Carbon nanotubes constitute a novel class of nanomaterials with potential applications in many areas. The attachment of metal nanoparticles to carbon nanotubes is new way to obtain novel hybrid materials with interesting properties for various applications such as catalysts and gas sensors as well as electronic and magnetic devices. Their unique properties such as excellent electronic properties, a good chemical stability, and a large surface area make carbon nanotubes very useful as a support for gold nanoparticles in many potential applications, ranging from advanced catalytic systems through very sensitive electrochemical sensors and biosensors to highly efficient fuel cells. Here we give an overview on the recent progress in this area by exploring the various synthesis approaches and types of assemblies, in which nanotubes can be decorated with gold nanoparticles and explore the diverse applications of the resulting composites.

Carbon nanotubes show exceptional properties that render them promising candidates as building blocks for nanostructured materials. Many ambitious applications, ranging from molecular detection to membrane separation, require the delivery of fluids, in particular aqueous solutions, through the interior of carbon nanotubes (CNT). To foster such applications, an understanding of the properties of water molecules confined in carbon nanotubes at the molecular level is needed. In this work we report a study of temperature and helicity effects on static properties of water molecules confined in modified CNT by molecular dynamics simulations. It was found that the temperature has little effect on the confined water molecules in carbon nanotubes. But on the other hand, the simulation results showed that because of the difference in helicity between (6, 6) and (10, 0) CNTs, the modification by hydrophilic carboxyl acid functional groups (-COOH) results in a different response to the CNTs, which in turn have control over the flow direction of water molecules in these CNTs.

A single-wall carbon nanotubes (SWNT)-Nafion film coated glassy carbon electrode (GCE) was described for the determination of 4-aminophenol. In pH 3.0 sodium citrate-HCl buffer, the oxidation peak current of 4-aminophenol increases greatly at the SWNT-Nafion film coated GCE in contrast to that at both bare GCE and Nafion-film coated GCE. Moreover, the oxidation peak potential shifts to more negative potential. All the experimental parameters were optimized for the determination of 4-aminophenol. The oxidation peak current is proportional to the concentration of 4-aminophenol over the range from 5x10(-9) to 2x10(-6) mol l(-1). The detection limit is 8x10(-10) mol l(-1) at 4 min of accumulation. Using the proposed method, 4-aminophenol in water samples was determined.

Nanocomposite film composed of polyaniline (PANI) and multiwalled carbon nanotubes (MWCNT), prepared electrophoretically onto indium tin oxide (ITO)-coated glass plate, was used for covalent immobilization of cholesterol oxidase (ChOx) via N-ethyl-N'-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS) chemistry. Results of linear sweep voltammetric measurements reveal that ChOx/PANI-MWCNT/ITO bioelectrode can detect cholesterol in the range of 1.29 to 12.93 mM with high sensitivity of 6800 nA mM(-1) and a fast response time of 10 s. Photometric studies for ChOx/PANI-MWCNT/ITO bioelectrode indicate that it is thermally stable up to 45 degrees C and has a shelf life of approximately 12 weeks when stored at 4 degrees C. The results of these studies have implications for the application of this interesting matrix (PANI-MWCNT) toward the development of other biosensors.

In this study, we prepared carbon nanotube (CNT)/Nafion-modified ITO electrodes and investigated their electrochemical behavior. The CNTs were dissolved in a solution of the ionic polymer Nafion and then CNT/Nafion composite films were deposited onto ITO electrodes through spin-coating of this homogeneous solution. We studied the effects of chemical pretreatment of the CNTs and the pH of the buffer on the electroanalytical behavior of the CNT/Nafion-modified ITO electrodes toward catecholamines. The modified electrodes enhanced the peak current and lowered the overpotentials. We observed high electrooxidative performance for the modified ITO electrodes: the oxidative currents of the catecholamines were up to 125-fold higher than those obtained using bare ITO electrodes.

