Carboxylic Function Research Articles

Half-sandwich complexes of group 9 metals with N,Nʹ-ligands for CF3-carbenoid alkylation of N-(pyrimidin-2-yl)indole

The complexes [CpM(N,Nʹ-ligand)Br]PF6 (M = Rh, Ir; N,Nʹ-ligand = 2,2′-bipyridyl, 1,10-phenanthroline) were synthesized by reactions of bromides [CpMBr2]n with 2,2′-bipyridyl or 1,10-phenanthroline followed by a counterion exchange. The replacement of cyclooctadiene in [CpIr(cod)I]I3 with N,Nʹ-ligands leads to complexes [CpIr(N,Nʹ-ligand)I]I3 (N,Nʹ-ligand = 2,2′-bipyridyl, 1,10-phenanthroline). The structures of [CpRh(2,2′-bipyridyl)Br]PF6, [CpIr(2,2′-bipyridyl)I]I3, and [CpIr(1,10-phenanthroline)Br]PF6 were determined by X-ray diffraction. The compounds prepared as well as the related the tris(pyrazolyl)borate derivatives [CpCoTp]PF6 and [Cp*MTp]PF6 (M = Rh, Ir) efficiently catalyze the alkylation of N-(pyrimidin-2-yl)indole with methyl 3,3,3-trifluoro-2-diazopropionate to selectively introduce the CF3 and carboxylate functions at the C3 position of the indole moiety. In contrast, the tris(pyrazolyl)borate cobalt complex [Cp*CoTp]PF6 predominantly provides the alkylation at the C2 position.

Binary Biocompatible CNC–Gelatine Hydrogel as 3D Scaffolds Suitable for Cell Culture Adhesion and Growth

Binary nano-biocomposite 3D scaffolds of cellulose nanocrystals (CNCs)—gelatine were fabricated without using chemical crosslinking additives. Controlled oxidative treatment allowed introducing carboxyl or carbonyl functionalities on the surface of CNCs responsible for the crosslinking of gelatine polymers. The obtained composites were characterized for their physical-chemical properties. Their biocompatibility towards different cell cultures was evaluated through MTT and LDH assays, cellular adhesion and proliferation experiments. Gelatine composites reinforced with carbonyl-modified CNCs showed the most performing swelling/degradation profile and the most promising adhesion and proliferation properties towards cell lines, suggesting their potential application in the field of tissue engineering.

Understanding How Staphylococcal Autolysin Domains Interact With Polystyrene Surfaces.

Biofilms, when formed on medical devices, can cause malfunctions and reduce the efficiency of these devices, thus complicating treatments and serving as a source of infection. The autolysin protein of Staphylococcus epidermidis contributes to its biofilm forming ability, especially on polystyrene surfaces. R2ab and amidase are autolysin protein domains thought to have high affinity to polystyrene surfaces, and they are involved in initial bacterial attachment in S. epidermidis biofilm formation. However, the structural details of R2ab and amidase binding to surfaces are poorly understood. In this study, we have investigated how R2ab and amidase influence biofilm formation on polystyrene surfaces. We have also studied how these proteins interact with polystyrene nanoparticles (PSNPs) using biophysical techniques. Pretreating polystyrene plates with R2ab and amidase domains inhibits biofilm growth relative to a control protein, indicating that these domains bind tightly to polystyrene surfaces and can block bacterial attachment. Correspondingly, we find that both domains interact strongly with anionic, carboxylate-functionalized as well as neutral, non-functionalized PSNPs, suggesting a similar binding interaction for nanoparticles and macroscopic surfaces. Both anionic and neutral PSNPs induce changes to the secondary structure of both R2ab and amidase as monitored by circular dichroism (CD) spectroscopy. These changes are very similar, though not identical, for both types of PSNPs, suggesting that carboxylate functionalization is only a small perturbation for R2ab and amidase binding. This structural change is also seen in limited proteolysis experiments, which exhibit substantial differences for both proteins when in the presence of carboxylate PSNPs. Overall, our results demonstrate that the R2ab and amidase domains strongly favor adsorption to polystyrene surfaces, and that surface adsorption destabilizes the secondary structure of these domains. Bacterial attachment to polystyrene surfaces during the initial phases of biofilm formation, therefore, may be mediated by aromatic residues, since these residues are known to drive adsorption to PSNPs. Together, these experiments can be used to develop new strategies for biofilm eradication, ensuring the proper long-lived functioning of medical devices.

