Cyclooctyne [60]fullerene hexakis adducts: a globular scaffold for copper-free click chemistry

The synthesis of a new highly symmetric hexakis adduct of C60 appended with 12 cyclooctyne moieties has been carried out. This compound has been used for the copper-free strain-promoted cycloaddition reaction to a series of azides with excellent yields.This strategy for the obtention of clicked adducts of [60]fullerene is of special interest for biological applications

Supramolecular Complexation of Carbon Nanostructures by Crown Ethers

Since their discovery, crown ethers as well as the most recent carbon nanostructures, namely fullerenes, carbon nanotubes, and graphene, have received a lot of attention from the chemical community. Merging these singular chemical structures by noncovalent forces has provided a large number of unprecedented supramolecular assemblies with new geometric and electronic properties whose more representative examples are presented in this Synopsis organized according to the different nature of the carbon nanostructures

Cyclooctyne [60]fullerene hexakis adducts: a globular scaffold for copper-free click chemistry

The synthesis of a new highly symmetric hexakis adduct of C60 appended with 12 cyclooctyne moieties has been carried out. This compound has been used for the copper-free strain-promoted cycloaddition reaction to a series of azides with excellent yields. This strategy for the obtention of clicked adducts of [60]fullerene is of special interest for biological applicationsEuropean Research Council ERC-320441-Chir all carbonMinisterio de Economía y Competitividad CTQ2014-52045-R, CTQ2014-52328-PComunidad Autónoma de Madrid S2013/MIT-28

A Peptide/Fullerene Hybrid for Multivalent Recognition of E-Selectin

Molecular recognition through ligand-receptor interactions is a very important mechanism for metastatic processes. Among all of them, multivalent protein-carbohydrate interactions play a fundamental role in tumor cell-endothelial cell recognition processes. In particular, the interaction between SLex and SLea expressed in circulating tumor cells and proteins of the family of selectins, overexpressed in endothelial cells. Unlike tumor cells, vascular endothelial cells receptors are a stable target not subjected to genetic modifications. In addition, the elimination of a single endothelial cell involves the death of hundreds of tumor cells. Targeting endothelial receptors cells offers a high potential in tumor diagnosis and therapy. SLex and SLea are the natural ligands of selectins, but their complicated chemical synthesis and their low affinity for selectins made difficult to continue with their development. Recently, through "phase display" it was identified a simple peptide with a linear sequence of seven amino acids (Ile-Glu-Leu-Leu-Gln-Ala-Arg) called IELLQAR that interacts specifically with selectins. IELLQAR is a very simple compound, which can be synthesized using SPPS. IELLQAR can be functionalized and easily conjugated to fullerenes for its multivalent presentation. In addition, it can be combined with diagnostic and therapeutic agents. References [1] Smith, B. A. H.; Bertozzi, C. Nat. Rev. Drug Discov. 2021, 20, 217.243. [2] Fukuda, M. N. et al. Cancer Res. 2000, 60, 450-456 [3] (a) Ramos-Soriano, J. et al. Chem. Commun. 2016, 52, 10544-10546; (b) Ramos-Soriano, J. et al. J. Org. Chem. 2018, 83, 1727-1736.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tec

Conjugated Porphyrin Dimers: Cooperative Effects and Electronic Communication in Supramolecular Ensembles with C60

Two new conjugated porphyrin-based systems (dimers 3 and 4) endowed with suitable crown ethers have been synthesized as receptors for a fullerene-ammonium salt derivative (1). Association constants in solution have been determined by UVvis titration experiments in CH2Cl2 at room temperature. The designed hosts are able to associate up to two fullerene-based guest molecules and present association constants as high as 5 × 108 M‒1 . Calculation of the allosteric cooperative factor for supramolecular complexes [3·12] and [4·12] showed a negative cooperative effect in both cases. The interactions accounting for the formation of the associates are based, firstly, on the complementary ammonium-crown ether interaction and, secondly, on the π−π interactions between the porphyrin rings and the C60 moieties. Theoretical calculations have evidenced a significant decrease of the electron density in the porphyrin dimers 3 and 4 upon complexation of the first C60 molecule, in good agreement with the negative cooperativity found in these systems. This negative effect is partially compensated by the stabilizing C60-C60 interactions that take place in the more stable syn-disposition of [4·12]

