Photoelectron spectroscopic studies of some nitrosyl and nitryl halides and nitric acid

The He(I) photoelectron spectra of the compounds FNO, ClNO, BrNO, FNO₂ and ClNO₂ have been recorded on an instrument specifically designed to study reactive and short-lived species. The spectrum of HNO₃ (isoelectronic with the nitryl halides) is included for comparison. The spectra of the nitrosyl halides are interpreted by reference to SCF-MO calculations, by correlation with the known levels of NO, and by consideration of the electronic effect of the halide (X) substituent. The resulting assignments are in accord with weak bonding between the X and NO moieties. The assignments for the nitryl halides and nitric acid are assisted by correlation with the known levels of NO₂, by consideration of the electronic effects of the X substituent, by an analysis of vibrational structure, and by CNDO type MO calculations. On the basis of our assignments for these latter molecules we propose a reassignment of the photoelectron spectrum of CH₃NO₂.     

Pyrolysis of trimethyl hexahydro-s-triazines. The photoelectron spectra of N-methylmethylenimine,CH2NCH3, and C-methylmethylen

The unstable methylated imines CH₂NCH₃ and CH₃CHNH have been produced by low-pressure pyrolysis of the appropriate triazine     

Studies in the growth of ZnSe on GaAs(001)

This paper reports a study of the molecular beam epitaxial (MBE) growth of ZnSe on GaAs substrates using elemental sources. Growth rates of ZnSe as a function of Se:Zn flux ratio for constant Zn flux were determined over a wider range of values than previously reported. Careful measurements of atomic fluxes and sample thickness lead to a determination of the sticking coefficients of Zn and Se which are at variance with many previously reported values. The temperature dependence of the sticking coefficients of Zn and Se has been measured carefully and provides evidence for a greater desorption of Zn from the growing surface than previously thought, an effect which persists at low growth temperatures. Measurements at high flux ratios support the use of a precursor model to describe MBE growth of ZnSe on GaAs substrates.     

Calculation of the vertical ionization potentials of XBO and XBS molecules (X = H,F and Cl) by perturbation corrections to Koopmans' theorem

Vertical ionization potentials of the linear triatomic molecules, HBO, FBO, ClBO, HBS, FBS, and ClBS are computed by applying Rayleigh-Schrödinger perturbation corrections to Koopmans' theorem. Comparison with the experimental data for the XBS molecules gives us confidence that our theoretical values for the ionization potentials will greatly assist in the identification of the, as yet, unobserved photoelectron spectra of the XBO species.     

A comparison of the HAM/3 semiempirical method with the MINDO/3 and CNDO/2 semiempirical methods and the GAUSSIAN 70 ab initio method; a comparison of ionization potential calculations and experimental photoelectron spectra of some imines and diimines

Molecular orbital calculations have been performed on eight molecules (containing 16–80 electrons) using the GAUSSIAN 70, MINDO/3, CNDO/2 and HAM/3 programs. The molecules contain nitrogen—nitrogen (diimines) or carbon—nitrogen (imines) double bonds. A comparison of the results of each method with experimental photoelectron data and an analysis of the cost effectiveness indicates that the HAM/3 method will prove a useful tool for photoelectron spectroscopists.     

The small molecule tool (S)-(-)-blebbistatin: novel insights of relevance to myosin inhibitor design

The small molecule blebbistatin is now a front line tool in the study of myosin function. Chemical modification of the tricyclic core of blebbistatin could deliver the next generation of myosin inhibitors and to help address this we report here on the impact of structural changes in the methyl-substituted aromatic ring of blebbistatin on its biological activity. Chemical methods for the preparation of isomeric methyl-containing analogues are reported and a series of co-crystal structures are used to rationalise the observed variations in their biological activity. These studies further support the view that the previously identified binding mode of blebbistatin to Dictyostelium discoideum myosin II is of relevance to its mode of action. A discussion of the role that these observations have on planning the synthesis of focused libraries of blebbistatin analogues is also provided including an assessment of possibilities by computational methods. These studies are ultimately directed at the development of novel myosin inhibitors with improved affinity and different selectivity profiles from blebbistatin itself.     

