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Fullerene is one of carbon allotropes with extremely low solubility in aqueous solvents and most organic solvents, but high potential of application in various areas, such as medicine, photovoltaics and materials. To overcome this obstacle, fullerene needs to be functionalized. The Prato reaction is decent synthetic method that provides N- and C-substituted fulleropyrrolidines. We optimized the conditions of the Prato reaction in order to obtain fulleropyrrolidines containing phenol (3d) and protected phenol subunits (3a, 3b). (Figure 1) The desired products were purified by dry-flash chromatography and obtained in satisfactory yields.

An efficient encapsulation of the fullerene into two hydrophobized and one native polysaccharide provided water soluble supramolecular hybrids. After covalent modification of polysaccharides by cholesterol, noncovalent hybrids were prepared by a three-step procedure, including mixing of individual aqueous solutions of hydrophobized, as well as native sugar with solution of the fullerene in pyridine, dialysis and lyophilization. Although the degree of the fullerene incorporation into hydrophobized substrates, cholesterol-levan and cholesterol-pullulan, was lower in comparison to the native polysaccharide levan, hydrophobization provided nanoparticles with improved properties. The particle size distribution, studied by dynamic light scattering and scanning electron microscopy revealed formation of moderately polydisperse aggregates, with the diameter contraction in comparison to the corresponding free polysaccharide, especially in the case of hydrophobized substrates. The morphological examination, done by scanning electron microscopy indicated the self-organization of the fullerene-native polysaccharide to round individual structures, while fullerene-hydrophobized polysaccharide hybrids tend to form networks. The antioxidant activity of the synthesized polysaccharide-C60 noncovalent hybrids versus starting polysaccharides was investigated by the DPPH radical scavenging and the β-carotene-linoleic acid bleaching methods. In all three complexes, the radical scavenging ability of the fullerene remained preserved, and a positive effect of levan hydrophobization was observed.

The effects of twelve weeks of supplementation with fullerene C60 olive/coconut oil solution on a broad spectrum of parameters in rats were examined. The tissue bioaccumulation of C60 was shown to be tissue-specific, with the liver, heart, and adrenal glands being the organs of the greatest, and the kidney, brain, and spleen being the organs of the smallest accumulation. C60 did not change aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase serum activities level, nor the damage of liver cells DNA. There were no effects of fullerene on prooxidant-antioxidant balance in the liver, kidney, spleen, heart, and brain, nor any visible harmful effects on the liver, heart, aorta, spleen, kidney, and small intestine histology. Fullerene changed the gut microbiota structure towards the bacteria that ameliorate lipid homeostasis, causing a serum triglycerides concentration decrease. However, C60 significantly increased the insulin resistance, serum ascorbate oxidation, and brain malondialdehyde and advanced oxidation protein products level. The deteriorative effects of C60 on the brain and serum could be attributed to the specific physicochemical composition of these tissues, potentiating the C60 aggregation or biotransformation as the key element of its pro-oxidative action.

Objects of the present study are improved fullerene C60 drug carrier properties trough encapsulation by microbial polysaccharides, levan (LEV), pullulan (PUL), and their hydrophobized cholesterol-derivatives (CHL and CHP), that show better interaction with cancer cells. The zeta potential, polydispersity index, and the diameter of particles were determined, and their cytotoxicity against three cancer cell lines were tested. Biochemical changes in HeLa cells are analyzed by synchrotron radiation (SR) FTIR spectro-microscopy combined with the principal component analysis (PCA). The most significant changes occur in HeLa cells treated with LEV-C60 and correspond to the changes in the protein region, i.e. Amide I band, and the changes in the structure of lipid bodies and membrane fluidity are evident. The highest cytotoxicity was also induced by LEV-C60. In HeLa cells, cytotoxicity could not be strictly associated with biochemical changes in lipids, proteins and nucleic acids, but these findings are significant contribution to the study of the mechanism of interaction of C60-based nanoparticles with cellular biomolecules. In conclusion, LEV, PUL, CHL, and CHP enhanced fullerene C60 potential to be used as target drug delivery system with the ability to induce specific intracellular changes in HeLa cancer cells.

Four macrocyclic bis(pyrrolidino)fullerene regioisomers with e-edge, e-face, trans-4 and cis-2 addition patterns were synthesized from the corresponding monoadduct by Prato's cycloaddition in a yield of 50%, and fully characterized by spectroscopic techniques. Bisadduct regioisomers were isolated easily in a pure form using dry-flash column chromatography. The relative ratio of the isolated regioisomers e-edge/e-face/trans-41cis-2 was 1.0:1.9:1.5:4.9. Morphology of self-assembled structures of the four bisadduct regioisomers in solution was characterized using scanning electron microscopy. (C) 2017 Elsevier Ltd. All rights reserved.

