An evaluation of force-field treatments of aromatic interactions

Experimental measurements of edge-to-face aromatic interactions have been used to test a series of molecular mechanics force fields. The experimental data were determined for a range of differently substituted aromatic rings using chemical double mutant cycles on hydrogen-bonded zipper complexes. These complexes were truncated for the purposes of the molecular mechanics calculations so that problems of conformational searching and the optimisation of large structures could be avoided. Double-mutant cycles were then carried out in silico using these truncated systems. Comparison of the experimental aromatic interaction energies and the X-ray crystal structures of these truncated complexes with the calculated data show that conventional molecular mechanics force fields (MM2, MM3, AMBER and OPLS) do not perform well. However, the XED force field which explicitly represents electron anisotropy as an expansion of point charges around each atom reproduces the trends in interaction energy and the three-dimensional structures exceedingly well. Collapsing the XED charges onto atom centres or the use of semi-empirical atom-centred charges within the XED force field gives poor results. Thus the success of XED is not related to the methods used to assign the atomic charge distribution but can be directly attributed to the use of off-atom centre charges.     

SELECTIVE INACTIVATION OF MICROSOMAL DRUG METABOLIZING PROTEINS BY VISIBLE LIGHT

Abstract— Rat liver microsomes treated with heterochromatic visible light (λ > 400 nm) and O₂ showed a preferential inactivation of NADPH-cytochrome P₄₅₀ reductase and cytochrome P₄₅₀, proteins involved in drug metabolism. Cytochrome P₄₅₀ destruction correlates with lipid peroxidation; both are oxygen dependent and affected to the same extent by antioxidants and radical scavengers. Under anaerobic conditions. NADPH-cytochrome P₄₅₀ reductase is the only component which is inactivated; this is accompanied by FMN loss and activity can be restored by reconstitution.     

Insights into the Ultrafast Photodissociation Dynamics of Isoprene-Derived Criegee Intermediates

Isoprene is the most abundant nonmethane volatile organic compound emitted into the troposphere by terrestrial vegetation. Reaction with ozone represents an important isoprene removal process from the troposphere and is a well-known source of Criegee intermediates (CIs), which are reactive carbonyl oxides. Three CIs, formaldehyde oxide (CH₂OO), methyl vinyl ketone oxide (MVK-oxide) and methacrolein oxide (MACR-oxide) are formed during isoprene ozonolysis. All three CIs contain strongly absorbing ππ* states, electronic excitation, which leads to dissociation to form aldehyde/ketone + oxygen products. Here, we compare the excited state chemistry of CH₂OO, MVK-oxide and MACR-oxide in order to ascertain how increasing molecular complexity affects their photodynamics. In CH₂OO, vertical excitation to the S₂ state leads to prompt O-O bond fission with a unity quantum yield. Branching into both the O (¹D) + H₂CO (S₀) and O (³P) + H₂CO (T₁) product channels is predicted, with 80% of trajectories dissociating to form the former product pair. Analogous vertical excitation of the lowest energy conformers of MVK-oxide and MACR-oxide also undergoes O-O bond fission to form O + MVK/MACR products—albeit with a nonunity quantum yield. In the latter case, ca. 10% and 25% of trajectories remain as the parent MVK-oxide and MACR-oxide molecules, respectively. Additionally, at most only 5% of the dissociating trajectories form O (³P) + MVK/MACR (T₁) products, with a greater fraction forming O (¹D) + MVK/MACR (S₀) products (cf. CH₂OO). This latter observation coupled with the greater fraction of undissociated trajectories aligns with the bathochromic shift in the electronic absorption of the MACR-oxide and MVK-oxide (cf. CH₂OO). We discuss the implications of the results in a broader context, including those that are relevant to the atmosphere.     

Structural characterisation of the Ce1−xLaxNbO4+δ solid solution series: In-situ high-temperature powder diffraction studies

High-resolution neutron powder diffraction has been utilised to investigate the effect of lanthanum substitution on the structure of cerium niobate, CeNbO_4+δ, as a function of temperature. Two members of the Ce_1−xLa_xNbO_4+δ solid solution series, Ce_0.8La_0.2NbO_4+δ and Ce_0.2La_0.8NbO_4+δ, were examined over a temperature range of 293-923 K under a positive pressure of O₂ (500 mbar). From this data it was found that on increasing lanthanum substitution there was an associated reduction in the temperature of the monoclinic-to-tetragonal phase transition. The data also suggested that increasing lanthanum substitution caused an associated decrease in the excess oxygen content. In addition, high-temperature X-ray powder diffraction data recorded in static air were also examined for four compositions of the Ce_1−xLa_xNbO_4+δ series (x=0.2, 0.4, 0.6 and 0.8). These data corroborated the results of the neutron diffraction experiments and also suggested that there was formation of an intermediate phase, analogous to the CeNbO_4.08 phase of the parent material, during the phase transitions of the x=0.8 and 0.6 compositions.     

