Noncovalent Immobilization Research Articles

Non-covalent Immobilization of Metal N-Heterocyclic Carbene Complexes onto Carbon Cloth as Bifunctional Electrodes for Overall Water Splitting in Alkaline Medium

Non-covalent Immobilization of Metal N-Heterocyclic Carbene Complexes onto Carbon Cloth as Bifunctional Electrodes for Overall Water Splitting in Alkaline Medium

Covalent Functionalization of Silicon with Plasma-Grown "Fuzzy" Graphene: Robust Aqueous Photoelectrodes for CO2 Reduction by Molecular Catalysts.

Carbon electrodes are ideal for electrochemistry with molecular catalysts, exhibiting facile charge transfer and good stability. Yet for solar-driven catalysis with semiconductor light absorbers, stable semiconductor/carbon interfaces can be difficult to achieve, and carbon's high optical extinction means it can only be used in ultrathin layers. Here, we demonstrate a plasma-enhanced chemical vapor deposition process that achieves well-controlled deposition of out-of-plane "fuzzy" graphene (FG) on thermally oxidized Si substrates. The resulting Si|FG interfaces possess a silicon oxycarbide (SiOC) interfacial layer, implying covalent bonding between Si and the FG film that is consistent with the mechanical robustness observed from the films. The FG layer is uniform and tunable in thickness and optical transparency by deposition time. Using p-type Si|FG substrates, noncovalent immobilization of cobalt phthalocyanine (CoPc) molecular catalysts was employed for the photoelectrochemical reduction of CO2 in aqueous solution. The Si|FG|CoPc photocathodes exhibited good catalytic activity, yielding a current density of ∼1 mA/cm2, Faradaic efficiency for CO of ∼70% (balance H2), and stable photocurrent for at least 30 h at -1.5 V vs Ag/AgCl under 1-sun illumination. The results suggest that plasma-deposited FG is a robust carbon electrode for molecular catalysts and suitable for further development of aqueous-stable Si photocathodes for CO2 reduction.

One-Step Synthesis and Oriented Immobilization of Strep-Tag II Fused PDGFRβ for Screening Intracellular Domain-Targeted Ligands.

Accurate orientations and stable conformations of membrane receptor immobilization are particularly imperative for accurate drug screening and ligand-protein affinity analysis. However, there remain challenges associated with (1) traditional recombination, purification, and immobilization of membrane receptors, which are time-consuming and labor-intensive; (2) the orientations on the stationary phase are not easily controlled. Herein, a novel one-step synthesis and oriented-immobilization membrane-receptor affinity chromatography (oSOMAC) method was developed to realize high-throughput and accurate drug screening targeting specific domains of membrane receptors. We employed Strep-tag II as a noncovalent immobilization tag fused into platelet-derived growth factor receptor β (PDGFRβ) through CFPS, and meanwhile, the Strep-Tactin-modified monolithic columns are prepared in batches. The advantages of oSOMAC are as follows: (1) targeted membrane receptors can be expressed independent of living cell within 1-2 h; (2) orientation of membrane receptors can be flexibly controlled and active sites can expose accurately; and (3) targeted membrane receptors can be synthesized, purified, and orientation-immobilized on monolithic columns in one step. Accordingly, three potential PDGFRβ intracellular domain targeted ligands: tanshinone IIA (Tan IIA), hydroxytanshinone IIA, and dehydrotanshinone IIA were successfully screened out from Salvia miltiorrhiza extract through oSOMAC. Pharmacological experiments and molecular docking further demonstrated that Tan IIA could attenuate hepatic stellate cells activation by targeting the protein kinase domain of PDGFRβ with a KD value of 9.7 μM. Ultimately, the novel oSOMAC method provides an original insight for accurate drug screening and interaction analysis which can be applied in other membrane receptors.

