The reducing strength of the antioxidant ergothioneine (EGT) at physiological pH has been probed by spectroscopy and electrochemistry. Optical spectroscopy, used to follow the reductions of methylene blue, Fe(III) cytochrome c, and ferricyanide by EGT, showed that the traditionally accepted value of its redox potential (-0.06 V vs NHE) is not correct, and has led to EGT being classified as a much stronger reducing agent than is warranted. To obtain a more reasonable number for the redox potential, cyclic voltammetry (CV) experiments were carried out on EGT in pH 7.2 phosphate buffer solutions. Glassy carbon and edge-plane pyrolytic graphite working electrodes required either careful mechanical polishing or plasma activation of their surfaces to give reliable voltametric data. Repeatable results were obtained for CVs taken at scan rates at or below 0.2 V/s. They showed that the anodic oxidation of EGT is a diffusion-controlled, totally irreversible, one-electron process. Anodic peak potentials of 0.42 V to 0.47 V were observed within a group of different carbon-based electrodes, allowing a redox potential of 0.45 ± 0.02 V vs NHE to be assigned to EGT. This value is slightly positive of the accepted value for ascorbate anion (0.35 V), and some 500 mV positive of the previously employed value for EGT. Based on what appear to be the most reliable present and literature redox potentials, a ranking of the reducing strengths of several important antioxidants at the physiological pH is glutathione ≈ cysteine ≫ ascorbate > α-tocopherol ≈ ergothioneine > tyrosine.

The oxidation of [n]nickelocenophanes [Ni(eta(5)-C5H4)(2)(CH2)(3)] (3), [Ni(eta(5)-C5H4)(2)(SiMe2)(2)] (10), [Ni(eta(5)-C5H4)(2)(SiMe2)(2)O] (11), [Ni(eta(5)-C5H4)(2)(CH2)(4)] (12), and poly(nickelocenylpropylene) [Ni(eta(5)-C5H4)(2)(CH2)(3)]n (4) to both the monocationic and dicationic species was investigated in dichloromethane by cyclic voltammetry (CV) and square-wave voltammetry. The presence of acetonitrile on the oxidation potentials of 3 in dichloromethane was also investigated by CV. The [n]nickelocenophanes 3 and 10-12 exhibited two single-electron Nernstian redox processes, and the monocations [3](+), [10](+), [11](+), and [12](+) were isolable as [B(C6F5)(4)](-) salts after chemical oxidation, and were structurally characterized. Ni-Cp-cent distances in all four monomers decreased upon oxidation, with a structural distortion manifested in the ring-tilt angle, alpha, among other angles. CV studies of the reversible first oxidation process to the polyelectrolyte {[Ni(eta(5)-C5H4)(2)(CH2)(3)](+)}(n) ([4](n+)) were used to estimate the molecular weight of the polymeric material (Mw = 5300 g mol(-1)) by comparing its diffusion coefficient with that of a monomeric analogue, and the second electrochemical oxidation of polymer 4 was found to be only partially chemically reversible.

The oxidations of 1,1'-di-p-anisolyl-2-cymantrenylbutene (3b) and 1,1'-di-p-hydroxyphenyl-2-cymantrenylbutene (3c) were investigated by electrochemical and spectroscopic experiments and by density functional theory (DFT) calculations. Both compounds undergo a reversible one-electron oxidation followed closely by a partially chemically reversible second oxidation (E-1/2 values vs ferrocene: 0.60 and 0.74 V for 3b; 0.63 and 0.78 V for 3c). In comparison to the nonphenyl-functionalized parent, 1,1'diphenyl-2-cymantrenylbutene (3a), 3b,c have lower and more closely spaced oxidation potentials and more rapid follow-up reactions of their dications, 3b(2+) and 3c(2+). Shifts in the calculated charge distributions of the neutral compounds and their singly and doubly oxidized products corroborated trends in the measured shifts of Mn-CO nu(CO) frequencies in assigning the redox sites primarily to the diarylbutene fragment. Upon removal of electrons, the lost charge density is partially compensated by the polarizable cymantrenyl tag. The half-lives of the dications 3b(2+) and 3c(2+) are about 10 s at room temperature in dichloromethane/0.05 M [NBu4][B(C6F5)(4)]. Their follow-up reactions are initiated by loss of a proton either from a hydroxyl group or from the CH2 group of the diarylbutene unit, giving rise to two products having quinone methide structures. Although the initial oxidation sites of cymantrene-tagged diarylbutenes are primarily ligand based and those of ferrocene-tagged diarylbutenes are metal-based, the ultimate oxidation products of their p-OH- or p-OMe-functionalized derivatives are very similar.

