Preparation, chemistry and applications of novel carbon nanomaterials

The isolation of graphene in 2004, and subsequent Nobel Prize for Physics being awarded to Andre Geim and Konstantin Novoselov in 2010, has sparked a renewed interest in graphene around the world due to graphene’s remarkable physical properties such as mechanical stability, optical transparency, impermeability and electrical and thermal conductivity. Graphene Oxide (GO), the oxidised analogue of graphene, has also received much attention owing to its hydrophilic nature. This has made GO a very promising material for aqueous processing, giving it a significant advantage over graphene. In this way, GO has been used in many composite materials, involving biological molecules, metal-organic-frameworks (MOFs) and other hybrid systems. Unfortunately, much uncertainty surrounds the chemical nature of GO, and therefore its chemistry, thus creating a lot of controversy in the literature. Similarly, the preparation of GO also results in lengthy procedures and toxic by-products. To address these issues, this thesis describes the preparation of alternative carbon nanomaterials, as a potential substitute to GO, which have well-defined structures and chemistry and/or reduce the toxic waste produced. The chemistry and applications of these new materials are explored and benchmarked against conventional GO, which is prepared via permanganate oxidation (PM-GO). The preparation of three novel carbon materials, carboxylated graphene nanoflakes (cx-GNFs), nano-graphene oxide (nGO) and GO prepared via dichromate oxidation (DC-GO) are initially reported, along with extensive characterisations. The cx-GNFs are a highly soluble (~100 mg mL-1) and well-defined material consisting of carboxyl groups and unoxidised sp2 carbon only. nGO is prepared via an eco-friendly procedure producing nano-sized GO and DC-GO was prepared in order to elucidate its chemical structure which remains uncertain in the literature. The thermal annealing behaviour of the materials are reported next and the cx-GNFs and the nGO are shown to form carboxylic anhydrides in yields up to 81%, which is the first experimental evidence for this functional group at the graphene edge. The existence of carboxylic anhydrides in dynamic equilibrium with carboxylic acids in water was demonstrated at room temperature for the cx-GNFs, and was consequently exploited for room temperature chemical functionalisations with well-known amines such as ethylenediamine and cysteamine. These functionalised materials were then explored in the context of tagging gold nanoparticles and changing the zeta potential of the native cx-GNFs. The application of these novel materials in heavy-metal extraction is also presented and found to greatly exceed the capacity of PM-GO - by up to six times. Collaborations with other research groups in the field of nano-sensors, ice-nucleation and electrochemistry, revealed the cx-GNFs to be a particularly promising material

Sex- and age-related differences in the management and outcomes of chronic heart failure: an analysis of patients from the ESC HFA EORP Heart Failure Long-Term Registry

Aims: This study aimed to assess age- and sex-related differences in management and 1-year risk for all-cause mortality and hospitalization in chronic heart failure (HF) patients. Methods and results: Of 16 354 patients included in the European Society of Cardiology Heart Failure Long-Term Registry, 9428 chronic HF patients were analysed [median age: 66 years; 28.5% women; mean left ventricular ejection fraction (LVEF) 37%]. Rates of use of guideline-directed medical therapy (GDMT) were high (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers and mineralocorticoid receptor antagonists: 85.7%, 88.7% and 58.8%, respectively). Crude GDMT utilization rates were lower in women than in men (all differences: P\ua0 64 0.001), and GDMT use became lower with ageing in both sexes, at baseline and at 1-year follow-up. Sex was not an independent predictor of GDMT prescription; however, age >75 years was a significant predictor of GDMT underutilization. Rates of all-cause mortality were lower in women than in men (7.1% vs. 8.7%; P\ua0=\ua00.015), as were rates of all-cause hospitalization (21.9% vs. 27.3%; P\ua075 years. Conclusions: There was a decline in GDMT use with advanced age in both sexes. Sex was not an independent predictor of GDMT or adverse outcomes. However, age >75 years independently predicted lower GDMT use and higher all-cause mortality in patients with LVEF 6445%

Multi-functionalised graphene nanoflakes as tumour-targeting theranostic drug-delivery vehicles