Incorporation of organic photochromic molecules in mesoporous silica materials: Synthesis and applications

Abstract The ability to control the function and structure of some promising nanosystems using an external stimulus is attractive research to develop programmable and reconfigurable intelligent nanomaterials. The focal point of this review is the silicon-based nanoporous materials, and particularly the mesoporous silica materials (MSMs) class (pore size: 2–50 nm), due to their important intrinsic properties, such as high surface area, highly ordered nanostructure, narrow pore size distribution, various dimensions (one-dimensional, two-dimensional, and three-dimensional), and easily functionable. One of the most essential organic components that can be incorporated in MSMs is organic photochromic molecules (OPMs), such as azobenzene, stilbene, dithienylethenes, and spiropyrans. OPMs can be incorporated into MSMs, to form photochromic mesoporous organosilica materials (PMOMs), in two different ways: physical (non-covalent immobilization) or chemical (covalent immobilization) binding. PMOMs are considered smart nanomaterials because they have the ability to undergo reversible changes in the solid state when exposed to an external electromagnetic radiation. PMOMs have been the subject of many research studies during the last decade due to their potential applications, especially as chemosensors. This review discusses the main families of OPMs, their incorporation into MSMs using different methods, and the applications of some PMOMs as chemosensors.

An odorant-binding protein based electrical sensor to detect volatile organic compounds

Artificial olfaction systems, such as electronic nose devices (ENs), can be used in various fields, from healthcare to food industry and the environmental sector. ENs consist of an array of sensors composed of different sensing materials. Incorporating Odorant Binding Proteins (OBPs) into gas-sensing materials can increase volatile organic compounds (VOCs) recognition and selectivity. OBPs are small soluble proteins found in vertebrates and insects, responsible for VOCs solubilization and transportation. In this work, OBP3 from Rattus norvegicus was selected to develop an OBP-based electrical VOC sensor, by optimizing protein production and immobilization on sensors surface. OBP3 was successfully produced in E. coli host cells (94 mg/L) and purified with high purity (88% purification yield, 96% purity). The protein folding and thermal stability were assessed by circular dichroism (Tm=71±1ºC) whereas ligand binding activity was verified in solution by fluorescence displacement against diisopropylphenol (Kd=0.24 µM). For the immobilization of OBP3 on gold interdigitated electrodes modified with reduced graphene oxide, we explored two strategies (covalent and non-covalent), establishing a reproducible and cost-effective methodology to develop OBP3-based electrical sensors. The non-covalent immobilization of a linker to the graphene-modified surface showed improved outcomes compared to the carbodiimide crosslinking chemistry. OBP3-sensors presented selectivity towards distinct model compounds in the gas phase (diisopropylphenol, dimethylpyrazine, menthone and decanol), in correlation with the dissociation constants measured by fluorescence displacement assays in solution. As a result, this study expands the practical applications of OBPs for gas-phase sensors, showcasing their potential for enhancing VOC detection.

Ultrasensitive electrochemical sensor for detection of salivary cortisol in stress conditions.

A natural stress response induces elevated cortisol levels in biological fluids, such as saliva. While current sensor technologies can detect cortisol in real time, their sensitivity and reliability for human subjects have not been assured. This is due to relatively low concentrations of salivary cortisol, which fluctuate throughout the day and vary significantly between individuals. To address these challenges, we present an improved electrochemical biosensor leveraging graphene's exceptional conductivity and physicochemical properties. A1-pyrenebutyric acid N-hydroxysuccinimide ester (PBASE-NHS)-modified commercial graphene foam (GF) electrode is presentedto realize an ultra-sensitive biosensor for cortisol detection directly in human saliva. The biosensor fabrication process entails the attachment of anti-cortisol monoclonal antibodies (mAb-cort) onto a PBASE-NHS/GF electrode through noncovalent immobilization on the vertically stratified graphene foam electrode surface. This unique immobilization strategy preserves graphene's structural integrity and electrical conductivity while facilitating antibody immobilization. The binding of cortisol to immobilized mAb-cort is read out via differential pulse voltammetry using ferri/ferro redox reactions. The immunosensor demonstrates an exceptional dynamic range of 1.0fgmL-1 to 10,000pgmL-1 (R2 = 0.9914) with a detection limit of 0.24fgmL-1 (n = 3) for cortisol. Furthermore, we have established the reliability of cortisol sensors in monitoring human saliva. We have also performed multiple modes of validation, one against the established enzyme-linked immunosorbent assay (ELISA) and a second by a third-party service Salimetric on 16 student volunteers exposed to different stress levels, showing excellent correlation (r = 0.9961). These findings suggest the potential for using mAb-cort/PBASE-NHS/GF-based cortisol electrodes for monitoring salivary cortisol in the general population.