In six of seven cases, direct anodic oxidation of the ethynyl group of an ethynylphenyl-derivatized free-base porphyrin gave modified glassy carbon electrodes in which the porphyrin was strongly surface-bound, most likely in a perpendicular geometry through covalent attachment of the ethynyl group to a surface carbon atom. The porphyrins each contained an ethynylphenyl group in one meso position and varied in the groups present in the other three meso positions. Electrografted 5,10,15,20-tetrakis(ethynylphenyl)porphyrin, H21, which has ethynyl moieties in all four meso positions, has well-defined surface voltammetry and grows to multilayer levels upon repeated cyclic voltammetry (CV) deposition scans. Multilayering was not observed to the same degree for monoethynylphenyl-substituted porphyrins and became progressively less for porphyrins having groups in the 15-meso position that were more protective against ethynyl radical attack. Clean molecular monolayer-level coverage was observed for 5-ethynylphenyl-10,20-bis(3-methoxyphenyl)-15-hexylporphyrin, H25. Owing to the fact that the ethynyl oxidation potential (1.1 to 1.5 V vs ferrocene) is more positive than that of the second macrocycle oxidation, the longevities and follow-up reactions of the porphyrin dications were also studied by CV, chemical oxidation, and optical spectroscopy in homogeneous solution. The primary follow-up products of the doubly oxidized porphyrins, whether surface-bound or in solution, were pyrrole-protonated species that were easily reduced back to the neutral porphyrin.

Eight ferrocene derivatives linked by either an ether, amine, or phenylacetylene moiety to a terminal ethynyl group were covalently deposited on glassy carbon electrodes by anodic electrochemical methods. The lithio activation method, in which the terminal hydrogen of the ethynyl group is replaced by a lithium atom before anodic oxidation, was successfully employed in all cases. Direct oxidation of the unactivated ethynyl group also resulted in surface deposition. Surface coverages between 1 x 10 ‐10 mol cm ‐2 and 14 x 10 ‐10 mol cm ‐2 were achieved. Cyclic voltammetry scans of the modified electrodes in pure electrolytes differed depending on the size of the supporting electrolyte anion, as little as half the current being measured for a [B(C 6 F 5 ) 4 ] ‐ vs. [PF 6 ] ‐ solution, suggesting differences in ion transport near the electrode surface. An ether‐linked ethynylferrocenium ion ( 5 + ) was isolated after electrolytic and chemical oxidation of 5 and characterized by X‐Ray crystallography as its [SbCl 6 ] ‐ salt.

Electrochemical oxidation of the cymantrene derivative MnCp(CO)(2)(IDiip). 1, (Cp = eta(5)-C5H5, IDiip = 1,3-bis(2,6-diisopropylphenyl)imidazole-2-ylidene) is a quasi-Nernstian one-electron process in dichloromethane/0.1 M INBu4][PF6]. The E-1/2 potential of the l(0/+) couple, -0.34 V vs. ferrocene, is the most negative yet reported for a mono-substituted cymantrene derivative, reflecting the powerful electron-donating character of the N-heterocyclic carbene (NHC)IDiip ligand. The radical cation 1(+) has been characterized by IR spectroscopy (v(co) = 1958 and 2034 cm(-1)) and by X-ray crystallography as its [PF6](-) salt. Compared to its neutral counterpart MnCp'(CO)(2)(IDiip) (Cp' = eta(5)-C5H4Me), the Mn-C-NHC bond distance in 1(+) is lengthened by 0.031 angstrom and the average M-C(O) bond distances are lengthened by 0.069 angstrom. DFT-based computational results show that the largest contribution to the redox orbital of 1(0/)(+) is found at the metal atom (about 70% manganese-based in 1(+)). Comparison of the E-1/2 potential of 1 with those of other mono-CO-substituted cymantene complexes allows an estimate of the "ligand electronic parameter" of the IDiip ligand as -0.27 V vs. NHE. (C) 2018 Elsevier Ltd. All rights reserved.

