Triphenylphosphonium Ion Research Articles

Surface functionalized perovskite nanocrystals: a design strategy for organelle-specific fluorescence lifetime multiplexing.

Fluorescent molecules or materials with high photoluminescence quantum yields and stability towards photobleaching are ideally suited for multiplex imaging. Despite complying with such properties, perovskite nanocrystals (Pv-NCs) are rarely used for bioimaging owing to their toxicity and limited stability in aqueous media and towards human physiology. We aim to address these deficiencies by designing core-shell structures with Pv-NCs as the core and surface-engineered silica as the shell (SiO2@Pv-NCs) since silica is recognized as a biologically benign carrier material and is known to be excreted through urine. The post-grafting methodology is adopted for developing [SiO2@Pv-NCs]tpm and [SiO2@Pv-NCs]tsy (tpm: triphenylphosphonium ion, tsy: tosylsulfonamide) for specific imaging of mitochondria and endoplasmic reticulum (ER) of the live HeLa cell, respectively. A subtle difference in their average fluorescence decay times ([SiO2@Pv-NCs]tpm: tpm τ av = 3.1 ns and [SiO2@Pv-NCs]tsy: tsy τ av = 2.1 ns) is used for demonstrating a rare example of perovskite nanocrystals in fluorescence lifetime multiplex imaging.

Mitochondria-targeting EGCG derivatives protect H9c2 cardiomyocytes from H2O2-induced apoptosis: design, synthesis and biological evaluation.

Pathologies related to cardiovascular diseases mostly emerge as a result of oxidative stress buildup in cardiomyocytes. The heavy load of mitochondrial oxidative phosphorylation in cardiac tissues corresponds to a surge in oxidative stress leading to mitochondrial dysfunction and cellular apoptosis. Thus, scavenging the reactive oxygen species (ROS) linked to mitochondria can significantly improve cardio-protection. Epigallocatechin-3-gallate (EGCG), the major polyphenol found in green tea has been extensively studied for its profound health-beneficial activities. Herein, we designed and synthesized a series of mitochondrial-targeting EGCG derivatives, namely MitoEGCGn (n = 4, 6, 8) by incorporating triphenylphosphonium ion onto it using different linkers. MitoEGCGn were found to be non-toxic to H9c2 rat cardiomyocyte cells even at higher doses in comparison to its parent molecule EGCG. Interestingly, MitoEGCG4 and MitoEGCG6 protected the H9c2 cardiomyocyte cells from the oxidative damage induced by H2O2 whereas EGCG was found to be toxic and ineffective in protecting the cells from H2O2 damage. MitoEGCG4 and MitoEGCG6 also protected the cells from the H2O2-induced disruption of mitochondrial membrane potential as well as activation of apoptosis as revealed by pro-caspase 3 expression profile, DNA fragmentation assay, and AO/EtBr staining. Taken together, our study shows that the mitochondria targeting EGCG derivatives were able to effectively combat the H2O2-induced oxidative stress in H9c2 cardiomyocytes. They eventually augmented the mitochondrial health of cardiomyocytes by maintaining the mitochondrial function and attenuating apoptosis. Overall, MitoEGCG4 and MitoEGCG6 could provision a cardioprotective role to H9c2 cardiomyocytes at the time of oxidative insults related to mitochondrial dysfunction-associated injuries.

Mitochondriotropic Derivative of Ethyl Ferulate, a Dietary Phenylpropanoid, Exhibits Enhanced Cytotoxicity in Cancer Cells via Mitochondrial Superoxide-Mediated Activation of JNK and AKT Signalling.

