The synthesis and biological properties of mono(amino acid) derivatives of fullerenes (MAADFs) as well as hybrid nanostructures (HNSs) on their basis are reviewed. It is shown that these derivatives are highly effective non-toxic compounds in various fields of medicine and can be further used as potential drugs.

Synthesis, spectral properties, and photodynamic activity of water-soluble amino acid fullerene C-60 derivatives (AFD) and four original AFD-PPa dyads, obtained by covalent addition of dye pyropheophorbide (PPa) to AFD, were studied. In aqueous solution, these AFD-PPa dyads form nanoassociates as a result of self-assembly. In this case, a significant change in the absorption spectra and strong quenching of the dye fluorescence in the structure of the dyads were observed. A comparison of superoxide or singlet oxygen generation efficiency of the studied compounds in an aqueous solution showed the photodynamic mechanism switching from type II (singlet oxygen generation of the native dye) to I type (superoxide generation of dyads). All dyads have pronounced phototoxicity on cells Hela with IC50 9.2 mu M, 9.2 mu M, 12.2 mu M for dyads Val-C-60-PPa, Ala-C-60-PPa and Pro-C-60-PPa, respectively. Such facilitation of type I photodynamic mechanism could be perspective against hypoxic tumors. (C) 2021 Published by Elsevier B.V.

The kinetic characteristics, mechanisms of activity, and relationship between the antioxidant activity and the molecular and supramolecular structure of fullerene C 60 and some of its N -monosubstituted amino acid derivatives have been studied. The introduction of an amino acid substituent in the C 60 fullerene molecule led to an increase in its antiradical activity in the free radical oxidation of a water-soluble target (fluorescein). The mechanism of the antioxidant activity of amino acid derivatives of fullerene is not associated with the hydrogen atom transfer, electron donation, or catalysis of peroxide decomposition. It was demonstrated that the structure of the amino acid substituent does not affect the antiradical properties, which are thus determined only by the effective total surface area of ​​the nanoparticles of the fullerene C 60 derivatives and increase when their size decreases. This surface can be characterized as nanowalls on which the radical death occurs. A change in the concentration of the compounds in solution does not lead to a change in the relative antiradical activity and hence in the nanoparticle size. The results of this study are important for understanding the biological activity of this group of compounds.

Growth-stimulating effects of water-soluble nanoparticles of N-substituted monoamino-acid derivatives of fullerene C60 (L- and D-alanine, L- and D-valine, L- and D-aspartic acid, β-alanine, and γ-aminobutyric and ε-aminocaproic acids in potassium salt form) were investigated. It was found that the nanoparticle size and relative antiradical activity of fullerene derivatives were factors that influence such physiological parameters of field peas as seed germination rate, germination energy, and root growth capacity. It was shown that the relative antiradical activity of nanoparticles in the selected group of compounds was determined by the total surface area of the nanoparticles regardless of the structure of the amino-acid substituent. The possibility of using amino-acid derivatives of fullerene as effective growth stimulating substances has been demonstrated. A dose-dependent effect of N-(monohydrofullerenyl)-D-alanine potassium salt in a concentration range of 10–9–10–11 M on the seed-germination rate and germination energy of field peas has been demonstrated.

Amino acid derivatives of C60 fullerene were studied by solid-state NMR spectroscopy. The spectroscopic data given in this work suggest that the compounds under study are derivatives of C60 fullerene and corresponding amino acids. The fullerene core is attahced to the amino acids via the amino group.

A comparative study of the relative antioxidant activity (RAA) of fullerene С 60 and its amino acid derivatives is performed via amperometry and fluorimetry. The sizes of nanoparticles in the corresponding colloidal solutions are determined via dynamic light scattering (photon correlation spectroscopy) to study the effect the steric factors of the investigated compounds have on the magnitude of the RAA. Data are subjected to statistical correlation regression analysis using results obtained for the RAA dependence of fullerene С 60 and salt forms of its acid derivatives on the corresponding sizes of nanoparticles in colloidal aqueous solutions. A close negative (inverse) correlation is identified between the size of nanoparticles in a solution and their antioxidant properties, with a pronounced synergic effect related to the influence of both chemical structure of the studied compounds and their structural organization in colloid solution. It is found that the structure of a substituent in a molecule of amino acid derivative of fullerene С 60 also influences the size of the forming nanoparticles. At the same time, reductive properties of amino acid derivatives of fullerene С 60 are generally determined by the electron effects of substituents.

Free fluorescence spectra in solution and surface-enhanced Raman scattering (SERS) and surface enhanced fluorescence (SEF) spectra of chlorin e6 and water-soluble covalent fullerene–chlorin dyads have been studied. It has been demonstrated that chlorin e6 and covalent fullerene–chlorin dyads have similar characteristic SERS spectra. The fullerene–chlorin dyads show a pronounced SEF signal, while native chlorin e6 has no fluorescence on surface, which is consistent with the theory predicting an inverse dependence of the SEF intensity on the free fluorescence quantum yield. The concentration dependence of the SEF intensity is linear for the dyads in the range 0.1–2.0 μmol/L. These effects allow one to determine, with high sensitivity, the content of fullerene–chlorin dyads with a low quantum yield of free fluorescence in solutions, which opens wide opportunities for study of biological properties of fullerene–chlorin dyads and their applications in medicine.

The effect of fullerene-containing amphiphilic (co)polymers of N-vinylpyrrolidone (C60/PVP) differed in composition and topology of the polymer chains on the membrane structure of phosphatidylcholine liposomes was studied. Using the method of fluorescent probes it was found that the C60/PVP structures under study are localized in the phosphatidylcholine membrane in the region of glycerol fragments and fatty acid chains of phospholipids. The C60/PVP copolymers form complexes with 2,7-dibromoproflavin and pyrene probes. The effective equilibrium constants of the probe–C60/PVP complexes in aqueous solutions and in the liposome membrane were determined. It is most likely that the fullerene-containing (co)polymers of N-vinylpyrrolidone form complexes not only with fluorescent probes but also with phospholipids of the liposome membrane, which reduces the stability of the probe–C60/PVP complex.

The membranotropic and relaxation properties of novel water-soluble gadolinium endometallofullerene derivatives (EMFD) were studied. Localization of EMFD in membranes and EMFD-induced changes in the membrane structure were determined by measuring the emission quenching of pyrene as a fluorescent probe. It was demonstrated that EMFD efficiently interact with pyrene molecules in model membranes, thus changing their microviscosity. Pulsed 1H NMR experiments revealed that the hydroxylated endometallofullerene Gd@C82(OH)∼30 has the highest relaxivity (R 1 = 7.390 L mol−1 s−1) among the test EMFD and that its efficiency is 3.6 times that of the commercial MRI contrast agent Magnevist. The data obtained suggest that these EMFD are promising for use as low-toxicity contrast agents for magnetic resonance imaging.