Michael Brettreich

A highly water-soluble dendro[60]fullerene

Abstract The nucleophilic cyclopropanation of C60 with a second generation bis(polyamide)-malonate dendrimer and the subsequent deprotection of the terminal t-butyl groups provides a dendro[60]fullerene with 18 carboxylic groups in the periphery. This dendritic monoadduct of C60 is highly water-soluble.

Reactions of e−aq, co2•−, ho, o2•− and o2(1δg) with a dendro[60]fullerene and c60[c(cooh)2]n (n = 2–6)1

Using pulse radiolysis and laser flash photolysis, we have investigated the reactions of the deleterious species, e(-)(aq), HOz, O(2)(*)(-) and O(2)((1)Delta(g)) with 10 water-soluble cyclopropyl-fused C(60) derivatives including a mono-adduct dendro[60]fullerene (d) and C(60) derivatives based on C(60)[C(COOH)(2)](n=2-6), some of which are known to be neuroprotective in vivo. The rate constants for reactions of e(-)(aq) and HOz lie in the range 0.5-3.3 x 10(10) M(-1) s(-1). The d and bis-adduct monoanion radicals display sharp absorption peaks around 1000 nm (epsilon = 7 000-11 500 M(-1) cm(-1)); the anions of the tris-, tetra-, and penta-adduct derivatives have broader, weaker absorptions. The monohydroxylated radicals have their most intense absorption maxima around 390-440 nm (epsilon = 1000-3000 M(-1) cm(-1)). The anion and hydroxylated radical absorption spectra display a blue-shift as the number of addends increases. The radical anions react with oxygen (k approximately 10(7)-10(9) M(-1) s(-1)). The reaction of O(2)(*)(-) with the C(60) derivatives does not occur via an electron transfer. The rate constants for singlet oxygen reaction with the dendrofullerene and eee-derivative in D(2)O at pH 7.4 are k approximately 7 x 10(7) and approximately 2 x 10(7) M(-1) s(-1) respectively, in contrast to approximately 1.2 x 10(5) M(-1) s(-1) for the reaction with C(60) in C(6)D(6). The large acceleration of the rates for electron reduction and singlet oxygen reactions in water is due to a solvophobic process.

Photophysical properties of a dendritic methano[60]fullerene octadeca acid and its tert-butyl ester: evidence for aggregation of the acid form in water

The results of a laser flash photolysis investigation of a dendritic methano[60]fullerene octadeca-acid (DA) and its tert-butyl ester (DE) are reported. DE possesses photophysical properties typical of a [60]fullerene mono-adduct with a singlet oxygen quantum yield approaching unity in toluene and a triplet absorption spectrum with a maximum at 710 nm. In methanol DA also possesses properties typical of a [60]fullerene mono-adduct, but in aqueous solution its photophysical behaviour shows a degree of aggregation that is a function of pH and concentration. At pH 7.4 and higher, Coulombic repulsion between de-protonated carboxylate groups reduces the propensity to aggregation and dilute solutions (<∼10−4 M) of DA exhibit typical [60]fullerene mono-adduct behaviour, although the singlet oxygen yield of 0.75 is lower than in methanol (0.93). The rate constant for DA triplet state quenching by oxygen in water (pH 7.4) is relatively low, which reflects shielding of the hydrophobic C60 core by the dendrimer thus reducing the possibility of orbital overlap with oxygen due to restricted diffusion. Aggregation is evident from the UV-VIS absorption spectra at concentrations exceeding ∼10−4 M in water at pH 7.4, beyond which substantial positive deviations from the Beer–Lambert law are observed. In acidic solutions (pH 4.5) the degree of dissociation of the carboxylic acid groups is negligible and the lack of Coulombic repulsion between DA molecules leads to extensive aggregation, even in dilute solutions. In such solutions the singlet oxygen quantum yield is greatly reduced (∼0.13 at pH 4.5).

Triplet state properties of malonic acid C60 derivatives C60[C(COOR)2]n; R = H, et; n = 1-6

Laser flash photolysis and pulse radiolysis have been used to determine properties of the lowest triplet state of a series of water-soluble malonic acid derivatives of C60 , C60[C(COOH)2]n with n = 2–6, in water at pH 7.4. Similar studies were carried out on the corresponding ethyl esters, C60[C(COOEt)2]n with n = 1–6, in the non-polar solvents, benzene or toluene. The properties include the T–T absorption spectra, the triplet molar absorption coefficients and the quantum yields of formation, ΦT and ΦΔ of the triplet and of singlet oxygen, respectively. This study shows a general tendency of the λmax of the T–T absorption spectra, and of the ΦΔ values to decrease with increasing number of addends. For regioisomers, the spectroscopic and photophysical parameters are modulated with the pattern of addition. The ΦΔ quantum yields for the acids in aqueous solution are systematically lower than those of the ethyl esters in toluene. The lower ΦΔ values observed for the acids in aqueous solution, and to a lesser extent for the esters in benzonitrile, can be interpreted as due to the presence of solute clusters in polar solvents.

