A subsystem density-functional theory approach for the quantum chemical treatment of proteins

We present an extension of the frozen-density embedding (FDE) scheme within density-functional theory [T. A. Wesolowski and A. Warshel, J. Phys. Chem. 97, 8050 (1993)] that can be applied to subsystems connected by covalent bonds, as well as a practical implementation of such an extended FDE scheme. We show how the proposed scheme can be employed for quantum chemical calculations of proteins by treating each constituting amino acid as a separate subsystem. To assess the accuracy of the extended FDE scheme, we present calculations for several dipeptides and for the protein ubiquitin.     

Cell-SELEX-based aptamer-conjugated nanomaterials for enhanced targeting of cancer cells

Early detection and treatment of cancer depends on developing highly sensitive and specific methods for targeting cancer cells. To do this, aptamers, which are generated by a novel technique called cell-SELEX (systematic evolution of ligands by exponential enrichment), have been widely applied in cancer cell targeting based on such merits as high target affinity and specificity, small size, minimal immunogenicity, and ease of chemical modification. Furthermore, aptamers can gain more flexibility as cancer c...     

Cell-based screening: a high throughput flow cytometry platform for identification of cell-specific targeting molecules

Targeting of drugs and genes to specific cell types is an emerging paradigm in the treatment of many medical conditions. However, targeting structures such as peptides are susceptible to rapid inactivation in vivo. To address this problem, novel targeting molecules can now be rapidly synthesized using a combinatorial approach. Methods to screen the large libraries created in this process are often lacking or compatible only with solution-based screening. This report describes a high-throughput cell-based method utilizing flow cytometry, capable of rapidly screening large libraries of molecules simultaneously for biological functionality and stability. In this method, each library molecule is attached to a microsphere exhibiting a unique set of optical properties, or "fingerprint", conferring modularity and multiplex capability. We investigated the multiplex capability of our flow cytometric method to determine its capacity for high-throughput screening. Current instrumentation in our laboratory allows the screening of at least 75 unique compounds in a single well, a number comparable to available solution-based assays. In state-of-the-art configuration, however, this methodology can support the screening of up to 1875 compounds per well, achieving high-throughput potential in a single multiwell plate. We also investigated the binding capability of targeted microspheres to adherent target cells. These microspheres exhibited a 12-fold increase in binding over control, untargeted microspheres. Competitive inhibition experiments with soluble ligand confirmed the specificity of microsphere binding. Overall, the methodology proposed here is capable of quickly and effectively screening large libraries of targeting molecules using instrumentation readily available to the greater research community.     

Sensitive detection of Penicillin-G chemical using SnO2.YbO nanomaterials by electrochemical approach

In this approach, binary tin oxide doped ytterbium oxide nanosheets (SnO₂.YbO NSs) were synthesized in an alkaline phase using under low-temperature facile hydrothermal technique. Traditional methods such as UV–Visible spectroscopy, Fourier Transform Infra-Red Spectroscopy (FTIR), Powder X-ray diffraction (XRD), Field Emission Scanning Microscopy (FESEM) equipped with X-ray electron dispersive spectroscopy (XEDS), and X-ray photoelectron spectroscopy (XPS) were used to fully characterize the prepared SnO₂.YbO NSs. Fabrication of a thin-coating with doped NSs onto GCE by using 5% nafion conducting binder resulted in development of a selective and enzyme-free penicillin-G sensor probe. A reliable I-V technique was used to perform electrochemical performances of good sensitivity, large LDR, and long-term stability of the desired Penicillin-G sensor (SnO₂.YbO NSs/GCE/Nf). With a wide range of Penicillin-G concentration, the proposed calibration plot is noticed good linearity (R² = 0.9830). Sensitivity and LOD of the sensor were calculated as 24.75 μAμM^-1cm^?2 and 30.0 pM, respectively based on S/N = 3 formula. Real samples (Human and rabbit serum, milk, and red-sea water) were analyzed with the fabricated SnO₂.YbO NSs/GCE/Nf sensor probe and the findings results were acceptable and satisfactory. This approach could be a noble development of in-situ Penicillin-G sensor based on binary SnO₂.YbO NSs/GCE/Nf by reliable I-V technique for important sensing applications including beneficial doped nanomaterials and nano-technological system.     