Carminic acid extracted from cochineal insect as photosensitizer for dye‐sensitized solar cells

In an attempt to investigate influence of the utilization of organic dyes on photovoltaic performance of low-cost dye-sensitized solar cells (DSSCs), carminic acid (CA) obtained from cochineal insect was employed as photosensitizer to fabricate DSSCs. To recognize light absorption behavior of the CA, UV-Vis spectroscopy was taken. The CA comprises noticeable spectrum of solar radiation, 430 to 540 nm that makes it appropriate for use as a photosensitizer in DSSCs. Fourier transform infrared (FTIR) spectra of the CA revealed the presence of carboxylic functionality, enabling good anchorage to the surface of TiO2. The electrochemical impedance spectroscopy (EIS) analysis manifests that the suppression of the electron recombination at the TiO2/CA/electrolyte interface was insufficient. Quantum chemical calculations of the CA dye were performed by using the density functional theory (DFT). The lowest unoccupied molecular orbital (LUMO) level of the CA matched well for the injection of electron from the CA to the conduction band edge of TiO2. The achieved photo-conversion efficiency of a DSSC employing the CA photosensitizer was 1%, which was found to be much higher than that of several natural dyes-based DSSCs under a simulated solar light illumination of 100 mW/cm2.

Responsive Polyesters with Alkene and Carboxylic Acid Side-Groups for Tissue Engineering Applications.

Main chain polyesters have been extensively used in the biomedical field. Despite their many advantages, including biocompatibility, biodegradability, and others, these materials are rather inert and lack specific functionalities which will endow them with additional biological and responsive properties. In this work, novel pH-responsive main chain polyesters have been prepared by a conventional condensation polymerization of a vinyl functionalized diol with a diacid chloride, followed by a photo-induced thiol-ene click reaction to attach functional carboxylic acid side-groups along the polymer chains. Two different mercaptocarboxylic acids were employed, allowing to vary the alkyl chain length of the polymer pendant groups. Moreover, the degree of modification, and as a result, the carboxylic acid content of the polymers, was easily tuned by varying the irradiation time during the click reaction. Both these parameters, were shown to strongly influence the responsive behavior of the polyesters, which presented adjustable pKα values and water solubilities. Finally, the difunctional polyesters bearing the alkene and carboxylic acid functionalities enabled the preparation of cross-linked polyester films by chemically linking the pendant vinyl bonds on the polymer side groups. The biocompatibility of the cross-linked polymers films was assessed in L929 fibroblast cultures and showed that the cell viability, proliferation, and attachment were greatly promoted on the polyester surface, bearing the shorter alkyl chain length side groups and the higher fraction of carboxylic acid functionalities.

Design and Synthesis of Sulindac New Derivitives as Possible Mutual Prodrug with Potential to Maximized Therapeutic Area

The urgent necessity today for development of anti cancer agent is crucial so highly dependent for searchingfor new anti neoplastic action ,the drug discovery process is costly and consume long time ,in my studyfocusing my efforts toward drug optimization process using sulindac (NSAID) which has a fantasticattractive area as anti cancer and anticancer in addition to it is anti inflammatory action .The study describes design and synthesis of mutual pro-drug of sulindac in combination with thenaturalanti oxidants (menthol ,thymol ,vanillin,guiacol) as a single integral pharmaceutical unit byan chloro acetylchlorideas spacer to form an ester mutual prodrug with expected to improve the anti inflammatory ,anticancer , antioxidant action of sulindac by the conjugation with natural anti oxidative integral moiety andminimized the ulcerogenic adverse effect of sulindacit is carboxylic acid functionality .The synthesis isconferred byH1NMR, FT-IR, CHN and physiochemical properties.