The oxidative electrochemical behavior of 1,1'-diphenyl-2-cymantrenylbutene (1), a cymantrene analogue of the breast cancer drug ferrocifen, was shown to involve the sequential electron-transfer series 1/1(+)/1(2+) in dichloromethane/0.05 M [NBu4][B(C6F5)(4)] (E-1/2 values 0.78 and 1.18 V vs ferrocene). By a combination of spectroscopic and computational techniques, it was shown that the cymantrene functionality plays an important role in dissipating the positive charges in the oxidized compounds and is therefore an active participant in the redox events. The redox-active orbital goes from roughly equal degrees of organometallic and x-organic (diphenylolefin) makeup in 1 to increasingly organic based fractions in 1(+) and 1(2+). Structural changes mimicking those of oxidized tetrakis(aryl)ethylenes accompany the one-electron oxidations. There is sufficient unpaired electron density on the manganese center in 1(+) to allow for oxidatively induced ligand exchange of one or more of the carbonyl ligands with donor ligands, including phosphites and pyridine. The complex Mn(CO)2 P(OPh) 3 (eta(5)-C5H4(Et)C=C(C6H5)(2)) was prepared by the "electrochemical switch" method, wherein [Mn(CO)(2)P(OPh)(3) (eta(5)-C5H4(Et)C=C(C6H5)(2)](+), produced by the oxidation of 1 in the presence of P(OPh)(3), was reduced back to the neutral CO-substituted complex.

An integrated pair of experiments has been developed to introduce undergraduate students to the ways in which electrochemistry can complement conventional synthetic chemistry involving redox reactions. Students first use cyclic voltammetry and linear scan voltammetry to characterize and quantify the products of the reaction between decamethylferrocene and the 4-nitrophenyldiazonium ion. In the following lab period, they synthesize the decamethylferrocenium ion as its tetrafluoroborate salt.

Two ethynyl-derivatized isomers of bis(fulvalene)diiron (BFD, 1,1'-biferrocenylene) were prepared and covalently attached to glassy carbon electrodes through their ethynyl group by three different electrode modification methods. Cyclic voltammetry and square wave (SW) voltammetry were used to characterize surface coverages of 1.4-5.5 × 10-10 mol cm-2, the higher of these corresponding to roughly a monolayer, based on computation of an idealized close-packing structure for ethynylbis(fulvalene)diiron (E-BFD) on a solid surface. In a dichloromethane solution containing a smaller electrolyte anion such as [PF6]- or [ClO4]-, the E-BFD-modified electrodes exhibited two quasi-Nernstian one-electron oxidations. In contrast, the current for the second oxidation process, [E-BFD]+/2+, was diminished in electrolytes containing one of the large fluoroaryl borate anions, [B(C6F5)4]- or [B(C6H3(CF3)2)4]-. The effect was enhanced for electrodes having higher surface coverages being probed at shorter voltammetric time scales. SW voltammetry showed that the diminished currents for [E-BFD]+/2+ in large-anion electrolytes are not caused by slow electron transfer. Rather, they are attributed to mixed diffusivity of the counter-anions at the electrode/solution interface, as [E-BFD]+ and the anion form the optimum (lowest-energy) configuration of a 1:1 ion pair. The interior transport of the anion required to reach this configuration may be sterically encumbered, accounting for the diminished charge transfer observed with electrolytes containing large anions.

The anodic oxidation of a series of secondary-amine-substituted chloroquinoline derivatives, 1–5, has been studied in dichloromethane/0.05M [NBu4][B(C6F5)4]. Compounds 4 and 5 contain organometallic moieties of the cymantrene family as part of the amine group. All five compounds undergo an electrochemically irreversible one-electron oxidation. For compounds 2–4, this occurs at the secondary amine group (0.86 to 0.98V vs ferrocene). The oxidations of others occur at tertiary amines located either in the side chain of the quinoline secondary amine (1, 0.68V) or in the cyclopentadienyl ring of the cymantrene moiety (5, 0.82V). The anodic reaction products have been isolated and shown to be ring-nitrogen protonated aminochloroquinolinium ions. Abstraction of a hydrogen atom from the solvent by the putative aminochloroquinoline radical cation is thought to be responsible for formation of the protonated oxidation product. Cathodic reduction of the latter regenerates the neutral starting material in an overall chemically reversible process that mimics a simple acid/base reaction at the quinoline ring nitrogen.

