Development of a pharmaceutical cocrystal of a monophosphate salt with phosphoric acid

We report the first case of a pharmaceutical cocrystal formed between an inorganic acid and an active pharmaceutical ingredient (API), which enabled us to develop a stable crystalline and bioavailable solid dosage form for pharmaceutical development where otherwise only unstable amorphous free form or salts could have been used.     

Feynman formulas and path integrals for some evolution semigroups related to τ-quantization

This note is devoted to Feynman formulas (i.e., representations of semigroups by limits of n-fold iterated integrals as n → ∞) and their connections with phase space Feynman path integrals. Some pseudodifferential operators corresponding to different types of quantization of a quadratic Hamiltonian function are considered. Lagrangian and Hamiltonian Feynman formulas for semigroups generated by these operators are obtained. Further, a construction of Hamiltonian (phase space) Feynman path integrals is introduced. Due to this construction, the Hamiltonian Feynman formulas obtained here and in our previous papers do coincide with Hamiltonian Feynman path integrals. This connects phase space Feynman path integrals with some integrals with respect to probability measures. These connections enable us to make a contribution to the theory of phase space Feynman path integrals, to prove the existence of some of these integrals, and to study their properties by means of stochastic analysis. The Feynman path integrals thus obtained are different for different types of quantization. This makes it possible to distinguish the process of quantization in the language of Feynman path integrals.     

Bioconjugation via azide-Staudinger ligation: an overview

Bioconjugation techniques using organic azides are compared in this critical review. A particular focus is on chemical ligation reactions and their application to chemical biology (179 references).     

Correlation of amine number and pDNA binding mechanism for trehalose-based polycations

Glycopolymers with repeat units comprised of the disaccharide trehalose and an oligoamine of increasing amine have been previously synthesized by our group and shown to efficiently deliver pDNA (plasmid DNA) to HeLa cells while remaining relatively nontoxic. Complexes formed between the most amine-dense of these polycations and pDNA were also found to be relatively stable in serum and have low aggregation, which is desirable for in vivo gene delivery. To lend insight into these interesting results, this study was aimed at investigating the binding strength and mechanism of interaction between these macromolecules, via isothermal titration calorimetry (ITC) and ethidium bromide exclusion assays. The size of these pDNA-polymer complexes, or polyplexes, at various states of formation was determined through light scattering and zeta-potential measurements. Varying degrees of pDNA secondary structure change occurred upon interaction with the polymers, as evidenced by circular dichroism spectra through increasing molar ratios of polymer amine to DNA phosphate, and Fourier transform infrared (FT-IR) results demonstrated stronger electrostatic binding with the phosphate backbone with the least amine-dense of the series. It was concluded that, depending on the number of secondary amines in the repeat unit, these polymers interact with pDNA via different mechanisms with varying extents of electrostatic interaction and hydrogen bonding. These differing mechanisms may affect the ability of trehalose to serve as a deterrent against aggregation in serum conditions and lend insight into the roles of polymer-pDNA binding during the complex transfection process.     

A structural transition in duplex DNA induced by ethylene glycol

The twist energy parameter ( E T) that governs the supercoiling free energy, and the linking difference (Delta l) are measured for p30delta DNA in solutions containing 0-40 w/v % ethylene glycol (EG). A plot of E T vs -ln a w, where a w is the water activity, displays the full (reverse) sigmoidal profile of a discrete structural transition. A general theory for the effect of added osmolyte on a cooperative structural transition between two duplex states, 1 right arrow over left arrow 2, is formulated in terms of parameters applicable to individual base-pair subunits. The resulting fraction of base pairs in the 2-state ( f 2 (0)) is incorporated into expressions for the effective torsion and bending elastic constants, the effective twist energy parameter ( E T (eff)), and the change in intrinsic twist (delta l 0). Fitting the expression for E T (eff) to the measured E T values yields reasonably unambiguous estimates of E T 1 and E T 2 , the midpoint value (ln a w) 1/2, and the midpoint slope ( partial differential E T/ partial differential ln a w) 1/2, but does not yield unambiguous estimates of the equilibrium constant ( K 0), the difference in DNA-water preferential interaction coefficient (DeltaGamma), or the inverse cooperativity parameter ( J). Fitting a noncooperative model (assumed J = 1.0) to the data yields K 0 = 0.067 and DeltaGamma = -30.0 per base pair (bp). Essentially equivalent fits are provided by models with a wide range of correlated J, DeltaGamma, and K 0 values. Other results favor DeltaGamma in the range -1.0 to 0, which then requires K 0 > or = 0.914, and a cooperativity parameter, 1/ J > or = 30.0 bp. The measured delta l 0 and circular dichroism (CD) at 272 nm are found to be compatible with curves predicted using the same f 2 (0) values that best-fit the E T data. At least 7-10% of the base pairs are inferred to exist in the 2-state in 0.1 M NaCl in the complete absence of added osmolyte. Compared with the 1-state, the 2-state has a approximately 2.0- to 2.1-fold greater torsion elastic constant, a approximately 0.70-fold smaller bending elastic constant, a approximately 0.91-fold smaller E T value, a approximately 0.2% lower intrinsic twist, a somewhat lower CD near both 272 and 245 nm, and less water and/or more EG in its neighborhood. However, the relative change in preferential interaction coefficient associated with the transition is likely rather slight.     

Isotropic-nematic interface and wetting in suspensions of colloidal platelets

We study interfacial phenomena in a colloidal dispersion of sterically stabilized gibbsite platelets, exhibiting coexisting isotropic and nematic phases separated by a sharp horizontal interface. The nematic phase wets a vertical glass wall and polarized light micrographs reveal homeotropic surface anchoring both at the free isotropic-nematic interface and at the wall. On the basis of complete wetting of the wall by the nematic phase, as found in our density functional calculations and computer simulations, we analyze the balance between Frank elasticity and surface anchoring near the contact line. Because of weak surface anchoring, the director field in the capillary rise region is uniform. From the measured rise (6 microm) of the meniscus at the wall we determine the isotropic-nematic surface tension to be 3 nN/m, in quantitative agreement with our theoretical and simulation results.     

Substrate changes associated with the chemistry of self-assembled monolayers on silicon

Alkylsiloxane self-assembled monolayers (SAMs) are used in the semiconductor industry and, more recently, as proxies for organics adsorbed on airborne mineral dust and on buildings and construction materials. A number of methods have been used for removing the SAM from the substrate after reaction or use, particularly plasmas or piranha (H2SO4/H2O2) solution. However, when the substrates are reused to make new SAMs, the impact of the cleaning methods on the chemistry of subsequently formed SAMs on the surface is not known. Here we report atomic force microscopy, X-ray photoelectron spectroscopy, Auger electron spectroscopy, and Fourier transform infrared studies of changes in a silicon substrate upon repetitive deposition and removal of SAMs by these two methods. It is shown that a thicker layer of silicon oxide is formed, and the surface becomes irregular and roughened, particularly after the piranha treatment. This layer of silica impacts the structure of the SAMs attached to it and can serve as a reservoir for trace gases that adsorb on it, potentially contributing to the subsequent reactions of the SAM. The implications for the use of such surfaces as a proxy for reactions of organics on airborne dust particles and on structures in the boundary layer are discussed.     

On the coupling property and the Liouville theorem for Ornstein–Uhlenbeck processes

Using a coupling for the weighted sum of independent random variables and the explicit expression of the transition semigroup of Ornstein–Uhlenbeck processes driven by compound Poisson processes, we establish the existence of a successful coupling and the Liouville theorem for general Ornstein–Uhlenbeck processes. Then we present the explicit coupling property of Ornstein–Uhlenbeck processes directly from the behaviour of the corresponding symbol or characteristic exponent. This approach allows us to derive gradient estimates for Ornstein–Uhlenbeck processes via the symbol.