A Novel pH-sensitive Nanocomposite Based on Graphene Oxide for Improving Doxorubicin Release.

Doxorubicin (DOX) as a chemotherapeutic drug has been widely used for treatment of cancer but because of adverse side effects of this drug, different drug delivery systems have been tested. One of them has been immobilization of DOX on the graphene oxide (GO) sheets through non-covalent interactions (GO-DOX) with high efficiency however the release was very low and slow due to strong forces between DOX and GO. The aim of this research was to increase the release of DOX and this goal was achieved through the covalent binding of DOX to the GO-poly(ethyleneimine) 2KDa conjugate. A novel nanocarrier for delivering DOX was fabricated using GO as a basic plane for conjugating and assembling other compounds. DOX was attached to GO-poly(ethyleneimine) 2KDa conjugate via</i> a linker containing hydrazide bond. Drug loading and release was investigated at pH 7.5 and pH 5.5. Cytotoxicity was determined by MTT on MCF7 cells and compared with previous nanocarrier. The fabrication of the nanocarrier and the covalent attachment of DOX to the nanocarrier were confirmed through FT-IR spectroscopy. The capacity of nanocarrier to load drug was as high as 383%. 96% of initial drug was loaded in the nanocarrier. The weight percentage of the drug in the nanocarrierdrug conjugate was 79%. Release of drug at pH 5.5 was two times more than release at pH 7.5 and this evidence supports conjugation of DOX to nanocarrier through hydrazide bond and pH-sensitivity of related bond. Because of the reliable results, ease of operation, safety and high reproducibility, MTT was chosen to evaluate the cytotoxicity of samples. Nanocarrier didn't show significant toxicity even at high concentrations. IC50 value for chemically-bound DOX to hydrazide-containing GO nanocomposite was 9.5 μg/ml whereas the IC50 value for GO-DOX was 39 μg/ml after 72 h. Loading of DOX via hydrazide bond was as low as 4% versus near 75% physical loading of drug while hydrazide bondcontaining nanocomposite was 4 to 6 fold more toxic than GO-DOX. Based on the obtained data, the covalent attachment of DOX to the nanocarrier through hydrazide linkers was an interesting idea that increased drug release and toxicity despite much lower percentage of covalent attachment compared to non-covalent immobilization. As could be concluded from this study, nanocarriers based on hydrazide bond could be a good candidate for drug delivery.

Flax fiber-chitosan biocomposites with tailored structure and switchable physicochemical properties

A facile and sustainable synthesis of unique flax fiber composites (FFCs) is reported, where raw flax fiber (FFR) was immobilized with variable chitosan content. FFCs were structurally characterized via TGA, XRD, SEM analysis, and spectroscopy (IR, NMR, and Raman mapping). Physicochemical characterization of FFCs enabled estimation of the point-of-zero-charge (PZC), solvent swelling at variable pH. Dye adsorption with Rose Bengal (RB) and Methylene Blue (MB) afforded characterization of the surface chemistry of the materials. This contribution study is a first reported example that highlights the unique structure-property relationships of FFC materials and the role of electrostatic interactions between the pristine fiber substrate and chitosan. FFCs with incremental chitosan content display the following trends: (i) greater solvent swelling at variable pH (350 % for FFCs and ca. 100 % for FFR and commercial absorbents), (ii) two-fold enhanced adsorption of RB (FFC 0.5 to FFC 2.0) and (iii) 1.5-fold decreased adsorption of MB (FFC 2.0 to FFC 0.5). The unique “switchable” sorption properties of the FFCs toward solvent and dyes was revealed upon facile and noncovalent immobilization of chitosan onto FFR. The sustainable composites reported herein offer a potential adsorption-based technology suitable for filter-based applications in “smart textiles” to biomedical sorbents for wound healing.

