Molecular Factors Controlling the Isomerization of Azobenzenes in the Cavity of a Flexible Coordination Cage

Abstract

Photoswitchable molecules are employed for many applications, from the development of active materials to the design of stimuli-responsive molecular systems and light-powered molecular machines. To fully exploit their potential, we must learn ways to control the mechanism and kinetics of their photoinduced isomerization. One possible strategy involves confinement of photoresponsive switches such as azobenzenes or spiropyrans within crowded molecular environments, which may allow control over their light-induced conversion. However, the molecular factors that influence and control the switching process under realistic conditions and within dynamic molecular regimes often remain difficult to ascertain. As a case study, here we have employed molecular models to probe the isomerization of azobenzene guests within a Pd(II)-based coordination cage host in water. Atomistic molecular dynamics and metadynamics simulations allow us to characterize the flexibility of the cage in the solvent, the (rare) guest encapsulation and release events, and the relative probability/kinetics of light-induced isomerization of azobenzene analogues in these host-guest systems. In this way, we can reconstruct the mechanism of azobenzene switching inside the cage cavity and explore key molecular factors that may control this event. We obtain a molecular-level insight on the effects of crowding and host-guest interactions on azobenzene isomerization. The detailed picture elucidated by this study may enable the rational design of photoswitchable systems whose reactivity can be controlled via host-guest interactions.

Figure 1

Model host–guest systems. (A, top) Structure of the supramolecular cage studied herein, formed via the self-assembly of triimidazole-based donors and cis-blocked Pd acceptors. (A, bottom) Atomistic model of the supramolecular host cage, along with a schematic representation of its octahedral structure, which can be described by the axial and equatorial distances, D1 (red) and D2 (green). (B) Structural formulas and atomistic models of the guests studied herein: azobenzene (AZB), methoxylated azobenzene (M-AZB), fluorinated azobenzene (F-AZB), and arylazopyrazole (AZP) (here shown as trans isomers).

Figure 2

Conformational free-energy landscape of the empty cage. (A) Free-energy surface (FES) as a function of D1 (distance between the axial/red Pd atoms) and D2 (distance between the midpoints of opposite edges of the cage identified by the equatorial/green Pd atoms). The color scale in the FES indicates the free-energy associated with cage conformations on the D1–D2 plane (scale and legend shown in B). Four representative snapshots are shown: the starting, extended configuration (top right) corresponding to the crystal structure of the cage, the energetic minimum of the FES (top left), a D1-elongated structure (bottom right), and a D2-elongated structure (bottom left). Axial and equatorial Pd atoms are colored in red and green, respectively, while the connectivity scheme is colored in orange to facilitate interpretation of the structures. (B) Probability associated with all cage conformations as a function of the relative free-energy (bin width, 0.5 kcal/mol).

Figure 3

Free-energy cost of guest encapsulation. Representative equilibrium conformations (in the D1–D2 plane) of the cage encapsulating different trans (left) or cis (right) guests. For each host–guest system, we report the position of the minimum-energy conformation (colored points) and the associated isolines (same colors) enclosing all conformations within 0.5 kcal/mol from the minimum of each system. The data are projected onto the FES of the empty cage (same as Figure 2), for which we also indicate the global minimum and associated 0.5 kcal/mol isoline (in white).

Figure 4

Trans → cis transitions of azo-switches inside and outside the cage. (A) Kinetics of trans → cis isomerization of the excited M-AZB (top) and F-AZB (bottom) outside the cage (in solution) reported as examples. The measured transition times, reported below the isomerization arrows, are obtained from MD simulations using an atomistic model where the CNNC dihedral potential term for the trans-azobenzene derivatives (E_dih, reported in the plot as a function of the dihedral angle), is changed from the black curve (native/unperturbed state) to the blue curve (excited trans-azobenzene, S*). (B) Kinetics of trans → cis isomerization of excited M-AZB (top) and F-AZB (bottom) switches confined inside the cage. Transition times for all the guests in the cage are reported in Table 1.

Figure 5

Thermodynamics and kinetics of trans guest binding/release. (A) Representative MetaD snapshots of the reversible binding and release of trans-M-AZB inside the cage; k_off and k_on denote the kinetic constants for the expulsion and encapsulation processes (the k_on value inside the brackets is explicitly calculated, accounting for the guest concentration used in the model ∼11.4 mM, providing the actual rate). (B) Thermodynamic and kinetic scheme representing the expulsion and encapsulation mechanisms for trans-AZB in/out the cage as a function of the distance between the guests’ and the cage’s centers of mass (identifying IN and OUT states). (C) Thermodynamic schemes representing the expulsion/encapsulation of the trans isomers of M-AZB (green), F-AZB (cyan), and AZP (violet) guests. All ΔG differences between IN vs OUT states were computed from converged MetaD simulations, while the transition barriers were more accurately estimated from multiple infrequent MetaD runs (see the SI Methods section for further details).

Figure 6

Molecular determinants of isomerization under confinement. (A) Relationship between isomerization rate (τ_trans–cis) and residence times (τ_off) of the guests inside the cage. (B) Relationship between τ_trans–cis and potential energy of host–guest interactions, ΔE_HG. (C) Relationship between τ_trans–cis and the number of contacts between the cage and the guest. (D) Relationship between τ_trans–cis and the volume (V) of guest molecules (see the SI Methods section for details on guest volume estimation). (E) Switching deceleration, τ_trans–cis/τ₀, as a function of the increase in guest volume (%ΔV_guest), in which τ₀ denotes isomerization time measured at the original volume of each guest. In plots A–E, the points correspond to guests AZB (black), M-AZB (green), F-AZB (cyan), and AZP (violet). (F) Average τ_trans–cis/τ₀ as a function of the average increase in guest volume (%ΔV_guest), obtained by averaging all data from plot E between systems with similar %ΔV_guest. The error bars indicate the standard deviation of %ΔV_guest and τ_trans–cis/τ₀ values. Inset: cartoon showing the volume of encapsulated M-AZB (green) inside the cage (white). The dashed lines in all plots are the logarithmic fit of the data.