Dicyclohexylcarbodiimide Research Articles

Thiourea-functionalized graphene aerogel for the aqueous phase sensing of toxic Pb(II) metal ions and H2O2

A simpler approach of functionalization for the fabrication of thiourea-functionalized-Graphene Aerogel (t-GA) is described here. Graphene Aerogel (GA) was synthesized from bio-mass, which on a simpler oxidative treatment get converted to its water-soluble version due to the impregnation of several oxygenous functionalities like carboxylic, hydroxyl, etc. Further, these carboxylated groups have been functionalized with the molecules of thiourea using the long known dicyclohexylcarbodiimide (DCC) as a coupling agent. The as-synthesized t-GA shows bright yellow fluorescence with a quantum yield of ~3% and holds the high-aqueous solubility and photostability. The fluorescence property of t-GA has been used here for the specific and selective sensing of toxic lead (Pb(II)) metal ions from the used many other metal ions via the fluorescence quenching and showed a limit of detection ~7.3 nM. Further, the mechanism for selective sensing was studied in detail and found to be preferable via ligand to metal charge transfer quenching mechanism. The cyclic voltammetry studies supported the selective sensing of Pb(II). Moreover, t-GA has also been studied for the sensing of hydrogen peroxide and as a yellow fluorescent ink.

Study on removal of organic dyes by Fe3O4/amidation modified waste polystyrene composites

Design and fabrication of structurally optimized absorbents are important for wastewater treatment such as dyes removal. Herein, modifying the environmentally harmful waste polystyrene foam as an efficient recyclable adsorbent for organic dyes is important Magnetic amidated modified polystyrene (Fe 3 O 4 /PS-SD) was prepared by Friedel–Crafts reaction, N,N”-dicyclohexylcarbodiimide (DCC) dehydration condensation, and chemical co-precipitation reaction. Fe 3 O 4 /PS-SD had highly efficient removing performance for organic dyes in large volume of water sample solutions, and the equilibrium was achieved in 0.5 h. The maximum adsorption capacity for Methylene blue (MB), Safranine T (ST), and Congo red (CR) were 620.32 mg g −1 , 679.63 mg g −1 , and 1425.77 mg g −1 , respectively, at room temperature according to the Langmuir adsorption isotherm (R 2 > 0.91). The kinetic data of the three dyes followed pseudo-second-order kinetics. After ten regeneration cycles, the removal rate remained high (> 80%). Experimental results showed that Fe 3 O 4 /PS-SD was an excellent adsorbent for water treatment with high regeneration property and thermal stability. • Modification of waste materials. • High adsorption capacity. • Separable and thermally stable. • Recyclable.

Influence of two carbodiimides on the bond strength of universal adhesives to dentin.

The pretreatment of dentin with cross-linking agents during bonding procedures has been proposed to improve the mechanical properties of the collagen in the hybrid layer and reduce the biodegradation of the adhesive interface. The aim of this study was to evaluate the influence of pretreatment with two carbodiimides on the dentin bond strength of universal adhesives, after thermocycling. Three universal adhesives in the self-etching mode were used (Single Bond Universal-SBU, Clearfil Universal-CLU and Ambar Universal-ABU). A self-etching adhesive system (Clearfil SE Bond-CSB) was used as control. Two carbodiimides, 1-ethyl-3-(3'-dimethylaminopropyl)-carbodiimide (EDC) and N,N'-dicyclohexylcarbodiimide (DCC), were applied for 1min. The excess solution was removed with absorbent paper and the universal adhesives were applied. The specimens were stored for 24h in distilled water at 37°C or 10,000 thermal cycles (5-55°C, 30s) and then were prepared for microtensile bond strength test (n = 4 teeth, average of 21 sticks per group). Data were analyzed using three-way ANOVA and Tukey's (α = 5%). After 24h, SBU and CSB had statistically similar bond strength values for the control groups (22.07 ± 9.03 and 19.82 ± 7.28MPa), with EDC (30.21 ± 11.30 and 19.67 ± 5.36MPa) and DCC (30.12 ± 13.43 and 19.82 ± 7.28MPa) pretreatments (p > 0.05). The use of EDC (32.57 ± 9.60MPa) and DCC (24.71 ± 9.87MPa) showed statistically higher bond strength for CLU than for the control group (14.62 ± 6.16MPa; p < 0.05). After thermocycling, the SBU, CLU, and CSB groups showed statistically similar bond strengths with the use of EDC (27.08 ± 8.44; 18.74 ± 5.41; and 24.55 ± 10.43MPa) and without the use of cross linkers (20.06 ± 7.99; 22.55 ± 9.04; and 26.54 ± 10.13MPa; p > 0.05). Groups tested after 24h in distilled water presented higher bond strength than those submitted to thermocycling. It can be concluded that the use of cross linkers influenced the immediate bond strength of the universal adhesives, and this was dependent on the combination of the adhesive system and type of carbodiimide. The use of EDC increased the immediate bond strength of CLU. DCC increased the bond strength of ABU at 24h, but the values were lower than those of the control group after aging for three out of the four adhesives.

