Françisco M. Raymo

Artificial Molecular Machines.

The miniaturization of components used in the construction of working devices is being pursued currently by the large-downward (top-down) fabrication. This approach, however, which obliges solid-state physicists and electronic engineers to manipulate progressively smaller and smaller pieces of matter, has its intrinsic limitations. An alternative approach is a small-upward (bottom-up) one, starting from the smallest compositions of matter that have distinct shapes and unique properties-namely molecules. In the context of this particular challenge, chemists have been extending the concept of a macroscopic machine to the molecular level. A molecular-level machine can be defined as an assembly of a distinct number of molecular components that are designed to perform machinelike movements (output) as a result of an appropriate external stimulation (input). In common with their macroscopic counterparts, a molecular machine is characterized by 1) the kind of energy input supplied to make it work, 2) the nature of the movements of its component parts, 3) the way in which its operation can be monitored and controlled, 4) the ability to make it repeat its operation in a cyclic fashion, 5) the timescale needed to complete a full cycle of movements, and 6) the purpose of its operation. Undoubtedly, the best energy inputs to make molecular machines work are photons or electrons. Indeed, with appropriately chosen photochemically and electrochemically driven reactions, it is possible to design and synthesize molecular machines that do work. Moreover, the dramatic increase in our fundamental understanding of self-assembly and self-organizational processes in chemical synthesis has aided and abetted the construction of artificial molecular machines through the development of new methods of noncovalent synthesis and the emergence of supramolecular assistance to covalent synthesis as a uniquely powerful synthetic tool. The aim of this review is to present a unified view of the field of molecular machines by focusing on past achievements, present limitations, and future perspectives. After analyzing a few important examples of natural molecular machines, the most significant developments in the field of artificial molecular machines are highlighted. The systems reviewed include 1) chemical rotors, 2) photochemically and electrochemically induced molecular (conformational) rearrangements, and 3) chemically, photochemically, and electrochemically controllable (co-conformational) motions in interlocked molecules (catenanes and rotaxanes), as well as in coordination and supramolecular complexes, including pseudorotaxanes. Artificial molecular machines based on biomolecules and interfacing artificial molecular machines with surfaces and solid supports are amongst some of the cutting-edge topics featured in this review. The extension of the concept of a machine to the molecular level is of interest not only for the sake of basic research, but also for the growth of nanoscience and the subsequent development of nanotechnology.

Künstliche molekulare Maschinen

Die zum Bau kleiner Maschinen notwendige Miniaturisierung von Komponenten erfolgt derzeit nach dem Verkleinerungsprinzip (top-down approach). Diesem Ansatz, der Festkorperphysiker und Elektronikingenieure zwingt, mit immer kleineren Materialbausteinen zu arbeiten, sind allerdings Grenzen gesetzt. Eine Alternative besteht im Vergroserungsprinzip (bottom-up approach), bei dem man von den kleinsten Teilen der Materie mit eindeutiger Form und definierten Eigenschaften, den Molekulen, ausgeht. Vor dem Hintergrund dieser Herausforderung haben Chemiker das Konzept der makroskopischen Maschine auf die molekulare Ebene ubertragen. Eine molekulare Maschine kann als eine Anordnung einer definierten Anzahl von molekularen Komponenten definiert werden, die so konzipiert wurden, dass sie als Reaktion auf geeignete externe Stimulation (input) maschinenahnliche Bewegungen ausfuhren (output). Genau wie ihr makroskopisches Gegenstuck ist eine molekulare Maschine durch folgende Merkmale charakterisiert: 1) die Art der Energie, die ihr zugefuhrt werden muss, damit sie funktioniert, 2) die Art der Bewegungen ihrer Komponenten, 3) die Methoden, durch die ihre Funktionen verfolgt und gesteuert werden konnen, 4) die Moglichkeit der cyclischen Wiederholung, 5) die Zeit, die fur die Durchfuhrung eines vollstandigen Arbeitscyclus benotigt wird, und 6) der Zweck ihrer Funktion. Zweifellos sind Photonen oder Elektronen die besten Energielieferanten fur molekulare Maschinen. So ist es moglich, mit sorgfaltig ausgewahlten photochemischen oder elektrochemischen Reaktionen, funktionierende molekulare Maschinen zu entwerfen und zu synthetisieren. Daruber hinaus hat unser rasch angewachsenes, fundamentales Verstandnis uber die Selbstorganisation und die ihr zugrunde liegenden Prozesse in der chemischen Synthese zum Aufbau kunstlicher molekularer Maschinen beigetragen. Dies geschah vor allem durch die Entwicklung neuer Methoden in der nichtkovalenten Synthese und das Aufkommen der supramolekular unterstutzten kovalenten Synthese als ausgesprochen leistungsfahiges Syntheseprinzip. Ziel dieses Ubersichtsartikels ist eine einheitliche Darstellung des Gebiets der molekularen Maschinen, wobei besonderes Augenmerk auf das in der Vergangenheit Erreichte, auf gegenwartig bestehende Grenzen und auf Zukunftsperspektiven gelegt werden soll. Nach der Beschreibung einiger naturlicher molekularer Maschinen werden die wichtigsten Entwicklungen auf dem Gebiet der kunstlichen molekularen Maschinen vorgestellt. Dabei wird auf folgende Systeme naher eingegangen: 1) chemische Rotoren, 2) photochemisch und elektrochemisch induzierte molekulare (konformative) Umlagerungen und 3) chemisch, photochemisch und elektrochemisch steuerbare (cokonformative) Bewegungen in ineinander greifenden (interlocked) Molekulen (Catenanen und Rotaxanen) sowie in Koordinationsverbindungen und supramolekularen Komplexen (darunter Pseudorotaxanen). Kunstliche, auf Biomolekulen basierende molekulare Maschinen und kunstliche molekulare Maschinen, die auf Oberflachen oder festen Tragern aufgebracht wurden, sind zwei der spannenden Entwicklungen, die besprochen werden. Die Erweiterung des Konzepts einer Maschine auf die molekulare Ebene ist nicht nur fur die Grundlagenforschung von Interesse, sondern auch fur die Weiterentwicklung der Nanowissenschaften und der daraus erwachsenden Nanotechnologie.