Label-free immunosensor for detection of hepatitis C (HCV) core antigen using ternary polypyrrole-Ag doped ZnO-exfoliated graphene nanocomposite

A label-free immunosensor for detection of hepatitis C (HCV) core antigen was fabricated using a ternary nanocomposite based on polypyrrole (PPy), silver doped zinc oxide (Ag-ZnO) and exfoliated graphene (Ex-Gr). The negatively charged anticore mAbs 19D9D6 (1 NLB monoclonal antibodies) were immobilized at the PPy/Ag-ZnO/Ex-Gr 9 % nanocomposite surface as it is suitable for non-covalent (electrostatic) immobilization for fabricating the label-free immunosensor. The isoelectric point (IEP) achieved at around pH 7 for PPy shifts to the lower value of pH 5.75 for PPy/Ag-ZnO/Ex-Gr 9 % nanocomposite. The linear sweep voltammetric (LSV) analysis of the as-prepared samples indicate high electrochemical activity. Similarly, electrochemical impedance spectroscopy (EIS) and cyclic voltammetry confirmed the hindrance in the faradaic processes due to the presence of the interfacial biomolecules layer, after surface modification confirming the fabrication of the immunosensor. The LSV current signal response decrement for the concentration range of antigen [HCV core nucleocapsid polypeptide (residues 13–40) (RNTNRRPQ DVKFPGGGQI VGGVYLLPRR)] ranging from 0.001 ng mL-1 to 200 ng mL-1 was performed depicting the hindrance to electron transfer increases with increase in the antigen concentration as antigen antibody interaction takes place thickening the insulative layer of biomolecules at the interface leading to gradual decrease in the current response. The limit of detection was measured to be approximately 0.41 pg mL-1, respectively (S/N = 3). The single interfering protein doesn’t decrease the LSV current response for HCV (50 ng mL-1) depicting the immunospecificity i-e selectivity of the fabricated immunosensor. The as prepared label-free immunosensor displayed lower limit of detection, high selectivity and stability.

Adsorption of flexible linker for siRNA on carbon nanotube using pyrene anchor: Molecular dynamics simulation

Carbon nanotubes are considered an effective nanoplatform for drug delivery, including therapeutic nucleic acids such as small interfering RNAs (siRNAs), which are used in cancer therapy. In this work, a noncovalent immobilization of a single-stranded oligonucleotide (with 17 nucleotides in length) on the single-walled carbon nanotube (SWNT) surface using a pyrene molecule as an anchor is simulated by molecular dynamics method. This oligonucleotide design supposes the following binding with siRNA ends to provide its keeping near the nanotube surface. In the model, the pyrene molecule is covalently conjugated to the oligonucleotide through an hexaethylene glycol oligomer (EG)6 and attached to the SWNT’s surface by means of π-π stacking interaction. Structures of the complex and the binding energy of pyrene in the complex with SWNT are determined. Two possible orientations of the oligonucleotide arrangement relative to SWNT were considered: mutually perpendicular orientation and arrangement of an oligonucleotide along the nanotube. In both cases, the pyrene-terminated flexible polyethylene glycol linker plays an important role in keeping the oligonucleotide near the nanotube surface and provides sufficiently rapid adsorption of the biopolymer on SWNT, which is important for the creation of new drug delivery systems into the cell and for biosensor design.