2‐Aminotrimesic Acid‐Functionalized Graphene Oxide‐Modified Screen‐Printed Electrodes for Sensitive Electrochemical Detection of Cardiac Marker Troponin I

An electrochemical impedance‐based immunosensor is reported for the sensitive detection of cardiac Troponin I (cTnI). The sensor is made up of the amine‐functionalized graphene oxide (GO)‐coated screen‐printed electrodes (SPEs). As a novel concept, GO is functionalized with aminotrimesic acid (1‐aminobenzene‐3,4,5‐tricarboxylic acid), which provides efficient water dispersion and desirable carboxyl functionality for subsequent biomodification with antibodies. Such a functionalized GO surface is useful to immobilize the anti‐cTnI antibodies efficiently and conveniently. The modification of antibodies is verified with spectroscopic and morphological investigations. Further, the application of the immunosensor electrodes toward the detection of cTnI is demonstrated through the measurements of Rct (charge transfer resistance) values in the presence of varying antigen concentration. The limit of detection (LOD) of the present method is 0.08 ng mL−1 with the range of detection as 0.1–100 ng mL−1. The specificity of the developed immunosensor is studied in the presence of ferritin, and bovine serum albumin (BSA). Thus, the herein proposed a new design of graphene‐based immunosensor is very convenient and offers highly selective and sensitive detection of cTnI.

The Decade-long Evolution and Toxicity of Oil Transformation Compounds in Louisiana Salt Marsh Sediments Revealed by FT-ICR Mass Spectrometry

The 2010 explosion of the Deepwater Horizon (DWH) drilling rig provides a unique opportunity to advance the understanding of the evolution of lingering oil in Louisiana salt marshes for nearly a decade after the initial spill. After an oil spill, petroleum hydrocarbons undergo physical and chemical processes that transform the native oil composition to a polyfunctional oxygenated hydrocarbon matrix that contains ketones, hydroxyl, and carboxylic acid functional groups. Preliminary analysis of saltmarsh sediments impacted by the DWH spill between 2010–2014 identifies highly polar oxygenated hydrocarbons with carboxylic acid functionalities. These highly polar, high molecular weight compounds are not detectable by conventional gas chromatography (GC) based techniques. Here, we employ advanced analytical technologies such as targeted fractionation and isolation methods with Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) to document and catalog oil transformation compounds detected in oiled saltmarsh sediments. The toxicities of these environmental transformation products are determined by commercial Microtox bioassay. Samples have been continuously collected from 21 previously established sampling stations located in northern Barataria Bay for the past ten years post-spill. The concentration of oil contamination from heavily and moderately oiled sites exceed non-oiled reference sites for years after the spill. Combining chromatographic fractionation, conventional GC MS, and ultrahigh-resolution FT-ICR Mass Spectrometry analyses, we identified tens-of-thousands of biotic and abiotic crude oil transformation products that remain persistent and keep evolving in the environment. Heavily oxygenated transformation products, which are mostly only accessible by FT-ICR MS, span a wide range of chemical functionalities. Toxicity of the non-GC amenable fraction of oil contaminants was measured to determine the health risk of weathered oil residues left in the salt marsh environment. The current study creates a decade-long assessment record, and a comprehensive understanding of petroleum compounds evolution of oil-impacted wetlands ecosystem.

Aqueous Modification of Chitosan with Itaconic Acid to Produce Strong Oxygen Barrier Film.

In this study, the chemical modification of chitosan using itaconic acid as a natural-based unsaturated dicarboxylic acid was investigated. In an aqueous environment, the amine group of chitosan reacts with itaconic acid to produce a chitosan derivative with pyrrolidone-4-carboxylic acid group. On the basis of the elemental analysis, 15% of the amine groups of chitosan reacted, thus creating modified chitosan with amine and carboxylic acid functionalities. Due to the presence of amine and carboxylic acid groups, the surface charge properties of the chitosan were notably altered after itaconic acid modification. In an aqueous solution, the modified chitosan exhibited zwitterionic properties, being cationic at low pH and turning anionic when the pH was increased over 6.5, whereas the original chitosan remained cationic until pH 9. Furthermore, it was demostrated that the modified chitosan was suitable for the preparation of a self-standing film with similarly high transparency but notably higher mechanical strength and oxygen barrier properties compared to a film made from the original chitosan. In addition, the thermal stability of the modified chitosan film was higher than that of the original chitosan film, and the modified chitosan exhibited flame-retardant properties.

