The Redox‐Neutral Approach to C?H Functionalization

The direct functionalization of C? H bonds is an attractive strategy in organic synthesis. Although several advances have been made in this area, the selective activation of inert sp³ C? H bonds remains a daunting challenge. Recently, a new type of sp³ C? H activation mode through internal hydride transfer has demonstrated the potential to activate remote sp³ C? H linkages in an atom‐economic manner. This Minireview attempts to classify recent advances in this area including the transition to non‐activated sp³ C? H bonds and asymmetric hydride transfers.     

Dual pH‐ and Temperature‐Responsive Metallosupramolecular Block Copolymers with Tunable Critical Micelle Temperature by Modulation of the Self‐Assembly of NIR‐Emissive Alkynylplatinum(II) Complexes Induced by Changes in Hydrophilicity and Electrostatic Effects

Terpyridylplatinum(II)‐based metallosupramolecular triblock copolymers with hydrophilic alkynyl ligands have been synthesised and characterised. As a result of the intrinsic properties of Pluronics, reversible temperature‐induced micellisation occurred at high temperature leading to aggregation of the platinum(II) complex moieties through Pt???Pt and π–π interactions, resulting in significant UV/Vis absorption and near‐infrared (NIR) emission spectral changes. The critical micelle temperatures of the complexes were found to vary from 21 to 30 °C due to differences in the hydrophilicity of the alkynyl ligands and the electrostatic repulsions between the positively charged platinum(II) complex moieties. One of the complexes with pH‐responsive CH₂NMe₂ groups on the alkynyl ligand was found to show NIR emission that is sensitive to both pH and temperature. Such dual‐responsive behaviour has been ascribed to the modulation of the self‐assembly of the complex moieties by temperature‐induced micellisation and the changes in the hydrophilicity as well as electrostatic interactions upon protonation/deprotonation of the CH₂NMe₂ groups on the alkynyl ligand.     

Blood Proteins Strongly Reduce the Mobility of Artificial Self‐Propelled Micromotors

Autonomous self‐propelled catalytic microjets are envisaged as an important technology in biomedical applications, including drug delivery, micro/nanosurgery, and active dynamic bioassays. The direct in vivo application of these microjets, specifically in blood, is however impeded by insufficient knowledge on the in vivo viability of the technique. This study highlights the effect of blood proteins on the viability of the microjets. The presence of blood proteins, including serum albumin and γ‐globulins at physiological concentrations, has been found to dramatically reduce the viability of the microjets. The reduction of viability has been measured in terms of a lower number of active microjets and a decrease in the velocity of propulsion. It is clear from this study that in order for microjets to function in biomedical applications, different modes of propulsion besides platinum‐catalyzed oxygen bubble ejection must be employed. These findings have serious implications for the biomedical applications of catalytic microjets.     

Instant Visual Detection of Picogram Levels of Trinitrotoluene by Using Luminescent Metal–Organic Framework Gel‐Coated Filter Paper

There is an ongoing need for explosive detection strategies to uncover threats to human security including illegal transport and terrorist activities. The widespread military use of the explosive trinitrotoluene (TNT) for landmines poses another particular threat to human health in the form of contamination of the surrounding environment and groundwater. The detection of explosives, particularly at low picogram levels, by using a molecular sensor is seen as an important challenge. Herein, we report on the use of a fluorescent metal–organic framework hydrogel that exhibits a higher detection capability for TNT in the gel state compared with that in the solution state. A portable sensor prepared from filter paper coated by the hydrogel was able to detect TNT at the picogram level with a detection limit of 1.82 ppt (parts per trillon). Our results present a simple and new means to provide selective detection of TNT on a surface or in aqueous solution, as afforded by the unique molecular packing through the metal–organic framework structure in the gel formation and the associated photophysical properties. Furthermore, the rheological properties of the MOF‐based gel were similar to those of a typical hydrogel.     

Design and Synthesis of a γ1β8‐Cyclodextrin Oligomer: A New Platform with Potential Application as a Dendrimeric Multicarrier

We report the synthesis and characterization of a water‐soluble, star‐shaped macromolecular platform consisting of eight β‐cyclodextrin (β‐CD) units anchored to the narrower rim of a γ‐CD core through bis(triazolyl)alkyl spacers. The efficient synthetic protocol is based on the microwave (MW)‐promoted Cu‐catalyzed 1,3‐dipolar cycloaddition of CD monoazides to CD monoacetylenes. The ligand‐hosting capability of the construct has been assessed by relaxometric titration and nuclear magnetic relaxation dispersion (NMRD) profiling, which showed it to be good, and this was supported by molecular dynamics simulations. To demonstrate the feasibility of obtaining supramolecular structures with high hosting ability, we designed a dimeric platform, formed by joining two nonamers through the γ‐CD cores through a bis(lithocholic acid) linker. With a view to the potential biological applications, cytotoxicity and extent of binding to human serum albumin were assessed. The properties of this dendrimeric multicarrier make it suitable for pharmaceutical and diagnostic purposes, ranging from targeted drug delivery to molecular imaging.     

