Adrian V. George

Carbon isotope ratio (δ13C) values of urinary steroids for doping control in sport

The detection of steroids originating from synthetic precursors in relation to their chemically identical natural analogues has proven to be a significant challenge for doping control laboratories accredited by the World Anti-Doping Agency (WADA). Endogenous steroid abuse may be confirmed by utilising the atomic specificity of gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS) that enables the precise measurement of differences in stable isotope ratios that arise as a result of fractionation patterns inherent in the source of steroids. A comprehensive carbon isotope ratio (delta(13)C) profiling study (n=1262) of urinary ketosteroids is reported that demonstrates the inter-individual variation that can be expected from factors such as diet, ethnicity, gender and age within and between different populations (13 countries). This delta(13)C distribution is shown by principal component analysis (PCA) to provide a statistical comparison to delta(13)C values observed following administration of testosterone enanthate. A limited collection of steroid diol data (n=100; consisting of three countries) is also presented with comparison to delta(13)C values of excreted testosterone to validate criteria for WADA accredited laboratories to prove doping offences.

Advancing chemistry by enhancing learning in the laboratory (ACELL): A model for providing professional and personal development and facilitating improved student laboratory learning outcomes

The Advancing Chemistry by Enhancing Learning in the Laboratory (ACELL) project aims to improve the quality of learning in undergraduate laboratories through two interlocking mechanisms. The first is to build a database of experiments that are both chemically and educationally sound by testing them in a third-party laboratory, usually through an ACELL workshop involving both academic staff and students, to ensure that they work. The second mechanism provides personal and professional development for staff and students through a workshop process, and reinforced through on-going engagement with the ACELL community via the project website and experiment assessment and evaluation. The ACELL workshops include discussion of educational issues, both in abstract (through discussing laboratory learning in general) and concrete (through debriefing of each experiment tested) terms. This paper discusses the design of the ACELL project, and illustrates some of the successes of the staff and student personal and professional development aims. [Chem. Educ. Res. Pract., 2007, 8 (2), 232-254]

The detection of androstenedione abuse in sport: a mass spectrometry strategy to identify the 4-hydroxyandrostenedione metabolite.

Studies have shown that the administration of androstenedione (ADIONE) significantly increases the urinary ratio of testosterone glucuronide to epitestosterone glucuronide (T/E) - measured by gas chromatography/mass spectrometry (GC/MS) - in subjects with a normal ( approximately 1) or naturally high (>1) initial values. However, the urinary T/E ratio has been shown not to increase in subjects with naturally low (<1) initial values. Such cases then rely on the detection of C(6)-hydroxylated metabolites shown to be indicative of ADIONE administration. While these markers may be measured in the routine GC/MS steroid profile, their relatively low urinary excretion limits the use of gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS) to specifically confirm ADIONE administration based on depleted (13)C content. A mass spectrometry strategy was used in this study to identify metabolites of ADIONE with the potential to provide compound-specific detection. C(4)-hydroxylation was subsequently shown to be a major metabolic pathway following ADIONE administration, thereby resulting in urinary excretion of 4-hydroxyandrostenedione (4OH-ADIONE). Complementary analysis of 4OH-ADIONE by GC/MS and GC/C/IRMS was used to confirm ADIONE administration.

Electrochemistry of acetylide complexes of iron

Abstract The synthesis of a symmetrical acetylide-bridged, diiron(II) complex, ClFe(DMPE) 2 (CCC 6 H 4 CC)-(DMPE) 2 FeCl ( 1 ) (DMPE = bis(dimethylphosphine)ethane) is reported. Electrochemistry and EPR spectroscopy are used to examine the redox properties of 1 as well as the mononuclear iron(II) complexes Fe(DMPE) 2 Cl 2 ( 2 ), ClFe(DMPE) 2 (CCPh) ( 3 ), and Fe(DMPE) 2 (CCPh) 2 ( 4 ). Evidence for the corresponding iron(III) and iron(IV) species is provided. The structural rearrangements accompanying redox changes are discussed on the basis of the electrochemical characteristics. The electrochemical behaviour of the bridged diiron species 1 provides evidence that the two metal centres interact electronically.