Pyrene-TEMPO-Modified Carbon Electrodes for Organic Radical Lithium-Ion Batteries

Organic radical batteries (ORBs) are a promising alternative to traditional lithium-ion batteries (LIBs) because of their environmentally friendly materials and potential to be low-cost, light weight, and mechanically flexible. Among ORB materials, stable organic radical polymers have great potential as high energy density and high power density cathode materials due to their small molecular weight and fast, reversible redox reactions. A stable radical polymer for LIB applications contains an organic radical unit with redox potentials suitable for the LIB anode or cathode that is immobilized on an electrode via a main chain polymer. Conductive and light-weight polymer main chains are necessary to ensure fast electron transfer to the current collector, without adding significant weight to the cell. Despite extensive research, organic radical materials present some key challenges which limit their present use in electrochemical cells. Many polymer backbones are non-conductive, leading to increased electrode resistance and poor cell performance at high charge/discharge rates. Many organic radical materials also have relatively low thermal stability and low packing density. Moreover, many organic radicals are soluble in typical organic battery electrolytes, resulting in capacity fading.In this research, we apply pyrene as a polymer backbone to 2,2,6,6-tetramethyl-piperidine-1-oxyl radical (TEMPO) for the first time in LIB applications to reduce the solubility of the active organic radical and enable π−π stacking interactions with aromatic carbons. We prepared a surface-immobilized p–TEMPO on fullerene C60 and graphene foam (GF) electrodes via π−π stacking interactions to increase electrode conductivity. Pyrene is used to modify certain carbon allotropes via π−π stacking interactions. It was hypothesized that this approach would enable strong bond formation of the TEMPO radical with the electrode, while providing a non-destructive and simple modification approach of conductive carbon surfaces. The successful conjugation of pyrene and TEMPO molecules was established by NMR spectroscopy. The redox activity of p-TEMPO in LIB electrolytes was validated in solution. The non-covalent attachment of p-TEMPO to fullerene C60 and GF electrodes was established by XPS. The mechanisms and reversibility of the TEMPO redox reaction was then explored for p-TEMPO immobilized on the carbon electrodes. While both electrodes showed diffusion-limited current, and quasi-reversible reactions, C60-p-TEMPO has better reversibility and less resistance than GF-p-TEMPO. C60-p-TEMPO electrodes exhibit exceptional cycling stability over 600 cycles. These results are outstanding as the C60 has a high tendency to dissolve in LIB electrolytes. LIB half-cell testing identified challenges and opportunities for the p-TEMPO-modified electrodes. C60-p-TEMPO discharge capacity at ~5C rate is comparable to PTMA-based literature, however no distinct TEMPO response was observed in the charge or discharge curves. GF-p-TEMPO electrodes showed a TEMPO response in cycle 1 only, suggesting possible p-TEMPO dissolution in the electrolyte. Overall, the results show that the use of a noncovalent immobilization method allows facile preparation of p-TEMPO functionalized electrodes and demonstrates the potential of p-TEMPO noncovalent bonding in organic LIB applications. Figure 1

Optimal Synthesis of Novel Phosphonic Acid Modified Diatomite Adsorbents for Effective Removal of Uranium(VI) Ions from Aqueous Solutions.

The authors synthesized a series of functionalized diatomite-based materials and assessed their U(VI) removal performance. Phosphor-derivative-modified diatomite adsorbents were synthesized by the three-route procedures: polymerisation (DIT-Vin-PAin), covalent (DIT-Vin-PAcov), and non-covalent (DIT-PA) immobilization of the functional groups. The effects of the diatomite modification have been studied using powder XRD, solid state NMR, FTIR spectroscopy, electronic microscopy, EDX, acid-base titrations, etc. The maximum adsorption capacities of DIT-Vin-PAcov, DIT-PA, and DIT-Vin-PAin samples were 294.3 mg/g, 253.8 mg/g, and 315.9 mg/g, respectively, at pH0 = 9.0. The adsorption amount of U(VI) ions using the prepared DIT-Vin-PAin was 95.63%, which is higher compared with that of the natural diatomite at the same concentration. The adsorption studies demonstrated that the phosphonic and hydroxyl groups on the surface of the diatomite played pivotal roles in the U(VI) adsorption. The U(VI) ions as a "hard" Lewis acid could easily form bonds with the "hard" donor P-containing ligands, so that the as-prepared DIT-Vin-PAin sample had excellent adsorption properties. The monolayer adsorption of the analyte on the surface of the raw diatomite and DIT-PA was observed. It was found from the thermodynamic parameters that the uptake of the U(VI) ions by the obtained adsorbents was a spontaneous process with an endothermic effect. Findings of the present work highlight the potential for using modified diatomite as effective and reusable adsorbents for the extraction of U(VI) in the waste, river, and tap waters with satisfactory results.

