Reductive electrochemistry of spiromethanofullerenes.

The synthesis and electrochemical properties of spiromethanofullerenes 1-6 are described. The syntheses were achieved via the diazomethane route, and the regioisomeric distribution of bis-adducts 3 was determined by (1)H NMR, UV-vis, and HPLC analysis. The electrochemistry of these compounds in dichloromethane exhibits, besides several reversible reductions, some irreversible waves. Reductive electrolysis of 1 and 3-5 in dichloromethane leads to the removal of the addend and thus to the formation of C60. Reductive electrolysis of 1, 2 and 6 in dichloromethane leads to a different reaction, which we tentatively assign to a reaction with the solvent to form fullerene-CH2Cl products. Electrolyses in the less reactive solvent THF lead to adduct removal for 1 and 3-5. Interestingly, significant formation of bis-adducts from the corresponding monoadducts was observed for 4 and 5. These electrochemically induced reactions, namely addend removal, reaction with the solvent, and addend transfer are influenced by the structure of the addend and by the choice of solvent.

Synthesis and electrochemical properties of phthalocyanine--fullerene hybrids

Phthalocyanines linked to C60 have been synthesized by two general strategies. One of them involves the addition of an azomethine ylide prepared in situ from a formyl phthalocyanine to C60, and the other one involves a statistical condensation of two substituted phthalonitriles, one of them bearing the C60 moiety covalently attached. These new phthalocyanine-fullerene dyads have been studied by cyclic voltammetry and Osteryoung square wave voltammetry, and inter- and intramolecular electronic interactions between the two electroactive subunits have been demonstrated.

Electrochemical studies of seven regioisomers of Tris

Seven of the possible 46 constitutional isomers of tris[di(ethoxycarbonyl)methano[60]fullerene have been isolated and their electrochemical properties studied in CH(2)Cl(2). A two-electron controlled potential electrolysis of each of these isomers results in competing retro-Bingel and isomerization reactions with preferential loss of one or two of the addends. PM3 and AM1 computational studies indicate that while the reactivity of neutral precursors is kinetically controlled, charging of the neutral species with two electrons results in an umpolung of reactivity and introduction of thermodynamic control. Lowering the electrolysis temperature increases the proportion of isomerization, and a new tris-isomer never obtained before via synthetic methods has been isolated.

Selective electrolytic removal of bis(alkoxycarbonyl)methano addends from C60 bis-adducts and electrochemical stability of C70 derivatives

The novel mixed bis-adducts of C60, (+/-)-4-(+/-)-8 and 9, with a bis(ethoxycarbonyl)methano addend (Bingel addend) and a second addend ([1,2]benzeno, but[2]eno, methaniminomethano, or diarylmethano) bridging 6,6-closed bonds of the carbon sphere were synthesized in two-step reactions. Each bis-adduct was exhaustively electrolyzed at the potential of the second fullerene-centered reduction step, resulting in the selective removal of the Bingel addend (retro-Bingel reaction) to produce the corresponding mono-adducts, which were isolated in yields of over 60%. These results open up the possibility of using the Bingel addend as a temporary protecting and directing group in the construction of multiple adducts of C60 with unusual addition patterns. The Bingel-type mono-adduct of C70 10 and the constitutionally isomeric bis-adducts 11, (+/-)-12, and (+/-)-13 were also included in this investigation. A large difference in the electrochemical behavior between C70 bis-adducts and the corresponding C60 derivatives was observed. Thus, the intramolecular "walk-on-the-sphere" isomerization which occurs readily with Bingel-type bis-adducts of C60 under the conditions of two-electron controlled potential electrolysis (CPE) is only a minor reaction pathway in the series of C70 derivatives. The latter preferentially undergo retro-Bingel reaction.

Synthesis and properties of conjugated hybrid tetrathiafulvalene dimers

The synthesis of new hybrid tetrathiafulvalene (TTF) dimers (11a-c) has been carried out by a Wittig-Horner reaction of the respective phosphonate esters (10a-c) with 2-(tetrathiafulvalenylvinyl)-9, 10-anthraquinone (9) prepared by olefination of formyltetrathiafulvalene (7) and the phosphonium salt of anthraquinone 8. Electrochemical studies show that the dimers 11a-c mainly retain the electrochemical properties of both TTF and the pi-extended TTF components, and most importantly, intramolecular electronic interactions between the two moieties are observed by cyclic voltammetry and Osteryoung square wave voltammetry. Semiempirical PM3 calculations reveal an almost planar geometry for the TTF and the benzene ring connected through the vinyl spacer. These compounds can form stable charge-transfer complexes with 2, 3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) showing a stoichiometry of 1:3 (D:A). Attempts to electrocrystallize the dimeric donors with different counteranions are discussed.