Derivati fulerena C60, zahvaljujući svojim jedinstvenim fizičkohemijskim ielektronskim svojstvima, koja proističu iz visoko konjugovanog π-sistema, činezanimljive gradivne elemente u sintezama složenijih ciljnih molekula. Različitimderivatizacijama hidrofobne ugljenične sfere dobija se niz proizvoda primenljivih uhemiji materijala, supramolekulskoj i medicinskoj hemiji. Imajući u vidu povećanjerastvorljivosti, kao i promenu stereoelektronskih osobina sa povećenjem broja adenadana fulerenskom jezgru, korisna je svaka metoda višestruke derivatizacije fulerena kojase odigrava pod kontrolisanim uslovima.Prato-va reakcija jedan je od najzastupljenijih vidova kovalentne modifikacijefulerena. U njoj nastaju fuleropirolidini, proizvodi jasno definisane strukture i čestiintermedijeri u složenim hemijskim tranformacijama fulerena. Ozbiljno ograničenje overeakcije predstavlja lako i neselektivno građenje bis- i tris-pirolidinskih adukata, kojiznačajno umanjuju prinose i čistoću monoadukata. S druge strane, bisadukti su sepokazali korisnima u nekim sferama medicinske hemije i elektrohemije.Regioselektivno dobijanje bisadukata fulerena upotrebom posebno dizajniranihpremošćenih supstrata bio je predmet interesovanja nekolicine istraživačkih grupa uproteklom periodu.U toku ovog rada sintetisan je niz alkil-premošćenih diglicina, u cilju dobijanjapremošćenih bis-pirolidinskih adukata fulerena u reakciji dvostruke Prato-vecikloadicije. U prvom delu rada, na supstratu premošćenom oktametilenskim nizom,optimizovani su reakcioni uslovi za dobijanje bisadukata. Optimalnim reakcionimuslovima podvrgnuti su i ostali supstrati, premošćeni alkil-nizovima dužine od 6 do 12C-atoma i utvrđena je zavisnost regioselektivnosti od dužine niza. Istim reakcionimuslovima podvrgnuta su i dva supstrata koji sadrže dve, odnosno tri etarske podstruktureu mostu i ispitan je uticaj kiseonikovih atoma u linkeru na selektivnost reakcije..., Due to their unique physicochemical and electronic properties, emerging fromhighly conjugated π-system, derivatives of the fullerene C60 are interesting buildingblocks in the synthesis of the more complex target molecules. Diverse derivatizationsof hydrophobic carbone sphere provide a wide range of products for the use inmatherial, supramolecular and medicinal chemistry. Since the increase of the numberof addends on the carbon core improves the solubility and varies the stereoelectronicproperties, each method of the controlable multiple derivatization of fullerenes ishighly useful.Prato's reaction is one of the most common methodes for the covalentmodification of fullerenes. The fulleropyrrolidines, products with well definedstructures, are frequently used as intermediers in further chemical transformations offullerenes. This reaction is limited with the easy and unselective formation of bis- andtris(pyrrolidino) adducts and, hence, decrease of the yields and the purity ofmonoadducts. On the other hand, bisadducts are very useful in some aspects of themedicinal and electrochemistry. During the recent period, the regioselective synthesisof the fullerene bisadducts via templated supstrates has been the topic of interest ofseveral researcher groups.In this work, a series of alkyl-tethered diglycines were synthesized andunderwent the Prato's biscycloaddition conditions in aim to obtain templatedbis(pyrrolidino)fullerenes. The first part of the work refers to the optimization of thebiscycloaddition conditions on the octamethylene-tethered substrate. Other diglycines,wearing from C6 to C12 alkyl-linkers, were subjected to this optimal reactionconditions and the correlation between the distribution of the regioisomers and thelenght of the linker is determined. Another two diglycines, wearing two and threeoxygen atoms in the tether, underwent the same reaction conditions in aim toinvestigate the influence of the etheric subunits on the selectivity of the reaction...

