Interactions between Endohedral Metallofullerenes and Proteins: The Gd@C₆₀–Lysozyme Model

Abstract

Endohedral metallofullerenes (EMFs) have great potential as radioisotope carriers for nuclear medicine and as contrast agents for X-ray and magnetic resonance imaging. EMFs have still important restrictions for their use due to low solubility in physiological environments, low biocompatibility, nonspecific cellular uptake, and a strong dependence of their peculiar properties on physiological parameters, such as pH and salt content. Conjugation of the EMFs with proteins can overcome many of these limitations. Here we investigated the thermodynamics of binding of a model EMF (Gd@C 60 ) with a protein (lysozyme) that is known to act as a host for the empty fullerene. As a rule, even if the shape of an EMF is exactly the same as that of the related fullerene, the interactions with a protein are significantly different. The estimated interaction energy (Δ G binding ) between Gd@C 60 and lysozyme is −18.7 kcal mol –1 , suggesting the possibility of using proteins as supramolecular carriers for EMFs. π–π stacking, hydrophobic interactions, surfactant-like interactions, and electrostatic interactions govern the formation of the hybrid between Gd@C 60 and lysozyme. The comparison of the energy contributions to the binding between C 60 or Gd@C 60 and lysozyme suggests that, although shape complementarity remains the driving force of the binding, the presence of electron transfer from the gadolinium atom to the carbon cage induces a charge distribution on the fullerene cage that strongly affects its interaction with the protein.

Computational insights into the Multi-Diels-Alder reactions of neutral C60 and its Li+ encapsulated analogue: A DFT study

“…The functionalization of the fullerene cages including polymeric derivatives has sorted out some of the problems associated with low solubility and miscibility of corresponding C 60 systems [11 ] .In the past decades, a large number of fullerene derivatives have been synthesized and characterized with desirable applications [12][13][14][15] , such as photoelectric conversion [16 ] , magnetic resonance imaging [17 ] , cancer therapy [18 ] and so on. Among the experimental and theoretical methods implemented for fullerene modifications, Diels-Alder cycloaddition reaction [19][20][21][22][23] on the fullerene surface and encapsulation of atom/metal cluster/small molecules into the hollow cage of fullerene [24][25][26][27] are drawing great scientific attention. In this aspect, selective encapsulation of fullerene cages is also observed to offer one of the key techniques in their purification [28 ] .…”

Fullerenes against COVID-19: Repurposing C60 and C70 to Clog the Active Site of SARS-CoV-2 Protease

“…Using a docking protocol able to identify the fullerene binding pockets of proteins [ 18 , 19 , 49 , 50 , 51 , 52 , 53 , 54 ], we docked the C 60 in SARS-CoV-2 M pro . C 60 binds on the substrate binding pocket of M pro ( Figure 2 B).…”

Incorporation of Molecular Nanoparticles Inside Proteins: The Trojan Horse Approach in Theranostics

“…In these systems, the intrafullerene electron transfer from the encaged metal atom(s) to the fullerene cage, induces a net charge distribution on the fullerene cage that strongly affects their interaction with proteins. In this case the contribution of electrostatic interactions, which is negligible for pristine fullerenes, becomes important in the binding to a protein. , …”