Specific targeting of anti-cancer drugs to mitochondria is an emerging strategy to enhance cancer cell killing whilst simultaneously overcoming the problem of drug resistance, low bioavailability and limited clinical success of natural products. We have synthesized a mitochondria targeted derivative of Ethyl Ferulate (EF, a naturally occurring ester of ferulic acid), by conjugating it with triphenylphosphonium ion and compared its cytotoxicity with the parent molecule. Mito-Ethyl Ferulate (M-EF) was found to be more potent than EF (~ 400-fold) in inhibiting the growth of A549 and MCF-7 cells and suppressing the clonogenic potential of A549 cells. Notably, M-EF did not induce any cytotoxicity in normal cells (mouse normal fibroblast cells) up to a concentration of 25μM. Furthermore, M-EF treatment induced significantly higher cell death in MCF-7 and A549 cells, as compared to EF via induction of apoptosis. M-EF treatment increased mitochondrial superoxide production and induced mitochondrial DNA damage and phosphorylation of JNK and AKT in A549 cells. Furthermore, M-EF induced increase in mitochondrial superoxide production and cytotoxicity was attenuated on pre-treatment with mitochondria-targeted antioxidant (mitoTEMPO) indicating the involvement of mitochondrial ROS in the cytotoxic effects of M-EF. Finally, in silico prediction revealed putative mitochondrial targets of M-EF which are known to regulate mitochondrial ROS and cell viability. In conclusion, the improved cytotoxic efficacy of M-EF exemplifies the use of mitochondria-specific drug delivery in future development of natural product based mitochondrial pharmacology.

Development of AB3-Type Novel Phthalocyanine and Porphyrin Photosensitizers Conjugated with Triphenylphosphonium for Higher Photodynamic Efficacy.

There are a number of lipophilic cations that can be chosen; the triphenylphosphonium (TPP) ion is particularly unique for mitochondrion targeting, mainly due to its simplicity in structure and ease to be linked to the target molecules. In this work, mitochondrion-targeted AB3-type novel phthalocyanine and porphyrin photosensitizers (PSs) were synthesized and their photophysical photochemical properties were defined. Fluorescence quantum yields (ΦF) are 0.009, 0.14, 0.13, and 0.13, and the singlet-oxygen quantum yields (ΦΔ) are 0.27, 0.75, 0.57, and 0.58 for LuPcPox(OAc), AB 3 TPP-Pc, AB 3 TPP-Por-C4, and AB 3 TPP-Por-C6, respectively. To evaluate the photodynamic efficacy of the TPP-conjugated PS cell viabilities of A549 and BEAS-2B lung cells were comparatively measured and IC-50 values were determined. AB 3 TPP-Por-C4, AB 3 TPP-Por-C6, and AB 3 TPP-Pc compounds compared to the reference molecules ZnPc and H 2 TPP were found to be highly cytotoxic (sub-micromolar concentration) under the light. LuPcPox(OAc) is the most effective molecule regarding cell killing (the activity). The cell killing of the TPP-conjugated porphyrin derivatives exhibits a similar response compared to LuPcPox(OAc) when the light absorbing factor of the PS is normalized at 660 nm: TPP-conjugated porphyrins absorb less light (lower extinction coefficient) but produce more radical species (higher singlet-oxygen quantum yield) and therefore effectively kill the cells. The singlet oxygen-producing capacity of AB 3 TPP-Pc is almost 3 times higher compared to LuPcPox(OAc) and 50% more efficient with respect to ZnPc, suggesting that TPP-conjugated phthalocyanine may serve as a good photosensitizer for photodynamic therapy (PDT). The high singlet oxygen generation capacity of these novel TPP-conjugated porphyrin and phthalocyanine PS suggests that they might be useful for PDT requiring lower photosensitizer concentration and reduced energy deposited through less light exposure.

Electrochemically Enabled, Nickel-Catalyzed Dehydroxylative Cross-Coupling of Alcohols with Aryl Halides.

As alcohols are ubiquitous throughout chemical science, this functional group represents a highly attractive starting material for forging new C-C bonds. Here, we demonstrate that the combination of anodic preparation of the alkoxy triphenylphosphonium ion and nickel-catalyzed cathodic reductive cross-coupling provides an efficient method to construct C(sp2)-C(sp3) bonds, in which free alcohols and aryl bromides-both readily available chemicals-can be directly used as coupling partners. This nickel-catalyzed paired electrolysis reaction features a broad substrate scope bearing a wide gamut of functionalities, which was illustrated by the late-stage arylation of several structurally complex natural products and pharmaceuticals.

