A General One-Step Synthesis of Alkanethiyl-Stabilized Gold Nanoparticles with Control over Core Size and Monolayer Functionality.

In spite of widespread interest in the unique size-dependent properties and consequent applications of gold nanoparticles (AuNPs), synthetic protocols that reliably allow for independent tuning of surface chemistry and core size, the two critical determinants of AuNP properties, remain limited. Often, core size is inherently affected by the ligand structure in an unpredictable fashion. Functionalized ligands are commonly introduced using postsynthesis exchange procedures, which can be inefficient and operationally delicate. Here, we report a one-step protocol for preparing monolayer-stabilized AuNPs that is compatible with a wide range of ligand functional groups and also allows for the systematic control of core size. In a single-phase reaction using the mild reducing agent tert-butylamine borane, AuNPs that are compatible with solvents spanning a wide range of polarities from toluene to water can be produced without damaging reactive chemical functionalities within the small-molecule surface-stabilizing ligands. We demonstrate that the rate of reduction, which is easily controlled by adjusting the period over which the reducing agent is added, is a simple parameter that can be used irrespective of the ligand structure to adjust the core size of AuNPs without broadening the size distribution. Core sizes in the range of 2-10 nm can thus be generated. The upper size limit appears to be determined by the nature of each specific ligand/solvent pairing. This protocol produces high quality, functionally sophisticated nanoparticles in a single step. By combining the ability to vary size-related nanoparticle properties with the option to incorporate reactive functional groups at the nanoparticle-solvent interface, it is possible to generate chemically reactive colloidal building blocks from which more complex nanoparticle-based devices and materials may subsequently be constructed.

A Dissipative Reaction Network Drives Transient Solid-Liquid and Liquid-Liquid Phase Cycling of Nanoparticles.

Transient states maintained by energy dissipation are an essential feature of dynamic systems where structures and functions are regulated by fluxes of energy and matter through chemical reaction networks. Perfected in biology, chemically fueled dissipative networks incorporating nanoscale components allow the unique properties of nanomaterials to be bestowed with spatiotemporal adaptability and chemical responsiveness. We report the transient dispersion of gold nanoparticles in water, powered by dissipation of a chemical fuel. A dispersed state that is generated under non-equilibrium conditions permits fully reversible solid-liquid or liquid-liquid phase transfer. The molecular basis of the out-of-equilibrium process is reversible covalent modification of nanoparticle-bound ligands by a simple inorganic activator. Activator consumption by a coupled dissipative reaction network leads to autonomous cycling between phases. The out-of-equilibrium lifetime is tunable by adjusting the pH value, and reversible phase cycling is reproducible over several cycles.

Constitutionally Selective Dynamic Covalent Nanoparticle Assembly.

The future of materials chemistry will be defined by our ability to precisely arrange components that have considerably larger dimensions and more complex compositions than conventional molecular or macromolecular building blocks. However, exerting structural and constitutional control in the assembly of nanoscale entities presents a considerable challenge. Dynamic covalent nanoparticles are emerging as an attractive category of reaction-enabled solution-processable nanosized building block through which the rational principles of molecular synthetic chemistry can be extended into the nanoscale. From a mixture of two hydrazone-based dynamic covalent nanoparticles with complementary reactivity, specific molecular instructions trigger selective assembly of intimately mixed heteromaterial (Au-Pd) aggregates or materials highly enriched in either one of the two core materials. In much the same way as complementary reactivity is exploited in synthetic molecular chemistry, chemospecific nanoparticle-bound reactions dictate building block connectivity; meanwhile, kinetic regioselectivity on the nanoscale regulates the detailed composition of the materials produced. Selectivity, and hence aggregate composition, is sensitive to several system parameters. By characterizing the nanoparticle-bound reactions in isolation, kinetic models of the multiscale assembly network can be constructed. Despite ignoring heterogeneous physical processes such as aggregation and precipitation, these simple kinetic models successfully link the underlying molecular events with the nanoscale assembly outcome, guiding rational optimization to maximize selectivity for each of the three assembly pathways. With such predictive construction strategies, we can anticipate that reaction-enabled nanoparticles can become fully incorporated in the lexicon of synthetic chemistry, ultimately establishing a synthetic science that manipulates molecular and nanoscale components with equal proficiency.

Probing Multiscale Factors Affecting the Reactivity of Nanoparticle-Bound Molecules.

