Can density functional theory (DFT) be used as an aid to a deeper understanding of tandem mass spectrometric fragmentation pathways?

Prediction of tandem mass spectrometric (MS/MS) fragmentation for non-peptidic molecules based on structure is of immense interest to the mass spectrometrist. If a reliable approach to MS/MS prediction could be achieved its impact within the pharmaceutical industry could be immense. Many publications have stressed that the fragmentation of a molecular ion or protonated molecule is a complex process that depends on many parameters, making prediction difficult. Commercial prediction software relies on a collection of general heuristic rules of fragmentation, which involve cleaving every bond in the structure to produce a list of 'expected' masses which can be compared with the experimental data. These approaches do not take into account the thermodynamic or molecular orbital effects that impact on the molecule at the point of protonation which could influence the potential sites of bond cleavage based on the structural motif. A series of compounds have been studied by examining the experimentally derived high-resolution MS/MS data and comparing it with the in silico modelling of the neutral and protonated structures. The effect that protonation at specific sites can have on the bond lengths has also been determined. We have calculated the thermodynamically most stable protonated species and have observed how that information can help predict the cleavage site for that ion. The data have shown that this use of in silico techniques could be a possible way to predict MS/MS spectra. Copyright (C) 2009 John Wiley & Sons, Ltd.

Synthesis and enzymatic evaluation of the guanosine analogue 2-amino-6-mercapto-7-methylpurine ribonucleoside (MESG): insights into the phosphorolysis reaction mechanism based on the blueprint transition state: SN1 or SN2?

A modified experimental procedure for the synthesis of MESG (2-amino-6-mercapto-7-methylpurine ribonucleoside) 1 has been successfully performed and its full characterization is presented. High resolution ESI(+)-MSMS indicates both the nucleoside bond cleavage as the main fragmentation in the gas phase and a possible SN1 mechanism. Ab initio transition state calculations based on the blue print transition state support this mechanistic rationale and discard an alternative SN2 mechanism. Assays using purine nucleoside phosphorylase (PNP) enzyme (human and M. tuberculosis sources) indicate its efficiency in the phosphorolysis of MESG and allow the quantitative determination of inorganic phosphate in real time assay.

Wire bond reliability for power electronic modules - effect of bonding temperature

In this paper, thermal cycling reliability along with ANSYS analysis of the residual stress generated in heavy-gauge Al bond wires at different bonding temperatures is reported. 99.999% pure Al wires of 375 mum in diameter, were ultrasonically bonded to silicon dies coated with a 5mum thick Al metallisation at 25degC (room temperature), 100degC and 200degC, respectively (with the same bonding parameters). The wire bonded samples were then subjected to thermal cycling in air from -60degC to +150degC. The degradation rate of the wire bonds was assessed by means of bond shear test and via microstructural characterisation. Prior to thermal cycling, the shear strength of all of the wire bonds was approximately equal to the shear strength of pure aluminum and independent of bonding temperature. During thermal cycling, however, the shear strength of room temperature bonded samples was observed to decrease more rapidly (as compared to bonds formed at 100degC and 200degC) as a result of a high crack propagation rate across the bonding area. In addition, modification of the grain structure at the bonding interface was also observed with bonding temperature, leading to changes in the mechanical properties of the wire. The heat and pressure induced by the high temperature bonding is believed to promote grain recovery and recrystallisation, softening the wires through removal of the dislocations and plastic strain energy. Coarse grains formed at the bonding interface after bonding at elevated temperatures may also contribute to greater resistance for crack propagation, thus lowering the wire bond degradation rate

Shear bond strengths of glass-ionomer cements to sound and to prepared carious dentine

The aim of this study was determine whether bonding of glass-ionomer cements to non-carious dentine differed from that to carious dentine. Five commercial cements were used, namely Fuji IX GP, Fuji IX capsulated, Fuji IX Fast capsulated (all GC, Japan), Ketac-Molar and Ketac-Molar Aplicap (both 3M-ESPE, Germany). Following conditioning of the substrate with 10% poly (acrylic acid) for 10 s, sets of 10 samples of the cements were bonded to prepared teeth that had been removed for orthodontic reasons. The teeth used had either sound dentine or sclerotic dentine. Shear bond strengths were determined following 24 h storage. For the auto-mixed cements, shear bond strength to sound dentine was found not to differ statistically from shear bond strength to sclerotic dentine whereas for hand-mixed cements, shear bond to sound dentine was found to be higher than to carious dentine (to at least p < 0.05). This shows that the chemical effects arising from interactions of glass-ionomer cements with the mineral phase of the tooth are the most important in developing strong bonds, at least in the shorter term.