Labeled Nanoparticles Based on Pharmaceutical EUDRAGIT® S 100 Polymers

The pharmaceutically important polymer P(MAA–r–MMA)_1:2 (EUDRAGIT ^® S100) was investigated concerning its behavior to form nanoparticles via nanoprecipitation. The particles obtained were characterized regarding their size, shape, and characteristics using DLS, SEM, and AUC. Furthermore, the P(MAA–r–MMA)_1:2 copolymer was modified with different markers in order to achieve polymer‐based nanocarrier systems, which are detectable and may be useful for controlled drug delivery devices to monitor the drug pathways. The particles were labeled by physical entrapment as well as by covalent attachment of various markers, e.g., radicals, fluorescent‐, and near‐infrared dyes, to the polymer. Physical entrapment of radicals into the polymeric units was performed by co‐nanoprecipitation of P(MAA–r–MMA)_1:2 and a radical marker. By means of covalent binding of the markers to the polymer, a stable and more defined labeling of the particles was also performed, leading only to a low degree of modification of the pharmaceutical polymer. After nanoprecipitation, the resulting labeled particles were characterized by SEM and DLS, whereas their biocompatibility was proven by in vitro studies. In order to ensure the possibility of detection of the particles inside the body for drug delivery‐, sensor‐, and imaging applications, the polymeric carriers were also investigated by electron spin resonance, fluorescence, as well as near‐infrared spectroscopy.

     

Manganese carbonyls bearing tripodal polypyridine ligands as photoactive carbon monoxide-releasing molecules

The recently discovered cytoprotective action of CO has raised interest in exogenous CO-releasing materials (CORMs) such as metal carbonyls (CO complexes of transition metals). To achieve control on CO delivery with metal carbonyls, we synthesized and characterized three Mn(I) carbonyls, namely, [Mn(tpa)(CO)(3)]ClO(4) [1, where tpa = tris(2-pyridyl)amine], [Mn(dpa)(CO)(3)]Br [2, where dpa = N,N-bis(2-pyridylmethyl)amine], and [Mn(pqa)(CO)(3)]ClO(4) [3, where pqa = (2-pyridylmethyl)(2-quinolylmethyl)amine], by crystallography and various spectroscopic techniques. All three carbonyls are sensitive to light and release CO when illuminated with low-power UV (5-10 mW) and visible (λ > 350 nm, ~100 mW) light. The sensitivity of 1-3 to light has been assessed with respect to the number of pyridine groups in their ligand frames. When a pyridine ring is replaced with quinoline, extended conjugation in the ligand frame increases the absorptivity and makes the resulting carbonyl 3 more sensitive to visible light. These photosensitive CORMs (photoCORMs) have been employed to deliver CO to myoglobin under the control of light. The superior stability of 3 in aqueous media makes it a photoCORM suitable for inducing vasorelaxation in mouse aortic muscle rings.     

