Solvation of cationic copper clusters in molecular hydrogen.

Multiply charged superfluid helium nanodroplets are utilized to facilitate the growth of cationic copper clusters (Cun+, where n = 1-8) that are subsequently solvated with up to 50 H2 molecules. Production of both pristine and protonated cationic Cu clusters are detected mass spectrometrically. A joint effort between experiment and theory allows us to understand the nature of the interactions determining the bonding between pristine and protonated Cu+ and Cu2+ cations and molecular hydrogen. The analysis reveals that in all investigated cationic clusters, the primary solvation shell predominantly exhibits a covalent bonding character, which gradually decreases in strength, while for the subsequent shells an exclusive non-covalent behaviour is found. Interestingly, the calculated evaporation energies associated with the first solvation shell markedly surpass thermal values, positioning them within the desirable range for hydrogen storage applications. This comprehensive study not only provides insights into the solvation of pristine and protonated cationic Cu clusters but also sheds light on their unique bonding properties.

Pharmacology and toxicology of xylazine: quid novum?

The current opioid overdose crisis is characterized by the presence of unknown psychoactive adulterants. Xylazine is an alpha-2 receptor agonist that is not approved for human use but is commonly used in veterinary medicine due to its sedative and muscle-relaxant properties. Cases of human intoxication due to accidental or voluntary use have been reported since the 1980s. However, reports of adulteration of illicit opioids (heroin and illicit fentanyl) with xylazine have been increasing all over Western countries. In humans, xylazine causes respiratory depression, bradycardia, and hypotension-posing individuals, using xylazine-adulterated opioids. We present a narrative review of the latest intoxication cases related to xylazine, to bring awareness to readers and also to help pathologists to detect and deal with xylazine cases.

Substance abuse in times of COVID-19 pandemic: a "perfect storm" for substance use disorder and mental health?

ABSTRACT: Our lives and communities have been besieged by COVID-19 for almost two years, and society and its functioning have been turned upside down and upset, through limitations and restrictions aimed at stemming the spread of the SARS-CoV-2 virus. Severe levels of anxiety, distress and uncertainty have taken a huge toll on our daily lives from the social, professional and emotional perspectives, but it is still rather unclear how serious an impact the emergency has had on a class of particularly vulnerable individuals: those with substance abuse issues. Particularly, we would like to draw attention to a uniquely troublesome development: forced isolation resulting from pandemic-related restrictions and how it has impacted drug users and their efforts to achieve recovery.

Determination of nine new fentanyl analogues and metabolites in consumers' urine by ultra-high-performance liquid chromatography-tandem mass spectrometry.

OBJECTIVE: New fentanyl analogues have been constantly emerging into the illegal drug market as cheap substitutes of heroin posing a serious health threat for consumers because of their high toxicity. Analytical methods to disclose the presence of these compounds in biological fluids of intoxicated individuals need to be updated to keep up with the new trends. In this study, we updated an ultra-high-performance liquid chromatography-tandem mass spectrometry method previously developed, for detecting some new fentanyl analogues and metabolites (sufentanil and norsufentanil, cis-3-methylnorfentanyl, trans-3-methylnorfentanyl, metabolites of cis and transmethylfentanyl, beta-phenylfentanyl, phenylfentanyl, para-fluoro furanyl fentanyl, isobutyryl fentanyl and ocfentanil) in urine sample. MATERIALS AND METHODS: Urine samples were simply diluted before injection in the chromatograph equipped with a reversed phase microcolumn. Detection was achieved with a triple quadrupole mass spectrometer with an electrospray ionization source in positive ion mode and operated in multiple reaction monitoring. RESULTS: The chromatographic separation was short (5 min) and the method was fully validated with a high sensitivity being limits of quantifications from 0.003 to 0.006 µg/L urine for the analytes under investigation. CONCLUSIONS: The suitability of the method was tested with urine specimens from former heroin addicts, which resulted positive by immunological screening to the class of fentanyl analogues. This method represents a valid tool to document recent exposure to the above-reported compounds for clinical and forensic purposes.

Hair determination of per- and polyfluoroalkyl substances (PFAS) in the Italian population.