Colorimetric detection of cyanide with a chromogenic oxazine.

[reaction: see text] We have designed a chromogenic oxazine for the colorimetric detection of cyanide. Indeed, the [1,3]oxazine ring of our compound opens to form a 4-nitrophenylazophenolate chromophore in response to cyanide. This quantitative chromogenic transformation permits the detection of micromolar concentrations of cyanide in water. Furthermore, our chromogenic oxazine is insensitive to the presence of large concentrations of fluoride, chloride, bromide, or iodide anions, which are generally the principal interferents in the colorimetric detection of cyanide.

Fluorescence modulation with photochromic switches in nanostructured constructs

This tutorial review illustrates the structural design, photochemical and photophysical properties of nanostructured constructs incorporating luminescent and photochromic components. In these systems, the pronounced structural and electronic modifications that accompany the transformations of the photochromic components can be exploited to modulate the emission intensity of the luminescent components on the basis of electron and energy transfer processes. These photoresponsive systems can be assembled by: (1) integrating fluorescent and photochromic components within the main chain of the same polymer; (2) attaching multiple photochromes to a fluorescent organic polymer or luminescent inorganic nanoparticle; (3) appending either independent fluorophores and photochromes or fluorophore-photochrome dyads to a common polymer scaffold; (4) trapping distinct fluorophores and photochromes within the hydrophobic interior of the same cross-linked polymer. In all instances, the changes in absorbance and/or redox potentials associated with the reversible interconversion of the two states of each photochromic component regulate the radiative deactivation of the luminescent components. As a result, the emission intensity of these nanoscaled assemblies can reversibly be switched between high and low values under the influence of optical stimulations. Thus, these clever operating principles for fluorescence modulation can lead to the development of innovative functional and nanostructured materials with photoresponsive character. In particular, protocols for the optical writing and reading of data as well as luminescent probes for bioimaging applications might ultimately emerge from these fundamental studies on photoresponsive molecular switches.

All-optical processing with molecular switches.

A gradual transition from electrical to optical networks is accompanying the rapid progress of telecommunication technology. The urge for enhanced transmission capacity and speed is dictating this trend. In fact, large volumes of data encoded on optical signals can be transported rapidly over long distances. Their propagation along specific routes across a communication network is ensured by a combination of optical fibers and optoelectronic switches. It is becoming apparent, however, that the interplay between the routing electrical stimulations and the traveling optical signals will not be able to support the terabit-per-second capacities that will be needed in the near future. Electrical inputs cannot handle the immense parallelism potentially possible with optical signals. Operating principles to control optical signals with optical signals must be developed. Molecular and supramolecular switches are promising candidates for the realization of innovative materials for information technology. Binary digits can be encoded in their chemical, electrical, or optical inputs and outputs to execute specific logic functions. We have developed a simple strategy to gate optical signals with optical signals by using a photoactive molecular switch. We have demonstrated that NAND, NOR, and NOT operations can be implemented exclusively with optical inputs and optical outputs coupling from one to three switching elements. Our remarkably simple approach to all-optical switching might lead to the development of a new generation of devices for digital processing and communication technology.