The electrochemical oxidation of the chemotherapeutic anti-cancer agent tamoxifen, 1, was studied by voltammetry and electrolysis. Three successive one-electron anodic reactions were observed for 1 in dichloromethane containing weakly-coordinating [B(C6F5)4]− as the supporting electrolyte anion. The first (totally irreversible) oxidation (ca 0.64V vs ferrocene) occurs at the tertiary amine, giving a putative amine radical cation 1+ that abstracts a hydrogen atom, most likely from solvent, to give the corresponding ammonium ion 1-H+. The latter is responsible for the two further one-electron oxidations, which take place at the triarylethenyl part of the molecule (E1/2 values of 0.94V and 1.33V vs ferrocene). Bulk oxidation of 1 at Eappl=0.6V produces the ammonium ion 1-H+, which can be cathodically reduced back to neutral tamoxifen in an overall chemically reversible process. The present findings are not consistent with the mechanism described in previous literature for the anodic oxidation of tamoxifen.

Three compounds have been prepared in which a 4-aminochloroquinoline moiety is covalently linked to a cyclopentadienyl manganese tricarbonyl moiety. One of these (“cymanquine”, 4) is the analogue of the potent antimalarial drug ferroquine in which an FeCp group has been replaced by a Mn(CO)3 group. The anodic electrochemistry of the new compounds was investigated in dichloromethane, using [NBu4][B(C6F5)4] as the supporting electrolyte. Compared to ferroquine, oxidations of the new compounds occur at considerably more positive potentials and are highly irreversible, being located at their amine groups rather than at the organometallic center.

Ferrocenes derivatized with a terminal lithioacetylide group react rapidly with unconnected glassy carbon and gold electrodes, giving up to monolayer-level surface coverage. The molecule-to-surface bonding is sufficiently robust to resist sonication, extended storage under dinitrogen, and thousands of repetitive voltammetric scans through the ferrocenyl oxidation wave. This “spontaneous” modification method provides a non-electrochemical pathway to the strong, apparently covalent, attachment of alkynyl-linked molecular tags to carbon and metal surfaces.

Cis-Cyclooctene, C8H14, undergoes an efficient electron-transfer (ET) catalyzed cycloaddition reaction in dichloromethane containing [NBu4][B(C6F5)(4)] as supporting electrolyte. The reactions were initiated by in-situ anodic generation of catalytic amounts of either [N(2,4-C6H3Br2)(3)](+) (1(+), "magic green") or [ReCp(CO)(3)](+) (2(+), Cp (eta(5)-C5H5)). The olefin radical chain reaction induced by ET mediation was complete in less than 10 min, some 100-1000 times faster than the optimum photochemically induced preparations of cyclobutane derivatives from cyclic olefins. Yields of up to 87% of mixtures of C16H28 isomers were obtained at an electro-synthetic level. Use of the weakly coordinating [B(C6F5)(4)](-) anion, rather than a traditional small anion such as [PF6](-) or [CIO4](-), was required to carry out the cyclization reactions. The more easily oxidized trans-cyclooctene, when anodized directly at an electrode, gave a similar isomeric mixture of cyclobutanes. Cycloheptene and cyclohexene underwent similar [2 + 2] coupling to give cyclobutane products. Cyclopentene gave a [2 + 2 + 2] cyclized trimer. The mechanism appears to involve a key radical-substrate propagation step in which an olefin radical cation reacts with a neutral olefin to give a cyclobutyl radical cation, which then accepts an electron, most likely from another olefin, to form the final neutral compound. Although the E-1/2 potentials of the ET mediators are 660-900 mV lower than the estimated oxidation potentials of the olefins, the endergonic nature of the ET initiation step works to the advantage of the chain process by favoring the radical-substrate propagation step. (C) 2015 Elsevier B.V. All rights reserved.