Electrophoretic behavior of a highly water‐soluble dendro[60]fullerene

The aim of the present study was to develop an analytical method for measuring amounts of a dendro[60]fullerene (DF) which is a highly water‐soluble [60]fullerene derivative. We tried to define a straightforward methodology using capillary zone electrophoresis, a method which, to our knowledge, has not yet been used to that purpose. Preliminary assays showed that DF has almost the same mobility than the electroosmotic flow (EOF) but in the opposite direction. Attempts were carried out to reduce the EOF and positive results were obtained by adding hydroxypropylcellulose to the background electrolyte. In order to define optimal operating conditions, a Taguchi experimental plan was used to study simultaneously the effects of the main parameters that are pH, ionic strength, methanol amount and hydroxypropylcellulose concentration. Two parameters are of the utmost importance as to their effect on the migration time and separation efficiency: pH and ionic strength whose actions are opposite.

INTERACTION OF A WATER SOLUBLE FULLERENE DERIVATIVE WITH REACTIVE OXYGEN SPECIES AND MODEL ENZYMATIC SYSTEMS

Fullerenes are a new class of compounds with potential uses in biology and medicine but little is known about their interaction with biological systems. Fullerenes were reported to be pro- or anti-oxidants depending on their structure or on experimental conditions. This work presents the effects of dendrofullerene, a water soluble derivative of C60, on model biological systems from both perspectives. The relative importance of type I and type II mechanisms involved in the production of the reactive forms of oxygen leading to inhibition of GST activity was studied using dendrofullerene, white light and the quenching agents. The addition of mannitol or superoxide dismutase, known quenchers of the type I mechanism had no effect on the rate of GST inactivation. Significant inhibition of the inactivation provided by the dendrofullerene was observed on addition of tryptophan, a known quencher of the type II mechanism. Activity towards the basic enzymatic system cytochrome P-450 has also been investigated and at a concentration of 250 μM dendrofullerene exhibits selective inhibition of progesterone metabolism which is attributed to the fullerene moiety rather than the dendritic chain.

Charge Transfer in Sapphyrin−Fullerene Hybrids Employing Dendritic Ensembles†

A new approach to creating noncovalent charge transfer ensembles is described. It is based on two components that are linked through anion-receptor interactions. The first component is sapphyrin, a pentapyrrolic expanded porphyrin, which is capable of carboxylate anion recognition and more importantly can act as a photodonor when irradiated in the presence of a suitable electron acceptor. The second component is the electron acceptor and consists of one of two different C(60) fullerene cores functionalized with multiple carboxylate anion groups arranged in a dendritic fashion. Depending on the specific choice of the fullerene carboxylate anion dendrimer employed in ensemble construction, 1:1 or 1:2 complexes are formed when the C(60) cores are titrated with sapphyrin. The resulting noncovalent arrays undergo sapphyrin-to-fullerene electron transfer when irradiated with 387 nm light. This gives rise to charge separated states with lifetimes of ca. 470 and 600 ps in the case of the 1:1 and 1:2 sapphyrin-fullerene ensembles, respectively.

Highly Efficient Synthesis of Globular (Bola)amphiphilic [5:1]Hexakisadducts of C60

We report on the very facile access of a new family of amphiphilic and bola-amphiphilic fullerene [5:1]hexakisadducts 9a-f and 11a-e. The key point for this successful approach is the use of C(2v)-symmetrical fullerene pentakisadduct precursors 2b-f allowing for the completely regioselective addition of a sixth malonate addend to complete the octahedral [5:1] addition pattern. For the synthesis of the new amphiphiles we first developed a new second-generation dendrimer containing 9 tert-butoxycarbonyl (Boc)-protected amino functions at the periphery and two new malonates containing 6 or 18 Boc-protected amino termini, respectively. The hexakisadducts contain up to 18 positive or negative charges at the dendritic moiety and either no or ten positive or negative charges at the unbranched malonate positions after deprotection with trifluoroacetic acid (TFA). The charge state at the termini is pH-dependent. Complete structural characterization of the new compounds was carried out by ESI mass spectrometry and by UV/Vis, FTIR, (1)H NMR and (13)C NMR spectroscopy. We were also able to obtain the first X-ray crystal structure of pentakisadduct (2a) with a C(2v)-symmetrical addition pattern. The new amphiphilic hexakisadducts show interesting solubility properties in water. Initial investigations on the aggregation properties of the amphiphilic hexakisadduct 12c by using dynamic light scattering (DLS) and conductivity measurements, show aggregates with a radius up to 200 nm and a critical micelle concentration (CMC) of approximately 8 mg L(-1).