Atomistic Insight Into the Host–Guest Interaction of a Photoresponsive Metal–Organic Framework

Abstract Photoresponsive functional materials have gained increasing attention due to their externally tunable properties. Molecular switches embedded in these materials enable the control of phenomena at the atomic level by light. Metal–organic frameworks (MOFs) provide a versatile platform to immobilize these photoresponsive units within defined molecular environments to optimize the intended functionality. For the application of these photoresponsive MOFs (pho‐MOFs), it is crucial to understand the influence of the switching state on the host–guest interaction. Therefore, we present a detailed insight into the impact of molecular switching on the intermolecular interactions. By performing atomistic simulations, we revealed that due to different interactions of the guest molecules with the two isomeric states of an azobenzene‐functionalized MOF, both the adsorption sites and the orientation of the molecules within the pores are modulated. By shedding light on the host–guest interaction, our study highlights the unique potential of pho‐MOFs to tailor molecular interaction by light.

Stimuli-responsivem olecular switches enablet he transfer of externals timuli such as light into well-defined molecular motion.E mbedded in precise moleculare nvironments, these stimuli-responsivem olecular units perform av ariety of essential functions in biological systems. [1] Understanding the externally induced process and in particular the influence on the molecular surrounding opens the door for designing new functional materials with tunable properties. [2] The potential of corresponding functional materials has been showna nd the field of applications ranges from on-command drug delivery over molecular sensing and catalysis to gas-storage. [3] Alike to the biological systems, in all these applications, intermoleculari nteractions and dynamic processes at the nanoscale modified by the molecular switching unit play af undamental rolefor the resulting functionality.T hus, for the developmento fa dvancedphotoresponsive functional materials, ad etailed insight into structurala nd dynamic phenomenai nfluenced by the moleculars witch is crucial to tune the functionality.
In this context, azobenzene has been one of the most employedm olecular buildingu nits. [4] By photoexcitation, azobenzene can be interconverted between two states (cis/trans), which differ distinctively in their physical and chemical properties. [5] To transmit the local photoinduced structural change into long-range outcome, the molecular embedding of the azobenzene unit is fundamental. It is important to distinguish the case of high molecular confinement, in which the interconversionp rocess mightd irectly be influenced by the surrounding, [6] and the case of integrating in open molecular structures, wherei nterferences with the switching dynamics can be minimized.
Soft porousm aterials such as metal-organic frameworks (MOFs) enable, due to their tool-kit assembly, [7] the construction of highly ordereda nd tunable 3D structures with high porosity,p roviding av ersatile approach to immobilize photoswitches. However, despite the increasing numberso fs ynthesized photoresponsiveM OFs (pho-MOFs), which exhibit promising properties, [8] at horoughu nderstandingof the influence of the photoresponsive units on the host-guest interaction is still limited and only af ew numbers of theoretical studies have been reported. [9] Herein, we reveal the impact of the different stateso ft he photoswitch on the host-guest interaction. In particular, we predict how the positiona nd orientation of guestm olecules within the pho-MOFa re modulated, whichi s fundamental for applicationss uch as catalysis. Therefore, we investigated af unctionalized MOF-5,w hich has ac ubic network topology [7c, 10] and extended the terephthalic acidl inkers connecting the Zn 4 Ot etrahedra corners in MOF-5 by azobenzene derivatives (azo-MOF-5, Figure1a) similar to reported pho-MOFs. [9a, 11] By studying benzene derivativesasp rototypical guestm olecules in two azo-MOF-5 states (all-trans/all-cis), we show further that the effect of the switchingu nit depends on even minor structural modificationsa nd differences of the guestm olecules, opening the path to tailor multicomponent systems by light.
