Ubiquinol and plastoquinol triphenylphosphonium conjugates can carry electrons through phospholipid membranes

Rokitskaya, Tatyana I.; Murphy, Michael P.; Vp, Skulachev; Antonenko, Yuri N.

doi:10.1016/j.bioelechem.2016.04.009

Cited by 15 publications

(9 citation statements)

References 64 publications

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“…TBB − was reported to facilitate the transfer of cations through lipid membranes by absorption to the membranes and lowering the energy barrier for the transport, and by forming ion pairs with the lipophilic cations. 166,167 For example, the rate of mitochondrial uptake of the neurotoxin 1-methyl-4-phenylpyridinium cation was shown to increase 20-fold in the presence of TBB − 67,69. …”

Section: Transport Of Small Cationic Compounds and Biomolecules Tomentioning

confidence: 99%

“…Note that, even for cations exhibiting relatively slow uptake due to a large energy barrier for transport through the lipid bilayer, the rate of uptake can be increased when paired with the lipophilic tetraphenylborate anion (TBB – , Chart ). TBB – was reported to facilitate the transfer of cations through lipid membranes by absorption to the membranes and lowering the energy barrier for the transport, and by forming ion pairs with the lipophilic cations. , For example, the rate of mitochondrial uptake of the neurotoxin 1-methyl-4-phenylpyridinium cation was shown to increase 20-fold in the presence of TBB – . , …”

Section: Transport Of Small Cationic Compounds and Biomolecules To Mi...mentioning

confidence: 99%

See 1 more Smart Citation

Mitochondria-Targeted Triphenylphosphonium-Based Compounds: Syntheses, Mechanisms of Action, and Therapeutic and Diagnostic Applications

Zielonka¹,

Joseph²,

et al. 2017

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Mitochondria are recognized as one of the most important targets for new drug design in cancer, cardiovascular, and neurological diseases. Currently, the most effective way to deliver drugs specifically to mitochondria is by covalent linking a lipophilic cation such as an alkyltriphenylphosphonium moiety to a pharmacophore of interest. Other delocalized lipophilic cations, such as rhodamine, natural and synthetic mitochondria-targeting peptides, and nanoparticle vehicles, have also been used for mitochondrial delivery of small molecules. Depending on the approach used, and the potentials of cell and mitochondrial membranes, more than 1000-fold higher mitochondrial concentration can be achieved. Mitochondrial targeting has been developed to study mitochondrial physiology and dysfunction and the interaction between mitochondria and other subcellular organelles and for treatment of a variety of diseases such as neurodegeneration and cancer. In this review, we discuss efforts to target small-molecule compounds to mitochondria for probing mitochondria function, as diagnostic tools and potential therapeutics. We describe the physicochemical basis for mitochondrial accumulation of lipophilic cations, synthetic chemistry strategies to target compounds to mitochondria, mitochondrial probes and sensors, and examples of mitochondrial targeting of bioactive compounds. Finally, we review published attempts to apply mitochondria-targeted agents for the treatment of cancer and neurodegenerative diseases.

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Section: Transport Of Small Cationic Compounds and Biomolecules Tomentioning

confidence: 99%

Section: Transport Of Small Cationic Compounds and Biomolecules To Mi...mentioning

confidence: 99%

Mitochondria-Targeted Triphenylphosphonium-Based Compounds: Syntheses, Mechanisms of Action, and Therapeutic and Diagnostic Applications

Zielonka¹,

Joseph²,

et al. 2017

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“…The essential cofactor ubiquinone (coenzyme Q10), situated in the hydrophobic core of the inner mitochondrial membrane lipid bilayer is actively involved in the transport of the electrons through the membrane. Due to its lipophilicity and its redox reversibility, ubiquinone may serve as both a mobile transporter of electrons in the redox reactions of the electron transport chain, and as a hydrogen carrier to create a proton gradient between the mitochondrial matrix and the mitochondrial intermembrane space. − Importantly, ubiquinone has three redox states: ubiquinone (oxidized), ubisemiquinone (1 electron reduction from ubiquinone to yield a semiquinone radical), and ubiquinol (2 electron reduced form). Various protonation states are also possible for the reduced species, leading to complex proton-coupled electron transfer processes. , Besides acting as a transporter of electrons and protons in the electron transport chain, ubiquinol is also involved in preventing lipid peroxidation within the mitochondrial membrane via trapping peroxyl radicals either by itself or via regenerating other antioxidants such as α-tocopherol (vitamin E). , The intermediate ubisemiquinone radical formed in these processes is however considered to promote oxidation through direct reaction with molecular oxygen to generate superoxide radical anion …”

