A Brief Review of Radiolabelling Nucleic Acid-Based Molecules for Tracking and Monitoring.

The rise of nucleic acid-based therapeutics continues apace. At the same time, the need for radiolabelled oligonucleotides for determination of spatial distribution is increasing. Complex molecular structures with mostly multiple charges and low solubility in organic solvents increase the challenge of integrating radionuclides.

Intramolecular through-space NMR spectroscopic effect of steric compression on H NMR spectroscopy.

The intramolecular through-space NMR spectroscopic effect of steric compression is related to intramolecular through-space van der Waals repulsion. The electron cloud of a proton can be pushed away by the electron cloud of a nearby proton or functional group. As the electron population of the sterically compressed proton is decreased (therefore deshielded), the chemical shift sharply moves downfield, which may result in ambiguity for the proton signal assignment.

Gold Nanoparticles: Tunable Characteristics and Potential for Nasal Drug Delivery.

A general procedure to prepare gold nanourchins (GNUs) via a seed-mediated method was followed using dopamine hydrochloride as a reducing agent and silver nitrate salt (AgNO) as a shape-directing agent. The novelty of this study comes from the successful incorporation of the prepared gold urchins as an aqueous suspension in a nasal pressurized metered dose inhaler (pMDI) formulation and the investigation of their potential for olfactory targeting for direct nose-to-brain drug delivery (NTBDD). The developed pMDI formulation was composed of 0.

A Cell-Based Nasal Model for Screening the Deposition, Biocompatibility, and Transport of Aerosolized PLGA Nanoparticles.

The olfactory region of the nasal cavity directly links the brain to the external environment, presenting a potential direct route to the central nervous system (CNS). However, targeting drugs to the olfactory region is challenging and relies on a combination of drug formulation, delivery device, and administration technique to navigate human nasal anatomy. In addition, in vitro and in vivo models utilized to evaluate the performance of nasal formulations do not accurately reflect deposition and uptake in the human nasal cavity.

Synthetic cannabinoid use in an adult male prison in the UK.

Introduction: Synthetic cannabinoids (i.e. Spice) are a major public health problem in UK prisons, however, research in this area is limited.

Instant Detection of Synthetic Cannabinoids on Physical Matrices, Implemented on a Low-Cost, Ultraportable Device.

Synthetic cannabinoids (SCs) make up a class of novel psychoactive substances (NPS), used predominantly in prisons and homeless communities in the U.K. SCs can have severe side effects, including psychosis, stroke, and seizures, with numerous reported deaths associated with their use.

Practical Synthesis of Antimicrobial Long Linear Polyamine Succinamides.

There are many severe bacterial infections notorious for their ability to become resistant to clinically relevant antibiotics. Indeed, antibiotic resistance is a growing threat to human health, further exacerbated by the lack of new antibiotics. We now describe the practical synthesis of a series of substituted long linear polyamines that produce rapid antibacterial activity against both Gram-positive and Gram-negative bacteria, including meticillin-resistant .

Synthesis and Antagonist Activity of Methyllycaconitine Analogues on Human α7 Nicotinic Acetylcholine Receptors.

Methyllycaconitine (MLA), , is a naturally occurring norditerpenoid alkaloid that is a highly potent (IC = 2 nM) selective antagonist of α7 nicotinic acetylcholine receptors (nAChRs). Several structural factors affect its activity such as the neopentyl ester side-chain and the piperidine ring N-side-chain. The synthesis of simplified AE-bicyclic analogues - possessing different ester and nitrogen side-chains was achieved in three steps.

Synthetic cannabinoid receptor agonists are monoamine oxidase-A selective inhibitors.

Synthetic cannabinoid receptor agonists (SCRAs) are one of the fastest growing classes of recreational drugs. Despite their growth in use, their vast chemical diversity and rapidly changing landscape of structures make understanding their effects challenging. In particular, the side effects for SCRA use are extremely diverse, but notably include severe outcomes such as cardiac arrest.

Photochemical Fingerprinting Is a Sensitive Probe for the Detection of Synthetic Cannabinoid Receptor Agonists; toward Robust Point-of-Care Detection.

With synthetic cannabinoid receptor agonist (SCRA) use still prevalent across Europe and structurally advanced generations emerging, it is imperative that drug detection methods advance in parallel. SCRAs are a chemically diverse and evolving group, which makes rapid detection challenging. We have previously shown that fluorescence spectral fingerprinting (FSF) has the potential to provide rapid assessment of SCRA presence directly from street material with minimal processing and in saliva.

Effect of Position 1 Substituent and Configuration on APCI-MS Fragmentation of Norditerpenoid Alkaloids Including 1--Condelphine.

Norditerpenoid alkaloids (NDA) are hexacyclic highly oxygenated compounds, and the analysis of their 3D configuration is important as it helps to interpret their bioactive conformations. High-performance liquid chromatography/atmospheric pressure chemical ionization mass spectrometry (LC/MS-APCI) is a promising technique to investigate NDA stereochemistry. The effect of the alpha (α)-substituent at carbon 1 and its configuration on the stability of NDA in the mass spectrometer was studied.

Poisonous Piperidine Plants and the Biodiversity of Norditerpenoid Alkaloids for Leads in Drug Discovery: Experimental Aspects.

There are famous examples of simple (e.g., hemlock, L.

Practical Synthesis of Polyamine Succinamides and Branched Polyamines.

Antibiotic resistance is now a growing threat to human health, further exacerbated by the lack of new antibiotics. We describe the practical synthesis of a series of substituted polyamine succinamides and branched polyamines that are potential new antibiotics against both Gram-positive and Gram-negative bacteria, including MRSA and Pseudomonas aeruginosa. They are prepared via 1,4-Michael addition of acrylonitrile and then hydrogenation of the nitrile functional groups to primary amines.

Antibacterial activity of novel linear polyamines against .

New therapeutic options are urgently required for the treatment of infections. Accordingly, we sought to exploit the vulnerability of to naturally occurring polyamines. We have developed and tested the anti-staphylococcal activity of three novel linear polyamines based on spermine and norspermine.

Design and synthesis of hybrid compounds as novel drugs and medicines.

The development of highly effective conjugate chemistry approaches is a way to improve the quality of drugs and of medicines. The aim of this paper is to highlight and review such hybrid compounds and the strategies underpinning their design. A variety of unique hybrid compounds provide an excellent toolkit for novel biological activity, anticancer and non-viral gene therapy (NVGT), and as templates for killing bacteria and preventing antibiotic drug resistance.

Trends in hospital presentations following analytically confirmed synthetic cannabinoid receptor agonist exposure before and after implementation of the 2016 UK Psychoactive Substances Act.

Background And Aims: The United Kingdom (UK) Psychoactive Substances Act (PSA), implemented on the 26  May 2016, made the production, supply and sale of all non-exempted psychoactive substances illegal. The aim of this study was to measure trends in hospital presentations for severe toxicity following analytically confirmed synthetic cannabinoid receptor agonist (SCRA) exposure before and after implementation of the PSA.

Design: Observational study.

Norditerpenoid alkaloids from and : structural relevance in medicine, toxicology, and metabolism.

Covering: 77 A.D. up to 2020Norditerpenoid alkaloids (NDA), typically -ethylpiperidine containing C19 or C18 natural product diterpenes, are hexacycles with several contiguous often oxygenated stereocentres.

In Vitro Evaluation of Nasal Aerosol Depositions: An Insight for Direct Nose to Brain Drug Delivery.

The nasal cavity is an attractive route for both local and systemic drug delivery and holds great potential for access to the brain via the olfactory region, an area where the blood-brain barrier (BBB) is effectively absent. However, the olfactory region is located at the roof of the nasal cavity and only represents ~5-7% of the epithelial surface area, presenting significant challenges for the deposition of drug molecules for nose to brain drug delivery (NTBDD). Aerosolized particles have the potential to be directed to the olfactory region, but their specific deposition within this area is confounded by a complex combination of factors, which include the properties of the formulation, the delivery device and how it is used, and differences in inter-patient physiology.