Charge-transfer interactions in face-to-face porphyrin-fullerene systems: solvent-dependent luminescence in the infrared spectral region

The cyclophane-type molecular dyads 1 x 2H and 1 x Zn, in which a doubly bridged porphyrin donor adopts a close, tangential orientation relative to the surface of a fullerene acceptor, were prepared by Bingel macrocylization. The porphyrin derivatives 2 x 2H and 2 x Zn with two appended, singly linked C60 moieties were also formed as side products. NMR investigations revealed that the latter compounds strongly prefer conformations with one of the carbon spheres nesting on the porphyrin surface, thereby taking a similar orientation to that of the fullerene moiety in the doubly bridged systems. Cyclic voltammetric measurements showed that the mutual electronic effects exerted by the fullerene on the porphyrin and vice versa are only small in all four dyads, despite the close proximity of the donor and acceptor components. The steady-state and time-resolved absorption and luminescence properties of 1 x Zn and 2 x Zn were investigated in toluene solution and it was shown that, upon light excitation, both the porphyrin- and the fullerene-centered excited states are deactivated to a lower-lying CT state, emitting in the IR spectral region (lambda max = 890 and 800 nm at 298 and 77 K, respectively). In the more polar solvent benzonitrile, this CT state is still detected but, owing to its very low energy (below 1.4 eV), is not luminescent and shorter-lived than in toluene. The remarkable observation of similar photophysical behavior of 1 x Zn and 2 x Zn suggests that a tight donor-acceptor distance cannot only be established in doubly bridged cyclophane-type structures but also in singly bridged dyads, by taking advantage of favourable fullerene-porphyrin ground-state interactions.

Dithia-crown-annelated tetrathiafulvalene disulfides: synthesis, electrochemistry, self-assembled films, and metal ion recognition

The synthesis and electrochemistry of a series of tetrathiafulvalene (TTF) and dithia-crown-TTF derivatives attached with one or two disulfide group(s) 7a-f are reported. The self-assembled monolayers (SAMs) of these TTF disulfides on gold were prepared and characterized by reflection-absorption infrared spectroscopy. The SAMs are extremely stable under a wide variety of conditions and over extended periods of time and show remarkable electrochemical stability upon repeated potential scans. SAMs of the crown-TTF disulfides 7c,d,f can recognize alkali metal ions, and the process can be monitored following the electrochemical potential shift of the surface-confined TTF group.

Intramolecular electronic interactions in conjugated ferrocene-pi-extended-tetrathiafulvalene donor-pi-donor molecular hybrids

The synthesis of new hybrid ferrocene and pi-extended tetrathiafulvalene (TTF) donor(1)-pi-donor(2) molecular assemblies 16a-c has been carried out by a Wittig-Horner reaction of the respective phosphonate esters 15a-c with 2-(2-ferrocenylvinyl)-9, 10-anthraquinone (18) prepared by olefination of ferrocenecarboxaldehyde (14) and the anthraquinone phosphonium salt 17. Electrochemical studies show that the D(1)-pi-D(2) (D = donor) molecular assemblies 16a-c essentially retain the redox characteristics of both ferrocene and the pi-extended TTF components and the effects of solvent, temperature, scan rate, and working electrode are significant. Most importantly, pronounced intramolecular electronic interactions between the two donor moieties were observed by cyclic voltammetry and Osteryoung square wave voltammetry in both the ground and charged states. Semiempirical calculations support the electrochemical observations.

Ion recognition at the interface of self-assembled monolayers (SAMs) of bis-thioctic ester derivatives of oligo(ethyleneglycols).

Self-assembled monolayers (SAMs) of bis-thioctic ester derivatives of oligoethylene glycols were prepared. When the number of (-CH2-CH2-O-)n units in these podands was either five or six, the corresponding SAMs showed ion binding properties and selectivities similar to those exhibited by 15-crown-5 or 18-crown-6 in aqueous solution, respectively. Impedance data for the SAMs as a function of metal ion concentrations were fitted by using a Langmuir isotherm to determine the association constants (Ka) with the different ions. The SAM derived from the n = 5 compound is selective for Na+ while that with n = 6 is selective for K+. Results presented here confirm the formation of ion recognition domains during self-assembly of acyclic polyethylene glycol derivatives on gold surfaces; this suggests that surface-confined pseudocrown ether structures are formed.

Electrochemical studies of S-nitrosothiols.

S-nitrosothiols (RSNO), such as SNAP, GSNO, and Glc-SNAP-1 exhibited a single, totally irreversible, diffusion controlled reduction peak at potentials of -0.97 V, -0.98 V and -0.91 V, respectively, vs. Ag/AgCl (3 M NaCl) reference electrode. This corresponded to the nitric oxide (NO) release from the S-nitrosothiols. A possible mechanism is proposed for the reduction process.

Binding of vanadium (IV) to the phosphatase calcineurin.

X-band electron spin resonance spectroscopy was used to study the binding of vanadium (IV), or vanadyl, to the brain serine/threonine phosphatase-2B, calcineurin. Spectra were determined on frozen solutions of vanadyl and calcineurin at pH 7.4 in the presence of 20% (v/v) glycerol. The binding of vanadyl to the enzyme was established, and the data suggested the presence of two classes of sites, the higher affinity class of which contained two binding sites for vanadyl. The calcium-binding B subunit of the heterodimeric protein was also shown to bind vanadyl. The holoprotein appeared to be stabilized by vanadyl, and vanadyl enhanced enzymatic activity when assayed with or without calmodulin in the absence of calcium.

