Weakly Bound Complex Formation between HCN and CH3Cl: A Matrix-Isolation and Computational Study.

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.

Storage and release of hydrogen cyanide in a chelicerate (Oribatula tibialis).

Cyanogenesis denotes a chemical defensive strategy where hydrogen cyanide (HCN, hydrocyanic or prussic acid) is produced, stored, and released toward an attacking enemy. The high toxicity and volatility of HCN requires both chemical stabilization for storage and prevention of accidental self-poisoning. The few known cyanogenic animals are exclusively mandibulate arthropods (certain myriapods and insects) that store HCN as cyanogenic glycosides, lipids, or cyanohydrins. Here, we show that cyanogenesis has also evolved in the speciose Chelicerata. The oribatid mite Oribatula tibialis uses the cyanogenic aromatic ester mandelonitrile hexanoate (MNH) for HCN storage, which degrades via two different pathways, both of which release HCN. MNH is emitted from exocrine opisthonotal oil glands, which are potent organs for chemical defense in most oribatid mites.

Polymorphism and electronic structure of polyimine and its potential significance for prebiotic chemistry on Titan.

The chemistry of hydrogen cyanide (HCN) is believed to be central to the origin of life question. Contradictions between Cassini-Huygens mission measurements of the atmosphere and the surface of Saturn's moon Titan suggest that HCN-based polymers may have formed on the surface from products of atmospheric chemistry. This makes Titan a valuable "natural laboratory" for exploring potential nonterrestrial forms of prebiotic chemistry. We have used theoretical calculations to investigate the chain conformations of polyimine (pI), a polymer identified as one major component of polymerized HCN in laboratory experiments. Thanks to its flexible backbone, the polymer can exist in several different polymorphs, which are relatively close in energy. The electronic and structural variability among them is extraordinary. The band gap changes over a 3-eV range when moving from a planar sheet-like structure to increasingly coiled conformations. The primary photon absorption is predicted to occur in a window of relative transparency in Titan's atmosphere, indicating that pI could be photochemically active and drive chemistry on the surface. The thermodynamics for adding and removing HCN from pI under Titan conditions suggests that such dynamics is plausible, provided that catalysis or photochemistry is available to sufficiently lower reaction barriers. We speculate that the directionality of pI's intermolecular and intramolecular =N-H(…)N hydrogen bonds may drive the formation of partially ordered structures, some of which may synergize with photon absorption and act catalytically. Future detailed studies on proposed mechanisms and the solubility and density of the polymers will aid in the design of future missions to Titan.

Detection of Macromolecular Fractions in HCN Polymers Using Electrophoretic and Ultrafiltration Techniques.

Elucidating the origin of life involves synthetic as well as analytical challenges. Herein, for the first time, we describe the use of gel electrophoresis and ultrafiltration to fractionate HCN polymers. Since the first prebiotic synthesis of adenine by Oró, HCN polymers have gained much interest in studies on the origins of life due to the identification of biomonomers and related compounds within them. Here, we demonstrate that macromolecular fractions with electrophoretic mobility can also be detected within HCN polymers. The migration of polymers under the influence of an electric field depends not only on their sizes (one-dimensional electrophoresis) but also their different isoelectric points (two-dimensional electrophoresis, 2-DE). The same behaviour was observed for several macromolecular fractions detected in HCN polymers. Macromolecular fractions with apparent molecular weights as high as 250 kDa were detected by tricine-SDS gel electrophoresis. Cationic macromolecular fractions with apparent molecular weights as high as 140 kDa were also detected by 2-DE. The HCN polymers synthesized were fractionated by ultrafiltration. As a result, the molecular weight distributions of the macromolecular fractions detected in the HCN polymers directly depended on the synthetic conditions used to produce these polymers. The implications of these results for prebiotic chemistry will be discussed.

New insights into the characterization of 'insoluble black HCN polymers'.

The data presented here provide a novel contribution to the understanding of the structural features of HCN polymers and could be useful in further development of models for prebiotic chemistry. The interpretation of spectroscopic and analytical data, along with previous results reported by other authors, allowed us to propose a mechanism for the aqueous polymerization of HCN from its primary and simplest isolated oligomer, the diaminomaleonitrile (DAMN) tetramer. We suggest that 'insoluble black HCN polymers' are formed by an unsaturated complex matrix, which retains a significant amount of H(2) O and important bioorganic compounds or their precursors. This polymeric matrix can be formed by various motifs of imidazoles and cyclic amides, among others. The robust formation of HCN polymers assayed under several conditions seems to explain the plausible ubiquity of these complex substances in space.