Synthesis, antioxidant and antimicrobial activities for new 4,4'-methylenedianiline amide compounds

Free radicals are particles that have an unpaired electron. If they produced in high level in our bodies, they can produce damage to lipids, proteins, and DNA. Antioxidants are any compounds that can incorporate free radicals in a safe way, cease the reaction, and switch them to a risk-free molecule by donating a proton. On the other side, the infectious diseases are among the chief causes of death worldwide, and antimicrobial resistance has been regularly reported globally. Thus, these complications necessitate the investigation for new therapies with potential antioxidant and antimicrobial activities. This study aims to design, synthesize and evaluate the antioxidant and antimicrobial activities of new N,N'-(dialkoyl/diaroyl)-4,4'-methylenedianiline compounds. These compounds were synthesized by the reaction of carboxylic acids with 4,4'-methylenedianiline in presence of dicyclohexylcarbodiimide (DCC) as coupling agent. The structures of the synthesized compounds were characterized on the basis of the physical and spectral data. The antioxidant activity of these compounds was evaluated by testing their free radical scavenging activity of DPPH and H2O2 and their antimicrobial activity was evaluated via measuring the inhibition zones in the disk diffusion method. The tested synthesized compounds show varied antioxidant and antimicrobial activities. The hydroxyl and the amide moieties in the synthesized compound possess similar potent antioxidant activities. The fluoro-aromatic compound showed potent antibacterial and antifungal activities. While the chloro aliphatic and aromatic compounds showed only antibacterial activity. Whereas fluoro-aromatic compounds and compounds with the ether group exposed a potent antifungal activity.

Excited-State Charge Transfer and Extended Charge Separation within Covalently Tethered Type-II CdSe/CdTe Quantum Dot Heterostructures: Colloidal and Multilayered Systems.

We used N,N'-dicyclohexylcarbodiimide (DCC) coupling chemistry to synthesize (1) heterostructures of CdSe and CdTe quantum dots (QDs) in colloidal dispersions and (2) heterostructures of CdSe and CdTe QDs, as well as CdS and CdSe QDs, immobilized on metal oxide thin films. The DCC-mediated formation of amide bonds between terminal carboxylic acid and amine groups of ligands on different QDs drove the formation of heterostructures. This cross-linking mechanism selectively yields heterostructures and prohibits the undesired formation of homostructures consisting of just one type of QD. Products of adsorption, ligand-exchange, and covalent-coupling reactions were characterized by transmission electron microscopy and ATR-FTIR, 1H NMR, electronic absorption, steady-state emission, and time-resolved emission spectroscopy. Ground-state absorption spectra of constituent QDs were unperturbed upon incorporation into heterostructures, enabling control over electronic properties. Heterostructures of CdSe and CdTe QDs exhibit type-II interfacial energetic offsets that promote charge separation following excitation of either QD. Indeed, photoexcited CdTe QDs transferred electrons to CdSe, and photoexcited CdSe QDs transferred holes to CdTe, on time scales of 10-100 ns, as evidenced by dynamic quenching of band-edge and trap-state emission. Mixed dispersions of noninteracting QDs did not undergo excited-state charge transfer. Constructing heterostructures on TiO2 thin films introduced an additional charge-transfer pathway, electron transfer from QDs to TiO2, which occurred on subnanosecond time scales and enabled extended spatial separation of photogenerated electrons and holes. Our results reveal that carbodiimide coupling chemistry can be used to tether colloidal QDs selectively and covalently to each other, yielding dispersed or immobilized heterostructures with programmable compositions and energetic offsets that can undergo efficient excited-state interfacial electron transfer.