A gold nanoparticle based approach for screening triplex DNA binders

Nanoparticle assemblies interconnected with DNA triple helixes can be used to colorimetrically screen for triplex DNA binding molecules and simultaneously determine their relative binding affinities based on melting temperatures. Nanoparticles assemble only when DNA triple helixes form between DNA from two different particles and a third strand of free DNA. In addition, the triple helix structure is unstable at room temperature and only forms in the presence of triplex DNA binding molecules which stabilize the triple helix. The resulting melting transition of the nanoparticle assembly is much sharper and at a significantly higher Tm than the analogous triplex structure without nanoparticles. Upon nanoparticle assembly, a concomitant red-to-blue color change occurs. The assembly process and color change do not occur in the presence of duplex DNA binders and therefore provide a significantly better screening process for triplex DNA binding molecules compared to standard methods.     

A review of the chemical manipulation of nanomaterials using solvents: Gelation dependent structures

The hydrolysis of Mg, Zr, and Ti alkoxides by water in solvent-alcohol mixtures has been examined in the absence of added acid or base catalysts, and herein, these data are reviewed. The presence of low dielectric constant solvents (benzene, toluene, or anisole), in varying ratios with methanol (or other alcohols), caused much more rapid gelation, subsequently yielding mesoporous materials with higher surface areas and larger pore volumes as fibrous, open web-like structures. The presence of high dielectric constant (polar aprotic) solvents such as acetone, acetonitrile, DMF, DMSO, or dimethyaniline was not effective in this way. A partial charge model was employed to explain why the low dielectric solvents forced more rapid hydrolysis, and it is concluded that the hydrolysis step is rate determining, approaching diffusion control, in this gelation process. The use of these “spectator solvents” helps simplify and enhance sol-gel and xerogel/aerogel synthesis schemes, and yields higher quality materials.     

A simple approach for fabricating solid-contact ion-selective electrodes using nanomaterials as transducers

A simple and robust approach for the development of solid-state ion-selective electrodes (ISEs) using nanomaterials as solid contacts is described. The electrodes are fabricated by using the mixture of an ionic liquid (IL) and a nanomaterial as intermediate layer, formed by melting the IL. Tetradodecylammonium tetrakis(4-chlorophenyl)borate (ETH 500) is chosen as an model of IL to provide strong adhesion between the inner glassy carbon electrode and the intermediate layer. Nanomaterials including single-walled carbon nanotubes (SWCNTs) and graphene were used as active ion-to-electron transducers between the glassy carbon electrode and the ionophore-doped ISE membrane. By using the proposed approach, the solid-contact Cu²⁺- and Pb²⁺-selective electrodes based on ETH 500/SWCNTs and ETH 500/graphene as transducers, respectively, have been fabricated. The proposed electrodes show detection limits in the nanomolar range and exhibit a good response time and excellent stability.     

Synthesis and functional evaluation of DNA-assembled polyamidoamine dendrimer clusters for cancer cell-specific targeting

We sought to produce dendrimers conjugated to different biofunctional moieties (fluorescein [FITC] and folic acid [FA]), and then link them together using complementary DNA oligonucleotides to produce clustered molecules that target cancer cells that overexpress the high-affinity folate receptor. Amine-terminated, generation 5 polyamidoamine (G5 PAMAM) dendrimers are first partially acetylated and then conjugated with FITC or FA, followed by the covalent attachment of complementary, 5'-phosphate-modified 34-base-long oligonucleotides. Hybridization of these oligonucleotide conjugates led to the self-assembly of the FITC- and FA-conjugated dendrimers. In vitro studies of the DNA-linked dendrimer clusters indicated specific binding to KB cells expressing the folate receptor. Confocal microscopy also showed the internalization of the dendrimer cluster. These results demonstrate the ability to design and produce supramolecular arrays of dendrimers using oligonucleotide bridges. This will also allow for further development of DNA-linked dendrimer clusters as imaging agents and therapeutics.     

