The widespread use of controlled molecular-level motion in key natural processes suggests that great rewards could come from bridging the gap between the present generation of synthetic molecular systems, which by and large rely upon electronic and chemical effects to carry out their functions, and the machines of the macroscopic world, which utilize the synchronized movements of smaller parts to perform specific tasks. This is a scientific area of great contemporary interest and extraordinary recent growth, yet the notion of molecular-level machines dates back to a time when the ideas surrounding the statistical nature of matter and the laws of thermodynamics were first being formulated. Here we outline the exciting successes in taming molecular-level movement thus far, the underlying principles that all experimental designs must follow, and the early progress made towards utilizing synthetic molecular structures to perform tasks using mechanical motion. We also highlight some of the issues and challenges that still need to be overcome.

Synthetic molecular motors and mechanical machines.

The widespread use of molecular machines in biology has long suggested that great rewards could come from bridging the gap between synthetic molecular systems and the machines of the macroscopic world. In the last two decades, it has proved possible to design synthetic molecular systems with architectures where triggered large amplitude positional changes of submolecular components occur. Perhaps the best way to appreciate the technological potential of controlled molecular-level motion is to recognize that nanomotors and molecular-level machines lie at the heart of every significant biological process. Over billions of years of evolution, nature has not repeatedly chosen this solution for performing complex tasks without good reason. When mankind learns how to build artificial structures that can control and exploit molecular level motion and interface their effects directly with other molecular-level substructures and the outside world, it will potentially impact on every aspect of functional molecule and materials design. An improved understanding of physics and biology will surely follow.

The first steps on the long path to the invention of artificial molecular machines were arguably taken in 1827 when the Scottish botanist Robert Brown observed the haphazard motion of tiny particles under his microscope.1,2 The explanation for Brownian motion, that it is caused by bombardment of the particles by molecules as a consequence of the kinetic theory of matter, was later provided by Einstein, followed by experimental verification by Perrin.3,4 The random thermal motion of molecules and its implications for the laws of thermodynamics in turn inspired Gedankenexperiments (“thought experiments”) that explored the interplay (and apparent paradoxes) of Brownian motion and the Second Law of Thermodynamics. Richard Feynman’s famous 1959 lecture “There’s plenty of room at the bottom” outlined some of the promise that manmade molecular machines might hold.5,6 However, Feynman’s talk came at a time before chemists had the necessary synthetic and analytical tools to make molecular machines. While interest among synthetic chemists began to grow in the 1970s and 1980s, progress accelerated in the 1990s, particularly with the invention of methods to make mechanically interlocked molecular systems (catenanes and rotaxanes) and control and switch the relative positions of their components.7−24

Here, we review triggered large-amplitude motions in molecular structures and the changes in properties these can produce. We concentrate on conformational and configurational changes in wholly covalently bonded molecules and on catenanes and rotaxanes in which switching is brought about by various stimuli (light, electrochemistry, pH, heat, solvent polarity, cation or anion binding, allosteric effects, temperature, reversible covalent bond formation, etc.). Finally, we discuss the latest generations of sophisticated synthetic molecular machine systems in which the controlled motion of subcomponents is used to perform complex tasks, paving the way to applications and the realization of a new era of “molecular nanotechnology”.

1.1. The Language Used To Describe Molecular Machines
Terminology needs to be properly and appropriately defined and these meanings used consistently to effectively convey scientific concepts. Nowhere is the need for accurate scientific language more apparent than in the field of molecular machines. Much of the terminology used to describe molecular-level machines has its origins in observations made by biologists and physicists, and their findings and descriptions have often been misinterpreted and misunderstood by chemists. In 2007 we formalized definitions of some common terms used in the field (e.g., “machine”, “switch”, “motor”, “ratchet”, etc.) so that chemists could use them in a manner consistent with the meanings understood by biologists and physicists who study molecular-level machines.14

