Pick your Pd partners: A number of catalytic systems have been developed for palladium-catalyzed CH activation/CC bond formation. Recent studies concerning the palladium(II)-catalyzed coupling of CH bonds with organometallic reagents through a PdII/Pd0 catalytic cycle are discussed (see scheme), and the versatility and practicality of this new mode of catalysis are presented. Unaddressed questions and the potential for development in the field are also addressed.

In the past decade, palladium-catalyzed CH activation/CC bond-forming reactions have emerged as promising new catalytic transformations; however, development in this field is still at an early stage compared to the state of the art in cross-coupling reactions using aryl and alkyl halides. This Review begins with a brief introduction of four extensively investigated modes of catalysis for forming CC bonds from CH bonds: PdII/Pd0, PdII/PdIV, Pd0/PdII/PdIV, and Pd0/PdII catalysis. A more detailed discussion is then directed towards the recent development of palladium(II)-catalyzed coupling of CH bonds with organometallic reagents through a PdII/Pd0 catalytic cycle. Despite the progress made to date, improving the versatility and practicality of this new reaction remains a tremendous challenge.

/pdf/palladium-ii-catalyzed-c-h-activation-c-c-cross-coupling-2546yox1wp.pdf

Palladium(II)-catalyzed C-H activation/C-C cross-coupling reactions: versatility and practicality.

Recent applications of the Suzuki–Miyaura cross-coupling reaction in organic synthesis

Our understanding of the cellular implementation of systems-level neural processes like action, thought and emotion has been limited by the availability of tools to interrogate specific classes of neural cells within intact, living brain tissue. Here we identify and develop an archaeal light-driven chloride pump (NpHR) from Natronomonas pharaonis for temporally precise optical inhibition of neural activity. NpHR allows either knockout of single action potentials, or sustained blockade of spiking. NpHR is compatible with ChR2, the previous optical excitation technology we have described, in that the two opposing probes operate at similar light powers but with well-separated action spectra. NpHR, like ChR2, functions in mammals without exogenous cofactors, and the two probes can be integrated with calcium imaging in mammalian brain tissue for bidirectional optical modulation and readout of neural activity. Likewise, NpHR and ChR2 can be targeted together to Caenorhabditis elegans muscle and cholinergic motor neurons to control locomotion bidirectionally. NpHR and ChR2 form a complete system for multimodal, high-speed, genetically targeted, all-optical interrogation of living neural circuits.

Multimodal fast optical interrogation of neural circuitry

Design strategies for water-soluble small molecular chromogenic and fluorogenic probes.

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

https://research.birmingham.ac.uk/portal/files/31024248/Johnston_et_al_Beta_cell_hubs_Cell_Metabolism.pdf

Beta Cell Hubs Dictate Pancreatic Islet Responses to Glucose

Since the advent of click chemistry in 2001, the 1,4-disubstituted triazole has become an increasingly common motif in chemical sensors. Although these click-derived triazoles are generally used as a convenient method of ligation, their prevalence in chemosensors can be attributed to their ability to bind both cations and anions. In this critical review, we present an overview of the wide range of chemosensors that contain click-derived triazoles, with a particular focus on those cases where the triazole plays a functional, rather than merely a structural, role. Examples are categorised based on method of detection and key structural features, providing a complete picture of the current state of click-based chemosensors, as well as potential future directions for sensor design. (140 references)

Chemical sensors that incorporate click-derived triazoles.

There has been a recent drive to develop asymmetric catalytic methods to produce epoxides using environmentally benign oxidants, especially hydrogen peroxide. This critical review discusses the advances that have been made using both metal-based and organocatalytic homogeneous catalysts (142 references).

Recent advances in catalytic asymmetric epoxidation using the environmentally benign oxidant hydrogen peroxide and its derivatives.

Terahertz spectroscopy is only now beginning to make its transition from initial development by physicists and engineers to broader use by chemists, materials scientists and biologists, thanks to the increasing availability of commercial terahertz spectrometers. With the unique insights that terahertz spectroscopy can provide into intermolecular bonding and crystalline matter, it could prove to be an invaluable addition to the chemist's analytical toolset. This tutorial review aims to give an introduction to terahertz spectroscopy, its techniques, equipment, current applications and potential for the chemical sciences to a broad readership.

Terahertz spectroscopy: a powerful new tool for the chemical sciences?

Kharasch and Sosnovsky reported the allylic oxidation of alkenes to give racemic allylic benzoates. This could be achieved efficiently using a tert-butyl perester as the oxidant, in the presence of a copper or cobalt salt. The use of C(2)-symmetric bis(oxazoline) ligands in the presence of copper(I) triflate with cyclic olefinic substrates gave the first synthetically useful asymmetric variant. The enantioselective control was good (up to 84 % ee) although yields were variable. In all cases the facial preference of the newly formed C-O bond was the same giving an S configuration at the allylic stereocenter. Lower stereocontrol was observed for large-ring alkenes and substantially reduced enantioselectivities were found with open-chain alkenes. This reaction has been further screened using a variety bis(oxazoline) and proline-derived ligands, which give a direct correlation between the chirality of the ligand and the enantioselectivity obtained. Individual substrates were found to be extremely sensitive to both the ligand structure and copper salt used as well as the presence of additives such as zinc, hydrazine, and molecular sieves.

Michael Watkinson

Papers

Beta Cell Hubs Dictate Pancreatic Islet Responses to Glucose

Chemical sensors that incorporate click-derived triazoles.

Recent advances in catalytic asymmetric epoxidation using the environmentally benign oxidant hydrogen peroxide and its derivatives.

Terahertz spectroscopy: a powerful new tool for the chemical sciences?

Catalytic Allylic Oxidation of Alkenes Using an Asymmetric Kharasch–Sosnovsky Reaction