Little is known about how pharmacological and toxicological knowledge evolves. The aim of this study was to investigate the changes in the presentation of the poison hydrogen cyanide in sixteen German-language pharmacology and toxicology textbooks from 1878 to 2020. The categories of structure, molecular mechanism of action, occurrence, effects, resorption, areas of application, lethal dose, acute symptoms of intoxication, treatment of hydrogen cyanide poisoning, and recommended therapeutic preparations were evaluated. The knowledge on the structure, lethal dosage, and occurrence of hydrogen cyanide has remained constant. In contrast, knowledge on molecular mechanism of action and recommended preparations of the poison has changed dramatically. Until 1944, the binding of hydrogen cyanide to hemoglobin was considered the mechanism of action, whereas from 1951 onwards, the interaction of hydrogen cyanide with the Fe3+ of cytochrome oxidase was described. The number of preparations containing hydrogen cyanide decreased into obsolescence until 1951. The areas of application of hydrogen cyanide also show a change, as from 1919 onwards, mainly industrial areas of application of the poison are described instead of medical ones, and from 1951 onwards, criminalistic areas of application are also mentioned. Thus, pharmacological and toxicological knowledge develops non-linearly, molecular mechanism and uses being the most dynamic areas, whereas the knowledge about hydrogen cyanide\'s chemical structure, lethal dose, and occurrence remained constant. Older pharmacology and toxicology textbooks were better than newer ones at discussing changes in scientific concepts. Pharmacology and toxicology textbooks also mostly failed to discuss the misuse of hydrogen cyanide (Zyklon B) during the Nazi regime, missing an important opportunity to showcase the ethical responsibility of pharmacology and toxicology. Thus, future pharmacology and toxicology textbooks should improve on discussing the development of pharmacological and toxicological concepts and the ethical responsibility of the discipline.

Cassava extracts containing cyanogenic compounds demonstrate anticancer properties. The cyanogenic glucoside linamarin found abundantly in cassava can release hydrogen cyanide (HCN) upon hydrolysis, a potent cytotoxin. However, linamarin\'s hydrolysis mechanism by human enzymes is poorly delineated and constitutes a bottleneck for therapeutic development. This study aimed to investigate linamarin\'s hydrolysis mechanism by human β-glucosidase and identify structural derivatives with enhanced hydrolytic potential using density functional theory calculations. Results revealed α-anomeric derivatives as promising, with leaving group ability and steric bulk strongly governing hydrolysability. We identified several linamarin analogs with predicted rapid hydrolysis kinetics that may enable swift cytotoxic HCN release against cancer cells. This investigation enriches understanding of cyanogenic glycoside reactivity to facilitate their development as targeted antineoplastic agents. The identified derivatives set the groundwork for experimental evaluation of enhanced linamarin-inspired compounds as innovative cancer therapeutics.

BACKGROUND: The hydrogen cyanide (HCN) hydrolysis reaction mechanism over Al-doped graphene was investigated through the density functional theory method. HCN preferentially adsorbed vertically on the Al top site to form a stable adsorption configuration. H2O preferentially adsorbed parallel on the Al top site to form a stable adsorption configuration. The competitive adsorption of HCN and H2O weakened the adsorption stability of each molecule over Al-doped graphene. The break of C-N and H-O bonds was the key process in the preferential fracture pathway of the C-H bond. The break of C-N and C-H bonds was the key process in the preferential fracture pathway of the H-O bond. HCN played the role of bridge in the joint adsorption process. H atom transfer and C-N bond cleavage promoted the generation of CO and NH3. The change in the order of H atom transfer determined the reaction energy barrier. NH2CHO was more likely to act as an intermediate to promote the hydrolysis process.
METHODS: The calculation work was achieved from the Dmol3 program in Material Studio 2017 using the GGA/PBE method with DNP basis, including the geometric structure and reaction pathway optimization, and adsorption energy calculation. All calculations were performed using a spin-polarized set and the TS method was used for DFT-D correction.

