Biochemical synthesis, purification and preliminary pharmacological evaluation of normorphine-3-glucuronide

Normorphine was synthesised from morphine by thermal decomposition of an N-alpha-chloroethylchloroformate adduct, and purified (> 98% purity) using semipreparative HPLC with ultraviolet detection. Normorphine-3-glucuronide (NM3G) was biochemically synthesised using the substrate normorphine, uridine diphosphoglucuronic acid and Sprague-Dawley rat liver microsomes in a 75% yield (relative to normorphine base). The synthesised NM3G was purified by precipitation and washing with acetonitrile. Determinations of purity using HPLC with electrochemical and ultraviolet detection confirmed that the NM3G produced was of high (> 99%) purity. Mass spectrometry, fourier transform infrared spectrophotometry and nuclear magnetic resonance spectrometry confirmed the structure, especially placement of the glucuronide moiety at the 3-phenolic position and not at the 17-nitrogen. Administration of NM3G by the intracerebroventricular (icy) route to rats in doses of 2.5 and 7.5 mu g resulted in the development of central nervous system (CNS) excitatory behavioural effects including myoclonus, chewing, wet-dog shakes, ataxia and explosive motor behaviour. At an icy dose of 7.5 mu g, NM3G also induced short periods of tonic-clonic convulsive activity. Thus, NM3G elicits CNS excitation following supraspinal administration in a manner analogous to morphine-3-glucuronide (M3G), the major metabolite of morphine (1). Further studies are required to determine whether NM3G attenuates morphine-induced antinociception in se similar manner to M3G.

Conformational dynamics of thyroid hormones by variable temperature nuclear magnetic resonance: The role of side chain rotations and cisoid/transoid interconversions

H-1 NMR spectra of the thyroid hormone thyroxine recorded at low temperature and high field show splitting into two peaks of the resonance due to the H2,6 protons of the inner (tyrosyl) ring. A single resonance is observed in 600 MHz spectra at temperatures above 185 K. An analysis of the line shape as a function of temperature shows that the coalescence phenomenon is due to an exchange process with a barrier of 37 kJ mol(-1). This is identical to the barrier for coalescence of the H2',6' protons of the outer (phenolic) ring reported previously for the thyroid hormones and their analogues. It is proposed that the separate peaks at low temperature are due to resonances for H2,6 in cisoid and transoid conformers which are populated in approximately equal populations. These two peaks are averaged resonances for the individual H2 and H6 protons. Conversion of cisoid to transoid forms can occur via rotation of either the alanyl side chain or the outer ring, from one face of the inner ring to the other. It is proposed that the latter process is the one responsible for the observed coalescence phenomenon. The barrier to rotation of the alanyl side chain is greater than or equal to 37 kJ mol(-1), which is significantly larger than has previously been reported for Csp(2)-Csp(3) bonds in other Ph-CH2-X systems. The recent crystal structure of a hormone agonist bound to the ligand-binding domain of the rat thyroid hormone receptor (Wagner et al. Nature 1995, 378, 690-697) shows the transoid form to be the bound conformation. The significant energy barrier to cisoid/transoid interconversion determined in the current study combined with the tight fit of the hormone to its receptor suggests that interconversion between the forms cannot occur at the receptor site but that selection for the preferred bound form occurs from the 50% population of the transoid form in solution.

The chemistry of novolac resins .3. C-13 and N-15 nmr studies of curing with hexamethylenetetramine

The reactions between novolac resins and hexamethylenetetramine (HMTA) which occur on curing have been studied by C-13 and N-15 high-resolution n.m.r. in both solution and the solid state. Strong evidence for the existence of many curing intermediates is obtained. New curing intermediates are reported along with experimental data to support previously postulated intermediates. The initial curing reactions between novolac and HMTA produce various substituted benzoxazines and benzylamines. Thermal decomposition/oxidation and further reactions of these initial intermediates generate methylene linkages between phenolic rings for chain extension and cross-linking. Among the three kinds of methylene linkages, the para-para methylene linkages are formed at relatively lower temperatures. Various imine, amide and imide side-products also concurrently appear during the process. The initial amount of HMTA plays a critical role in the curing reactivity and chemical structures of the cured resins. The lower the amount of HMTA, the lower the temperature at which curing occurs, and the lower the amount of the nitrogen-containing side-products in the finally cured resins. The ortho-linked intermediates are relatively stable, and can remain in the cured resins up to higher temperatures. The study provides an extensive description of the curing reactions of novolac resins. (C) 1997 Elsevier Science Ltd.

The biomimetic synthesis of marine epoxylipids: Bisepoxides to tetrahydrofurans

The biomimetic synthesis of novel lipids 1, 2, 8 and 10 obtained from the southern Australian marine brown alga Notheia anomala has been achieved, and features the acid mediated conversion of methylene interrupted bisepoxides to tetrahydrofurans. (C) 1997 Elsevier Science Ltd.

Slagging propensities of blended coals

This paper presents the experimental results on the slagging propensity of three pairs of blended coals tested in the Australian Coal Industry Research Laboratory furnace. The results showed that none of the coals or blends produced strongly molten deposit. At worst, the deposits contained some moderately sintered material. Most of the blends have (slightly) worse slagging behavior than the component coals. In order to rank the slagging propensity numerically, we defined the minimum heat flux ratio and total heat flux ratio based on the heat flux profiles. They are better in ranking the slagging propensities than other measures such as the build-up rate and visual physical characteristics. The Fe2O3/CaO molar ratio correlates the slagging propensity for five coals and six blends of this study. The worst slagging occurs when the ratio approaches 1.0. This ratio provides explanation of why the blends had worse slagging than the component coals for the pairs of blends: A-B and C-D. However, we note that there are causes of slagging other than the Fe2O3/CaO molar ratio. (C) 2001 Elsevier Science Ltd. All rights reserved.

