A curved host and second guest cooperatively inhibit the dynamic motion of corannulene

The study addresses how host–guest interactions can reciprocally influence both host conformation and guest dynamics, mimicking induced-fit and ternary-complex regulation seen in biomolecular systems. Curved aromatic molecules such as fullerenes and corannulene provide ideal testbeds due to dominant dispersion interactions and well-defined curvature. Corannulene exhibits rapid bowl-to-bowl inversion at room temperature, historically difficult to slow without chemical modification. Metal–organic cages offer confined, chiral, and shape-defined spaces to modulate guest behavior. The authors designed a self-assembled cage with concave, chiral walls to (i) adapt stereochemically when binding curved fullerenes and (ii) modulate the dynamic inversion of corannulene, including in ternary complexes where an additional co-guest further influences dynamics and allows stereochemical sensing.

Prior studies established induced fit and ternary complex formation as key features of biomolecular recognition. Curved aromatics (fullerenes and corannulene) have been widely investigated; corannulene’s bowl-to-bowl inversion barrier is low (ca. 10–12 kcal mol−1), with acceleration of inversion reported via stabilization of the planar transition state in macrocyclic hosts (e.g., ExBox) and compression within an anthracene-walled host. Conversely, slowing corannulene inversion has mostly required covalent modification. Metal–organic cages provide confined environments for stabilization, separation, and catalysis, with design principles emphasizing shape complementarity for selective and strong binding. Phosphangulene-based concave, chiral receptors have shown affinity for fullerenes through concave/convex interactions. This work builds on these concepts to create a chirotopic, concave-walled cage that can reconfigure upon fullerene uptake and modulate the dynamics of corannulene, including in the presence of secondary guests.

- Design and synthesis: A concave, chiral phosphangulene-based triamine subcomponent (A) was synthesized and self-assembled with 2-formylpyridine and Zn(NTf2)2 in acetonitrile to form a Zn4L4 cage (1) with a spherical, chirotopic cavity. Racemic A produced a single diastereomeric pair of enantiomers (T1 configuration), inferred by 1H NMR and confirmed by X-ray crystallography. Racemic A was also resolved by chiral HPLC to access enantiopure cages ((P-A4)1 and (M-A4)1). - Guest binding studies: Host 1 was combined with C60, C70, corannulene, pyrene, coronene, and cycloalkanes (C5–C8). Binding was monitored by 1H NMR (including VT, EXSY, NOESY), DOSY NMR, ESI-MS, and X-ray crystallography. Binding constants were determined by NMR titration. - Host reconfiguration analysis: For fullerene binding, in situ and thermally equilibrated samples were analyzed by 1H NMR to track T1→T2 cage diastereomer interconversion. CD spectroscopy on enantiopure cages and their fullerene complexes probed changes in metal-vertex handedness upon guest uptake. VOIDOO cavity-volume calculations were performed from X-ray structures for empty 1 (T1) and its C60/C70 adducts (T2) to quantify induced fit. - Corannulene dynamics: Encapsulated corannulene was studied by VT 1H NMR; diastereotopic splitting enabled exchange monitoring. Line-shape analysis yielded exchange rate constants k; Eyring analysis provided ΔG‡. EXSY verified exchange of adjacent protons during inversion. Effects of co-encapsulated cycloalkanes on corannulene inversion were quantified by additional VT NMR and line-shape constraints. - Ternary complexes: Formation with cycloalkanes was evidenced by large upfield shifts of second-guest signals, DOSY co-diffusion with cage, NOESY cross-peaks between guests, ESI-MS, and an X-ray structure of C6H12·corannulene⊂1 (showing cyclohexane nested in corannulene within the T1 cage). - Chiral sensing: Enantiopure cage with corannulene and R/S-3-methyl-2-butanol (MB) was examined by 1H NMR and DOSY to assess diastereomer formation and upfield separation. Mixtures of known ee were tested; integrals of bound R- and S-MB and associated corannulene signals were correlated with solution ee.