Postmortem carbon monoxide (CO) and hydrogen cyanide (HCN) diffusion under ambient conditions was assessed in a human cadaver model. The main objective of this study was to determine whether the postmortem diffusion of HCN and CO greatly affected the determination of HCN, carboxyhemoglobin (COHb), and carboxymyoglobin (COMb). Layered samples of blood, musculocutaneous, and muscular specimens were collected from the adult cadavers and placed in the tight chambers designed for the purpose of this experiment. The specimens were treated with CO and HCN for 24 h. COHb and COMb were determined using headspace gas chromatography (GC) with an O-FID detector while the HCN values were assessed using a GC headspace with an NPD detector. It was shown that the skin substantially limited the diffusion of CO which penetrated the superficial layers of the muscle very slightly, all the while not affecting the blood level of COHb in the 4.5 cm layer of the muscle located underneath. There were no differences regarding the CO diffusion between superficially charred and thermally coagulated compared to that observed in intact integuments. In addition, the cutaneous sample deprived of the adipose layer was not shown to be a barrier to the moderate diffusion of CO into the blood layer below. HCN was found to easily diffuse from the skin to the blood vessels (vein specimens), and partial charring and thermocoagulation of the superficial muscular layer favored the diffusion of cyanides into the tissues. Similarly to CO, HCN diffusion to the blood and muscles was greatly limited by the adipose layer.

The matrix-isolated infrared spectrum of a hydrogen cyanide-methyl chloride complex was investigated in a solid argon matrix. HCN and CH3Cl were co-condensed onto a substrate held at 10 K with an excess of argon gas, and the infrared spectrum was measured using Fourier-transform infrared spectroscopy. Quantum chemical geometry optimization, harmonic frequency, and natural bonding orbital calculations indicate stabilized hydrogen- and halogen-bonded structures. The two resulting weakly bound complexes are both composed of one CH3Cl molecule bound to a (HCN)3 subunit, where the three HCN molecules are bound head-to-tail in a ring formation. Our study suggests that─in the presence of CH3Cl─the formation of (HCN)3 is promoted through complexation. Since HCN aggregates are an important precursor to prebiotic monomers (amino acids and nucleobases) and other life-bearing polymers, this study has astrophysical implications toward the search for life in space.

Manihot esculenta (cassava) is a root crop originating from South America that is a major staple in the tropics, including in marginal environments. This study focused on South American and African germplasm and investigated the genetic architecture of hydrogen cyanide (HCN), a major component of root quality. HCN, representing total cyanogenic glucosides, is a plant defense component against herbivory but is also toxic for human consumption. We genotyped 3354 landraces and modern breeding lines originating from 26 Brazilian states and 1389 individuals were phenotypically characterized across multi-year trials for HCN. All plant material was subjected to high-density genotyping using genotyping by sequencing. We performed genome-wide association mapping to characterize the genetic architecture and gene mapping of HCN. Field experiments revealed strong broad- and narrow-sense trait heritability (0.82 and 0.41, respectively). Two major loci were identified, encoding for an ATPase and a MATE protein, and contributing up to 7 and 30% of the HCN concentration in roots, respectively. We developed diagnostic markers for breeding applications, validated trait architecture consistency in African germplasm and investigated further evidence for the domestication of sweet and bitter cassava. Fine genomic characterization revealed: (i) the major role played by vacuolar transporters in regulating HCN content; (ii) the co-domestication of sweet and bitter cassava major alleles are dependent upon geographical zone; and (iii) the major loci allele for high HCN in M. esculenta Crantz seems to originate from its ancestor, M. esculenta subsp. flabellifolia. Taken together, these findings expand our insights into cyanogenic glucosides in cassava roots and its glycosylated derivatives in plants.

The nitrogen-containing gases pyrolyzed from sewage sludge can be converted into NOx compounds, which would cause severe environmental pollution. This study developed a new strategy to reduce the emission of NOx precursors such as ammonia (NH3) and hydrogen cyanide (HCN) using red mud. The highest reduction efficiencies (15.10% for NH3 and 24.72% for HCN) were achieved at 900 °C while compared with those pyrolyzed from raw sludge without the addition of red mud. The transformation and distribution of nitrogenous compounds in three-phase pyrolysates were studied at 400-800 °C for pyrolysis process of a model soybean protein compound. The nitrogenous compounds, i.e., amine-N, heterocyclic-N, and nitrile-N, were identified as the three main intermediates related with the production of NOx precursors. Ferric oxide (Fe2O3) and calcium oxide (CaO) presented in red mud were identified as the driving force which facilitated nitrogen stabilization in char (e.g., at 800 °C, 21.63% increase of char-N after addition of Fe2O3, and 41.54% increase of char-N after addition of CaO). These metal oxides possibly reacted with protein-N to form FexN and CaCxNy, inhibited the secondary cracking of amine-N compounds in tar (e.g., at 800 °C, 2.33% increase of amine-N after addition of Fe2O3, and 0.38% increase of amine-N after addition of CaO), and reduced the production of nitrile-N (e.g., at 800 °C, 30.41% reduction of nitrile-N after addition of Fe2O3, and 27.40% reduction of nitrile-N after addition of CaO) and heterocyclic-N compounds (e.g., at 800 °C, 21.60% reduction of heterocyclic-N after addition of Fe2O3, and 13.98% reduction of heterocyclic-N after addition of CaO). Hence, the emission of NH3 and HCN in gas phase can be controlled. Moreover, Fe2O3 showed better capability in controlling the emission of NOx precursors than CaO (higher reduction of NH3-N and higher reduction of HCN-N). These results indicate that red mud is an efficient catalyst to reduce emission of NOx precursors through controlling intermediates at 400-800 °C.