Poly(Ethylene Glycol)/β-Cyclodextrin Pseudorotaxane Complexes as Sustainable Dispersing and Retarding Materials in a Cement-Based Mortar.

Pseudorotaxane complexes between β-CD and mPEG derivatives bearing a carboxylic acid function (mPEG–COOH) were synthesized and investigated for their dispersing properties in a cement-based mortar. The formation of mPEG–COOH derivatives and their pseudorotaxanes was investigated by 1D nuclear magnetic resonance, diffusion ordered spectroscopy, and thermogravimetric analysis experiments. Mortar tests clearly indicate that mPEG–COOH@β-CD-interpenetrated supramolecules show excellent dispersing abilities. In addition, the supramolecular complexes show a retarding effect, analogously to other known β-CD-based superplasticizers in which the β-CD is covalently grafted on a polymeric backbone.

Observing spontaneous, accelerated substrate binding in molecular dynamics simulations of glutamate transporters.

Glutamate transporters are essential for removing the neurotransmitter glutamate from the synaptic cleft. Glutamate transport across the membrane is associated with elevator-like structural changes of the transport domain. These structural changes require initial binding of the organic substrate to the transporter. Studying the binding pathway of ligands to their protein binding sites using molecular dynamics (MD) simulations requires micro-second level simulation times. Here, we used three methods to accelerate aspartate binding to the glutamate transporter homologue Gltph and to investigate the binding pathway. 1) Two methods using user-defined forces to prevent the substrate from diffusing too far from the binding site. 2) Conventional MD simulations using very high substrate concentrations in the 0.1 M range. The final, substrate bound states from these methods are comparable to the binding pose observed in crystallographic studies, although they show more flexibility in the side chain carboxylate function. We also captured an intermediate on the binding pathway, where conserved residues D390 and D394 stabilize the aspartate molecule. Finally, we investigated glutamate binding to the mammalian glutamate transporter, excitatory amino acid transporter 1 (EAAT1), for which a crystal structure is known, but not in the glutamate-bound state. Overall, the results obtained in this study reveal new insights into the pathway of substrate binding to glutamate transporters, highlighting intermediates on the binding pathway and flexible conformational states of the side chain, which most likely become locked in once the hairpin loop 2 closes to occlude the substrate.

Mechanism of Heterogenization of Dirhodium Catalysts: Insights from DFT Calculations.

Dirhodium(II) complexes such as [Rh2(TFA)4] bound to a functionalized mesoporous SBA-15 carrier material have proven to be valuable candidates for heterogeneous catalysis in the field of pharmaceutical synthesis. However, the mechanistic steps of immobilization by linker molecules containing carboxyl or amine functionalities remain the subject of discussion. Here we present a theoretical study of possible mechanistic binding pathways for the [Rh2(TFA)4] complex through model representations of synthetically investigated linkers, namely n-butylamine and n-butyric acid. Experimentally proposed intermediates of the immobilization process are investigated and analyzed by density functional theory calculations to gain insights into structural properties and the influence of solvation. An evaluation of the thermodynamic data for all identified intermediates allowed distinguishing between two possible reaction pathways that are characterized by a first axial complexation of either n-butyric acid or n-butylamine. In agreement with results from NMR spectroscopy, singly or doubly n-butylamine-fixated complexes were found to present possible immobilization products. Initial binding through a carboxy-functionalized linker is proposed as the most favorable reaction pathway for the formation of the mixed linker pattern [Rh2(TFA)3]·(n-butylamine)·(n-butyrate). The linkers n-butyric acid and n-butyrate, respectively, are found to exhibit an unaltered binding affinity to the dirhodium complex despite their protonation states, indicating invariance to the acidic environment unlike an immobilization by n-butylamine. These results present a theoretical framework for the rationalization of observed product distributions while also providing inspiration and guidance for the preparation of functionalized heterogeneous SBA-15/dirhodium catalyst systems.