Development of criteria for the detection of adrenosterone administration by gas chromatography‐mass spectrometry and gas chromatography‐combustion‐isotope ratio mass spectrometry for doping control

Adrenosterone (androst-4-ene-3,11,17-trione, 11-oxoandrostenedione) is an endogenous steroid hormone that has been promoted as a dietary supplement capable of reducing body fat and increasing muscle mass. It is proposed that adrenosterone may function as an inhibitor of the 11beta-hydroxysteroid dehydrogenase type 1 enzyme (11beta-HSD1), which is primarily responsible for reactivation of cortisol from cortisone. The urinary metabolism of adrenosterone was investigated, after a single oral administration in two male subjects, by gas chromatography-mass spectrometry (GC-MS) and gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS). Substantially increased excretion of 11beta-hydroxyandrosterone, 11beta-hydroxyetiocholanolone, 11-oxoandrosterone and 11-oxoetiocholanolone was observed. Minor metabolites such as 3alpha,17beta-dihydroxy-5beta-androstan-11-one, 3alpha-hydroxyandrost-4-ene-11,17-dione and 3alpha,11beta-dihydroxyandrost-4-en-17-one were also identified. The exogenous origin of the most abundant adrenosterone metabolites was confirmed by GC-C-IRMS according to World Anti-Doping Agency criteria. Through analysis of a reference population data set obtained from urine samples provided by elite athlete volunteers (n = 85), GC-MS doping control screening criteria are proposed: 11beta-hydroxyandrosterone concentration greater than 10 000 ng/mL (specific gravity adjusted to 1.020) or 11beta-hydroxyandrosterone/11beta-hydroxyetiocholanolone ratio greater than 20.Urine samples fulfilling these screening criteria may be subjected to GC-C-IRMS analysis for confirmation of adrenosterone administration.

Synthesis and characterisation of nitrile complexes of iron

Abstract The reaction of cis-[FeH2(DMPE)2] (DMPE = 1,2-bis(dimethylphosphino)ethane) (1a) and trans-[FeCl2(DMPE)2] (7a) with acetonitrile, cyanocyclopropane, benzonitrile, p-bromobenzonitrile and terephthalonitrile and reaction of trans-[FeCl2(DEPE)2] (DEPE = 1,2-bis(diethylphosphino)ethane) (7b) with acetonitrile, cyanocyclopropane and benzonitrile in methanol solution resulted in a series of nitrile chloride complexes trans-[FeCl(N≡C-R)(PP)2]+ and bis-nitrile complexes trans-[Fe(N≡C-R)2(PP)2]2+ of iron. All of the complexes have been characterised spectroscopically and four bis-nitrile complexes have been characterised crystallographically. Crystals of trans-[Fe(N≡CCH3)2(DMPE)2][2PF6] (3a) are monoclinic, space group P2/c, with a = 8.697(3), b = 9.165(5), c = 20.026(5) A, β = 107.54(3)°, Z= 2 and R = 0.058 (2300 F values). Crystals of trans-[Fe(N≡CC3H5)2(DEPE)2][2BF4] (4b) are monoclinic, space group P21/n, with a = 11.146(1), b = 15.396(2), c = 11.810(2) A, β = 111.06(1)°, Z = 2 and R = 0.050 (3011 F values). Crystals of trans-[Fe(N≡CPh)2(DMPE)2][2PF6] (5a) are monoclinic, space group P21/n, with a = 11.006(2), b = 12.351(3), c = 13.650(4) A, β = 93.60(2)°, Z = 2 and R = 0.035 (2650 F values). Crystals of trans-[Fe(p-N≡CC6H4Br)2(DMPE)2][2PF6][0.5KPF6] (6a) are tetragonal, space group I4¯c2, with a = b = 20.015(6), c = 21.610(3) A, β = 90.00°, Z = 8 and R = 0.049 (2235 F values).

