Noreen Morris

Synthesis, characterization and monoamine transporter activity of the new psychoactive substance mexedrone and its N-methoxy positional isomer, N-methoxymephedrone.

3-Methoxy-2-(methylamino)-1-(4-methylphenyl)propan-1-one (mexedrone) appeared in 2015 and was advertised by UK Internet retailers as a non-controlled mephedrone derivative (2-(methylamino)-1-(4-methylphenyl)propan-1-one), which was of particular interest to countries who operate generic drugs legislation. This study describes the synthesis and analytical characterization of mexedrone and the differentiation from its isomer, N-methoxymephedrone, which was predicted to be a suitable candidate before the identity of mexedrone was revealed. A full analytical characterization is described using various chromatographic, spectroscopic and mass spectrometric platforms and X-ray crystal structure analysis. The analytical data obtained for a vendor sample were consistent with the synthesized mexedrone reference standard and analytical differentiation between the mexedrone and N-methoxymephedrone positional isomers was achieved. Furthermore, α-chloromethylmephedrone was identified as a by-product during mexedrone synthesis. All three substances were also studied for their uptake and releasing properties at dopamine transporters (DAT), norepinephrine transporters (NET) and serotonin transporters (SERT) using in vitro monoamine transporter assays in rat brain synaptosomes and compared to mephedrone. Mexedrone was a weak non-selective uptake blocker with IC50 values in the low μM range. It was also devoid of releasing activity at DAT and NET but displayed weak releasing activity at SERT (EC50  = 2.5 μM). The isomer N-methoxymephedrone was found to be a weak uptake blocker at DAT, NET and SERT, as well as a fully efficacious substrate-type releasing agent across all three transporters with EC50 values in the low micromolar range. The synthesis by-product α-chloromethylmephedrone was inactive in all assays. Copyright

Synthesis and Characterisation of Novel ι-Carrageenan Hydrogel Blends for Agricultural Seed Coating Application

Radical science and innovation in farming is vital to produce the food that the world will need by 2050. To feed an estimated world population of nine billion people in 2050, 70 % to 100 % increase in food production will be required if it continues rising at the current rate. The aim of this project is to develop novel revolutionary super absorbent hydrogel coatings for agricultural use. Hydrogel seed coatings improve the rate of seed germination and emergence and enhance seed survival during critical development periods, especially under less than optimal conditions. Preliminary work with ι-carrageenan hydrogel showed a promising results including higher seed germination rates, faster plant emergence, lower water requirement, enhanced root development and potential carrier of nutrients. Two hydrogel blends – agar/ι-carrageenan and xanthan/κ-carrageenan/ι-carrageenan – were synthesised and characterised in this project as potential seed coating materials based on their biodegradable, non-toxic sugar based natural polymers and their excellent water absorbing/holding capability. The newly formulated hydrogels were characterised by swelling studies, rheological measurements and infrared spectroscopy. It was found that the addition of xanthan/κ-carrageenan into ι-carrageenan hydrogel improved the water absorbing capacity from 117.90 % to 139.05 %, the life-span of the hydrogel from 6 hr to 24 hr in excess water and the gel strength from 108.4 Pa to 267.98 Pa. The addition of agar into ι-carrageenan showed an increase in gel strength and a greater improvement in water holding capacity giving 67.33 % water content while ι-carrageenan on its own had only 39.64 % after 72 hr of incubation at 30 °C, which showed higher potential to be used in drought conditions. The ATR-FTIR results proved that the hydrogels were physically cross-linked. A further evaluation such as the germination profile test is required to test the effectiveness of the hydrogel coatings on seeds. It is anticipated that this work will be extended to coating different seed varieties in the future with these newly developed hydrogels.

Synthesis, analytical characterization and monoamine transporter activity of the new psychoactive substance 4-methylphenmetrazine (4-MPM), with differentiation from its ortho- and meta- positional isomers.

The availability of new psychoactive substances (NPS) on the recreational drug market continues to create challenges for scientists in the forensic, clinical and toxicology fields. Phenmetrazine (3-methyl-2-phenylmorpholine) and an array of its analogs form a class of psychostimulants that are well documented in the patent and scientific literature. The present study reports on two phenmetrazine analogs that have been encountered on the NPS market following the introduction of 3-fluorophenmetrazine (3-FPM), namely 4-methylphenmetrazine (4-MPM), and 3-methylphenmetrazine (3-MPM). This study describes the syntheses, analytical characterization, and pharmacological evaluation of the positional isomers of MPM. Analytical characterizations employed various chromatographic, spectroscopic, and mass spectrometric platforms. Pharmacological studies were conducted to assess whether MPM isomers might display stimulant-like effects similar to the parent compound phenmetrazine. The isomers were tested for their ability to inhibit uptake or stimulate release of tritiated substrates at dopamine, norepinephrine and serotonin transporters using in vitro transporter assays in rat brain synaptosomes. The analytical characterization of three vendor samples revealed the presence of 4-MPM in two of the samples and 3-MPM in the third sample, which agreed with the product label. The pharmacological findings suggest that 2-MPM and 3-MPM will exhibit stimulant properties similar to the parent compound phenmetrazine, whereas 4-MPM may display entactogen properties more similar to 3,4-methylenedioxymethamphetamine (MDMA). The combination of test purchases, analytical characterization, targeted organic synthesis, and pharmacological evaluation of NPS and their isomers is an effective approach for the provision of data on these substances as they emerge in the marketplace.