Kinetics of Non-Enzymatic Synthesis of Dipeptide Cbz-Phe-Leu with AOT Reversed Micelles

The non-enzymatic synthesis of N-benzyloxycarbonyl-L-phenylalanyl-L-leucine (Cbz-Phe-Leu) from lipophilic N-benzyloxycarbonyl-L-phenylalanine (Cbz-Phe) and hydrophilic L-leucine (Leu), by N, N’-dicyclohexylcarbodiimide (DCC) as a condensing agent, was carried out using a reversed micellar system composed of bis(2-ethylhexyl) sodium sulfosuccinate (AOT) as a surfactant and isooctane. We successfully synthesized Cbz-Phe-Leu in a short time and investigated the effects of its operational conditions, the DCC concentration, w0, and the pH on the kinetic parameters and the maximum yields. For dipeptide synthesis, we had to add an excess of DCC with the substrates because of the side reactions of Cbz-Phe. From the pH dependency of the reactivity, a partially cationic form of Leu was better for a synthesis reaction because of the enrichment of Leu at the interface by anionic AOT. The optimum water content on the dipeptide synthesis was w0 = 28 due to the competition of the peptide synthesis and the side reactions. The maximum yield of Cbz-Phe-Leu was 0.565 at 80 h under optimum experimental conditions.

Escherichia coli Dcu C4-dicarboxylate transporters dependent proton and potassium fluxes and FOF1-ATPase activity during glucose fermentation at pH 7.5

During fermentation in Escherichia coli succinate is transported via Dcu transporters, encoded dcuA, dcuB, dcuC and dcuD although the role of DcuD protein has not been elucidated yet. It has been shown contribution of Dcu transporters in the N,N’-dicyclohexylcarbodiimide (DCCD) sensitive proton and potassium transport through the cytoplasmic membrane and membrane-associated ATPase activity. Total H± efflux was decreased ~ 40% while K± uptake was absent in dcuD mutant. DCCD-sensitive H± flux was absent in dcuD nevertheless it was increased ~ 3 fold in dcuACB. K± uptake in dcuACB was stimulated ~ 30% compared to wild type but in DCCD assays K± ions were effluxed with the rate of 0.15 mmol/min per 109 cells/ml. In dcuACB mutant membrane potential (ΔΨ) was ~ 30 mV higher than in wild type. dcuD gene expression was increased in the dcuACB mutant respect to wild type at pH 7.5 (~120%), suggesting that an increment of DcuD activity compensates the lack of DcuA, DcuC and DcuB carriers. It can be concluded that active DcuD is important for H± efflux via the FOF1-ATPase and K± uptake at pH 7.5. In addition, DcuA, DcuB and DcuC transporters are crucial for regulating DCCD-sensitive K± transport and ΔΨ in E. coli.

