The resolution of a microscope is determined by the diffraction limit in classical microscopy, whereby objects that are separated by half a wavelength can no longer be visually separated. To go below the diffraction limit required several tricks and discoveries. In his Nobel Lecture, E. Betzig describes the developments that have led to modern super high-resolution microscopy.

A picture is worth a thousand words—This doesn't only apply to everyday life but also to the natural sciences. It is, therefore, probably not by chance that the historical beginning of modern natural sciences very much coincides with the invention of light microscopy. S. W. Hell shows in his Nobel Lecture that the diffraction resolution barrier has been overcome by using molecular state transitions (e.g. on/off) to make nearby molecules transiently discernible.

In the early 90s, many fascinating physical effects were observed when ensemble averaging was removed to allow study of individual molecules. The imaging of single molecules as well as observations of spectral diffusion, optical switching, and the ability to select different single molecules in the same focal volume by tuning the pumping laser frequency provided important forerunners of the later super-resolution microscopy with single molecules.

Tracking down cancer: A hypoxia-sensitive optical oxygen nanosensor is reported for tracking cancer metastasis in vivo. After systemic administration of the nanosensor, cancer cells metastasizing to the lungs through the blood stream or to the lymph node through lymphatics can be effectively detected by whole-body optical imaging.

Electrochemical polarization of a de-alloyed nanoporous NiCuMn alloy was employed to synthesize a novel multicomponent mixed-valence oxyhydroxide based electrode. The oxyhydroxide/metal electrode possesses both high specific capacitance (627 F cm⁻³) at a current density of 0.25 A cm⁻³ and a wide working-potential window (1.8 V) in aqueous electrolyte, thereby resulting in a high energy and power densities with excellent cyclic stability.

Synergetic therapy: Strong hypoxia created by upconversion photodynamic therapy (UC-PDT) activates bioreductive pro-drugs co-delivered to form cytotoxic species, thereby potentiating the synergetic anticancer efficacy of UC-PDT. This process was accomplished by using upconversion-based nanoparticles designed to simultaneously deliver photosensitizer molecules and bioreductive pro-drugs in silica layers.

A chemically selective electrochemical proton pump creates a concentration perturbation in a thin-layer sample that is detected by a pH probe placed opposite. The proposed methodology is applicable for a range of ions and is demonstrated here for direct alkalinity measurements. L=ionophore; R⁻=cation exchanger; J=proton flux; IFS=inner filling solution.

Controlling nanoparticle morphology was achieved by tuning the overgrowth of gold nanorods using DNA as a capping ligand. Kinetic studies show two representative pathways for the shape control. Furthermore, the geometric and plasmonic properties of the gold nanoparticles could be precisely controlled by adjusting the base composition of the DNA sequences or by introducing phosphorothioate modifications in the DNA.

Off the beaten track: Sequence-dependent kinetic pathway selection in chemically fueled catalytic self-assembly of tripeptides is demonstrated, in which the control of the lifetime of the nanostructures is dictated by chemical design. Mimicking the unique features of these systems may open up opportunities to create supramolecular systems for non-equilibrium motility and shape control.

Getting the green light: Hispidin is shown to be a luciferin precursor in at least four evolutionary distant genera of luminous fungi. However, its biosynthesis alone does not result in fungal bioluminescence. Two enzymes are required: first a hydroxylase converts the hispidin into 3-hydroxyhispidin, which acts as the luciferin, which undergoes a subsequent oxidation in the presence of a luciferase.

Distant but decisive: Kinetic cooperativity is an intrinsic property of glucokinase that enables it to maintain whole-body glucose homeostasis. The small-domain dynamics of glucokinase on the millisecond timescale have now been quantified by NMR spectroscopic experiments and found to be responsible for this effect by interfering with the turnover rate constant and generating non-Michaelis–Menten kinetics (see picture).