Ni, Pd, Pt, and Ru complexes of phosphine-borate ligands

The species Cy(2)PHC(6)F(4)BF(C(6)F(5))(2) reacts with Pt(PPh(3))(4) to yield the new product cis-(PPh(3))(2)PtH(Cy(2)PC(6)F(4)BF(C(6)F(5))(2)) 1 via oxidative addition of the P-H bond of the phosphonium borate to Pt(0). The corresponding reaction with Pd(PPh(3))(4) affords the Pd analogue of 1, namely, cis-(PPh(3))(2)PdH(Cy(2)PC(6)F(4)BF(C(6)F(5))(2)) 3; while modification of the phosphonium borate gave the salt [(PPh(3))(3)PtH][(tBu(2)PC(6)F(4)BF(C(6)F(5))(2))] 2. Alternatively initial deprotonation of the phosphonium borate gave [tBu(3)PH][Cy(2)PC(6)F(4)BF(C(6)F(5))(2)] 4, [SIMesH][Cy(2)PC(6)F(4)BF(C(6)F(5))(2)] 5 which reacted with NiCl(2)(DME) yielding [BaseH](2)[trans-Cl(2)Ni(Cy(2)PC(6)F(4)BF(C(6)F(5))(2))(2)] (Base = tBu(3)P 6, SIMes 7) or with PdCl(2)(PhCN)(2) to give [BaseH](2)[trans-Cl(2)Pd(Cy(2)PC(6)F(4)BF(C(6)F(5))(2))(2)] (Base = tBu(3)P 8, SIMes 9). While [C(10)H(6)N(2)(Me)(4)H][tBu(2)PC(6)F(4)BF(C(6)F(5))(2)] 10 was also prepared. A third strategy for formation of a metal complex of anionic phosphine-borate derivatives was demonstrated in the reaction of (COD)PtMe(2) with the neutral phosphine-borane Mes(2)PC(6)F(4)B(C(6)F(5))(2) affording (COD)PtMe(Mes(2)PC(6)F(4)BMe(C(6)F(5))(2)) 11. Extension of this reactivity to tBu(2)PH(CH(2))(4)OB(C(6)F(5))(3)) was demonstrated in the reaction with Pt(PPh(3))(4) which yielded cis-(PPh(3))(2)PtH(tBu(2)P(CH(2))(4)OB(C(6)F(5))(3)) 12, while the reaction of [SIMesH][tBu(2)P(CH(2))(4)OB(C(6)F(5))(3)] 13 with NiCl(2)(DME) and PdCl(2)(PhCN)(2) afforded the complexes [SIMesH](2)[trans-Cl(2)Ni(tBu(2)PC(4)H(8)OB(C(6)F(5))(3))(2)] 14 and [SIMesH](2)[trans-PdCl(2)(tBu(2)P(CH(2))(4)OB(C(6)F(5))(3))(2)] 15, respectively, analogous to those prepared with 4 and 5. Finally, the reaction of 7 and 13with [(p-cymene)RuCl(2)](2) proceeds to give the new orange products [SIMesH][(p-cymene)RuCl(2)(Cy(2)PC(6)F(4)BF(C(6)F(5))(2))] 16 and [SIMesH][(p-cymene)RuCl(2)(tBu(2)P(CH(2))(4)OB(C(6)F(5))(3))] 17, respectively. Crystal structures of 1, 6, 10, 11, 12, and 16 are reported.     

Uptake of SO2 to aqueous formaldehyde surfaces

Aqueous surfaces act as a gateway to absorption and aqueous-phase reaction of gases in the atmosphere. The composition of aerosols varies greatly and is expected to influence the structure of the interface. For example, aldehydes comprise a significant fraction of atmospheric organics and are likely to accumulate at aqueous surfaces. But it is difficult to anticipate their effect on the migration of gaseous species through the interfacial region. Surface organics may act as a barrier to absorption, or they may facilitate uptake via cooperative interactions with absorbing compounds. The surface spectroscopic studies presented here examine the nature of the vapor/water interface during uptake of SO(2) to aqueous formaldehyde solutions, elucidating the role of surface species in a multicomponent interfacial system. The results show that the product of the reaction between SO(2) and formaldehyde, hydroxymethanesulfonate, shows a surface affinity that is enhanced in the presence of SO(2).     

Three-Dimensional DNA Crystals with pH-Responsive Noncanonical Junctions

Three-dimensional (3D) DNA crystals have been envisioned as programmable biomaterial scaffolds for creating ordered arrays of biological and nonbiological molecules. Despite having excellent programmable properties, the linearity of the Watson-Crick B-form duplex imposes limitations on 3D crystal design. Predictable noncanonical base pairing motifs have the potential to serve as junctions to connect linear DNA segments into complex 3D lattices. Here, we designed crystals based on a template structure with parallel-stranded noncanonical base pairs. Depending on pH, the structures we determined contained all but one or two of the designed secondary structure interactions. Surprisingly, a conformational change of the designed Watson-Crick duplex region resulted in crystal packing differences between the predicted and observed structures. However, the designed noncanonical motif was virtually identical to the template when crystals were grown at pH 5.5, highlighting the motif's predictability. At pH 7.0 we observed a structurally similar variation on this motif that contains a previously unobserved C-G?G-C quadruple base pair. We demonstrate that these two variants can interconvert in crystallo in response to pH perturbations. This study spotlights several important considerations in DNA crystal design, describes the first 3D DNA lattice composed of A-DNA helical sheets, and reveals a noncanonical DNA motif that has adaptive features that may be useful for designing dynamic crystals or biomaterial assemblies.     