A conventional an 2DCOS infrared approach to the kinetics of protein misfolding

Cell viability depends on the correct folding of the proteins involved in metabolism. Proteins are synthesized on the endoplasmic reticulum and must follow a pathway to a correct, metastable, tridimensional structure. Changes in structure or in environmental conditions can drive an instability of the folding conditions and produce non-active aggregates that in principle are proteolysed by the cellular mechanisms. However, these aggregates can be even more stable than the native proteins, escaping the cellular control. They can be classified as amorphous, if there is not a well-organized structural pattern, or ordered if a repetitive pattern is produced. These ordered structures, known as fibrils, are involved in many diseases. Infrared spectroscopy is a method of choice to study its formation because it is not affected by turbidity or the formation of high molecular weight aggregates. Moreover, in both cases, two bands characteristic of intermolecular β-sheets allow the monitoring of the aggregate formation. In both cases, the appearance of these bands involves a non-reversible path in protein folding. It has been suggested that a difference in the ordered structures involves an increasing in band intensity. This change can be the origin in variations on the 2DCOS maps. The synchronous map gives an overall idea of the process involved. The asynchronous is more informative because reflects the kinetic changes produced. The outcome of both processes, amorphous or ordered is that 2DCOS can provide a further insight to the knowledge of the kinetic processes giving rise to aggregated structures. This outcome could consist on the order in which the different secondary structures are prone to form the aggregates.     

Preferential hydration of proteins: A Kirkwood-Buff approach

The presence of cosolvents affects the stability of proteins in aqueous solutions. Some (such as trehalose and polyethelene glycol) enhances the stability of proteins, whereas others (such as urea) denatures the proteins. We explain different actions of cosolvents based upon the recent theoretical developments in the application of Kirkwood-Buff theory.     

A novel approach of preparation and patterning of organic fluorescent nanomaterials

Different fluorescent organic nanoparticles (FONs) from microemulsion were prepared with semi-continuous emulsion copolymerization of methyl methacrylate (MMA) and a polymerizable anionic surfactant. The diameters of particles ranged from 40 to 80 nm. The reactive surfactants were copolymerized with the main monomer. So the desorption of the surfactant from the polymer particles or the migration within the polymer film was impeded and avoided negative influences on the optoelectronic properties of the material. The microemulsion containing FONs was used in an ink-printing process to form different patterns. The photoluminescence properties of the films were investigated. It was expected that the approach of micro-droplet ink-jet printing of FONs would have bright future because no complicated preparation processes were required.     

An efficient first-principle approach for electronic structures calculations of nanomaterials

An efficient parallel implementation has been realized for a recently proposed central insertion scheme (Jiang, Liu, Lu, Luo. J Chem Phys 2006, 124, 214711; J Chem Phys 2006, 125, 149902) that allows to calculate electronic structures of nanomaterials at various density functional theory levels. It has adopted the sparse-matrix format for Fock/Kohn-Sham and overlap matrices, as well as a combination of implicitly restarted Arnoldi methods (IRAM) and spectral transformation for computing selected eigenvalues/eigenvectors. A systematic error analysis and control for the proposed method has been provided based on a strict mathematical basis. The efficiency and applicability of the new implementation have been demonstrated by calculations of electronic structures of two different nanomaterials consisting of one hundred thousand electrons.     

CrAsH-quantum dot nanohybrids for smart targeting of proteins

Smart nanohybrids were prepared by conjugation of CrAsH to hydrosoluble and biocompatible quantum dots (QDs). The resulting probes were shown to bind efficiently and selectively to Cys-tagged proteins. The interaction with the protein was detected by an increase of the fluorescence emission of CrAsH. While the latter faded rapidly under continuous excitation, emission of the QD remained unaffected. The persistent fluorescence of the QD should thus allow extended monitoring of the target protein.     