Nanohybrid compositions based on (6,5) chirality-enriched SWNTs and a chiral n-type polymer (S-PBN(b)-Ph₄PDI) that exploits a perylenediimide-containing repeat unit undergo light-driven electron–hole pair generation. Rigorously controlled SWNT:electron acceptor stoichiometry and organization enable spectroscopic characterization of the photoinduced charge carrier signatures and evaluation of the associated charge separation and charge migration dynamics by pump-probe transient absorption spectroscopy.

Enhanced immunostimulation: A multivalent polymer nanocomplex for the effective intracellular delivery and subsequent multivalent display of immunostimulatory cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODNs) in antigen-presenting cells is described. Mice vaccinated with dendritic cells treated with the nanocomplex exhibited tumor growth inhibition as well as a strong antitumor memory response. HA=hyaluronic acid, PLL=poly(L-lysine).

DNA branches out: A hyperbranched hybridization chain reaction is reported for the self-assembly of dendritic DNA structures triggered by an initiator DNA strand. By using this method, ultrasensitive detection of target DNA was achieved and three-input concatenated logic circuits have been constructed which can operate as keypad locks for biocomputing security systems at the molecular level.

Anionic doping: Cosubstitution of CdS and ZnS by P, Cl and N, F brings about remarkable changes in the electronic structure of these materials as the electronic band gaps are significantly decreased (E_g=band-gap energy). The effect of both P, Cl and N, F in CdS and ZnS were studied by DFT calculations, and the changes were measured by high-resolution X-ray photoelectron spectroscopy.

Unbiased selection: A kinase inhibitor screening approach was developed that uses a radically different basis of detection than existing methods. Engineered protein nanopores allow the label-free determination of inhibition constants, are scalable to high-throughput, and circumvent biases inherent in prevailing technologies.

Chiral cations: Following the recently observed C₃/C₂ B₃₉⁻ and D_2d B₄₀, two new chiral members C₁ B₄₁⁺ and C₂ B₄₂²⁺ are introduced to the borospherene family. These chiral borospherene cations are composed of twelve interwoven boron double chains with six hexagonal and heptagonal faces and exhibit σ plus π double delocalization, which can be viewed as cuborenes analogous to cubane (C₈H₈).

Stable superoxide found in gold ORR: An in situ spectroscopic study of the oxygen reduction reaction (ORR) on gold in a DMSO electrolyte containing phenol as a proton source shows that the ORR can begin with 1e⁻ transfer to O₂. Thus O₂⁻, not HO₂, is the first stable intermediate during the ORR to hydrogen peroxide. The unusual stability of O₂⁻ is explained using DFT calculations.

Fatal attraction: The noncovalent interaction of a hydroxy group with pyrazines and quinoxalines involves a lone pair (lp)–heteroarene attraction which is stronger and solvent independent when measured relative to the π-facial hydrogen bond to a benzene ring. Organic fluorides also prefer the heteroarene ring over benzene. The attraction between a quinoxaline and a terminal alkyne is stronger than an OH–arene interaction.

Triple the fun: Synthesis of an all-carbon conjugated tetrabenzoperipentacene was achieved. The single-crystal X-ray structure revealed that the molecules form a triple-layered cluster-like β-graphite. The remarkably rigid carbon framework results in a small Stokes shift and fully reversible five-electron oxidation potentials.

Nanocomposite electrocatalyst: A high-performance electrocatalyst for the oxygen reduction reaction (ORR) is based on Fe₃C nanoparticles encapsulated in mesoporous Fe-N-doped carbon nanofibers. It can be synthesized from low-cost and abundant precursors and exhibits excellent electrocatalytic performance for the ORR in both alkaline and acidic media.

Chemical gardens: Self-assembling membranes in iron sulfide and iron hydroxide reaction systems were studied. The electrical potential and current generated by precipitation of the inorganic membranes were measured. The battery-like properties of the chemical gardens were demonstrated by linking multiple experiments in series, which produced sufficient electrical power to light an external light-emitting diode.

