Graphene oxide (GO) nanoparticles, due to their favorable water solubility, compared to graphene (GA), are a hot research topic in biomedical and pharmaceutical research. However, GO clinical translation may be complicated by its high surface/volume ratio enhancing the interaction with human blood components. In fact, GO’s bi-dimensional nature and strong negative charge may lead to severe biological effects, such as thrombogenicity and immune cell activation. This study explores the impact of further GO surface chemical modulation on major adverse effects: blood plasma coagulation and hemolysis. To this aim, we refined GO nanoparticles by fine-tuned reduction chemistry, esterification and introduction of negative or positive charges. With this approach, we were able to mitigate plasma coagulation and hemolysis at variable degrees and to identify GO derivatives with improved biocompatibility. This opens the door to the progress of graphene-based nanotheranostic applications.

The development of active, selective, and durable (photo)electrocatalytic hybrid systems by combining molecular catalysts and semiconductor substrates is crucial for efficiently converting solar light into high-value products. Herein, a one-step synthesis method to obtain carbon nitride (CN) nanosheets, which allows the direct covalent polymerization with molecular catalysts, was developed. Copper-porphyrin (CuPor) units were embedded in the CN structure as a case-study. The single and hybrid materials were fully characterized by combining microscopic and spectroscopic techniques and tested as (photo)electrocatalysts for the CO2 reduction reaction (CO2RR) in aqueous solution. Experimental evidence confirmed an effective boost of the CN photoelectrocatalytic activity by introducing the CuPor units. Formate was identified as the only CO2RR product on both CuPor and CuPor-CN, simultaneously with hydrogen from the competitive hydrogen evolution reaction. However, the formate/hydrogen ratio was higher when the hybrid material was used as catalyst, suggesting a synergetic effect between CuPor and CN, that favors the CO2RR and hinders the HER. In addition, the stability of the CuPor units in the CN matrix under catalytic conditions was studied by in situ X-ray absorption. No changes of the Cu porphyrin structure or formation of copper clusters/nanoparticles was observed as a function of the applied potential nor after an accelerated ageing treatment, suggesting that the CN matrix is able to stabilize the Cu sites avoiding their agglomeration.

In this protocol, we describe how to perform the photo-isomerization of cyclic peptides containing an unsaturated β-amino acid. This process triggers the formation or disassembly of cyclic peptide nanotubes under appropriate light irradiation. Specifically, we start by describing the solid-phase synthesis of the cyclic peptide component. We also present a technique for performing isomerization studies in solution and how to extend it to microfluidic aqueous droplets.For complete details on the use and execution of this protocol, please refer to Vilela-Picos et al.1

Cyclic peptides containing a 0-unsaturated amino acid are programmed to switch between monomeric form and self-assembled peptide nanotube structures upon light irradiation. The process is triggered by the reversible E -Z isomerization of the unsaturated 0-amino acid that forces the peptide to swap from the folded (unassembled) to the flat conformation (assembled). The process is also tuned by the pH media, which provides a double checkpoint control in the molecular assembly of the peptide nanotubes. The light driven assembly process can be triggered in a confined environment, and the resulting nanotubes allow the inter-vesicle communication, providing droplets with self-fusiogenic properties.

Proteins reconfigure their 3D-structure, and consequently their function, under the control of specific molecular interactions that sense, process and transmit information from the surrounding environment. When this fundamental process is hampered, many pathologies occur as in the case of protein misfolding diseases. In this work, we follow the early steps of α-synuclein (aS) aggregation, a process associated with Parkinson's disease etiopathogenesis, that is promptly promoted by a light-mediated binding between the protein and a photoactive foldamer. The latter can switch between two conformations, one of which generates supramolecular fibrillar seeds that act as molecular templates able to induce a fast β-sheet transition for aS monomers that successively undergo fibrillar polymerization. The proposed method represents a powerful tool to study protein aggregation relevant to misfolding diseases in a controlled and inducible system.

We report a catalytic foldamer in which a fumaramide chromophore links a Ser residue to a helical domain that contains within its sequence the residues His and Asp. Photoisomerization of the fumaramide chromophore (with E geometry) to the corresponding maleamide (with Z geometry) brings together a 'catalytic triad' of Ser, His, and Asp, triggering esterase activity that is absent in the fumaramide isomer. The fumaramide/maleamide linker thus acts as a light-sensitive switchable cofactor for activation of catalytic activity in short foldamers.

We report the study of two-dimensional graphitic carbon nitride (GCN) functionalized with copper single atoms as a catalyst for the reduction of CO 2 (CO2RR). The correct GCN structure, as well as the adsorption sites and the coordination of the Cu atoms, was carefully determined by combining experimental techniques, such as X-ray diffraction, transmission electron microscopy, X-ray absorption, and X-ray photoemission spectroscopy, with DFT theoretical calculations. The CO2RR products in KHCO 3 and phosphate buffer solutions were determined by rotating ring disk electrode measurements and confirmed by 1 H-NMR and gas chromatography. Formate was the only liquid product obtained in bicarbonate solution, whereas only hydrogen was obtained in phosphate solution. Finally, we demonstrated that GCN is a promising substrate able to stabilize metal atoms, since the characterization of the Cu-GCN system after the electrochemical work did not show the aggregation of the copper atoms.