Supramolecular strategies to construct biocompatible and photoswitchable fluorescent assemblies.

We designed and synthesized an amphiphilic copolymer with pendant hydrophobic decyl and hydrophilic poly(ethylene glycol) chains along a common poly(methacrylate) backbone. This macromolecular construct captures hydrophobic boron dipyrromethene fluorophores and hydrophobic spiropyran photochromes and transfers mixtures of both components in aqueous environments. Within the resulting hydrophilic supramolecular assemblies, the spiropyran components retain their photochemical properties and switch reversibly to the corresponding merocyanine isomers upon ultraviolet illumination. Their photoinduced transformations activate intermolecular electron and energy transfer pathways, which culminate in the quenching of the boron dipyrromethene fluorescence. As a result, the emission intensity of these supramolecular constructs can be modulated in aqueous environments under optical control. Furthermore, the macromolecular envelope around the fluorescent and photochromic components can cross the membrane of Chinese hamster ovarian cells and transport its cargo unaffected into the cytosol. Indeed, the fluorescence of these supramolecular constructs can be modulated also intracellularly by operating the photochromic component with optical inputs. In addition, cytotoxicity tests demonstrate that these supramolecular assemblies and the illumination conditions required for their operation have essentially no influence on cell viability. Thus, supramolecular events can be invoked to construct fluorescent and photoswitchable systems from separate components, while imposing aqueous solubility and biocompatibility on the resulting assemblies. In principle, this simple protocol can evolve into a general strategy to deliver and operate intracellularly functional molecular components under optical control.

Self‐Assembling Supramolecular Daisy Chains

Self-complementary monomers, incorporating a macrocyclic polyether “head” with an acyclic bipyridinium-based “tail”, self-assemble spontaneously in solution to afford an equilibrium mixture of dimeric, trimeric, tetrameric, and pentameric supermolecules (see schematic diagram on the right) having masses of up to at least 5000 u. A cyclic dimer, which crystallized from the mixture of acyclic and cyclic supermolecules, has been characterized by X-ray crystallography.

On-the-fly decoding luminescence lifetimes in the microsecond region for lanthanide-encoded suspension arrays

Significant multiplexing capacity of optical time-domain coding has been recently demonstrated by tuning luminescence lifetimes of the upconversion nanoparticles called ‘τ-Dots’. It provides a large dynamic range of lifetimes from microseconds to milliseconds, which allows creating large libraries of nanotags/microcarriers. However, a robust approach is required to rapidly and accurately measure the luminescence lifetimes from the relatively slow-decaying signals. Here we show a fast algorithm suitable for the microsecond region with precision closely approaching the theoretical limit and compatible with the rapid scanning cytometry technique. We exploit this approach to further extend optical time-domain multiplexing to the downconversion luminescence, using luminescence microspheres wherein lifetimes are tuned through luminescence resonance energy transfer. We demonstrate real-time discrimination of these microspheres in the rapid scanning cytometry, and apply them to the multiplexed probing of pathogen DNA strands. Our results indicate that tunable luminescence lifetimes have considerable potential in high-throughput analytical sciences.

Photoactivatable synthetic fluorophores.

Photoactivatable fluorophores switch from a nonemissive state to an emissive one under irradiation at an activation wavelength and then emit light in the form of fluorescence upon illumination at an excitation wavelength. Such a concatenation of activation and excitation events translates into the possibility of switching fluorescence on within a defined region of space at a given interval of time. In turn, the spatiotemporal control of fluorescence offers the opportunity to monitor dynamic processes in real time as well as to reconstruct images with resolution at the nanometer level. As a result, these photoresponsive molecular switches are becoming invaluable analytical tools to probe the structures and dynamics of a diversity of materials relying on the noninvasive character of fluorescence imaging.

Tight inclusion complexation of 2,7-dimethyldiazapyrenium in cucurbit[7]uril

The dicationic guest 2,7-dimethyldiazapyrenium is bound inside the host cucurbit[7]uril, forming a very stable inclusion complex in which the host undergoes structural distortions to accommodate the guest.