Triphenylphosphonium-Derived Protein Sulfenic Acid Trapping Agents: Synthesis, Reactivity, and Effect on Mitochondrial Function.

Redox-mediated protein modifications control numerous processes in both normal and disease metabolism. Protein sulfenic acids, formed from the oxidation of protein cysteine residues, play a critical role in thiol-based redox signaling. The reactivity of protein sulfenic acids requires their identification through chemical trapping, and this paper describes the use of the triphenylphosphonium (TPP) ion to direct known sulfenic acid traps to the mitochondria, a verified source of cellular reactive oxygen species. Coupling of the TPP group with the 2,4-(dioxocyclohexyl)propoxy (DCP) unit and the bicyclo[6.1.0]nonyne (BCN) group produces two new probes, DCP-TPP and BCN-TPP. DCP-TPP and BCN-TPP react with C165A AhpC-SOH, a model protein sulfenic acid, to form the expected adducts with second-order rate constants of k = 1.1 M-1 s-1 and k = 5.99 M-1 s-1, respectively, as determined by electrospray ionization time-of-flight mass spectrometry. The TPP group does not alter the rate of DCP-TPP reaction with protein sulfenic acid compared to dimedone but slows the rate of BCN-TPP reaction compared to a non-TPP-containing BCN-OH control by 4.6-fold. The hydrophobic TPP group may interact with the protein, preventing an optimal reaction orientation for BCN-TPP. Unlike BCN-OH, BCN-TPP does not react with the protein persulfide, C165A AhpC-SSH. Extracellular flux measurements using A549 cells show that DCP-TPP and BCN-TPP influence mitochondrial energetics, with BCN-TPP producing a drastic decrease in basal respiration, perhaps due to its faster reaction kinetics with sulfenylated proteins. Further control experiments with BCN-OH, TPP-COOH, and dimedone provide strong evidence for mitochondrial localization and accumulation of DCP-TPP and BCN-TPP. These results reveal the compatibility of the TPP group with reactive sulfenic acid probes as a mitochondrial director and support the use of the TPP group in the design of sulfenic acid traps.

Simultaneous Detection of Mitochondrial Hydrogen Selenide and Superoxide Anion in HepG2 Cells under Hypoxic Conditions.

Previous studies proposed that sodium selenite (Na2SeO3) was reduced to hydrogen selenide (H2Se) and that H2Se subsequently reacted with oxygen to generate superoxide anion (O2•-), resulting in tumor cell oxidative stress and apoptosis. However, under the hypoxic conditions of a solid tumor, the anticancer mechanism of sodium selenite remains unclear. To reveal the exact anticancer mechanism of selenite in the real tumor microenvironment, we developed a mitochondria-targeting fluorescent nanosensor, Mito-N-D-MSN, which was fabricated from mesoporous silica nanoparticles (MSNs) loaded with two small-molecule fluorescent probes and a triphenylphosphonium ion as a mitochondria-targeting moiety. With Mito-N-D-MSN, the fluctuations in the contents of mitochondrial hydrogen selenide (H2Se) and superoxide anion (O2•-) in HepG2 cells induced by Na2SeO3 were investigated in detail under normoxic and hypoxic conditions. The results showed that the mitochondrial H2Se content increased gradually, while the O2•- content remained unchanged in HepG2 cells under hypoxic conditions, which indicated that the anticancer mechanism of selenite involves nonoxidative stress in the real tumor microenvironment.

Application of Mitochondria-Targeted Pharmaceuticals for the Treatment of Heart Disease.