The structures and physicochemical properties of surface-stabilizing molecules play a critical role in defining the properties, interactions, and functionality of hybrid nanomaterials such as monolayer-stabilized nanoparticles. Concurrently, the distinct surface-bound interfacial environment imposes very specific conditions on molecular reactivity and behavior in this setting. Our ability to probe hybrid nanoscale systems experimentally remains limited, yet understanding the consequences of surface confinement on molecular reactivity is crucial for enabling predictive nanoparticle synthon approaches for postsynthesis engineering of nanoparticle surface chemistry and construction of devices and materials from nanoparticle components. Here, we have undertaken an integrated experimental and computational study of the reaction kinetics for nanoparticle-bound hydrazones, which provide a prototypical platform for understanding chemical reactivity in a nanoconfined setting. Systematic variation of just one molecular-scale structural parameter-the distance between reactive site and nanoparticle surface-showed that the surface-bound reactivity is influenced by multiscale effects. Nanoparticle-bound reactions were tracked in situ using 19F NMR spectroscopy, allowing direct comparison to the reactions of analogous substrates in bulk solution. The surface-confined reactions proceed more slowly than their solution-phase counterparts, and kinetic inhibition becomes more significant for reactive sites positioned closer to the nanoparticle surface. Molecular dynamics simulations allowed us to identify distinct supramolecular architectures and unexpected dynamic features of the surface-bound molecules that underpin the experimentally observed trends in reactivity. This study allows us to draw general conclusions regarding interlinked structural and dynamical features across several length scales that influence interfacial reactivity in monolayer-confined environments.

Rapidly Adaptive All-covalent Nanoparticle Surface Engineering.

Emerging nanotechnologies demand the manipulation of nanoscale components with the same predictability and programmability as is taken for granted in molecular synthetic methodologies. Yet installing appropriately reactive chemical functionality on nanomaterial surfaces has previously entailed compromises in terms of reactivity scope, functionalization density, or both. Here, we introduce an idealized dynamic covalent nanoparticle building block for divergent and adaptive post-synthesis modification of colloidal nanomaterials. Acetal-protected monolayer-stabilized gold nanoparticles are prepared via operationally simple protocols and are stable to long-term storage. Tunable surface densities of reactive aldehyde functionalities are revealed on-demand, leading to a wide range of adaptive surface engineering options from one nanoscale synthon. Analytically tractable with molecular precision, interfacial reaction kinetics and dynamic surface constitutions can be probed in situ at the ensemble level. High functionalization densities combined with rapid equilibration kinetics enable environmentally adaptive surface constitutions and rapid nanoparticle property switching in response to simple chemical effectors.

Programmable dynamic covalent nanoparticle building blocks with complementary reactivity.

Nanoparticle-based devices, materials and technologies will demand a new era of synthetic chemistry where predictive principles familiar in the molecular regime are extended to nanoscale building blocks. Typical covalent strategies for modifying nanoparticle-bound species rely on kinetically controlled reactions optimised for efficiency but with limited capacity for selective and divergent access to a range of product constitutions. In this work, monolayer-stabilized nanoparticles displaying complementary dynamic covalent hydrazone exchange reactivity undergo distinct chemospecific transformations by selecting appropriate combinations of 'nucleophilic' or 'electrophilic' nanoparticle-bound monolayers with nucleophilic or electrophilic molecular modifiers. Thermodynamically governed reactions allow modulation of product compositions, spanning mixed-ligand monolayers to exhaustive exchange. High-density nanoparticle-stabilizing monolayers facilitate in situ reaction monitoring by quantitative 19F NMR spectroscopy. Kinetic analysis reveals that hydrazone exchange rates are moderately diminished by surface confinement, and that the magnitude of this effect is dependent on mechanistic details: surface-bound electrophiles react intrinsically faster, but are more significantly affected by surface immobilization than nucleophiles. Complementary nanoparticles react with each other to form robust covalently connected binary aggregates. Endowed with the adaptive characteristics of the dynamic covalent linking process, the nanoscale assemblies can be tuned from extended aggregates to colloidally stable clusters of equilibrium sizes that depend on the concentration of a monofunctional capping agent. Just two 'dynamic covalent nanoparticles' with complementary thermodynamically governed reactivities therefore institute a programmable toolkit offering flexible control over nanoparticle surface functionalization, and construction of adaptive assemblies that selectively combine several nanoscale building blocks.

Probing the interaction of nanoparticles with small molecules in real time via quartz crystal microbalance monitoring.

