Toxic Effect of Fullerene and Its Derivatives upon the Transmembrane β2-Adrenergic Receptors

Abstract

Numerous experiments have revealed that fullerene (C60) and its derivatives can bind to proteins and affect their biological functions. In this study, we explored the interaction between fullerine and the β2-adrenergic receptor (β2AR). The MD simulation results show that fullerene binds with the extracellular loop 2 (ECL2) and intracellular loop 2 (ICL2) of β2AR through hydrophobic interactions and π–π stacking interactions. In the C60_in1 trajectory, due to the π–π stacking interactions of fullerene molecules with PHE and PRO residues on ICL2, ICL2 completely flipped towards the fullerene direction and the fullerene moved slowly into the lipid membrane. When five fullerene molecules were placed on the extracellular side, they preferred to stack into a stable fullerene cluster (a deformed tetrahedral aggregate), and had almost no effect on the structure of β2AR. The hydroxyl groups of fullerene derivatives (C60(OH)X, X represents the number of hydroxyl groups, X = 4, 8) can form strong hydrogen bonds with the ECL2, helix6, and helix7 of β2AR. The hydroxyl groups firmly grasp the β2AR receptor like several claws, blocking the binding entry of ligands. The simulation results show that fullerene and fullerene derivatives may have a significant effect on the local structure of β2AR, especially the distortion of helix4, but bring about no great changes within the overall structure. It was found that C60 did not compete with ligands for binding sites, but blocked the ligands’ entry into the pocket channel. All the above observations suggest that fullerene and its derivatives exhibit certain cytotoxicity.

Molecular Modelling of Ionic Liquids: Perfluorinated Anionic Species with Enlarged Halogen Substitutions

“…[5][6][7][8] Atomistic simulation as a complementary tool to experimental observations has become a popular and powerful instrument in modern chemical research. [9][10][11][12][13][14] Besides validating experimental observations, computational techniques are currently able to provide detailed descriptions of processes of interest at atomic level, and even predicting properties of unexplored species and guiding experimental investigation. [15][16][17][18][19][20] Due to the large size of individual component and the complex composition of the solvent (at least one type of cation and one type of anion), the simulation cell of ionic solvents is often much larger than water boxes in order to eliminate finite-size artifacts.…”

Fullertubes inhibit mycobacterial viability and prevent biofilm formation by disrupting the cell wall

“…The interactions of fullerenes with biological membranes have been well‐studied in other organisms. These findings suggest that fullerenes can aggregate in hydrophobic membranes, causing damage 3,38,39 . This aggregation has primarily been attributed to the π–π stacking resulting from the highly conjugated electronic systems on the surface of fullerenes 38 .…”

“…These findings suggest that fullerenes can aggregate in hydrophobic membranes, causing damage. 3,38,39 This aggregation has primarily been attributed to the π-π stacking resulting from the highly conjugated electronic systems on the surface of fullerenes. 38 The hydrophobic nature of the mycobacterial cell wall possibly predisposes it to fullertube and fullerene insertion and damage.…”

“…3,38,39 This aggregation has primarily been attributed to the π-π stacking resulting from the highly conjugated electronic systems on the surface of fullerenes. 38 The hydrophobic nature of the mycobacterial cell wall possibly predisposes it to fullertube and fullerene insertion and damage. Our scanning electron micrographs of Msm and Mab exposed to fullertubes and fullerenes reveal that the bacilli were damaged after 24 h exposure (Figure 2).…”

Cytotoxicity of Carbon Nanotubes, Graphene, Fullerenes, and Dots

“…The toxicology of carbon nanomaterials was studied for carbon nanotubes [1][2][3][4][5][6][7][8][9][10][11][12][13][14], graphene [15][16][17][18][19][20][21][22][23][24][25][26][27][28], fullerenes [29][30][31][32][33], and dots [34][35][36][37][38]. Most of the work deals with microorganisms, animals, and humans.…”