Membrane Transport, Molecular Machines, and Maxwell's Demon

The spontaneous generation of transmembrane gradients is an important fundamental research goal for artificial nanotechnology. The active transport processes that give rise to such gradients directly mirror the famous Maxwell's Demon thought experiment, where a Demon partitions particles between two chambers to generate a nonequilibrium state. Despite these similarities, discussion of Maxwell's Demon is absent in the literature on artificial membrane transport. By contrast, the emergence of rational design principles for nonequilibrium artificial molecular motors can trace its intellectual roots directly to this famous thought experiment. This perspective highlights the links between Maxwell's Demon and nonequilibrium machines, and argues that understanding the implications of this 19th century thought experiment is crucial to the future development of transmembrane active transport processes

Dynamic covalent assembly and disassembly of nanoparticle aggregates

This work was supported by the EPSRC (EP/K016342/1 and EP/J500549/1), the University of St Andrews and by a Royal Society of Edinburgh/Scottish Government Fellowship (E.R.K.).The quantitative assembly and disassembly of a new type of dynamic covalent nanoparticle (NP) building block is reported. In situ spectroscopic characterization reveals constitutionally adaptive NP-bound monolayers of boronate esters. Ditopic linker molecules are used to produce covalently connected AuNP assemblies, displaying open dendritic morphologies, and which, despite being linked by covalent bonds, can be fully disassembled on application of an appropriate chemical stimulus.PostprintPeer reviewe

Dynamic molecular control of nanoparticle building block assembly

Nanoparticles have generated much excitement as a result of their often unique properties, inherently dependent on nanoparticle material, shape and size. Virtually all conceivable nanoparticle applications will require excellent control over how nanoparticles are assembled and linked to other components. When several nanoparticles are brought together, the assembly structure is crucial in determining their newly emergent properties. However, the synthetic chemistry techniques required to control nanoparticle functionalisation and assembly are still under-developed, with complex biological or supramolecular systems being the current best approaches. There remains a need for simple, generalisable strategies for molecular-level control over nanoparticle functionalisation and assembly. This thesis presents the development of a toolkit of nanoparticle building blocks, which may be assembled in a predictable and controlled way, governed by simple and easily optimised abiotic molecular systems. Efficient, size-controlled, direct synthesis of functionalised gold nanoparticle building blocks with control over size and dispersity is developed. ¹⁹F NMR spectroscopy studies provide a fundamental understanding of the implications of confinement at the nanoparticle surface for molecular reactivity. Two self-assembly strategies, each resulting in structures of high order and predictability, are presented. First, the reversible nature of dynamic covalent boronic ester formation is exploited to induce reversible nanoparticle self-assembly. Links between molecular details and resulting morphology are demonstrated and rationalised. A second strategy exploits multivalent non-covalent interactions, resulting in ‘planet–satellite’ structures displaying high order, stability and predictability. This thesis demonstrates that relatively simple molecular systems present a viable, and ultimately more flexible, alternative to existing methods of directing precise, predictable control of nanoparticle functionalisation and assembly. Advancing a molecular-level understanding of the underlying processes enables a high level of control. Future application of this molecular approach to dynamic nanomaterial control will lead to more complex and sophisticated nanostructures, helping nanotechnology progress towards its undoubtedly revolutionary full potential

The Energetic Significance of Metallophilic Interactions

Metallophilic interactions are increasingly recognized as playing an important role in molecular assembly, catalysis, and bio‐imaging. However, present knowledge of these interactions is largely derived from solid‐state structures and gas‐phase computational studies rather than quantitative experimental measurements. Here, we have experimentally quantified the role of aurophilic (AuI⋅⋅⋅AuI), platinophilic (PtII⋅⋅⋅PtII), palladophilic (PdII⋅⋅⋅PdII), and nickelophilic (NiII⋅⋅⋅NiII) interactions in self‐association and ligand‐exchange processes. All of these metallophilic interactions were found to be too weak to be well‐expressed in several solvents. Computational energy decomposition analyses supported the experimental finding that metallophilic interactions are overall weak, meaning that favorable dispersion and orbital hybridization contributions from M⋅⋅⋅M binding are largely outcompeted by electrostatic or dispersion interactions involving ligand or solvent molecules. This combined experimental and computational study provides a general understanding of metallophilic interactions and indicates that great care must be taken to avoid over‐attributing the energetic significance of metallophilic interactions

Synthetically Diversified Protein Nanopores: Resolving Click Reaction Mechanisms

Nanopores are emerging as a powerful tool for the investigation of nanoscale processes at the single-molecule level. Here, we demonstrate the methionine-selective synthetic diversification of α-hemolysin (α-HL) protein nanopores and their exploitation as a platform for investigating reaction mechanisms. A wide range of functionalities, including azides, alkynes, nucleotides, and single-stranded DNA, were incorporated into individual pores in a divergent fashion. The ion currents flowing through the modified pores were used to observe the trajectory of a range of azide–alkyne click reactions and revealed several short-lived intermediates in Cu­(I)-catalyzed azide–alkyne [3 + 2] cycloadditions (CuAAC) at the single-molecule level. Analysis of ion-current fluctuations enabled the populations of species involved in rapidly exchanging equilibria to be determined, facilitating the resolution of several transient intermediates in the CuAAC reaction mechanism. The versatile pore-modification chemistry offers a useful approach for enabling future physical organic investigations of reaction mechanisms at the single-molecule level

Ratcheting synthesis

Synthetic chemistry has traditionally relied on reactions between reactants of high chemical potential and transformations that proceed energetically downhill to either a global or local minimum (thermodynamic or kinetic control). Catalysts can be used to manipulate kinetic control, lowering activation energies to influence reaction outcomes. However, such chemistry is still constrained by the shape of one-dimensional reaction coordinates. Coupling synthesis to an orthogonal energy input can allow ratcheting of chemical reaction outcomes, reminiscent of the ways that molecular machines ratchet random thermal motion to bias conformational dynamics. This fundamentally distinct approach to synthesis allows multi-dimensional potential energy surfaces to be navigated, enabling reaction outcomes that cannot be achieved under conventional kinetic or thermodynamic control. In this Review, we discuss how ratcheted synthesis is ubiquitous throughout biology and consider how chemists might harness ratchet mechanisms to accelerate catalysis, drive chemical reactions uphill and programme complex reaction sequences.<br/