Performance of a Flow-Through Enzyme Reactor Prepared from a Silica Monolith and an α-Poly(D-Lysine)-Enzyme Conjugate.

Horseradish peroxidase (HRP) is covalently bound in aqueous solution to polycationic α-poly(D-lysine) chains of ≈1000 repeating units length, PDL, via a bis-aryl hydrazone bond (BAH). Under the experimental conditions used, about 15 HRP molecules are bound along the PDL chain. The purified PDL-BAH-HRP conjugate is very stable when stored at micromolar HRP concentration in a pH 7.2 phosphate buffer solution at 4°C. When a defined volume of such a conjugate solution of desired HRP concentration (i.e., HRP activity) is added to a macro- and mesoporous silica monolith with pore sizes of 20-30µm as well as below 30nm, quantitative and stable noncovalent conjugate immobilization is achieved. The HRP-containing monolith can be used as flow-through enzyme reactor for bioanalytical applications at neutral or slightly alkaline pH, as demonstrated for the determination of hydrogen peroxide in diluted honey. The conjugate can be detached from the monolith by simple enzyme reactor washing with an aqueous solution of pH 5.0, enabling reloading with fresh conjugate solution at pH 7.2. Compared to previously investigated polycationic dendronized polymer-enzyme conjugates with approximately the same average polymer chain length, the PDL-BAH-HRP conjugate appears to be equally suitable for HRP immobilization on silica surfaces.

Long-Period Fiber Grating Sensors for Chemical and Biomedical Applications.

Optical fiber biosensors (OFBS) are being increasingly proposed due to their intrinsic advantages over conventional sensors, including their compactness, potential remote control and immunity to electromagnetic interference. This review systematically introduces the advances of OFBS based on long-period fiber gratings (LPFGs) for chemical and biomedical applications from the perspective of design and functionalization. The sensitivity of such a sensor can be enhanced by designing the device working at or near the dispersion turning point, or working around the mode transition, or their combination. In addition, several common functionalization methods are summarized in detail, such as the covalent immobilization of 3-aminopropyltriethoxysilane (APTES) silanization and graphene oxide (GO) functionalization, and the noncovalent immobilization of the layer-by-layer assembly method. Moreover, reflective LPFG-based sensors with different configurations have also been introduced. This work aims to provide a comprehensive understanding of LPFG-based biosensors and to suggest some future directions for exploration.

Covalent conjugation of proteins onto fluorescent single-walled carbon nanotubes for biological and medical applications.

Single-walled carbon nanotubes (SWCNTs) have optical properties that are conducive for biological applications such as sensing, delivery, and imaging. These applications necessitate the immobilization of macromolecules that can serve as therapeutic drugs, molecular templates, or modulators of surface interactions. Although previous studies have focused on non-covalent immobilization strategies, recent advances have introduced covalent functional handles that can preserve or even enhance the SWCNT optical properties. This review presents an overview of covalent sidewall modifications of SWCNTs, with a focus on the latest generation of "sp3 defect" modifications. We summarize and compare the reaction conditions and the reported products of these sp3 chemistries. We further review the underlying photophysics governing SWCNT fluorescence and apply these principles to the fluorescence emitted from these covalently modified SWCNTs. Finally, we provide an outlook on additional chemistries that could be applied to covalently conjugate proteins to these chemically modified, fluorescent SWCNTs. We review the advantages of these approaches, emerging opportunities for further improvement, as well as their implications for enabling new technologies.

