Hydrodynamic fractionation of finite size gold nanoparticle clusters

We demonstrate a high-resolution in situ experimental method for performing simultaneous size classification and characterization of functional gold nanoparticle clusters (GNCs) based on asymmetric-flow field flow fractionation (AFFF). Field emission scanning electron microscopy, atomic force microscopy, multi-angle light scattering (MALS), and in situ ultraviolet-visible optical spectroscopy provide complementary data and imagery confirming the cluster state (e.g., dimer, trimer, tetramer), packing structure, and purity of fractionated populations. An orthogonal analysis of GNC size distributions is obtained using electrospray-differential mobility analysis (ES-DMA). We find a linear correlation between the normalized MALS intensity (measured during AFFF elution) and the corresponding number concentration (measured by ES-DMA), establishing the capacity for AFFF to quantify the absolute number concentration of GNCs. The results and corresponding methodology summarized here provide the proof of concept for general applications involving the formation, isolation, and in situ analysis of both functional and adventitious nanoparticle clusters of finite size.     

Collapse transition of a square-lattice polymer with next nearest-neighbor interaction

We study the collapse transition of a polymer on a square lattice with both nearest-neighbor and next nearest-neighbor interactions, by calculating the exact partition function zeros up to chain length 36. The transition behavior is much more pronounced than that of the model with nearest-neighbor interactions only. The crossover exponent and the transition temperature are estimated from the scaling behavior of the first zeros with increasing chain length. The results suggest that the model is of the same universality class as the usual θ point described by the model with only nearest-neighbor interaction.     

The lipoproteins of cyanobacterial photosystem II

Photosystem II (PSII) complexes from cyanobacteria and plants perform water splitting and plastoquinone reduction and yet have a different complement of lumenal extrinsic proteins. Whereas PSII from all organisms has the PsbO extrinsic protein, crystal structures of PSII from cyanobacteria have PsbV and PsbU while green algae and higher plants instead contain the extrinsic PsbP and PsbQ subunits. Proteomic studies in Synechocystis sp. PCC 6803 identified three further extrinsic proteins in the thylakoid lumen that are associated with cyanobacterial PSII and these are predicted to attach to the thylakoid membrane via a lipidated N-terminus. These proteins are cyanobacterial homologues to the PsbP and PsbQ subunits as well as to Psb27, an additional extrinsic protein associated with "inactive" photosystems that lack the other extrinsic polypeptides. The PsbQ homologue is not present in Prochlorococcus species but otherwise these proteins have been identified in most cyanobacteria although our phylogenetic analyses identified some strains that lack an apparent motif for lipidation in one or other of these subunits. Over the past decade the physiological function of these additional lipoproteins has been investigated in several cyanobacterial strains and recently the structures for each have been solved. This review will evaluate the physiological and structural results obtained for these lipid-attached extrinsic proteins and in silico protein docking of these proteins to PSII centers will be presented.     

Early development drug formulation on a chip: fabrication of nanoparticles using a microfluidic spray dryer

Early development drug formulation is exacerbated by increasingly poor bioavailability of potential candidates. Prevention of attrition due to formulation problems necessitates physicochemical analysis and formulation studies at a very early stage during development, where the availability of a new substance is limited to small quantities, thus impeding extensive experiments. Miniaturization of common formulation processes is a strategy to overcome those limitations. We present a versatile technique for fabricating drug nanoformulations using a microfluidic spray dryer. Nanoparticles are formed by evaporative precipitation of the drug-loaded spray in air at room temperature. Using danazol as a model drug, amorphous nanoparticles of 20-60 nm in diameter are prepared with a narrow size distribution. We design the device with a geometry that allows the injection of two separate solvent streams, thus enabling co-spray drying of two substances for the production of drug co-precipitates with tailor-made composition for optimization of therapeutic efficiency.     

Mixed phosphine and group-13 metal ligator complexes [(PR3)(a)M(ECp*)b] (M = Mo, Ni; E = Ga, Al; R = C6H5, cyclo-C6H11, CH3)

Treatment of [Mo(N(2))(PMe(3))(5)] with two equivalents GaCp* (Cp* = η(5)-C(5)(CH(3))(5)) leads to the formation of cis-[Mo(GaCp*)(2)(PMe(3))(4)] (1), while AlCp* did not react with this precursor. In addition, [Ni(GaCp*)(2)(PPh(3))(2)] (2a), [Ni(AlCp*)(2)(PPh(3))(2)] (2b), [Ni(GaCp*)(2)(PCy(3))(2)] (3a), [Ni(GaCp*)(2)(PMe(3))(2)] (3b), [Ni(GaCp*)(3)(PCy(3))] (4) and [Ni(GaCp*)(PMe(3))(3)] (5) have been prepared in high yields by a direct synthesis from [Ni(COD)(2)] and stoichiometric amounts of the ligands PR(3) and ECp* (E = Al, Ga), respectively. All compounds have been fully characterized by (1)H, (13)C, and (31)P NMR spectroscopy, elemental analysis and single crystal X-ray diffraction studies.     

