Recognition-Encoded Molecules: A Minimal Self-Replicator.

Nucleic acids, with their unique duplex structure, which is key for information replication, have sparked interest in self-replication's role in life's origins. Early template-based replicators, initially built on short oligonucleotides, expanded to include peptides and synthetic molecules. We explore here the potential of a class of synthetic duplex-forming oligoanilines, as self-replicators.

Chemical Information Processing by a Responsive Chemical System.

Nature has an extraordinary capacity to precisely regulate the chemical reactivity in a highly complex mixture of molecules that is present in the cell. External stimuli lead to transient up- and downregulation of chemical reactions and provide a means for a cell to process information arriving from the environment. The development of synthetic chemical systems with life-like properties requires strategies that allow likewise control over chemical reactivity in a complex environment.

Sequence-selective duplex formation and template effect in recognition-encoded oligoanilines.

A new family of duplex-forming recognition encoded oligomers, capable of sequence selective duplex formation and template directed synthesis, was developed. Monomers equipped with both amine and aldehyde groups were functionalized with 2-trifluoromethylphenol or phosphine oxide as H-bond recognition units. Duplex formation and assembly properties of homo- and hetero-oligomers were studied by F and H NMR experiments in chloroform.

ATP Drives the Formation of a Catalytic Hydrazone through an Energy Ratchet Mechanism.

An energy ratchet mechanism is exploited for the synthesis of a molecule. In the presence of adenosine triphosphate (ATP), hydrazone-bond formation between an aldehyde and hydrazide is accelerated and the composition at thermodynamic equilibrium is shifted towards the hydrazone. Enzymatic hydrolysis of ATP installs a kinetically stable state, at which hydrazone is present at a higher concentration compared to the composition at thermodynamic equilibrium in the presence of the degradation products of ATP.

Formation of Catalytic Hotspots in ATP-Templated Assemblies.

The self-assembly of surfactant-based structures that rely for their formation on the combination of a thermodynamically controlled and a dissipative pathway is described. Adenosine triphosphate (ATP) acts as a high-affinity template and triggers assembly formation at low surfactant concentrations. The presence of these assemblies creates the conditions for the activation of a dissipative self-assembly process by a weak-affinity substrate.

Persistent ATP-Concentration Gradients in a Hydrogel Sustained by Chemical Fuel Consumption.

We show the formation of macroscopic ATP-concentrations in an agarose gel and demonstrate that these gradients can be sustained in time at the expense of the consumption of a chemical fuel. The approach relies on the spatially controlled activation of ATP-producing and ATP-consuming reactions through the local injection of enzymes in the matrix. The reaction-diffusion system is maintained in a stationary non-equilibrium state as long as chemical fuel, phosphocreatine, is present.

Progressive Local Accumulation of Self-Assembled Nanoreactors in a Hydrogel Matrix through Repetitive Injections of ATP.

Cellular functions are regulated with high spatial control through the local activation of chemical processes in a complex inhomogeneous matrix. The development of synthetic macroscopic systems with a similar capacity allows fundamental studies aimed at understanding the relationship between local molecular events and the emergence of functional properties at the macroscopic level. Here, we show that a kinetically stable inhomogeneous hydrogel matrix is spontaneously formed upon the local injection of ATP.

Duplex folding: tuning the self-assembly of synthetic recognition-encoded aniline oligomers.

One of the challenges in the realization of synthetic oligomers capable of sequence-selective duplex formation is intramolecular folding interaction between complementary recognition units. To assess whether complementary hetero-oligomers can assemble into high fidelity duplex structures, the competing folding equilibria must be carefully considered. A family of recognition-encoded aniline oligomers were assembled reductive amination of dianiline linkers and dialdehyde monomers, which were equipped with either a 2-trifluoromethylphenol or a phosphine oxide H-bond recognition unit.

Supramolecular catalysis by recognition-encoded oligomers: discovery of a synthetic imine polymerase.