THE ROLE OF PROTON ATPase SPECIFIC INHIBITOR $N,N'$-DICYCLOHEXYLCARBODIIMIDE AND EXTERNAL FORMATE CONCENTRATION ON $E.~COLI$ GROWTH DURING MIXED CARBON SOURCES FERMENTATION AT DIFFERENT pHs

This research is focused on the investigation of specific growth rate changes of $E.~coli$ wild type and mutant strains with defect of Hyd, FDH enzymes and FhlA regulatory protein in the presence of $N,N'$-dicyclohexylcarbodiimide (DCCD) and external formate various concentration during co-fermentation of glucose, glycerol and formate at pHs $5.5-7.5.$ The highest value of SGR was observed at pH 7.5. It was revealed that SGR depends on external formate concentration at all pHs. DCCD inhibitory effect was shown mainly at pH 7.5 and partially at pH 6.5 and 5.5. In the case of the F0F1-ATPase inhibition, FhlA compensatory effect on SGR was revealed.

Regio- and stereo-selective ring expansion of keto-aziridines to the corresponding thiomorpholines

In this research, an efficient process for the synthesis of the some novel 3-thiomorpholines from a regio- and stereo-selective reaction of ketoaziridines with 2-mercaptoacetic acid in the presence of dicyclohexyl carbodiimide is reported. A plausible mechanism has been proposed.

The role of Escherichia coli FhlA transcriptional activator in generation of proton motive force and FO F1 -ATPase activity at pH 7.5.

Escherichia coli is able to utilize the mixture of carbon sources and produce molecular hydrogen (H2 ) via formate hydrogen lyase (FHL) complexes. In current work role of transcriptional activator of formate regulon FhlA in generation of fermentation end products and proton motive force, N'N'-dicyclohexylcarbodiimide (DCCD)-sensitive ATPase activity at 20 and 72 hr growth during utilization of mixture of glucose, glycerol, and formate were investigated. It was shown that in fhlA mutant specific growth rate was ~1.5 fold lower compared to wt, while addition of DCCD abolished the growth in fhlA but not in wt. Formate was not utilized in fhlA mutant but wt cells simultaneously utilized formate with glucose. Glycerol utilization started earlier (from 2hr) in fhlA than in wt. The DCCD-sensitive ATPase activity in wt cells membrane vesicles increased ~2 fold at 72 hr and was decreased 70% in fhlA. Addition of formate in the assays increased proton ATPase activity in wt and mutant strain. FhlA absence mainly affected the ΔpH but not ΔΨ component of Δp in the cells grown at 72 hr but not in 24 hr. The Δp in wt cells decreased from 24 to 72 hr of growth ~40 mV while in fhlA mutant it was stable. Taken together, it is suggested that FhlA regulates the concentration of fermentation end products and via influencing FO F1 -ATPase activity contributes to the proton motive force generation.

Amidation modified waste polystyrene foam as an efficient recyclable adsorbent for organic dyes removal.

Modifying environmentally harmful waste polystyrene foam as an efficient recyclable adsorbent for organic dyes is important. Amidation modified polystyrene (PS-SD) was prepared by the Friedel-Crafts reaction and N,N'-dicyclohexylcarbodiimide (DCC) dehydration condensation reaction of waste polystyrene foam. PS-SD had highly efficient removal performance for organic dyes in large volume water sample solutions, and equilibrium was achieved in 0.5 h. The maximum adsorption capacities for Methylene blue (MB) and Congo red (CR) were 881.62 and 1,880.91 mg/g, respectively, at room temperature according to the Langmuir adsorption isotherm (R2 > 0.99). The kinetic data of the two dyes followed pseudo-second-order kinetics. The removal percentage remained high (>85%) after eight filtration-regeneration cycles. Experimental results showed that PS-SD was an excellent adsorbent for water treatment with high recyclability and long life.

Targeting the ATP Synthase in Staphylococcus aureus Small Colony Variants, Streptococcus pyogenes and Pathogenic Fungi.

