Roles of Metal Ions in Foldamers and Other Conformationally Flexible Supramolecular Systems

Abstract

Conformational control is a key prerequisite for much molecular function. As chemists seek to create complex molecules that have applications beyond the academic laboratory, correct spatial positioning is critical. This is particularly true of flexible systems. Conformationally flexible molecules show potential because they resemble in many cases naturally occurring analogues such as the secondary structures found in proteins and peptides such as α-helices and β-sheets. One of the ways in which conformation can be controlled in these molecules is through interaction with or coordination to metal ions. This review explores how secondary structure (i.e., controlled local conformation) in foldamers and other conformationally flexible systems can be enforced or modified through coordination to metal ions. We hope to provide examples that illustrate the power of metal ions to influence this structure toward multiple different outcomes.

Assessment of Density Functional Theory Methods for the Structural Prediction of Transition and Post-Transition Metal–Nucleic Acid Complexes

“…In addition to complications arising from the nitrate ligands, the inability of DFT to reproduce these crystal structure geometries may be due to the inherent flexibility of the Hg 2+ and Pb 2+ coordination spheres, which are known to adopt irregular geometries. 105,106 In summary, the 12 complexes that result in large heavyatom RMSDs upon gas-phase optimization regardless of the functional (Figure 3) can be subcategorized according to (1) those with improved structural features upon optimization in water, (2) those with improved structural features upon constraining the model truncation points to the crystallographic coordinates, and (3) those that cannot be reproduced regardless of the environment and constraints. The challenges faced reproducing the ligand orientation and/or inner-sphere coordination highlight the importance of the surrounding environment in stabilizing the structures of these metal− nucleic acid complexes.…”

“…Metal ions play vital roles in nucleic acid chemistry. − For example, metals provide charge and structural stabilization that aid the formation of higher-order structural motifs with distinct functions such as DNA double or triple helices, G-quadruplexes, loops, and helical junctions. ,, Beyond structural stability, metal ions can act as catalytic co-factors in nucleic acid systems. Indeed, ribozymes and DNAzymes often use metals to aid phosphodiester bond cleavage or general organic reactions (e.g., Diels–Alder reactions) .…”

Exploring Helical Peptides and Foldamers for the Design of Metal Helix Frameworks: Current Trends and Future Perspectives

“…However, the field of metal and hydrogen bond-driven helical peptide selfassembly into 3D-crystalline porous frameworks has only recently emerged and is expanding rapidly. [95,96] As a result, we anticipate significant future advancements such as the establishment of specific design rules, optimizing the method to obtain high-resolution structures, and implementing these highly versatile structures in chemical biology, bio-nanotechnology, and material science.…”

“…Moreover, since the number of side chains associated with longer folded peptides and foldamers is higher than that of ultra‐short peptides, their interference in the formation of pores is always a possibility, hence reducing the likelihood of the development of a porous framework. However, the field of metal and hydrogen bond‐driven helical peptide self‐assembly into 3D‐crystalline porous frameworks has only recently emerged and is expanding rapidly [95, 96] . As a result, we anticipate significant future advancements such as the establishment of specific design rules, optimizing the method to obtain high‐resolution structures, and implementing these highly versatile structures in chemical biology, bio‐nanotechnology, and material science.…”

Stoichiometric Control of Guest Recognition of Self‐Assembled Palladium(II)‐Based Supramolecular Architectures

“…But switchability has also been incorporated into flexible systems, using acid/base chemistry, [19] the presence or absence of a metal ion, [20] or charge. [21] We are interested in systems that have a degree of flexibility, [22] which often rely upon π-π interactions to enforce their persistent conformation. [23] These π-π interactions are similarly useful for molecular recognition events, and are accentuated between electron-rich aromatic guests and electron deficient hosts, with the cationic regions of the host particularly well suited to carrying out this role.…”