The prospects of a control for a novel gallium nitride pseudo-halide vapor phase epitaxy (PHVPE) with HCN were thoroughly analyzed for hydrocarbons-NH3-Ga gas phase on the basis of quantum chemical investigation with DFT (B3LYP, B3LYP with D3 empirical correction on dispersion interaction) and ab-initio (CASSCF, coupled clusters, and multireference configuration interaction including MRCI+Q) methods. The computational screening of reactions for different hydrocarbons (CH4, C2H6, C3H8, C2H4, and C2H2) as readily available carbon precursors for HCN formation, potential chemical transport agents, and for controlled carbon doping of deposited GaN was carried out with the B3LYP method in conjunction with basis sets up to aug-cc-pVTZ. The gas phase intermediates for the reactions in the Ga-hydrocarbon systems were predicted at different theory levels. The located π-complexes Ga…C2H2 and Ga…C2H4 were studied to determine a probable catalytic activity in reactions with NH3. A limited influence of the carbon-containing atmosphere was exhibited for the carbon doping of GaN crystal in the conventional GaN chemical vapor deposition (CVD) process with hydrocarbons injected in the gas phase. Our results provide a basis for experimental studies of GaN crystal growth with C2H4 and C2H2 as auxiliary carbon reagents for the Ga-NH3 and Ga-C-NH3 CVD systems and prerequisites for reactor design to enhance and control the PHVPE process through the HCN synthesis.

Halogen bonding, a noncovalent interaction between a halogen atom X in one molecule and a negative site in another, plays an important role in fields as diverse as molecular biology, drug design, and crystal engineering. In this work, the H3N∙∙∙XCN∙∙∙SF2 and H3N∙∙∙XCN∙∙∙SO2 (X  =  F, Cl, Br, I) complexes are theoretically investigated to find ways to enhance the halogen bond interaction. Cooperative effects are found when X∙∙∙N and S∙∙∙N bonds coexist in the same complex. The ab initio calculations are carried out using at the MP2/aug-cc-pVTZ level, through analysis of surface electrostatic potentials VS(r), interaction energies and the topological analysis based on the quantum theory of atoms in molecules. Particular attention is paid to understand the origin of the X∙∙∙N and S∙∙∙N interactions in the ternary complexes. The cooperativity between both types of the interaction is mainly caused by the electrostatic effects.

The U.S. Occupational Safety and Health Administration (OSHA) estimates that half a million health-care workers are exposed to laser surgical smoke each year. The purpose of this study was to establish a methodology to (1) estimate emission rates of laser-generated air contaminants (LGACs) using an emission chamber, and to (2) perform a screening study to differentiate the effects of three laser operational parameters. An emission chamber was designed, fabricated, and assessed for performance to estimate the emission rates of gases and particles associated with LGACs during a simulated surgical procedure. Two medical lasers (Holmium Yttrium Aluminum Garnet [Ho:YAG] and carbon dioxide [CO2]) were set to a range of plausible medical laser operational parameters in a simulated surgery to pyrolyze porcine skin generating plume in the emission chamber. Power, pulse repetition frequency (PRF), and beam diameter were evaluated to determine the effect of each operational parameter on emission rate using a fractional factorial design. The plume was sampled for particulate matter and seven gas phase combustion byproduct contaminants (benzene, ethylbenzene, toluene, formaldehyde, hydrogen cyanide, carbon dioxide, and carbon monoxide): the gas phase emission results are presented here. Most of the measured concentrations of gas phase contaminants were below their limit of detection (LOD), but detectable measurements enabled us to determine laser operation parameter influence on CO2 emissions. Confined to the experimental conditions of this screening study, results indicated that beam diameter was statistically significantly influential and power was marginally statistically significant to emission rates of CO2 when using the Ho:YAG laser but not with the carbon dioxide laser; PRF was not influential vis-a-vis emission rates of these gas phase contaminants.