Sarah J. Pike

Stimuli-Responsive Reversible Assembly of 2D and 3D Metallosupramolecular Architectures

The discovery of interconvertible platinum coordination modes, which reveals and masks cis coordinating groups upon addition of acid and base, respectively, has been exploited to facilitate stimuli-responsive assembly and disassembly of both two- and three-dimensional metallosupramolecular architectures. Treatment of a binclear platinum complex with acid along with ditopic and tritopic donor ligands generated a molecular square and a trigonal prism, respectively, in good to high yield. These complexes were unambiguously identified using electrospray mass spectrometry, (1)H NMR spectroscopy, and X-ray crystallography. Both assemblies can be disassembled into their constituent parts simply by treatment with base, and the prism can be cycled between the assembled and disassembled states by the alternate addition of acid and base.

Shapes of supramolecular cages by ion mobility mass spectrometry

Mass spectrometry and drift tube ion mobility mass spectrometry have been used to analyse several isobaric, multicomponent cages yielding information on three dimensional structure, interactions and dynamics of assembly in the gas phase.

Conformational Switching of a Foldamer in a Multicomponent System by pH-Filtered Selection between Competing Noncovalent Interactions

Biomolecular systems are able to respond to their chemical environment through reversible, selective, noncovalent intermolecular interactions. Typically, these interactions induce conformational changes that initiate a signaling cascade, allowing the regulation of biochemical pathways. In this work, we describe an artificial molecular system that mimics this ability to translate selective noncovalent interactions into reversible conformational changes. An achiral but helical foldamer carrying a basic binding site interacts selectively with the most acidic member of a suite of chiral ligands. As a consequence of this noncovalent interaction, a global absolute screw sense preference, detectable by 13C NMR, is induced in the foldamer. Addition of base, or acid, to the mixture of ligands competitively modulates their interaction with the binding site, and reversibly switches the foldamer chain between its left and right-handed conformations. As a result, the foldamer–ligand mixture behaves as a biomimetic chemical system with emergent properties, functioning as a “proton-counting” molecular device capable of providing a tunable, pH-dependent conformational response to its environment.

Diastereotopic fluorine substituents as 19F NMR probes of screw-sense preference in helical foldamers.

Ligating simple amino alcohol or amino ester monomers containing enantiotopic fluorine substituents to the C-terminus of a helical peptide places the fluorine atoms in diastereotopic environments, and gives two distinct and easily identifiable signals in the (19)F NMR spectrum. In the case of a dynamically inverting helix built from achiral monomers, the chemical shift separation between the (19)F signals provides a simple means of analysing the ratio of screw-sense conformers in the oligomer, in cases where an asymmetric bias leads to a screw-sense preference.

H-Bond Acceptor Parameters for Anions

UV/vis absorption titrations have been used to investigate the formation of H-bonded complexes between anionic H-bond acceptors (HBAs) and neutral H-bond donors (HBDs) in organic solvents. Complexes formed by three different HBDs with 15 different anions were studied in chloroform and in acetonitrile. The data were used to determine self-consistent HBA parameters (β) for chloride, bromide, iodide, phosphate diester, acetate, benzoate, perrhenate, nitrate, triflimide, perchlorate, hexafluorophosphate, hydrogen sulfate, methyl sulfonate, triflate, and perfluorobutyl sulfonate. The results demonstrate the transferability of H-bond parameters for anions between different solvents and different HBD partners, allowing reliable prediction of anion recognition properties in other scenarios. Carboxylates are the strongest HBAs studied, with β parameters (≈ 15) that are significantly higher than those of neutral organic HBAs, and the non-coordinating anion hexafluorophosphate is the weakest acceptor, with a β parameter comparable to that of pyridine. The effects of ion pairing with the counter-cation were found to be negligible, provided small polar cations were avoided in the less polar solvent (chloroform). There is no correlation between the H-bonding properties of the anions and the pKa values of the conjugate acids.

Designing Foldamer–Foldamer Interactions in Solution: The Roles of Helix Length and Terminus Functionality in Promoting the Self‐Association of Aminoisobutyric Acid Oligomers

The biological activity of antibiotic peptaibols has been linked to their ability to aggregate, but the structure-activity relationship for aggregation is not well understood. Herein, we report a systematic study of a class of synthetic helical oligomer (foldamer) composed of aminoisobutyric acid (Aib) residues, which mimic the folding behavior of peptaibols. NMR spectroscopic analysis was used to quantify the dimerization constants in solution, which showed hydrogen-bond donors at the N terminus promoted aggregation more effectively than similar modifications at the C terminus. Elongation of the peptide chain also favored aggregation. The geometry of aggregation in solution was investigated by means of titrations with [D6]DMSO and 2D NOE NMR spectroscopy, which allowed the NH protons most involved in intermolecular hydrogen bonds in solution to be identified. X-ray crystallography studies of two oligomers allowed a comparison of the inter- and intramolecular hydrogen-bonding interactions in the solid state and in solution and gave further insight into the geometry of foldamer-foldamer interactions. These solution-based and solid-state studies indicated that the preferred geometry for aggregation is through head-to-tail interactions between the N and C termini of adjacent Aib oligomers.

Dual stimuli-responsive interconvertible heteroleptic platinum coordination modes

The exchange between different equilibrium and out-of-equilibrium platinum coordination modes can be orthogonally controlled thermodynamically with a proton input and kinetically using light.

Conformational analysis of helical aminoisobutyric acid (Aib) oligomers bearing C-terminal ester Schellman motifs

The effect of Schellman motifs on the adoption of stable 310 helical conformations in a series of aminoisobutyric (Aib) oligomers has been studied in the solid state and solution. The destabilising effect of the Schellman motif (a local inversion of helical screw-sense due to a C-terminal ester residue) was quantified in the solid state using X-ray crystallography through analysis of the torsion angles and their deviation from those observed in an ideal 310 helix. Investigation of the intramolecular hydrogen-bonding interactions in the solid state led to the identification of a fully extended C5 conformation in one oligomer, which is a novel folding motif for Aib oligomers. The effect of ester groups with differing steric demands on intermolecular hydrogen-bonding contacts in the solid state was also ascertained. In solution, the adoption of a 310 conformation in Aib oligomers appeared to be more finely tuned, depending on a number of factors, including chain length and the steric demands of the C-terminal destabilising Schellman motif.

Acid–base responsive switching between “3+1” and “2+2” platinum complexes

We report that the acid-base induced changes to a cyclometallated platinum complex can be used to drive the exchange of accompanying ligands with different denticities.

Optically Active Vibrational Spectroscopy of α‐Aminoisobutyric Acid Foldamers in Organic Solvents and Phospholipid Bilayers

Helical α-aminoisobutyric acid (Aib) foldamers show great potential as devices for the communication of conformational information across phospholipid bilayers, but determining their conformation in bilayers remains a challenge. In the present study, Raman, Raman optical activity (ROA), infrared (IR) and vibrational circular dichroism (VCD) spectroscopies have been used to analyze the conformational preferences of Aib foldamers in solution and when interacting with bilayers. A 310 -helix marker band at 1665-1668 cm-1 in Raman spectra was used to show that net helical content increased strongly with oligomer length. ROA and VCD spectra of chiral Aib foldamers provided the chiroptical signature for both left- and right-handed 310 -helices in organic solvents, with VCD establishing that foldamer screw-sense was preserved when the foldamers became embedded within bilayers. However, the population distribution between different secondary structures was perturbed by the chiral phospholipid. These studies indicate that ROA and VCD spectroscopies are valuable tools for the study of biomimetic structures, such as artificial signal transduction molecules, in phospholipid bilayers.