Gene delivery with polycationic fullerene hexakis-adducts

Sigwalt, David; Holler, Michel; Iehl, Julien; Nierengarten, Jean‐François; Nothisen, Marc; Morin, Emmanuelle; Rémy, Jean-Serge

doi:10.1039/c0cc05783e

Cited by 74 publications

(55 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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.…”

mentioning

confidence: 99%

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

et al. 2016

View full text Add to dashboard Cite

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...

show abstract

mentioning

confidence: 99%

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

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Apart from their unique architecture, hexakis adducts derived from the functionalization of the six e double bonds of C 60 are very attractive structures in the synthesis of functional fullerene materials. [45][46][47][48][49][50] The results of the present study lead to the conclusion that the [4+2] cycloaddition of orthoquinodimethanes with the C 60 is a kinetically controlled reaction. The in situ thermal generation of ortho-quinodimethanes from the corresponding 1,2-bis(bromomethyl)benzene precursors requires high temperatures (110 o C) and is followed by the fast, irreversible [4+2] cycloaddition reaction with C 60 to afford thermally stable products.…”

Section: Scheme 6 Synthesis Of Macrocyclic Tether 21mentioning

confidence: 63%

A study towards the regioselective synthesis of the e,e,e trisadduct of C60 via the [4+2] Diels-Alder reaction with tethers bearing ortho-quinodimethane precursors

Ioannou¹,

Chronakis²

2015

Arkivoc

View full text Add to dashboard Cite

The regioselective synthesis of an e,e,e trisadduct of C 60 via the Diels-Alder reaction with orthoquinodimethanes has been attempted employing the tether-directed remote functionalization approach. Opened-structure tether 10 and macrocyclic tethers 16 and 21 were synthesized for this purpose. The functionalization of C 60 afforded inseparable mixtures of regiomeric trisadducts and the regioselective formation of the e,e,e trisadduct was not feasible even when the more preorganized tethers 16 and 21 were employed. The in situ thermal generation of orthoquinodimethanes from the 1,2-bis(bromomethyl)benzene precursors requires high temperatures and is followed by fast, irreversible cycloaddition with C 60 to afford thermally stable products, which prevents the achievement of high regioselectivities.

show abstract

“…[5] A recent extension to the fullerenebased gene delivery systems in the form of a polycationic [60]fullerene hexakis-adduct has been identified. [6] We have recently reported on the synthesis of a globular heptafullerene that is the largest well-defined and monodisperse polyelectrolyte known to date. [7] This heptafullerene consists of one central and six peripheral fullerene building to 12+.…”

Section: Introductionmentioning

confidence: 99%

“…[11,12] However, the generation of quasi-molecular ions of certain C 60 hexakisadducts has proven difficult. Nierengarten and co-workers encountered several examples [6,13] in which the target molecule was found too unstable for analysis by soft ionization methods, including electrospray ionization (ESI). Problem cases that proved inappropriate for analysis included, for example, hexakis adducts with sugar termini [13] or with preformed cations within the ligands.…”

Section: Introductionmentioning

confidence: 99%

Formation of Highly Charged Quasi‐Molecular Ions of a Polycationic [60]Fullerene Hexakis‐Adduct and Their Fragmentation Behavior in the Gas Phase

Nye

Wasserthal

et al. 2015

Eur J Org Chem

View full text Add to dashboard Cite

A novel polycationic [60]fullerene hexakis-adduct has been synthesized and investigated by electrospray ionization and tandem mass spectrometry. The polycationic ligand system comprises 12 pre-formed positive charges, compensated in the neutral molecule by bromide anions. Stable quasi-molecular cations were obtained through the release of the anionic counter ions covering a charge-state envelope from 3+

show abstract

Gene delivery with polycationic fullerene hexakis-adducts

Abstract: Polyplexes prepared from DNA and globular compact polycationic derivatives constructed around a fullerene hexakis-adduct core have shown remarkable gene delivery capabilities.

Cited by 74 publications

References 37 publications

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

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

A study towards the regioselective synthesis of the e,e,e trisadduct of C60 via the [4+2] Diels-Alder reaction with tethers bearing ortho-quinodimethane precursors

Formation of Highly Charged Quasi‐Molecular Ions of a Polycationic [60]Fullerene Hexakis‐Adduct and Their Fragmentation Behavior in the Gas Phase

Contact Info

Product

Resources

About