Mitochondria fulfill the massive energy demands of the human heart through oxidative phosphorylation (OXPHOS) which couples nutrient oxidation and the reduction of molecular oxygen (O2) to the phosphorylation of ADP. Reactive oxygen species (ROS) are also generated during OXPHOS which can be damaging at high levels but serve as secondary messengers when produced in a controlled manner. Here, I review how disruption of control over mitochondrial ROS production can lead to the pathogenesis of a range of cardiovascular diseases (CVD) including decompensated left ventricular hypertrophy, alcoholic and diabetic hypertrophy, myocardial infarction (MI), ischemic-reperfusion injury (IR), and heart failure. In particular I focus on the function of protein S-glutathionylation (PGlu) reactions, a rapid and reversible redox signaling mechanism that involves the conjugation and removal of glutathione from cysteine switches, in the modulation of ROS production in myocardial mitochondria and how these reactions become deregulated in heart disease. I also discuss the use of mitochondria penetrating antioxidants in the treatment of heart disease. I propose that heart disease related to deregulated PGlu reactions can be treated with a novel and hypothetical class of mitochondria penetrating reduced glutathione (GSH) molecules called MitoGSH. This synthetic form of GSH can be tagged with either SS peptides or triphenylphosphonium ions to ensure accumulation in mitochondria which could restore glutathione levels and preserve redox buffering networks. Mitochondria penetrating antioxidants have been shown to be efficient at restoring mitochondrial antioxidant defense in CVD. However, CVD and various other disorders are associated with a depletion of GSH pools. Use of mitochondria-targeted GSH analogs could serve as a more efficient means of treating heart disease since it would allow for the direct restoration of GSH levels and preserve mitochondrial redox buffering and signaling capacity.

Optically transparent polycarbonate/clay nanocomposites with improved performance using phosphonium modified organoclay: Preparation and characterizations

The present work focuses on the morphology and properties of polycarbonate (PC)/clay nanocomposites prepared through melt blending and solution blending at two different loadings of organoclay (0.5 and 1 phr). The oraganoclay was prepared by incorporating thermally 2‐oxopropyl triphenyl phosphonium ion (OTPP) into the clay gallery with an intention to preserve the optical transparency of PC in the PC/clay nanocomposites. An increase in gallery height from 1.24 to 1.86 nm along with the extraordinary thermal stability (∼1.34% wt loss at 280°C, after 20 min) of the OTPP modified montmorillonite (OTPP‐MMT) made it suitable for retention of optical transparency of PC and delamination of the clay platelets in the nanocomposites. The morphological analysis revealed that the clay platelets were randomly dispersed into the PC matrix. An increase in glass transition temperature (Tg) as well as thermal stability of the PC in the nanocomposites was evident from thermal analysis. The strength and modulus of PC increased extensively with increase in OTPP‐MMT loading in the nanocomposites. The nanocomposites were found to retain optical transparency of PC without generation of any color in both the blending technique. POLYM. COMPOS., 199–212, 2016. © 2014 Society of Plastics Engineers

Molybdenum Trioxide Nanoparticles with Intrinsic Sulfite Oxidase Activity

Sulfite oxidase is a mitochondria-located molybdenum-containing enzyme catalyzing the oxidation of sulfite to sulfate in the amino acid and lipid metabolism. Therefore, it plays a major role in detoxification processes, where defects in the enzyme cause a severe infant disease leading to early death with no efficient or cost-effective therapy in sight. Here we report that molybdenum trioxide (MoO3) nanoparticles display an intrinsic biomimetic sulfite oxidase activity under physiological conditions, and, functionalized with a customized bifunctional ligand containing dopamine as anchor group and triphenylphosphonium ion as targeting agent, they selectively target the mitochondria while being highly dispersible in aqueous solutions. Chemically induced sulfite oxidase knockdown cells treated with MoO3 nanoparticles recovered their sulfite oxidase activity in vitro, which makes MoO3 nanoparticles a potential therapeutic for sulfite oxidase deficiency and opens new avenues for cost-effective therapies for gene-induced deficiencies.

Cell-penetrating peptoids: Introduction of novel cationic side chains

During the last decade peptoid-based molecular transporters have been broadly applied. They are highly valued for their easy synthesis and their superior stability against enzymatic degradation. The special structure of peptoids generally allows introducing a variety of different side chains. Yet, the cationic side chains of cell-penetrating peptoids displayed solely lysine- or arginine-like structures. Thus this report is intended to extend the spectrum of cationic peptoid side chains. Herein, we present novel functional groups, like polyamines, aza-crown ethers, or triphenylphosphonium ions that are introduced into peptoids for the first time. In addition, the obtained peptoids were tested for their cell-penetrating properties.