Dramatic enhancement of CO2 uptake by poly(ethyleneimine) using zirconosilicate supports

The CO(2) adsorption characteristics of prototypical poly(ethyleneimine)/silica composite adsorbents can be drastically enhanced by altering the acid/base properties of the oxide support via incorporation of Zr into the silica support. Introduction of an optimal amount of Zr resulted in a significant improvement in the CO(2) capacity and amine efficiency under dilute (simulated flue gas) and ultradilute (simulated ambient air) conditions. Adsorption experiments combined with detailed characterization by thermogravimetric analysis, temperature-programmed desorption, and in situ FT-IR spectroscopy clearly demonstrate a stabilizing effect of amphoteric Zr sites that enhances the adsorbent capacity, regenerability, and stability over continued recycling. It is suggested that the important role of the surface properties of the oxide support in these polymer/oxide composite adsorbents has been largely overlooked and that the properties may be even further enhanced in the future by tuning the acid/base properties of the support.     

In-situ probe of gate dielectric-semiconductor interfacial order in organic transistors: origin and control of large performance sensitivities

Organic thin film transistor (OTFT) performance is highly materials interface-dependent, and dramatic performance enhancements can be achieved by properly modifying the semiconductor/gate dielectric interface. However, the origin of these effects is not well understood, as this is a classic "buried interface" problem that has traditionally been difficult to address. Here we address the question of how n-octadecylsilane (OTS)-derived self-assembled monolayers (SAMs) on Si/SiO(2) gate dielectrics affect the OTFT performance of the archetypical small-molecule p-type semiconductors P-BTDT (phenylbenzo[d,d]thieno[3,2-b;4,5-b]dithiophene) and pentacene using combined in situ sum frequency generation spectroscopy, atomic force microscopy, and grazing incidence and reflectance X-ray scattering. The molecular order and orientation of the OTFT components at the dielectric/semiconductor interface is probed as a function of SAM growth mode in order to understand how this impacts the overlying semiconductor growth mode, packing, crystallinity, and carrier mobility, and hence, transistor performance. This understanding, using a new, humidity-specific growth procedure, leads to a reproducible, scalable process for highly ordered OTS SAMs, which in turn nucleates highly ordered p-type semiconductor film growth, and optimizes OTFT performance. Surprisingly, the combined data reveal that while SAM molecular order dramatically impacts semiconductor crystalline domain size and carrier mobility, it does not significantly influence the local orientation of the overlying organic semiconductor molecules.     

From large N nonplanar anomalous dimensions to open spring theory

In this Letter we compute the nonplanar one-loop anomalous dimension of restricted Schur polynomials that have a bare dimension of O(N)$O(N)$. This is achieved by mapping the restricted Schur polynomials into states of a specific U(p)$U(p)$ irreducible representation. In this way the dilatation operator is mapped into a u(p)$u(p)$ valued operator and, as a result, can easily be diagonalized. The resulting spectrum is reproduced by a model of springs between masses.     

Study of Effective 2+1 Dimensional Gravity in Ferrofluid-Based Hyperbolic Metamaterials

Recent theoretical and experimental work demonstrated that nonlinear optics of ferrofluid-based hyperbolic metamaterials exhibit very unusual spatiotemporal dynamics. Here a detailed theoretical and experimental study of mutual interactions of individual self-focused optical filaments inside this metamaterial is reported. In agreement with theoretical expectations, the observed mutual interactions of individual filaments exhibit strong similarities with general relativity in 2+1 dimensions, which predicts that these interactions must have predominantly non-Newtonian topological character. This observation is important since 2+1-dimensional gravity is an exactly solvable theory even in the quantum gravity limit.     

HPLC-SPE-NMR in pharmaceutical development: capabilities and applications

High-performance liquid chromatography-solid phase extraction-NMR spectroscopy (HPLC-SPE-NMR) has recently become commercially available and has been evaluated with regard to its applicability in a pharmaceutical environment. The addition of an automated SPE unit to an HPLC-NMR system for peak trapping results in an improved NMR signal-to-noise ratio (S/N) and also has other practical advantages. The trapping efficiency is shown to depend on compound polarity and is highest for compounds eluting late on reversed-phase HPLC systems. Multiple peak trapping further increases the S/N, again with the best results for less polar compounds. For polar compounds, multiple peak trapping resulted in no S/N gain as the amount of material retained on the SPE cartridge was equivalent to that from a single injection. When compared with conventional HPLC-NMR, a S/N gain of up to five-fold could be achieved for some compounds in a single trapping step. A major advantage of the technique is the independence of the chromatographic step from the NMR step, resulting in greater versatility than conventional HPLC-NMR in the HPLC solvents and NMR solvents that can be used. Practical applications from both drug metabolite and drug impurity identification are presented.