SPECTROSCOPIC STUDIES OF CUTANEOUS PHOTOSENSITIZING AGENTS—IV. THE PHOTOLYSIS OF BENOXAPROFEN, AN ANTI-INFLAMMATORY DRUG WITH PHOTOTOXIC PROPERTIES

Abstract— Benoxaprofen [2-(4-chlorophenyl)-α-methyl-5-benzoxazole acetic acid] is an anti-inflammatory drug that causes acute phototoxicity in many patients. Photolysis studies in organic solvents (ethanol, benzene, dimethylsulfoxide) showed that benoxaprofen underwent both Type I and Type II reactions. Irradiation of an anerobic solution of benoxaprofen in ethanol resulted in hydrogen abstraction from the solvent to yield hydroxyethyl and ethoxyl radicals. In the presence of oxygen, superoxide, singlet oxygen and hydroxyethyl radicals were detected. Photolysis of benoxaprofen in air-saturated benzene or dimethylsulfoxide gave superoxide. However, under anerobic conditions the drug yielded a carbon-centered radical in benzene that could not be identified. These findings suggest that both oxygen-dependent and oxygen-independent processes may be important in the phototoxic reactions of benoxaprofen.     

T-shaped platinum boryl complexes: synthesis and structure

A series of cationic T-shaped 14-electron boryl complexes of the type trans-[(Cy(3)P)(2)Pt{B(X)X'}](+) (X=Br; X'=ortho-tolyl, tBu, NMe(2), piperidyl, Br; XX'=(NMe(2))(2), catecholato) were synthesized by halide abstraction from trans-[(Cy(3)P)(2)Pt(Br){B(X)X'}] (Cy=cyclohexyl) with Na[BAr(f) (4)] (Ar(f)=3,5-(CF(3))(2)C(6)H(3)), K[B(C(6)F(5))(4)], or Na[BPh(4)]. X-ray diffraction studies were performed on all compounds, revealing a subtle correlation between the trans-influence of the boryl moiety and the Pt--H and Pt--C separations. However, no notable agostic C--H interaction with the platinum center was detected. trans-[(Cy(3)P)(2)Pt(BCat)](+) (Cat=catecholato), the complex with the shortest Pt--H and Pt--C distances, was treated with Lewis bases (L), forming compounds of the type trans-[(Cy(3)P)(2)Pt(L)(BCat)](+), thus proving a decisive influence of the degree of trans-influence exerted by the boryl ligands on the chemical reactivity of the title complexes. Another point that was investigated and clarified is the different behavior of trans-[(Cy(3)P)(2)Pt(Br){B(Br)Mes}] (Mes=mesityl) towards K[B(C(6)F(5))(4)] with formation of the borylene species trans-[(Cy(3)P)(2)Pt(Br)(BMes)](+).     

Characterisation of the steady state tube furnace (ISO TS 19700) for fire toxicity assessment

The steady state tube furnace (Purser furnace, ISO TS 19700) has been developed specifically to replicate the generation of toxic products from real fires under different fire conditions on a bench-scale. Steady state burning is achieved by driving the sample into a furnace of increasing heat flux at a fixed rate and recording the product yields over a steady state period in the middle of the run. The furnace, sample, and effluent dilution chamber temperature profiles are presented to characterise the conditions in the apparatus. The distribution of smoke in the mixing chamber has been investigated to demonstrate the efficiency of mixing in the effluent dilution chamber. The heat flux applied to the sample at various points through the furnace has been measured, showing that conditions vary from those typical of pre-flaming to fully developed fires. An initial investigation of the repeatability and interlaboratory reproducibility has been undertaken, showing acceptable low levels of uncertainty in the toxic product yields.     

Mechanistic and Synthetic Aspects of Atom Transfer Radical Polymerization

Abstract

Mechanistic and synthetic aspects of atom transfer radical polymerization (ATRP) are reviewed. This controlled/“living” system polymerizes many monomers including styrenes, (meth)acrylates, acrylonitrile and dienes. The halogen end groups can be converted to other functional groups such as amines and azides. In addition to producing well-defined linear homopolymers, statistical copolymers, block copolymers, and gradient copolymers, ATRP can be used to synthesize graft and hyperbranched copolymers through copolymerization with functionalized monomers. Selection of appropriate conditions for ATRP depends on targeted molecular weight and degree of polymer chain end-functionality and includes considering the monomer(s) to be polymerized, initiator structure/reactivity, amount of catalyst/deactivator used, halogen end-group used, and temperature.     

Spontaneous formation of liquid crystalline phases and phase transitions in highly concentrated plasmid DNA

The liquid crystalline (LC) properties of two supercoiled plasmid DNA samples, pBSK (2958 bp) and pGEM (3000 bp), have been studied using polarised light microscopy (PLM), circular dichroism (CD) and UV–Vis spectroscopy. The influence of methods of isolation on plasmid LC behaviour is described, and using PLM we have demonstrated the spontaneous formation of cholesteric fingerprint-like textures. Preliminary studies of LC phase transitions in pGEM show the irreversibility of LC phase formation, as a consequence of changes in the tertiary structure of supercoiled plasmids. Using UV–Vis spectroscopy a hyperchromic effect was observed with increasing temperature. The CD spectra clearly showed structural changes, and probably mismatching of DNA bases, during cooling. Finally, we have observed an irreversible phase transition in plasmid DNA which is very different from that previously reported in linear DNA.     

An efficient parallel algorithm for the calculation of unrestricted canonical MP2 energies

We present details of our efficient implementation of full accuracy unrestricted open‐shell second‐order canonical Møller–Plesset (MP2) energies, both serial and parallel. The algorithm is based on our previous restricted closed‐shell MP2 code using the Saebo–Almlöf direct integral transformation. Depending on system details, UMP2 energies take from less than 1.5 to about 3.0 times as long as a closed‐shell RMP2 energy on a similar system using the same algorithm. Several examples are given including timings for some large stable radicals with 90+ atoms and over 3600 basis functions. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011     

Stereocontrol at the steady state in radical cyclizations of acyclic dihalides

The first examples of manipulating stereocontrol solely by reaction topography in radical cyclizations starting from acyclic precursors are reported. The kinetic model for acyclic compound stereoselection is verified experimentally by conducting a series of radical cyclizations of 1,3-dihalo-2-(1-phenyl-3-butynyl)propanes with triphenyltin hydride and measuring the ratios of the products. Monohalide intermediates are observed for the first time, and evidence that bromide- and iodide-substituted radicals have different cyclization rate constants is provided.     

Base‐Stabilized Boryl and Cationic Haloborylene Complexes of Iron

The synthesis of base‐stabilized boryl and borylene complexes is reported. An N‐heterocyclic carbene (NHC)‐stabilized iron–dihydroboryl complex was prepared by two different routes including methane liberation and salt elimination. A range of base‐stabilized iron–dichloroboryl complexes was prepared by addition of Lewis bases to boryl complexes. Base‐stabilized, cationic monochloroborylene complexes were synthesized from these boryl complexes by halide abstraction by using weakly coordinating anions.