Green properties of dry-pressed alumina using a new synthesized copolymer able to act simultaneously as dispersant and binder with plastic character

Statistical copolymers containing both carboxylate and hydroxyl functions have been synthesized in order to promote the dispersion of alumina suspensions in addition to the binding of pressed green disc-shaped specimens. In aqueous suspensions, the carboxylate groups are responsible for maintaining a high adsorption of the copolymer onto the alumina surface particles, thus increasing surface charges promoting a high electrostatic stabilization. The hydroxyl functions, which are not preferentially adsorbed on the surface i) participate in the steric stability of the suspension and, ii) confer a high mechanical resistance to green powder compacts compared to specimens classically shaped with 3 wt% of commercial polyvinyl alcohol and 1 wt% polyethylene glycol. Indeed, tensile stress to rupture evaluated by diametral compression is always greater than 3.5 MPa. The transition temperature of synthesized copolymers ranges from -10 to 57 °C, makes it possible to confer a plastic character to the organic system and to reach a high relative green density (around 63%) after compaction under 190 MPa at room temperature. Moreover, the effect of various molecular weights (from 11000 to 47000) on properties of spray-dried granules and of pressed compacts has been studied. A narrow spray-dried granule size distribution of corresponds to an optimal content of added copolymer, which in turn results in an optimal density of compacted parts. Optimal density values of the compacted parts follow the same trend as the highest particle size distribution corresponding to the optimal added copolymer content. The optimal values of densities correspond to an added amount of 1, 1.5 and 2 wt% respectively of high, medium and low copolymer's molecular weight.

Advantages of Covalent Immobilization of Metal‐Salophen on Amino‐Functionalized Mesoporous Silica in Terms of Recycling and Catalytic Activity for CO2 Cycloaddition onto Epoxides

AbstractNiII and MnIII Schiff base complexes (Salophen‐Ni and Salophen‐MnCl) bearing a pending carboxylic group were prepared and characterized. Both complexes were grafted onto a mesoporous amino‐functionalized SBA‐15 silica, by formation of an amide function between the propylamine groups of the support and the carboxylic acid functions of the salophen ligand (corresponding respective to 1.30 wt.% of Ni and 1.06 wt.% of Mn). The co‐catalytic behaviour of the free and grafted complexes was then evaluated in the CO2 cycloaddition reaction onto styrene oxide, using tetra‐butylammonium bromide (n−Bu4NBr) as the main catalyst. In homogeneous conditions, the MnIII Schiff base complex and the NiII one, to a lesser extent, behave as efficient co‐catalysts for this reaction (styrene conversion of 100 % and 65 % respectively after 3 h at 120 °C, under 15 bars of CO2). Upon immobilization at the surface of the amino‐functionalized SBA‐15, we showed that the co‐catalytic activity of the less efficient one, i. e. Ni2+ salophen complex, could be enhanced (reaching a full conversion after 7 h), hence highlighting a potential synergistic effect between the unused amine functions of the support and the Ni2+ salophen co‐catalyst. Both salophen complexes were successfully re‐used in homogeneous conditions or after their immobilization without any appreciable loss of activity. This work is only a first step towards a completely heterogeneous catalytic system, in which the tetraalkylammonium halide catalyst and the metal‐salophen co‐catalyst will both be covalently anchored on the same support.

Tuning the Acceptor Unit of Push-Pull Porphyrazines for Dye-Sensitized Solar Cells.