The ATP synthase has been validated as a druggable target with the approval of the ATP synthase inhibitor, bedaquiline, for treatment of drug-resistant Mycobacterium tuberculosis, a bacterial species in which the ATP synthase is essential for viability. Gene inactivation studies have also shown that the ATP synthase is essential among Streptococci, and some studies even suggest that inhibition of the ATP synthase is a strategy for the elimination of Staphylococcus aureus small colony variants with deficiencies in the electron transport chain, as well as pathogenic fungi, such as Candida albicans. Here we investigated five structurally diverse ATP synthase inhibitors, namely N,N′-dicyclohexylcarbodiimide (DCCD), oligomycin A, tomatidine, resveratrol and piceatannol, for their growth inhibitory activity against the bacterial strains Streptococcus pyogenes, S. aureus and two isogenic small colony variants, as well as the pathogenic fungal species, C. albicans and Aspergillus niger. DCCD showed broad-spectrum inhibitory activity against all the strains (minimum inhibitory concentration (MIC) 2–16 µg/mL), except for S. aureus, where the ATP synthase is dispensable for growth. Contrarily, oligomycin A selectively inhibited the fungal strains (MIC 1–8 µg/mL), while tomatidine showed very potent, but selective, activity against small colony variants of S. aureus with compromised electron transport chain activity (MIC 0.0625 µg/mL). Small colony variants of S. aureus were also more sensitive to resveratrol and piceatannol than the wild-type strain, and piceatannol inhibited S. pyogenes at 16–32 µg/mL. We previously showed that transposon inactivation of the ATP synthase sensitizes S. aureus towards polymyxin B and colistin, and here we demonstrate that treatment with structurally diverse ATP synthase inhibitors sensitized S. aureus towards polymyxin B. Collectively, our data show that ATP synthase inhibitors can have selective inhibitory activity against pathogenic microorganisms in which the ATP synthase is essential. The data also show that the inhibition of the ATP synthase in Streptococcus pyogenes may be a new strategy for development of a narrow-spectrum antibiotic class. In other major bacterial pathogens, such as S. aureus and potentially Escherichia coli, where the ATP synthase is dispensable, the ATP synthase inhibitors may be applied in combination with antimicrobial peptides to provide new therapeutic options.

Surface functionalization of ZnO nanoparticles with functionalized bovine serum albumin as a biocompatible photochemical and antimicrobial agent

The present study reports the surface functionalization of ZnO nanoparticles with functionalized bovine serum albumin (BSA) as a biocompatible system. Sol gel method was adopted for the synthesis of zinc oxide nanoparticles (ZnO NPs). BSA was functionalized with 2-oxo-2H-chromene-3-carboxylic acid (3-CCA) by the DCC (Dicyclohexyl carbodiimide) coupling method. The presence of hydroxyl functional groups in the biopolymer makes it easier to get coupled with carboxylic acid group of the dye. Finally, the ZnO NPs are incorporated into the biomacromolecular system, BSA, which was functionally modified. The various characterizations done for the surface functionalized ZnO NPs are ultraviolet (UV)/visible, Fourier transform infrared (FTIR), nuclear magnetic resonance (NMR), X-ray diffraction analysis (XRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The antimicrobial resistance of the surface functionalized ZnO NP product were also investigated. The present study also demonstrates the cytotoxicity of this system against Dalton's lymphoma ascites (DLA) cell lines in vitro.

Photophysical Studies on Drug Conjugates of Stavudine/Zidovudine and 1,8-Naphthalimide in Different Solvent Systems

A number of fluorescent conjugates of popular anti-HIV drugs 2′,3′-didehydro-2′,3′-dideoxythymidine (stavudine, d4T) and 3′-azido-3′-deoxythymidine (zidovudine, AZT) with 1,8-naphthalimide were synthesized using the coupling reagent dicyclohexylcarbodiimide (DCC) in the presence of 4-dimethylaminopyridine (DMAP) and N,N-dimethylformamide (DMF) as solvent at room temperature. The steady-state fluorescence measurement studies on these conjugates showed solvatochromic effect. Further, the fluorescence of drug conjugates was recorded in the presence of ions like Na+ and K+ at body level concentration of 135-145 mmol L-1 and 3.6-5.1 mmol L-1, respectively, in phosphate buffer at pH 7.4 in aqueous media. It was observed that the drug conjugates did not show appreciable fluorescence quenching in presence of ions and buffer.