Minor groove binders and drugs targeting proteins cover complementary regions in chemical shape space

DNA minor groove binders (MGBs) are known to influence gene expression and are therefore widely studied to explore their therapeutic potential. We identified shape-based virtual screening with ROCS as a highly effective computational approach to enrich known MGBs in top-ranked molecules. Discovery of ten previously unknown MGBs by shape-based screening further confirmed the relevance of ligand shape for minor groove affinity. Based on experimental testing we propose three simple rules (at least two positive charges, four nitrogen atoms, and one aromatic ring) as filters to reach even better enrichment of true positives in ROCS hit lists. Interestingly, shape-based ranking of MGBs versus FDA-approved drugs again leads to high enrichment rates, indicating complementary coverage of chemical shape space and indicating minor groove affinity to be unfavorable for approval of drugs targeting proteins.     

Use of nanomaterials for impedimetric DNA sensors: A review

This review presents the state of the art of DNA sensors (or genosensors) that utilize electrochemical impedance spectroscopy as the transduction technique. As issue of current interest, it is centered on the use of nanomaterials to develop or to improve performance of these specific biosensors. It will describe the different principles that may be employed in the measuring step and the different formats adopted for detection of a DNA sequence or confirmation or amplification of the finally obtained signal. The use of nanomaterials for the above listed aspects, viz. the use of carbon nanotubes or other nanoscopic elements in the construction of the electrodes, or the use of nanoparticles, mainly gold or quantum dots, for signal enhancement will be fully revised.     

Biological entities as chemical reactors for synthesis of nanomaterials: Progress,challenges and future perspective

Synthesis of nanomaterials is being gained extensive attention in the fields of chemistry, applied physics, catalysis, drug delivery and the most important in diagnosis and therapeutic applications. Recently, many reports have been published on physical and chemical synthesis of magnetic as well as metallic nanoparticles (NPs) with viable surface functionalization, but still there is a dire need of such strategies that can combine synthetic methodology with stable surface modification found in nature. Synthesis of NPs via biological methods is the possible way to solve these barriers. However, systematized summary and outlooks of NPs synthesis via biological entities with various influencing factors e.g. temperature, pH, concentration of reactants and reaction time has rarely been reported. This review will present the distinct advantages of biological synthesis of NPs over physical and chemical methods. It will also highlight the recent progress on synthesis of NPs via various biological systems i.e. plant, fungus, bacteria, and yeast. Furthermore, it will explain various factors that control the size, shape, and morphology of these NPs. Finally, it would present the future perspectives of green chemistry for the development of nano-science and -biotechnology.     

Layered hydrazinium titanate: advanced reductive adsorbent and chemical toolkit for design of titanium dioxide nanomaterials

LHT-9, a layered hydrazinium titanate with an interlayer spacing of ~9 ?, is a new nanohybrid compound combining the redox functionality of hydrazine, the ion-exchange properties of layered titanate, the large surface area of quasi-two-dimensional crystallites, surface Br?nsted acidity, and the occurrence of surface titanyl bonds. LHT-9, ideally formulated as (N(2)H(5))(1/2)Ti(1.87)O(4), relates to a family of lepidocrocite-type titanates. It possesses a high uptake capacity of ~50 elements of the periodic table. Irreversibility of reductive adsorption allows LHT-9 to be used for cumulative extraction of reducible moieties (noble metals, chromate, mercury, etc.) from industrial solutions and wastewaters. Unlike sodium titanates that do not tolerate an acidic environment, LHT-9 is capable of uptake of transition metals and lanthanides at pH > 3. Adsorption products loaded with the desired elements retain their layered structures and can be used as precursors for tailored titanium dioxide nanomaterials. In this respect, the uptake of metal ions by LHT-9 can be considered as a method complementary to electrostatic self-assembly deposition (ESD) and layer-by-layer self-assembly (LBL) techniques. LHT-9 is readily synthesized in one step by a mild fluoride route involving hydrazine-induced hydrolysis of hexafluorotitanic acid under near-ambient conditions.