In this work, we studied and discussed a relevant aspect of peptide science, strictly related to the scientific production of Prof. Louis A. Carpino who passed away in early 2019. Specifically, we carried out a statistical survey on the significant 3D-structural parameters (bond lengths, bond angles, and torsion angles) of the currently extensively used 9-fluorenylmethyloxycarbonyl (Fmoc) a-amino protecting group introduced by Carpino in peptide synthesis. In this compilation, we considered all 131 X-ray diffraction structures available in the literature on amino acid / linear peptide derivatives and Fmoc-labeled amines. Both Fmoc secondary and tertiary urethane functionalities were examined and separately analyzed.

The burgeoning interest raised by Carbon Dots (CDs) is an epitome of the urgency of developing green and biocompatible alternatives to inorganic and hybrid quantum dots. The fast-paced development ...

Peptides are well-known to play a fundamental therapeutic role and to represent building blocks for numerous useful biomaterials. Stabilizing their active 3D-structure by appropriate modifications remains, however, a challenge. In this study, we have expanded the available literature information on the conformational propensities of a promising backbone change of a terminally blocked δ-amino acid residue, a dipeptide mimic, by replacing its central amide moiety with an (E) Cβ═Cγ alkene unit. Specifically, we have examined by DFT calculations, X-ray diffraction in the crystalline state, and FT-IR absorption/NMR spectroscopies in solution the extended vs folded preferences of analogues of this prototype system either unmodified or possessing single or multiple methyl group substituents on each of its four −CH2-CH═CH-CH2– main-chain carbon atoms. The theoretical and experimental results obtained clearly point to the conclusion that increasing the number of adequately positioned methylations will enhance the preference of the original sequence to fold, thus opening interesting perspectives in the design of conformationally constrained peptidomimetics.

Peptide sequences functionalized with primary amines at the N- and C-terminus are able to induce the aggregation of gold nanoparticles in ethanol as a consequence of their folding into a helical conformation. Random coil peptides are unable to induce such an aggregation process. Aggregation can be monitored spectrophotometrically by following the shift of the surface plasmon resonance (SPR) band of the nanoparticles and is confirmed by transmission electron microscopy and dynamic light scattering analyses. Partial denaturation of the peptides results in diminished cross-linking ability. The helicity parameter theta(222)/theta(208) correlates fairly well with the shift of the SPR band to longer wavelengths, supporting the relationship between the amount of helical content of a peptide sequence and its ability to induce aggregation.

Systems in which an external stimulus elicits a response through some sort of modification at the molecular or supramolecular level bear potential for the development of smart materials and devices. This work describes a versatile synthetic approach suitable for the stepwise incorporation of multiple, even consecutive, units of the simplest Cα,β-unsaturated β-amino acid, (E/Z)-3-aminoprop-2-enoic acid, in peptide-based foldamers. The properties of these, including photoinduced E/Z isomerizations, were investigated.

A set of four organogelators from an alpha-amino acid derivative to a tetrapeptide, covalently linked to an acetylenic moiety, was studied in terms of polymerization efficiencies to afford peptide polyacetylenes and polydiacetylenes. Peptides were designed to improve the organogelator behavior via formation of intermolecular H-bonding-mediated beta-sheet networks as a function of their main-chain length. The polymerization experiments were run under appropriate conditions for the various monomers with the aim at elucidating how the monomer self-assembly process might influence polymer formation. Starting compounds and their corresponding polymers were characterized by a variety of spectroscopic and microscopic techniques.

AbstractA simple, unsaturated, E–Z photoisomerizable β‐amino acid, (Z)‐3‐aminoprop‐2‐enoic acid, has been introduced into peptide foldamers through a one‐pot chemical coupling, based on Pd/Cu‐catalyzed olefin oxidative amidation, between two peptide segments carrying, respectively, a ‐Gly‐NH2 residue at the C‐terminus and an acryloyl group at the N‐terminus. Reversible conversion between the Z and E configurations of the 3‐aminoprop‐2‐enoic linkage was achieved photochemically. A crystallographic analysis on two model compounds shed light on the consequences, in terms of 3D structure and self‐association properties, brought about by the different configuration of the unsaturated linkage. As a proof of concept, E–Z photoisomerization of a 3‐aminoprop‐2‐enoic acid residue, inserted as the junction between two conformationally distinct peptide domains (one helical while the other β‐sheet promoter), allowed supramolecular self‐association to be reversibly turned on/off.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.