuring “open” cyclodextrins (Bn → OMe) have been developed. The corresponding Rh(I) bimetallic complexes enable the hexaphyrin to adopt an antiaromatic configuration; these are simpler platforms than the initially envisioned sandwich dimers and show promise for the preorganization of other (anti)aromatic molecules via inclusion processes within the CDs. Moreover, Zn(II) complexation with acetylacetonate (acac) derivatives has been initiated as a metal-template approach to preorganize molecules within CDs, with the aim of forming (pseudo)rotaxanes. A major breakthrough involves the redox control of (anti)aromatic character in Möbius-type HCDs. Achieving such control opens up new possibilities for information-processing systems. The redox behavior of Ni(II) and Pd(II) complexes of a doubly linked [28]π Möbius-aromatic hexaphyrin with an α-cyclodextrin has been investigated. This totemic architecture incorporates three types of chiral elements and generates two pseudo-enantiomers depending on the coordinated metal, each displaying strong and opposite chiroptical signatures corresponding to the P and M configurations of the Möbius π-systems. Upon chemical oxidation to [26]π systems, the behavior echoed the fable of the Oak and the Reeds: the Ni(II) complex, with a more robust N3C coordination sphere, acts like the “Oak” - maintaining the Möbius conformation at the expense of π-conjugation, which is disrupted by unavoidable water insertion. In contrast, oxidation of the Pd(II) complexes (the “Reeds”) transforms the Möbius-aromatic systems into rectangular Hückel-aromatic systems, which are retained within the chiral environment defined by the CD linkage. This provides an effective chiral instruction site, as reduction back to the original Möbius configuration occurs with high stereoselectivity. This reversible shape-shifting process represents a form of chiral memory, where the stereochemistry of a cyclic π-system is encoded in the molecular architecture and expressed upon changes in electronic state. Spectroelectrochemical studies have revealed robust chiroptical switches, an unprecedented innovation in Möbius π-systems. This work has also been successfully extended to the out-of-equilibrium control of chiroptical activity via protonation, opening new avenues for information encoding.

The scientific impact of the project is undeniable. The redox control of the chiroptical properties of a Möbius π-system is unprecedented. Part of our work has been published in the prestigious Journal of the American Chemical Society (https://doi.org/10.1021/jacs.5c00524), and was highlighted in a feature by CNRS Chemistry (https://www.inc.cnrs.fr/fr/cnrsinfo/les-anneaux-de-mobius-ont-de-la-memoire). Oral presentations have also been selected at renowned international conferences, including ICS Dunkerque 2024, ICPP Niagara Falls 2024 and ISMSC Kyoto 2025. Additional manuscripts are currently in preparation, for example on the out-of-equilibrium control of the chiroptical activity of HCD architectures. Furthermore, through a PhD fellowship and a postdoctoral contract, this project has significantly contributed to the training of two highly qualified researchers, who are continuing their development in research through postdoctoral positions in France and the United States.

F. Robert, B. Boitrel, M. Ménand, S. Le Gac, J. Porphyrins Phthalocyanines 2021, 25, 1022–1032.

Nature builds complex architectures and organizes them into sophisticated dynamic networks thanks to an intensive use of a limited set of weak and reversible interactions. Unorthodox ones recently joined the toolbox and changed the paradigm of device conception. Besides, whereas aromatic p-type interactions are ubiquitous, those originating from antiaromatic p-systems remain to be discovered. MixAr general aim is to lay down the foundations of conceptually new molecular systems taking advantage of antiaromaticity. Tuneable (anti)aromatic porphyrinoids- cyclodextrins edifices will be prepared and their recognition properties, combined to aromaticity reversal emerging from conformational (Möbius twisting) or stacking events (three-dimensional aromaticity), will be studied. While face-to-face species will be devoted to antiaromatic p-type interactions, oligomeric hybrids will target multiple (anti)aromaticity switching through iterative twisting events.