Ion‐Pairing of Phosphonium Salts in Solution: CH⋅⋅⋅Halogen and CH⋅⋅⋅π Hydrogen Bonds

The (1) H NMR chemical shifts of the C(α)H protons of arylmethyl triphenylphosphonium ions in CD2 Cl2 solution strongly depend on the counteranions X(-) . The values for the benzhydryl derivatives Ph2 CHPPh3 (+) X(-) , for example, range from δH =8.25 (X(-) =Cl(-) ) over 6.23 (X(-) =BF4 (-) ) to 5.72 ppm (X(-) =BPh4 (-) ). Similar, albeit weaker, counterion-induced shifts are observed for the ortho-protons of all aryl groups. Concentration-dependent NMR studies show that the large shifts result from the deshielding of the protons by the anions, which decreases in the order Cl(-) > Br(-) ≫ BF4 (-) > SbF6 (-) . For the less bulky derivatives PhCH2 PPh3 (+) X(-) , we also find CH⋅⋅⋅Ph interactions between C(α)H and a phenyl group of the BPh4 (-) anion, which result in upfield NMR chemical shifts of the C(α)H protons. These interactions could also be observed in crystals of (p-CF3 -C6 H4 )CH2 PPh3 (+) BPh4 (-) . However, the dominant effects causing the counterion-induced shifts in the NMR spectra are the CH⋅⋅⋅X(-) hydrogen bonds between the phosphonium ion and anions, in particular Cl(-) or Br(-) . This observation contradicts earlier interpretations which assigned these shifts predominantly to the ring current of the BPh4 (-) anions. The concentration dependence of the (1) H NMR chemical shifts allowed us to determine the dissociation constants of the phosphonium salts in CD2 Cl2 solution. The cation-anion interactions increase with the acidity of the C(α)H protons and the basicity of the anion. The existence of CH⋅⋅⋅X(-) hydrogen bonds between the cations and anions is confirmed by quantum chemical calculations of the ion pair structures, as well as by X-ray analyses of the crystals. The IR spectra of the Cl(-) and Br(-) salts in CD2 Cl2 solution show strong red-shifts of the CH stretch bands. The CH stretch bands of the tetrafluoroborate salt PhCH2 PPh3 (+) BF4 (-) in CD2 Cl2 , however, show a blue-shift compared to the corresponding BPh4 (-) salt.

Phosphonium modified organoclay as potential nanofiller for the development of exfoliated and optically transparent polycarbonate/clay nanocomposites: Preparation and characterizations

Here, we report the preparation and properties of optically transparent polycarbonate (PC)/clay nanocomposites through the conventional methods of nanocomposites preparation (melt blending and solution blending) leading mainly to the exfoliation of thermally stable phosphonium modified organoclay. The organic modification of the sodium montmorillonite (Na-MMT) was done by the inclusion of ethyl triphenylphosphonium (ETPP) ion inside the layer spacing of Na-MMT clay through ion exchange reaction. The resulting quaternary phosphonium modified organoclay showed outstanding stability against thermal degradation in isothermal TGA analysis at the processing temperature of PC (280°C). Wide angle X-ray diffraction (WAXD) and transmission electron microscopy (TEM) studies revealed that, the MMT layers were well exfoliated at lower loading (0.5phr) of ETPP-MMT, whereas, presence of a mixed clay morphology of exfoliation with minor intercalation was obtained at higher loading (1phr) of the clay in both the melt and solution blended PC/ETPP-MMT nanocomposites. The tensile strength and Young modulus were increased, whereas, elongation at break was decreased with increase in clay loading in both the melt and solution blended ETPP-MMT nanocomposites. The thermo-mechanical properties of the nanocomposites were superior to that of the neat PC in both the glassy and rubbery regions. The optical transparency of PC was retained without development of any colour in the PC/ETPP-MMT nanocomposites.