Per- and polyfluoroalkyl substances (PFAS) are anthropogenic chemicals present in the environment and defined as persistent organic pollutants (POPs). The interest in these forms of contaminants is related to the toxic consequences for health derived from exposures and bioaccumulation processes. The present research aims at assessing differences in the exposure of PFAS in the Italian population by hair analyses. To this aim, 20 compounds of the PFAS family were investigated in hair of 86 Italian subjects distributed across the regions of Veneto, Emilia-Romagna, Lombardy and Marche. The applied method was ad hoc developed in a previous research and included SPE extraction and LC-QTOF analysis. In the analyzed population, 66.4 % had quantifiable amounts of one or more PFAS molecules (up to 4 compounds); mean PFAS content, expressed as sum of PFAS, was 0.1457 ng/g, ranging from "not detected" to 0.85 ng/g (SD 0.1867). PFOA and PFOS were the chemicals most frequently detected, with mean concentrations of 0.1402 ng/g and 0.1155 ng/g, respectively. PFBA was detected in 9.3 % of subjects with a mean concentration of 0.3760 ng/g; PFNA in 3.5 % of subjects with mean concentration 0.12 ng/g; PFDA was found in one subject at the concentration of 0.541 ng/g. PFUnA and PFHxS were detected below the limit of quantification. The overall results displayed differences in the presence and prevalence of PFAS in hair of the Italian population on a geographical base. On the contrary, no significatively differences in the amount of PFAS were observed when considering gender or age classes. On this base, hair can be considered a good diagnostic tool to assess PFAS exposure on a regional-scaled base. Of course, more studies are required to infer PFAS internal dose from hair results due to its peculiar detection window and to interpretative issues derived from external contamination.

Aggregation of coronene: the effect of carboxyl and amine functional groups.

The aggregation of coronene is relevant to understand the formation of carbon nanomaterials, including graphene quantum dots (GQDs) that show exceptional photophysical properties. This article evaluates the influence of carboxyl and amine substituting groups on the aggregation of coronene by performing a global optimization study based on a new potential energy surface. The structures of clusters with substituted coronene are similar to those formed by un-substituted monomers, that is, stacked (non-stacked) motifs are favoured for small-size (large-size) clusters. Nonetheless, the presence of carboxyl and amine groups leads to an increase of the number of local minima of comparable energy. The clusters with substituted monomers have also shown to enhance the attractive component interaction, which can be attributed to weak induction and charge transfer effects and to stronger electrostatic contributions. Moreover, the calculated height of magic-number structures of the clusters in this work is compatible with the morphology of the GQDs reported in the literature.

SARS-CoV-2 identification in lungs, heart and kidney specimens by transmission and scanning electron microscopy.

From two COVID-19-related deaths, samples of lung, heart and kidney were collected and processed for Transmission and Scanning Electron Microscopy (TEM and SEM) with the aim of identifying the virus. Virions of SARS-CoV-2 were found in all tissues by TEM and SEM, corroborating the hypothesis that the virus enters the cells of different organs. This is the first report identifying SARS-CoV-2 in different human tissues by TEM and SEM.

Is the issue of Chemsex changing?

In this letter, which is meant as a response to the letter titled "Sex enhancers: challenges, threats and the need for targeted measures", the Authors discuss the evolution of Chemsex phenomenon towards at least two directions: firstly, the use of psychoactive and non-psychoactive substances usually implicated in Chemsex, such as GHB/GBL, ketamine, mephedrone and other synthetic cathinones and erectile dysfunction medications, is currently accompanied by the use of illicit opioids, which have recently been indicated as a new serious health threat for consumers. In addition, as reported by the last European Drug report, the simultaneous use of illicit benzodiazepines with non-medical opioids misuse has also been observed. Secondly, strictly linked to the rising use of non-medical opioids is the risk of transition towards heroine followed by the adoption of risky injection practices frequently accompanied by high-risk sexual behaviors. In this sense, the current definition of the phenomenon as "the voluntary intake of certain psychoactive and non- psychoactive drugs in the context of sex parties and sexual intercourses with the intention of facilitating and/or enhancing the sexual encounter mostly among men who have sex with other men (MSM)" has been expanded to "heterosexual chemsex".

