Spherical Nucleic Acid Nanoparticle Conjugates Enhance G‐Quadruplex Formation and Increase Serum Protein Interactions

To understand the effect of three‐dimensional oligonucleotide structure on protein corona formation, we studied the identity and quantity of human serum proteins that bind to spherical nucleic acid (SNA) nanoparticle conjugates. SNAs exhibit cellular uptake properties that are remarkably different from those of linear nucleic acids, which have been related to their interaction with certain classes of proteins. Through a proteomic analysis, this work shows that the protein binding properties of SNAs are sequence‐specific and supports the conclusion that the oligonucleotide tertiary structure can significantly alter the chemical composition of the SNA protein corona. This knowledge will impact our understanding of how nucleic acid‐based nanostructures, and SNAs in particular, function in complex biological milieu.     

Inverse Scattering Transform and Solitons for Square Matrix Nonlinear Schrödinger Equations with Mixed Sign Reductions and Nonzero Boundary Conditions

The inverse scattering transform (IST) with nonzero boundary conditions at infinity is developed for a class of 2 × 2 matrix nonlinear Schrödinger-type systems whose reductions include two equations that model certain hyperfine spin F = 1 spinor Bose-Einstein condensates, and two novel equations that were recently shown to be integrable, and that have applications in nonlinear optics and four-component fermionic condensates. In our formulation, both the direct and the inverse problems are posed in terms of a suitable uniformization variable which allows us to develop the IST on the standard complex plane instead of a two-sheeted Riemann surface or the cut plane with discontinuities along the cuts. Analyticity, symmetries and asymptotics of the scattering eigenfunctions and scattering data are derived, and properties of the discrete spectrum are analyzed in detail. In addition, the general behavior of the soliton solutions for all four reductions is discussed, and some novel soliton solutions are presented.     

Towards Discovery and Targeted Peptide Biomarker Detection Using nanoESI-TIMS-TOF MS

In the present work, the potential of trapped ion mobility spectrometry coupled to TOF mass spectrometry (TIMS-TOF MS) for discovery and targeted monitoring of peptide biomarkers from human-in-mouse xenograft tumor tissue was evaluated. In particular, a TIMS-MS workflow was developed for the detection and quantification of peptide biomarkers using internal heavy analogs, taking advantage of the high mobility resolution (R = 150–250) prior to mass analysis. Five peptide biomarkers were separated, identified, and quantified using offline nanoESI-TIMS-CID-TOF MS; the results were in good agreement with measurements using a traditional LC-ESI-MS/MS proteomics workflow. The TIMS-TOF MS analysis permitted peptide biomarker detection based on accurate mobility, mass measurements, and high sequence coverage for concentrations in the 10–200 nM range, while simultaneously achieving discovery measurements of not initially targeted peptides as markers from the same proteins and, eventually, other proteins.

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Anion–π Catalysis of Enolate Chemistry: Rigidified Leonard Turns as a General Motif to Run Reactions on Aromatic Surfaces

To integrate anion–π, cation–π, and ion pair–π interactions in catalysis, the fundamental challenge is to run reactions reliably on aromatic surfaces. Addressing a specific question concerning enolate addition to nitroolefins, this study elaborates on Leonard turns to tackle this problem in a general manner. Increasingly refined turns are constructed to position malonate half thioesters as close as possible on π‐acidic surfaces. The resulting preorganization of reactive intermediates is shown to support the disfavored addition to enolate acceptors to an absolutely unexpected extent. This decisive impact on anion–π catalysis increases with the rigidity of the turns. The new, rigidified Leonard turns are most effective with weak anion–π interactions, whereas stronger interactions do not require such ideal substrate positioning to operate well. The stunning simplicity of the motif and its surprisingly strong relevance for function should render the introduced approach generally useful.     

