Contrasting Voltammetric Behavior of Different Forms of Vitamin A in Aprotic Organic Solvents

Six of the major vitamers and provitamins comprising vitamin A (β-carotene, retinoic acid, retinol, retinyl palmitate, retinyl acetate, and retinal) were examined using voltammetric and controlled potential electrolysis techniques in the aprotic organic solvents acetonitrile and dichloromethane at glassy carbon and platinum electrodes. All of the compounds underwent oxidation and reduction processes and displayed a number of similarities and differences in terms of the number of redox processes and chemical reversibility of the voltammetric responses. The electrochemical properties of the compounds were strongly influenced by the functional groups on the unsaturated phytyl chains (carboxylic acid, alcohol, ester, or aldehyde groups), and not only on the fully conjugated hydrocarbon unit which is common to all forms of vitamin A. The compounds were reduced at potentials between approximately −1.7 and −2.6 vs (Fc/Fc⁺)/V (Fc = ferrocene) and oxidized at potentials between approximately +0.2 and +0.7 vs (Fc/Fc⁺)/V. The average number of electrons transferred per molecule under long time scale electrolysis experiments were found to vary between 0.4 and 4 electrons depending on the exact molecular structure and experimental conditions

Electrochemical Properties of Phenols and Quinones in Organic Solvents are Strongly Influenced by Hydrogen-Bonding with Water

The electrochemical behavior of several phenols, quinones and hydroquinone in acetonitrile (CH₃CN) with varying amounts of water were investigated to understand the effect of hydrogen-bonding on their voltammetric responses. Karl Fischer coulometric titrations were performed to obtain an accurate reading of the water concentrations. The solvent/electrolyte mixture was carefully dried using 3 Å molecular sieves to obtain an initial water content that was close to the substrate concentration (∼1 × 10^–3 M), and higher water contents were then achieved via the addition from microliter syringes. It was found that small changes in what is often considered “trace” amounts of water were sufficient to substantially change the potential and in some cases the appearance of the voltammetric waves observed during the oxidation of the phenols/hydroquinones and reduction of the quinones. Density functional theory calculations were performed on the reduced/oxidized species in the presence of varying numbers of water molecules to better understand the hydrogen-bonding interactions at the molecular level. The results highlight the importance of accurately knowing the trace water content of organic solvents when used for voltammetric experiments

Effects of Low to Intermediate Water Concentrations on Proton-Coupled Electron Transfer (PCET) Reactions of Flavins in Aprotic Solvents and a Comparison with the PCET Reactions of Quinones

The electrochemical reduction mechanisms of 2 synthesized flavins (Fl_ox) were examined in detail in deoxygenated solutions of DMSO containing varying amounts of water, utilizing variable scan rate cyclic voltammetry (ν = 0.1–20 V s^–1), controlled-potential bulk electrolysis, and UV–vis spectroscopy. Flavin <b>1</b>, which contains a hydrogen atom at N(3), is capable of donating its proton to other reduced flavin species. After 1e^– reduction, the initially formed Fl^•– receives a proton from another Fl_ox to form FlH^• (and concomitantly produce the deprotonated flavin, Fl^–), although the equilibrium constant for this process favors the back reaction. Any FlH^• formed at the electrode surface immediately undergoes another 1e^– reduction to form FlH^–, which reacts with Fl^– to form 2 molecules of Fl^•–. Further 1e^– reduction of Fl^•– at more negative potentials produces the dianion, Fl^2–, which can also be protonated by another Fl_ox to form FlH^– and Fl^–. Flavin <b>2</b>, which is methylated at N(3) (and therefore has no acidic proton), undergoes a simple chemically reversible 1e^– reduction process in DMSO provided the water content is low (<100 mM). Further 1e^– reduction of Fl^•– (from flavin <b>2</b>) at more negative potentials leads to the dianion, Fl^2–, which is protonated by trace water in solution to form FlH^–, similar to the mechanism of flavin <b>1</b> at high scan rates. Addition of sufficient amounts of water to nonaqueous solvents results in protonation of the anion radical species, Fl^•–, for both flavins, causing an increase in the amount of FlH^– in solution. This behavior contrasts with what is observed for quinones, which are also reduced in two 1e^– steps in aprotic organic solvents to form the radical anions and dianions, but are able to exist in hydrogen-bonded forms (with trace or added water) without undergoing protonation