Derivati fulerena C60, zahvaljujući svojim jedinstvenim fizičkohemijskim i elektronskim svojstvima, koja proističu iz visoko konjugovanog π-sistema, čine zanimljive gradivne elemente u sintezama složenijih ciljnih molekula. Različitim derivatizacijama hidrofobne ugljenične sfere dobija se niz proizvoda primenljivih u hemiji materijala, supramolekulskoj i medicinskoj hemiji. Imajući u vidu povećanje rastvorljivosti, kao i promenu stereoelektronskih osobina sa povećenjem broja adenada na fulerenskom jezgru, korisna je svaka metoda višestruke derivatizacije fulerena koja se odigrava pod kontrolisanim uslovima. Prato-va reakcija jedan je od najzastupljenijih vidova kovalentne modifikacije fulerena. U njoj nastaju fuleropirolidini, proizvodi jasno definisane strukture i česti intermedijeri u složenim hemijskim tranformacijama fulerena. Ozbiljno ograničenje ove reakcije predstavlja lako i neselektivno građenje bis- i tris-pirolidinskih adukata, koji značajno umanjuju prinose i čistoću monoadukata. S druge strane, bisadukti su se pokazali korisnima u nekim sferama medicinske hemije i elektrohemije. Regioselektivno dobijanje bisadukata fulerena upotrebom posebno dizajniranih premošćenih supstrata bio je predmet interesovanja nekolicine istraživačkih grupa u proteklom periodu. U toku ovog rada sintetisan je niz alkil-premošćenih diglicina, u cilju dobijanja premošćenih bis-pirolidinskih adukata fulerena u reakciji dvostruke Prato-ve cikloadicije. U prvom delu rada, na supstratu premošćenom oktametilenskim nizom, optimizovani su reakcioni uslovi za dobijanje bisadukata. Optimalnim reakcionim uslovima podvrgnuti su i ostali supstrati, premošćeni alkil-nizovima dužine od 6 do 12 C-atoma i utvrđena je zavisnost regioselektivnosti od dužine niza. Istim reakcionim uslovima podvrgnuta su i dva supstrata koji sadrže dve, odnosno tri etarske podstrukture u mostu i ispitan je uticaj kiseonikovih atoma u linkeru na selektivnost reakcije..., Due to their unique physicochemical and electronic properties, emerging from highly conjugated π-system, derivatives of the fullerene C60 are interesting building blocks in the synthesis of the more complex target molecules. Diverse derivatizations of hydrophobic carbone sphere provide a wide range of products for the use in matherial, supramolecular and medicinal chemistry. Since the increase of the number of addends on the carbon core improves the solubility and varies the stereoelectronic properties, each method of the controlable multiple derivatization of fullerenes is highly useful. Prato's reaction is one of the most common methodes for the covalent modification of fullerenes. The fulleropyrrolidines, products with well defined structures, are frequently used as intermediers in further chemical transformations of fullerenes. This reaction is limited with the easy and unselective formation of bis- and tris(pyrrolidino) adducts and, hence, decrease of the yields and the purity of monoadducts. On the other hand, bisadducts are very useful in some aspects of the medicinal and electrochemistry. During the recent period, the regioselective synthesis of the fullerene bisadducts via templated supstrates has been the topic of interest of several researcher groups. In this work, a series of alkyl-tethered diglycines were synthesized and underwent the Prato's biscycloaddition conditions in aim to obtain templated bis(pyrrolidino)fullerenes. The first part of the work refers to the optimization of the biscycloaddition conditions on the octamethylene-tethered substrate. Other diglycines, wearing from C6 to C12 alkyl-linkers, were subjected to this optimal reaction conditions and the correlation between the distribution of the regioisomers and the lenght of the linker is determined. Another two diglycines, wearing two and three oxygen atoms in the tether, underwent the same reaction conditions in aim to investigate the influence of the etheric subunits on the selectivity o

A series of N-substituted fulleropyrrolidines containing peptide side chain was synthesized by the quantitative, TFA-mediated deprotection of the corresponding tert-butyl esters. The structures of all compounds were determined by comparative analysis of spectroscopic and spectrometric data. The electrochemical characterization, conducted by cyclic voltammetry at room temperature confirmed slightly attenuated reducibility in comparison to pristine C-60 and a weak long-range electron-accepting effect of the Gly(3)-fragment. The introduction of the peptide subunit led to improved solubility and enabled examination of the antioxidant properties in water environment. A notable radical scavenging activity of the fullerene subunit remained almost unchanged in all compounds. The investigation of the supramolecular self-assembling, performed by the scanning electron microscopy revealed an influence of the side chain, particularly the fraction of the hydrophobic residue, as well as the substrate structure on the final morphology. Most of the compounds underwent highly ordered multi-stage hierarchical assembling to the attractive, flower-shaped supramolecular aggregates during both the precipitation and slow evaporation of the solvent.

Two different alpha,omega-diglicynes linked by linear polyoxaalkyl chains in the presence of formaldehyde underwent Prato reaction to the fullerene C-60. The shorter linker templated formation of only cis-bisadducts, while the longer one afforded a mixture of four bisadducts (all cis and the equatorial) and difullerene dumbbell compound. Their structures were confirmed by the extensive analysis of the spectral data and molecular symmetry, as well. All compounds expressed an ability to arrange into hierarchically ordered supramolecular aggregates, the form of which depended both on the addition pattern and the spacer structure. The attenuated electron-accepting affinity, examined by cyclic voltammetry was in agreement with diminished delocalization of the pi-electronic system. In addition, all compounds exerted a notable radical scavenging activity.