In contrast to ruthenocene [Ru(η(5) -C5 H5 )2 ] and dimethylruthenocene [Ru(η(5) -C5 H4 Me)2 ] (7), chemical oxidation of highly strained, ring-tilted [2]ruthenocenophane [Ru(η(5) -C5 H4 )2 (CH2 )2 ] (5) and slightly strained [3]ruthenocenophane [Ru(η(5) -C5 H4 )2 (CH2 )3 ] (6) with cationic oxidants containing the non-coordinating [B(C6 F5 )4 ](-) anion was found to afford stable and isolable metalmetal bonded dicationic dimer salts [Ru(η(5) -C5 H4 )2 (CH2 )2 ]2 [B(C6 F5 )4 ]2 (8) and [Ru(η(5) -C5 H4 )2 (CH2 )3 ]2 [B(C6 F5 )4 ]2 (17), respectively. Cyclic voltammetry and DFT studies indicated that the oxidation potential, propensity for dimerization, and strength of the resulting RuRu bond is strongly dependent on the degree of tilt present in 5 and 6 and thereby degree of exposure of the Ru center. Cleavage of the RuRu bond in 8 was achieved through reaction with the radical source [(CH3 )2 NC(S)SSC(S)N(CH3 )2 ] (thiram), affording unusual dimer [(CH3 )2 NCS2 Ru(η(5) -C5 H4 )(η(3) -C5 H4 )C2 H4 ]2 [B(C6 F5 )4 ]2 (9) through a haptotropic η(5) -η(3) ring-slippage followed by an apparent [2+2] cyclodimerization of the cyclopentadienyl ligand. Analogs of possible intermediates in the reaction pathway [C6 H5 ERu(η(5) -C5 H4 )2 C2 H4 ][B(C6 F5 )4 ] [E=S (15) or Se (16)] were synthesized through reaction of 8 with C6 H5 EEC6 H5 (E=S or Se).

A series of piano-stool complexes of the cymantrene family (cymantrene = Mn(η5-C5H5)(CO)3, 1) undergoes facile replacement of a carbonyl ligand by P(OPh)3 when oxidized by one-electron in CH2Cl2/[NBu4][B(C6F5)4]. Data on the previously characterized complexes 1, Mn(η5-C5H4NH2)(CO)3 (3) and Mn(η5-C5Me5)(CO)3 (6) have been supplemented by cyclic voltammetry (CV) and IR spectroscopy on Mn(η5-C5H4Me)(CO)3 (2), Mn(η5-C5H4I)(CO)3 (4), and Mn(η5-C5H4C(O)H)(CO)3 (5). The substitution rates, determined by digital simulations of CV scans, ranged from 4 M−1 s−1 for 6 + to 3 × 105 M−1 s−1 for 5 +. In general, a more strongly donating cyclopentadienyl substituent slows down the CO substitution rate. For mono-cyclopentadienyl substituted complexes, the logarithm of ksub is shown to increase linearly with either the weighted average of the CO stretching frequencies or the E1/2 value of the redox process. An exception to this generalization is the amine-substituted complex 3, for which the CO-substitution rate is higher than predicted by its E1/2 potential. The substitution rate of the pentamethylated Cp complex 6 + is slowed by about an order of magnitude owing to steric effects. The efficacy of this method to predict the CO-substitution rate of a cymantrene-tagged molecule was tested with a cymamtrene-derivatized diarylethene complex, 7. The measured P(OPh)3-for-CO substitution rate of 3.7 × 102 M−1 s−1 for 7 + was very close to that predicted by the E1/2 value of 7. A ligand electronic parameter, EL, of 0.62 was determined for the triphenylphosphite ligand. These studies build on the previous CO substitution-rate analyses by Sweigart and others.