Despite extensive advances in the field of molecular recognition, the real-time monitoring of small molecule binding to nanoparticles (NP) remains a challenge. To this end, we report on a versatile approach, based on quartz crystal microbalance with dissipation monitoring, for the stepwise in situ quantification of gold nanoparticle (AuNPs) immobilisation and subsequent uptake and release of binding partners. AuNPs stabilised by thiol-bound ligand shells of prescribed chemical composition were densely immobilised onto gold surfaces via dithiol linkers. The boronate ester formation between salicylic acid derivatives in solution and boronic acids in the AuNP ligand shell was then studied in real time, revealing a drastic effect of both ligand architecture and Lewis base concentration on the interaction strength. The binding kinetics were analysed with frequency response modelling for a thorough comparison of binding parameters including relaxation time as well as association rate constant. The results directly mirror those from previously reported in-depth studies using nuclear magnetic resonance spectroscopy. By achieving quantitative characterisation of selective binding of analytes with molecular weight below 300 Da, this new method enables rapid, low cost, rational screening of AuNP candidates for molecular recognition.

Continuum tuning of nanoparticle interfacial properties by dynamic covalent exchange.

Surface chemical composition is fundamental to determining properties on the nanoscale, making precise control over surface chemistry critical to being able to optimise nanomaterials for virtually any application. Surface-engineering independent of the preparation of the underlying nanomaterial is particularly attractive for efficient, divergent synthetic strategies, and for the potential to create reactive, responsive and smart nanodevices. For monolayer-stabilised nanoparticles, established methods include ligand exchange to replace the ligand shell in its entirety, encapsulation with amphiphilic (macro)molecules, noncovalent interactions with surface-bound biomolecules, or a relatively limited number of covalent bond forming reactions. Yet, each of these approaches has considerable drawbacks. Here we show that dynamic covalent exchange at the periphery of the nanoparticle-stabilizing monolayer allows surface-bound ligand molecular structure to be substantially modified in mild and reversible processes that are independent of the nanoparticle-molecule interface. Simple stoichiometric variation allows the extent of exchange to be controlled, generating a range of kinetically stable mixed-monolayer compositions across an otherwise identical, self-consistent series of nanoparticles. This approach can be used to modulate nanoparticle properties that are defined by the monolayer composition. We demonstrate switching of nanoparticle solvent compatibility between widely differing solvents - spanning hexane to water - and the ability to tune solubility across the entire continuum between these extremes, all from a single nanoparticle starting point. We also demonstrate that fine control over mixed-monolayer composition influences the assembly of discrete, colloidally stable nanoparticle clusters. By carefully assessing monolayer composition in each state, using both in situ and ex situ methods, we are able to correlate the molecular-level details of the nanoparticle-bound monolayer with system-level properties and behaviour. These empirically determined relationships contribute fundamental insights on nanoscale structure-function relationships, which are currently beyond the capabilities of ab initio prediction.

Dynamic Covalent Nanoparticle Building Blocks.

Rational and generalisable methods for engineering surface functionality will be crucial to realising the technological potential of nanomaterials. Nanoparticle-bound dynamic covalent exchange combines the error-correcting and environment-responsive features of equilibrium processes with the stability, structural precision, and vast diversity of covalent chemistry, defining a new and powerful approach for manipulating structure, function and properties at nanomaterial surfaces. Dynamic covalent nanoparticle (DCNP) building blocks thus present a whole host of possibilities for constructing adaptive systems, devices and materials that incorporate both nanoscale and molecular functional components. At the same time, DCNPs have the potential to reveal fundamental insights regarding dynamic and complex chemical systems confined to nanoscale interfaces.

Dynamic covalent assembly and disassembly of nanoparticle aggregates.

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.

Successive Translocation of the Rings in a [3]Rotaxane.

A [2]rotaxane, a [3]rotaxane and the corresponding thread containing two succinamide (succ) binding stations and a central redox-active pyromellitimide (pmi) station were studied. Infrared spectroelectrochemical experiments revealed the translocation of the macrocycle between the succinamide station and the electrochemically reduced pmi station (radical anion and dianion). Remarkably, in the [3]rotaxane, the rings can be selectively translocated. One-electron reduction leads to the translocation of one of the two macrocycles from the succinamide to the pyromellitimide station, whereas activation of the shuttle through two-electron reduction results in the translocation of both macrocycles: the dianion, due to its higher electron density and hence greater hydrogen-bond accepting affinity, is hydrogen bonded to both macrocycles. Systems with such an on-command contraction are known as molecular muscles. The relative strengths of the binding between the macrocycle and the imide anions could be estimated from the hydrogen-bond-induced shifts in the C=O stretching frequencies of hydrogen-bond accepting amide groups of the macrocycle.

Reversible control of nanoparticle functionalization and physicochemical properties by dynamic covalent exchange.

Existing methods for the covalent functionalization of nanoparticles rely on kinetically controlled reactions, and largely lack the sophistication of the preeminent oligonucleotide-based noncovalent strategies. Here we report the application of dynamic covalent chemistry for the reversible modification of nanoparticle (NP) surface functionality, combining the benefits of non-biomolecular covalent chemistry with the favorable features of equilibrium processes. A homogeneous monolayer of nanoparticle-bound hydrazones can undergo quantitative dynamic covalent exchange. The pseudomolecular nature of the NP system allows for the in situ characterization of surface-bound species, and real-time tracking of the exchange reactions. Furthermore, dynamic covalent exchange offers a simple approach for reversibly switching­and subtly tuning­NP properties such as solvophilicity.

