Molecular Compton profiles from SCF-MO wavefunctions

This paper considers the dependence of Compton profiles calculated from molecular wavefunctions on the atomic basis set used. For fluoromethane there is no significant difference between profiles calculated with a Slater minimal basis set and with STO-3G, STO-4G and STO-5G sets. A Slater double-zeta set and Dunning's gaussian basis give essentially the same profile and the addition of polarization functions to the Dunning basis has little effect. For methanol, methylamine and ethane there is a significant difference between the STO-3G profiles and those calculated from extended basis sets but again the addition of polarization functions has little effect. The use of Dunning's basis would seem to be adequate for Compton profile calculations for molecules of medium size. As one goes along the series from ethane to fluoromethane the Compton profile becomes broader.     

Semi-empirical π-electron calculations of proton,nitrogen and fluorine hyperfine-coupling constants

The application of the parameterization scheme of Beveridge and Hinze for π-electron molecular orbital calculations to spin density calculations is examined for a series of radicals including anions derived from pyridine derivatives, substituted styrenes, aromatic carboxylic acids, benzonitriles and fluoronitrobenzene derivatives and azabenzyl and fluorobenzyl radicals. The method correlates proton hyperfine coupling constants satisfactorily and gives a reasonable correlation of nitrogen coupling constants. The application to fluorine couplings is less satisfactory.     

Synthesis of (±)-solanapyrones A and B

In this paper we report the development of a stereoselective IMDA approach to the phytotoxic polyketides (±)-solanapyrones A and B. The stereoselectivity of the key IMDA cycloaddition was optimized by investigating a range of 2,8,10-dodecatrienoic acid derivatives. This established that use of the Weinreb amide led to the desired exo-selectivity and also facilitated construction of the pyrone moiety. A novel approach to the installation of the C-3 formyl group in solanapyrone A is also described.     

Experimental and theoretical compton profiles of CIS and trans-2-butene

The Compton profiles of the geometric isomers cis and trans-2-butne (C₄H₈) have been measured in the gas phase using 59.54 keV gamma rays. The measured profiles are compared with profiles derived from SCF and LMO models. No significant differences between the measured profiles are observed. However, comparison with the theoretical profiles shows that in both cases the measured profiles are broader, having J(0) values between 1 and 5% lower than those predicted by theory.     

Focal length variability and protein leakage as tools for measuring photooxidative damage to the lens

Hypericin is the ingredient used to standardize the popular over-the-counter antidepressant medication St. John's Wort. Because hypericin readily produces singlet oxygen and other excited state intermediates, it is a very efficient phototoxic agent in the eye that can potentially induce the development of the cataract photooxidative mechanism. Hypericin absorbs in the UV and visible ranges, binds to the lens crystallins (alpha, beta and gamma) and damages these proteins through a photooxidative mechanism. Effects were measured previously using fluorescence, UV and mass spectrometry. We report here two additional methods to monitor lens damage: (1) measuring focal length variability using a ScanTox instrument and (2) measuring protein leakage from the damaged lens. Because nonenzymic glycation results in free radical production, we chose to use elevated glucose concentrations as a convenient model for studying oxidative stress. To compare and contrast photooxidative damage against oxidative damage to the lens, we also measured the focal length variability and protein leakage induced by the presence of elevated glucose concentrations. We found that the total accumulated protein leakage was positively correlated (r = 0.9) with variability in focal length. Lenses treated with hypericin and irradiated with UVB had an increase in focal length variability as compared with the lenses that were only UVB-irradiated. Lenses without UVB irradiation had much lower focal length variability than irradiated lenses. For non-hypericin-treated lenses, UVB-irradiated lenses had a larger variability (4.58 mm) than the unirradiated lenses (1.78 mm). The lenses incubated in elevated glucose concentrations had a focal length variability (3.23 mm) equivalent to that of the unirradiated hypericin-treated lenses (3.54 mm). We conclude that photooxidative damage by hypericin results in changes in the optical properties of the lens, protein leakage and finally cataract formation. In contrast to this, high concentrations of glucose induced protein leakage but not changes in optical properties or the opacity associated with a cataract. This work provides further evidence that people should protect their eyes from intense sunlight when taking St. John's Wort.     

Self-assembly of two-component peptidic dendrimers: dendritic effects on gel-phase materials

The self-assembly of diaminododecane solubilised by different dendritic peptides, possessing increasing levels of dendritic branching, was investigated. The dendritic peptides were based on l-lysine building blocks and were of first, second and third generation, containing one, three and seven amino acid repeat units respectively. By applying these structures as potential gelator units, the dendritic effect on gelation was investigated. The degree of structuring was modulated, with the dendritic peptide controlling the aggregate morphology and the ability of the self-assembled state to manifest itself macroscopically as gelation. First generation gelator units (G1) did not induce macroscopic gelation with diaminododecane under any conditions, whilst those self-assemblies based on second (G2) and third (G3) generation branches did form gel-phase materials. Furthermore, gel-phase materials based on G2 exhibited optimum gelation behaviour compared to those based on G3(in terms of the thermal strength of the materials). Circular dichroism showed that the dendritic effect, programmed in at the molecular level, is directly related to the degree of chiral organisation within the self-assembled state. The dendritic generation of the peptide controls the pattern of amide-amide hydrogen bonding in terms of binding strength and alignment as determined using NMR methods. The mode of self-assembly can be qualitatively rationalised in terms of an attractive enthalpic interaction (i.e., amide-amide hydrogen bonding), a repulsive interaction (i.e., steric interactions between dendritic peptides) and an entropic term related to the hierarchical organisation of the gelator building blocks. It is argued that the balance between these factors determines the nature of the dendritic effect.     

New functionalised silicas for highly selective cation exchange SPE purification in medicinal chemistry

Functionalised silicas 2 and 3 are effective for the cation exchange SPE purification of basic molecules containing acid-sensitive functionalities, the selective separations of mixtures of basic compounds and accelerated reaction work-ups/product isolations.     

A protecting group free synthesis of (+/-)-neostenine via the [5 + 2] photocycloaddition of maleimides

A concise, linear synthesis of the Stemona alkaloid (+/-)-neostenine is reported. Key features include an organocopper-mediated bislactone C2-desymmetrization for the stereoselective construction of the cyclohexane-lactone C,D-rings. The assembly of the fused pyrrolo[1,2-a]azepine core was achieved by application of a [5 + 2] maleimide photocycloaddition. A custom FEP flow reactor was used to successfully overcome the scale limitations imposed by a classical immersion well batch reactor. The synthesis was completed in 14 steps from furan, in 9.5% overall yield, without the use of any protecting groups.     

Tunable Supramolecular Gel Properties by Varying Thermal History

The possibility of using differential pre-heating prior to supramolecular gelation to control the balance between hydrogen-bonding and aromatic stacking interactions in supramolecular gels and obtain consequent systematic regulation of structure and properties is demonstrated. Using a model aromatic peptide amphiphile, Fmoc-tyrosyl-leucine (Fmoc-YL) and a combination of fluorescence, infrared, circular dichroism and NMR spectroscopy, it is shown that the balance of these interactions can be adjusted by temporary exposure to elevated temperatures in the range 313–365 K, followed by supramolecular locking in the gel state by cooling to room temperature. Distinct regimes can be identified regarding the balance between H-bonding and aromatic stacking interactions, with a transition point at 333 K. Consequently, gels can be obtained with customizable properties, including supramolecular chirality and gel stiffness. The differential supramolecular structures also result in changes in proteolytic stability, highlighting the possibility of obtaining a range of supramolecular architectures from a single molecular structure by simply controlling the pre-assembly temperature.