A new ultrafast and high-throughput mass spectrometric approach for the therapeutic drug monitoring of the multi-targeted anti-folate pemetrexed in plasma from lung cancer patients

An analytical assay has been developed and validated for ultrafast and high-throughput mass spectrometric determination of pemetrexed concentrations in plasma using matrix assisted laser desorption/ionization–triple quadrupole–tandem mass spectrometry. Patient plasma samples spiked with the internal standard methotrexate were measured by multiple reaction monitoring. The detection limit was 0.4 fmol/μL, lower limit of quantification was 0.9 fmol/μL, and upper limit of quantification was 60 fmol/μL, respectively. Overall observed pemetrexed concentrations in patient samples ranged between 8.7 (1.4) and 142.7 (20.3)?pmol/μL (SD). The newly developed mass spectrometric assay is applicable for (routine) therapeutic drug monitoring of pemetrexed concentrations in plasma from non-small cell lung cancer patients.     

Resolving the Heat Generated from ZrO2 Atomic Layer Deposition Surface Reactions

In situ pyroelectric calorimetry and spectroscopic ellipsometry were used to investigate surface reactions in atomic layer deposition (ALD) of zirconium oxide (ZrO₂). Calibrated and time-resolved in situ ALD calorimetry provides new insights into the thermodynamics and kinetics of saturating surface reactions for tetrakis(dimethylamino)zirconium(IV) (TDMAZr) and water. The net ALD reaction heat ranged from 0.197 mJ cm⁻² at 76 °C to 0.155 mJ cm⁻² at 158 °C, corresponding to an average of 4.0 eV/Zr at all temperatures. A temperature dependence for reaction kinetics was not resolved over the range investigated. The temperature dependence of net reaction heat and distribution among metalorganic and oxygen source exposure is attributed to factors including growth rate, equilibrium surface hydroxylation, and the extent of the reaction. ZrO₂-forming surface reactions were investigated computationally using DFT methods to better understand the influence of surface hydration on reaction thermodynamics.     

Synthesis and characterization of divalent metal complexes with bipyridylamide ligands

Reaction of N-(4-pyridyl)picolinamide (4-ppa), N-(4-pyridyl)nicotinamide (4-pna), N-(4-pyridyl)isonicotinamide (4-pina), and N-(2-pyridyl)isonicotinamide (2-pina) with divalent metal salts led to the formation of six new coordination complexes. The X-ray structure of [Zn(4-ppa)₂Cl₂] (1) shows a mononuclear structure with interesting intermolecular hydrogen bonding interactions. [Zn(4-pna)(OAc)₂]_n (2), Cu(4-pna)(OTf)₂(DMF)₂]_n (3), {[Zn(4-pina)(DMF)₄](OTf)₂}_n (4), {[Fe(4-pina)(DMF)₄](OTf)₂}_n (5), and [Cu(2-pina)(OTf)₂(DMF)₂]_n (6) are one-dimensional coordination polymers with conformational differences caused by the coordination donor disposition, which demonstrates the flexibility of the pyridylamide ligands in polymeric structures. Reflectance UV-visible spectra and thermal properties of the coordination polymers are also reported.     

Triiodide‐Mediated δ‐Amination of Secondary C−H Bonds

The C_δ?H amination of unactivated, secondary C?H bonds to form a broad range of functionalized pyrrolidines has been developed by a triiodide (I₃^?)‐mediated strategy. By in situ 1) oxidation of sodium iodide and 2) sequestration of the transiently generated iodine (I₂) as I₃^?, this approach precludes undesired I₂‐mediated decomposition which can otherwise limit synthetic utility to only weak C(sp³)?H bonds. The mechanism of this triiodide‐mediated cyclization of unbiased, secondary C(sp³)?H bonds, by either thermal or photolytic initiation, is supported by NMR and UV/Vis data, as well as intercepted intermediates.     

PNA-DNA duplexes, triplexes, and quadruplexes are stabilized with trans-cyclopentane units

Peptide nucleic acids (PNAs) are non-natural nucleic acid mimics that bind to complementary DNA and RNA with high affinity and selectivity. PNA can bind to nucleic acids in a number of different ways. Currently, the formation of PNA-oligonucleotide duplex, triplex, and quadruplex structures have been reported. PNAs have been used in numerous biomedicial applications, but there are few strategies to predictably improve the binding properties of PNAs by backbone modification. We have been studying the benefits of incorporating (S,S)-trans-cyclopentane diamine units (tcyp) into the PNA backbone. In this Communication, we report the improvement in stability associated with tcyp incorporation into PNA-DNA duplexes, triplexes, and quadruplexes. The broad utility of this modification across multiple types of PNA structures is unique and should prove useful in the development of applications that rely on PNA.     

Cellular responses to patterned poly(acrylic acid) brushes

We use patterned poly(acrylic acid) (PAA) polymer brushes to explore the effects of surface chemistry and topography on cell-surface interactions. Most past studies of surface topography effects on cell adhesion have focused on patterned feature sizes that are larger than the dimensions of a cell, and PAA brushes have been characterized as cell repellent. Here we report cell adhesion studies for RBL mast cells incubated on PAA brush surfaces patterned with a variety of different feature sizes. We find that when patterned at subcellular dimensions on silicon surfaces, PAA brushes that are 30 or 15 nm thick facilitate cell adhesion. This appears to be mediated by fibronectin, which is secreted by the cells, adsorbing to the brushes and then engaging cell-surface integrins. The result is detectable accumulation of plasma membrane within the brushes, and this involves cytoskeletal remodeling at the cell-surface interface. By decreasing brush thickness, we find that PAA can be 'tuned' to promote cell adhesion with down-modulated membrane accumulation. We exemplify the utility of patterned PAA brush arrays for spatially controlling the activation of cells by modifying brushes with ligands that specifically engage IgE bound to high-affinity receptors on mast cells.     

Topological conjugacy to given constant length substitution minimal systems

We find necessary and sufficient conditions for a symbolic dynamical system to be topologically conjugate to any given constant length substitution minimal system, thus extending the results in Coven et al. (2008) for the Morse and Toeplitz substitutions.     

Dark forces at the Tevatron

A simple explanation of the W+dijet excess recently reported by the CDF collaboration involves the introduction of a new gauge boson with sizable couplings to quarks, but with no or highly suppressed couplings to leptons. Anomaly-free theories which include such a leptophobic gauge boson must also include additional particle content, which may include a stable and otherwise viable candidate for dark matter. Based on the couplings and mass of the Z^′ required to generate the CDF excess, we predict such a dark matter candidate to possess an elastic scattering cross section with nucleons on the order of σ∼¹⁰−40 cm², providing a natural explanation for the signals reported by the CoGeNT and DAMA/LIBRA collaborations. In this light, CDF may be observing the gauge boson responsible for the force which mediates the interactions between the dark and visible matter of our universe.