Fullerene Amino Acid Derivatives Research Articles

Mechanism of the Antioxidant Activity and Structure\u2013Activity Relationship of N-Monosubstituted Amino Acid Derivatives of Fullerene \u042160

The kinetic characteristics, mechanisms of activity, and relationship between the antioxidant activity and the molecular and supramolecular structure of fullerene C60 and some of its N-monosubstituted amino acid derivatives have been studied. The introduction of an amino acid substituent in the C60 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 C60 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.

New Plant Growth Stimulants Based on Water-Soluble Nanoparticles of N-Substituted Monoamino-Acid Derivatives of Fullerene C60 and the Study of their Mechanisms of Action

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 e-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 modified [70] fullerene derivatives with high radical scavenging activity as promising bodyguards for chemotherapy protection

Despite the great efforts for tumor therapy in the last decades, currently chemotherapy induced toxicity remains a formidable problem for cancer patients, and it usually prohibits the cancer therapy from successful completion due to severe side effects. In general, the main side effects of chemotherapeutic agents are from the as-produced reactive oxygen species (ROS) that not only harm the tumor cells but also damage the patients’ organs. Here we report the application of amino acid derivatives of fullerene (AADF) in the chemotherapy which strongly scavenge the excess ROS to protect the tested mice against the chemotherapy-induced hepatotoxicity and cardiotoxicity. Two amino acids, i.e., L-lysine and β-alanine were separately employed to chemically modify C70 fullerene, and L-lysine derivative of fullerene (C70-Lys) exhibits superior radical scavenging activity to β-alanine derivative of C70 (C70-Ala). As expected, C70-Lys show much better protective effect than C70-Ala against the chemotherapy injuries in vivo, which is verified by various histopathological, haematological examinations and antioxidative enzyme studies. Moreover, the L-glutathione level is increased and the cytochrome P-450 2E1 expression is inhibited. They are potentially developed as promising bodyguards for chemotherapy protection.

Fullerene (C60) nanoparticles exert photocytotoxicity through modulation of reactive oxygen species and p38 mitogen-activated protein kinase activation in the MCF-7 cancer cell line

The photocytotoxicity of water-dispersed 100–300 nm fullerene amino acid derivatives nanoparticles was studied. The nanoparticle solution of fullerene derivatives, l-phenylalanine (C60-phe) and glycine (C60-gly), suppressed the in vitro growth of MCF-7 cells lines, induced cancer cells apoptosis, and caused a perturbation of the cell cycle. These nanoparticle solutions increased intracellular reactive oxygen species after irradiation. C60-phe or C60-gly upregulated the expression of phosphorylated (p)p38 mitogen-activated protein kinase (MAPK). N-Acetyl-l-cysteine significantly depressed the composite-induced activation of p38MAPK, and the kinase inhibitor SB203580 significantly prevented C60 derivative-induced cell apoptosis. This study revealed that p38MAPK is activated by C60 nanoparticles through triggering reactive oxygen species generation, leading to cancer cell injuries.

Quantum chemical calculations of the molecular structures of hybrid amino acid derivatives of fullerene C60

The stereoselectivity of the formation of hybrid amino acid derivatives of fullerene (AADF) C60 was studied. The energies of the model addition reactions C60 + n C2H6 ⇆ Men-C60-Men(1) and C60 + n EtNC4H7Me ⇆ Etn-C60-(NC4H7Me)n (2) (n = 1–3) were calculated by the DFT method B3LYP/6-31G*. The most stable products of reaction (1) are hexamethylated fullerene derivatives in which five Me groups are arranged in the form of a regular pentagon. Among the AADF obtained by reaction (2), 1,4-disubstituted fullerene isomers are most stable. The molecular structures of such isomers were calculated for six biologically active hybrid AADF; the solvent contact areas of these molecules were evaluated.

Antioxidant properties of water-soluble amino acid derivatives of fullerenes and their role in the inhibition of herpes virus infection

The antioxidant properties of water-soluble amino acid derivatives of fullerene C60 (ADF) were studied. It was shown by the change in the concentration of malonic dialdehyde in rat brain mitochondria that the ADF are antioxidants. They were shown by the change in the luminol glow to possess antiradical activity, which is determined by the acceptor properties of the fullerene spheroid and is independent of the structure of the attached addends. Stereoselectivity of the antioxidant properties of the enantiomers of amino acid derivatives of fullerene C60 was found. The L-isomers of ADF inhibit lipid peroxidation, whereas the D-isomers do not inhibit. A reliable correlation between the development of cytomegalovirus (CMV) infection and the process of lipid peroxidation in the cell culture was established. An efficient inhibitor of the CMV infection from the class of amino acid derivatives of fullerene with antioxidant activity was obtained.