Novel microwave synthesis of half‐sandwich [(η6‐C6H6)Ru] complexes and an evaluation of the biological activity and biochemical reactivity

We have used a novel microwave‐assisted method to synthesize a pair of half‐sandwich ruthenium–arene–thiosemicarbazone complexes of the type [(η⁶‐C₆H₆Ru(TSC)Cl]PF₆. The thiosemicarbazone (TSC) ligands are 2‐(anthracen‐9‐ylmethylene)hydrazinecarbothioamide and 2‐(anthracen‐9‐ylmethylene)‐N‐ethylhydrazinecarbothioamide derived from 9‐anthraldehyde. The complexes are moderately strong binders of DNA, with binding constants of 10⁴ m ^?1. They are also strong binders of human serum albumin, having binding constants of the order of 10⁵ m ^?1. The complexes show some in vitro anticancer activity against human colon cancer cells, Caco‐2 and HCT‐116, with positive therapeutic indices. They did not show any activity as antibacterial agents against the organisms that were studied. Copyright © 2013 John Wiley & Sons, Ltd.     

Antiviral and Antibacterial Polyurethanes of Various Modalities

We have prepared and characterized a new polyurethane-based antimicrobial material, N,N-dodecyl,methyl-polyurethane (Quat-12-PU). It exhibits strong antiviral and antibacterial activities when coated (as an organic solution or an aqueous nanosuspension) onto surfaces and antibacterial activity when electrospun into nanofibers. Quat-12-PU surfaces are able to kill airborne Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli bacteria, as well as inactivate the enveloped influenza virus (but not the non-enveloped poliovirus).     

Synthesis and characterization of mixed-ligand diimine-piperonal thiosemicarbazone complexes of ruthenium(II): Biophysical investigations and biological evaluation as anticancer and antibacterial agents

We have used a novel microwave-assisted method developed in our laboratories to synthesize a series of ruthenium-thiosemicarbazone complexes. The new thiosemicarbazone ligands are derived from benzo[d][1,3]dioxole-5-carbaldehyde (piperonal) and the complexes are formulated as [(diimine)(2)Ru(TSC)](PF(6))(2) (where the TSC is the bidentate thiosemicarbazone ligand). The diimine in the complexes is either 2,2'-bipyridine or 1,10-phenanthroline. The complexes have been characterized by spectroscopic means (NMR, IR and UV-Vis) as well as by elemental analysis. We have studied the biophysical characteristics of the complexes by investigating their anti-oxidant ability as well as their ability to disrupt the function of the human topoisomerase II enzyme. The complexes are moderately strong binders of DNA with binding constants of 10(4) M(-1). They are also strong binders of human serum albumin having binding constants on the order of 10(4) M(-1). The complexes show good in vitro anticancer activity against human colon cancer cells, Caco-2 and HCT-116 and indeed show some cytotoxic selectivity for cancer cells. The IC(50) values range from 7 - 159 μM (after 72 h drug incubation). They also have antibacterial activity against Gram-positive strains of pathogenic bacteria with IC(50) values as low as 10 μM; little activity was seen against Gram-negative strains. It has been established that all the compounds are catalytic inhibitors of human topoisomerase II.     

The Role of Lewis Acid Sites in γ-Al2O3 Oligomerization

Olefin oligomerization by γ-Al₂O₃ has recently been reported, and it was suggested that Lewis acid sites are catalytic. The goal of this study is to determine the number of active sites per gram of alumina to confirm that Lewis acid sites are indeed catalytic. Addition of an inorganic Sr oxide base resulted in a linear decrease in the propylene oligomerization conversion at loadings up to 0.3 wt %; while, there is a >95 % loss in conversion above 1 wt % Sr. Additionally, there was a linear decrease in the intensity of the Lewis acid peaks of absorbed pyridine in the IR spectra with an increase in Sr loading, which correlates with the loss in propylene conversion, suggesting that Lewis acid sites are catalytic. Characterization of the Sr structure by XAS and STEM indicates that single Sr²⁺ ions are bound to the γ-Al₂O₃ surface and poison one catalytic site per Sr ion. The maximum loading needed to poison all catalytic sites, assuming uniform surface coverage, was ∼0.4 wt % Sr, giving an acid site density of ∼0.2 sites per nm² of γ-Al₂O₃, or approximately 3 % of the alumina surface.