School of Chemistry - Research Publications

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    Trace residue identification, characterization, and longitudinal monitoring of the novel synthetic opioid β-U10, from discarded drug paraphernalia
    West, H ; Fitzgerald, JL ; Hopkins, KL ; Leeming, MG ; DiRago, M ; Gerostamoulos, D ; Clark, N ; Dietze, P ; White, JM ; Ziogas, J ; Reid, GE (WILEY, 2022-09)
    Empirical data regarding dynamic alterations in illicit drug supply markets in response to the COVID-19 pandemic, including the potential for introduction of novel drug substances and/or increased poly-drug combination use at the "street" level, that is, directly proximal to the point of consumption, are currently lacking. Here, a high-throughput strategy employing ambient ionization-mass spectrometry is described for the trace residue identification, characterization, and longitudinal monitoring of illicit drug substances found within >6,600 discarded drug paraphernalia (DDP) samples collected during a pilot study of an early warning system for illicit drug use in Melbourne, Australia from August 2020 to February 2021, while significant COVID-19 lockdown conditions were imposed. The utility of this approach is demonstrated for the de novo identification and structural characterization of β-U10, a previously unreported naphthamide analog within the "U-series" of synthetic opioid drugs, including differentiation from its α-U10 isomer without need for sample preparation or chromatographic separation prior to analysis. Notably, β-U10 was observed with 23 other drug substances, most commonly in temporally distinct clusters with heroin, etizolam, and diphenhydramine, and in a total of 182 different poly-drug combinations. Longitudinal monitoring of the number and weekly "average signal intensity" (ASI) values of identified substances, developed here as a semi-quantitative proxy indicator of changes in availability, relative purity and compositions of street level drug samples, revealed that increases in the number of identifications and ASI for β-U10 and etizolam coincided with a 50% decrease in the number of positive detections and an order of magnitude decrease in the ASI for heroin.
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    Mobile Proton Triggered Radical Fragmentation of Nitroarginine Containing Peptides
    Leeming, MG ; White, JM ; O'Hair, RAJ ; Donald, WA (SPRINGER, 2014-03)
    Protonated nitroarginine, [R(NO2) + H](+), which contains the nitroguanidine 'explosophore,' undergoes homolytic N - N nitro-imine bond cleavage to expel NO2(•) and form a radical cation of arginine in high yield (100% relative abundance) upon low-energy collision-induced dissociation (CID). Other ionization states of nitroarginine, including [R(NO2) - H](-), and a fixed-charge derivative of nitroarginine do not expel NO2(•) (<1%), but instead dissociate via heterolytic bond cleavage with abundant losses of small molecules (N2O and H2N2O2) from the nitroguanidine group. The effects of proton mobility on the CID reactions of nitroarginine containing peptides was investigated for peptide derivatives of leucine enkephalin, including XYGGFLR(NO2), X = D, G, K, and R, by examining the different protonation states: [M - H](-); [M + H](+); and [M + 2H](2+). For [M + H](+) containing the less basic N-terminal residues (X = D, G) and all [M + 2H](2+), mobile proton fragmentation reactions that result in peptide sequence ions dominate. In contrast, for peptides containing the basic N-terminal residues (R and K), the CID spectra of both the [M - H](-) and [M + H](+) are dominated by the losses of small even-electron neutrals from the nitroarginine side-chain. The fraction of nitroguanidine directed fragmentation of the nitroarginine side chain that results in bond homolysis to form [XYGGFLR](+•) by expulsion of NO2(•) increases by more than 10 times as the protonation state changes from [M - H](-) (<10%) to [M + 2H](2+) (ca. 90%) and by about four times as the acidity of the [M + H](+) N-terminal residue increases from R (19.0%) to D (76.5%). These results indicate that protonated peptides containing nitroarginine can undergo non-canonical mobile proton triggered radical fragmentation.