[Characterization of flaxseed (Linum usitatissimum L.) grown in Venezuela]. / Caracterización de semillas de linaza (Linum usitatissimum L.) cultivadas en Venezuela.

In recent years, the consumption of flaxseed (Linum usitatissimum L.) has been promoted as a functional food for its health benefits, mainly attributable to its content of omega-3 fatty acids, lignans and dietary fiber. This study evaluated the microbiological quality, chemical composition and antioxidant properties of flaxseed grown in Venezuela and compared them to the values of a Canadian variety widely sold in the country. Total coliforms, molds and yeasts, S. aureus and sporulated of the genera Bacillus (aerobic) and Clostridium (anaerobic), moisture, fat, protein, total dietary fiber, soluble and insoluble, mucilage, minerals, fatty acid profile, equivalent HCN content, aw, color, polyphenols and antioxidant properties, like antiradical efficiency (AE), concentration of antioxidant needed to decrease the initial concentration by 50 %EC50) and the time required to reach the EC50 (TEC50) were evaluated. Significant differences in seed composition were determined, where its high content of fat, protein, alfa-linolenic acid and dietary fiber stand out. Differences were observed in the mucilage content, but not in soluble, insoluble and total fiber content. Equivalent HCN concentration in both seeds is in the order of 40 mg/100 g, which poses no health risks, considering their consumption patterns. Venezuelan flaxseed contains higher content of polyphenols than the Canadian does, but the antioxidant capacity of the latter is higher; both have an EA rated as average and a slow reaction time (TEC50 > 30 min).

Assessment of chemical asphyxia caused by toxic gases generated from rigid polyurethane foam (RPUF) fires.

Rigid polyurethane foam (RPUF) is widely used for thermal and sound insulation owing to their low thermal conductivity and light weight. However, they have serious disadvantages, including flammability and toxic gas generation, which can cause chemical asphyxia during a fire. Carbon monoxide (CO) and hydrogen cyanide (HCN) are representative toxic gases formed by incomplete combustion and HCN, in particular, is closely related to polyurethane product fires. In this study, the risk of inhalation of toxic gases such as CO, HCN and NO2 during RPUF fires was demonstrated convincingly through the analysis of carboxyhemoglobin (COHb), cyanide (CN-) and methemoglobin (MetHb) in the postmortem blood samples of 38 victims of RPUF fires. To better understand the toxic gas poisoning and chemical asphyxia, we classified all cases into two groups based on the extent of injuries and location where the victim was found. Mean concentrations of COHb and cyanide in group 1 without injuries were approximately two times higher than in group 2 with severe injuries, while concentrations of free MetHb showing possibility of NO2 inhalation were approximately six times lower than in group 2. Furthermore, we presumed concentrations of cyanide at the time of death and five cases showed the possibility of cyanide poisoning.

An FTIR study of the induction and release of kiwifruit buds from dormancy.

BACKGROUND: Many deciduous, perennial fruit crops require winter chilling for adequate budbreak and flowering. Recent research has shown that changes in sugar and amino acid profiles are associated with the release of buds from dormancy. This paper uses FTIR spectrometry to provide an alternative mechanism for tracking metabolic changes in the meristems of kiwifruit buds during winter dormancy. The results suggest that the application of multivariate analysis to FTIR spectra has the potential to be a reliable and fast method for detecting structural and compositional changes in fruit crops. RESULTS: Ten wave numbers of the FTIR spectra are used to calculate a bud development function. This function has been validated using data from two seasons and four orchards, and by monitoring the effects of hydrogen cyanamide application, sugar concentrations and soil temperatures on this function. These wave numbers appear to be associated with carbohydrate, pectin and cellulose levels in the meristems. CONCLUSION: It is expected that this FTIR signature can be used to advance our understanding of the influence of the various environmental and physiological factors on the breaking of bud dormancy and shoot outgrowth, including the optimum timing and concentrations of applications of budbreak regulators, such as hydrogen cyanamide.

Highly selective and sensitive online measurement of trace exhaled HCN by acetone-assisted negative photoionization time-of-flight mass spectrometry with in-source CID.

