Humphrey A. Moynihan

Selective Nanomolar Detection of Dopamine Using a Boron-Doped Diamond Electrode Modified with an Electropolymerized Sulfobutylether-β-cyclodextrin-Doped Poly(N-acetyltyramine) and Polypyrrole Composite Film

N-acetyltyramine was synthesized and electropolymerized together with a negatively charged sulfobutylether-beta-cyclodextrin on a boron-doped diamond (BDD) electrode followed by the electropolymerization of pyrrole to form a stable and permselective film for selective dopamine detection. The selectivity and sensitivity of the formed layer-by-layer film was governed by the sequence of deposition and the applied potential. Raman results showed a decrease in the peak intensity at 1329 cm(-1) (sp(3)), the main feature of BDD, upon each electrodeposition step. Such a decrease was correlated well with the change of the charge-transfer resistance derived from impedance data, i.e., reflecting the formation of the layer-by-layer film. The polycrystalline BDD surface became more even with lower surface roughness as revealed by scanning electron and atomic force microscopy. The modified BDD electrode exhibited rapid response to dopamine within 1.5-2 s and a low detection limit of 4-5 nM with excellent reproducibility. Electroactive interferences caused by 4-dihydroxyphenylalanine, 3,4-dihydroxyphenylacetic acid, ascorbic acid, and uric acid were completely eliminated, whereas the signal response of epinephrine and norepinephrine was significantly suppressed by the permselective film.

Spectroscopic characterisation of the monoclinic and orthorhombic forms of paracetamol.

The metastable orthorhombic form of paracetamol was prepared from the melt of the commercially available monoclinic form. Distinct differences were observed in the infrared spectra of both forms, especially in the region 1260-1225 cm(-1), in which is observed three strong absorptions of approximately equal intensity in spectra of the monoclinic form, and two absorptions, one strong and one medium, in spectra of the orthorhombic form. No diagnostically useful differences were observed in the Raman spectra of the two forms. A 13C CP/MAS solid-state NMR spectrum of the monoclinic form and a spectrum of a mixture of forms prepared from a melt were obtained. A spectrum of the orthorhombic form was obtained from these spectra by difference spectroscopy. The spectra show that the carbons in the paracetamol molecules are all in unique chemical environments in both crystalline forms, and that clear well-resolved differences in the chemical shifts of particular carbons in both forms can be observed.

Evaluation of the Bruker SMART X2S: crystallography for the nonspecialist?

An evaluation of the Bruker SMART X2S for the collection of crystallographic diffraction data, structure solution and refinement is carried out with a variety of materials with different electron densities, presenting some of the successes and challenges of automation in chemical crystallography.

Preparation of some novel S-nitroso compounds as potential slow-release agents of nitric oxide in vivo

The optimum conditions for the preparation of N-acetyl-S-nitrosopenicillamine (SNAP)3 were determined and applied to the synthesis of the corresponding N-formyl compound 7. The nitrosation of penicillamine dipeptides was investigated and bis-thionitroso compounds 13, 18, 26 and 27 were isolated. S, S′-Dinitroso dithiol 13 showed biological activity akin to that of glyceryl trinitrate in decreasing systemic arterial blood pressure in anaesthetized rats and rabbits. Concomitant inhibition of collagen- or ADP-induced platelet aggregation was observed.

Monomeric and polymeric derivatives of 5-aminoisophthalic acid as selective inhibitors of the β-polymorph of L-glutamic acid

The effect of 5-aminoisophthalic acid, 3, 5-acetamidoisophthalic acid, 4, a polymer-bound 5-amidoisophthalic acid, 5, and a cross-linked analogue of the latter, 5*, on crystallisations of L-glutamic acid from water were examined. The metastable α-polymorph was crystallised in the presence of additive at minimum loadings of 10, 5 and 1% w/w for 3, 4 and 5, respectively. The cross-linked polymer 5* was less effective compared to the parent polymer 5.

Effect of the steric demand and hydrogen bonding capability of additives on the crystal polymorphism of sulfathiazole

The N-acylsulfathiazole deriviatives 2, 3 and 4, the polymeric N-acylsulfathiazole 6 and the phenolic sulfathiazole analogue 7 were prepared and were found to promote crystallization of form I sulfathiazole from water with inhibition of forms II, III and IV; suggesting that the mode of action of the additives may involve other factors in addition to compatibility with the hydrogen-bonding structure of the various forms.

Synthesis and biological activity of the novel nitric oxide synthase inhibitor Nω′-hydroxy-Nω-methyl-L-arginine

N ω′ Hydroxy-Nω-methyl-L-arginine has been synthesised in eight steps from Nδ-(benzyloxycarbonyl)-L-ornithine and has been found to inhibit the biosynthesis of nitric oxide.

Telescoped Approach to Aryl Hydroxymethylation in the Synthesis of a Key Pharmaceutical Intermediate

An efficient synthetic approach leading to introduction of the hydroxymethyl group to an aryl moiety via combination of the Bouveault formylation and hydride reduction has been optimized using a rational, mechanistic-based approach. This approach enabled telescoping of the two steps into a single efficient process, readily amenable to scaleup.

Preparation and characterisation of solid state forms of paracetamol-O-glucuronide

The synthesis and crystallisation of the pharmaceutically important metabolite, paracetamol-O-glucuronide, is described. Hydrated and anhydrous forms of the target molecule have been characterised by PXRD, DSC and TGA. In addition, a methanol solvate has been analysed, including single crystal analysis, which represents the first structure solution for this system.

Radiolabelling studies of free radical reactions using muonium (the second hydrogen radioisotope): evidence of a direct antioxidant role for vitamin k in repair of oxidative damage to lipids

Following the recent suggestion that oxidative damage to lipids might involve the formation of C‐2 glyceryl radicals, in addition to main‐chain allylic radicals, which are generally thought important, we studied the kinetics of potential ‘repair’ reactions by vitamin E and vitamin K1 (which are lipophilic and tend to locate in cell membranes) with 1,1,2‐trimethylallyl and 1‐acetoxyprop‐2‐yl radicals as models of, respectively, main‐chain and glyceryl‐type radicals. The second‐order rate constants for the reaction between trimethylallyl radicals and vitamin E and vitamin K1 are 9.38 × 106 and 3.54 × 108 l mol−1 s−1 and those between 1‐acetoxyprop‐2‐yl radicals and vitamin E and vitamin K1 are 1.76 × 108 and 2.03 × 106 l mol−1 s−1, respectively. The results suggest that direct scavenging of glyceryl radicals by vitamin E should be an efficient process, and of main‐chain allylic radicals fairly so. Additionally, it appears that vitamin K1 can act directly as a ‘radical repair agent,’ given its relatively high reactivity with allylic radicals (four times faster than with vitamin E), so prior reduction to the quinol form may be unnecessary. Copyright