Vanadium (IV) inhibits calmodulin-stimulated skeletal muscle myosin light chain kinase activity.

Vanadium, believed to be an essential trace metal, exhibits numerous biological effects. Using electron spin resonance spectroscopy, we have demonstrated that vanadyl, vanadium (IV), the predominant intracellular form of vanadate (vanadium V), binds to calmodulin in the presence of physiological concentrations of magnesium, extending earlier work which showed competitive binding of vanadyl and calcium to calmodulin. In the presence of a magnesium-containing buffer, vanadyl does not lead to calmodulin activation of the calmodulin-dependent enzyme, rabbit skeletal muscle myosin light chain kinase; in the presence of calcium, vanadyl is a potent inhibitor of the calmodulin-activated form of the kinase. Thus, vanadyl can potentially interfere with some of the intracellular actions of calcium, presumably via binding to calmodulin. This observation deserves consideration in view of the potential clinical application of vanadium treatment to mimick insulin action and lower blood glucose.

Electron spin resonance of calmodulin-vanadyl complexes.

X-band (9.2 GHz) electron spin resonance spectroscopy was used to investigate the binding of vanadyl to calmodulin. Solution spectra, obtained at ambient temperature with various VO2+:calmodulin molar ratios, suggested a binding stoichioimetry of 4 mol of VO2+/mol of protein and the possibility of two classes of binding sites. The latter was confirmed by using frozen solutions of calmodulin-VO2+ complexes that gave splitting of the spectral bands corresponding to the parallel components, which was particularly pronounced with the three high-field peaks. Competition of Ca2+ for the VO2+ binding sites was investigated, and the results indicated that two of the VO2+ sites corresponded to two of the Ca2+ sites; the other two VO2+ binding sites may have a higher affinity for VO2+ than for Ca2+ or they may correspond to Ca2+-independent sites. These results demonstrate that electron spin resonance spectroscopy can be used advantageously to probe subtle differences in the microenvironments of metal-binding sites in calmodulin.

Mechanism of inhibition of glycolysis by vanadate.

Vanadate is known to inhibit several phosphatases including Na+, K+-ATPase, alkaline phosphatase, and glyceraldehyde-3-P dehydrogenase. Inhibition presumably results because vanadium adopts a stable structure which resembles the transition state of phosphate during the reactions involving these enzymes. We performed experiments to further examine the effects of vanadate (VO3-4) on erythrocyte (red blood cells (RBC] glycolytic intermediates. RBC obtained from human subjects were centrifuged and washed with lactated Ringer's 5% dextrose. 31P nuclear magnetic resonance analysis of the RBC revealed the characteristic peaks for the 3-phosphate and 2-phosphate of 2,3-diphosphoglycerate (DPG), inorganic phosphate (Pi), and ATP. Incubation of RBC with 10(-6) M VO3-4 led to a disappearance of ATP and 2,3-DPG while the peak for Pi increased. By the end of 4 h over 90% of the VO3-4 had been reduced to VO2+ (vanadyl) in the RBC. The effects of 10(-4) M iodoacetamide and 10(-5) M ethacrynic acid, known inhibitors of glyceraldehyde-3-P dehydrogenase that act by interactions with sulfhydryl groups (-SH) of the enzyme, were similar to those of VO3-4. Incubation with vanadyl did not affect the peaks for Pi, 2-DPG, or 3-DPG. Furthermore, using electron spin resonance we demonstrated that in the presence of glyceraldehyde-3-P dehydrogenase, VO3-4 is reduced to VO2+. The findings demonstrate that VO3-4 inhibits glycolysis at micromolar concentrations and that the ion is reduced to VO2+ in the cell. The similarity of the effect of VO3-4 to those of iodoacetamide and ethacrynic acid suggests that interactions with -SH groups is its mechanism of inhibition. Since under physiological conditions intracellular VO3-4 concentrations are in the micromolar range and may exist in oxidized and/or reduced forms, VO3-4 could regulate the activity of glyceraldehyde-3-P dehydrogenase through changes in the redox state of the enzyme rather than by substituting for the PO3-4 ion.

Influence of solvent, anion and presence of nitrogen in the ring structure on the mechanism of complexation of alkali metal cations with crown ethers.

The mechanism of complexation of alkali metal cations with macrocyclic ligands such as the simple crown ethers and the role of desolvation vs. ligand rearrangement are discussed. The unique role of water solvent in the rate-determining step of complexations in aqueous solutions is brought into focus. The competitive role of the anion, which becomes of paramount importance in solvents of low permittivity, is reiterated. Monoazo crown ethers are shown to possess isomeric equilibria in methanol solvent. The rate-determining process for the first step of complexation of these macrocycles with Na+ in methanol appears to be the rearrangement of the ligand through inversion to an exo position of the nitrogen lone electron pair. The rate-determining step of the overall complexation is the entrance of the Na+ into the ring with (possibly) concomitant rotation of the lone electron of the nitrogen to an endo configuration.