Exhaled hydrogen cyanide (HCN) has been extensively investigated as a promising biomarker of the presence of Pseudomonas aeruginosa in the airways of patients with cystic fibrosis (CF) disease. Its concentration profile for exhalation can provide useful information for medical disease diagnosis and therapeutic procedures. However, the complexity of breath gas, like high humidity, carbon dioxide (CO2) and trace organic compounds, usually leads to quantitative error, poor selectivity and sensitivity for HCN with some of existing analytical techniques. In this work, acetone-assisted negative photoionization (AANP) based on a vacuum ultraviolet (VUV) lamp with a time-of- flight mass spectrometer (AANP-TOFMS) was firstly proposed for online measurement of trace HCN in human breath. In-source collision-induced dissociation (CID) was adopted for sensitivity improvement and the signal response of the characteristic ion CN- (m/z 26) was improved by about 24-fold. For accurate and reliable analysis of the exhaled HCN, matrix influences in the human breath including humidity and CO2 were investigated, respectively. A Nafion tube was used for online dehumidification of breath samples. Matrix-adapted calibration in the concentration range of 0.5-50 ppbv with satisfactory dynamic linearity and repeatability was obtained. The limit of quantitation (LOQ) for HCN at 0.5 ppbv was achieved in the presence of 100% relative humidity and 4% CO2. Finally, the method was successfully applied for online determination of human mouth- and nose-exhaled HCN, and the nose-exhaled HCN were proved to be reliable for assessing systemic HCN levels for individuals. The results are encouraging and highlight the potential of AANP-TOFMS with in-source CID as a selective, accurate, sensitive and noninvasive technique for determination of the exhaled HCN for CF clinical diagnosis and HCN poisoning assessment.

Heteropolypeptides from poly-alpha-cyanoglycine and hydrogen cyanide: a model for the origin of proteins.

Poly-alpha-cyanoglycine, a homopolymer synthesized from the N-carboxyanhydride of alpha-cyanoglycine, is converted by cumulative reaction of hydrogen cyanide to heteropolypeptides that can be hydrolyzed to protein amino acids, including glycine, alanine, valine, aspartic acid, and glutamic acid. These results are consistent with the hypothesis that the original heteropolypeptides on the earth arose spontaneously from hydrogen cyanide and water without the intervening formation of alpha-amino acids.

Was adenine the first purine?

Oligomerization of HCN (1 molar) in the presence of added formaldehyde (0.5 molar) produced an order of magnitude more 8-hydroxymethyladenine than adenine or any other biologically significant purine. This result suggests that on the prebiotic Earth, nucleoside analogs may have been synthesized directly in more complex mixtures of HCN with other aldehydes.

HCN polymers characterized by solid state NMR: chains and sheets formed in the neat liquid.

Hydrogen cyanide polymerizes readily under a variety of conditions and significant prebiotic roles have been suggested for these polymers due to the abundance of HCN in universe. However, the structures of HCN polymers have been more speculative than grounded in experimental data. Here we show that (13)C and (15)N solid state NMR spectra of polymers formed in neat HCN are inconsistent with the previously proposed structures and suggest instead that the polymers are formed by simple monomer addition, first in head-to-tail fashion to form linear, conjugated chains, and then laterally to form saturated two-dimensional networks. This interpretation of the NMR spectra finds support in other information about the polymerization of neat HCN, including the presence of free radicals. As expected from the literature, formation of the HCN tetramer, diaminomaleonitrile, is also observed, but only when the reaction is catalyzed exclusively by base and then in crystalline form.

HCN polymers characterized by SSNMR: solid state reaction of crystalline tetramer (diaminomaleonitrile).

The HCN tetramer, diaminomaleonitrile, crystallizes in sheets with amine and nitrile groups of neighboring molecules in close proximity. This suggests the possibility of relatively facile acid-base addition to form a protopeptide polymer. We find that moderate heating under argon indeed results in an unmistakable reaction, with the abrupt transformation of pale crystallites to shrunken dark particles that become electrically conductive upon doping with iodine. Since nearly a quarter of the mass is lost in the process and the released gas condenses, polymerizes, and reacts with aqueous AgNO(3) like HCN, it seems likely that the dark solid is a polymer of HCN trimer. (13)C and (15)N solid state NMR spectra show the formation of new N-C bonds, and entirely different functional groups from those observed in polymers formed by liquid HCN. These include three different types of nitrogen functionalities and an absence of saturated carbon or nitrile. The observed chemical shifts, optical properties, and electrical conductivity are consistent with polymers of HCN trimer that have undergone cyclization to form poly-[aminoimidazole].

New approach for data evaluation of industrial wastewater treatment plant: methodology and case study for a coke and steel-processing plant.