Amphiphilic copolymers with light-pH-temperature triple stimuli-responses: Preparation, self-assembly and controlled drug release

Poly(2-(2-methoxyethoxy)ethylmethacrylate-co-oligo(ethylene glycol) methacrylate)-block-poly(methacrylic acid-co-spiropyran methacrylate) (P(MEO2MA-co-OEGMA)-b-P(MAA-co-SPMA)) was prepared by atom transfer radical polymerization (ATRP), acidolysis and dicyclohexylcarbodiimide (DCC) reaction and can self-assemble into spherical micelles. Poly(2-(2-methoxyethoxy)ethylmethacrylate-co-oligo(ethylene glycol) methacrylate) (P(MEO2MA-co-OEGMA)) segment can respond to changes in temperature, and poly(methacrylic acid) (PMAA) segments show pH-responsive property. The reversible conversion between spiropyran (SP) which is hydrophobic and hydrophilic anthocyanins H+(MCH)/anthocyanins (MC) makes the poly(spiropyran methacrylate) (PSPMA) segments show light-pH-temperature triple-stimulus responses. As a result, the micelles presented light, pH and temperature triple stimuli-responsive properties. The micelles showed different sizes and morphologies under different environmental stimuli. Therefore, the intelligent micelles could be used as the carrier for the multiple controlled release of doxorubicin (DOX) drug molecules.

Effect of an ethanol cross-linker on universal adhesive

ObjectiveTo evaluate the effects of N,N'-dicyclohexylcarbodiimide (DCC), an ethanol-based dentin cross-linker, on the immediate and long-term microtensile bond strength (μTBS) and nanoleakage expression of a universal adhesive employed in self-etch mode (SE) or etch-and-rinse mode (ER). The effect of DCC on the dentinal MMP activity was also investigated by means of in-situ zymography. MethodsEighty freshly extracted human molars were sectioned to expose mid-coronal dentin surfaces. The teeth were assigned to one of the following groups, according to the dentin surface priming/adhesive approach: (G1): DCC pre-treatment and Scotchbond Universal (SBU) in ER mode; (G2): SBU in ER mode; (G3): DCC pretreatment and SBU in SE mode; (G4): SBU in SE mode. μTBS test was performed immediately (T0) or after 1-year aging (T12) in artificial saliva. Ten additional teeth per group were prepared for nanoleakage evaluation (N = 5) and for in-situ zymography (N = 5). ResultsThree-factor analysis of variance revealed significant difference for the variables DCC pretreatment, application mode and aging (p < 0.05) for both microtensile bond strength testing and in-situ zymography. Nanoleakage analysis revealed reduced marginal infiltration of DCC experimental groups both at T0 and T12. SignificanceThe use of an ethanol-based primer containing DCC appears to be promising in preserving the stability of the adhesive interface of a universal adhesive, especially in the SE mode.

Synthesis of ester derivatives of Rhein and their in vitro antitumor activities on cervical cancer cells (Hela)

Taking Rhein as the lead compound, ten esters of rhein were synthesized by esterification. For synthesis of smaller steric hindrance alcohols, SOCl 2 was used as a catalyst to synthesize methyl, ethyl and butyl esters. For lager steric hindrance alcohols, dicyclohexyl carbodiimide (DCC) was used as dehydrating agent, and 4-dimethylaminopyridine (DMAP) was used as the catalyst to synthesize isopropyl, isobutyl, tertbutyl, isoamyl, benzyl, 2-phenyl ethyl, 2-chloroethyl esters. Structural characterization of the target compounds were done using melting point, 1 H NMR, 13 C NMR and HRMS. Five out of the 10 compounds were new. All the compounds were evaluated for antitumor activities in vitro against Hela human cervical carcinoma cell lines. Study found that all the ten compounds showed differences in their growth inhibitory effect on tumor cells. Compound with benzyl groups improved the antitumor activity. Results showed that compound 3b exhibited maximum activity against Hela cell lines at 100 μg mL –1 (IC 50 value) with an inhibition rate of 70%, while the derivative 3i showed the lowest inhibitory activity (IC 50 &lt;64.3 μg mL –1 ).

