Functionalization of carbon nanotubes with -CHn, -NHn fragments, -COOH and -OH groups

We present results of extensive theoretical studies concerning stability, morphology, and band structure of single wall carbon nanotubes (CNTs) covalently functionalized by -CHn(for n=2,3,4),-NHn(for n=1,2,3,4),-COOH and -OH groups. Our studies are based on ab initio calculations in the framework of the density functional theory. We determine the dependence of the binding energies on the concentration of the adsorbed molecules, critical densities of adsorbed molecules, global and local changes in the morphology, and electronic structure paying particular attention to the functionalization induced changes of the band gaps. These studies reveal physical mechanisms that determine stability and electronic structure of those systems and also provide valuable theoretical predictions relevant for application. Functionalization of CNTs causes generally their elongation and locally sp2 -> sp3 rehybridization in the neighborhood of chemisorbed groups. For adsorbants making particularly strong covalent bonds with the CNTs(-CH2), we observe formation of the 5/7 defects. In CNTs functionalized with -CH2,-NH4, and -OH, we determine critical density of molecules that could be covalently bound to CNTs. Functionalization of CNTs can be utilized for band gap engineering and also lead to changes in their metallic/semiconductor character. In semiconducting CNTs, adsorbants such as -CH3,-NH2,-OH and -COOH, introduce 'impurity' bands in the band gap of pristine CNTs. In the case of -CH3,-NH2, the induced band gaps are typically smaller than in the pure CNT and depend strongly on the concentration of adsorbants. However, functionalization of semiconducting CNTs with -OH leads to the metallization of CNTs. On the other hand, the functionalization of semi-metallic (9,0)CNT with -CH2 causes the increase of the band gap and induces semi-metal to semiconductor transition.Comment: accepted in Journal of Chemical Physic

Dynamic Combinatorial Libraries: From Exploring Molecular Recognition to Systems Chemistry

Dynamic combinatorial chemistry (DCC) is a subset of combinatorial chemistry where the library members interconvert continuously by exchanging building blocks with each other. Dynamic combinatorial libraries (DCLs) are powerful tools for discovering the unexpected and have given rise to many fascinating molecules, ranging from interlocked structures to self-replicators. Furthermore, dynamic combinatorial molecular networks can produce emergent properties at systems level, which provide exciting new opportunities in systems chemistry. In this perspective we will highlight some new methodologies in this field and analyze selected examples of DCLs that are under thermodynamic control, leading to synthetic receptors, catalytic systems, and complex self-assembled supramolecular architectures. Also reviewed are extensions of the principles of DCC to systems that are not at equilibrium and may therefore harbor richer functional behavior. Examples include self-replication and molecular machines.

Calcium Carbonate Suppresses Haem Toxicity Markers without Calcium Phosphate Side Effect on Colon Carcinogenesis

Red meat intake is associated with increased risk of colorectal cancer. We have previously shown that haemin, haemoglobin and red meat promote carcinogen-induced preneoplastic lesions, aberrant crypt foci, in the colon of rats. We have also shown that dietary calcium phosphate inhibits haemin-induced promotion, and normalizes faecal lipoperoxides and cytotoxicity. Unexpectedly, high-calcium phosphate control diet-fed rats had more preneoplastic lesions in the colon than low-calcium control diet-fed rats. The present study was designed to find a calcium supplementation with no adverse effect, by testing several doses and types of calcium salts. One in vitro study and two short-term studies in rats identified calcium carbonate as the most effective calcium salt to bind haem in vitro and to decrease faecal biomarkers previously associated with increased carcinogenesis: faecal water cytotoxicity, thiobarbituric acid reactive substances. A long term carcinogenesis study in dimethylhydrazine-injected rats demonstrated that a diet containing 100 µmol/g calcium carbonate did not promote aberrant crypt foci, in contrast with previously tested calcium phosphate diet. The results suggest that calcium carbonate, and not calcium phosphate, should be used to reduce haem-associated colorectal cancer risk in meat-eaters. They support the concept that the nature of the associated anion to a protective metal ion is important for chemoprevention

Prediction and classification for GPCR sequences based on ligand specific features

Functional identification of G-Protein Coupled Receptors (GPCRs) is one of the current focus areas of pharmaceutical research. Although thousands of GPCR sequences are known, many of them are orphan sequences (the activating ligand is unknown). Therefore, classification methods for automated characterization of orphan GPCRs are imperative. In this study, for predicting Level 1 subfamilies of GPCRs, a novel method for obtaining class specific features, based on the existence of activating ligand specific patterns, has been developed and utilized for a majority voting classification. Exploiting the fact that there is a non-promiscuous relationship between the specific binding of GPCRs into their ligands and their functional classification, our method classifies Level 1 subfamilies of GPCRs with a high predictive accuracy between 99% and 87% in a three-fold cross validation test. The method also tells us which motifs are significant for class determination which has important design implications. The presented machine learning approach, bridges the gulf between the excess amount of GPCR sequence data and their poor functional characterization

Synthetic metallomolecules as agents for the control of DNA structure

This tutorial review summarises B-DNA structure and metallomolecule binding modes and illustrates some DNA structures induced by molecules containing metallic cations. The effects of aquated metal ions, cobalt amines, ruthenium octahedral metal complexes, metallohelicates and platinum complexes such as cis-platin are discussed alongside the techniques of NMR, X-ray crystallography, gel electrophoresis, circular dichroism, linear dichroism and molecular dynamics. The review will be of interest to people interested in both DNA structure and roles of metallomolecules in biological systems

Stable, covalent attachment of laminin to microposts improves the contractility of mouse neonatal cardiomyocytes.

