Photodegradation of cannabidiol (CBD) and Δ9-THC in cannabis plant material.

Δ9-THC, the psychotropic cannabinoid in Cannabis sativa L., for many years has been the focus of all the pharmacological attention as the main promising principle of the plant. Recently, however, cannabidiol (CBD) has brought a sudden change in the scenario, exponentially increasing the interest in pharmacology as the main non-psychotropic cannabinoid with potential therapeutic, cosmetical and clinical applications. Although the reactivity of CBD and Δ9-THC has been considered, little attention has been paid to the possible photodegradation of these cannabinoids in the vegetal matrix and the data available in the literature are, in some cases, contradictory. The aim of the present work is to provide a characterization of the photochemical behaviour of CBD and Δ9-THC in three cannabis chemotypes, namely I (Δ9-THC 2.50%w/w), II (CBD:Δ9-THC 5.82%w/w:3.19%w/w) and III (CBD 3.02%w/w).

Easy and Accessible Synthesis of Cannabinoids from CBD.

Cannabidiol (CBD), a prominent phytocannabinoid found in various Cannabis chemotypes, is under extensive investigation for its therapeutic potential. Moreover, because it is nonpsychoactive, it can also be utilized as a functional ingredient in foods and supplements in certain countries, depending on its legal status. From a chemical reactivity point of view, CBD can undergo conversion into different structurally related compounds both during storage and after the consumption of CBD-based products. The analytical determination of these compounds is of paramount concern due to potential toxicity and the risk of losing the active ingredient (CBD) title. Consequently, the complete stereoselective total synthesis of representative CBD-derived compounds has become a matter of great interest. The synthesis of pure CBD-derived compounds, achievable in a few synthetic steps, is essential for preparing analytical standards and facilitating biological studies. This paper details the transformation of the readily available CBD into Δ8-THC, Δ9-THC, Δ8-iso-THC, CBE, HCDN, CBDQ, Δ6-iso-CBD, and 1,8-cineol cannabinoid (CCB). The described protocols were executed without the extensive use of protecting groups, avoiding tedious purifications, and ensuring complete control over the structural features.

Arylazo Sulfones as Nonionic Visible-Light Photoacid Generators.

The selective visible-light-driven generation of a weak acid (sulfinic acid, in nitrogen-purged solutions) or a strong acid (sulfonic acid, in oxygen-purged solutions) by using shelf-stable arylazo sulfones was developed. These sulfones were then used for the green, smooth, and efficient photochemical catalytic protection of several (substituted) alcohols (and phenols) as tetrahydropyranyl ethers or acetals.

Electrifying Friedel-Crafts Intramolecular Alkylation toward 1,1-Disubstituted Tetrahydronaphthalenes.

In this work, we successfully employed electrochemical conditions to promote a Hofer-Moest, intramolecular Friedel-Crafts alkylation sequence. The reaction proceeds under mild conditions, employing carboxylic acids as starting materials. Notably, the electrochemical process performed in batch was adapted to a continuous flow electrolysis apparatus to provide a significant improvement. This catalyst-free, electrochemical approach produces an array of tetrahydronaphthalenes that could be used for API synthesis.

Carbon dioxide photoreduction in prebiotic environments.

The reduction of carbon dioxide is one of the hottest topics due to the concern of global warming. Carbon dioxide reduction is also an essential step for life's origins as photoautotrophs arose soon after Earth formation. Both the topics are of high general interest, and possibly, there could be a fruitful cross-fertilization of the two fields. Herein, we selected and collected papers related to photoreduction of carbon dioxide using compounds easily available on the Earth and considered of prebiotic relevance. This work might be useful also to scientists interested in carbon dioxide photoreduction and/or to have an overview of the techniques available.

Photochemistry of Cannabidiol (CBD) Revised. A Combined Preparative and Spectrometric Investigation.

Cannabis is a plant with an astonishing ability to biosynthesize cannabinoids, and more than 100 molecules belonging to this class have been isolated. Among them in recent years cannabidiol (CBD) has received the interest of pharmacology as the major nonpsychotropic cannabinoid with many potential clinical applications. Although the reactivity of CBD has been widely investigated, only little attention has been given to the possible photodegradation of this cannabinoid, and the data available in the literature are outdated and, in some cases, conflicting. The aim of the present work is providing a characterization of the photochemical behavior of CBD in organic solvents, through a detailed GC-MS analyses, isolation, and NMR characterization of the photoproducts obtained.