Scaffold diversity of exemplified medicinal chemistry space

The scaffold diversity of 7 representative commercial and proprietary compound libraries is explored for the first time using both Murcko frameworks and Scaffold Trees. We show that Level 1 of the Scaffold Tree is useful for the characterization of scaffold diversity in compound libraries and offers advantages over the use of Murcko frameworks. This analysis also demonstrates that the majority of compounds in the libraries we analyzed contain only a small number of well represented scaffolds and that a high percentage of singleton scaffolds represent the remaining compounds. We use Tree Maps to clearly visualize the scaffold space of representative compound libraries, for example, to display highly populated scaffolds and clusters of structurally similar scaffolds. This study further highlights the need for diversification of compound libraries used in hit discovery by focusing library enrichment on the synthesis of compounds with novel or underrepresented scaffolds.     

Recent progress in biopolymer nanoparticle and microparticle formation by heat-treating electrostatic protein-polysaccharide complexes

Functional biopolymer nanoparticles or microparticles can be formed by heat treatment of globular protein-ionic polysaccharide electrostatic complexes under appropriate solution conditions. These biopolymer particles can be used as encapsulation and delivery systems, fat mimetics, lightening agents, or texture modifiers. This review highlights recent progress in the design and fabrication of biopolymer particles based on heating globular protein-ionic polysaccharide complexes above the thermal denaturation temperature of the proteins. The influence of biopolymer type, protein-polysaccharide ratio, pH, ionic strength, and thermal history on the characteristics of the biopolymer particles formed is reviewed. Our current understanding of the underlying physicochemical mechanisms of particle formation and properties is given. The information provided in this review should facilitate the rational design of biopolymer particles with specific physicochemical and functional attributes, as well as stimulate further research in identifying the physicochemical origin of particle formation.     

Radical conversion and migration in electron capture dissociation

Electron capture dissociation (ECD) is an important analytical technique which is used frequently in proteomics experiments to reveal information about both primary sequence and post-translational modifications. Although the utility of ECD is unquestioned, the underlying chemistry which leads to the observed fragmentation is still under debate. Backbone dissociation is frequently the exclusive focus when mechanistic questions about ECD are posed, despite the fact that numerous other abundant dissociation channels exist. Herein, the focus is shifted to side chain loss and other dissociation channels which offer clues about the underlying mechanism(s). It is found that the initially formed hydrogen abundant radicals in ECD can convert quickly to hydrogen deficient radicals via a variety of pathways. Dissociation which occurs subsequent to this conversion is mediated by hydrogen deficient radical chemistry, which has been the subject of extensive study in experiments which are independent from ECD. Statistical analysis of fragments observed in ECD is in excellent agreement with predictions made by an understanding of hydrogen deficient radical chemistry. Furthermore, hydrogen deficient radical mediated dissociation likely contributes to observed ECD fragmentation patterns in unexpected ways, such as the selective dissociation observed at disulfide bonds. Many aspects of dissociation observed in ECD are easily reproduced in well-controlled experiments examining hydrogen deficient radicals generated by non-ECD methods. All of these observations indicate that when considering the means by which electron capture leads to dissociation, hydrogen deficient radical chemistry must be given careful consideration.     

2,2']paracyclophane-based π-conjugated molecular wires reveal molecular-junction behavior

The electronic coupling as well as the attenuation factor (β), which depends primarily on the nature of the molecular bridge and is used as a benchmark to test the molecular wire behavior, have been determined in a systematic study carried out on a series of ZnP/C(60) conjugates connected through a [2,2']paracyclophane-oligophenylenevinylene (pCp-oPPV). The convergent synthesis involves a series of Horner-Emmons olefination reactions or double palladium-catalized Heck-type reactions. ZnP-pCp-C(60) conjugates were finally obtained by the 1,3-dipolar cycloaddition reaction of the in situ-generated azomethyne ylide containing the ZnP-pCp moiety to the [60]fullerene using Prato conditions. Experimental (UV-vis, fluorescence, transient absorption spectroscopy, and solution electrochemistry) and theoretical studies revealed that the pCps act as molecular junctions. If hole transfer is assumed to be the dominant charge transfer (CT) mechanism, CT is facilitated in one direction (from C(60) to ZnP via pCp) but disfavored in the other direction (from ZnP to C(60) via pCp).     

Coupling asymmetric flow-field flow fractionation and fluorescence parallel factor analysis reveals stratification of dissolved organic matter in a drinking water reservoir

Using asymmetrical flow field-flow fractionation (AF4) and fluorescence parallel factor analysis (PARAFAC), we showed physicochemical properties of chromophoric dissolved organic matter (CDOM) in the Beaver Lake Reservoir (Lowell, AR) were stratified by depth. Sampling was performed at a drinking water intake structure from May to July 2010 at three depths (3-, 10-, and 18-m) below the water surface. AF4-fractograms showed that the CDOM had diffusion coefficient peak maximums between 3.5 and 2.8 × 10⁻⁶ cm² s⁻¹, which corresponded to a molecular weight range of 680–1950 Da and a size of 1.6–2.5 nm. Fluorescence excitation–emission matrices of whole water samples and AF4-generated fractions were decomposed with a PARAFAC model into five principal components. For the whole water samples, the average total maximum fluorescence was highest for the 10-m depth samples and lowest (about 40% less) for 18-m depth samples. While humic-like fluorophores comprised the majority of the total fluorescence at each depth, a protein-like fluorophore was in the least abundance at the 10-m depth, indicating stratification of both total fluorescence and the type of fluorophores. The results present a powerful approach to investigate CDOM properties and can be extended to investigate CDOM reactivity, with particular applications in areas such as disinfection byproduct formation and control and evaluating changes in drinking water source quality driven by climate change.