Differences in Proton-Coupled Electron-Transfer Reactions of Flavin Mononucleotide (FMN) and Flavin Adenine Dinucleotide (FAD) between Buffered and Unbuffered Aqueous Solutions

The electrochemical reduction mechanisms of flavin mononucleotide (FMN) in buffered aqueous solutions at pH 3–11 and unbuffered aqueous solutions at pH 2–11 were examined in detail using variable-scan-rate cyclic voltammetry (ν = 0.1–20 V s^–1), controlled-potential bulk electrolysis, UV–vis spectroscopy, and rotating-disk-electrode voltammetry. In buffered solutions at pH 3–5, FMN undergoes a two-electron/two-proton (2e^–/2H⁺) reduction to form FMNH₂ at all scan rates. When the buffered pH is increased to 7–9, FMN undergoes a 2e^– reduction to form FMN^2–, which initially undergoes hydrogen bonding with water molecules, followed by protonation to form FMNH^–. At a low voltammetric scan rate of 0.1 V s^–1, the protonation reaction has sufficient time to take place. However, at a higher scan rate of 20 V s^–1, the proton-transfer reaction is outrun, and upon reversal of the scan direction, less of the FMNH^– is available for oxidation, causing its oxidation peak to decrease in magnitude. In unbuffered aqueous solutions, three major voltammetric waves were observed in different pH ranges. At low pH in unbuffered solutions, where [H⁺] ≥ [FMN], (FMN)­H^– undergoes a 2e^–/2H⁺ reduction to form (FMNH₂)­H^– (wave 1), similar to the mechanism in buffered aqueous solutions at low pH. At midrange pH values (unbuffered), where pH ≤ p<i>K</i>_a of the phosphate group and [FMN] ≥ [H⁺], (FMN)­H^– undergoes a 2e^– reduction to form (FMN^2–)­H^– (wave 2), similar to the mechanism in buffered aqueous solutions at high pH. At high pH (unbuffered), where pH ≥ p<i>K</i>_a = 6.2 of the phosphate group, the phosphate group loses its second proton to be fully deprotonated, forming (FMN)^2–, and this species undergoes a 2e^– reduction to form (FMN^2–)^2– (wave 3)

Palladium-Catalyzed Intermolecular Heck-Type Reaction of Epoxides

The palladium-catalyzed intermolecular Heck-type reaction of both cyclic and acyclic epoxides is reported with tolerance of typical polar groups and acidic protons. Suitable alkenes include styrenes, conjugate dienes, and some electron-deficient olefins. In reactions of aliphatic terminal epoxides, ring opening occurs selectively at terminal positions, and stereocenters of epoxides are fully retained. Mechanistic studies provide evidence for in situ conversion of epoxides to <i>β-</i>halohydrins, generation of alkyl radicals, and radical addition to alkenes as key steps. Cyclovoltammetric determination of reduction potentials suggests that during activation of alkyl iodides by palladium(0) complexes, inner-sphere halogen abstraction is more likely than outer-sphere single electron transfer

Palladium-Catalyzed Intermolecular Heck-Type Reaction of Epoxides

The palladium-catalyzed intermolecular Heck-type reaction of both cyclic and acyclic epoxides is reported with tolerance of typical polar groups and acidic protons. Suitable alkenes include styrenes, conjugate dienes, and some electron-deficient olefins. In reactions of aliphatic terminal epoxides, ring opening occurs selectively at terminal positions, and stereocenters of epoxides are fully retained. Mechanistic studies provide evidence for in situ conversion of epoxides to <i>β-</i>halohydrins, generation of alkyl radicals, and radical addition to alkenes as key steps. Cyclovoltammetric determination of reduction potentials suggests that during activation of alkyl iodides by palladium(0) complexes, inner-sphere halogen abstraction is more likely than outer-sphere single electron transfer