The H NMR Spectroscopic Effect of Steric Compression Is Found in [3.3.1]Oxa- and Azabicycles and Their Analogues.

The through-space H NMR effect of steric compression by the lone-pair electrons of O- and N-atoms is shown in synthetic [3.3.1]oxa- and azabicycles.

Multinuclear Nuclear Magnetic Resonance Spectroscopy Is Used to Determine Rapidly and Accurately the Individual p Values of 2-Deoxystreptamine, Neamine, Neomycin, Paromomycin, and Streptomycin.

Unambiguous assignments have been made for each individual p value of the amino group and guanidine substituents on 2-deoxystreptamine, neamine, neomycin, paromomycin, and streptomycin by pH-titration evaluation of their H, C, and N (by H-N heteronuclear multiple-bond correlation (HMBC) spectra) NMR chemical shifts (δs) as the reporter nuclei. These data require minor revisions of the literature data in terms of the assignment order for neomycin and paromomycin. In situ titrations and NMR spectroscopy are shown to be a powerful combination for rapidly (minutes) obtaining each distinct p value of the similar amine and guanidine functional groups, which decorate aminoglycoside antibiotics.

Individual p Values of Tobramycin, Kanamycin B, Amikacin, Sisomicin, and Netilmicin Determined by Multinuclear NMR Spectroscopy.

NMR spectroscopy is a powerful technique for separating and measuring each distinct p value of the amino groups around aminoglycoside antibiotics. Unambiguous assignments were made for each individual amine substituent on 2-deoxystreptamine, tobramycin, kanamycin B, amikacin, sisomicin, and netilmicin using variations in the NMR spectroscopic chemical shift (δ) with H, C, and N HMBC; the individual p values of netilmicin are reported for the first time.

Impacts of Steric Compression, Protonation, and Intramolecular Hydrogen Bonding on the N NMR Spectroscopy of Norditerpenoid Alkaloids and Their Piperidine-Ring Analogues.

H-N HMBC spectra of norditerpenoid alkaloids and their synthetic azabicyclic analogues were obtained to investigate the impacts of the through-space effect of steric compression, protonation, and formation of intramolecular hydrogen bonding on the N NMR spectroscopy of these natural products and their piperidine-containing analogues. A rare N NMR effect of steric compression is demonstrated in half-cage A/E-rings of norditerpenoid alkaloid free bases and their synthetic azabicyclic analogues, in which the distribution of the lone pair of electrons of the tertiary amine -atom is sterically restricted by bridged cycloalkanes, e.g.

The 1α-hydroxy-A-rings of norditerpenoid alkaloids are twisted-boat conformers.

The skeletal conformations of naturally occurring norditerpenoid alkaloids fix their substituent functional groups in space, thereby directing their bioactivities. Solution conformations of the A-rings of 4 selected norditerpenoid alkaloid free bases: mesaconitine, karacoline (karakoline), condelphine, and neoline (bullatine B), were analysed by NMR spectroscopy and single-crystal X-ray crystallography. They adopt twisted-chair, twisted-boat, twisted-boat, twisted-boat conformations, respectively.

Synthetic Cannabinoid Receptor Agonists Detection Using Fluorescence Spectral Fingerprinting.

Synthetic cannabinoid receptor agonists (SCRAs), termed "Spice" or "K2", are molecules that emulate the effects of the active ingredient of marijuana, and they have gained enormous popularity over the past decade. SCRAs are Schedule 1 drugs that are highly prevalent in the U.K.

Additive Effects of 3,4-Methylenedioxymethamphetamine (MDMA) and Compassionate Imagery on Self-Compassion in Recreational Users of Ecstasy.

3,4-Methylenedioxymethylamphetamine (MDMA;'ecstasy') produces prosocial subjective effects that may extend to affiliative feelings towards . Behavioural techniques can produce similar self-directed affiliation. For example, compassionate imagery (CI) and ecstasy reduce self-criticism and increase self-compassion to a similar extent, with the effects of CI enhanced in the presence of ecstasy.