Direct electrochemistry of hemoglobin/peptide-carbon nanotube modified electrode for hydrogen peroxide biosensing

Mediatorless enzymatic biosensors based on direct electron transfer show promise due to their high stability and remarkable electrocatalytical performance. In this study, the direct electrochemistry of a glassy carbon electrode modified with hemoglobin (Hb) embedded in a hybrid layer of self-assembling EFK8 peptide and single-walled carbon nanotubes (SWNTs) was investigated. Electrochemical studies in 0.1 M phosphate buffer (PB) revealed that the immobilized Hb did not denature and retained its bio-catalytic activity. The resulting biosensor was used to detect and measure the hydrogen peroxide (H2O2) concentration in 0.1 M PB (pH 7.0), yielding a linear detection range from 20 to 960 µM and a detection limit of 7.54 µM (S/N = 3). The EFK8-SWNT hybrid layer shows promise as a biocompatible layer for simple non-covalent enzyme immobilization as the basis for future mediatorless enzymatic biosensors.

Surface Control of Nanodiamond: From Homogeneous Termination to Complex Functional Architectures for Biomedical Applications.

ConspectusInterest in nanodiamond (ND) has been spurred by its unique properties such as high biocompatibility, versatile surface chemistry, and the possibility to apply it as drug delivery agent, cross-linker, or coating and for sensing applications when luminescent lattice defects such as the NV centers are present in the crystal lattice. Currently, nanodiamond has been used for targeted drug delivery, phototherapeutic applications, and sensing and imaging in cellular environments and in vitro. Furthermore, suitably functionalized nanodiamond is a promising material for tissue engineering applications. However, the application of nanodiamond has long been hampered by a number of obstacles and challenges met with commercially available nanodiamonds of different origins. A major issue is related to the strong agglomeration of the individual particles resulting in covalently linked aggregates with larger sizes and a broad size distribution. Furthermore, the surface termination of typical nanodiamond particles tends to be rather inhomogeneous, containing a multitude of different functional groups. The retention of functionality of immobilized moieties for bioapplications is often not known. And finally, the surface of nanodiamond possesses a strong propensity for nonspecific interaction, especially proteins from serum, cell fluids, or the culture media used for the incubation of cells with nanodiamond. The resulting protein corona influences the possibility to access functional moieties on the diamond surface and leads to a reduced reproducibility of observations in physiological environments and a limited attribution of effects to the presence of the functional moieties on the diamond surface. In this Account, we describe our efforts to address these challenges using multiple strategies mainly for the example of detonation nanodiamond (DND). First, a homogeneous size distribution of the nanoparticles and an initial surface termination with a unique type of atoms or groups can be achieved using mechanochemical methods and treatments with different reagents in both solution and gas phases. Reactions in liquid media typically lead to more uniform results as the entire surface of the particles becomes equally accessible. We have then worked on the development of different covalent linker strategies to accommodate the grafting needs of different functional moieties and thus to enable the production of orthogonally functionalized ND particles, which can be modified with multiple moieties in a controlled fashion. The noncovalent immobilization of functional units is equally useful as it permits the conservation of functionality for sensitive proteins, which denature upon covalent immobilization. In summary, our work aims to gain full control over the surface properties of diamond nanoparticles and to develop a toolbox of chemical methods to provide functionalized and tailored nanodiamond for a plethora of biomedical applications. Further research in the field of diamond functionalization will cover also the transfer of already existing methods to other types of diamond surfaces, the production of stoichiometrically functionalized particles, the covalent and dynamic self-assembly of nanodiamond particles, and the continuing development of suitable characterization techniques.