Evaluation of (4-[18F]Fluorophenyl)triphenylphosphonium Ion. A Potential Myocardial Blood Flow Agent for PET

The lipophilic cationic compound, (4-[¹⁸F]fluorophenyl)triphenylphosphonium ion (¹⁸F-FTPP) was synthesized and evaluated as a potential positron emission tomography (PET) myocardial perfusion agent. ¹⁸F-FTPP was prepared from (4-nitrophenyl)triphenylphosphonium nitrate and ammonium [¹⁸F]fluoride by nucleophilic aromatic substitution and was purified by high performance liquid chromatography before use. Biodistribution studies were performed in rats at 5, 30, 60 min (five rats per time point). Three rats were evaluated by microPET imaging after injection of ¹⁸F-FTPP. In addition, microPET imaging in rabbits (three) was performed before and after occlusion of the left anterior descending (LAD) artery with ¹³NH₃ (111 MBq) and ¹⁸F-FTPP (74 MBq). Biodistribution data in rats showed rapid blood clearance and high levels of accumulation in the heart; 75:1 heart-to-blood ratio at 30 min. Uptake of radioactivity in the heart was 1.64% ID/G, 1.51% ID/g, and 1.57% ID/g at 5, 30, and 60 min. At 5, 30, and 60 min, lung activity was 0.69% ID/g, 0.03% ID/g, and 0.38% ID/g, and liver uptake was 0.34% ID/g, 0.18% ID/g, and 0.17% ID/g. Heart-to-lung ratios at 5, 30, and 60 min were 2, 5, and 4. Bone accumulation was minimal. MicroPET imaging in both rats and rabbits after injection of ¹⁸F-FTPP demonstrated an initial spike of activity in the myocardium corresponding to blood flow followed by a plateau after 1 min. Region of interest analysis of microPET images of normal and LAD-occluded rabbits with ¹³NH₃ and ¹⁸F-FTPP indicated similar distributions of the two tracers in both normal and altered blood flow regions. The excellent heart-to-blood ratio of ¹⁸F-FTPP and its correlation with ¹³NH₃ distribution in normal and LAD-occluded rabbits suggest that this radiopharmaceutical may have potential as a PET agent for characterizing mitochondrial damage and/or myocardial blood flow.

Mitochondria-targeting properties and photodynamic activities of porphyrin derivatives bearing cationic pendant

Four meso-tetraphenylporphyrin derivatives bearing either triphenylphosphonium ion-(P1 and P2) or triethylammonium ion-(P3 and P4) terminated alkoxy group at either para-(P1 and P3) or meta-(P2 and P4) position of one meso-phenyl group were designed and synthesized. P1-P4 show similar absorption and fluorescence emission spectra and (1)O(2) quantum yields. The more lipophilic nature of triphenylphosphonium ion over triethylammonium ion renders P1 and P2 higher octanol/water partition coefficients than P3 and P4. Confocal fluorescence microscopy proved that P1-P4 are all mitochondria-targeting. MTT assay showed that P1-P4 presented significant phototoxicity at the concentrations that dark toxicity is negligible towards human breast cancer cell line MCF-7 cells, displaying their application potential in PDT.

Comparative study of the N-isobutyl-(2E,6Z)-dodecadienamide chemical and electrochemical syntheses