The potential use of amphiphilic fullerene derivatives as a bionanomaterial was investigated by cyclic voltammetry (CV), scanning electron microscopy (SEM), and the ferrous ion oxidation-xylenol orange (FOX) method. Despite the disrupted delocalization of the pi-electronic system over the C-60 sphere, its antioxidant capacity remained high for all twelve derivatives. The compounds expressed up to two-fold and 5-12-fold better peroxide quenching capacity as compared to pristine C-60 and standard antioxidant vitamin C, respectively. During precipitation and slow evaporation of the solvent, all compounds underwent spontaneous self-assembly giving ordered structures. The size and morphology of the resulting particles depend primarily on the sample concentration, and somewhat on the side chain structure.

The potential use of amphiphilic fullerene derivatives as a bionanomaterial was investigated by cyclic voltammetry (CV), scanning electron microscopy (SEM), and the ferrous ion oxidation-xylenol orange (FOX) method. Despite the disrupted delocalization of the pi-electronic system over the C-60 sphere, its antioxidant capacity remained high for all twelve derivatives. The compounds expressed up to two-fold and 5-12-fold better peroxide quenching capacity as compared to pristine C-60 and standard antioxidant vitamin C, respectively. During precipitation and slow evaporation of the solvent, all compounds underwent spontaneous self-assembly giving ordered structures. The size and morphology of the resulting particles depend primarily on the sample concentration, and somewhat on the side chain structure.

Four fullerosteroidal conjugates, previously confirmed to express two- to threefold better antioxidant activity in vitro than C-60, were subjected to additional studies, including electrochemical, theoretical, and morphological examination. All tested compounds underwent reversible, diffusion-controlled reductions. A notable influence of the solvent properties on the reduction potential, the level of aggregation, and the lowest unoccupied molecular orbital (LUMO) energy was observed. Theoretical calculations indicated that the energy gain obtained by an intermediate formation, together with compounds' polarizability, polarity, and lipophilicity contributed to the radical quenching capacity. Very large supramolecular aggregates of all fullerosteroidal esters with no hierarchical arrangement were observed in precipitated samples, while solvent induced self-assembling led to round nanoplates, which further arranged to flower-shaped hierarchically ordered architectures or uniformly distributed discoid particles. As in electrochemical studies, fine tuning of the aggregation level was achieved by the solvent.

The present study reports the synthesis, spectral characterization, self-assembly properties, and preliminary in vitro study of antioxidant capacity of two triple covalent hybrids consisting of fullerene C-60, peptide, and steroidal moiety. Previously synthesized fulleropyrrolidinic acid and pregnenolone were connected by peptide linker using a multistep DCC/DMAP and/or EDC/HOBT esterification/amidation procedure. The hybrids were characterized by comparative analysis of spectroscopic data obtained from FUR, UV-vis, HRMS, and extensive NMR experiments (H-1, C-13, COSY, HSQC, and HMBC). The self-assembling properties and morphology of triads samples prepared by drop-drying method were examined by scanning electron microscopy (SEM). Preliminary in vitro antioxidant activity was studied by Ferrous ion Oxidation-Xylenol orange (FOX) method.

The present study is concerned with the oxidative behaviour of unsaturated and epoxy 5-oxo-5,10-secosteroids in the presence of m-CPBA or TFAA-UHP as oxidants in order to investigate potential parameters controlling the chemoselectivity and regioselectivity. In the study we discovered a striking difference in the chemical behaviour of stereoisomeric compounds, (Z)- and (E)-3 beta-acetoxy-5,10-secocholest-1(10)-en-5-ones, as well as 1S,10R- and 1R,10R-epoxides. The secoketones were oxidized with exclusively C-6 migration and Baeyer-Villiger rearrangement product formation, whereas their stereoisomers provided the ring-contracted products, without lactone formation. The preferred conformation of expanded and contracted rings was established by NOESY correlations. The structures of two obtained lactones were also confirmed by X-ray analysis. The mechanistic and stereochemical aspects of these transformations are discussed.

Synthesis of a steroidal dendrimercore possessing various functional termini, such as ester, carboxy and hydroxy, is presented. The approach described enables further simple manipulations for the introduction of more complex functionalities., U ovom radu prikazana je sinteza dendrimerskog steroidnog jezgra sa estarskim karboksilnim i hidroksilnim završecima. Opisani pristup sintezi omogućava dalju, kompleksniju funkcionalizaciju jednostavnim manipulacijama.

Based on biological properties of epoxyquinols from natural sources, bromo and epoxyquinols derived from estrone were synthesized and screened against Fem-X. HeLa and K-562 cell lines. Evidence was found that the bromine atom and the epoxy moiety significantly increase the antiproliferative activity within the series. (C) 2001 Elsevier Science Ltd. All rights reserved.