Isotope Exchange Reaction Research Articles

Selection of a carrying agent for obtaining radioactive methyliodide vapors under dynamic conditions

A method for preparing “reagent” for radioactive methyliodide vapors production using an isotopic exchange reaction has been developed. Based on the obtained data of the isotopic exchange efficiency and hydraulic resistance, white fused alumina (700–840 μm) was selected as the carrying agent material for “reagent” production. The radioiodine isotopic exchange dependences on such parameters as temperature, gas flow velocity, and the methyliodide concentration in it were determined. Optimal conditions have been selected to achieve 85% of the isotopic exchange rate in 1 h of the experiment. The obtained data allowed to develop an approach to the test of iodine filters for nuclear power plants and to determine their efficiency.

Dynamics of the isotope exchange reaction of D with H3 +, H2D+, and D2H.

We have measured the merged-beams rate coefficient for the titular isotope exchange reactions as a function of the relative collision energy in the range of ∼3 meV-10 eV. The results appear to scale with the number of available sites for deuteration. We have performed extensive theoretical calculations to characterize the zero-point energy corrected reaction path. Vibrationally adiabatic minimum energy paths were obtained using a combination of unrestricted quadratic configuration interaction of single and double excitations and internally contracted multireference configuration interaction calculations. The resulting barrier height, ranging from 68 meV to 89 meV, together with the various asymptotes that may be reached in the collision, was used in a classical over-the-barrier model. All competing endoergic reaction channels were taken into account using a flux reduction factor. This model reproduces all three experimental sets quite satisfactorily. In order to generate thermal rate coefficients down to 10 K, the internal excitation energy distribution of each H3 + isotopologue is evaluated level by level using available line lists and accurate spectroscopic parameters. Tunneling is accounted for by a direct inclusion of the exact quantum tunneling probability in the evaluation of the cross section. We derive a thermal rate coefficient of <1×10-12 cm3 s-1 for temperatures below 44 K, 86 K, and 139 K for the reaction of D with H3 +, H2D+, and D2H+, respectively, with tunneling effects included. The derived thermal rate coefficients exceed the ring polymer molecular dynamics prediction of Bulut et al. [J. Phys. Chem. A 123, 8766 (2019)] at all temperatures.

Nanocatalyzed Hydrogen Isotope Exchange

Recently, hydrogen isotope exchange (HIE) reactions have experienced impressive development due to the growing importance of isotope containing compounds in various fields including materials and life sciences, in addition to their classical use for mechanistic studies in chemistry and biology. Tritium-labeled compounds are also of crucial interest to study the in vivo fate of a bioactive substance or in radioligand binding assays. Over the past few years, deuterium-labeled drugs have been extensively studied for the improvement of ADME (absorption, distribution, metabolism, excretion) properties of existing bioactive molecules as a consequence of the primary kinetic isotope effect. Furthermore, in the emergent "omic" fields, the need for new stable isotopically labeled internal standards (SILS) for quantitative GC- or LC-MS analyses is increasing. Because of their numerous applications, the development of powerful synthetic methods to access deuterated and tritiated molecules with either high isotope incorporation and/or selectivities is of paramount importance.HIE reactions allow a late-stage incorporation of hydrogen isotopes in a single synthetic step, thus representing an advantageous alternative to conventional multistep synthesis approaches which are time- and resource-consuming. Moreover, HIE reactions can be considered as the most fundamental C-H functionalization processes and are therefore of great interest for the chemists' community. Depending on the purpose, HIE reactions must either be highly regioselective or allow a maximal incorporation of hydrogen isotopes, sometimes both. In this context, metal-catalyzed HIE reactions are generally performed using either homogeneous or heterogeneous catalysis which may have considerable drawbacks including an insufficient isotope incorporation and a lack of chemo- and/or regioselectivity, respectively.Over the past 6 years, we have shown that nanocatalysis can be considered as a powerful tool to access complex labeled molecules (e.g., pharmaceuticals, peptides and oligonucleotides) via regio- and chemoselective or even enantiospecific labeling processes occurring at the surface of metallic nanoclusters (Ru or Ir). Numerous heterocyclic (both saturated and unsaturated) and acyclic scaffolds have been labeled with an impressive functional group tolerance, and highly deuterated compounds or high molar activity tritiated drugs have been obtained. An insight into mechanisms has also been provided by theoretical calculations to explain the regioselectivities of the isotope incorporation. Our studies have suggested that undisclosed key intermediates, including 4- and 5-membered dimetallacycles, account for the particular regioselectivities observed during the process, in contrast to the 5- or 6-membered metallacycle key intermediates usually encountered in homogeneous catalysis. These findings together with the important number of available coordination sites explain the compelling reactivity of metal nanoparticles, in between homogeneous and heterogeneous catalysis. They represent innovative tools combining the advantages of both methods for the isotopic labeling and activation of C-H bonds of complex molecules.