Rapid and simple preparation of remarkably stable binary nanoparticle planet-satellite assemblies.

We demonstrate a straightforward nonbiomolecular approach for self-assembly of binary NP planet-satellite superstructures, which display remarkable colloidal and structural stability under variations in temperature, pH, ionic strength and solvent. The readily scalable process produces highly homogeneous samples and is tolerant to variations in building block size and shape, giving rapid access to a structurally diverse range of robust binary NP assemblies.

Reversible Control of Nanoparticle Functionalization and Physicochemical Properties by Dynamic Covalent Exchange.

Existing methods for the covalent functionalization of nanoparticles rely on kinetically controlled reactions, and largely lack the sophistication of the preeminent oligonucleotide-based noncovalent strategies. Here we report the application of dynamic covalent chemistry for the reversible modification of nanoparticle (NP) surface functionality, combining the benefits of non-biomolecular covalent chemistry with the favorable features of equilibrium processes. A homogeneous monolayer of nanoparticle-bound hydrazones can undergo quantitative dynamic covalent exchange. The pseudomolecular nature of the NP system allows for the in situ characterization of surface-bound species, and real-time tracking of the exchange reactions. Furthermore, dynamic covalent exchange offers a simple approach for reversibly switching-and subtly tuning-NP properties such as solvophilicity.

Water lubricates hydrogen-bonded molecular machines.

The mechanical behaviour of molecular machines differs greatly from that of their macroscopic counterparts. This applies particularly when considering concepts such as friction and lubrication, which are key to optimizing the operation of macroscopic machinery. Here, using time-resolved vibrational spectroscopy and NMR-lineshape analysis, we show that for molecular machinery consisting of hydrogen-bonded components the relative motion of the components is accelerated strongly by adding small amounts of water. The translation of a macrocycle along a thread and the rotation of a molecular wheel around an axle both accelerate significantly on the addition of water, whereas other protic liquids have much weaker or opposite effects. We tentatively assign the superior accelerating effect of water to its ability to form a three-dimensional hydrogen-bond network between the moving parts of the molecular machine. These results may indicate a more general phenomenon that helps explain the function of water as the 'lubricant of life'.

Induction of motion in a synthetic molecular machine: effect of tuning the driving force.

Rotaxane molecular shuttles were studied in which a tetralactam macrocyclic ring moves between a succinamide station and a second station in which the structure is varied. Station 2 in all cases is an aromatic imide, which is a poor hydrogen-bond acceptor in the neutral form, but a strong one when reduced with one or two electrons. When the charge density on the hydrogen-bond-accepting carbonyl groups in station 2 is reduced by changing a naphthalimide into a naphthalene diimide radical anion, the shuttling rate changes only slightly. When station 2 is a pyromellitimide radical anion, however, the shuttling rate is significantly reduced. This implies that the shuttling rate is not only determined by the initial unbinding of the ring from the first station, as previously supposed. An alternative reaction mechanism is proposed in which the ring binds to both stations in the transition state.

Time-resolved vibrational spectroscopy of a molecular shuttle.

Time-resolved vibrational spectroscopy is used to investigate the inter-component motion of an ultraviolet-triggered two-station molecular shuttle. The operation cycle of this molecular shuttle involves several intermediate species, which are observable in the amide I and amide II regions of the mid-IR spectrum. Using ab initio calculations on specific parts of the rotaxane, and by comparing the transient spectra of the normal rotaxane with that of the N-deuterated version, we can assign the observed vibrational modes of each species occurring during the shuttling cycle in an unambiguous way. The complete time- and frequency-dependent data set is analyzed using singular value decomposition (SVD). Using a kinetic model to describe the time-dependent concentrations of the transient species, we derive the absorption spectra associated with each stage in the operation cycle of the molecular shuttle, including the recombination of the charged species.

IR spectroscopy on jet-cooled isolated two-station rotaxanes.

High-resolution IR spectroscopy has been employed to study isolated, switchable [2]rotaxanes. IR absorption spectra of two-station rotaxanes, their separate thread, and macrocycle components, as well as those of the individual stations incorporated into the thread, have been measured in the 1800-1000 cm(-1) region. These spectra have been fully analyzed, aided by quantum chemical predictions of the IR spectra. From these analyses, a comprehensive picture emerges of the conformational structure and binding interactions between the mechanically interlocked components of the rotaxane.