Multisite Binding of Drugs and Natural Products in an Entropically Favorable, Heteroleptic Receptor

Abstract

The cavities of artificial receptors are defined by how their components fit together.The encapsulation of specific molecules can thus be engineered by considering geometric principles; however, intermolecular interactions and steric fit scale with receptor size, such that the ability to bind multiple guests from a specific class of compounds remains a current challenge.By employing metal-organic self-assembly, we have prepared a triangular prism from two different ligands that is capable of binding more than twenty different natural products, drugs and steroid derivatives within its prolate cavity. Encapsulation inflates the host, enhancing its ability to bind other guests in peripheral pockets, and thus enabling our system to bind combinations of different drug and natural product cargoes in different locations simultaneously. This new mode of entropically-favorable self-assembly thus enables central encapsulation to amplify guest binding events around the periphery of an artificial receptor.

Oxidation triggers guest dissociation during reorganization of an FeII4L6twisted parallelogram

“…8,[17][18][19][20][21] Such assemblies may be better able to mimic the recognition processes of biological receptors, which oen bind complex, asymmetrical guests. 22 The phenomenon of mer or fac coordination is exclusive to octahedral coordination geometries around metal vertices. Other geometries, such as square planar motifs, lead to the formation of entirely different polyhedra, [23][24][25][26][27] while tetrahedral metal-binding pockets can lead to helicates or interlocked structures.…”

Guest Encapsulation within Surface‐Adsorbed Self‐Assembled Cages

“…The ability to trap and release compounds with high selectivity from mixtures flowing over solid supports may enable new methods of chemical purifications; for example, in the purification of freshly synthesized drugs. [56] The immobilization of cages might also enable the translation of these versatile homogeneous catalysts into heterogeneous catalysts. [4,[24][25][26][27][28][29][30][31]…”

Rückgrat‐verknüpfte Liganden erhöhen die Vielfalt in heteroleptischen Koordinationskäfigen

“…Die Assoziationskonstanten wurden mit K 1 =(2.08±0.08)×10 3 und K 2 =(2.11±0.28)×10 3 m −1 für das erste bzw. das zweite Bindungsereignis berechnet ( 1 H‐NMR‐Integration gemittelt über drei verschiedene Wirt/Gast‐Verhältnisse) [32] . Der Kooperativitätsparameter α =4 K 2 / K 1 =4 deutet auf eine positiv‐kooperative Bindung hin, was angesichts der Tatsache, dass der erste bis‐anionische Gast die positive Gesamtladung des Komplexes reduziert, überraschend ist (Tabelle S1) [33] .…”

“…das zweite Bindungsereignis berechnet ( 1 H-NMR-Integration gemittelt über drei verschiedene Wirt/Gast-Verhältnisse). [32] Der Kooperativitätsparameter a = 4 K 2 /K 1 = 4 deutet auf eine positiv-kooperative Bindung hin, was angesichts der Tatsache, dass der erste bis-anionische Gast die positive Gesamtladung des Komplexes reduziert, überraschend ist (Tabelle S1). [33] Bei einem Versuch, Einkristalle des Wirt-Gast-Komplexes zu züchten, erhielten wir stattdessen unerwartet einen neuen heteroleptischen, prismatischen Käfig [Pd 6 (L A2 ) 3 (L B ) 6 ] 12+ (P2).…”