Graphene nanoflakes (GNFs) consist of a graphene sheet approximately 30 nm in diameter with a pristine aromatic system and an edge terminated with carboxylic acid groups. Their high water solubility and relative ease of functionalisation using carboxylate chemistry means that GNFs are potential scaffolds for the synthesis of theranostic agents. In this work, GNFs were multi-functionalised with derivatives of (i) a peptide-based Glu-NH-C(O)-NH-Lys ligand that binds prostate-specific membrane antigen (PSMA), (ii) a potent anti-mitotic drug (R)-ispinesib, (iii) the chelate desferrioxamine B (DFO), and (iv) an albumin-binding tag reported to extend pharmacokinetic half-life in vivo. Subsequent 68Ga radiochemistry and experiments in vitro and in vivo were used to evaluate the performance of GNFs in theranostic drug design. Efficient 68Ga-radiolabelling was achieved and the particle-loading of (R)-ispinesib and Glu-NH-C(O)-NH-Lys was confirmed using cellular assays. Using dose–response curves and FACS analysis it was shown that GNFs loaded with (R)-ispinesib inhibited the kinesin spindle protein (KSP) and induced G2/M-phase cell cycle arrest. Cellular uptake and blocking experiments demonstrated that GNFs functionalised with the Glu-NH-C(O)-NH-Lys ligand showed specificity toward PSMA expressing cells (LNCaP). The distribution profile and excretion rates of 68Ga-radiolabelled GNFs in athymic nude mice was evaluated using time–activity curves derived from dynamic positron-emission tomography (PET). Image analysis indicated that GNFs have low accumulation and retention in background tissue, with rapid renal clearance. In summary, our study shows that GNFs are suitable candidates for use in theranostic drug design

Ice Nucleation Properties of Oxidized Carbon Nanomaterials

Heterogeneous ice nucleation is an important process in many fields, particularly atmospheric science, but is still poorly understood. All known inorganic ice nucleating particles are relatively large in size and tend to be hydrophilic. Hence it is not obvious that carbon nanomaterials should nucleate ice. However, in this paper we show that four different readily water-dispersible carbon nanomaterials are capable of nucleating ice. The tested materials were carboxylated graphene nanoflakes, graphene oxide, oxidized single walled carbon nanotubes and oxidized multiwalled carbon nanotubes. The carboxylated graphene nanoflakes have a diameter of ~30 nm and are among the smallest entities observed so far to nucleate ice. Overall, carbon nanotubes were found to nucleate ice more efficiently than flat graphene species, and less oxidized materials nucleated ice more efficiently than more oxidized species. These well-defined carbon nanomaterials may pave the way to bridging the gap between experimental and computational studies of ice nucleation

Electrochemical genosensor based on carboxylated graphene for detection of water-borne pathogen

This work reports the application of newly synthesized carboxylated graphene nanoflakes (Cx-Gnfs). The Cx-Gnfs were synthesized by wet chemical method in sulfuric acid/nitric acid mixture and was further electrophoretically deposited on indium fin oxide (ITO) coated glass substrates using Mg(2+ )ions which provides an overall charge to the materials for deposition onto the anode. The materials were characterized using SEM, TEM, contact angle, UV-vis spectroscopy, FT-IR, XRD and electrochemically characterized by cyclic voltammetry, chronocoulometry and electrochemical impedance spectroscopy. The sensitive quantitative determination of nucleic acid Escherichia coli O157: H7 (E. coil) has been achieved using Cx-Gnfs and r-GO as the sensing layer using electrochemical impedance spectroscopy. The electrochemical results reveal that the Cx-Gnfs based genosensor exhibits a linear response to complementary DNA (10(-6) M to 10(-17) M) with a detection limit of 1 x 10(-17) M while the rGO based genosensor shows a detection limit of 1 x 10(-15) M. Under optimal conditions, this Cx-Gnfs based genosensor was found to retain about 85% of its initial activity after being used for 6 times

Selectively Sized Graphene-Based Nanopores for in Situ Single Molecule Sensing

The use of nanopore biosensors is set to be extremely important in developing precise single molecule detectors and providing highly sensitive advanced analysis of biological molecules. The precise tailoring of nanopore size is a significant step toward achieving this, as it would allow for a nanopore to be tuned to a corresponding analyte. The work presented here details a methodology for selectively opening nanopores in real-time. The tunable nanopores on a quartz nanopipette platform are fabricated using the electroetching of a graphene-based membrane constructed from individual graphene nanoflakes (ø ∼30 nm). The device design allows for in situ opening of the graphene membrane, from fully closed to fully opened (ø ∼25 nm), a feature that has yet to be reported in the literature. The translocation of DNA is studied as the pore size is varied, allowing for subfeatures of DNA to be detected with slower DNA translocations at smaller pore sizes, and the ability to observe trends as the pore is opened. This approach opens the door to creating a device that can be target to detect specific analytes

The stakeholder approach to the construction of performance measures

A report to the British Library Research and Development Dept.Available from British Library Document Supply Centre-DSC:2327.6831(31) / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo