Synthesis and formulation of self-immolative PEG-aryl azide block copolymers and click-to-release reactivity with trans-cyclooctene

Self-immolative aryl azides can react with trans-cyclooctenes (TCO), triphenylphosphines or hydrogen sulfide (H₂S) to activate prodrugs, imaging probes and drug delivery systems. To date, the synthesis of polymers containing these aryl azide self-immolative linkers and their reactivity with a strained alkene (i.e., in a bioorthogonal reaction) has not been explored. Also, due to the instability of aryl azides towards light and high temperatures, the polymerization methods compatible with aryl azides are limited. Through systematic investigation of the reversible addition-fragmentation chain transfer (RAFT) and atom transfer radical polymerization (ATRP) methods, a self-immolative PEG-aryl azide block copolymer (PEG₄₅-b-ABOC₂₈ 2 ) and a non-responsive 4-fluoroaryl block copolymer (PEG₄₅-b-FBOC₂₄ 3 ) was prepared. ATRP provided the desired polymers in a highly controlled manner, whereas the RAFT conditions led to higher levels of aryl azide polymer degradation. The ATRP derived polymers 2 and 3 were formulated into nanoparticles of approximately 200 nm diameter, and particle triggering was demonstrated by the [3+2]-cycloaddition reaction of TCO with PEG₄₅-b-ABOC₂₈ 2 in solution (pure polymer) and as a formulated nanoparticle. Preliminary in vitro cell viability studies suggested that the stimuli-responsive aryl azide polymers/nanoparticles are not cytotoxic up to 200 μg/ml concentrations.     

Monitoring FET flow control and wall adsorption of charged fluorescent dye molecules in nanochannels integrated into a multiple internal reflection infrared waveguide

Using Si as the substrate, we have fabricated multiple internal reflection infrared waveguides embedded with a parallel array of nanofluidic channels. The channel width is maintained substantially below the mid-infrared wavelength to minimize infrared scattering from the channel structure and to ensure total internal reflection at the channel bottom. A Pyrex slide is anodically bonded to the top of the waveguide to seal the nanochannels, while simultaneously enabling optical access in the visible range from the top. The Si channel bottom and sidewalls are thermally oxidized to provide an electrically insulating barrier, and the Si substrate surrounding the insulating SiO(2) layer is selectively doped to function as a gate. For fluidic field effect transistor (FET) control, a DC potential is applied to the gate to manipulate the surface charge on SiO(2) channel bottom and sidewalls and therefore their zeta-potential. Depending on the polarity and magnitude, the gate potential can accelerate, decelerate, or reverse the flow. Here, we demonstrate that this nanofluidic infrared waveguide can be used to monitor the FET flow control of charged, fluorescent dye molecules during electroosmosis by multiple internal reflection Fourier transform infrared spectroscopy. Laser scanning confocal fluorescence microscopy is simultaneously used to provide a comparison and verification of the IR analysis. Using the infrared technique, we probe the vibrational modes of dye molecules, as well as those of the solvent. The observed infrared absorbance accounts for the amount of dye molecules advancing or retracting in the nanochannels, as well as adsorbing to and desorbing from the channel bottom and sidewalls.     

Allylic C-H activations using Cu(II) 2-quinoxalinol salen and tert-butyl hydroperoxide

Using a Cu(II) 2-quinoxalinol salen complex as the catalyst and tert-butyl hydroperoxide (TBHP) as the oxidant, allylic activations of olefin substrates can be converted to the corresponding enones or 1,4-enediones. Excellent yields can be achieved (up to 99%) within a very short reaction time and with great tolerance for additional functional groups. Possible mechanistic pathways have been characterized using Raman spectroscopy, cyclic voltammetry, and theoretical calculations.     

Laser-fluorescence diagnostics for condensation in laser-ablated copper plasmas

We are investigating the thermodynamic conditions under which condensation occurs in laser ablated copper plasma plumes. The plasma is created by XeCl excimer laser ablation (308 nm, 300 mJ/pulse) at power densities from 500–1000 MW/cm² into backing pressures of helium in the range 0–50 torr. We use laser-induced fluorescence (LIF) to probe velocity and relative density of both atomic copper and the copper dimer molecule, Cu₂, which is formed during condensation onset. At low pressure (10 mtorr), the atomic Cu velocity peaks at approximately 2×10⁶ cm/s. Copper dimer time-of-flight data suggest that condensation onset occurs after the Cu atoms have slowed very significantly. Excitation scans of the Cu₂A-X (0,0) and (1,1) bands yield a rotational and vibrational temperature in the neighborhood of 300 K for all conditions studied. Such low temperatures support the theory that Cu₂ is formed under thermally and translationally cold conditions. Direct laser beam absorption is used to determine the number density of atomic copper. Typical densities attained with 5 torr of helium backing gas are 6–8×10¹³ cm^–3. Rayleigh scattering from particulate is easily observable under conditions favorable to particulate production.     