In order to show the advantages and limitations of organic electrosynthesis in the total synthesis of a natural product, one of the promising green chemistry techniques in organic chemistry, the synthesis of N-isobutyl-(2E,6Z)-dodecadienamide (3) was undertaken. Chemical and electrochemical routes that use the same intermediates were used to carry out the syntheses. Four reactions were compared from a green chemistry point of view in the synthesis of 3: (a) alcohol to aldehyde oxidation, (b) the Horner–Emmons reaction, (c) carboxylic acid amidation with triphenylphosphonium ions and (d) the Wittig reaction. All the electrolyses were carried out in non-divided cells at a constant current. The electrochemical method in the oxidation reaction of alcohols and the carboxylic acid amidation gave better yields (95% and 67%, respectively) than the corresponding chemical reactions. The Horner–Emmons reaction gave the same yields in both techniques (80–85%); however, the electrochemical method was more environmentally friendly, due to the fact that the base used was electrogenerated, avoiding corrosive and sensitive base manipulation. Finally, the electrochemical Wittig reaction was unsuccessful in the different experimental conditions attempted, and only the chemical method produced the target product. This study demonstrated that organic electrochemistry can be a reliable method for the synthesis of important intermediates, but not all electrochemical reactions can compete with the already well-established methods of organic chemistry.

Novel HPMA Copolymer-Bound Constructs for Combined Tumor and Mitochondrial Targeting

A wide variety of therapeutic agents may benefit by specifically directing them to the mitochondria in tumor cells. The current work aimed to design delivery systems that would enable a combination of tumor and mitochondrial targeting for such therapeutic entities. To this end, novel HPMA copolymer-based delivery systems that employ triphenylphosphonium (TPP) ions as mitochondriotropic agents were developed. Constructs were initially synthesized with fluorescent labels substituting for drug and were used for validation experiments. Microinjection and incubation experiments performed using these fluorescently labeled constructs confirmed the mitochondrial targeting ability. Subsequently, HPMA copolymer-drug conjugates were synthesized using a photosensitizer mesochlorin e 6 (Mce 6). Mitochondrial targeting of HPMA copolymer-bound Mce 6 enhanced cytotoxicity as compared to nontargeted HPMA copolymer-Mce 6 conjugates. Minor modifications may be required to adapt the current design and allow for tumor site-specific mitochondrial targeting of other therapeutic agents.

ChemInform Abstract: Electrochemical Preparation and Some Reactions of Alkoxy Triphenylphosphonium Ions.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Electrochemical Preparation and Some Reactions of Alkoxy Triphenylphosphonium Ions.

The formation of an alkoxy triphenylphosphonium ion by anodic oxidation of Ph3 P in the presence of an alcohol was reinvestigated. When a CH2CL2 solution of Ph3P, Ph3P+H·ClO-4, and an alcohol was subjected to constantcurrent electrolysis in an undivided cell equipped with a graphite anode and a Pt cathode, the 31P-NMR spectra of the resulting electrolyte showed that alkoxy triphenylphosphonium perchlorates (2) were formed in good to fair yields from primary and secondary aliphatic alcohols, while allylic and benzylic alcohols were transformed to the correspinding alkyl phosphonium ions, and in the case of tertiary aliphatic alcohols, no formation of the corresponding alkoxy or alkyl phosphonium ions was recognized at all. The isolation of 2 thus formed was achieved in good yields by a simple procedure. For the electrolysis, Ph3P+H·BF-4 could be utilized insted of the perchlorate salt, giving an alkoxy triphenylphosphonium tetrafluoroborate (3) from primary and secondary aliphatic alcohols. The reaction of the alkoxy phosphonium ions prepared from β- and α-cholestanol with various nucleophiles such as Bu4N+·X- (X=Br, Cl, F, N3, SCN), PhSH, and PhOH was examined. The results indicated that the reaction site of the phosphonium ions is dictated by the identity of the nucleophile. A soft nucleophile was apt to attack at the α-carbon, giving the corresponding SN2 reaction product in a good yield, while a hard one tended to react at the phosphorus of the phosphonium ion, leading to the regeneration of the cholestanol.

Structural study of arylmethyldiphenylferrocenylphosphonium salts

The effect of the ferrocenyl group (Fc) directly bonded to the phosphonium phosphorus atom has been compared with the effect of the phenyl group by examining crystal and molecular structure of two benzyldiphenylferrocenylphosphonium salts, and the shielding effects in the NMR spectra of four pairs of diphenylferrocenyl and triphenylphosphonium ions. The results indicate weak electron-donating effects of the Fc group, with some contribution of theCp +PR 3 ylidic resonance structure.