The Delicate Balance of Preorganisation and Adaptability in Multiply Bonded Host–Guest Complexes

Abstract

Rigidity and preorganisation are believed to be required for high affinity in multiply bonded supramolecular complexes as they help reduce the entropic penalty of the binding event. This comes at the price that such rigid complexes are sensitive to small geometric mismatches. In marked contrast, nature uses more flexible building blocks. Thus, one might consider putting the rigidity/high-affinity notion to the test. Multivalent crown/ammonium complexes are ideal for this purpose as the monovalent interaction is well understood. A series of divalent complexes with different spacer lengths and rigidities has thus been analysed to correlate chelate cooperativities and spacer properties. Too long spacers reduce chelate cooperativity compared to exactly matching ones. However, in contrast to expectation, flexible guests bind with chelate cooperativities clearly exceeding those of rigid structures. Flexible spacers adapt to small geometric host-guest mismatches. Spacer-spacer interactions help overcome the entropic penalty of conformational fixation during binding and a delicate balance of preorganisation and adaptability is at play in multivalent complexes.

Supramolecular Engineering for Formamidinium‐Based Layered 2D Perovskite Solar Cells: Structural Complexity and Dynamics Revealed by Solid‐State NMR Spectroscopy

“…The adamantane scaffold was functionalized with an ammonium moiety to ensure interaction with the inorganic layers through hydrogen bonding. Moreover, the hydrogen bond donating group was linked through a flexible methylene unit that was assumed to feature a higher level of adaptability to the geometrical mismatches in the overall structure in order to achieve a more robust structural framework . To elucidate the effect of adaptability as a factor in the molecular design on the properties of the material, we also explored an alternative rigid spacer, 1‐adamantylammonium (A′), which does not feature a methylene linker (Figure b).…”

“…[13][14][15] This was shown to result in remarkable electronic properties of functionalized adamantane monolayers. [20,21] To elucidate the effect of adaptability as a factor in the molecular design on the properties of the material, we also explored an alternative rigid spacer, 1-adamantylammonium (A′), which does not feature a methylene linker (Figure 1b). [6] Our approach incorporates the adamantane core to provide a 2D backbone through Van der Waals interactions within the hydrophobic spacer bilayer, which could enable higher electronic quality of the resulting material.…”

Dimerization in tailoring uptake efficacy of the HSV-1 derived membranotropic peptide gH625

“…Moreover, recently great attention has been dedicated to the key role of multivalency as an important parameter to be modulated for enhancing binding strength and hence for developing novel assemblies with potential biomedical applications 29 – 31 . Multivalency will result in an increased local concentration of the active peptide at the site where it is supposed to interact with the cellular components; thus enhancing its binding to targets.…”

Supramolecular forces and their interplay in stabilizing complexes of organic anions: tuning binding selectivity in water

“…In this framework, phthalate and isophthalate, provided the chance of checking the effect of a second anionic group and the influence of the mutual disposition of the divergent binding sites on the anion. Finally, effect of host-guest size was evaluated varying the length of the aliphatic spacer in the ligand, affecting also flexibility and preorganization, 15 to properly prosecute the evaluation carried out in previous works.…”