SWCNTs, MWCNTs, and SWCNHs have been employed as virus-mimicking nanocarbon platforms for the multivalent presentation of carbohydrates in an artificial Ebola virus infection model assay. These carbon nanoforms have been chemically modified by the covalent attachment of glycodendrons and glycofullerenes using the CuAAC "click chemistry" approach. This modification dramatically increases the water solubility of these structurally different nanocarbons. Their efficiency in blocking DC-SIGN-mediated viral infection by an artificial Ebola virus has been tested in a cellular experimental assay, finding that glycoconjugates based on MWCNTs functionalized with glycofullerenes are potent inhibitors of viral infection.

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.[60]Fullerene hexakis adducts with Th symmetry constitute an attractive class of compounds that allow the globular disposition of substituents around the C60 core. 1 These compounds have attracted much attention in the last recent years, both in the areas of materials science and biomedicine. Thus, some of them present liquid crystal behavior, 2 have been employed for the study of electronic and energy transfer processes, 3 as organic connectivity centers for the synthesis of Metal Organic Frameworks (MOFs), 4 or as catalysts. 5 On the other hand, in the area of biological applications, their activity has been tested in different fields showing interesting properties and good biocompatibility. Hexakis adducts of [60]fullerene have been tested as gene transfection vectors, 6 multiplying units for photodynamic therapy, 7 glycosidase and glycosyltransferase inhibitors, 8 or efficient antibacterial 9 or antiviral systems. 10 The synthesis of these adducts was first studied by Hirsch by the one-pot addition of malonates templated by 9,10-dimethylanthracene 11 and later modified by Sun. 12 However, these procedures are often limited by the size of the malonates, as the steric aspects limit the yield of the reaction. To overcome this drawback, Nierengarten proposed the employment of an azide appended malonate to obtain a clickable hexakis adduct of C60 to effectively allow the covalent functionalization of [60]fullerene by Cu(I) alkyne-azide cycloaddition (CuAAC) reaction. 13 Lately, Nierengarten and we described the 12-alkyne modified hexakis adduct of [60]fullerene and its use in the click chemistry addition of azides and alkynes. 14 This effective reaction requires, however, the use of copper (I) as catalyst, which involves a subsequent purification step for the removal of copper, especially with those materials for bio-medical applications, owing to its high cytotoxicity. This step can be hampered by the presence in the final products of functional groups, and even the triazole rings themselves, capable of binding copper, thus limiting their biological applications. 15 A strategy to avoid this purification step is to employ of strain promoted alkyne-azide cycloaddition (SPAAC) click reaction. This reaction, developed by Bertozzi and coworkers, 16 consists of the reaction of strained cyclooctynes with azides and has received considerable attention owing to its simplicity and faster reaction rates, avoiding the use of a metal as catalyst. As it does not require the use of copper, it has especial relevance for biological applications. In the present communication we report the synthesis of a new hexakis adduct of [60]fullerene substituted with twelve c...

The re-emergence of chikungunya virus (CHIKV) is a serious global health threat. CHIKV is an alphavirus that is transmitted to humans by Aedes mosquitoes; therefore, their wide distribution significantly contributes to the globalization of the disease. Unfortunately, no effective antiviral drugs are available. We have identified a series of 3-aryl-[1,2,3]triazolo[4,5- d]pyrimidin-7(6 H)-ones as selective inhibitors of CHIKV replication. New series of compounds have now been synthesized with the aim to improve their physicochemical properties and to potentiate the inhibitory activity against different CHIKV strains. Among these newly synthesized compounds modified at position 3 of the aryl ring, tetrahydropyranyl and N- t-butylpiperidine carboxamide derivatives have shown to elicit potent antiviral activity against different clinically relevant CHIKV isolates with 50% effective concentration (EC) values ranging from 0.30 to 4.5 μM in Vero cells, as well as anti-CHIKV activity in human skin fibroblasts (EC = 0.1 μM), a clinically relevant cell system for CHIKV infection.

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.

Suitably engineered molecular systems exhibiting triplet excited states with very long lifetimes are important for high‐end applications in nonlinear optics, photocatalysis, or biomedicine. We report the finding of an ultra‐long‐lived triplet state with a mean lifetime of 93 ms in an aqueous phase at room temperature, measured for a globular tridecafullerene with a highly compact glycodendrimeric structure. A series of three tridecafullerenes bearing different glycodendrons and spacers to the C60 units have been synthesized and characterized. UV/Vis spectra and DLS experiments confirm their aggregation in water. Steady‐state and time‐resolved fluorescence experiments suggest a different degree of inner solvation of the multifullerenes depending on their molecular design. Efficient quenching of the triplet states by O2 but not by waterborne azide anions has been observed. Molecular modelling reveals dissimilar access of the aqueous phase to the internal structure of the tridecafullerenes, differently shielded by the glycodendrimeric shell.