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It’s not known how life’s essential properties of replication, metabolism and compartmentalization were first integrated. Two recent articles now shed light on how metabolic characteristics may be incorporated into replicating systems, harnessing an external energy source to increase their rate of replication and acquiring catalytic activity.

Enzymes accelerate chemical reactions by forming cooperative interactions using precisely positioned functional groups. This has inspired the construction of artificial catalysts by the attachment ...

A catalytic system based on monolayer-functionalized gold nanoparticles (Au NPs) that can be electrochemically modulated and reversibly activated is reported. The catalytic activity relies on the presence of metal ions (Cd(2+) and Cu(2+) ), which can be complexed by the nanoparticle-bound monolayer. This activates the system towards the catalytic cleavage of 2-hydroxypropyl-p-nitrophenyl phosphate (HPNPP), which can be monitored by UV/Vis spectroscopy. It is shown that Cu(2+) metal ions can be delivered to the system by applying an oxidative potential to an electrode on which Cu(0) was deposited. By exploiting the different affinity of Cd(2+) and Cu(2+) ions for the monolayer, it was also possible to upregulate the catalytic activity after releasing Cu(2+) from an electrode into a solution containing Cd(2+) . Finally, it is shown that the activity of this supramolecular nanosystem can be reversibly switched on or off by oxidizing/reducing Cu/Cu(2+) ions under controlled conditions.

A photoresponsive system where structure formation is coupled to catalytic activity is presented. The observed catalytic activity is reliant on intermolecular cooperative effects that are present when amphiphiles assemble into vesicular structures. Photoresponsive units within the amphiphilic pre-catalysts allow for switching between assembled and disassembled states, thereby modulating the catalytic activity. The ability to reversibly form cooperative catalysts within a dynamic self-assembled system represents a conceptually new tool for the design of complex artificial systems in water.

Dissipative self‐assembly processes in nature rely on chemical fuels that activate proteins for assembly through the formation of a noncovalent complex. The catalytic activity of the assemblies causes fuel degradation, resulting in the formation of an assembly in a high‐energy, out‐of‐equilibrium state. Herein, we apply this concept to a synthetic system and demonstrate that a substrate can induce the formation of vesicular assemblies, which act as cooperative catalysts for cleavage of the same substrate., Self‐destruction for good: A substrate is shown to induce the self‐assembly of a cooperative catalyst, leading to its own destruction. Nature exploits the same strategy to obtain high‐energy structures such as microtubules and to drive non‐equilibrium phenomena.

3,3-Disubstituted allylic boronic esters are not sufficiently reactive to react with ketones and imines. However, they can be converted into the corresponding borinic esters by the sequential addition of nBuLi and TFAA. These reactive intermediates possess the perfect balance between reactivity and configurational stability. Their enhanced reactivity allows the highly selective allylation of both ketones and ketimines, and facile access to adjacent quaternary stereocenters with full stereocontrol. The versatility of the methodology is demonstrated in the construction of all possible stereoisomers of a quaternary-quaternary motif and by the allylation of the heterocycles, dihydroisoquinoline and indole.

The next generation of adaptive, intelligent chemical systems will rely on a continuous supply of energy to maintain the functional state. Such systems will require chemical methodology that provides precise control over the energy dissipation process, and thus, the lifetime of the transiently activated function. This manuscript reports on the use of structurally diverse chemical fuels to control the lifetime of two different systems under dissipative conditions: transient signal generation and the transient formation of self-assembled aggregates. The energy stored in the fuels is dissipated at different rates by an enzyme, which installs a dependence of the lifetime of the active system on the chemical structure of the fuel. In the case of transient signal generation, it is shown that different chemical fuels can be used to generate a vast range of signal profiles, allowing temporal control over two orders of magnitude. Regarding self-assembly under dissipative conditions, the ability to control the lifetime using different fuels turns out to be particularly important as stable aggregates are formed only at well-defined surfactant/fuel ratios, meaning that temporal control cannot be achieved by simply changing the fuel concentration.

Over the past decades, chemists have mastered the art of assembling small molecules into complex nanostructures using non-covalent interactions. The driving force for self-assembly is thermodynamics: the self-assembled structure is more stable than the separate components. However, biological self-assembly processes are often energetically uphill and require the consumption of chemical energy. This allows nature to control the activation and duration of chemical functions associated with the assembled state. Synthetic chemical systems that operate in the same way are essential for creating the next generation of intelligent, adaptive materials, nanomachines and delivery systems. This review focuses on synthetic molecular nanostructures which self-assemble under dissipative conditions. The chemical function associated with the transient assemblies is operational as long as chemical fuel is present.

Tetrahydropyrans are common motifs in natural products and have now been constructed with high stereocontrol through a three-component allylboration-Prins reaction sequence. This methodology has been applied to a concise (13 steps) and efficient (14 % overall yield) synthesis of the macrolide (−)-clavosolide A. The synthesis also features an early stage glycosidation reaction to introduce the xylose moiety and a lithiation-borylation reaction to attach the cyclopropyl-containing side chain.