Activation of Molecular Hydrogen by Inter‐ and Intramolecular Al−N Lewis Pairs

AbstractThe field of frustrated Lewis pair chemistry offers many opportunities to activate molecular hydrogen, but Al−N systems have not been established yet. In this work, we describe several intermolecular classical Al−N Lewis pairs and an intramolecular ortho‐ala‐aminoarene for the activation of molecular hydrogen. Their ability was investigated using the isotope exchange reaction from HD to H2 and D2. The herein studied intermolecular Lewis pairs were based on alkylalanes and N‐methyldiphenylamine, while the intramolecular Lewis pair was (o‐TMP−C6H4)AlH2 ((2‐(2,2,6,6‐tetramethyl‐piperidin‐1‐yl)phenyl)‐aluminium dihydride). The activation of molecular hydrogen was carried out in toluene under mild conditions and monitored by 1H and 2H NMR spectroscopy. Furthermore, the Al−N interaction has been probed by 27Al NMR and crystallographic studies. Additionally, the crystal structure of pure AliBu3 was determined. These studies may attribute the pronounced reactivities of these Al−N compounds to elongated Al−N bond lengths.

Catalytic Hydrogen Isotope Exchange Reactions in Late-Stage Functionalization

AbstractThe introduction of deuterium and tritium into molecules is of great importance in drug discovery. Many attempts have been made to develop late-stage hydrogen isotope exchange (HIE) reactions to avoid multistep syntheses using commercially available labeled precursors. In this review, we summarize recent progress in catalytic HIE reactions, with our main focus on their applications in the late-stage labeling of bioactive complex molecules and pharmaceuticals1 Introduction2 Non-Transition-Metal-Catalyzed Hydrogen Isotope Exchange2.1 Organocatalysis2.2 Photoredox Catalysis3 Transition-Metal-Catalyzed Hydrogen Isotope Exchang3.1 Palladium3.2 Ruthenium3.3 Iridium3.4 Other Metals4 Summary

Are rate and selectivity correlated in iridium-catalysed hydrogen isotope exchange reactions?

We have qualitatively examined the relationship between reaction rate and reaction selectivity in iridium-catalysed hydrogen isotope exchange (HIE) reactions directed by Lewis basic functional groups.

Ultrafast Laplace NMR to study metal-ligand interactions in reversible polarisation transfer from parahydrogen.