The mechanical output of contracting cardiomyocytes, the muscle cells of the heart, relates to healthy and disease states of the heart. Culturing cardiomyocytes on arrays of elastomeric microposts can enable inexpensive and high-throughput studies of heart disease at the single-cell level. However, cardiomyocytes weakly adhere to these microposts, which limits the possibility of using biomechanical assays of single cardiomyocytes to study heart disease. We hypothesized that a stable covalent attachment of laminin to the surface of microposts improves cardiomyocyte contractility. We cultured cells on polydimethylsiloxane microposts with laminin covalently bonded with the organosilanes 3-glycidoxypropyltrimethoxysilane and 3-aminopropyltriethoxysilane with glutaraldehyde. We measured displacement of microposts induced by the contractility of mouse neonatal cardiomyocytes, which attach better than mature cardiomyocytes to substrates. We observed time-dependent changes in contractile parameters such as micropost deformation, contractility rates, contraction and relaxation speeds, and the times of contractions. These parameters were affected by the density of laminin on microposts and by the stability of laminin binding to micropost surfaces. Organosilane-mediated binding resulted in higher laminin surface density and laminin binding stability. 3-glycidoxypropyltrimethoxysilane provided the highest laminin density but did not provide stable protein binding with time. Higher surface protein binding stability and strength were observed with 3-aminopropyltriethoxysilane with glutaraldehyde. In cultured cardiomyocytes, contractility rate, contraction speeds, and contraction time increased with higher laminin stability. Given these variations in contractile function, we conclude that binding of laminin to microposts via 3-aminopropyltriethoxysilane with glutaraldehyde improves contractility observed by an increase in beating rate and contraction speed as it occurs during the postnatal maturation of cardiomyocytes. This approach is promising for future studies to mimic in vivo tissue environments

Enantioselective Organocatalytic Diels-Alder Trapping of Photochemically Generated Hydroxy-o-Quinodimethanes

The photoenolization/Diels-Alder strategy offers straightforward access to synthetically valuable benzannulated carbocyclic products. This historical light-triggered process has never before succumbed to efforts to develop an enantioselective catalytic approach. Herein, we demonstrate how asymmetric organocatalysis provides simple yet effective catalytic tools to intercept photochemically generated hydroxy-o-quinodimethanes with high stereoselectivity. We used a chiral organic catalyst, derived from natural cinchona alkaloids, to activate maleimides toward highly stereoselective Diels-Alder reactions. An unconventional mechanism of stereocontrol is operative, wherein the organocatalyst is actively involved in both the photochemical pathway, by leveraging the formation of the reactive photoenol, and the stereoselectivity-defining event

From ligands to binding motifs and beyond; the enhanced versatility of nanocrystal surfaces

Surface chemistry bridges the gap between nanocrystal synthesis and their applications. In this respect, the discovery of complex ligand binding motifs on semiconductor quantum dots and metal oxide nanocrystals opens a gateway to new areas of research. The implications are far-reaching, from catalytic model systems to the performance of solar cells

Hydrocarbon molar water solubility predicts NMDA vs. GABAA receptor modulation.

BackgroundMany anesthetics modulate 3-transmembrane (such as NMDA) and 4-transmembrane (such as GABAA) receptors. Clinical and experimental anesthetics exhibiting receptor family specificity often have low water solubility. We hypothesized that the molar water solubility of a hydrocarbon could be used to predict receptor modulation in vitro.MethodsGABAA (α1β2γ2s) or NMDA (NR1/NR2A) receptors were expressed in oocytes and studied using standard two-electrode voltage clamp techniques. Hydrocarbons from 14 different organic functional groups were studied at saturated concentrations, and compounds within each group differed only by the carbon number at the ω-position or within a saturated ring. An effect on GABAA or NMDA receptors was defined as a 10% or greater reversible current change from baseline that was statistically different from zero.ResultsHydrocarbon moieties potentiated GABAA and inhibited NMDA receptor currents with at least some members from each functional group modulating both receptor types. A water solubility cut-off for NMDA receptors occurred at 1.1 mM with a 95% CI = 0.45 to 2.8 mM. NMDA receptor cut-off effects were not well correlated with hydrocarbon chain length or molecular volume. No cut-off was observed for GABAA receptors within the solubility range of hydrocarbons studied.ConclusionsHydrocarbon modulation of NMDA receptor function exhibits a molar water solubility cut-off. Differences between unrelated receptor cut-off values suggest that the number, affinity, or efficacy of protein-hydrocarbon interactions at these sites likely differ