The high potential of atomistic simulationsa pplyingc lassical force fields, which allow to cover large time and length scales, to advance the understanding of MOF-based materials has been discussed extensively. [12] Since for an accurate description of the host-guest system the employed force field is crucial, we extended our previously developeda b-initiop arametrized force field for MOF-5 (see Figure S13 and Ta bles S1-S6, Supporting Information). [13] Our main goal is to cover relevant parts of the ground-state energy landscapet oa ccurately describe both switchings tates within one force field (Scheme 1), which is different to other studies, in which af orce field was developed to describe the switching process. [14] In line with our reported approach and utilizing ag enetica lgorithm, [15] we parametrized the force fieldb ased on quantum mechanical (QM) reference data calculated for an onperiodic modelo fa zo-MOF-5,c onsisting of one inorganic clusterw ith as ingle azo-benzene unit ( Figure 1a). We used the structurala nd dynamic properties (geometry and hessian matrix) of one trans isomer (trans A )t ogether with the energy differences( with respect to trans A )o fi nt otal four stationary points of both cis and trans isomers, which differ mainly by the torsion around C5-C4-N6-N7 (C-N b ,F igure 1a), ando ftrans A rotated by 908 around C2À C3 ( Figure S1, Supporting Information).T he derived classical model is ablet od escribe both the structural and dynamic properties of the four isomerso ft he model in excellent agreement with the QM data ( Figures S2-S7, Supporting Information). Going beyondt he stationary points, we validated further our force field by calculating the energy profile connecting the trans A/B conformers. Although the intermediate structures were not included in the fitting procedure, the energyd ata calculated by our parametrized forced are well in line with corresponding QM calculations ( Figure 1b). Due to small structural differences of the optimized trans A state (mainly the CÀN ß :5 8 (force field) and 368 (B3LYP + GD3), respectively,s ee also Figures S2-S6,S upportingI nformation), as mall deviation around 08 is found. However,s ince we are interested in calculating the host-guest interactions at 300 K, the low energy barrierb etween the two configurations around0 8 of 4.3 kJ mol À1 at the DFT level can be readily be overcome during the molecular dynamics simulations and thuso nly play am inor role for the further analysis.
The influence of the rotationald egrees of freedom of the flexible units on the adsorption sites in MOFs has previously been investigated in different studies. [16] In the current work we want to go as tep further by analyzing the contribution of an externally tunable linker on the adsorption sites in order to understand the correlation between the photoresponsive linkers and the guest molecules. Therefore, we appliedt he validated force field to perform Molecular Dynamic (MD) simulations of the unloaded and loaded azo-MOF-5. Interestingly,a lready the analysis of the MD trajectories of the empty azo-MOF-5 indicatesa ni nfluence of the linker conformation on the guest molecules ( Figure 1a). Before going into the analysis,i ts hould be pointedo ut that due to the orientation of the organic linker two cell types (A and B) are presenti nM OF-5-type systems. [10b] Figure 1. a) Ball and stick model of the optimized trans (trans A , trans B )a nd cis isomers (cis A , cis B )oft he nonperiodic reference system (carbon:black, hydrogen; white,o xygen:red, zinc:b rown). b) Energy profile along the rotation of CÀN b connecting trans A and trans B calculated with the force field (blue circles)and at the B3LYP + GD3 level (green crosses). The local minimum around 08 corresponds to trans A and the absolute minimum around AE 1548 corresponds to trans B .T he energyisg iven with respect to trans A calculatedo nD FT level. Keepingt his in mind, the free phenylu nits of the azobenzene linkersi nall-trans azo-MOF-5p oint predominately into the B-cells. In contrast, the free phenyl rings in all-cis azo-MOF-5c an be considered as immobilized benzene molecules (IBM, Scheme 1) sincet hey occupy the so-called a-pockets in the corners of the A-cells (Figure 2a), whichh ave been previously identified as the primary adsorption sites for guest molecules in MOF-5r elated systems. [15d, 17] Since the two switching states alter the a-pocket, am odulation of the host-guest interaction is expected.