Techniques to determine ignition, flame stability and burnout of blended coals in p.f. power station boilers

The blending of coals has become popular to improve the performance of coals, to meet specifications of power plants and, to reduce the cost of coals, This article reviews the results and provides new information on ignition, flame stability, and carbon burnout studies of blended coals. The reviewed studies were conducted in laboratory-, pilot-, and full-scale facilities. The new information was taken in pilot-scale studies. The results generally show that blending a high-volatile coal with a low-volatile coal or anthracite can improve the ignition, flame stability and burnout of the blends. This paper discusses two general methods to predict the performance of blended coals: (1) experiment; and (2) indices. Laboratory- and pilot-scale tests, at least, provide a relative ranking of the combustion performance of coal/blends in power station boilers. Several indices, volatile matter content, heating value and a maceral index, can be used to predict the relative ranking of ignitability and flame stability of coals and blends. The maceral index, fuel ratio, and vitrinite reflectance can also be used to predict the absolute carbon burnout of coal and blends within limits. (C) 2000 Elsevier Science Ltd. All rights reserved.

A proposed maceral index to predict combustion behavior of coal

To predict the combustion performance in pulverized coal-fired boilers, this paper examines existing indices and develops a maceral index (MI). These indices were compared with the data of 68 coals and blends in a range of the mean vitrinite reflectance from 0.25 to 1.63. The results showed that the fuel ratio and the mean vitrinite reflectance could qualitatively indicate the burnout of the coals and blends. The new MI, MI = L + V/R-2/I-1.25(HV/30)(2.5), provides a useful correlation for the burnout of the coals and blends. The correlation coefficient (I-) is 0.982 for the EER data, and 0.808 for the ACIRL data. The MI also has potential to correlate ignition and flame stability of the coals and blends. The MI predicts the burnout better than the other indices. (C) 2001 Elsevier Science Ltd. All rights reserved.

Liquid phase sintering of aluminium alloys

The principle that alloys are designed to accommodate the manufacture of goods made from them as much as the properties required of them in service has not been widely applied to pressed and sintered P/M aluminium alloys. Most commercial alloys made from mixed elemental blends are identical to standard wrought alloys. Alternatively, alloys can be designed systematically using the phase diagram characteristics of ideal liquid phase sintering systems. This requires consideration of the solubilities of the alloying elements in aluminium, the melting points of the elements, the eutectics they form with aluminium and the nature of the liquid phase. The relative diffusivities are also important. Here we show that Al-Sn, which closely follows these ideal characteristics, has a much stronger sintering response than either Al-Cu or Al-Zn, both of which have at least one non-ideal characteristic. (C) 2001 Elsevier Science B.V. All rights reserved.

Dental erosion patterns from intrinsic acid regurgitation and vomiting

Background: The distribution of lesions from dental erosion due to intrinsic acid regurgitation and vomiting may be different from patterns of dental erosion due to extrinsic acids. To date studies have failed to validate this assumption. This study described the sites and nature of lesions from dental erosion in cases of intrinsic acid regurgitation, and compared them with the distribution of lesions occurring in age and sex matched controls, whose lesions are due to extrinsic acids. Methods: The University of Queensland tooth wear clinic patients were screened to select 30 cases, 21 self-identified bulimics and nine medically diagnosed chronic gastric acid regurgitators, and 30 controls. Epoxy resin models of the subjects' dentition were examined under stereoscopic light microscope at magnification 16 to 40. The patterns and sites of tooth wear were recorded for teeth representative of 20 tooth sites in every subject. Results: While the incisal edges of maxillary and mandibular anterior teeth of acid regurgitators were more frequently affected by erosion, incisal attrition was more common on controls' teeth. Cervical lesions were more commonly found in association with incisal attrition in the controls, and in association with incisal erosion in the cases. In 10 per cent of sites in case subjects, cervical lesions associated with incisal erosion were found on the lingual aspects of their mandibular incisors, canines and premolars. These lesions were almost exclusive to the case subjects. Conclusions: These results validate that lingual cervical lesions associated with incisal erosion on the mandibular anterior teeth are strong discriminators between tooth wear in patients with bulimia nervosa or chronic gastro-oesophageal reflux and those whose dental erosion is due to extrinsic acids.

Sites of dental erosion are saliva-dependent

Acid demineralization of teeth causes occlusal erosion and attrition and associated non-carious cervical lesions at sites relatively unprotected by saliva. Associations of occlusal pathology and cervical lesions were looked for in 450 patients with toothwear, and 174 subjects with cervical lesions were identified. Associations of occlusal attrition, or erosion, or no wear, with cervical lesions at 72 buccal and lingual sites were recorded from epoxy resin replicas of the subjects' dentitions (3241 teeth). Criteria used to discriminate occlusal erosion from attrition; and shallow from grooved and wedge-shaped cervical lesions were delineated by scanning electron microscopy (SEM). In the absence of occlusal pathology, cervical lesions were very rare (