A concise and flexible synthesis of the morpholine-spiroketal natural product acortatarin A, isolated from the traditional Chinese medicine Acorus tatarinowii, is reported. The key step involves a Maillard-type condensation of an amine derived from d -mannitol with a dihydropyranone. The approach also enables access to analogues of acortatarin A for biological evaluation and can be applied to the synthesis of related 2-formylpyrrole natural products.

The spirastrellolides are a family of potent antimitotic agents isolated from the marine sponge Spirastrella coccinea . Synthetic studies toward the DEF bis-spiroacetal core of spirastrellolide B are reported. A modular approach was pursued by the use of two dithiane disconnections to enable a highly convergent synthesis. The ease of lithiation and nucleophilicity of these 2-substituted-1,3-dithianes were investigated during the course of the synthesis, and the alkylations were found to proceed most efficiently at elevated temperatures. Formation of the [5,6,6]-bis-spiroacetal ring system was achieved via a double dithiane deprotection/spiroacetalization strategy.

Enantioselectivity in RNA cleavage by a synthetic metalloenzyme has been demonstrated for the first time. Thiols containing chiral Zn(II) -binding head groups have been self-assembled on the surface of gold nanoparticles. This results in the spontaneous formation of chiral bimetallic catalytic sites that display different activities (kcat ) towards the enantiomers of an RNA model substrate. Substrate selectivity is observed when the nanozyme is applied to the cleavage of the dinucleotides UpU, GpG, ApA, and CpC, and remarkable differences in reactivity are observed for the cleavage of the enantiomerically pure dinucleotide UpU.

Diagnostic assays that incorporate a signal amplification mechanism permit the detection of analytes with enhanced selectivity. Herein, we report a gold nanoparticle-based chemical system able to differentiate ATP from ADP by means of catalytic signal amplification. The discrimination between ATP and ADP is of relevance for the development of universal assays for the detection of enzymes which consume ATP. For example, protein kinases are a class of enzymes critical for the regulation of cellular functions, and act to modulate the activity of other proteins by transphosphorylation, transferring a phosphate group from ATP to give ADP as a byproduct. The system described here exploits the ability of cooperative catalytic head groups on gold nanoparticles to very efficiently catalyze chromogenic reactions such as the transphosphorylation of 2-hydroxypropyl-4-nitrophenyl phosphate (HPNPP). A series of chromogenic substrates have been synthesized and evaluated by means of Michaelis-Menten kinetics (compounds 2, 4-6). 2-Hydroxypropyl-(3-trifluoromethyl-4-nitro)phenyl phosphate (5) was found to display higher reactivity (kcat) and higher binding affinity (KM) when compared to HPNPP. This higher binding affinity allows phosphate 5 to compete with ATP and ADP to different extents for binding on the monolayer surface, thus enabling a catalytically amplified signal only when ATP is absent. Overall, this represents a viable new approach for monitoring the conversion of ATP into ADP with high sensitivity.

Tetrahydropyrans are common motifs in natural products and have now been constructed with high stereocontrol through a three‐component allylboration‐Prins reaction sequence. This methodology has been applied to a concise (13 steps) and efficient (14 % overall yield) synthesis of the macrolide (−)‐clavosolide A. The synthesis also features an early stage glycosidation reaction to introduce the xylose moiety and a lithiation‐borylation reaction to attach the cyclopropyl‐containing side chain.

In this review we describe the use of monolayer protected gold nanoparticles (Au NPs) for chemosensing applications. The attention is focused on a special subclass of Au NPs, namely those that contain binding sites for metal ions in the monolayer. It will be shown that these systems are very well-equipped for metal ion sensing as the complexation of the metal ions can affect the properties of the system in many ways leading to detectable output signals even at very low analyte concentrations. In addition, the presence of metal ions in the monolayer themselves can serve as recognition units for the highly selective interaction with small organic molecules or biomacromolecules. Key examples will be discussed that underscore the attractive properties and potential of this class of Au NPs as components of chemosensing assays.

Key step in the total synthesis of the unusual morpholine-spiroketal acortatarin A (I) is a novel Maillard-type condensation reaction between a primary amine derived from D-mannitol and a dihydropyranone.

3,3-Disubstituted allylic boronic esters are not sufficiently reactive to react with ketones and imines. However, they can be converted into the corresponding borinic esters by the sequential addition of nBuLi and TFAA. These reactive intermediates possess the perfect balance between reactivity and configurational stability. Their enhanced reactivity allows the highly selective allylation of both ketones and ketimines, and facile access to adjacent quaternary stereocenters with full stereocontrol. The versatility of the methodology is demonstrated in the construction of all possible stereoisomers of a quaternary-quaternary motif and by the allylation of the heterocycles, dihydroisoquinoline and indole.