A family of four push–pull porphyrazines of A3B type, where each unit A contains two peripheral propyl chains and the unit B is endowed with a carboxylic acid, were prepared. The carboxylic acid was attached to the β-position of the pyrrolic unit, either directly (Pz 10), or through cyanovinyl (Pz 11) and phenyl (Pz 7) groups. The fourth Pz (14) consisted in a pyrazinoporphyrazine wherein the dinitrogenated heterocycle provided intrinsic donor–acceptor character to the macrocycle and contained a carboxyphenyl substituent. The direct attachment of the carboxylic acid functions and their linkers to the porphyrazine core produces stronger perturbation on the electronic properties of the macrocycle, with respect to their connection through fused benzene or pyrazine rings in TT112 and 14, respectively. The HOMO and LUMO energies of the Pzs, which were estimated with DFT calculations, show little variation within the series, except upon introduction of the cyanovinyl spacer, which produces a decrease in both frontier orbital energetic levels. This effective interaction of cyanovinyl substitution with the macrocycle is also evidenced in UV/Vis spectroscopy, where a large splitting of the Q-band indicates strong desymmetrization of the Pz. The performance of the four Pzs as photosensitizers in DSSCs were also investigated.

Experimental investigation and mass transfer modelling of 3D printed monolithic cation exchangers

3D printing has recently found application in chromatography as a means to create ordered stationary phases with improved separation efficiency. Currently, 3D printed stationary phases are limited by the lack of 3D printing materials suitable for chromatographic applications, and require a strict compromise in terms of desired resolution, model size and the associated print time. Modelling of mass transfer in 3D printed monoliths is also fundamental to understand and further optimise separation performance of 3D printed stationary phases. In this work, a novel 3D printing material was formulated and employed to fabricate monolithic cation exchangers (CEXs) with carboxyl functionalities. CEXs were printed with ligand densities of 0.7, 1.4, 2.1 and 2.8 mmol/g and used in batch adsorption experiments with lysozyme as model protein. All CEXs demonstrated high binding strength towards lysozyme, with maximum binding capacities of up to 108 mg/mL. The experimental results were described using mass transfer models based on lumped pore diffusion and lumped solid diffusion mechanisms adapted to reflect the complex geometry of the 3D printed monoliths. An exact 3D model as well as less computationally demanding 1D and 2D approximations were evaluated in terms of their quality to capture the experimental trend of batch adsorption kinetic data. Overall, the model results indicate that mass transfer in the fabricated CEXs is mostly controlled by pore diffusion at high protein concentrations in the mobile phase, with solid diffusion becoming important at low protein concentrations. Also, the kinetic data were approximated equally well by both the full 3D model as well as the 2D approximation, indicating leaner mathematical models of lower dimensionality can be employed to describe mass transfer in complex three dimensional geometries. We believe this work will help spur the development of 3D printable materials for separations and aid in the development of quantitative platforms to evaluate and optimise the performance of 3D printed monoliths.

Photophysical studies of organostannoxane supported hexafluorophore assemblies

The condensation reaction between n-butylstannoic acid and ArCOOH (Ar = 1-naphthyl-CH2 (1), 9-anthracenyl (2), 9-xanthenyl (3), 1-pyrenyl-(CH2)3 (4), 1-pyrenyl (5)) afforded hexameric organostannoxanes [n-BuSn(O)(O2CAr)]6 in high yield. The molecular structures of compounds 2 and 3 were confirmed by single crystal X-ray diffraction analysis. These compounds possess a drum-like structure and each molecule is attached with six fluorophores through carboxylate functionality. 119Sn NMR and MALDI-TOF analyses suggest that the compounds 1, 4, and 5 also belong to the family of organotin drum structure. There are also various intra- and intermolecular interaction between the fluorophores. In particular, compound 2 shows a strong intramolecular hydrogen bond (CH····π 2.489 Å) between two anthracene moieties. However, such interaction is weaker in 3. The absorption spectra of 1–5 indicate that λmax was very slightly red-shifted with respect to their fluorophore carboxylic acid. Fluorescence measurements reveal that these molecules are good blue emitters in solution state but red-shifted in the solid-state. Quantum yield calculation shows that emission efficiencies decreased for smaller spacers between fluorophore and stannoxane core. We have carried out thermal studies for all compounds. These suggest that the compounds are robust and stable until about 300 °C. Interestingly, we have demonstrated the synthesis of SnO2 from the hexameric organotin drum 3 by heating in the temperature range 600–1200 °C.

