Reversible Formation of a Light-Responsive Catalyst by Utilizing Intermolecular Cooperative Effects.

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.

Substrate-Induced Self-Assembly of Cooperative Catalysts.

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.

Stereospecific Allylic Functionalization: The Reactions of Allylboronate Complexes with Electrophiles.

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.

Temporal Control over Transient Chemical Systems using Structurally Diverse Chemical Fuels.

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.

Chiral Nanozymes-Gold Nanoparticle-Based Transphosphorylation Catalysts Capable of Enantiomeric Discrimination.

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.

Catalytic signal amplification for the discrimination of ATP and ADP using functionalised gold nanoparticles.

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.

Tandem Allylboration-Prins Reaction for the Rapid Construction of Substituted Tetrahydropyrans: Application to the Total Synthesis of (-)-Clavosolide†A.

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.

Reversible Electrochemical Modulation of a Catalytic Nanosystem.

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.

Highly diastereoselective and enantiospecific allylation of ketones and imines using borinic esters: contiguous quaternary stereogenic centers.

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.

Highly diastereo- and enantioselective allylboration of aldehydes using α-substituted allyl/crotyl pinacol boronic esters via in situ generated borinic esters.

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 ß-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 (11)B NMR confirmed that the reaction proceeds through a borinic ester intermediate.

Interfacial colloidal assembly guided by optical tweezers and tuned via surface charge.

HYPOTHESIS: The size, shape and dynamics of assemblies of colloidal particles optically-trapped at an air-water interface can be tuned by controlling the optical potential, particle concentration, surface charge density and wettability of the particles and the surface tension of the solution. EXPERIMENTS: The assembly dynamics of different colloidal particle types (silica, polystyrene and carboxyl coated polystyrene particles) at an air-water interface in an optical potential were systematically explored allowing the effect of surface charge on assembly dynamics to be investigated. Additionally, the pH of the solutions were varied in order to modulate surface charge in a controllable fashion. The effect of surface tension on these assemblies was also explored by reducing the surface tension of the supporting solution by mixing ethanol with water. FINDINGS: Silica, polystyrene and carboxyl coated polystyrene particles showed distinct assembly behaviours at the air-water interface that could be rationalised taking into account changes in surface charge (which in addition to being different between the particles could be modified systematically by changing the solution pH). Additionally, this is the first report showing that wettability of the colloidal particles and the surface tension of the solution are critical in determining the resulting assembly at the solution surface.

Light-Switchable Membrane Permeability in Giant Unilamellar Vesicles.

In this work, giant unilamellar vesicles (GUVs) were synthesized by blending the natural phospholipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) with a photoswitchable amphiphile (1) that undergoes photoisomerization upon irradiation with UV-A (E to Z) and blue (Z to E) light. The mixed vesicles showed marked changes in behavior in response to UV light, including changes in morphology and the opening of pores. The fine control of membrane permeability with consequent cargo release could be attained by modulating either the UV irradiation intensity or the membrane composition. As a proof of concept, the photocontrolled release of sucrose from mixed GUVs is demonstrated using microscopy (phase contrast) and confocal studies. The permeability of the GUVs to sucrose could be increased to ~4 × 10-2 µm/s when the system was illuminated by UV light. With respect to previously reported systems (entirely composed of synthetic amphiphiles), our findings demonstrate the potential of photosensitive GUVs that are mainly composed of natural lipids to be used in medical and biomedical applications, such as targeted drug delivery and localized topical treatments.

Substrate-Induced Self-Assembly of Cooperative Catalysts.

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.

Transient self-assembly of molecular nanostructures driven by chemical fuels.

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.