Metallosupramolecular hosts of nanoscopic dimensions, which are able to serve as selective receptors and catalysts, are usually composed of only one type of organic ligand, restricting diversity in terms of cavity shape and functional group decoration. We report a series of heteroleptic [Pd2A2B2] coordination cages that self‐assemble from a library of shape complementary bis‐monodentate ligands in a non‐statistical fashion. Ligands A feature an inward pointing NH function, able to engage in hydrogen bonding and amenable to being functionalized with amide and alkyl substituents. Ligands B comprise tricyclic aromatic backbones of different shape and electronic situation. The obtained heteroleptic coordination cages were investigated for their ability to bind phosphate diesters as guests. All‐atom molecular dynamics (MD) simulations in explicit solvent were conducted to understand the mechanistic relationships behind the experimentally determined guest affinities.
Molecular simulations of intrinsically disordered proteins (IDPs) are challenging because they require sampling a very large number of relevant conformations, corresponding to a multitude of shallow minima in a flat free energy landscape. However, in the presence of a binding partner, the free energy landscape of an IDP can be dominated by few deep minima. This characteristic imposes high demands on the accuracy of the force field used to describe the molecular interactions. Here, as a model system for an IDP that is unstructured in solution but folds upon binding to a structured interaction partner, the transactivation domain of c-Myb was studied both in the unbound (free) form and when bound to the KIX domain. Six modern biomolecular force fields were systematically tested and compared in terms of their ability to describe the structural ensemble of the IDP. The protein force field/water model combinations included in this study are AMBER ff99SB-disp with its corresponding water model that was derived from TIP4P-D, CHARMM36m with TIP3P, ff15ipq with SPC/Eb, ff99SB*-ILDNP with TIP3P and TIP4P-D, and FB15 with TIP3P-FB water. Comparing the results from REST2-enhanced sampling simulations with experimental CD spectra and secondary chemical shifts reveals that the ff99SB-disp force field can realistically capture the broad and mildly helical structural ensemble of free c-Myb. The structural ensembles yielded by CHARMM36m, ff99SB*-ILDNP together with TIP4P-D water, and FB15 are also mildly helical; however, each of these force fields can be assigned a specific subset of c-Myb residues for which the simulations could not reproduce the experimental secondary chemical shifts. In addition, microsecond-timescale MD simulations of the KIX/c-Myb complex show that most force fields used preserve a stable helix fold of c-Myb in the complex. Still, all force fields predict a KIX/c-Myb complex interface that differs slightly from the structures provided by NMR because several NOE-derived distances between KIX and c-Myb were exceeded in the simulations. Taken together, the ff99SB-disp force field in the first place but also CHARMM36m, ff99SB*-ILDNP together with TIP4P-D water, and FB15 can be suitable choices for future simulation studies of the coupled folding and binding mechanism of the KIX/c-Myb complex and potentially also other IDPs.
Photoswitchable cages that confine small guest molecules inside their cavities offer a way to control the binding/unbinding process through irradiation with light of different wavelengths. However, a detailed characterization of...
Photochemical studies on supramolecular hosts that can encapsulate small guest molecules commonly focus on three aspects: photoswitching the cage to release or trap the guest, the effect of the confining environment on the guest, and light-induced exciton or charge transfer within the cage structure. Here, we exploit ultrafast spectroscopy to address how the guest alters the photoswitching characteristics of the cage. For this, the impacts of three disparate guest compounds on ring-opening or ring-closure of a dithienylethene (DTE) ligand in a photoswitchable DTEbased coordination cage are juxtaposed. The guest modulates both outcome and timescale of the cage's photodynamics, by an interplay of structural strain, heavy-atom effect, and enhancement of charge-transfer processes exercised by the guest on the photo-excited cage. The approach might prove beneficial for attuning the applicability of photoswitchable nanocontainers and desired guest compounds.
Metallosupramolekulare, nanoskopische Wirte, die als selektive Rezeptoren und Katalysatoren dienen können, bestehen in der Regel je aus nur einem Typ organischer Liganden, was die Vielfalt in Bezug auf die Form der Hohlräume und die Dekoration mit funktionellen Gruppen einschränkt. Wir berichten über eine Reihe von heteroleptischen [Pd2A2B2]‐Koordinationskäfigen, die sich aus einer Bibliothek formkomplementärer bis‐monodentater Liganden auf nicht‐statistische Weise bilden. Ligand A besitzt eine nach innen gerichtete NH‐Funktionalität, die Wasserstoffbrückenbindungen eingehen und mit Amid‐ und Alkylsubstituenten funktionalisiert werden kann. Die Liganden B bestehen aus trizyklischen aromatischen Grundgerüsten unterschiedlicher Form und elektronischer Beschaffenheit. Die so erhaltenen heteroleptischen Koordinationskäfige wurden auf ihre Fähigkeit untersucht, Phosphatdiester als Gäste zu binden. Es wurden atomistische “Molecular Dynamics” (MD) Simulationen in einem expliziten Lösungsmittel durchgeführt, um den Gastbindungsmechanismus im Einklang mit den experimentell ermittelten Affinitäten zu verstehen.
Photochemische Studien über supramolekulare Wirte, die kleine Gastmoleküle einkapseln können, konzentrieren sich zumeist auf drei Aspekte: Die Photoschaltung des Käfigs, um den Gast freizusetzen oder einzufangen, die Wirkung der Käfigumgebung auf den Gast und die lichtinduzierte Exzitonen-oder Ladungsübertragung innerhalb der Käfigstruktur. Hier nutzen wir ultraschnelle Spektroskopie, um zu untersuchen, wie der Gast die Photoschaltcharakteristik des Käfigs verändert. Zu diesem Zweck werden die Auswirkungen von drei unterschiedlichen Gastmolekülen auf die Ringöffnung oder den Ringschluss eines Dithienylethen (DTE)-Liganden in einem photoschaltbaren Koordinationskäfig auf DTE-Basis einander gegenübergestellt. Der Gast moduliert sowohl das Ergebnis als auch die Zeitskala der Photodynamik des Käfigs durch ein Zusammenspiel von struktureller Wechselwirkung, dem Schweratomeffekt und einer Verstärkung von Ladungstransferprozessen, die der Gast auf den photoangeregten Käfig ausübt. Der Ansatz könnte sich als nützlich erweisen, um die Anwendbarkeit von photoschaltbaren Nanocontainern und gewünschten Gastverbindungen aufeinander abzustimmen.
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