ChemInform Abstract: A Simple Quick Route to Fullerene Amino Acid Derivatives.

AbstractSeveral novel fullerene amino acid derivatives, e.g. compounds (III) and (IV), are prepared and readily separated with flash chromatography.

Optical circular dichroism of the fullerene amino acid derivatives

The dependence of the circular dichroism spectra of the amino acid derivatives of fullerene C60 on the structure of the initial α-amino acid was studied.

A simple quick route to fullerene amino acid derivatives

Two new fullerene amino acids have been prepared by dipolar addition to C(60) of either the Boc- or Fmoc-Nalpha-protected azido amino acids derived from phenylalanine and lysine. UV-visible and CV studies indicate the as prepared amino acids are a mixture of 5,6-open (major product) and 6,6-closed (minor product) derivatives that may be readily separated.

Functionalization of C60 via organometallic reagents

The reaction of [60]fullerene with organolithium and Grignard reagents carrying orthoester, acetal or other end groups yielded adducts 3– 5 at the 6–6 bond of C60 after quenching with trifluoroacetic acid. The adducts could be easily methylated or benzylated with methyl iodide or benzyl bromide in the presence of potassium tert-butoxide to yield exclusively the 1,4-disubstituted C60 6 and 7a, b. Cleavage of the orthoester, acetal and silylether groups gave the corresponding carboxylic acid 9, aldehydes 10a, b and 11 and alcohols 12 and 13a, b. The carboxylic acid 9 readily reacted with alanine ethyl ester under standard peptide coupling conditions to give 14 in 55% yield. Attempts to generate a silyl enol ether from the reaction of aldehyde 10b with TIPSOTf and triethylamine failed. Instead the reaction led to a cyclized ether 16a (or alcohol 16b in the absence of silylating agent) resulting from the addition of an initially formed fulleride anion to the aldehyde group. The corresponding acetal 4b reacted similarly. The reaction of aldehyde 10b with aniline also gave a cyclized product 19. Surprisingly, aldehyde 11, which no longer carried an acidic fullerene proton reacted with aniline to give a product 20 resulting from an intramolecular Diels–Alder reaction followed by aromatization of a primarily formed N-phenylimine. Alcohol 13b could be readily converted to the corresponding bromide using tetramethyl-α-bromoenamine. The bromide was reacted with the carbanion derived from the protected glycine derivative to yield the diastereomeric fullerene amino acid derivatives 1-benzyl-4-[α-propyl- tert-butylglycinate benzophenone imine] 1,4-dihydro[60]fullerenes 24a and 24b.

Creation of a donor-acceptor pair for studying intraprotein electron transfer with the participation of amino-acid derivatives of fullerene C60

Efficient quenching of eosin phosphorescence by amino-acid derivatives of fullerene (AADFs) such as C60-alanine and C60-glycine in aqueous solutions indicates the possibility of transferring electrons from eosin to fullerene upon collisions or in the exciplex state. To investigate electron transfer in the protein structure, we studied the process of incorporation of C60-alanine and C60-glycine into the heme pocket of myoglobin by controlling Forster quenching. The dissociation constant for the protein-AADF complex was estimated.

ChemInform Abstract: Synthesis of Fullerene Amino Acid Derivatives by Direct Interaction of Amino Acid Ester with C60.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Synthesis of Fullerene Amino Acid Derivatives by Direct Interaction of Amino Acid Ester with C60

Amino acid esters react with C60 both thermally and photochemically to give different products. Refluxing a mixture of C60 and glycine ethyl ester afforded C60(Me2CHNHCHCOOEt) 1, whereas irradiation of the same mixture produced C60(EtOOCCHNHCHCOOEt) 2b as the main product. Photochemical reactions between C60 and sarcosine esters yielded two pyrrolidine derivatives C60(CH2N(Me)CHCOOR) 3 and C60(ROOCCHNHCHCOOR) 2 (R = Me, Et, CH2Ph). Compound 2a is also prepared from the photochemical reaction between C60 and iminodiacetic methyl ester in high yield. These ester derivatives are difficult to hydrolyze in excess mineral acids. The fullerene dicarboxylic acid C60(HOOCCHNHCHCOOH) 5 is synthesized from the tert-butyl derivative C60(tBuOOCCHNHCHCOOtBu) 4. A possible radical reaction mechanism for the photochemical reactions is proposed which involves an unprecedented C−N bond breakage.