Fernández-Labandeira, N.; Montes de Oca, I.; Pazos, E.; Blanco-Gómez, A.; Peinador, C.; García, M. D. Modulating the Dimensions of Rectangular Hydrazone-Based Bispyridinium Macrocyclic Receptors. J. Org. Chem. 2025, 90, accepted. DOI: 10.1021/acs.joc.5c00695
The development of new macrocyclic molecular receptors has driven major advances in supramolecular chemistry. However, realizing the full potential of host–guest systems requires addressing persistent challenges such as improved synthesis, aqueous performance, and implementation of stimuli-responsiveness. Herein, we present a new family of self-assembled polycationic molecular rectangles, derived from our previously reported redbox host. These novel cyclophanes share a common structural core with the parent compound─two pyridinium units linked by a hydrazone bond─but are designed with varying dimensions on the short sides, separating the bispyridinium walls. Synthesized via acid-catalyzed imine condensation reactions in water, these compounds were obtained in acceptable yields in gram scale through a modular and highly efficient approach. The aqueous molecular recognition properties of these new hosts were investigated using NMR spectroscopy with a 1,5-dihydroxynaphthalene derivative as a model aromatic electron donor. These studies demonstrate the formation of highly stable binary or ternary inclusion complexes in aqueous media, highlighting the tunability of the binding properties and applicative potential of this family of pH-responsive macrocyclic receptors.
Díaz-Abellás, M.; Neira, I.; Blanco-Gómez, A.; Peinador, C.; García, M. D. Synergy-Promoted Specific Alkyltriphenylphosphonium Binding to CB[8] J. Org. Chem. 2025, 90, 4149-4157. DOI: 10.1021/acs.joc.4c02546
Biological substrate specificity ensures that organisms interact accurately with biomolecular receptors, crucial for key functions such as signaling and immunity. Nevertheless, this phenomenon is still poorly understood, with host–guest chemistry offering a suitable platform for studying simplified models. Herein, we report an in-depth study of the host–guest chemistry of alkyltriphenylphosphonium cations with cucurbit[8]uril (CB[8]), initiated by the serendipitous discovery of salt forming a tightly bound pseudoheteroternary 1:1 complex with CB[8]. A first generation of model substrates was designed to explore an unusual binding mode characterized by the simultaneous introduction of two distinct guest fragments within the host cavity. Structural features of the complexes were elucidated using ESI-MS and NMR 1D/2D techniques; thermodynamic properties were assessed by isothermal titration calorimetry, and kinetic parameters were derived from selective inversion–recovery NMR. Experimental results aligned well with electronic structure calculations, revealing a reproducible binding motif with submicromolar affinities. This peculiar complexation mode involves a synergistic effect caused by steric crowding around the P+ atom, facilitating the insertion of two aromatic units into CB[8] while hindering association with CB[7]. Based on these findings, a second generation of minimalistic substrates was developed, preserving the synergistic interaction mode and exhibiting specific binding to CB[8].