Strongly Hydrophobic and Superoleophilic PMMA Based Nanocoated Cotton Fabrics

Oil–water separation is among the critical issues worldwide due to recent massive oil spills. Moreover, domestic and industrial water pollution due to oil discharge affects marine and aquatic life. Cotton is the most predominant fiber globally because of its use as a principal and popular clothing material. Cotton is also the leading raw material for technical and functional textile applications. In this study, the fabric was cured with poly (methyl methacrylate) (PMMA) nanoparticles to develop hydrophobic and oleophilic cotton fabrics. The dehydrating agents, N,N′-dicyclohexylcarbodiimide (DCC) and dimethyl aminopyridine (DMAP), were used to catalyze the esterification. The results proved that the excellent hydrophobicity of modified cotton fabric provides a water contact angle higher than 140°. In addition, Fourier transforms infrared (FTIR) spectroscopy, as well as X-ray photoelectron spectroscopy (XPS) analysis, confirmed the fabric surface modification. Surface morphological analysis by scanning electron microscope (SEM) revealed the uniform rough surface structure of the modified fabric with nano-coating. The modified fabric resulted in the high separation efficiency of oil and water, suggesting this strategy to be suitable for advanced oil–water separation.

Palladium/Norbornene‐Catalyzed Sequential ortho‐Acylation and ipso‐Alkenylation with Carboxylic Acid: Access to Polysubstituted Aryl Ketones

AbstractHerein a palladium/norbornene‐catalyzed sequential ortho‐acylation and ispo‐alkenylation for access to polysubstituted aryl ketones has been developed. By exploiting dicyclohexylcarbodiimide (DCC) as activator, aryl with electron‐donating or electron‐withdrawing functionalities, alkyl, and heteroaryl carboxylic acids were compatible in this transformation, affording the desired products in decent to good yields.magnified image

Undesirable effects of chemical inhibitors of NAD(P)+ transhydrogenase on mitochondrial respiratory function

NAD(P)+ transhydrogenase (NNT) is located in the inner mitochondrial membrane and catalyzes a reversible hydride transfer between NAD(H) and NADP(H) that is coupled to proton translocation between the intermembrane space and mitochondrial matrix. NNT activity has an essential role in maintaining the NADPH supply for antioxidant defense and biosynthetic pathways. In the present report, we evaluated the effects of chemical compounds used as inhibitors of NNT over the last five decades, namely, 4-chloro-7-nitrobenzofurazan (NBD-Cl), N,N′-dicyclohexylcarbodiimide (DCC), palmitoyl-CoA, palmitoyl-l-carnitine, and rhein, on NNT activity and mitochondrial respiratory function. Concentrations of these compounds that partially inhibited the forward and reverse NNT reactions in detergent-solubilized mouse liver mitochondria significantly impaired mitochondrial respiratory function, as estimated by ADP-stimulated and nonphosphorylating respiration. Among the tested compounds, NBD-Cl showed the best relationship between NNT inhibition and low impact on respiratory function. Despite this, NBD-Cl concentrations that partially inhibited NNT activity impaired mitochondrial respiratory function and significantly decreased the viability of cultured Nnt−/− mouse astrocytes. We conclude that even though the tested compounds indeed presented inhibitory effects on NNT activity, at effective concentrations, they cause important undesirable effects on mitochondrial respiratory function and cell viability.