Reversible Control over Molecular Recognition in Surface‐Bound Photoswitchable Hydrogen‐Bonding Receptors: Towards Read–Write–Erase Molecular Printboards

The synthesis of an anthracene‐bearing photoactive barbituric acid receptor and its subsequent grafting onto azide‐terminated alkanethiol/Au self‐assembled monolayers by using an Cu^I‐catalyzed azide–alkyne reaction is reported. Monolayer characterization using contact‐angle measurements, electrochemistry, and spectroscopic ellipsometry indicate that the monolayer conversion is fast and complete. Irradiation of the receptor leads to photodimerization of the anthracenes, which induces the open‐to‐closed gating of the receptor by blocking access to the binding site. The process is thermally reversible, and polarization‐modulated IR reflection–absorption spectroscopy indicates that photochemical closure and thermal opening of the surface‐bound receptors occur in 70 and 100 % conversion, respectively. Affinity of the open and closed surface‐bound receptor was characterized by using force spectroscopy with a barbituric‐acid‐modified atomic force microscope tip.     

A Click Approach to Polymetallic Chromium(0) and Tungsten(0) Fischer‐Carbene Complexes and Their Use in the Synthesis of Functionalized Polymetallic Metal?Carbene Complexes

Alkynylamino Cr⁰ and W⁰ Fischer carbenes undergo a CuAAC reaction with a diverse range of di‐, tri‐, and tetra‐azides to produce polymetallic chromium(0) and tungsten(0) (Fischer)‐carbene complexes in good‐to‐excellent yields. This method is simple, versatile, and is suitable for the preparation of a diverse range of structures with a high level of symmetry. Moreover, the resulting polymetallic carbene complexes are suitable partners for the peripheral functionalization of the metal nuclei, whilst retaining the metal fragment. This fact has been demonstrated in a simultaneous Pauson–Khand reaction, which, in some cases, allows for the generation of four bicyclic [5,5] rings on the periphery of a tetrametallic molecule in a process that involves the formation of 12 new C? C bonds, with four simultaneous CO‐insertion processes. The electrochemistry of the polymetallic Fischer carbenes show completely independent behavior for each nucleus, as well as an anomalous observation of the reversible oxidation of the allyl substituents, which has not been reported before in this class of chemistry.     

Progress in the Understanding of the Key Pharmacophoric Features of the Antimalarial Drug Dihydroartemisinin: An Experimental and Theoretical Charge Density Study

The accurate, experimental charge density distribution, ρ( r ), of the potent antimalarial drug dihydroartemisinin (DHA) has been derived for the first time from single‐crystal X‐ray diffraction data at T=100(2) K. Gas‐phase and solid‐state DFT simulations have also been performed to provide a firm basis of comparison with experimental results. The quantum theory of atoms in molecules (QTAIM) has been employed to analyse the ρ( r ) scalar field, with the aim of classifying and quantifying the key real‐space elements responsible for the known pharmacophoric features of DHA. From the conformational perspective, the bicyclo[3.2.2]nonane system fixes the three‐dimensional arrangement of the 1,2,4‐trioxane bearing the active O? O redox centre. This is the most nucleophilic function in DHA and acts as an important CH???O acceptor. On the contrary, the rest of the molecular backbone is almost neutral, in accordance with the lipophilic character of the compound. Another remarkable feature is the C? O bond length alternation along the O‐C‐O‐C polyether chain, due to correlations between pairs of adjacent C? O bonds. These bonding features have been related with possible reactivity routes of the α‐ and β‐DHA epimers, namely 1) the base‐catalysed hemiacetal breakdown and 2) the peroxide reduction. As a general conclusion, the base‐driven proton transfer has significant non‐local effects on the whole polyether chain, whereas DHA reduction is thermodynamically favourable and invariably leads to a significant weakening (or even breaking) of the O? O bond. The influence of the hemiacetal stereochemistry on the electronic properties of the system has also been considered. Such findings are discussed in the context of the known chemical reactivity of this class of important antimalarial drugs.     

Quantum‐Chemical and Electrochemical Investigation of the Electrochemical Windows of Halogenated Carborate Anions

The range of electrochemical stability of a series of weakly coordinating halogenated (Hal=F, Cl, Br, I) 1‐carba‐closo‐dodecaborate anions, [1‐R‐CB₁₁X₅Y₆]^? (R=H, Me; X=H, Hal, Me; Y=Hal), has been established by using quantum chemical calculations and electrochemical methods. The structures of the neutral and dianionic radicals, as well as the anions, have been optimized by using DFT calculations at the PBE0/def2‐TZVPP level. The calculated structures are in good agreement with existing experimental data and with previous calculations. Their gas‐phase ionization energies and electron affinities were calculated based on their optimized structures and were compared with experimental (cyclic and square‐wave) voltammetry data. Electrochemical oxidation was performed in MeCN at room temperature and in liquid sulfur dioxide at lower temperatures. All of the anions show a very high resistance to the onset of oxidation (2.15–2.85 V versus Fc^0/+), with only a minor dependence of the oxidation potential on the different halogen substituents. In contrast, the reduction potentials in MeCN are strongly substituent dependent (?1.93 to ?3.32 V versus Fc^0/+). The calculated ionization energies and electron affinities correlate well with the experimental redox potentials, which provide important verification of the thermodynamic validity of the mostly irreversible redox processes that are observed for this series. The large electrochemical windows that are afforded by these anions indicate their suitability for electrochemical applications, for example, as supporting electrolytes.