Laplace Nuclear Magnetic Resonance (NMR) can determine relaxation parameters and diffusion constants, giving valuable information about molecular structure and dynamics. Information about relaxation times (T1 and T2) and the self-diffusion coefficient (D) can be extracted from exponentially decaying NMR signals by performing a Laplace transform, which is a different approach to traditional NMR involving Fourier transform of a free induction decay. Ultrafast Laplace NMR uses spatial encoding to collect the entire data set in just a single scan which provides orders of magnitude time savings. In this work we use ultrafast Laplace NMR D–T2 correlation sequences to measure key relaxation (T2) and diffusion (D) parameters of methanolic solutions containing pyridine. For the first time we combine this technique with the hyperpolarisation technique Signal Amplification By Reversible Exchange (SABRE), which employs an iridium catalyst to reversibly transfer polarisation from parahydrogen, to boost the 1H NMR signals of pyridine by up to 300-fold. We demonstrate use of ultrafast Laplace NMR to monitor changes in pyridine T2 and D associated with ligation to the iridium SABRE catalyst and kinetic isotope exchange reactions. The combined 1440-fold reduction in experiment time and 300-fold 1H NMR signal enhancement allow the determination of pyridine D coefficients and T2 values at 25 mM concentrations in just 3 seconds using SABRE hyperpolarised ultrafast Laplace NMR.

Iodinated Choline Transport-Targeted Tracers.

We present a novel series of radioiodinated tracers and potential theranostics for diseases accompanied by pathological function of proteins involved in choline transport. Unlike choline analogues labeled with 11C or 18F that are currently used in the clinic, the iodinated compounds described herein are applicable in positron emission tomography, single-photon emission computed tomography, and potentially in therapy, depending on the iodine isotope selection. Moreover, favorable half-lives of iodine isotopes result in much less challenging synthesis by isotope exchange reaction. Six of the described compounds were nanomolar ligands, and the best compound possessed an affinity 100-fold greater than that of choline. Biodistribution data of 125I-labeled ligands in human prostate carcinoma bearing (PC-3) mice revealed two compounds with a biodistribution profile superior to that of [18F]fluorocholine.

Erratum: Quantum-tunneling isotope-exchange reaction H2+D−→HD+H− [Phys. Rev. A 97 , 022705 (2018)

Received 13 November 2020DOI:https://doi.org/10.1103/PhysRevA.102.069901©2020 American Physical SocietyPhysics Subject Headings (PhySH)Research AreasAtom & ion coolingCharge-transfer collisionsScattering of atoms, molecules, clusters & ionsScattering theoryAtomic, Molecular & Optical

Using Carbon-14 of dissolved organic carbon to determine groundwater ages and travel times in aquifers with low organic carbon

This study used dissolved organic carbon (DOC) carbon-14 (14C) to determine groundwater ages that were then used to calculate groundwater travel times in southern Nevada aquifers that have low organic content. These travel times are compared with the more standard dissolved inorganic (DIC) 14C method for determining groundwater ages and travel times. Groundwater travel times for aquifers in southern Nevada using DOC 14C are thousands of years shorter than DIC 14C travel times for groundwater flow outside of recharge areas along four of the five flow paths evaluated for this study. The DOC 14C travel times range from 2,300 to 2,900 years (yrs) as compared to DIC 14C travel times that range from 8,200 to 22,000 yrs (uncorrected ages) and 4,700 to 19,000 yrs (corrected ages). The DOC 14C groundwater travel times in carbonate-rock and volcanic-rock aquifers of southern Nevada are similar to travel times determined from: (1) hydrogeologic data; (2) observations of rapid high-level tritium transport at the Nevada National Security Site; and (3) 550,000-yr δ18O and δ13C global climate records for calcite precipitated in Devils Hole, Nevada at the end of one of the flow paths. DOC 14C travel time calculations need to account for fewer processes than DIC 14C for aquifers that contain little organic matter and do not have redox reactions. DOC 14C travel-times can be calculated directly from the DOC 14C data in these aquifers without corrections if dissolution of organic carbon and sorption and matrix diffusion of DOC 14C onto or into the aquifer matrix is minimal. Laboratory experiments showed that little organic carbon was being leached from aquifer rocks, sorption of organic carbon ranged from 4.3% sorbed in carbonate rocks to 0.5% sorbed in volcanic rocks, and matrix diffusion coefficients were slower in lower porosity carbonate rocks (1.7 × 10−7 cm2/s) than in higher porosity volcanic rocks (2.9 × 10−7 cm2/s). The lack of dissolution of organic carbon in study area aquifers is also supported by the decrease in DOC along flow paths and the DOC composition of groundwater changing little as groundwater flows from recharge areas into the adjacent valleys. In contrast, DIC 14C groundwater travel-time calculations must be corrected for complex chemical reactions and physical processes, including mineral/gas dissolution, mineral/gas precipitation/exsolution, cation exchange, and carbon isotopic exchange that can significantly change the amount of DIC 14C in groundwater along flow paths by processes other than radioactive decay. DIC 14C can also be affected by sorption and matrix diffusion, but these processes may, or may not, be captured in geochemical modeling of precipitation/dissolution and carbon isotopic exchange reactions. Corrected DIC 14C ages, therefore, represent maximum ages.