Molecular tips in scanning tunneling microscopy can directly detect intermolecular electron tunneling between sample and tip molecules and reveal the tunneling facilitation through chemical interactions that provide overlap of respective electronic wave functions, that is, hydrogen-bond, metal-coordination-bond, and charge-transfer interactions. Nucleobase molecular tips were prepared by chemical modification of underlying metal tips with thiol derivatives of adenine, guanine, cytosine, and uracil and the outmost single nucleobase adsorbate probes intermolecular electron tunneling to or from a sample nucleobase molecule. We found that the electron tunneling between a sample nucleobase and its complementary nucleobase molecular tip was much facilitated compared with its noncomplementary counterpart. The complementary nucleobase tip was thereby capable of electrically pinpointing each nucleobase. Chemically selective imaging using molecular tips may be coined "intermolecular tunneling microscopy" as its principle goes and is of general significance for novel molecular imaging of chemical identities at the membrane and solid surfaces.

A fullerene molecular tip was used to detect electron tunneling from a single porphyrin molecule. Electron tunneling was found to occur locally from an electron-donating moiety of the porphyrin to the fullerene through charge-transfer interaction between them. In addition, electron tunneling within the single fullerene-porphyrin pair exhibited rectifying behavior in which electrons can be driven only at the direction from the porphyrin to the fullerene. It is demonstrated that localized electron tunneling enables us to spatially visualize the frontier orbital of the porphyrin involved in electron tunneling. In addition, rectification demonstrates that the fullerene-porphyrin pair constitutes a molecular rectifier. We believe that molecular tips bring insight into intermolecular electron transmission toward realization of molecular electronics as shown here.

For nondestructive analysis of chemical processes in living cells, we developed novel intracellular fluorescent indicators for second messengers, protein phosphorylation, and protein/protein interactions that work in single living cells. Key molecules and steps of cellular signaling pathways were visualized under a confocal laser microscope in target live cells using developed fluorescent indicators. A second new approach to molecular imaging is also described. When chemically modified tips were used for STM measurements, contrast enhancements at specific regions in the STM images occurred on the basis of hydrogen bond and metal-coordination interactions. This enabled us to detect not only the distribution of specific chemical species and functional groups but also the orientation of functional groups. The contrast enhancements reflect the increase in a tunneling current due to the overlap of electronic wave functions induced by the chemical interactions between tip and sample.

A fullerene molecular tip was used to detect electron tunneling from a single porphyrin molecule. Electron tunneling was found to occur locally from an electron-donating moiety of the porphyrin to the fullerene through charge-transfer interaction between them. In addition, electron tunneling within the single fullerene-porphyrin pair exhibited rectifying behavior in which electrons can be driven only at the direction from the porphyrin to the fullerene. It is demonstrated that localized electron tunneling enables us to spatially visualize the frontier orbital of the porphyrin involved in electron tunneling. In addition, rectification demonstrates that the fullerene-porphyrin pair constitutes a molecular rectifier. We believe that molecular tips bring insight into intermolecular electron transmission toward realization of molecular electronics as shown here.

Electron-donating molecular tips were used for the observation of single-walled carbon nanotubes (SWNTs). Defects in SWNTs were selectively visualized at the atomic scale on the basis of charge-transfer interaction with the molecular tip.

Chiral surfaces attract increasing interest due to their vital role in a variety of scientific fields, such as chiral separation and heterogeneous enantioselective catalysis. The most urgent issue in research on such two-dimensional chirality is a lack of methodologies that recognize molecular chirality on a surface. Here we show that the chiral molecular tips enable for the first time discrimination of enantiomers on a single-molecule basis. The chiral selectivity is attributed to favorable chemical interactions that the molecular tips form with only one of two enantiomers. The stereoselective observation reveals spatial distribution of the enantiomers on a surface at the molecular level. The chiral molecular tips open a way for control of organization of enantiomers toward the advanced functionality of these chiral surfaces through knowledge on pivotal roles of chirality on molecular assemblies as shown here.