All key chemical transformations in biology are catalysed by linear oligomers. Catalytic properties could be programmed into synthetic oligomers in the same way as they are programmed into proteins, and an example of the discovery of emergent catalytic properties in a synthetic oligomer is reported. Dynamic combinatorial chemistry experiments designed to study the templating of a recognition-encoded oligomer by the complementary sequence have uncovered an unexpected imine polymerase activity.

Chemically Fueled Self-Assembly in Biology and Chemistry.

Life is a non-equilibrium state of matter maintained at the expense of energy. Nature uses predominantly chemical energy stored in thermodynamically activated, but kinetically stable, molecules. These high-energy molecules are exploited for the synthesis of other biomolecules, for the activation of biological machinery such as pumps and motors, and for the maintenance of structural order.

Time-gated fluorescence signalling under dissipative conditions.

Precise control over specific functions in the time domain is ubiquitous in biological systems. Here, we demonstrate time-gated fluorescence signalling under dissipative conditions exploiting an ATP-fueled self-assembly process. A temporal ATP-concentration gradient allows the system to pass through three states, among which only the intermediate state generates a fluorescent signal from a hydrophobic dye entrapped in the assemblies.

Nucleotide-Selective Templated Self-Assembly of Nanoreactors under Dissipative Conditions.

Nature adopts complex chemical networks to finely tune biochemical processes. Indeed, small biomolecules play a key role in regulating the flux of metabolic pathways. Chemistry, which was traditionally focused on reactions in simple mixtures, is dedicating increasing attention to the network reactivity of highly complex synthetic systems, able to display new kinetic phenomena.

Two-component assembly of recognition-encoded oligomers that form stable H-bonded duplexes.

A new family of recognition-encoded oligomers that form stable duplexes in chloroform have been prepared. Monomer building blocks composed of dialdehydes functionalised with either a trifluoromethylphenol or phosphine oxide H-bond recognition unit were prepared. The dialdehydes were coupled with diamines by imine formation and then reduction to give homo-oligomers between one and three recognition units in length.

Multifunctional, CD44v6-Targeted ORMOSIL Nanoparticles Enhance Drugs Toxicity in Cancer Cells.

Drug-loaded, PEGylated, organic-modified silica (ORMOSIL) nanoparticles prepared by microemulsion condensation of vinyltriethoxysilane (VTES) were investigated as potential nanovectors for cancer therapy. To target cancer stem cells, anti-CD44v6 antibody and hyaluronic acid (HA) were conjugated to amine-functionalized PEGylated ORMOSIL nanoparticles through thiol-maleimide and amide coupling chemistries, respectively. Specific binding and uptake of conjugated nanoparticles were studied on cells overexpressing the CD44v6 receptor.

Towards hydrophobic carminic acid derivatives and their incorporation in polyacrylates.

Carminic acid, a natural hydrophilic dye extensively used in the food and cosmetic industries, is converted in hydrophobic dyes by acetylation or pivaloylation. These derivatives are successfully used as biocolourants for rubber objects. In this paper, spectroscopic properties of the carminic acid derivatives in dimethyl sulfoxide and in polybutylacrylate are studied by means of photoluminescence and time-resolved photoluminescence decays, revealing a hypsochromic effect due to the presence of bulky substituents as the acetyl or pivaloyl groups.

Detection and identification of designer drugs by nanoparticle-based NMR chemosensing.

Properly designed monolayer-protected nanoparticles (2 nm core diameter) can be used as nanoreceptors for selective detection and identification of phenethylamine derivatives (designer drugs) in water. The molecular recognition mechanism is driven by the combination of electrostatic and hydrophobic interactions within the coating monolayer. Each nanoparticle can bind up to 30-40 analyte molecules.

Multimodal F NMR Dopamine Detection and Imaging with a Nanoparticle-Based Displacement Assay.

Nanoconjugates composed of gold nanoparticles (core diameter=1.9 nm) coated with thioundecyl-d-glucopyranosides and fluorinated phenylboronic acids can detect diol-containing derivatives by means of F NMR spectroscopic analysis. The spectra of nanoconjugate solutions display broad signals due to the fast relaxation of the F nuclei caused by nanoparticle grafting.