Aggregation enhancement of coronene molecules by seeding with alkali-metal ions.

Microsolvation constitutes the first step in the formation of cluster structures of molecules that surround a solute in the bulk and it allows for a deep insight into the relationship between the structure of the solvation shells and other physical properties. We propose semiempirical potential energy functions that are able to describe the interaction between K+ or Cs+ with coronene. Such functions were calibrated through the comparison with accurate estimations of the interaction between the cation and the planar hydrocarbon, obtained by means of ab initio electronic-structure calculations. By employing the potential energy functions and an evolutionary algorithm (EA), we have investigated the structure and energetics of the clusters resulting from the microsolvation of either K+ or Cs+ with coronene molecules. The reliability of the results for smaller clusters was checked by performing geometry re-optimization exploiting a suitable DFT level of theory. This has allowed for the characterization of the first solvation shells of planar molecules of coronene around an alkali-metal ion. It has also been found that the presence of metal ion impurities considerably enhances the formation of small coronene clusters leading to much stronger binding energies for heterogeneous with respect to homogeneous aggregates. These clusters could represent relevant species involved in the early stages of soot nucleation.

Use of cognitive enhancers: methylphenidate and analogs.

OBJECTIVE: In the last decades, several cognitive-enhancing drugs have been sold onto the drug market. Methylphenidate and analogs represent a sub-class of these new psychoactive substances (NPS). We aimed to review the use and misuse of methylphenidate and analogs, and the risk associated. Moreover, we exhaustively reviewed the scientific data on the most recent methylphenidate analogs (methylphenidate and ethylphenidate excluded). MATERIALS AND METHODS: Literature search was performed on methylphenidate and analogs, using specialized search engines accessing scientific databases. Additional reports were retrieved from international agencies, institutional websites, and drug user forums. RESULTS: Methylphenidate/Ritalin has been used for decades to treat attention deficit disorders and narcolepsy. More recently, it has been used as a cognitive enhancer and a recreational drug. Acute intoxications and fatalities involving methylphenidate were reported. Methylphenidate was scheduled as an illegal drug in many countries, but NPS circumventing the ban and mimicking the psychostimulant effects of methylphenidate started being available: ethylphenidate, 3,4-dichloromethylphenidate, 3,4-dichloroethylphenidate, 4-fluoromethylphenidate, 4-fluoroethylphenidate, methylnaphthidate, ethylnaphthidate, isopropylphenidate, propylphenidate, 4-methylmethylphenidate, and N-benzylethylphenidate have been available in the past few years. Only little data is currently available for these substances. Many intoxications involving methylphenidate analogs were reported. To date, ethylphenidate was involved in 28 fatalities, although it was reportedly directly related to the cause of death in only 7 cases; 3,4-dichloroethylphenidate was involved in 1 death. CONCLUSIONS: The rapid expansion of methylphenidate analogs onto the drug market in the past few years makes likely the occurrence of intoxications and fatalities in the next years. Careful monitoring and systematic control of methylphenidate analogs should be undertaken to reduce the uprising threat, and education efforts should be made among high-risk populations.

Closer versus Long Range Interaction Effects on the Non-Arrhenius Behavior of Quasi-Resonant O2 + N2 Collisions.

We report in this paper an investigation on energy transfer processes from vibration to vibration and/or translation in thermal and subthermal regimes for the O2 + N2 system performed using quantum-classical calculations on different empirical, semiempirical, and ab initio potential energy surfaces. In particular, the paper focuses on the rationalization of the non-Arrhenius behavior (inversion of the temperature dependence) of the quasi-resonant vibration-to-vibration energy transfer transition rate coefficients at threshold. To better understand the microscopic nature of the involved processes, we pushed the calculations to the detail of the related cross sections and analyzed the impact of the medium and long-range components of the interaction on them. Furthermore, the variation with temperature of the dependence of the quasi-resonant rate coefficient on the vibrational energy gap between initial and final vibrational states and the effectiveness of quantum-classical calculations to overcome the limitations of the purely classical treatments were also investigated. These treatments, handled in an open molecular science fashion by chaining data and competencies of the various laboratories using a grid empowered molecular simulator, have allowed a rationalization of the dependence of the computed rate coefficients in terms of the distortion of the O2-N2 configuration during the diatom-diatom collisions. A way of relating such distortions to a smooth and continuous progress variable, allowing a proper evolution from both long to closer range formulation of the interaction and from its entrance to exit channel (through the strong interaction region) relaxed graphical representations, is also discussed in the paper.