Impurity identification and determination for the peptide hormone angiotensin I by liquid chromatography–high-resolution tandem mass spectrometry and the metrological impact on value assignments by amino acid analysis

It is common practice to quantify the mass concentration of a peptide solution through quantitative determination of selected chemically stable amino acids produced following complete hydrolysis of the parent peptide. This is because there is generally an insufficient quantity of material available to allow for the obvious alternative of a direct purity analysis characterization of the parent peptide, and the subsequent constitution of a calibration solution. However, selected accurately characterized pure peptide reference materials are required to establish reference points for the dissemination of metrologically traceable measurements and to develop reference measurement systems for laboratory medicine. In principle, purity assignment of a peptide can be performed by using the so-called mass balance approach, by employing a range of analytical techniques to obtain an estimate of the mass fraction content of all impurities present in the intact peptide, and by utilizing the difference from the theoretical limit value to assign the mass fraction content of the main peptide. Liquid chromatography–high-resolution tandem mass spectrometry (LC-hrMS/MS) is a key technique for the detection, identification, and determination of structurally related impurities present in a peptide material, and experiments characterizing the model peptide hormone angiotensin I (ANG I) are described in the present work. Degradation products that were generated from ANG I after storage at elevated temperatures were screened. The formation of peptide fragments such as ANG II or ANG III was determined by comparison of measured mass values with calculated mass values. The use of a data-dependent acquisition technique enabled the detection and structural characterization of ANG II and other peptide fragments as major impurities in the same LC-hrMS/MS analysis run. Subsequent quantification using external calibration allowed the mass fraction of the major impurities in a candidate reference material to be estimated as 10.4 mg/g. Failure to correct for these impurities would lead to a 1 % error in the determination of the concentration of the peptide in solution by amino acid analysis techniques.

Synthesis and chemical characterisation of target identification reagents based on an inhibitor of human cell invasion by the parasite Toxoplasma gondii

The use of phenotype-based screens as an approach for identifying novel small molecule tools is reliant on successful protein target identification strategies. Here we report on the synthesis and chemical characterisation of a novel reagent for protein target identification based on a small molecule inhibitor of human cell invasion by the parasite Toxoplasma gondii. A detailed (1)H NMR study and biological testing confirmed that incorporation of an amino-containing functional group into the aryl ring of this inhibitor was possible without loss of biological activity. Interesting chemical reactivity differences were identified resulting from incorporation of the new substituent. The amine functionality was then used to prepare a biotinylated reagent that is central to our current protein target identification studies with this inhibitor.     

Synthetic studies related to diketopyrrolopyrrole (DPP) pigments. Part 3: Syntheses of tri- and tetra-aryl DPPs

Novel synthetic methodologies leading towards 2,3,5-triaryl- and 2,3,5,6-tetraaryl-2,5-dihydropyrrolo[3,4-c]pyrrole-1,4-diones (tri- and tetra-aryl-DPPs) and their derivatives have been investigated. Direct arylation of 3,6-diphenyl-DPP was possible using 1-fluoro-2,4-dinitrobenzene. Acylation of ethyl 2-aryl-4,5-dihydro-5-oxopyrrole-3-carboxylates with N-arylbenzimidoyl chlorides in the presence of a strong base gives the novel 2,3,6-triaryl-DPPs together with the corresponding uncyclised enamines. A new and simple method for the synthesis of ethyl 1,2-diaryl-4,5-dihydro-5-oxopyrrole-3-carboxylates has led to an alternative route to triaryl-DPPs via reaction with benzonitrile under basic conditions, and combination of this with the benzimidoyl chloride methodology has enabled the synthesis of variously substituted 2,3,5,6-tetraphenyl-DPPs.     

A novel pycnometer for density measurements of liquids at elevated temperatures

A novel pycnometer has been designed for density measurements at elevated temperatures (up to T=473.15 K). The pycnometer consists of a stainless steel cell connected to a small-bore tube. The main feature of the design includes a bored-through expansion fitting, which allows the overflow due to thermal expansion from the cell (via the small-bore tube) to collect in a pressurized line. Densities were measured for pure 1-butanol, pure n-heptane, and for mixtures {x_bCH₃(CH₂)₃OH + (1−x_b)CH₃(CH₂)₅CH₃}, from T=316.85 K to T=458.15 K, at a pressure of 4.93 MPa. Excess volumes were calculated and reported for these mixtures.