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.

Artificial Molecular Machines.

Condensation of 1,4-dimethoxybenzene (DMB) with paraformaldehyde in the presence of BF3·O(C2H5)2 gave novel para-bridged pentacyclic pillar DMB (DMpillar[5]arene). Moreover, para-bridged pentacyclic hydroquinone (pillar[5]arene) was prepared. Pillar[5]arene formed 1:1 host–guest complexes with dialkyl viologen and alkyl pyridinium derivatives. However, pillar[5]arene did not form complexes with the diadamantyl viologen derivative since a bulky adamantyl group was unable to thread the cavity of pillar[5]arene.

para-Bridged symmetrical pillar[5]arenes: their Lewis acid catalyzed synthesis and host-guest property.

Crown ethers: sensors for ions and molecular scaffolds for materials and biological models.

Stimuli-Responsive Motions to Applications Min Xue,† Yong Yang,‡ Xiaodong Chi,† Xuzhou Yan,† and Feihe Huang*,† †State Key Laboratory of Chemical Engineering, Center for Chemistry of High-Performance & Novel Materials, Department of Chemistry, Zhejiang University, Hangzhou 310027, People’s Republic of China ‡Department of Chemistry, Zhejiang Sci-Tech University, Hangzhou 310018, People’s Republic of China

Development of Pseudorotaxanes and Rotaxanes: From Synthesis to Stimuli-Responsive Motions to Applications

The affinities of hosts-ranging from small synthetic cavitands to large proteins-for organic molecules are well documented. The average association constants for the binding of organic molecules by cyclodextrins, synthetic hosts, and albumins in water, as well as of catalytic antibodies or enzymes for substrates are 10(3.5+/-2.5) M(-1). Binding affinities are elevated to 10(8+/-2) M(-1) for the complexation of transition states and biological antigens by antibodies or inhibitors by enzymes, and to 10(16+/-4) M(-1) for transition states with enzymes. The origins of the distributions of association constants observed for the broad range of host-guest systems are explored in this Review, and typical approaches to compute and analyze host-guest binding in solution are discussed. In many classes of complexes a rough correlation is found between the binding affinity and the surface area that is buried upon complexation. Enzymes transcend this effect and achieve transition-state binding much greater than is expected from the surface areas.

https://www.onlinelibrary.wiley.com/doi/pdf/10.1002/anie.200200565

Binding Affinities of Host–Guest, Protein–Ligand, and Protein–Transition‐State Complexes

Mixed monolayers formed by the self-assembly on gold of thiol-functionalized anthraquinones and 1-alkanethiols

The first surface-attached catenane: self-assembly of a two-component monolayer

Molecular Recognition at an Interface: Binding of Monolayer‐Anchored Ferrocenyl Groups by an Amphiphilic Calixarene Host

The complexation of trimethyl(ferrocenylmethyl)ammonium hexafluorophosphate 1·(BF6), heptyldimethyl(ferrocenylmethyl)ammonium bromide 2·(Br) and ferrocenylmethanol 3 by a sulfonated calix[6]arene host was investigated in aqueous media using electrochemical and 1H NMR spectroscopic techniques; the binding interactions between the calixarene host and the surveyed guests are similar to those operating in the complexation of organic compounds by cyclodextrin or cyclophane hosts in aqueous media

Calixarenes as hosts in aqueous media: inclusion complexation of ferrocene derivatives by a water-soluble calix[6]arene

Saccharomyces cerevisiae myristoyl-CoA:protein N-myristoyltransferase (Nmt1p; EC 2.3.1.97) is an essential enzyme that is highly selective for myristoyl-CoA in vivo. It is unclear why myristate (C14:0), a rare cellular fatty acid, has been selected for this covalent protein modification over more abundant fatty acids such as palmitate (C16:0), nor is it obvious how the enzyme's acyl-CoA binding site is able to discriminate between these two fatty acids. Introduction of a cis double bond between C5 and C6 of palmitate [(Z)-5-hexadecenoic acid] or a triple bond between C4 and C5 or C6 and C7 (Y4- and Y6-hexadecenoic acids) yields compounds that, when converted to their CoA derivatives, approach the activity of myristoyl-CoA as Nmt1p substrates in vitro. Kinetic studies of 42 C12-C18 fatty acids containing triple bonds, para-phenylene, or a 2,5-furyl group, as well as cis and trans double bonds, suggest that the geometry of the enzyme's acyl-CoA binding site requires that the acyl chain of active substrates assume a bent conformation in the vicinity of C5. Moreover, the distance between C1 and the bend appears to be a critical determinant for optimal positioning of the acyl-CoA in this binding site so that peptide substrates can subsequently bind in the sequential ordered bi-bi reaction mechanism. Identification of active, conformationally restricted analogs of palmitate offers an opportunity to "convert" wild-type or mutant Nmts to palmitoyltransferases so that they can deliver these C16 fatty acids to critical N-myristoylproteins in vivo. nmt181p contains a Gly-451-->Asp mutation, which causes a marked reduction in the enzyme's affinity for myristoyl-CoA. Strains of S. cerevisiae containing nmt1-181 exhibit temperature-sensitive myristic acid auxotrophy: their complete growth arrest at 37 degrees C is relieved when the medium is supplemented with 500 microM C14:0 but not with C16:0. The CoA derivatives of (Z)-5-hexadecenoic and Y6-hexadecynoic acids are as active substrates for the mutant enzyme as myristoyl-CoA at 24 degrees C. However, unlike C16:0, they produce growth arrest of nmt181p-producing cells at this "permissive" temperature, suggesting that these C16 fatty acids do not allow expression of the biological functions of essential S. cerevisiae N-myristoylproteins.

Tianbao Lu

Papers

Mixed monolayers formed by the self-assembly on gold of thiol-functionalized anthraquinones and 1-alkanethiols

The first surface-attached catenane: self-assembly of a two-component monolayer

Molecular Recognition at an Interface: Binding of Monolayer‐Anchored Ferrocenyl Groups by an Amphiphilic Calixarene Host

Calixarenes as hosts in aqueous media: inclusion complexation of ferrocene derivatives by a water-soluble calix[6]arene

Analogs of palmitoyl-CoA that are substrates for myristoyl-CoA:protein N-myristoyltransferase