The role of charge transfer in the stability and reactivity of chemical systems from experimental findings.

A variety of phenomena, of apparently different natures, are described within a unifying picture, by properly isolating the role of charge/electron transfer as an interaction component triggering chemical reactivity. This basic quantity is isolated by analyzing, with advanced theoretical methods developed by our group, experimental findings characterized with different techniques, such as double photo-ionization spectra, scattering cross sections and auto-ionization reaction probabilities. Suitable rationalization of such phenomena appears to be crucial for modeling the selectivity of basic elementary processes occurring in systems at increasing complexity of fundamental/applied interest, such as plasmas, flames, interstellar media, planetary atmospheres and biological environments.

A global optimization perspective on molecular clusters.

Although there is a long history behind the idea of chemical structure, this is a key concept that continues to challenge chemists. Chemical structure is fundamental to understanding most of the properties of matter and its knowledge for complex systems requires the use of state-of-the-art techniques, either experimental or theoretical. From the theoretical view point, one needs to establish the interaction potential among the atoms or molecules of the system, which contains all the information regarding the energy landscape, and employ optimization algorithms to discover the relevant stationary points. In particular, global optimization methods are of major importance to search for the low-energy structures of molecular aggregates. We review the application of global optimization techniques to several molecular clusters; some new results are also reported. Emphasis is given to evolutionary algorithms and their application in the study of the microsolvation of alkali-metal and Ca2+ ions with various types of solvents.This article is part of the themed issue 'Theoretical and computational studies of non-equilibrium and non-statistical dynamics in the gas phase, in the condensed phase and at interfaces'.

Enhanced Flexibility of the O2 + N2 Interaction and Its Effect on Collisional Vibrational Energy Exchange.

Prompted by a comparison of measured and computed rate coefficients of Vibration-to-Vibration and Vibration-to-Translation energy transfer in O2 + N2 non-reactive collisions, extended semiclassical calculations of the related cross sections were performed to rationalize the role played by attractive and repulsive components of the interaction on two different potential energy surfaces. By exploiting the distributed concurrent scheme of the Grid Empowered Molecular Simulator we extended the computational work to quasiclassical techniques, investigated in this way more in detail the underlying microscopic mechanisms, singled out the interaction components facilitating the energy transfer, improved the formulation of the potential, and performed additional calculations that confirmed the effectiveness of the improvement introduced.

Molecular Dynamics Simulations of Small Clusters and Liquid Hydrogen Sulfide at Different Thermodynamic Conditions.

A new force field for the intermolecular H2S-H2S interaction has been used to study the most relevant properties of the hydrogen sulfide system from gaseous to liquid phases by means of molecular dynamics (MD) simulations. In order to check the validity of the interaction formulation, ab initio CCSD(T)/aug-cc-pVTZ calculations, including the counterpoise correction on the H2S, (H2S)2, and (H2S)3 structures optimized at the MP2/aug-cc-pVDZ level, have been performed. The (H2S)2,3 systems have been characterized by performing NVE MD simulations at decreasing values of the temperature, while the liquid sulfide behavior has been investigated considering a NpT ensemble of 512 molecules at several thermodynamic states, defined by different pressure and temperature values. Additional calculations using an ensemble of 2197 molecules at two different temperatures have been performed to investigate the liquid/vapor interface of the system. The S-S, S-H, and H-H radial distribution functions and the coordination number, calculated at the same conditions used in X-ray and neutron diffraction experiments, and the evaluated thermodynamic and structural properties have been compared successfully with experimental data, thus confirming the reliability of the force field formulation and of the MD predictions.

Efficiency of Collisional O2 + N2 Vibrational Energy Exchange.