Taurine is an abundant β-amino acid that concentrates in the mitochondria, where it participates in the conjugation of tRNAs for leucine, lysine, glutamate and glutamine. The formation of 5-taurinomethyluridine-tRNA strengthens the interaction of the anticodon with the codon, thereby promoting the decoding of several codons, including those for AAG, UUG, CAG and GAG. By preventing these series of events, taurine deficiency appears to diminish the formation of 5-taurinomethyluridine and causes inefficient decoding for the mitochondrial codons of leucine, lysine, glutamate and glutamine. The resulting reduction in the biosynthesis of mitochondria-encoded proteins deprives the respiratory chain of subunits required for the assembly of respiratory chain complexes. Hence, taurine deficiency is associated with a reduction in oxygen consumption, an elevation in glycolysis and lactate production and a decline in ATP production. A similar sequence of events takes place in mitochondrial diseases MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) and MERRF (myoclonic epilepsy and ragged-red fiber syndrome). In both diseases, mutations in their respective tRNAs interfere with the formation of 5-taurinomethyluridine in the wobble position. Hence, the taurine-deficient phenotype resembles the phenotypes of MELAS and MERRF.

This paper reports the effects of linker length on electron propagation through ferrocene moieties covalently anchored onto insulator-based cylindrical nanopores derived from a cylinder-forming polystyrene-poly(methylmethacrylate) diblock copolymer. These nanopores (24 nm in diameter, 30 nm long) aligned perpendicular to an underlying gold electrode were modified via esterification of their surface COOH groups with OH-terminated ferrocene derivatives having different alkyl linkers (FcCO(CH2)nOH; n = 2, 5, 15). Cyclic voltammograms were measured in 0.1 M NaBF4 at different scan rates to assess the efficiency of electron propagation through the ferrocene moieties. The redox peaks of the anchored ferrocenes were observed at nanoporous films decorated with FcCO(CH2)15OH and FcCO(CH2)5OH, but not at those with FcCO(CH2)2OH. Importantly, the higher electron propagation efficiency was observed in the use of the longer linker, as shown by the apparent diffusion coefficients (ca. 10-12 cm2/s for n = 15; ca. 10-13 cm2/s for n = 5; no electron propagation for n = 2). The observed electron propagation resulted from electron hopping across relatively large spacing that was controlled by the motion of anchored redox sites (bounded diffusion). The longer linker led to the larger physical displacement range of anchored ferrocene moieties, facilitating the approach of the adjacent ferrocene moieties within a distance required for electron self-exchange reaction. The linker-based control of redox-involved electron propagation on nanostructured, insulating surfaces will provide a means for designing novel molecular electronics and electrochemical sensors.

The aim of this study was to determine whether features indicative of myocardial ischemia occur in the electrocardiograms (ECG) in myocardial infarction-prone Watanabe heritable hyperlipidemic (WHHLMI) rabbits, an animal model for human familial hypercholesterolemia. ECG were recorded in 110 anesthetized WHHLMI rabbits (age, 10 to 39 mo) by using unipolar and bipolar limb leads with or without chest leads. We noted the following electrocardiographic changes: T wave inversion (37.4%), ST segment depression (31.8%), deep Q wave (16.3%), reduced R wave amplitude (7.3%), ST segment elevation (2.7%), and high T wave (1.8%). These ECG changes resembled those in human patients with coronary heart disease. Histopathologic examination revealed that the left ventricular wall showed acute myocardial lesions, including loss of cross-striations, vacuolar degeneration, coagulation necrosis of cardiac myocytes, and edema between myofibrils, in addition to chronic myocardial lesions such as myocardial fibrosis. The coronary arteries that caused these ECG changes were severely stenosed due to atherosclerotic lesions. Ischemic ECG changes corresponded to the locations of the myocardial lesions. Normal ECG waveforms were similar between WHHLMI rabbits and humans, in contrast to the large differences between rabbits and mice or rats. In conclusion, ischemic ECG changes in WHHLMI rabbits reflect the location of myocardial lesions, making this model useful for studying coronary heart disease.

Stroke is a major cause of mortality and disability worldwide. During the past three decades, major advances have occurred in secondary prevention, which have demonstrated the broader potential for the prevention of stroke. Risk factors for stroke include previous stroke or transient ischemic attack, hypertension, high blood cholesterol and diabetes. Proven secondary prevention strategies are anti-platelet agents, antihypertensive drugs, statins and glycemic control. In the present review, we evaluated the secondary prevention of stroke in light of clinical studies and discuss new pleiotropic effects beyond the original effects and emerging clinical evidence, with a focus on the effect of optimal oral pharmacotherapy.