Hydrogen generation on self-supported three-dimensional nickel phosphide nanosheet array cathodes is reported. The nanosheets have been fabricated by direct phosphorization of commercial nickel foams using phosphorus vapor and show superior electrocatalytic activity and stability in acidic medium toward H₂ generation.

Crowd around: Oxindoles with adjacent fully substituted stereogenic centers were formed by mild organocatalytic addition reactions with high diastereo- and enantioselectivities. The synthetic versatility of the products with orthogonally addressable functional moieties was showcased in the synthesis of derivatives of the bioactive oxindole AG-041R.

Good yields and diastereo- and enantioselectivities were observed for the title reaction with various imines using chiral bis(imidazoline)/Pd catalysts. The reaction of α-aminonitriles with di-tert-butyl azodicarboxylate afforded chiral α,α-diaminonitrile in high yield with high enantioselectivity. acac=acetylacetonate, Boc=tert-butoxycarbonyl.

One six one four: Based on a 1,6-Friedel–Crafts/1,4-oxa-Michael sequence, an organocatalyst directs the reaction of hydroxyarenes with a vinylogous iminium-ion intermediate to give only one out of four possible regioisomers. The reaction provides optically active chromans in high yields with up to 99 % ee.

The influence of light and oxygen on the stability of CH₃NH₃PbI₃ perovskite-based photoactive layers is investigated. Upon exposure to both light and dry air, the mesoporous (mp) Al₂O₃/CH₃NH₃PbI₃ layers decompose to methylamine, PbI₂, and I₂. This degradation is initiated by the reaction of superoxide (O₂⁻) with the methylammonium moiety of the perovskite absorber. MA=methyl ammonium, CB=conduction band, VB=valence band.

Surprisingly radical was the outcome of an attempt to prepare sterically protected tungsten corroles. Instead of a heavy-metal chelate, a chlorinated corrole radical (see picture) was formed as an air-stable and easy-to-handle open-shell 17π (4n+1) porphyrinoid. The loss of one inner H atom results in a planar molecular structure with the ability to bind divalent metal ions, such as zinc(II).

Hexa- and decagalloylglucoses, which belong to the gallotannin plant polyphenols, were chemically synthesized for the first time, and a method for the selective synthesis of the monogalloylglucoses α- and β-glucogallin was developed. An in vitro evaluation showed that the non-natural α-glucogallin and a natural β-hexagalloylglucose are potent inhibitors of amyloid β-peptide aggregation.

Reuse and recycle: A tripodal nitroxide ligand is used in the separation of Nd and Dy and gives good recoveries from Nd/Dy(OTf)₃ mixtures. The separation factor S_Nd/Dy=359 achieved is an improvement over conventional separation methods involving liquid–liquid extractions. This method will contribute to incentivizing recycling of Nd/Dy permanent magnetic materials.

Take your Pic: Total synthesis of the glycosylated human interleukin-2 (IL-2) has been achieved. The poor solubility of the C-terminal half during purification and ligation was overcome by using the reverse polarity protection of the carboxylic acid by a picolyl (Pic) ester. Together with a new prolyl thioester synthesis for the (28–65) segment, the desired IL-2, having full biological activity, was successfully prepared.

CC bond cleavage under Pd catalysis induces a regioselective activation of gem-difluorinated cyclopropanes. The reaction provides access to a variety of 2-fluoroallylic scaffolds with high Z-selectivity and represents the first general application of gem-difluorinated cyclopropanes as reaction partners in transition-metal-catalyzed cross-coupling reactions.

Simply copper: Primary, secondary, and tertiary alkylzinc reagents couple with heteroaryl iodides in the presence of ligand-free CuI without complications arising from β-hydride elimination and rearrangement. The reactions can also be extended to the coupling of aryl- and alkynylzinc reagents. DMF=N,N-dimethylformamide.

