Influence of OH Groups of Hydroxyfullerene on the Mechanism of Its Complex Formation with the Lys-2Gly Peptide Dendrimer

Fullerenes are promising drug candidates, but they are virtually insoluble in water. Surface hydroxylation of fullerenes and their encapsulation in nanocarrier systems, such as dendrimers, can be used to increase their solubility. However, hydroxylated fullerene (hydroxyfullerene, fullerenol) has lower bioactivity than fullerene. Our previous research showed that fullerene is encapsulated by the Lys-2Gly dendrimer. This study demonstrates, for the first time, that hydroxylated fullerenes C60(OH)n with n = 12, 24, 36 form complexes with the same dendrimer. All these fullerenols are encapsulated near the dendrimer’s center, similar to fullerene. Surprisingly, the complex’s structure remains stable even at the maximal hydroxylation (n = 36), despite a significant reduction in hydrophobicity of the fullerene surface. We demonstrated that this stability results from an increase in the number of hydrogen bonds between the dendrimer and the fullerenol with increasing n. Thus, we established that the mechanism of complex formation changes from hydrophobic interactions to hydrogen bonding as hydroxylation increases. This means that simultaneous partial hydroxylation of the fullerene and encapsulation within a water-soluble dendrimeric nanocarrier enhances its solubility in water. This combined approach enables the use of less hydroxylated fullerene derivatives to achieve desired solubility while maintaining higher biological activity.