The Hydrogen-Bonded Dianion of Vitamin K₁ Produced in Aqueous–Organic Solutions Exists in Equilibrium with Its Hydrogen-Bonded Semiquinone Anion Radical

When the quinone, vitamin K₁ (VK₁), is electrochemically reduced in aqueous-acetonitrile solutions (CH₃CN with 7.22 M H₂O), it undergoes a two-electron reduction to form the dianion that is hydrogen-bonded with water [VK₁(H₂O)_<i>y</i>^2–]. EPR and voltammetry experiments have shown that the persistent existence of the semiquinone anion radical (also hydrogen-bonded with water) [VK₁(H₂O)_<i>x</i>^–•] in aqueous or organic–aqueous solutions is a result of VK₁(H₂O)_<i>y</i>^2– undergoing a net homogeneous electron transfer reaction (comproportionation) with VK₁, and not via direct one-electron reduction of VK₁. When 1 mM solutions of VK₁ were electrochemically reduced by two electrons in aqueous-acetonitrile solutions, quantitative EPR experiments indicated that the amount of VK₁(H₂O)_<i>x</i>^–• produced was up to approximately 35% of all the reduced species. <i>In situ</i> electrochemical ATR-FTIR experiments on sequentially one- and two-electron bulk reduced solutions of VK₁ (showing strong absorbances at 1664, 1598, and 1298 cm^–1) in CH₃CN containing <0.05 M H₂O led to the detection of VK₁^–• with strong absorbances at 1710, 1703, 1593, 1559, 1492, and 1466 cm^–1 and VK₁(H₂O)_<i>y</i>^2– with strong absorbances at 1372 and 1342 cm^–1

Palladium-Catalyzed Intermolecular Heck-Type Reaction of Epoxides

The palladium-catalyzed intermolecular Heck-type reaction of both cyclic and acyclic epoxides is reported with tolerance of typical polar groups and acidic protons. Suitable alkenes include styrenes, conjugate dienes, and some electron-deficient olefins. In reactions of aliphatic terminal epoxides, ring opening occurs selectively at terminal positions, and stereocenters of epoxides are fully retained. Mechanistic studies provide evidence for in situ conversion of epoxides to <i>β-</i>halohydrins, generation of alkyl radicals, and radical addition to alkenes as key steps. Cyclovoltammetric determination of reduction potentials suggests that during activation of alkyl iodides by palladium(0) complexes, inner-sphere halogen abstraction is more likely than outer-sphere single electron transfer

Palladium-Catalyzed Intermolecular Heck-Type Reaction of Epoxides

The palladium-catalyzed intermolecular Heck-type reaction of both cyclic and acyclic epoxides is reported with tolerance of typical polar groups and acidic protons. Suitable alkenes include styrenes, conjugate dienes, and some electron-deficient olefins. In reactions of aliphatic terminal epoxides, ring opening occurs selectively at terminal positions, and stereocenters of epoxides are fully retained. Mechanistic studies provide evidence for in situ conversion of epoxides to <i>β-</i>halohydrins, generation of alkyl radicals, and radical addition to alkenes as key steps. Cyclovoltammetric determination of reduction potentials suggests that during activation of alkyl iodides by palladium(0) complexes, inner-sphere halogen abstraction is more likely than outer-sphere single electron transfer

Palladium-Catalyzed Intermolecular Heck-Type Reaction of Epoxides

The palladium-catalyzed intermolecular Heck-type reaction of both cyclic and acyclic epoxides is reported with tolerance of typical polar groups and acidic protons. Suitable alkenes include styrenes, conjugate dienes, and some electron-deficient olefins. In reactions of aliphatic terminal epoxides, ring opening occurs selectively at terminal positions, and stereocenters of epoxides are fully retained. Mechanistic studies provide evidence for in situ conversion of epoxides to <i>β-</i>halohydrins, generation of alkyl radicals, and radical addition to alkenes as key steps. Cyclovoltammetric determination of reduction potentials suggests that during activation of alkyl iodides by palladium(0) complexes, inner-sphere halogen abstraction is more likely than outer-sphere single electron transfer