Electrophysiological Responses of the Mediterranean Fruit Fly, Ceratitis capitata, to the Cera Trap® Lure: Exploring Released Antennally-Active Compounds.

The Mediterranean fruit fly (medfly), Ceratitis capitata, is a worldwide pest of agriculture able to use olfactory cues to locate habitat, food sources, mates and oviposition sites. The sensitivity of medfly olfaction has been exploited to develop olfactory-based attractants that are currently important tools for detection, control and eradication of its populations. Among these is Cera Trap® (BIOIBERICA, S.A.U.), a cost-effective bait. Here we used coupled gas chromatography/electroantennographic detection (GC-EAD) and GC/mass spectrometry (GC-MS) approaches to characterize the medfly antennally-active compounds released by this lure. We identified GC peaks corresponding to chemicals belonging to six different classes including heterocyclic aromatic compounds, aliphatic alcohols, aldehydes, esters, sesquiterpene hydrocarbons, and aromatic alcohols. We tested ten potential candidate volatiles belonging to these classes and predicted to be emitted by the lure and found that they were eliciting electroantennographic responses in medfly adults. These results will help in unravelling the physiological mechanisms of odor perception in both sexes, especially in relation to Cera Trap® attractant activity, which in the field has been shown to be female-specific. These findings and their developments will ultimately expand the toolbox for medfly control in the field.

Increased Antibacterial and Antibiofilm Properties of Silver Nanoparticles Using Silver Fluoride as Precursor.

Silver nanoparticles were produced with AgF as the starting Ag(I) salt, with pectin as the reductant and protecting agent. While the obtained nanoparticles (pAgNP-F) have the same dimensional and physicochemical properties as those already described by us and obtained from AgNO3 and pectin (pAgNP-N), the silver nanoparticles from AgF display an increased antibacterial activity against E. coli PHL628 and Staphylococcus epidermidis RP62A (S. epidermidis RP62A), both as planktonic strains and as their biofilms with respect to pAgNP-N. In particular, a comparison of the antimicrobial and antibiofilm action of pAgNP-F has been carried out with pAgNP-N, pAgNP-N and added NaF, pure AgNO3, pure AgF, AgNO3 and added NaF and pure NaNO3 and NaF salts. By also measuring the concentration of the Ag+ cation released by pAgNP-F and pAgNP-N, we were able to unravel the separate contributions of each potential antibacterial agent, observing an evident synergy between p-AgNP and the F- anion: the F- anion increases the antibacterial power of the p-AgNP solutions even when F- is just 10 µM, a concentration at which F- alone (i.e., as its Na+ salt) is completely ineffective.

Voltammetric Determination of Binding Constant and Stoichiometry of Albumin (Human, Bovine, Ovine)-Drug Complexes.

The parameters characterizing the formation of complexes with albumin (in particular, human serum albumin (HSA)) are fundamental for the characterization of a drug for commercialization purposes and for the determination of common pharmacokinetic parameters. Electrochemical methods appear particularly attractive for the determination of the complexation constant, complex stoichiometry, and percentage of free/bound drug, due to the ease of operation and the wide availability. In this article, we propose an electrochemical method based on differential pulse voltammetry for the determination of albumin-drug interaction parameters, including the replacement of the drug-albumin adduct by a competitive compound, sulfanilamide. The formation of either single or multiple complexes between the considered drug and albumin has been considered. Typically, the method operates with a glassy carbon electrode in NaCl 0.9% as the supporting electrolyte.

An Optical Fiber Chemical Sensor for the Detection of Copper(II) in Drinking Water.