Edaravone was originally developed as a potent free radical scavenger and has been widely used to treat cerebral infarction in Japan since 2001. Several free radical scavengers have been developed and some of them have progressed to clinical trials for the treatment of cerebral infarction. One such scavenger, edaravone, has been approved by the regulatory authority in Japan for the treatment of patients with cerebral infarction. Of particular interest is the ability of edaravone to diffuse into the central nervous system in various neurologic diseases. Aside from its hydroxyl radical scavenging effect, edaravone has been found to have beneficial effects on inflammation, matrix metalloproteinases, nitric oxide production and apoptotic cell death. Concordantly, edaravone has been found to have neuroprotective effects in a number of animal models of disease, including stroke, spinal cord injury, traumatic brain injury, neurodegenerative diseases and brain tumors. The proven safety of edaravone following 9 years of use as a free radical scavenger suggests that it may have potential for development into an effective treatment of multiple neurologic conditions in humans.

Historically, clinical outcomes following spinal cord injury (SCI) have been dismal. Severe SCI leads to devastating neurological deficits, and there is no treatment available that restores the injury-induced loss of function to a degree that an independent life can be guaranteed. To address all the issues associated with SCI, a multidisciplinary approach is required, as it is unlikely that a single approach, such as surgical intervention, pharmacotherapy or cellular transplantation, will suffice. High mobility group box 1 (HMGB1) is an inflammatory cytokine. Various studies have shown that HMGB1 plays a critical role in SCI and that inhibition of HMGB1 release may be a novel therapeutic target for SCI and may support spinal cord repair. In addition, HMGB1 has been associated with graft rejection in the early phase. Therefore, HMGB1 may be a promising therapeutic target for SCI transplant patients. We hypothesize that inhibition of HMGB1 release rescues patients with SCI. Taken together, our findings suggest that anti-HMGB1 monoclonal antibodies or short hairpin RNA-mediated HMGB1 could be administered for spinal cord repair in SCI patients.

Free radicals play an important role in the pathogenesis of a variety of diseases; thus, they are an attractive target for therapeutic intervention in these diseases. Compounds capable of scavenging free radicals have been developed for this purpose and some, developed for the treatment of cerebral ischemic stroke, have progressed to clinical trials. One such scavenger, edaravone, is used to treat patients within 24 h of stroke. Edaravone, which can diffuse into many disease-affected organs, also shows protective effects in the heart, lung, intestine, liver, pancreas, kidney, bladder and testis. As well as scavenging free radicals, edaravone has anti-apoptotic, anti-necrotic and anti-cytokine effects in various diseases. Here, we critically review the literature on its clinical efficacy and examine whether edaravone should be considered a candidate for worldwide development, focusing on its effects on diseases other than cerebral infarction. Edaravone has been safely used as a free radical scavenger for more than 10 years; we propose that edaravone may offer a novel treatment option for several diseases.

Peptide-terminated monolayers were formed through a Huisgen clycloaddition reaction between an α-helical peptide containing two propargylglycine unnatural functional groups 20 Å apart and an alkanethiol self-assembled monolayer (SAM) on a gold surface containing 25% surface density of reactive azide terminal groups. The azide- and peptide-terminated sur-faces were imaged by scanning tunneling microscopy (STM) using a low tunneling current of 10 pA. On the peptide-terminated surface, oblong features approxi-mately 30 Å long and 20 Å wide were observed and at-tributed to individual surface bound α-helical peptides oriented parallel to the gold surface. These features covered an area of the surface that corresponded to a density of 0.11 ± 0.01 peptides nm-2, compared to a theoretical density of approximately 0.14 peptides nm-2 for a fully reacted surface. Finally, no evidence of pep-tide aggregation was observed either at short (< 10 nm) or long (~100 nm) length scales.

