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Since its introduction by Karas and co-workers in 1987, matrix-assisted laser desorption/ionization (MALDI) has rapidly become a vital tool in the study of large molecules.1-10 The mechanism of ionization during MALDI is still poorly understood, and no adequate quantitative model for the complete process exists. The MALDI technique involves both laser ablation and ionization of the matrix/analyte mixture. Spectra are dominated by matrix photoproducts, protonated molecules, and adduct ions. Several groups have developed models for the ablation process. [6][7][8]11 However, full models of MALDI await more detailed knowledge of ionization mechanisms, kinetics and thermodynamics of the species involved.Ablation models are the best developed aspect of MALDI theory. The majority of the energy absorbed by the matrix relaxes by rapid internal conversion from electronic states to vibrationally excited ground states and contributes to rapid heating. Ehring and Sundqvist 12 studied the luminescence of two common MALDI matrices and found that the luminescence quantum yields are very low (0.2) which indicates that most of the energy is converted into matrix heating following photoexcitation. Models proposed to describe the laser ablation of the matrix include quasi-thermal evaporation, layer-by-layer expansion and pressure pulse expansion. In all three models, analyte molecules are assumed to be entrained within the flux of matrix molecules ejected from the surface, but these models do not address the formation of ions.Evidence exists that analyte ionization occurs both in the surface and in the expanding plume. A small proportion of the analyte ionization occurs in the surface layers as proposed by Johnson and co-workers. 11,13,14 At the threshold fluence, the ion yield increases rapidly until a fixed layer depth is ejected, 15 but the ionization is heavily quenched when the ejection yields are large. 16 This model is supported by a recent study by Russell's group which reported two thresholds for analyte ion formation in MALDI.17 At low laser fluences of 2 mJ/cm 2 , vitamin B 12 gives an [M + H] + and a [M -CN + H] + ion in α-cyano-4-hydroxycinnamic acid. These ions are observed from the first laser shot on a spot and only the first shot. At three times higher laser fluences, the [M + H] + ion disappears. Russell and co-workers proposed that a surface component is desorbed and ionized in the first shot at the lower ionization threshold. At the higher laser fluence, a component from the bulk material is desorbed.There also appears to be an important component of ionization originating from analyte molecules entrained in the expanding plume. Mowry and Johnson, 18 studying the relative amounts of ions and neutrals desorbed from various matrices, found that the ratio of neutralsto-ions ejected was of the order of 10 000 or greater at threshold irradiances. The ratio decreases with increasing irradiance of the desorption laser. These authors favor a collisional mechanism for analyte ion formation. Temporal profile analysis o...

The photophysics of the series of tungsten and molybdenum arylcarbyne complexes Cp(CO){P(OMe)3}M⋮CAr (1a, M = W, Ar = phenyl; 1b, M = Mo, Ar = phenyl; 1c, M = W, Ar = o-tolyl; 1d, M = W, Ar = 2-naphthyl) has been examined by using absorption, emission, and transient absorption spectroscopy. Extended Hückel calculations indicate that the lowest excited state of these arylcarbyne complexes is based on a d(M) → π*(M⋮CAr) configuration. Consistent with this prediction, each of the complexes displays a weak, mid-visible absorption band which is attributed to the d → π* transition. The tungsten complexes 1a, 1c, and 1d also exhibit red luminescence with a lifetime in the 100−200 ns regime. Nanosecond laser flash photolysis studies indicate that the arylcarbyne complexes display a strong transient absorption with a maximum in the 400−450 nm region. Close correspondence between decay lifetimes obtained by luminescence and transient absorption indicate that the transient absorption may be assigned to the d → π* excited state.

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Gemcitabine is an intravenously administered nucleoside analog chemotherapeutic agent. The ability to deliver this agent as an oral drug would allow greater flexibility of administration and patient convenience; however, attempts have been fraught with high first-pass metabolism and potential intestinal toxicity. Alternatively, an amide prodrug of gemcitabine (LY2334737) was discovered, which is able to avoid the extensive first-pass metabolism that occurs following administration of gemcitabine. Preclinical in vitro and in vivo experiments were conducted to evaluate the hydrolysis and pharmacokinetics of LY2334737 and its downstream metabolites. In mice, rats, and dogs, the prodrug is absorbed largely intact across the intestinal epithelium and delivers LY2334737 to systemic circulation. The hydrolysis of LY2334737 is relatively slow, resulting in sustained release of gemcitabine in vivo. In vitro experiments identified carboxylesterase 2 (CES2) as a major enzyme involved in the hydrolysis of LY2334737, but with relatively low intrinsic clearance. Following hydrolysis of the prodrug, gemcitabine is cleared predominantly via the formation of its inactive metabolite dFdU. Both biliary and renal excretion was responsible for the elimination of LY2334737 and its metabolites in both mice and dogs.