C1q-Mediated Complement Activation and C3 Opsonization Trigger Recognition of Stealth Poly(2-methyl-2-oxazoline)-Coated Silica Nanoparticles by Human Phagocytes.

Poly(2-methyl-2-oxazoline) (PMOXA) is an alternative promising polymer to poly(ethylene glycol) (PEG) for design and engineering of macrophage-evading nanoparticles (NPs). Although PMOXA-engineered NPs have shown comparable pharmacokinetics and in vivo performance to PEGylated stealth NPs in the murine model, its interaction with elements of the human innate immune system has not been studied. From a translational angle, we studied the interaction of fully characterized PMOXA-coated vinyltriethoxysilane-derived organically modified silica NPs (PMOXA-coated NPs) of approximately 100 nm in diameter with human complement system, blood leukocytes, and macrophages and compared their performance with PEGylated and uncoated NP counterparts.

Nanoparticle-Based Receptors Mimic Protein-Ligand Recognition.

The self-assembly of a monolayer of ligands on the surface of noble-metal nanoparticles dictates the fundamental nanoparticle's behavior and its functionality. In this combined computational-experimental study, we analyze the structure, organization, and dynamics of functionalized coating thiols in monolayer-protected gold nanoparticles (AuNPs). We explain how functionalized coating thiols self-organize through a delicate and somehow counterintuitive balance of interactions within the monolayer itself and with the solvent.

Minimal Self-Immolative Probe for Multimodal Fluoride Detection.

Two single-molecule, self-immolative fluoride probes, namely tert-butyldimethylsilyl-protected 2- and 4-difluoromethylphenol, are described. Compared to similar systems previously described, the probes are characterized by a simpler structure and straightforward, two-step preparation. Nevertheless, they allow the detection of fluoride ions at micromolar concentration by the naked eye, UV-vis absorption, and fluorescence.

Photoswitchable NIR-Emitting Gold Nanoparticles.

Photo-switching of the NIR emission of gold nanoparticles (GNP) upon photo-isomerization of azobenzene ligands, bound to the surface, is demonstrated. Photophysical results confirm the occurrence of an excitation energy transfer process from the ligands to the GNP that produces sensitized NIR emission. Because of this process, the excitation efficiency of the gold core, upon excitation of the ligands, is much higher for the trans form than for the cis one, and t→c photo-isomerization causes a relevant decrease of the GNP NIR emission.

Synthetic sulfoglycolipids targeting the serine-threonine protein kinase Akt.

The serine-threonine protein kinase Akt, also known as protein kinase B, is a key component of the phosphoinositide 3-kinase (PI3K)-Akt-mTOR axis. Deregulated activation of this pathway is frequent in human tumors and Akt-dependent signaling appears to be critical in cell survival. PI3K activation generates 3-phosphorylated phosphatidylinositols that bind Akt pleckstrin homology (PH) domain.

Synthesis and biological evaluation of arabinose 5-phosphate mimics modified at position five.

A set of new metabolically stable arabinose 5-phosphate analogues possessing phosphate mimetic groups at position 5 was synthesised. Their ability to interact with arabinose 5-phosphate isomerase from Pseudomonas aeruginosa was evaluated by STD-NMR studies. The synthesised compounds were also characterised for their activity in vivo on P.

Arabinose 5-phosphate isomerase as a target for antibacterial design: studies with substrate analogues and inhibitors.

Structural requirements of D-arabinose 5-phosphate isomerase (KdsD, E.C. 5.

Thiol-ene mediated neoglycosylation of collagen patches: a preliminary study.

Despite the relevance of carbohydrates as cues in eliciting specific biological responses, the covalent surface modification of collagen-based matrices with small carbohydrate epitopes has been scarcely investigated. We report thereby the development of an efficient procedure for the chemoselective neoglycosylation of collagen matrices (patches) via a thiol-ene approach, between alkene-derived monosaccharides and the thiol-functionalized material surface. Synchrotron radiation-induced X-ray photoelectron spectroscopy (SR-XPS), Fourier transform-infrared (FT-IR), and enzyme-linked lectin assay (ELLA) confirmed the effectiveness of the collagen neoglycosylation.