Environmental monitoring of biological wastewater treatment plants (BWWTP) treating industrial effluents produces large amount of data. Frequent sampling is done in the influent and effluent but also in intermediate points. Samples are analyzed for classical and specific contaminants and physical-chemical parameters are monitored. In this paper data from a BWWTP treating the effluents of a coke and steel-processing factory are analyzed. Due to a complex situation, this BWWTP gave poor performances that did not match environmental regulations, meanwhile upgrading proved to be uneasy. Data analysis using principal component analyses (PCA) or kinetic modeling with a Haldane model was unsuccessful in handling these data, which was attributed to undetermined toxic effects. A new methodology is reported, that allowed to identify a kinetics for thiocyanate degradation and a relation between pH and toxic effects. This analysis of the plant data allowed to make hypothesis on the process control parameters and to recommend management modifications, allowing a further increase of the performances.

Solution degradant of mirabegron extended release tablets resulting from a Strecker-like reaction between mirabegron, minute amounts of hydrogen cyanide in acetonitrile, and formaldehyde in PEG during sample preparation.

During the related substances testing of mirabegron extended release tablets, an unknown peak was observed in HPLC chromatograms in a level exceeding the identification threshold. By using a strategy that combines LC-PDA/UV-MSn with mechanism-based stress studies, the unknown peak was rapidly identified as cyanomethyl mirabegron, a solution degradant that is caused by a Strecker-like reaction between the API, formaldehyde (an impurity in PEG), and HCN (an impurity in HPLC grade acetonitrile). The mechanism of the solution degradation chemistry was verified by stressing mirabegron with formaldehyde and trimethylsilyl cyanide (TMSCN, a synthetic reagent that generates HCN upon contact with water), in which the secondary amine group of mirabegron first reacts with formaldehyde to form the iminium ion intermediate; the latter then undergoes a nucleophilic attack by cyanide to yield the cyanomethyl mirabegron. The structure of the impurity was further confirmed through the synthesis of the impurity and subsequent structure characterization by 1D and 2D NMR. Due to the ubiquitous presence of formaldehyde in pharmaceutical excipients (e.g., PEG and polysorbate) and trace amount of HCN in HPLC grade acetonitrile, this type of solution degradation would likely occur in sample preparations of pharmaceutical finished products containing APIs with primary and secondary amine moieties. In a GMP environment, such an event may trigger undesirable out-of-specification (OOS) investigations; the results of this paper should help resolve such OOS investigations or even prevent these events from happening in the first place.

Prospective study of hydroxocobalamin for acute cyanide poisoning in smoke inhalation.

STUDY OBJECTIVE: To assess outcomes in patients treated with hydroxocobalamin at the fire scene or in the ICU for suspected smoke inhalation-associated cyanide poisoning. METHODS: Adult smoke inhalation victims with suspected cyanide poisoning as determined by soot in the face, mouth, or nose or expectorations and neurologic impairment received an intravenous infusion of hydroxocobalamin 5 g (maximum 15 g) at the fire scene or in the ICU in this observational case series conducted from 1987 to 1994. Blood cyanide specimens were collected before administration of hydroxocobalamin. The threshold for cyanide toxicity was predefined as greater than or equal to 39 micromol/L. RESULTS: The sample included 69 patients (mean age 49.6 years; 33 men), of whom 39 were comatose. Out-of-hospital deaths were excluded. Fifty of the 69 patients (72%) admitted to the ICU survived after administration of hydroxocobalamin. In the group in which cyanide poisoning was confirmed a posteriori (n=42), 67% (28/42) survived after administration of hydroxocobalamin. The most common adverse events were chromaturia (n=6), pink or red skin discoloration (n=4), hypertension (n=3), erythema (n=2), and increased blood pressure (n=2). No serious adverse events were attributed to hydroxocobalamin. Laboratory tests revealed transient alterations in renal and hepatic function consistent with the critical condition of the patients and mild anemia consistent with progressive hemodilution. CONCLUSION: Empiric administration of hydroxocobalamin was associated with survival among 67% of patients confirmed a posteriori to have had cyanide poisoning. Hydroxocobalamin was well tolerated irrespective of the presence of cyanide poisoning. Hydroxocobalamin appears to be safe for the out-of-hospital treatment of presumptive cyanide poisoning from smoke inhalation.

Formamide chemistry and the origin of informational polymers.

Formamide (HCONH2) provides a chemical frame potentially affording all the monomeric components necessary for the formation of nucleic polymers. In the presence of the appropriate catalysts, and by moderate heating, formamide yields a complete set of nucleic bases, acyclonucleosides, and favors both phosphorylations and transphosphorylations. Physico-chemical conditions exist in which formamide favors the stability of the phosphoester bonds in nucleic polymers more than that of the same bonds in monomers. This property establishes 'thermodynamic niches' in which the polymeric forms are favored. The hypothesis that these specific attributes of formamide allowed the onset of prebiotic chemical equilibria capable of Darwinian evolution is discussed.