Antiviral Activity of Self‐Assembled Glycodendro[60]fullerene Monoadducts

A series of amphiphilic glycodendro[60]fullerene monoadducts were efficiently synthesized using the CuAAC “click chemistry” approach. These glycodendrofullerenes can self‐assemble in aqueous media, in a process favoured through π‐ π interactions between the [60]fullerene moieties. This aggregation process leads to big and well‐defined compact micelles with a uniform size and spherical‐shape. The supramolecular aggregate was characterized using electronic microscopy (SEM and TEM), light scattering methods (DLS) and X‐ray methodologies (SAXS and XRD). The antiviral efficiency of these aggregates has been tested in an experimental infection assay using Ebola virus glycoprotein (EboGP) pseudotyped viral particles on Jurkat cells overexpressing DC‐SIGN and it is observed an improvement of the IC50 value with respect to other systems endowed with a higher number of carbohydrate ligands

Enhanced thermoelectricity in metal−[60]fullerene−graphene molecular junctions

The thermoelectric properties of molecular junctions consisting of a metal Pt electrode contacting [60]fullerene derivatives covalently bound to a graphene electrode have been studied by using a conducting-probe atomic force microscope (c-AFM). The [60]fullerene derivatives are covalently linked to the graphene via two meta-connected phenyl rings, two para-connected phenyl rings, or a single phenyl ring. We find that the magnitude of the Seebeck coefficient is up to nine times larger than that of Au-C60-Pt molecular junctions. Moreover, the sign of the thermopower can be either positive or negative depending on the details of the binding geometry and on the local value of the Fermi energy. Our results demonstrate the potential of using graphene electrodes for controlling and enhancing the thermoelectric properties of molecular junctions and confirm the outstanding performance of [60]fullerene derivativesThis work has been supported by the European Commission through FP7 ITN MOLESCO (Project Number 606728), the (MAD2D-CM)-UCM1-MRR project and through the EC H2020 FET Open Project Grant Agreement Number 767187 “QuIET”. The authors acknowledge support from the Spanish Ministry of Science and Innovation MCIN (Projects PID2020-114653RB-I00, PID2020-115120GB-I00, Centro de Excelencia Severo Ochoa SEV-2016-0686). L.R.-G. acknowledges support from Spanish MECD (Grant No. FPU14/03368) and, with N.A., funding from the Education and Research Council of the Comunidad de Madrid and the European Social Fund (ref. PEJD-2019-POST/IND-16353

Topological and Multivalent Effects in Glycofullerene Oligomers as EBOLA Virus Inhibitors

The synthesis of new biocompatible antiviral materials to fight against the development of multidrug resistance is being widely explored. Due to their unique globular structure and excellent properties, [60]fullerene-based antivirals are very promising bioconjugates. In this work, fullerene derivatives with different topologies and number of glycofullerene units were synthesized by using a SPAAC copper free strategy. This procedure allowed the synthesis of compounds 1–3, containing from 20 to 40 mannose units, in a very efficient manner and in short reaction times under MW irradiation. The glycoderivatives were studied in an infection assay by a pseudotyped viral particle with Ebola virus GP1. The results obtained show that these glycofullerene oligomers are efficient inhibitors of EBOV infection with IC50s in the nanomolar range. In particular, compound 3, with four glycofullerene moieties, presents an outstanding relative inhibitory potency (RIP). We propose that this high RIP value stems from the appropriate topological features that efficiently interact with DC-SIGN

Synthesis of giant globular multivalent glycofullerenes as potent inhibitors in a model of Ebola virus infection

The use of multivalent carbohydrate compounds to block cell-surface lectin receptors is a promising strategy to inhibit the entry of pathogens into cells and could lead to the discovery of novel antiviral agents. One of the main problems with this approach, however, is that it is difficult to make compounds of an adequate size and multivalency to mimic natural systems such as viruses. Hexakis adducts of [60]fullerene are useful building blocks in this regard because they maintain a globular shape at the same time as allowing control over the size and multivalency. Here we report water-soluble tridecafullerenes decorated with 120 peripheral carbohydrate subunits, so-called ‘superballs’, that can be synthesized efficiently from hexakis adducts of [60]fullerene in one step by using copper-catalysed azide–alkyne cycloaddition click chemistry. Infection assays show that these superballs are potent inhibitors of cell infection by an artificial Ebola virus with half-maximum inhibitory concentrations in the subnanomolar range