‘Cat nap’: The cationic Rh^I/H₈-binap complex catalyzes the [3+2+2] cycloaddition of 1,6-diynes with cyclopropylideneacetamides to produce cycloheptadienes. In contrast, the cationic Rh^I/(S)-binap complex catalyzes the enantioselective [2+2+2] cycloaddition of terminal alkynes, acetylenedicarboxylates, and cyclopropylideneacetamides to produce spiro-cyclohexadienes.

Swap gold for zinc: The title reaction was achieved by a zinc(II)-catalyzed alkyne oxidation/CH functionalization sequence. In contrast to the well-established gold-catalyzed intermolecular alkyne oxidation, the over-oxidation can be suppressed in this system and the reaction most likely proceeds by a Friedel–Crafts-type pathway. Tf=trifluoromethanesulfonyl, PG=protecting group.

Taking out the O: The salts of the title cations were used in the catalytic stepwise hydrosilylation and deoxygenation of ketones. The dependency of the reaction outcome on Lewis acidity was investigated. In addition, the mechanism of the reduction was probed experimentally as well as with DFT calculations.

Path finder: The mechanism of nitric oxide electroreduction to ammonia on Pt(111) is investigated using a combination of first principles calculations and electrokinetic rate theories. The results demonstrate that ammonia is produced through a series of water-assisted protonation and bond dissociation steps at modest voltages.

Coupled by design: The arylation of sterically demanding α-branched secondary amines was enabled through the design of new palladium catalyst systems. These catalysts help suppress the undesired β-hydride elimination pathways and are effective for the cross-coupling of a wide array of hindered amine nucleophiles with aryl and heteroaryl electrophiles.

Leaving-group activation: A Brønsted acid catalyzed intramolecular enantioselective S_N2′ reaction was developed utilizing trichloroacetimidate as a leaving group. The findings indicated that dual activation of the substrates is operative. This metal-free allylic alkylation allows highly enantioselective access to 2-vinylpyrrolidines bearing various substituents.

In a (closed) nut shell: A novel triphenylamine derivative having two phenoxy radicals appended to the amino nitrogen atom has been prepared. This molecule has an unexpected closed-shell electronic state, even at room temperature, in spite of its structural similarity to the galvinoxyl radical. The molecule features two CN bonds with multiple-bond character and a remarkably low HOMO–LUMO gap.

Taking advantage of poisons: The poisoning effect of lead(II) ions can alter the shapes of Pd–Pb alloy nanocrystals. It endows the alloy nanocrystals with superior selectivity for the semihydrogenation of alkynes.

Breaking into cores: Formal core orbitals sometimes may take part in bonding. An instance is provided in theoretical studies of the bonding of CsF₅ (see picture) and CsF₂⁺. The results also suggest that these metastable high fluorides of cesium may be experimentally accessible.

Give me F,F,F,F,F, five: The polyfluoride anions [F₅]⁻ and Cs⁺[F₃]⁻ have been identified by matrix-isolation spectroscopy and quantum-chemical methods. The V-shaped [F₅]⁻ ion gives rise to a band found in many IR laser ablation experiments that, up to now, could not be assigned.

A change of heart: The borazine derivative of hexa-peri-hexabenzocoronene was produced in a high-temperature reaction through multiple dehydrogenation of a borazine. The solid-state structure of this BN-doped HBC (BN-HBC) is isotypic with that of the parent HBC. Scanning tunneling microscopy shows that BN-HBC lies flat on Au(111) in a two-dimensional pattern.

Iodine does it! The first catalytic Hofmann–Löffler reaction proceeds with a combination of catalytic amounts of molecular iodine and a modified hypervalent iodine(III) reagent. The reaction proceeds under mild catalytic conditions and the intramolecular CH amination addresses primary, secondary, and tertiary CH groups.

Long-term separation: Charge-transfer complexes formed by electron-donating carbon nanodots and electron-accepting perylenediimides are prepared. In ultrafast pump-probe experiments (see picture) the charge-separated state with a lifetime of 210 ps was found.