Highly sensitive plasmonic optical fiber platforms combined with receptors have been recently used to obtain selective sensors. A low-cost configuration can be obtained exploiting a D-shaped plastic optical fiber covered with a multilayer sensing surface. The multilayer consists of a gold film, functionalized with a specific receptor, where the surface plasmon resonance (SPR) occurs. The signal is produced by the refractive index variation occurring as a consequence of the receptor-to analyte binding. In this work, a selective sensor for copper(II) detection in drinking water, exploiting a self-assembled monolayer (SAM) of d,l-penicillamine as the sensing layer, has been developed and tested. Different concentrations of copper(II) in NaCl 0.1 M solutions at different pH values and in a real matrix (drinking water) have been considered. The results show that the sensor is able to sense copper(II) at concentrations ranging from 4 × 10-6 M to 2 × 10-4 M. The use of this optical chemical sensor is a very attractive perspective for fast, in situ and low-cost detection of Cu(II) in drinking water for human health concerns. Furthermore, the possibility of remote control is feasible as well, because optical fibers are employed.

Larval Diet Affects Male Pheromone Blend in a Laboratory Strain of the Medfly, Ceratitis capitata (Diptera: Tephritidae).

The Mediterranean fruit fly (medfly) Ceratitis capitata is a polyphagous pest of fruits and crops with a worldwide distribution. Its ability to use different larval hosts may have multiple effects, including impacts on adult reproductive biology. The male sex pheromone, which plays a key role in attracting both other males to lekking arenas and females for mating, is a mixture of chemical compounds including esters, acids, alkanes and terpenes known to differ between laboratory strains and wild-type populations. The relationship between larval diet and adult pheromone composition remains unexplored. Here, we investigated the effect of larval diet, including laboratory media and fresh fruits, on the composition of the male pheromone mixture. Using Headspace Solid Phase Microextraction we collected the pheromone emitted by males reared as larvae on different substrates and found both qualitative and quantitative differences. A number of alkanes appeared to be typical of the pheromone of males reared on wheat bran-based larval medium, and these may be cuticular hydrocarbons involved in chemical communication. We also detected differences in pheromone composition related to adult male age, suggesting that variations in hormonal levels and/or adult diet could also play a role in determining the chemical profile emitted. Our findings highlight the plasticity of dietary responses of C. capitata, which may be important in determining the interactions of this pest with the environment and with conspecifics. These results also have applied relevance to increase the mating competitiveness of mass-reared C. capitata used in Sterile Insect Technique programs.

Direct Irradiaton of Aryl Sulfides: Homolytic Fragmentation and Sensitized S-Oxidation.

The direct irradiation of diphenyl sulfide and p-substituted thioanisoles in the presence of oxygen was investigated by means of both steady state and laser flash photolysis experiments. Two competitive pathways took place from the triplet excited state of thioanisoles, C-S bond cleavage, finally leading to aryl sulfinic acid and sensitized oxidation leading to S-oxidation. Co-oxidation of dodecyl methyl sulfide occurred efficiently implying that an S-persulfoxide intermediate is involved during the sensitized oxidation. On the other hand, triplet state of diphenyl sulfide also showed competitive C-S bond cleavage giving phenyl sulfinic acid and ionization to diphenyl sulfide radical cation that in turn led to diphenyl sulfoxide. The rate constants of the above reactions were determined by time-resolved experiments.

Sugar-Assisted Photogeneration of Didehydrotoluenes from Chlorobenzylphosphonic Acids.

Irradiation of the three isomeric chlorobenzylphophonic acids in aqueous buffer led to a pH-dependent photochemistry. Under acidic conditions (pH = 2.5), photocleavage of the Ar-Cl bond occurred and a phenyl cation chemistry resulted. Under basic conditions (pH = 11), a photoinduced release of the chloride anion followed by the detachment of the metaphosphate anion gave α,n-didehydrotoluene diradicals (α,n-DHTs), potential DNA cleaving intermediates. At a physiological pH (pH = 7.2), both a cationic and a diradical reactivity took place depending on the phosphonic acid used. It is noteworthy that the complexation exerted by a monosaccharide (glucose or methylglucopyranoside) present in solution induced an exclusive formation of α,n-DHTs. The mechanistic scenario of the different photoreactivities occurring when changing the pH of the solution and the role of the various intermediates (phenyl cations, diradicals, etc.) in the process was studied by computational analysis.

Photochemistry of N-Arylsulfonimides: An Easily Available Class of Nonionic Photoacid Generators (PAGs).