The word “machine” implies a mechanical movement that accomplishes a useful task. This Review concentrates on systems where a stimulus triggers the controlled, relatively large amplitude (or directional) motion of one molecular or submolecular component relative to another that can potentially result in a net task being performed. Molecular machines can be further categorized into various classes such as “motors” and “switches” whose behavior differs significantly.14 For example, in a rotaxane-based “switch”, the change in position of a macrocycle on the thread of the rotaxane influences the system only as a function of state. Returning the components of a molecular switch to their original position undoes any work done, and so a switch cannot be used repetitively and progressively to do work. A “motor”, on the other hand, influences a system as a function of trajectory, meaning that when the components of a molecular motor return to their original positions, for example, after a 360° directional rotation, any work that has been done is not undone unless the motor is subsequently rotated by 360° in the reverse direction. This difference in behavior is significant; no “switch-based” molecular machine can be used to progressively perform work in the way that biological motors can, such as those from the kinesin, myosin, and dynein superfamilies, unless the switch is part of a larger ratchet mechanism.14

Artificial Molecular Machines

Chirality-Sensing Supramolecular Systems

The past decade has witnessed renewed interest and numerous unexpected discoveries in the area of main group organometallic chemistry. Unusual bonding modes have been uncovered,1-4 new materials have been developed,5,6 and new applications are being pursued.7-12 With respect to new materials with unusual properties, an exciting field is the development of hybrid polymers that combine main group elements with typical organic structures in one framework.13,14 Among main group organic-inorganic hybrid polymers, those involving Group 14 and Group 15 elements have received tremendous attention over the past several decades, with silicones, polysilanes, and polyphosphazenes among the most thoroughly studied materials.15-17 A variety of other classes of new polymers containing not only silicon and phosphorus,18-22 but also the heavier homologues, such as germanium, tin, arsenic, and antimony have been introduced more recently.23-26

Advances in the Synthesis of Organoborane Polymers for Optical, Electronic, and Sensory Applications

Synthesis and Applications of Boronic Acid-Containing Polymers: From Materials to Medicine.

Modular photoinduced electron transfer (PET) sensors bearing two phenylboronic acid groups, a pyrene group and alkylene linkers, from trimethylene to octamethylene, have been prepared and evaluated. The diboronic acid systems with tetramethylene 3444 pentamethylene 3555 and hexamethylene 3666 linkers display the greatest enhancement in binding relative to monoboronic acid 4 with D-glucose. The diboronic acid system with the hexamethylene 3666 linker is particularly D-glucose selective and sensitive. Whilst the diboronic acid systems with the longer heptamethylene 3777 and octamethylene 3888 linkers display the greatest
enhancement in binding relative to monoboronic acid 4 with D-galactose. All saccharide titrations were performed in methanolic aqueous solution.

Modular fluorescence sensors for saccharides

A simple three step synthesis was developed to provide six novel modular sensors, consisting of three para sensors, and three meta sensors with naphthalene, anthracene and pyrene fluorophores. The interaction of the six sensors with the saccharides: D-glucose, D-fructose, D-galactose, and D-mannose, were evaluated. All sensors displayed increasing fluorescence intensity upon the addition of these saccharides, with all of the sensors showing enhanced selectivity for D-glucose over D-galactose, D-fructose and D-mannose. High affinity (Kobs) was also observed for the meta sensors with respect to the para sensors. The naphthalene and anthracene meta sensors showed particularly high affinity (Kobs) for D-galactose. Circular dichroism spectroscopy was used to probe the structures of the complexes formed. Cyclic complexes were formed between all six sensors and D-glucose. Whilst naphthalene and anthracene meta sensors which displayed high affinity for D-galactose also formed cyclic complexes with that saccharide.

Boronic acid based photoinduced electron transfer (PET) fluorescence sensors for saccharides

New cerium(IV) bis(porphyrinate) double decker bearing two pairs of anion binding sites was synthesized. This anion receptor can bind dianionic tartarate guest according to positive homotropic allosterism. Analysis using the Hill equation afforded log K (association constant) = 9.33 [(mol dm−3)−2] and n (Hill coefficient) = 2.1 (± 0.1). This is the first example where “static” anion binding has been combined with the “dynamic” allosteric system.

Karine A. Frimat

Papers

Modular fluorescence sensors for saccharides

Modular fluorescence sensors for saccharides

Boronic acid based photoinduced electron transfer (PET) fluorescence sensors for saccharides

Efficient Anion Binding to Cerium(IV) Bis(porphyrinate) Double Decker Utilizing Positive Homotropic Allosterism

Modular Fluorescence Sensors for Saccharides