Electronic energies of the hydrogen molecule D′∏u and B″ Σ states

Calculations of the electronic energies and wave-functions for the hydrogen molecule D'∏_u and B″Σ states have been carried out at the estimated curve crossing distance of 1,5307 atomic units. The results show good agreement with previous calculations.     

Photolysis wavelength dependence of the translational anisotropy and the angular momentum polarization of O2(a 1Deltag) formed from the UV photodissociation of O3

The translational anisotropy and angular momentum polarization of the O(2)(a (1)Delta(g),v = 0;J = 15-27) molecular photofragment produced from the UV photodissociation of O(3) in the range from 270 to 300 nm have been determined using resonance-enhanced multiphoton ionization in conjunction with time-of-flight mass spectrometry. At the shortest photolysis wavelengths used, the fragments exhibit the anisotropic vector correlations expected from a prompt dissociation via the (1)B(2) <--(1)A(1) transition. Deviations from this behavior are observed at longer photolysis wavelengths with, in particular, the angular momentum orientation showing a significant reduction in magnitude. This indicates that the dissociation can no longer be described by a purely impulsive model and a change in geometry of the dissociating molecule is implied. This observation is substantiated by the variation of the translational anisotropy with photolysis wavelength. We also observe that the bipolar moments describing the angular momentum polarization of the odd J states probed are consistently lower in magnitude than those of the even J states and that this variation is observed for all photolysis wavelengths.     

A new perspective on beta-sheet structures using vibrational Raman optical activity: from poly(L-lysine) to the prion protein

The vibrational Raman optical activity (ROA) spectrum of a polypeptide in a model beta-sheet conformation, that of poly(l-lysine), was measured for the first time, and the alpha-helix --> beta-sheet transition monitored as a function of temperature in H(2)O and D(2)O. Although no significant population of a disordered backbone state was detected at intermediate temperatures, some side chain bands not present in either the alpha-helix or beta-sheet state were observed. The observation of ROA bands in the extended amide III region assigned to beta-turns suggests that, under our experimental conditions, beta-sheet poly(L-lysine) contains up-and-down antiparallel beta-sheets based on the hairpin motif. The ROA spectrum of beta-sheet poly(L-lysine) was compared with ROA data on a number of native proteins containing different types of beta-sheet. Amide I and amide II ROA band patterns observed in beta-sheet poly(L-lysine) are different from those observed in typical beta-sheet proteins and may be characteristic of an extended flat multistranded beta-sheet, which is unlike the more irregular and twisted beta-sheet found in most proteins. However, a reduced isoform of the truncated ovine prion protein PrP(94-233) that is rich in beta-sheet shows amide I and amide II ROA bands similar to those of beta-sheet poly(L-lysine), which suggests that the C-terminal domain of the prion protein is able to support unusually flat beta-sheets. A principal component analysis (PCA) that identifies protein structural types from ROA band patterns provides a useful representation of the structural relationships among the polypeptide and protein states considered in the study.     

Influence of silica gel pretreatment and bonding technique on PAH selectivity of octadecyl bonded phases

Summary The effect of silica gel pretreatment and of different bonding techniques, on the chromatographic properties of octadecyl bonded phases is described. The experiments show that a monomeric octadecyl bonded phase, prepared from silica gel that has not been treated before bonding, has a poor selectivity towards polycyclic aromatic hydrocarbons (PAHs) and shows high adsorption of basic components. Silica gel treatment before the bonding of the monofunctional silane does not give a substantial improvement. Polymeric phases on the other hand show a much better PAH selectivity and a lower adsorptivity towards basic components. Further improvement can be achieved with the polymeric modification if silica gel treatment is carried out before bonding.     

High-throughput cytochrome p450 inhibition assays by ultrafast gradient liquid chromatography with tandem mass spectrometry using monolithic columns

A generic method employing ultrafast liquid chromatography with tandem mass spectrometry (LC/MS/MS) was developed and employed for routine screening of drug candidates for inhibition of five major human cytochrome p450 (CYP) isozymes, CYP3A4, CYP2D6, CYP2C9, CYP2C19, and CYP1A2. The method utilized a monolithic silica rod column to allow fast flow rates to significantly reduce chromatographic run time. The major metabolites of six CYP-specific probe substrates for the five p450 isoforms were monitored and quantified to determine IC(50) values of five drug compounds against each p450 isozyme. Human liver microsomal incubation samples at each test compound concentration were combined and analyzed simultaneously by the LC/MS/MS method. Each pooled sample containing six substrates and an internal standard was separated and detected in only 24 seconds. The combination of ultrafast chromatography and sample pooling techniques has significantly increased sample throughput and shortened assay turnaround time, allowing a large number of compounds to be screened rapidly for potential p450 inhibitory activity, to aid in compound selection and optimization in drug discovery.