The photochemical behavior of differently substituted N-arylsulfonimides was investigated. Homolysis of the S-N bond took place as the exclusive path from the singlet state to afford both N-arylsulfonamides and photo-Fries adducts, the amount of which depended on reaction conditions and aromatic substituents. Sulfinic and sulfonic acids were released upon irradiation under deaerated and oxygenated conditions, respectively. The nature of the excited states and intermediates involved were proved by laser flash photolysis and EPR experiments. These results highlighted the potential of such compounds as nonionic photoacid generators able to photorelease up to two equivalents of a strong acid for each mole of substrate.

Smooth Photocatalyzed Benzylation of Electrophilic Olefins via Decarboxylation of Arylacetic Acids.

Arylacetic acids were used as sources of benzyl radicals under tetrabutylammonium decatungstate photocatalyzed conditions for the benzylation of electron-poor olefins. The reaction proceeds smoothly in a mixed aqueous medium (MeCN/H2O 2/1) in the presence of NaHCO3, NaClO4, and an electron transfer agent (biphenyl). The reaction tolerates a wide variety of functional groups on the aromatic ring (whether electron donating or electron withdrawing) and can be extended to heteroaromatic analogues. The olefins have the double role of radical trap and electron acceptor. The present approach can also be extended to arylpropionic acids (including the nonsteroidal anti-inflammatory drugs ibuprofen and flurbiprofen), as well as mandelic acid derivatives.

The detection of gunshot residues in the nasal mucus of suspected shooters.

The identification and quantification of metallic residues produced by gunshots, called gunshot residues (GSR), provide crucial elements in forensic investigations. The research has been largely focused on their collection onto the hands of suspected shooters, but the method is often burdened by risks of contamination. This research was focused on the possibility of sampling GSR trapped inside the nasal mucus of consenting shooters. Samples of the nasal mucus of "blank" control subjects and shooters were chemically analysed by Instrumental Neutron Activation Analysis (INAA), for residues of antimony (Sb) and barium (Ba), while lead (Pb) was excluded as ubiquitously environmental contaminant and due to high instrumental quantification limit (IQL) of INAA for this element. Shots were fired using two types of weapons (pistols and revolvers) and different firing sequences. The mucus was sampled at different times: immediately after the shots, after 30-60-120 and 180 min. Different amounts of Sb and Ba were detected between controls and shooters, witnessing the ability of the nasal mucus to retain GSR at concentrations significantly different even from the highest basal levels. Moreover, in order to simulate actual cases, nasal mucus from five groups of shooters was sampled after different shots with the same weapon and cartridges, immediately and after 1, 3, 12, and 24 h. The highest values were always found in the first 3 h from firing, for both weapons. Interestingly, for all the weapons, significant Sb and Ba concentrations were also found up to 12 h after firing, contrary to what occurs on hands, even though a progressive decrease was detected, with values below the detection threshold only after 24 h, thus demonstrating that GSR are persistent in nasal mucus. These first results proving that both Sb and Ba were qualitatively detectable in the nasal mucus of shooters indicate that the chemical analysis of the nasal mucus of suspected shooters may represent a promising tool in the forensic field since it is less burdened by problems related to sampling or contamination than the usual sampling on hand, providing that ammunitions employed contain Ba and Sb.

Formation of Hexamethylenetetramine (HMT) from HCHO and NH3--Relevance to Prebiotic Chemistry and B3LYP Consideration.

Despite its importance in the prebiotic and biochemical fields, a complete theoretical study of the formation of hexamethylenetetramine (HMT) starting from its precursors ammonia and formaldehyde has not received due considerations in the literature with regard to the thermodynamic feasibility of many of the mechanistically proposed intermediates in its formation. Most of the studies in this area have been mostly concerned with the initial steps of the reaction between formaldehyde and ammonia, while poor attention is dedicated to successive steps. In this article, different results from published literature were critically considered and the most probable hypothesis regarding the mechanism of HMT formation is discussed on the basis of B3LYP calculations of free energies.

Solid-phase extraction of PFOA and PFOS from surface waters on functionalized multiwalled carbon nanotubes followed by UPLC-ESI-MS.