By following the scheme of the Grid Empowered Molecular Simulator (GEMS), a new O2 + N2 intermolecular potential, built on ab initio calculations and experimental (scattering and second virial coefficient) data, has been coupled with an appropriate intramolecular one. On the resulting potential energy surface detailed rate coefficients for collision induced vibrational energy exchanges have been computed using a semiclassical method. A cross comparison of the computed rate coefficients with the outcomes of previous semiclassical calculations and kinetic experiments has provided a foundation for characterizing the main features of the vibrational energy transfer processes of the title system as well as a critical reading of the trajectory outcomes and kinetic data. On the implemented procedures massive trajectory runs for the proper interval of initial conditions have singled out structures of the vibrational distributions useful to formulate scaling relationships for complex molecular simulations.

Low-energy structures of benzene clusters with a novel accurate potential surface.

The benzene-benzene (Bz-Bz) interaction is present in several chemical systems and it is known to be crucial in understanding the specificity of important biological phenomena. In this work, we propose a novel Bz-Bz analytical potential energy surface which is fine-tuned on accurate ab initio calculations in order to improve its reliability. Once the Bz-Bz interaction is modeled, an analytical function for the energy of the Bzn clusters may be obtained by summing up over all pair potentials. We apply an evolutionary algorithm (EA) to discover the lowest-energy structures of Bzn clusters (for n=2-25), and the results are compared with previous global optimization studies where different potential functions were employed. Besides the global minimum, the EA also gives the structures of other low-lying isomers ranked by the corresponding energy. Additional ab initio calculations are carried out for the low-lying isomers of Bz3 and Bz4 clusters, and the global minimum is confirmed as the most stable structure for both sizes. Finally, a detailed analysis of the low-energy isomers of the n = 13 and 19 magic-number clusters is performed. The two lowest-energy Bz13 isomers show S6 and C3 symmetry, respectively, which is compatible with the experimental results available in the literature. The Bz19 structures reported here are all non-symmetric, showing two central Bz molecules surrounded by 12 nearest-neighbor monomers in the case of the five lowest-energy structures.

Chirality of weakly bound complexes: the potential energy surfaces for the hydrogen-peroxide-noble-gas interactions.

We consider the analytical representation of the potential energy surfaces of relevance for the intermolecular dynamics of weakly bound complexes of chiral molecules. In this paper we study the H2O2-Ng (Ng=He, Ne, Ar, Kr, and Xe) systems providing the radial and the angular dependence of the potential energy surface on the relative position of the Ng atom. We accomplish this by introducing an analytical representation which is able to fit the ab initio energies of these complexes in a wide range of geometries. Our analysis sheds light on the role that the enantiomeric forms and the symmetry of the H2O2 molecule play on the resulting barriers and equilibrium geometries. The proposed theoretical framework is useful to study the dynamics of the H2O2 molecule, or other systems involving O-O and S-S bonds, interacting by non-covalent forces with atoms or molecules and to understand how the relative orientation of the O-H bonds changes along collisional events that may lead to a hydrogen bond formation or even to selectivity in chemical reactions.

Benzene-hydrogen bond (C6H6-HX) interactions: the influence of the X nature on their strength and anisotropy.

The intermolecular potential energy of the C6H6-SH2 and C6H6-NH3 dimers is formulated as combination of independent electrostatic and nonelectrostatic contributions. The relevant parameters of the nonelectrostatic terms, derived from molecular polarizability components, have been proved to be useful to describe in a consistent way both size repulsion and dispersion attraction forces. The representation adopted for the electrostatic contribution asymptotically reproduces the dipole quadrupole interaction. To test the validity of the proposed potential formulation, the features of the most stable configurations of the systems predicted have been compared with the available ab initio and experimental data. Moreover, the strength of the C6H6-HX interaction has been analyzed comparing the obtained results with the corresponding ones for the C6H6-H2O and C6H6-CH4 systems, investigated previously with the same methodology. Information on the relative orientation dependence of the partners, arising from the anisotropy of the intermolecular interaction, evaluated at different intermolecular distances, has been also obtained. Such information is crucial to evaluate sterodynamics effects in bimolecular collisions.