Electrochemical oxidation of ReCp(CO)(2)L (Cp = eta(5)-C5H5; L = PPh3 (2), eta(2)-2-C2Me2H2 (3), eta-C2Ph2 (4)) has been studied in CH2Cl2/[NBu4][B(C6F5)(4)]. All three complexes undergo quasi-Nernstian one-electron oxidations with E-1/2 values (vs ferrocene) of 0.49 V (2/2(+)), 0.45 V (3/3(+)), and 0.15 V (4/4(+)). A second reversible one-electron oxidation is observed for 4 at 0.97 V. The radical cation 2(+) efficiently forms the Re Re-bonded dimer dication 2(2)(2+), which was isolated after chemical oxidation of 2 by [thianthrene][B(C6F5)(4)]. The 17-electron complex 3(+) shows no tendency to dimerize. On the basis of the E-1/2 value of 3 and expected potential shifts when replacing a methyl group by a hydrogen, a ligand electronic parameter, E-L, of 0.38 was calculated for pi-bonded ethylene, which is much lower than the existing literature value of 0.76. IR, ESR, and UV-vis spectra were recorded for 4(+). DFT calculations were performed on the neutral complexes, the monocations 2, 3(+), and 4(+), and the dimer dication 2(2)(2+). The SOMO of 2(+) is similar to that of the parent piano-stool complex [ReCp(CO)(3)](+) (1(+)) in being metal-based (55%) and directionally disposed to formation of a metal metal bond with another radical cation. A Re Re bond distance of 3.315 angstrom was calculated for the resulting dimer 2(2)(2+). Although the SOMO of 3(+) is also predominantly (60%) metal-based, the orbital lacks the geometry necessary to form a metal metal-bonded dimer. The HOMO of 4 is highly delocalized, having only about one-third metal character and two-thirds coming from the Cp and diphenylactylene ligands. One-electron oxidation of 4 brings about a significant change in electronic structure, with the SOMO of 4(+) seeing increased contributions from diphenylacetylene and the two carbonyls (14%), along with a decreased metal contribution (27%). The diphenylacetylene contributions are large enough to justify pi-C2Ph2 being designated as a "non-innocent" ligand in this system.

The one-electron oxidations of two dimers of half-sandwich osmium carbonyl complexes have been examined by electrochemistry, spectro-electrochemistry, and computational methods. The all-terminal carbonyl complex Os2Cp2(CO)(4) (1, Cp = eta(5)-C5H5) undergoes a reversible one-electron anodic reaction at E-1/2 = 0.41 V vs ferrocene in CH2Cl2/0.05 M [NBu4][B(C6F5)(4)], giving a rare example of a metal metal bonded radical cation unsupported by bridging ligands. The IR spectrum of 1(+) is consistent with an approximately 1:1 mixture of anti and gauche structures for the 33 e(-) radical cation in which it has retained all-terminal bonding of the CO ligands. Density functional theory (DFT) calculations, including orbital-occupancy-perturbed Mayer bond-order analyses, show that the highest-occupied molecular orbitals (HOMOs) of anti-1 and gauche-1 are metal ligand delocalized. Removal of an electron from 1 has very little effect on the Os Os bond order, accounting for the resistance of 1(+) to heterolytic cleavage. The Os Os bond distance is calculated to decrease by 0.10 angstrom and 0.06 angstrom as a consequence of one-electron oxidation of anti-1 and gauche-1, respectively. The CO-bridged complex Os2Cp2*(mu-CO)(2)(CO)(2) (Cp* = eta(5)-C5Me5), trans-2, undergoes a more facile oxidation, E-1/2 = -0.11 V, giving a persistent radical cation shown by solution IR analysis to preserve its bridged-carbonyl structure. However, ESR analysis of frozen solutions of 2(+) is interpreted in terms of the presence of two isomers, most likely anti-2(+) and trans-2(+), at low temperature. Calculations show that the HOMO of trans-2 is highly delocalized over the metal-ligand framework, with the bridging carbonyls accounting for about half of the orbital makeup. The Os Os bond order again changes very little with removal of an electron, and the Os Os bond length actually undergoes minor shortening. Calculations suggest that the second isomer of 2(+) has the anti all-terminal CO structure.

One with the surface: A method is presented for electrode modification with terminal alkynes and alkenes. Direct oxidation of these moieties leads to efficient grafting onto glassy carbon, gold, platinum, and indium tin oxide surfaces. Various ferrocenes and 5,10,15,20-(4-ethynylphenyl)porphyrin were attached in this way.