- Host reconfiguration (induced fit): Cage 1 forms as T1 (X-ray). Upon binding fullerenes, 1 reconfigures to T2. For C60, two diastereomeric host configurations appear initially by 1H NMR, evolving over 7 days at 70 °C to a single T2 product; C70 yields only T2. VOIDOO-derived cavity volumes: empty 1 (T1) 490 Å3; C60⊂1 (T2) 718 Å3; C70⊂1 (T2) 925 Å3, evidencing guest-induced expansion. Encapsulated C70 shows desymmetrized 13C NMR (D5h→D5) in the chirotopic cavity. - Corannulene binding and dynamics: 1 selectively encapsulates corannulene over similar PAHs (pyrene cooperative binding; coronene not bound), consistent with shape complementarity. Binding constant for corannulene: K = (1.1 ± 0.1) × 10^3 M−1 in CD3CN. Encapsulation desymmetrizes corannulene (C5v→Cs), yielding two coupled 1H signals. VT NMR line-shape/Eyring analysis gave ΔG‡(298 K) = 17.9 ± 0.3 kcal mol−1 for bowl-to-bowl inversion inside 1, versus ~11.5 kcal mol−1 extrapolated for free corannulene, indicating ≈6 kcal mol−1 barrier increase due to encapsulation. - Ternary complexes and cooperative inhibition: Cycloalkanes (C5–C8) co-encapsulate with corannulene to form ternary complexes that are not observed without corannulene (e.g., cyclohexane). Encapsulated cyclohexane exhibits a singlet at −3.58 ppm (upfield by 5.05 ppm). DOSY shows a common diffusion coefficient (D = 4.0 × 10−6 cm2 s−1). NOESY indicates spatial proximity of the two guests. X-ray of C6H12·corannulene⊂1 shows cyclohexane nested in corannulene within T1. - Further suppression of dynamics in ternary complexes: Corannulene inversion is further slowed in the presence of a co-guest; for C8H16·corannulene⊂1, ΔG‡ at 348 K is at least 3.7 kcal mol−1 greater than for corannulene⊂1 at the same temperature (on top of the ≈6 kcal mol−1 increase from encapsulation). Cyclohexane chair inversion is also slowed: literature barrier 9.70 kcal mol−1 at 206.5 K vs ΔG‡ = 10.65 ± 0.03 kcal mol−1 inside C6H12·corannulene⊂1. - Chiral reporting and ee determination: With enantiopure cage, corannulene plus enantiopure R-3-methyl-2-butanol (MB) forms diastereomeric ternary complexes, giving distinct, well-separated upfield 1H signals for bound guests. Binding is non-enantioselective (equal intensities), allowing integrals of R- and S-MB signals (and corresponding corannulene signals) to directly report solution ee without spectral overlap (shifts >5 ppm upfield into <0 ppm region).

The results demonstrate a reciprocal host–guest interplay reminiscent of biomolecular induced fit and allosteric regulation. Curved fullerenes reshape the cage stereochemistry from T1 to T2, optimizing concave–convex contact, while the chirotopic cavity of the host desymmetrizes corannulene and stabilizes its bowl-shaped ground state, substantially increasing its inversion barrier. The presence of a secondary, size- and shape-matched guest (cycloalkanes) in ternary complexes further modulates guest dynamics—co-encapsulation both inhibits corannulene inversion beyond the effect of the host alone and slows cyclohexane ring-flips, indicating coupled motions within the confined space. The chiral environment transduces stereochemical information between guests, enabling direct, non-derivatized NMR-based determination of enantiomeric excess from clean, upfield-separated signals. Collectively, these findings validate the design principle that concave, chirotopic hosts can adapt to curved guests and exert fine control over molecular dynamics through shape complementarity and cooperative binding, offering a platform for functional supramolecular systems that mimic biological regulation.

A concave, chirotopic Zn4L4 cage reconfigures stereochemically upon fullerene binding (induced fit) and selectively binds corannulene, where confinement elevates the bowl inversion barrier by ~6 kcal mol−1 at 298 K. Co-encapsulation with cycloalkanes forms ternary complexes that further suppress corannulene inversion and slow cyclohexane chair inversion, evidencing mutually influenced guest dynamics. The chiral host–guest–guest system provides distinct NMR signatures enabling direct measurement of the ee of a chiral co-guest. These insights highlight how curved hosts and cooperative co-guests can tailor molecular motion in confined spaces. Future applications may harness mechanically coupled guest motions to influence reaction kinetics—e.g., leveraging corannulene ring-flipping to compress a second guest and accelerate transformations with unfavorable volumes of activation, such as intramolecular cycloadditions.