Stereochemical basis for the anti-chlamydial activity of the phosphonate protease inhibitor JO146

JO146, a mixture of two diastereomers of a peptidic phosphonate inhibitor for Chlamydial HtrA (CtHtrA), has reported activity against Chlamydia species in both human and koala. In this study we isolated the individual diastereomers JO146-D1 and JO146-D2 (in ≥90% purity) and assessed their individual inhibitory activity against the serine protease human neutrophil elastase (HNE) which is structurally and functionally related to CtHtrA, as well as in Chlamydia trachomatis cell culture. JO146-D2 [S,S,R-Boc-Val-Pro-Val^P(OPh)₂], the isomer with the physiologically relevant valine at P1, had an approximate 2.5 – fold increase in in vitro HNE inhibition potency over JO146-D1 [S,S,S-Boc-Val-Pro-Val^P(OPh)₂] and greater than 100 – fold increase in cellular anti-chlamydial activity compared to JO146-D1 which possesses the unnatural valine at P1. JO146 and the individual diastereomers had excellent selectivity for the serine protease HNE over the potential off-target serine proteases trypsin and chymotrypsin. Docking studies supported the biological data with a geometrically unfavoured interaction observed between the P1 valine residue of JO146-D1 and the enzyme S1 sub-pocket.     

Structure and reactivity studies of the first tungsten cyanoalkylidene complex

Alkylidene complex W(CHCMe2Ph)(NAr)[OCMe(CF3)2]2 (Ar = 2, 6 diisopropylphenyl) (4) reacts with one equivalent of acrylonitrile in methylene chloride to afford the tetrameric, cyanoalkylidene complex [W(CHCN)(NAr)[OCMe(CF3)2]2]4 (5) which reacts with excess acetonitrile to give the tetrameric complex [W(N(H)C(CH3)C(CN)C(CH3)N)(NAr)[OCMe(CF3)2]2]4 (6).     

Photochemical generation of cationic lewis acids via deligation of metal-sandwich complexes

Photoinduced loss of one or both ligands from bis(arene) metal complexes provides an attractive route to cationic Lewis acids that can function as initiators for polymerization and crosslinking reactions. In this article, we examine the spectroscopy, photochemistry and photoinitiation activity of two such complexes: Fe(mes)₂²⁺ (mes is mesitylene) and Cr(tol)₂⁺ (tol is toluene). Acetonitrile solutions of Fe(mes)₂²⁺ undergo photochemical loss of both mesitylene rings to yield solvated Fe²⁺. The quantum efficiency of deligation ranges from 0.6 to 1.0 depending upon excitation wavelength, but is independent of complex concentration, solvent, oxygen concentration and excess counter-ion. Reaction appears to occur from both ligand field and ligand-to-metal charge transfer excited states. Low thermal stability, however, limits the use of Fe(mes)₂²⁺ as a practical photoinitiator. Deligation of both arene rings also occurs upon 366 nm irradiation of Cr(tol)₂⁺ in acetonitrile. The quantum efficiency for this process is 0.04 and is independent of oxygen concentration. Photoinitiated crosslinking and insolubilization occur in a thin film of COP (copolymer of glycidyl methacrylate and ethyl acrylate) containing Cr(tol)₂⁺.     

The structure of [YC6H6N]+˙ ions in the spectra of substituted acetanilides

Evidence is adduced from steric effects on relative intensities that the [YC₆H₆N]⁺ ions from substituted acetanilides have the aniline structure.     

Involutory matrices over finite commutative rings

An n × n matrix A is called involutory iff A²=I_n, where I_n is the n × n identity matrix. This paper is concerned with involutory matrices over an arbitrary finite commutative ring R with identity and with the similarity relation among such matrices. In particular the authors seek a canonical set $\text{C}$ with respect to similarity for the n × n involutory matrices over R—i.e., a set $\text{C}$ of n × n involutory matrices over R with the property that each n × n involutory matrix over R is similar to exactly on matrix in $\text{C}$. Because of the structure of finite commutative rings and because of previous research, they are able to restrict their attention to finite local rings of characteristic a power of 2, and although their main result does not completely specify a canonical set $\text{C}$ for such a ring, it does solve the problem for a special class of rings and shows that a solution to the general case necessarily contains a solution to the classically unsolved problem of simultaneously bringing a sequence A₁,…,A_v of (not necessarily involutory) matrices over a finite field of characteristic 2 to canonical form (using the same similarity transformation on each A_i). (More generally, the authors observe that a theory of similarity fot matrices over an arbitrary local ring, such as the well-known rational canonical theory for matrices over a field, necessarily implies a solution to the simultaneous canonical form problem for matrices over a field.) In a final section they apply their results to find a canonical set for the involutory matrices over the ring of integers modulo 2^m and using this canonical set they are able to obtain a formula for the number of n × n involutory matrices over this ring.