Cristian Pezzato

Multivalent Interactions Regulate Signal Transduction in a Self-Assembled Hg2+ Sensor

A self-assembled sensing system able to detect Hg(2+) at low nanomolar concentrations is reported that operates through a signal transduction pathway involving multivalent interactions. The analyte causes dimerization of low-affinity ligands, resulting in a complex with a high affinity for a multivalent monolayer-protected gold nanoparticle (AuNP). This complex displaces a quenched fluorescent reporter from the AuNP, resulting in a turn ON of fluorescence. It is shown that the strength of the output signal can be regulated by tuning the multivalent interactions between the complex and the NP. Finally, it is shown that multivalent interactions drive the self-selection of a high-affinity complex from a mixture of low-affinity ligands.

Transient signal generation in a self-assembled nanosystem fueled by ATP.

A fundamental difference exists in the way signal generation is dealt with in natural and synthetic systems. While nature uses the transient activation of signalling pathways to regulate all cellular functions, chemists rely on sensory devices that convert the presence of an analyte into a steady output signal. The development of chemical systems that bear a closer analogy to living ones (that is, require energy for functioning, are transient in nature and operate out-of-equilibrium) requires a paradigm shift in the design of such systems. Here we report a straightforward strategy that enables transient signal generation in a self-assembled system and show that it can be used to mimic key features of natural signalling pathways, which are control over the output signal intensity and decay rate, the concentration-dependent activation of different signalling pathways and the transient downregulation of catalytic activity. Overall, the reported methodology provides temporal control over supramolecular processes.

Controlling supramolecular complex formation on the surface of a monolayer-protected gold nanoparticle in water.

A combination of hydrophobic and electrostatic interactions drives the self-assembly of a large number of small molecules on the surface of a monolayer-protected gold nanoparticle. The hydrophobic interactions originate from the insertion of an aromatic unit in the hydrophobic part of the monolayer. This is evidenced by a shift in the emission wavelength of the fluorogenic probe upon binding. Up to around 35 small molecules can be simultaneously bound to the monolayer surface at micromolar concentrations in water. It is shown that an understanding of the supramolecular interactions that drive complex formation on the monolayer surface provides unprecedented control over the supramolecular chemistry occurring on the surface. By taking advantage of the different kinds of noncovalent interactions present in different probes, it is possibile to displace one type of surface-bound molecule from a heteromeric surface selectively. Finally, it is also possible to catch and release one type of surface-bound molecule selectively.

Zn2+‐Regulated Self‐Sorting and Mixing of Phosphates and Carboxylates on the Surface of Functionalized Gold Nanoparticles

Herein, we describe the self-sorting of phosphate- and carboxylate-containing molecules on the surface of monolayer-protected gold nanoparticles. Self-sorting is driven by selective interactions between the phosphate probe and Zn(2+) complexes in one monolayer; these interactions force the carboxylate probe to move to a second type of nanoparticle. This process effectively separates the probes and causes their localization in well-defined spaces surrounding the nanoparticles. The removal/addition of Zn(2+) metal ions from the system is used to convert the system from an ordered to a disordered state and vice versa. The possibility to control the location and transport of populations of molecules in a complex mixture creates new perspectives for the development of innovative complex catalytic systems that mimic nature.

Photoswitchable Catalysis by a Nanozyme Mediated by a Light-Sensitive Cofactor

The activity of a gold nanoparticle-based catalyst can be reversibly up- and down-regulated by light. Light is used to switch a small molecule between cis- and trans-isomers, which inhibits the catalytic activity of the nanoparticles to different extent. The system is functional in aqueous buffer, which paves the way for integrating the system in biological networks.

Redox-Active Macrocycles for Organic Rechargeable Batteries

Organic rechargeable batteries, composed of redox-active molecules, are emerging as candidates for the next generation of energy storage materials because of their large specific capacities, cost effectiveness, and the abundance of organic precursors, when compared with conventional lithium-ion batteries. Although redox-active molecules often display multiple redox states, precise control of a molecules redox potential, leading to a single output voltage in a battery, remains a fundamental challenge in this popular field of research. By combining macrocyclic chemistry with density functional theory calculations (DFT), we have identified a structural motif that more effectively delocalizes electrons during lithiation events in battery operations-namely, through-space electron delocalization in triangular macrocyclic molecules that exhibit a single well-defined voltage profile-compared to the discrete multiple voltage plateaus observed for a homologous macrocyclic dimer and an acyclic derivative of pyromellitic diimide (PMDI). The triangular macrocycle, incorporating three PMDI units in close proximity to one another, exhibits a single output voltage at 2.33 V, compared with two peaks at (i) 2.2 and 1.95-1.60 V for reduction and (ii) 1.60-1.95 and 2.37 V for oxidation of the acyclic PMDI derivative. By investigating the two cyclic derivatives with different conformational dispositions of their PMDI units and the acyclic PMDI derivative, we identified noticeable changes in interactions between the PMDI units in the two cyclic derivatives under reducing conditions, as determined by differential pulse voltammetry, solution-state spectroelectrochemistry, and variable-temperature UV-Vis spectra. The numbers and relative geometries of the PMDI units are found to alter the voltage profile of the active materials significantly during galvanostatic measurements, resulting in a desirable single plateau for the triangular macrocycle. The present investigation reveals that understanding and controlling the relative conformational dispositions of redox-active units in macrocycles are key to achieving high energy density and long cycle-life electrodes for organic rechargeable batteries.

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.

Controlling Dual Molecular Pumps Electrochemically

Artificial molecular machines can be operated using either physical or chemical inputs. Light-powered motors display clean and autonomous operations, whereas chemically driven machines generate waste products and are intermittent in their motions. Herein, we show that controlled changes in applied electrochemical potentials can drive the operation of artificial molecular pumps in a semi-autonomous manner-that is, without the need for consecutive additions of chemical fuel(s). The electroanalytical approach described in this Communication promotes the assembly of cyclobis(paraquat-p-phenylene) rings along a positively charged oligomeric chain, providing easy access to the formation of multiple mechanical bonds by means of a controlled supply of electricity.

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.