Scanning tunneling microscopy (STM) and tunneling spectroscopy studies of nano-structured H6P2MoxW(18-x)O62 (x = 0, 3, 9, 15, 18) Wells-Dawson heteropolyacids (HPAs) were carried out to examine redox properties of the HPAs. STM images of H6P2MoxW(18-x)O62 HPAs clearly showed self-assembled and well-ordered 2-dimensional arrays on graphite surface. Tunneling spectroscopy measurements revealed that all H6P2MoxW(18-x)O62 HPAs exhibited a negative differential resistance (NDR) behavior in their tunneling spectra. NDR peak voltage of H6P2MoxW(18-x)O62 HPAs appeared at less negative applied voltage with increasing molybdenum substitution. Reduction potential of H6P2MoxW(18-x)O62 HPAs measured by an electrochemical method increased and absorption edge energy determined by UV-visible spectroscopy shifted to lower value with increasing molybdenum substitution. In other words, NDR peak voltage of H6P2MoxW(18-x)O62 HPAs appeared at less negative applied voltage with increasing reduction potential and with decreasing absorption edge energy of the HPAs; more reducible H6P2MoxW(18-x)O62 HPAs showed NDR behavior at less negative applied voltage. These results indicate that NDR peak voltage of nano-structured HPAs measured by STM could be utilized as a correlating parameter for the redox properties of bulk HPAs.

Two-component supramolecular networks have been constructed with a symmetric triphenylene derivative with three carboxyl groups (sym-TTT) and melamine. Two kinds of hydrogen bonds with different strength are involved in the multi-component self-assembly, one is H-bond between carboxyl group of sym-TTT and melamine, the other is intermolecular H-bond between melamine molecules. These interactions drive a structural transformation from close-packed network to hexagonal network with active amino groups inside of the cavity. Scanning tunneling microscopy (STM) measurements reveal that the functionalized network of sym-TTT/melamine could recognise Fe(3+). These results could be helpful for designing functionalized molecular networks by multi-component self-assembling strategy.

Individual pentacene and naphthalocyanine molecules adsorbed on a bilayer of NaCl grown on Cu(111) were investigated by means of scanning tunneling microscopy using CO-functionalized tips. The images of the frontier molecular orbitals show an increased lateral resolution compared with those of the bare tip and reflect the modulus squared of the lateral gradient of the wave functions. The contrast is explained by tunneling through the p-wave orbitals of the CO molecule. Comparison with calculations using a Tersoff-Hamann approach, including s- and p-wave tip states, demonstrates the significant contribution of p-wave tip states.

Human serum albumin (HSA) is the most abundant protein in blood plasma showing a remarkable ability to bind a broad range of hydrophobic substrates. We employed scanning tunneling microscopy and atomic force microscopy to characterize the morphology of HSA aggregates on highly-ordered pyrolytic graphite (HOPG) and single-walled carbon nanotubes (SWNTs). The morphologies found for albumin aggregates on HOPG are quite different from the ones observed on SWNTs. On HOPG, HSA forms aggregates of roughly 10-20 molecules; single protein molecules were observed as well. In the case of SWNTs, nanotubes were partially or totally covered with HSA, exhibiting four general types of aggregation:(i) SWNT sidewalls contain single molecules of albumin which are away from each other at distances longer than the HSA molecular size;(ii) SWNTs are completely covered with HSA, which forms a thin and relatively homogeneous layer;(iii) SWNTs have a complete layer of HSA with additional accumulation of protein at separate sites; and (iv) several SWNTs totally covered with albumin assemble into a bundle-like structure common for bare nanotubes. These observations are interpreted in terms of stronger interactions of HSA with nanotube sidewalls than with flat graphite surface.

