A study of oxaliplatin–nucleobase interactions using ion trap electrospray mass spectrometry

Oxaliplatin is an important anti-cancer drug that has been approved for the treatment of colorectal cancer. It is known that oxaliplatin, like other Pt-based drugs, interacts with DNA to form cytotoxic Pt-DNA adducts that disrupt important biological processes such as DNA replication and protein synthesis. Linear ion trap electrospray ionisation mass spectrometry (ESI-MS) was employed to study the interaction of oxaliplatin with DNA nucleobases. It was shown that oxaliplatin formed adducts with all four DNA nucleobases when present individually and in combination in solution. Multiple-stage tandem mass spectrometry (MSⁿ) enabled the fragmentation pathways of each adduct to be established. In addition, proposed structures for each product ion were obtained from the MS data. When all four bases were present together with the drug at near-equal molar concentrations, adducts containing predominantly adenine and guanine were formed, confirming that the drug preferentially binds to these nucleobases. A large molar excess of drug was required to ensure the formation of cytosine and thymine adducts in the presence of adenine and guanine. Even with a large excess of oxaliplatin, only mono-adducts of these nucleobases were observed when all four nucleobases were present. Figure Schematic of a linear ion trap mass spectrometer being used to isolate the diadduct of guanine with oxaliplatin showing the characteristic isotope pattern due to ¹⁹⁴Pt, ¹⁹⁵Pt and ¹⁹⁶Pt.     

Observation of the A-x electronic transition of the isomers and conformers of pentyl peroxy radical using cavity ringdown spectroscopy

Cavity ringdown spectra of the A-X electronic transition of all eight isomers of the pentyl peroxy radical are reported. Using the corresponding assignments from previously studied smaller alkyl peroxy radicals, assignments of origin bands are made for the pentyl peroxy isomers including some conformer-specific assignments for bands of a given isomer. Ab initio calculations also were performed to aid in the spectral assignments for neopentyl, t-butyl, and t-pentyl peroxies. In addition to the origins, vibrational bands have also been assigned for some species. Using the analyzed spectra, the relative reactivity of the primary, secondary, and tertiary hydrogen atoms in isopentane could be determined semiquantitatively.     

Surface transfer doping of hydrogen-terminated diamond by C60F48: energy level scheme and doping efficiency

Surface sensitive C1s core level photoelectron spectroscopy was used to examine the electronic properties of C(60)F(48) molecules on the C(100):H surface. An upward band bending of 0.74 eV in response to surface transfer doping by fluorofullerene molecules is measured. Two distinct molecular charge states of C(60)F(48) are identified and their relative concentration determined as a function of coverage. One corresponds to ionized molecules that participate in surface charge transfer and the other to neutral molecules that do not. The position of the lowest unoccupied molecular orbital of neutral C(60)F(48) which is the relevant acceptor level for transfer doping lies initially 0.6 eV below the valence band maximum and shifts upwards in the course of transfer doping by up to 0.43 eV due to a doping induced surface dipole. This upward shift in conjunction with the band bending determines the occupation of the acceptor level and limits the ultimately achievable hole concentration with C(60)F(48) as a surface acceptor to values close to 10(13) cm(-2) as reported in the literature.     

Inverse potential scattering in duct acoustics

The inverse problem of the noninvasive measurement of the shape of an acoustical duct in which one-dimensional wave propagation can be assumed is examined within the theoretical framework of the governing Klein-Gordon equation. Previous deterministic methods developed over the last 40 years have all required direct measurement of the reflectance or input impedance but now, by application of the methods of inverse quantum scattering to the acoustical system, it is shown that the reflectance can be algorithmically derived from the radiated wave. The potential and area functions of the duct can subsequently be reconstructed. The results are discussed with particular reference to acoustic pulse reflectometry.     

Spinodal wrinkling in thin-film poly(ethylene oxide)/polystyrene bilayers

Optical microscopy and atomic force microscopy were used to study a novel roughness-induced wrinkling instability in thin-film bilayers of poly(ethylene oxide) (PEO) and polystyrene (PS). The observed wrinkling morphology is manifested as a periodic undulation at the surface of the samples and occurs when the bilayers are heated above the melting temperature of the semi crystalline PEO (T_m = 63 ) layer. During the wrinkling of the glassy PS capping layers the system selects a characteristic wavelength that has the largest amplitude growth rate. This initial wavelength is shown to increase monotonically with increasing thickness of the PEO layer. We also show that for a given PEO film thickness, the wavelength can be varied independently by changing the thickness of the PS capping layers. A model based upon a simple linear stability analysis was developed to analyse the data collected for the PS and PEO film thickness dependences of the fastest growing wavelength in the system. The predictions of this theory are that the strain induced in the PS layer caused by changes in the area of the PEO/PS interface during the melting of the PEO are sufficient to drive the wrinkling instability. A consideration of the mechanical response of the PEO and PS layers to the deformations caused by wrinkling then allows us to use this simple theory to predict the fastest growing wavelength in the system.     

Reversible alkene extrusion from platinaoxetanes

Reversible alkene extrusion from platinaoxetanes has been observed. Catalytic amounts of electrophilic Pt complexes, HOTf, Ag+, or BF3 (best) result in dramatic rate enhancements.     

Microwave-induced generation and reactions of nitrile sulfides: an improved method for the synthesis of isothiazoles and 1,2,4-thiadiazoles

The 1,3-dipolar cycloaddition reactions of nitrile sulfides, generated by microwave-assisted decarboxylation of 1,3,4-oxathiazol-2-ones, have been investigated. By this approach ethyl 1,2,4-thiadiazole-5-carboxylates 3 were prepared in good yield by cycloaddition of the nitrile sulfides to ethyl cyanoformate. Similarly, reaction of benzonitrile sulfide with dimethyl acetylenedicarboxylate (DMAD) afforded dimethyl 3-phenylisothiazole-4,5-dicarboxylate (5). In contrast, o-hydroxybenzonitrile sulfide, generated from the corresponding oxathiazolone 2d, reacted with DMAD to give methyl 4-oxo-4H-[1]benzopyrano[4,3-c]isothiazole-3-carboxylate (8) in high yield. A ca. 1:1 mixture of ethyl 3-phenylisothiazole-4- and 5-carboxylates (6,7) was formed from benzonitrile sulfide and ethyl propiolate. The corresponding reaction with diethyl fumarate gave diethyl trans-4,5-dihydro-3-phenylisothiazole-4,5-dicarboylate (10). 3-Arylisothiazoles, unsubstituted at both the 4- and 5-positions, were prepared from the reaction of 5-aryl-1,3,4-oxathiazolones with norbornadiene by a pathway involving cycloaddition of the nitrile sulfide to the norbornadiene, followed by retro-Diels-Alder extrusion of cyclopentadiene from the resulting isothiazoline cycloadduct 12. In summary, the use of microwave irradiation, rather than conventional heating methods, allows nitrile sulfide generation and reactions to be carried out in shorter times, with easier work-up and, in some cases, in higher yields.