In this review we describe the use of monolayer protected gold nanoparticles (Au NPs) for chemosensing applications. The attention is focused on a special subclass of Au NPs, namely those that contain binding sites for metal ions in the monolayer. It will be shown that these systems are very well-equipped for metal ion sensing as the complexation of the metal ions can affect the properties of the system in many ways leading to detectable output signals even at very low analyte concentrations. In addition, the presence of metal ions in the monolayer themselves can serve as recognition units for the highly selective interaction with small organic molecules or biomacromolecules. Key examples will be discussed that underscore the attractive properties and potential of this class of Au NPs as components of chemosensing assays.

The Suzuki-Miyaura cross-coupling of enantioenriched secondary allylic boronic esters occurs with high γ-regioselectivity and high retention of chirality, proceeding via γ-selective transmetalation and subsequent reductive elimination.

Asymmetric cross-coupling reactions in which stereo- chemistry-bearing CC bonds are created are still in their infancy. Considering the wealth of compounds that can be prepared by cross-coupling methodologies, and the impor- tance of synthetic methods leading to enantiomerically en- riched products, this is a surprising reality. Advances in this area have occurred in the past few years, in the realm of enantioselective or enantiospecific cross-couplings of chiral electrophiles. (1) In the area of cross-coupling of stereodefined nucleo- philes, Crudden originally reported the enantiospecific cross-coupling of chiral enantiomerically enriched benzylic boronic esters (Eq. (1)). (2, 3)

Readily available, α-substituted allyl/crotyl pinacol boronic esters often give low E/Z selectivity (with Z favored) in reactions with aldehydes. We found that addition of nBuLi to the pinacol boronic ester followed by trapping of the alkoxide with TFAA leads to an intermediate allyl borinic ester which undergoes allylboration with very high E selectivity. The substrate scope includes primary to tertiary alkyl α-substituents, crotyl substrates, and the previously unreported β-methallyl pinacol boronic esters. The latter give very high Z selectivity under standard conditions which is completely reversed to high E selectivity under the new conditions. Monitoring the reaction by 11B NMR confirmed that the reaction proceeds through a borinic ester intermediate.

Readily available, alpha-substituted allyl/crotyl pinacol boronic esters often give low E/Z selectivity (with Z favored) in reactions with aldehydes. We found that addition of nBuLi to the pinacol boronic ester followed by trapping of the alkoxide with TFAA leads to an intermediate allyl borinic ester which undergoes allylboration with very high E selectivity. The substrate scope includes primary to tertiary alkyl alpha-substituents, crotyl substrates, and the previously unreported beta-methallyl pinacol boronic esters. The latter give very high Z selectivity under standard conditions which is completely reversed to high E selectivity under the new conditions. Monitoring the reaction by B-11 NMR confirmed that the reaction proceeds through a borinic ester intermediate.

The [5,6,6]-bis-spiroacetal moiety (II) of spirastrellolide B is prepared via a HgCl2-mediated double dithiane deprotection accompanied by a simultaneous bis-spiroacetalisation as a key step.

Twenty nine novel spiroketal derivatives related to the rubromycins were evaluated for their anti-telomerase activity using the real-time quantitative telomeric repeat amplification protocol assay. The parent compound γ-rubromycin exhibited the highest potency against human telomerase activity within the series. Modification of the spiroketal motif by the introduction of heteroatoms and substituents at different positions produced analogues with varying bioactivity. Variation at the isocoumarin subunit of the title compound resulted in weaker activity, indicative of its importance in telomerase inhibition.

Telomeres are repetitive sequences of DNA found at the ends of chromosomes which determine and restrict the number of replications a cell can undertake. In the majority of cancer cells, telomerase has been found to maintain the length of telomeres, conferring cell immortality and prevention of cell senescence. With the ready availability of assays to detect telomerase activity, numerous telomerase inhibitors have been discovered from a variety of natural sources. This article gives an outline of these natural product-based telomerase inhibitors and their inspiration for analogue design.

Use of a bis-dithiane deprotection-tandem bis-spiroacetalisation sequence was key to the successful synthesis of the [5,6,6]-bis-spiroacetal of the antimitotic agent spirastrellolide B, achieved in a highly convergent fashion involving successive dithiane alkylations.

Allylboronic esters react readily with carbonyls and imines (π-electrophiles), but are unreactive toward a range of other electrophiles. By addition of an aryllithium, the corresponding allylboronate complexes display enhanced nucleophilicity, enabling addition to a range of electrophiles (tropylium, benzodithiolylium, activated pyridines, Eschenmoser's salt, Togni's reagent, Selectfluor, diisopropyl azodicarboxylate (DIAD), MeSX) in high regio- and stereocontrol. This protocol provides access to key new functionalities, including quaternary stereogenic centers bearing moieties such as fluorine and the trifluoromethyl group. The allylboronate complexes were determined to be 7 to 10 orders of magnitude more reactive than the parent boronic ester.