This is the first report on the analytical application of multiwalled carbon nanotubes (MWCNTs) as solid-phase extraction (SPE) sorbents for determination in surface waters, at the nanograms per litre level, of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), the two predominant contaminants among the perfluorinated compounds detected. After the preconcentration step, the quantification was achieved by ultraperformance liquid chromatography-electrospray ionization mass spectrometry. To increase the extraction efficiency towards these amphiphilic compounds, MWCNTs were derivatized with amino-terminated alkyl chains, thus producing a mixed-mode material (MWCNT-R-NH2) combining hydrophobic affinity and anion-exchange properties. Experiments with distilled, tap and river water (pH 3) spiked at different concentrations (10, 15, 30, 100, 200 and 500 ng L(-1)) provided absolute recoveries in the range 71-102% (n = 3, relative standard deviations less than 10%). Analytes were eluted in a single fraction with 6 mL methanol (3 × 10(-4) M NaOH). The within-laboratory reproducibility of the MWCNT-R-NH2 SPE sorbent was evaluated with raw river water, and relative standard deviations less than 15% were obtained (n = 4). Preconcentration factors up to 125 (500-mL sample) made it possible to quantify PFOA and PFOS at low nanograms per litre levels in naturally contaminated river water. The method quantification limits of 10 ng L(-1) for PFOA and 15 ng L(-1) for PFOS were well below the advisory levels for drinking and surface waters. Comparison with non-derivatized MWCNTs highlighted the role of functionalization in improving the adsorption affinity towards these contaminants. MWCNT-R-NH2 maintained their extraction capability for at least eight repeated adsorption/desorption cycles.

Biocompatibility of functionalized boron phosphate (BPO4) nanoparticles for boron neutron capture therapy (BNCT) application.

Boron neutron capture therapy (BNCT) is a radiotherapy treatment based on the accumulation in the tumor of a (10)B-containing drug and subsequent irradiation with low energy neutrons, which bring about the decay of (10)B to (7)Li and an α particle, causing the death of the neoplastic cell. The effectiveness of BNCT is limited by the low delivery and accumulation of the used boron-containing compounds. Here we report the development and the characterization of BPO4 nanoparticles (NPs) as a novel possible alternative drug for BNCT. An extensive analysis of BPO4 NP biocompatibility was performed using both mature blood cells (erythrocytes, neutrophils and platelets) and a model of hematopoietic progenitor cells. A time- and concentration-dependent cytotoxicity study was performed on neoplastic coloncarcinoma and osteosarcoma cell lines. BPO4 functionalization with folic acid, introduced to improve the uptake by tumor cells, appeared to effectively limit the unwanted effects of NPs on the analyzed blood components. FROM THE CLINICAL EDITOR: Boron neutron capture therapy (BNCT) is a radiotherapy treatment modality based on the accumulation of a (10)B-containing drug and subsequent irradiation with low energy neutrons, inducing the decay of (10)B to (7)Li and an α particle, causing neoplastic cell death. This team of authors reports on a folic acid functionalized BPO4 nanoparticle with improved characteristics compared with conventional BNCT approaches, as demonstrated in tumor cell lines, and hopefully to be followed by translational human studies.

A new cysteamine-copper chemically modified screen-printed gold electrode for glyphosate determination.

A chemically modified screen-printed gold electrode has been prepared by covering the electrode surface with a cysteamine-copper self-assembled monolayer (SAM). The sensor was effective for the voltammetric sensing of glyphosate. The method exploits the interaction of glyphosate with copper ions complexed by cysteamine, which results in a decrease in the intensity of copper redox current. Cyclic voltammetry was employed as a measuring technique. When dealing with voltammograms with numerous peaks changing in shape and size, it is difficult to define which signal is the most significant for the analyte determination; in these cases, a helpful approach is chemometrics. In this work, PLS (Partial Least Square regression) has been applied to build models to correlate the signal with the glyphosate concentration in standard aqueous solutions and tap water samples (matrix-matched calibration). The method's figures of merits were evaluated, obtaining a limit of quantification of about 5 µM. The reliability of the proposed sensor was verified by analyzing tap water spiked with glyphosate; recoveries higher than 90 % were achieved.