Detection of hydrogen cyanide from oral anaerobes by cavity ring down spectroscopy.

Hydrogen cyanide (HCN) has been recognized as a potential biomarker for non-invasive diagnosis of Pseudomonas aeruginosa infection in the lung. However, the oral cavity is a dominant production site for exhaled HCN and this contribution can mask the HCN generated in the lung. It is thus important to understand the sources of HCN production in the oral cavity. By screening of oral anaerobes for HCN production, we observed that the genus of Porphyromonas, Prevotella and Fusobacterium generated low levels of HCN in vitro. This is the first study to show that oral anaerobes are capable of producing HCN in vitro. Further investigations were conducted on the species of P. gingivalis and we successfully detected HCN production (0.9-10.9 ppb) in the headspace of three P. gingivalis reference strains (ATCC 33277, W50 and OMG 434) and one clinical isolate. From P. gingivalis ATCC 33277 and W50, a strong correlation between HCN and CO2 concentrations (rs = 0.89, p < 0.001) was observed, indicating that the HCN production of P. gingivalis might be connected with the bacterial metabolic activity. These results indicate that our setup could be widely applied to the screening of in vitro HCN production by both aerobic and anaerobic bacteria.

Lepidopteran defence droplets - a composite physical and chemical weapon against potential predators.

Insects often release noxious substances for their defence. Larvae of Zygaena filipendulae (Lepidoptera) secrete viscous and cyanogenic glucoside-containing droplets, whose effectiveness was associated with their physical and chemical properties. The droplets glued mandibles and legs of potential predators together and immobilised them. Droplets were characterised by a matrix of an aqueous solution of glycine-rich peptides (H-WG11-NH2) with significant amounts of proteins and glucose. Among the proteins, defensive proteins such as protease inhibitors, proteases and oxidases were abundant. The neurotoxin ß-cyanoalanine was also found in the droplets. Despite the presence of cyanogenic glucosides, which release toxic hydrogen cyanide after hydrolysis by a specific ß-glucosidase, the only ß-glucosidase identified in the droplets (ZfBGD1) was inactive against cyanogenic glucosides. Accordingly, droplets did not release hydrogen cyanide, unless they were mixed with specific ß-glucosidases present in the Zygaena haemolymph. Droplets secreted onto the cuticle hardened and formed sharp crystalline-like precipitates that may act as mandible abrasives to chewing predators. Hardening followed water evaporation and formation of antiparallel ß-sheets of the peptide oligomers. Consequently, after mild irritation, Zygaena larvae deter predators by viscous and hardening droplets that contain defence proteins and ß-cyanoalanine. After severe injury, droplets may mix with exuding haemolymph to release hydrogen cyanide.

Pitfalls in the analysis of volatile breath biomarkers: suggested solutions and SIFT-MS quantification of single metabolites.

The experimental challenges presented by the analysis of trace volatile organic compounds (VOCs) in exhaled breath with the objective of identifying reliable biomarkers are brought into focus. It is stressed that positive identification and accurate quantification of the VOCs are imperative if they are to be considered as discreet biomarkers. Breath sampling procedures are discussed and it is suggested that for accurate quantification on-line real time sampling and analysis is desirable. Whilst recognizing such real time analysis is not always possible and sample collection is often required, objective recognition of the pitfalls involved in this is essential. It is also emphasized that mouth-exhaled breath is always contaminated to some degree by orally generated compounds and so, when possible, analysis of nose-exhaled breath should be performed. Some difficulties in breath analysis are mitigated by the choice of analytical instrumentation used, but no single instrument can provide solutions to all the analytical challenges. Analysis and interpretation of breath analysis data, however acquired, needs to be treated circumspectly. In particular, the excessive use of statistics to treat imperfect mass spectrometry/mobility spectra should be avoided, since it can result in unjustifiable conclusions. It is should be understood that recognition of combinations of VOCs in breath that, for example, apparently describe particular cancer states, will not be taken seriously until they are replicated in other laboratories and clinics. Finally, the inhibiting notion that single biomarkers of infection and disease will not be identified and utilized clinically should be dispelled by the exemplary and widely used single biomarkers NO and H2 and now, as indicated by recent selected ion flow tube mass spectroscopy (SIFT-MS) results, triatomic hydrogen cyanide and perhaps pentane and acetic acid. Hopefully, these discoveries will provide encouragement to research workers to be more open-minded on this important and desirable issue.