Effectiveness of a Short, Intense Bridging Course for Scaffolding Students Commencing University-level Study of Chemistry

Bridging courses designed to support students commencing tertiary education are widespread, and some evidence for the value of semester-length courses has been reported; however, little attention has been paid to short-but-intense bridging courses, and empirical evidence of their effectiveness is particularly sparse. The current study followed the academic performance of a cohort of students enrolled in a first-year chemistry unit of study designed for those with little or no background knowledge of chemistry. The aims of this study are two-fold: first to determine the strength of the linkage between prior knowledge in chemistry and performance on the end of semester exam, and secondly, to explore the reasons for any differences observed. In particular, the value of the week-long intensive-mode bridging course offered by the University of Sydney was analysed. Quantitative and qualitative data were collected. The research has shown that participation in the chemistry bridging course is associated with ‘bridging the gap’ in academic performance between students with No Prior Chemistry background and those with a Strong Background. While the content of the bridging course is a significant contributor to academic success, so too is the confidence in their own learning that the course engenders among participants.

Complementary stable carbon isotope ratio and amount of substance measurements in sports anti-doping.

The detection of steroids originating from synthetic precursors against a background of their chemically identical natural analogues has proven to be a significant challenge for doping control laboratories accredited by the World Anti-Doping Agency (WADA). The complementary application of gas chromatography-mass spectrometry (GC-MS) and gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS) has been demonstrated to provide specific detection of endogenous steroid misuse for improved anti-doping analysis. Markers of synthetically derived steroids are reviewed on the basis of abnormal urinary excretions and low (13)C content. A combinatorial approach is presented for the interpretation of GC-MS and GC-C-IRMS data in the anti-doping context. This methodology can allow all relevant information concerning an individuals metabolism to be assessed in order to make an informed decision with respect to a doping violation.

Synthesis and structure of dichlorodi-[1,2-bis(dimethylphosphino)ethane]iron(III) tetrachloroferrate(III), [Fe(DMPE)2Cl2]+[FeCl4]−

Abstract [Fe(DMPE)2Cl2]+[FeCl4]− was formed in high yield by the photochemical oxidation of Fe(DMPE)2Cl2 with chlorinated organic solvents CH2Cl2, CHCl3 or CCl4. Crystals of [Fe(DMPE)2Cl2]+[FeCl4]− are orthorhombic, space groupPcab, a = 16.250(3), b = 19.392(3), c = 34.451(7) A, Z = 16, R = 0.058 (3597 F). This represents the first structural characterization of an iron(III) complex with a P4Cl2 donor set and saturated phosphine ligands.

Isolation and identification of three by-products found in methylamphetamine synthesized by the Emde route.

This article describes the isolation and structural elucidation of three compounds produced during the synthesis of methylamphetamine by the so‐called “Emde” procedure. The “Emde” procedure involves the preparation of the intermediate chloropseudoephedrine or chloroephedrine from ephedrine or pseudoephedrine, respectively. The intermediates are then reduced to methylamphetamine with hydrogen under pressure in the presence of a catalyst. The by‐product compounds were isolated from methylamphetamine by column chromatography and liquid chromatography (LC). Proton nuclear magnetic resonance spectroscopy (1H NMR), carbon nuclear magnetic resonance spectroscopy (13C NMR), and nanospray quadrupole‐time of flight‐mass spectrometry (Q‐TOF‐MS) were used to identify them as two stereoisomers of the compound N, N′‐dimethyl‐3,4‐diphenylhexane‐2,5‐diamine and N‐methyl‐1‐{4‐[2‐(methylamino)propyl]phenyl}‐1‐phenylpropan‐2‐amine.