Section: Introductionmentioning

confidence: 99%

Fluorogenic Ubiquinone Analogue for Monitoring Chemical and Biological Redox Processes

2016

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We report herein the synthesis and characterization of a fluorogenic analogue of ubiquinone designed to reversibly report on redox reactions in biological systems. The analogue, H2B-Q, consists of the redox-active quinone segment found in ubiquinone, 2,3-dimethoxy-1,4-benzoquinone, coupled to a boron-dipyrromethene (BODIPY) fluorophore segment that both imparts lipophilicity in lieu of the isoprenyl tail of ubiquinone, and reports on redox changes at the quinone/quinol segment. Redox sensing is mediated by a photoinduced electron transfer intramolecular switch. In its reduced dihydroquinone form, H2B-QH2 is highly emissive in nonpolar media (quantum yields 55-66%), while once oxidized, the resulting quinone H2B-Q emission is suppressed. Cyclic voltammetry of H2B-Q shows two reversible, 1-electron reduction peaks at -1.05 V and -1.37 V (vs ferrocene) on par with those of ubiquinone. Chemical reduction of H2B-Q by NaBH4 resulted in >200 fold emission enhancement. H2B-QH2 is shown to react with peroxyl radicals, a form of reactive oxygen species (ROS) as well as to cooperatively interact with chromanol (the active segment of α-tocopherol). Kinetic analysis further shows the antioxidant reactivity of the nonfluorescent intermediate semiquinone. We anticipate that the H2B-Q/H2B-QH2 off/on reversible couple may serve as a tool to monitor chemical redox processes in real-time and in a noninvasive manner.

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“…Redox mediators are common in nature, for example, in photosynthesis, where ubiquinols and plastoquinols shuttle charges in the thylakoid membrane. 57,58 For electrosynthetic processes, alizarin red S is a good mediator (two-electron, two-proton) for the reduction of not only aqueous indigo particle suspensions 59 but also other solid anthraquinone derivatives. 60 The selective six-electron reduction of nitroarenes to aromatic amines has been demonstrated with aqueous-soluble titanocene derivatives.…”

Section: Redox Mediationmentioning

confidence: 99%

“…Many of these mediators could be applicable in dispersions and emulsions, but much less work has been done on these multiphase systems. Redox mediators are common in nature, for example, in photosynthesis, where ubiquinols and plastoquinols shuttle charges in the thylakoid membrane. , …”

Section: Introduction To Multiphase Electrosynthesismentioning

confidence: 99%

Multiphase Methods in Organic Electrosynthesis

Marken

Wadhawan

2019

Acc. Chem. Res.

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With water providing a highly favoured solution environment for industrial processes (and in biological processes), it is interesting to develop water-based electrolysis processes for the synthesis and conversion of organic and biomass-based molecules. Molecules with low solubility in aqueous media can be dispersed/solubilised (i) by physical dispersion tools (by milling, by power ultrasound, or by high shear ultra-turrax processing), (ii) in some cases by pressurising/super-saturation (e.g. for gases), (iii) by adding co-solvents or "carriers" such as chremophor EL, or (iv) by adding surfactants to generate micelles, microemulsions, and/or stabilised biphasic conditions. This review examines and compares methodologies to bring the dispersed or multi-phase system into contact with an electrode. Both the microscopic process based on the individual particle impact as well as the overall electro-organic transformation are of interest. Distinct mechanistic cases for multi-phase redox processes are considered.Most traditional electroorganic transformations are performed in homogeneous solution with reagents, products, electrolyte, and possibly mediators or redox catalysts all in the same (usually organic) solution phase. This may lead to challenges in the product separation step and in the re-use of solvents and electrolytes. When exploiting aqueous electrolyte media, reagents and products (or even electrolyte) may be present as microdroplets or nanoparticles. Redox transformations then occur during interfacial "collisions" under multiphase conditions or

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Ubiquinol and plastoquinol triphenylphosphonium conjugates can carry electrons through phospholipid membranes

Cited by 15 publications

References 64 publications

Mitochondria-Targeted Triphenylphosphonium-Based Compounds: Syntheses, Mechanisms of Action, and Therapeutic and Diagnostic Applications

Mitochondria-Targeted Triphenylphosphonium-Based Compounds: Syntheses, Mechanisms of Action, and Therapeutic and Diagnostic Applications

Fluorogenic Ubiquinone Analogue for Monitoring Chemical and Biological Redox Processes

Multiphase Methods in Organic Electrosynthesis

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