Preparation of a hyperbranched hybrid curing agent for epoxidized novolac resin

A hyperbranched hybrid curing agent (CSD) for epoxidized novolac resin (ENR) was prepared by grafting silica nanoparticles modified with poly(amidoamine) (PAMAM) dendritic structure (SD) to carbon nanotube (CNT) using an esterification reaction between the amino functional groups of SD and carboxylic acid functionalities of oxidized CNT. ENR was prepared by a reaction between novolac resin and epichlorohydrin. Curing of ENR was carried out with two different contents of CSD as the hyperbranched hybrid curing component of the epoxidized matrix. The amino-rich structure of CSD could result in its high dispersion in the ENR matrix and consequently high thermal stability of the hybrid composites. Fourier-transform infrared spectroscopy and thermal gravimetric analysis (TGA) showed successful modification of silica nanoparticles and CNT with the PAMAM dendritic structure and SD, respectively. Structure of the resulting hybrid curing agents (SD and CSD) was investigated by X-ray diffraction, scanning electron microscopy, and transmission electron microscopy. Thermal investigation of the resulted composites by TGA showed that the cured ENR with higher content of CSD has high thermal properties with a char residue of 44.4% among the other hybrid composites.

Electrografted Interfaces on Metal Oxide Electrodes for Enzyme Immobilization and Bioelectrocatalysis

AbstractIn this work, we demonstrate that diazonium electrografting of biocompatible interfaces on transparent conducting oxide indium tin oxide (ITO) can be controlled and optimized to achieve low charge transfer resistance, allowing highly efficient electron transfer to an immobilized model enzyme, the oxygen‐tolerant [NiFe]‐hydrogenase from Ralstonia eutropha. The use of a radical scavenger enables control of the interface thickness, and thus facilitates maximization of direct electron transfer processes between the enzyme's active center and the electrode. Using this approach, amine and carboxylic acid functionalities were grafted on ITO, allowing enzyme immobilization both under moderate electrostatic control and covalently via amide bond formation. Despite an initial decrease in catalytic activity, covalent immobilization led to an improvement in current stability compared to just electrostatically immobilized enzyme. Given the superior stability of electrografted interfaces in comparison to adsorbed or self‐assembled interfaces, we propose electrografting as an alternative approach for the functional immobilization of redox‐active enzymes on transparent conducting oxide (TCO) electrodes in bioelectronic devices.

Identification of the carboxylic acid functionality in protonated drug metabolite model compounds by using tandem mass spectrometry based on ion-molecule reactions coupled with high performance liquid chromatography

The carboxylic acid functionality is among the many functionalities that drug metabolites, degradation products and impurities may contain. Therefore, analytical techniques that can be used to rapidly identify the carboxylic acid functionality are important for pharmaceutical industry. In this study, a tandem mass spectrometric approach based on diagnostic gas-phase ion-molecule reactions with (isopropenoxy)trimethylsilane (ITS) was developed for the identification of protonated compounds containing the carboxylic acid functionality in a modified linear quadrupole ion trap mass spectrometer. All protonated carboxylic acid, N-oxide, sulfoxide, carboxamide, ketone, amine, hydroxylamine, sulfone, sulfonamide, amide, ether, ester and aldehyde model compounds studied react with ITS to form protonated ITS and an adduct that has lost an acetone molecule, [adduct – acetone]+. Protonated compounds containing the carboxylic acid functionality can be differentiated from most other types of protonated compounds based on the formation of a secondary product, 2° [adduct – acetone]+, upon reactions of the [adduct – acetone]+ primary product with a second ITS molecule via addition and elimination of an acetone molecule. Quantum chemical calculations suggest that both addition/acetone elimination reactions are initiated by proton transfer to ITS. Nucleophilic substitution of acetone at the silicon atom by the carbonyl oxygen atom of the carboxylic acid or the primary reaction product leads to elimination of acetone. An equimolar mixture of 4-aminobenzoic acid, clozapine N-oxide, oxcarbamazepine, diphenylsulfoxide, naproxen and celecoxib was subjected to analogous HPLC/tandem mass spectrometry experiments to demonstrate the utility of this method for high-throughput drug metabolite characterization. A limitation of this method is that compounds that contain a phenol group and an additional basic functionality can show a false positive result.