Proton spin relaxation and self-diffusion in some ‘isotropic’ nematogens

Angular distributions of reactive scattering arising from a long-lived collision complex dissociating via a transition state that approximates to a linear rotator are predicted for H atom displacement occurring over a distribution of bending angles β with respect to the rotator axis. A conical angular distribution may be generated when only a narrow range of bending angles contributes to the reactive scattering. However, the angular distribution may take on quite different character as the distribution of bending angles becomes broader. Thus, an isotropic angular distribution is generated by a bending angle distribution which follows the spherical polar weighting P(β) ∝ sin β. Forward and backward scattering is generated by bending angle distributions favouring less strongly bent displacement, while sideways scattering is generated by a bending angle distribution favouring more strongly bent displacement. The experimental angular distribution for OH + CO reactive scattering which shows mild forward and backward peaking, corresponds to a range of bending angles for H atom displacement from the H-OCO transition state which is broadened about the nominal preferred direction β = 45° but avoids strongly bent directions with β ≈ 90°.     

Validation of an inductively coupled plasma mass spectrometry (ICP-MS) method for the determination of cerium, strontium, and titanium in ceramic materials used in radiological dispersal devices (RDDs)

This work describes the optimization of a cloud point extraction (CPE) method for casein proteins from cow milk samples. To promote phase separation, polyoxyethylene(8) isooctylphenyl ether (Triton^® X-114) and sodium chloride (NaCl) were used as nonionic surfactant and electrolyte, respectively. Using multivariate studies, four major CPE variables were evaluated: Triton^® X-114 concentration, sample volume, NaCl concentration, and pH. The results show that surfactant concentration and sample volume were the main variable affecting the CPE process, with the following optimized parameters: 1% (w/v) Triton^® X-114 concentration, 50 μL of sample volume, 6% (w/v) NaCl concentration and extractions carried out at pH 7.0. At these conditions, 923 ± 66 and 67 ± 2 μg mL⁻¹ of total protein were found in the surfactant-rich and surfactant-poor phases, respectively. Finally, matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) was then used to evaluate those target proteins (_s1-casein, _s2-casein and β-casein) separation as well as to check the efficiency of the extraction procedure, making a fingerprint of those target proteins possible.     

Site-specific characterisation of densely O-glycosylated mucin-type peptides using electron transfer dissociation ESI-MS/MS

Site-specific characterisation of mucin-type O-linked glycosylation is an analytical challenge due to glycan heterogeneity, lack of glycosylation site consensus sequence and high density of occupied glycosylation sites. Here, we report the use of electron transfer dissociation (ETD) for the site-specific characterisation of densely glycosylated mucin-type O-linked glycopeptides using ESI-IT-MS/MS. Synthetic glycopeptides from the human mucin-1 (MUC-1) tandem repeat region containing a range of O-linked, tumour-associated carbohydrate antigens, namely Tn, T and sialyl T, with different glycosylation site occupancies and an increasing number of tandem repeats were studied. In addition, a glycopeptide from the anti-freeze glycoprotein of Antarctic and Arctic notothenoids, bearing four O-linked, per-acetylated T antigens was characterised. ETD MS/MS of infused or capillary LC-separated glycopeptides provided broad peptide sequence coverage (c/z·-type fragment ions) with intact glycans still attached to the Ser/Thr residues. Thus, the glycosylation sites were unambiguously determined, while simultaneously obtaining information about the attached glycan mass and peptide identity. Highly sialylated O-glycopeptides showed less efficient peptide fragmentation, but some sequence and glycosylation site information was still obtained. This study demonstrates the capabilities of ETD MS/MS for site-specific characterisation of mucin-type glycopeptides containing high-density O-linked glycan clusters, using accessible and relative low-resolution/low-mass accuracy IT MS instrumentation.