The Huisgen 1,3-dipolar cycloaddition reaction of organic azides and alkynes has gained considerable attention in recent years due to the introduction in 2001 of Cu(1) catalysis by Tornoe and Meldal, leading to a major improvement in both rate and regioselectivity of the reaction, as realized independently by the Meldal and the Sharpless laboratories. The great success of the Cu(1) catalyzed reaction is rooted in the fact that it is a virtually quantitative, very robust, insensitive, general, and orthogonal ligation reaction, suitable for even biomolecular ligation and in vivo tagging or as a polymerization reaction for synthesis of long linear polymers. The triazole formed is essentially chemically inert to reactive conditions, e.g. oxidation, reduction, and hydrolysis, and has an intermediate polarity with a dipolar moment of ∼5 D. The basis for the unique properties and rate enhancement for triazole formation under Cu(1) catalysis should be found in the high ∆G of the reaction in combination with the low character of polarity of the dipole of the noncatalyzed thermal reaction, which leads to a considerable activation barrier. In order to understand the reaction in detail, it therefore seems important to spend a moment to consider the structural and mechanistic aspects of the catalysis. The reaction is quite insensitive to reaction conditions as long as Cu(1) is present and may be performed in an aqueous or organic environment both in solution and on solid support.

Cu-catalyzed azide-alkyne cycloaddition.

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

Applications of Supramolecular Anion Recognition

Supramolecular Amphiphiles Based on Host-Guest Molecular Recognition Motifs.

This review covers advances in electrochemical and biochemical sensor development and usage during 2010 and 2011 In choosing scholarly articles to contribute to this review, special emphasis was placed on work published in the areas of reference electrodes, potentiometric sensors, voltammetric sensors, amperometric sensors, biosensors, immunosensors, and mass sensors In the past two years there have been a number of important papers, that do not fall into the general subsections contained within the larger sections Such novel advances are very important for the field of electrochemical sensors as they open up new avenues and methods for future research Each section above contains a subsection titled “Other Papers of Interest” that includes such articles and describes their importance to the field in general For example, while most electrochemical techniques for sensing analytes of interest are based on the changes in potential or current, Shan et al1 have developed a completely novel method for performing electrochemical measurements In their work, they report a method for imaging local electrochemical current using the optical signal of the electrode surface generated from a surface plasmon resonance (SPR) The electrochemical current image is based on the fact that the current density can be easily calculated from the local SPR signal The authors demonstrated this concept by imaging traces of TNT on a fingerprint on a gold substrate

Full articles and reviews were primarily amassed by searching the SciFinder Scholar and ISI Web of Knowledge Additional articles were found through alternate databases or by perusing analytical journals for pertinent publications Due to the reference limitation, only publications written in English were considered for inclusion Obviously, there have been more published accounts of groundbreaking work with electrochemical and biochemical sensors than those covered here This review is a small sampling of the available literature and not intended to cover every advance of the past two years The literature chosen focuses on new trends in materials, techniques, and clinically relevant applications of novel sensors To ensure proper coverage of these trends, theoretical publications and applications of previously reported sensor development were excluded

We want to remind our readers that this review is not intended to provide comprehensive coverage of electrochemical sensor development, but rather to provide a glimpse of the available depth of knowledge published in the past two years This review is meant to focus on novel methods and materials, with a particular focus on the increasing use of graphene sheets for sensor material development For readers seeking more information on the general principles behind electrochemical sensors and electrochemical methods, we recommend other sources with a broader scope2, 3 Electrochemical sensor research is continually providing new insights into a variety of fields and providing a breadth of relevant literature that is worthy of inclusion in this review Unfortunately, it is impossible to cover each publication and unintentional oversights are inevitable We sincerely apologize to the authors of electrochemical and biochemical sensor publications that were inadvertently overlooked

Electrochemical Sensors and Biosensors

Pure C-H hydrogen bonding to chloride ions: a preorganized and rigid macrocyclic receptor.

A series of shape-persistent [34]triazolophanes bearing t-butyl or triethylene glycol (OTg) substituents on the phenylene linkers have been prepared in a modular manner from simple building blocks. Triazolophane−halide binding affinities were determined using UV titrations in order to help in understanding the driving forces behind the large receptor−anion binding strengths supported solely by CH hydrogen-bond donors. The fixed size of the central cavity provides a means for selective recognition of Cl− and Br− anions with large binding strengths (Ka > 1 000 000 M−1; ΔG > −8.5 kcal mol−1). The smaller F− and larger I− anions are bound less tightly by ∼1 and ∼3 orders of magnitude, respectively. The four triazole-based H-bond donors are believed to be of primary importance, while the four phenylene CH H-bond donors take on a secondary role. Consistent with this idea, the binding affinity can be tuned by as much as 1 kcal mol−1 by changing the character of the four phenylene-based substituents from more (OT...

Strong, size-selective, and electronically tunable C-H...halide binding with steric control over aggregation from synthetically modular, shape-persistent [34]triazolophanes.

Can terdentate 2,6-bis(1,2,3-triazol-4-yl)pyridines form stable coordination compounds?

Triazolophanes that incorporate pyridyl subunits in place of phenylenes show a heightened propensity to form 2:1 sandwich complexes with halides Persistent iodide-based sandwiches are observed Binding constants confirm that the inward-facing electron pairs on the pyridyls destabilize the 1:1 complexes with halides The 1H NMR spectra verify that the sandwich complexes have two π-stacked triazolophanes rotated to allow registration between opposite dipoles on the pyridyls (directed inward) and triazoles (directed outward) These dipolar interactions cooperate to lower the pyridyl-based repulsions, therefore, increasing K2 Modest cooperative effects are observed for the snugly fitting F−, Cl−, and Br− halides while the too-large I− shows highly positive cooperativity

Dipole-Promoted and Size-Dependent Cooperativity between Pyridyl-Containing Triazolophanes and Halides Leads to Persistent Sandwich Complexes with Iodide

Triazolophanes, cyclic compounds containing 1,2,3-triazole units, are a new class of host molecules that demonstrate strong interactions with halides. These molecules are designed with a preorganized cavity that interacts through hydrogen bonding with spherical anions, such as chloride and bromide. We have explored the use of one such triazolophane as a halide-selective ionophore in poly(vinyl chloride) (PVC) membrane electrodes. Different membrane compositions were evaluated to identify concentrations of the ionophore, plasticizer, and lipophilic additive that give rise to the best chloride and bromide selectivity. The lipophilicity of the plasticizer was found to have a great impact on the electrode response. Additionally, the concentration of the lipophilic additive was found to be critical for optimal response. The utility of a triazolophane-based electrode was demonstrated by quantification of bromide in horse serum samples.

Yongjun Li

Papers

Pure C-H hydrogen bonding to chloride ions: a preorganized and rigid macrocyclic receptor.

Strong, size-selective, and electronically tunable C-H...halide binding with steric control over aggregation from synthetically modular, shape-persistent [34]triazolophanes.

Can terdentate 2,6-bis(1,2,3-triazol-4-yl)pyridines form stable coordination compounds?

Dipole-Promoted and Size-Dependent Cooperativity between Pyridyl-Containing Triazolophanes and Halides Leads to Persistent Sandwich Complexes with Iodide

Triazolophanes: a new class of halide-selective ionophores for potentiometric sensors.