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.

Azobenzene undergoes trans → cisisomerization when irradiated with light tuned to an appropriate wavelength. The reverse cis →transisomerization can be driven by light or occurs thermally in the dark. Azobenzene's photochromatic properties make it an ideal component of numerous molecular devices and functional materials. Despite the abundance of application-driven research, azobenzene photochemistry and the isomerization mechanism remain topics of investigation. Additional substituents on the azobenzene ring system change the spectroscopic properties and isomerization mechanism. This critical review details the studies completed to date on the 3 main classes of azobenzene derivatives. Understanding the differences in photochemistry, which originate from substitution, is imperative in exploiting azobenzene in the desired applications.

Photoisomerization in different classes of azobenzene

Two-photon absorption has important advantages over conventional one-photon absorption, which has led to applications in microscopy, microfabrication, three-dimensional data storage, optical power limiting, up-converted lasing, photodynamic therapy, and for the localized release of bio-active species. These applications have generated a demand for new dyes with high two-photon absorption cross-sections. This Review introduces the theory of two-photon absorption, surveys the wide range of potential applications, and highlights emerging structure-property correlations that can serve as guidelines for the development of efficient two-photon dyes.

Two-photon absorption and the design of two-photon dyes.

Functional π-Gelators and Their Applications

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

Photochemical uncaging of bio-active molecules was introduced in 1977, but since then, there has been no substantial improvement in the properties of generic caging chromophores. We have developed a new chromophore, nitrodibenzofuran (NDBF) for ultra-efficient uncaging of second messengers inside cells. Photolysis of a NDBF derivative of EGTA (caged calcium) is about 16-160 times more efficient than photolysis of the most widely used caged compounds (the quantum yield of photolysis is 0.7 and the extinction coefficient is 18,400 M(-1) cm(-1)). Ultraviolet (UV)-laser photolysis of NDBF-EGTA:Ca(2+) rapidly released Ca(2+) (rate of 20,000 s(-1)) and initiated contraction of skinned guinea pig cardiac muscle. NDBF-EGTA has a two-photon cross-section of approximately 0.6 GM and two-photon photolysis induced localized Ca(2+)-induced Ca(2+) release from the sarcoplasmic recticulum of intact cardiac myocytes. Thus, the NDBF chromophore has great promise as a generic and photochemically efficient protecting group for both one- and two-photon uncaging in living cells.

The nitrodibenzofuran chromophore: a new caging group for ultra-efficient photolysis in living cells.

A series of salicylideneaniline ( SA ) derivatives 1–3 were prepared to study the substituent effect on the chromic properties. Compounds 1 and 3 , introduced naphthyl group on the A ring in the parent compound SA , exhibited the solvatochromism, thermochromism and photochromism, while compound 2 , introduced the naphthyl group on the B ring in SA , did not show the solvatochromism or thermochromism. The discussion in this study is mainly focused on the behaviour of compounds 1 and 2 . The UV absorption spectra of 1 dramatically changed with increasing the solvent polarity as well as cooling temperature, suggesting that 1 takes Z -NH form in polar solvents at room temperature or even in non-polar solvents at below 120 K. Compound 1 emits fluorescence (FL) only at low temperature with small Stokes shift, while 2 exhibits fluorescence emission with considerably large Stokes shift. On UV irradiation, 1 in benzene underwent intramolecular hydrogen atom transfer to give E -NH form. The large Stokes shift observed in 2 indicates that 2 takes E -OH form even at low temperature in any solvents, and underwent intramolecular hydrogen atom transfer in the excited state to give Z -NH form, which emits the fluorescence at low temperature, or undergoes isomerization around CC double bond to give E -NH form. The potential energy diagrams for 1 and 2 were also determined.

Photochromism, thermochromism, and solvatochromism of naphthalene-based analogues of salicylideneaniline in solution

Intramolecularly hydrogen-bonded organic compounds often exhibit fluorescence emission at considerably longer wavelengths than typical fluorescence as a result of excited-state intramolecular proton transfer (ESIPT). The structure−property relationship of such ESIPT molecules, however, remains obscure. The present article reports the excited-state dynamics of a new family of ESIPT molecules, 2-(2′-hydroxynaphthyl)benzazoles 1−3, based on steady-state and time-resolved spectroscopy measurements. In comparison with the parent compound HBO, all three compounds 1−3 exhibited absorption bands at longer wavelengths and emitted fluorescence from the excited keto-tautomer K* at shorter wavelengths, indicating that the introduction of a naphthalene ring increases the energy gap between the ground and excited states for the keto-tautomer despite the expansion of the aromatic ring. Time-resolved fluorescence spectra revealed dual emission for compounds 1 and 3, consisting of two distinct fluorescence bands originati...

Excited-State Intramolecular Proton Transfer of Naphthalene-Fused 2-(2′-Hydroxyaryl)benzazole Family

The syntheses and reactions of photoresponsive dendrimers are described. Dendrimers with photoreversible stilbene cores undergo mutual cis–trans isomerization in organic solvents to give photostationary state mixtures of cis - and trans -isomers. Even stilbene dendrimers with molecular weights as high as 6500 underwent mutual cis–trans isomerization within the lifetime of the excited singlet state. The large dendron group surrounding the photoreactive core may affect the excited state properties of the core to induce the efficiency of photoisomerization and/or reduce the fluorescence efficiency. The photochemistry of stilbene dendrimers, with various types of dendron groups, azobenzene dendrimers and other photoresposive dendrimers is discussed.

Photochemistry and photophysics of stilbene dendrimers and related compounds

Second harmonic generation (SHG) imaging can be used to visualize unique biological phenomena, but currently available dyes limit its application owing to the strong fluorescent signals that they generate together with SHG. Here we report the first non-fluorescent and membrane potential-sensitive SHG-active organic dye Ap3. Ap3 is photostable and generates SH signals at the plasma membrane with virtually no fluorescent signals, in sharp contrast to the previously used fluorescent dye FM4-64. When tested in neurons, Ap3-SHG shows linear membrane potential sensitivity and fast responses to action potentials, and also shows significantly reduced photodamage compared with FM4-64. The SHG-specific nature of Ap3 allows simultaneous and completely independent imaging of SHG signals and fluorescent signals from various reporter molecules, including markers of cellular organelles and intracellular calcium. Therefore, this SHG-specific dye enables true multimodal two-photon imaging in biological samples.

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Atsuya Momotake

Papers

The nitrodibenzofuran chromophore: a new caging group for ultra-efficient photolysis in living cells.

Photochromism, thermochromism, and solvatochromism of naphthalene-based analogues of salicylideneaniline in solution

Excited-State Intramolecular Proton Transfer of Naphthalene-Fused 2-(2′-Hydroxyaryl)benzazole Family

Photochemistry and photophysics of stilbene dendrimers and related compounds

Multimodal two-photon imaging using a second harmonic generation-specific dye.