The self-assembly of porphyrins into highly organized functional arrays supported on appropriate solid substrates is an area of research with multiple potential applications in the "bottom-up" approach to manufacturing. In order to analyze the self-assembly of meso-tetraphenylporphine (H2TPP) on the surfaces of highly oriented pyrolytic graphite (HOPG) and single-walled carbon nanotubes (SWNTs), we performed molecular mechanics modeling (by MM+ force field) and scanning tunneling microscopy (STM) imaging. Molecular modeling predicted an energetic preference of the H2TPP molecules to adsorb in monolayers on the surfaces of graphite and SWNT sidewall, rather than their stacking or separation. On graphite, the most favorable arrays were predicted to be ribbons composed of interacting parallel chains of H2TPP molecules. On the SWNT sidewall, the energetic preference pointed toward the formation of parallel and interacting long-period helixes, resulting in an almost full coverage of the SWNT surface. These preferable arrays on both carbon materials assure the interaction of every porphyrin unit with as many neighbors as possible, thus lowering the potential energy of the adsorption complexes. STM imaging results are in good agreement with molecular modeling predictions. The formation of self-assembled ribbons was a frequently observed phenomenon on the HOPG surface, while on the SWNT surface a full coverage of the exposed portion of the sidewalls was observed, suggesting the formation of interacting long-period helixes. A preferential adsorption of H2TPP molecules near graphite topographic defects was also observed.

A thiophene-containing molecule attached to a scanning tunneling microscopy (STM) tip is used to transport gold atoms on a Au(111) surface. The molecule contains eight thiophene rings and therefore has sulfur atoms that are known to bind to gold atoms. Using a gold-coated tip, the molecules previously deposited on the surface bind to the lower-coordination gold atoms of the tip. When that tip is used to scan the surface, the still free thiophene rings (not all of the sulfur atoms bind to the tip) can attach to gold atoms from the surface and drag them along the scanning direction, depositing them either at the position where the tip changes its scanning direction or where the tip encounters an "up step", whichever event occurs first.

First-principles calculations show that the rich variety of image patterns found in carbon nanostructures with the atomic force and scanning tunneling microscopes can be rationalized in terms of the chemical reactivity of the tip and the distance range explored in the experiments. For weakly reactive tips, the Pauli repulsion dominates the atomic contrast and force maxima are expected on low electronic density positions as the hollow site. With reactive tips, the interaction is strong enough to change locally the hybridization of the carbon atoms, making it possible to observe atomic resolution in both the attractive and the repulsive regime although with inverted contrast. Regarding STM images, we show that in the near-contact regime, due to current saturation, bright spots correspond to hollow positions instead of atomic sites, providing an explanation for the most common hexagonal pattern found in the experiments.

Methylation of DNA nucleobases is an important control mechanism in biology applied, for example, in the regulation of gene expression. The effect of methylation on the intermolecular interactions between guanine molecules is studied through an interplay between scanning tunneling microscopy (STM) and density functional theory with empirical dispersion correction (DFT-D). The present STM and DFT-D results show that methylation of guanine can have subtle effects on the hydrogen-bond strength with a strong dependence on the position of methylation. It is demonstrated that the methylation of DNA nucleobases is a precise means to tune intermolecular interactions and consequently enables very specific recognition of DNA methylation by enzymes. This scheme is used to generate four different types of artificial 2D nanostructures from methylated guanine. For instance, a 2D guanine windmill motif that is stabilized by cooperative hydrogen bonding is revealed. It forms by self-assembly on a graphite surface under ambient conditions at the liquid-solid interface when the hydrogen-bonding donor at the N1 site of guanine is blocked by a methyl group.

Surface composition plays an important role in carbon nanotube dispersibility in different environments. Indeed, it determines the choice of dispersion medium. In this paper the effect of oxidation on the dispersion of HiPCO single-walled carbon nanotubes (SWNTs) in N-methyl-pyrrolidinone (NMP), N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMA), N-dodecyl-pyrrolidinone (N12P) and cyclohexyl-pyrrolidinone (CHP) was systematically studied. During the oxidation process, similar amounts of carboxylic acid and phenolic groups were introduced to mostly already existing defects. For each solvent the dispersion limits and the absorption coefficients were estimated by optical absorption analysis over a range of SWNT concentrations. The presence of acid oxygenated groups increased SWNT dispersibility in NMP, DMF and DMA, but decreased in N12P and CHP. The absorption coefficients, however, decreased for all solvents after oxidation, reflecting the weakening of the effective transition dipole of the π-π transition with even limited extension functionalization and solvent interaction. The analysis of the results in terms of Hansen and Flory-Huggins solubility parameters evidenced the influence of dipolar interactions and hydrogen bonding on the dispersibility of oxidized SWNTs.