Our atomistic simulations of the benzene loaded azo-MOF-5 indeed confirmt his hypothesis, by revealing ac hange of the interaction of the benzene molecules with the primary adsorption site. In the all-cis azo-MOF-5 the benzene molecules interact with both the inorganic unit and the IBMs. As ar esult, the primary adsorption site in the corners of the A-cellf eatures a threefold partitioning ( Figure 2b,F igure S9, SupportingI nformation). In addition, the g-site, which is located in the center of the A-cell and has only been reported at high guest molecule loading, [15d, 18] is already energeticallyp referred at the considered lower guest molecule loading due to the interaction with the IBMs. In the all-trans azo-MOF-5 the interaction with the a-pockets is significantly less influenced by the IBMs and the host-guest interaction is comparable with the loaded nonresponsive framework. [15d, 17, 19] Hence, the embedded molecular switches influence the primary interaction within the pores and, in addition, the host-guesti nteraction can be switched between al ow-density and ah igh-density configuration. Considering the toluene, m-xylene andm esitylene (Figure 2b,F igures S10-S12, Supporting Information), the modulation of the primary adsorption site becomes even more pronounced. Due to the increasings ize of the guest molecules, the interaction with the inorganic unit decreases and the attractive interaction with the IBMs increasesl eading to af urther shift of the guest molecules away from the corner towards the linkersi nall-cis azo-MOF-5. (Figure 2b). At the same time, an increased population of the B-cell and not of the g-site by the benzene derivative is observedi nall-trans azo-MOF-5 due the IBMs preferentially located in the B-cell (Figure 2b,t oluene, m-xylene).
In view of MOFs as solids olvents, the predicted modulation of host-guest interactions by molecular switches, highlights how molecular interaction and packingc an externally be tuned by light within pho-MOFs. However,f or applications such as catalysis, not only the position but also the relative orientation of the guest molecules plays ac rucial role. To map out if the different states of the embedded molecular switches affect the orientation of the guest molecules within the pores, we further evaluated our atomistic simulations andi ndeed observe an impact on theo rientation. Since more than 85 %o f the guest molecules are located in the A-cell, we concentrated on analyzing the orientation of the guest molecules in this cell. The orientationo ft he molecules within the framework is examined by considering an angle q,w hich describest he orientation between the surface normal of the aromatic ring of the guest molecules and av ector representing the diagonal of the A-cell nearest to the guest molecule ( Figure 3a). For benzene, toluene and m-xylene, no significant difference between all-cis and all-trans azo-MOF-5 is observed with respect to the orientation ( Figure S8a-c,S upporting Information). In contrast,i nspecting the probability distribution of q for mesitylene, ad ependency with respect to the switching state is evidenced ( Figure S8d, Supporting Information). Despite the preferred orientation for the mesitylene molecules at q = 30-608,adistinct change in the probability distribution is observed between allcis and all-trans azo-MOF-5. In all-cis azo-MOF-5 the probability of molecules with q = 60-908 increases by af actor of almost two, marking the influence of the two switching states on the orientation of the mesitylene within the pho-MOF.T og et ad etailed picture of the host-guest interaction, we dissected the orientation of each molecule with respect to its center of mass. The corresponding probability distribution illustrates a clear correlation between the adsorption sites andt he orientation (Figure 3a,b ). In all-cis azo-MOF-5t he mesitylene molecules with q = 60-908 are predominantlyl ocated at the corners of the A-cell but at al arger distance compared to the a-pockets. In contrast to the all-trans azo-MOF-5, the mesitylene molecules strongly interact with the IBMs in the cis configuration ( Figure 3d). As ar esult, three orientation-dependenta dsorp-  (Figure 3d): (i)primarily with the inorganic unit (q = 0-308); (ii)with both the inorganic unit and the organic linker (q = 30-608)a nd (iii)primarily with the IBMs (q = 60-908). This assignment is supported by the RDFs between the mesitylene molecules and the IBMs, which provide information about the linker-guest interaction at each ODAS ( Figure 3c). Comparing the first peak of these RDFs, shows a shift to smaller values, which indicates an increasing interaction between the IBMs and the molecules for higher q angles. This is in particulars hown for the all-cis MOF system.H ence, the ODAS with q = 75-908 (blue site in Figure 3) is clearly dominatedb yt he interaction between the linker and the guest molecules. The correlation between the linker rotationa nd the adsorption sites isf urther highlighted by as tructurala nalysis of the CÀN ß angle of the azobenzene linker,w hich is nearest to the guest molecule. From the MD simulations, two preferred positions can be identified for the loaded all-trans case (CÀN ß : 1588 (A) and 398 (B)). Note that the deviation compared to the reference models ( Figure 1) are due to the interaction of the linkers with the guest molecules and the MOF matrix itself. Remarkably,d epending on the ODAS, the population of the Aand B-state of the closestl inker changes.I nt he all-trans case the ration changes from 70:30 %f or q = 0-308 to 30:70 %f or q = 60-908.I nt he all-cis framework as imilar correlation between linker rotation and guest molecules orientationi so bserved. Here, the population of the preferred CÀN ß angle of around9 8 8 (C) and 568 (D), respectively,c hanges from 83:17 % for q = 0-308 to 75:25 %f or q = 60-908.T he significantly different host-guest interactions for different ODAS depending on the photo-switching state is further clarified by extracting the corresponding molecular configurations from our atomistic simulations (Figure 3e).
In conclusion, we have investigated the influence of molecular switching units, incorporated within the matrix of MOFs on the host-guest interaction by atomistic simulation. Ad etailed molecular picture of the impact of the two switching states on the intermolecular interaction within the porous of these pho-MOFs is presentedb ye mployinga na b-initiop arametrized force field. Experimentally so-far not accessible,w ep redict how the photoresponsive building units modulate the preferred adsorption sites within the framework. Moreover,o ur study reveals the potential to alter even the orientation of the guest molecules by tailoring the host-guest interaction by light. At the same time our study shows that guest molecules with only small structural variations are affected differently by the embedded photoswitch.T his highlights the potentialo f these photoresponsive functional materials to tailor systematically even multi-component reactants in catalytic applications.

Computational Details
The classical molecular mechanics calculations, including the Molecular Dynamic (MD) simulations, were performed using al ocally  [20] Following our previous scheme we utilized ag enetic algorithm (GA) [15a-c] to parametrized our MM3 extended force field [13,21] based on DFT calculations. For the periodic calculations of the pho-MOF,aunit cell consisting of eight Zn4O-corners and 24 organic linkers was used. In order to generate the starting configurations and velocities for the microcanonical ensemble (NVE) MD simulations, 10 unloaded and loaded (6 guest molecules per unit cell) pho-MOF systems (in both switching states (all-trans/all-cis)w ere equilibrated at 300 Kf or 0.5 ns using the Nose-Hoover thermostat. [22] The starting configurations for these NVT ensembles, were obtained by ah igh-temperature MD simulation. The Beeman algorithm is employed for the time propagation using at ime-step of 1.0 fs. The total simulation time of each of the independent MD simulations (NVE ensemble) was 4ns. The used van-der-Waals cutoffi s1 2 .T he default smooth particle mesh Ewald (SPME) approach [23] as implemented in the Tinker code was used to describe the electrostatic chargecharge interactions. All DFT calculations were done using the Gaussian 16 code [24] together with the B3LYP + GD3 functional [25] and the cc-pVDZ basis set [26] for C,H,N and Oa nd cc-pVDZ-PP basis set combined with the Stuttgart-Dresden pseudopotentials for Zn. [27] Acknowledgements Financials upport from the Deutsche Forschungsgemeinschaft (DFG) through the Collaborative Research center TRR 61, and the grants AM 460/2-1 is gratefully acknowledged. The computations have been carriedo ut using resources provided by PALMA@WWU.

Conflict of interest
The authors declare no conflict of interest.