Non-covalent immobilized sultone based protic ionic liquids on nano silica sulfuric acid as novel heterogeneous catalysts for the efficient synthesis of tetrazolopyrimidines

In this research work, a novel strategy for the heterogenization of sultone based acidic ionic liquids via their non-covalent immobilization on nano silica sulfuric acid is reported and the catalytic ability of the prepared heterogeneous catalysts for the synthesis of tetrazolopyrimidines derivatives is investigated. The physicochemical properties of the prepared catalysts were studied using thermal and spectroscopic techniques such as 1H and 13C NMR, FTIR, SEM, TEM, TGA, EDX and BET. In the following, three-component reaction of aromatic aldehydes, active methylene compounds and 5-aminotetrazole to achieve tetrazolopyrimidine products in the presence of the introduced nano silica sulfuric acid supported acidic ionic liquids as new organic–inorganic nanohybrid catalysts was performed. The obtained results showed that the supported protic ionic liquids have better catalytic activity than their non-supported forms. Moreover, the recoverability, reusability and thermal stability of the acidic ionic liquids were also significantly improved by immobilization on nano silica sulfuric acid.

Melimine-Modified 3D-Printed Polycaprolactone Scaffolds for the Prevention of Biofilm-Related Biomaterial Infections.

Biomaterial-associated infections are one of the major causes of implant failure. These infections result from persistent bacteria that have adhered to the biomaterial surface before, during, or after surgery and have formed a biofilm on the implant's surface. It is estimated that 4 to 10% of implant surfaces are contaminated with bacteria; however, the infection rate can be as high as 30% in intensive care units in developed countries and as high as 45% in developing countries. To date, there is no clinical solution to prevent implant infection without relying on the use of high doses of antibiotics supplied systemically and/or removal of the infected device. In this study, melimine, a chimeric cationic peptide that has been tested in Phase I and II human clinical trials, was immobilized onto the surface of 3D-printed medical-grade polycaprolactone (mPCL) scaffolds via covalent binding and adsorption. X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS) spectra of melimine-treated surfaces confirmed immobilization of the peptide, as well as its homogeneous distribution throughout the scaffold surface. Amino acid analysis showed that melimine covalent and noncovalent immobilization resulted in a peptide density of ∼156 and ∼533 ng/cm2, respectively. Furthermore, we demonstrated that the immobilization of melimine on mPCL scaffolds by 1-ethyl-3-[3-(dimethylamino)propyl] carbodiimide hydrochloride (EDC) coupling and noncovalent interactions resulted in a reduction of Staphylococcus aureus colonization by 78.7% and 76.0%, respectively, in comparison with the nonmodified control specimens. Particularly, the modified surfaces maintained their antibacterial properties for 3 days, which resulted in the inhibition of biofilm formation in vitro. This system offers a biomaterial strategy to effectively prevent biofilm-related infections on implant surfaces without relying on the use of prophylactic antibiotic treatment.

Fluorescent Molecular Logic Gates and Pourbaix Sensors in Polyacrylamide Hydrogels.

Polyacrylamide hydrogels formed by free radical polymerisation were formed by entrapping anthracene and 4-amino-1,8-naphthalimide fluorescent logic gates based on photoinduced electron transfer (PET) and/or internal charge transfer (ICT). The non-covalent immobilisation of the molecules in the hydrogels resulted in semi-solid YES, NOT, and AND logic gates. Two molecular AND gates, examples of Pourbaix sensors, were tested in acidic aqueous methanol with ammonium persulfate, a strong oxidant, and displayed greater fluorescence quantum yields than previously reported. The logic hydrogels were exposed to aqueous solutions with chemical inputs, and the fluorescence output response was viewed under 365 nm UV light. All of the molecular logic gates diffuse out of the hydrogels to some extent when placed in solution, particularly those with secondary basic amines. The study exemplifies an effort of taking molecular logic gates from homogeneous solutions into the realm of solid-solution environments. We demonstrate the use of Pourbaix sensors as pE-pH indicators for monitoring oxidative and acidic conditions, notably for excess ammonium persulfate, a reagent used in the polymerisation of SDS-polyacrylamide gels.