Radiosynthesis of [18F]SiFAlin-TATE for clinical neuroendocrine tumor positron emission tomography.

Here, we describe an extension of our silicon fluoride acceptor (SiFA) protocol for 18F-labeling of peptides that addresses challenges associated with preparing a clinical-grade (Tyr3)-octreotate (TATE) tracer for diagnosis of neuroendocrine tumors (NETs). After several iterations of protocol optimization (e.g., finding the optimal pH at which the isotopic exchange (IE) reaction produces high radiochemical yields (RCYs)), the SiFA technology achieved clinical applicability, as showcased by radiosynthesis of [18F]SiFAlin-TATE ([18F]SiTATE), the first SiFA peptide used in the clinical diagnosis of NETs. The TATE peptide binds to somatostatin receptors associated with NETs. Radiolabeled TATE derivatives are routinely applied in clinical oncological PET imaging. The (SiFA) 18F-labeling technology is based on the IE of a 19F atom for a radioactive 18F atom, a highly efficient labeling reaction under mild conditions. The 19F is part of a biomolecule bearing the SiFA building block, composed of a central silicon (Si) atom, a 19F atom connected to the Si atom, and two Si-bound tert-butyl groups. The IE proceeds through a penta-coordinate bipyramidal intermediate, followed by elimination of non-radioactive 19F, yielding the labeled compound in high RCYs at room temperature (22 °C). The simplicity and lack of side-product formation of this approach enable a one-step, kit-like preparation of structurally complex and unprotected radiopharmaceuticals. Compounds such as peptides used for tumor imaging in nuclear medicine can be 18F-labeled without the need for complex purification protocols. [18F]SiTATE can be synthesized within 30 min in preparative RCYs of 42%, radiochemical purity of >97% and high molar activity of 60 GBq/µmol.

Stepwise construction of silica-supported tantalum/iridium heteropolymetallic catalysts using surface organometallic chemistry

A stepwise surface organometallic chemistry (SOMC) methodology consisting in using a silica-supported tantalum species, [(≡SiO)Ta(CHtBu)(CH2tBu)2], as a reactive center to coordinate an iridium site, was developed to construct tantalum/iridium heterobimetallic edifices. The resulting material, MAT-2, exhibits enhanced catalytic performances - both in H/D isotopic exchange and alkane metathesis reactions - in comparison to MAT-1, which was prepared from the direct grafting on silica of a well-defined heterobimetallic Ta/Ir complex. We projected that the difference in catalytic activity was due to the presence of distinct active sites and we used a combination of advanced spectroscopic methods (IR, solid-state NMR and XAS spectroscopies) as well as modeling (computational studies and molecular models) to identify the structure of these surface species. These investigations point towards the presence of three types of active sites at the surface of MAT-2: the heterobimetallic surface species, [≡SiOTa(CH2tBu)2{IrH2(Cp*)}] 2-s, which is also found in MAT-1, as well as an unanticipated heterotrimetallic species, [≡SiOTa(CH2tBu)2{IrH2(Cp*)}], 3-s along with some unreacted monometallic Ta sites [(≡SiO)Ta(CHtBu)(CH2tBu)2], 1-s. The well-defined trimetallic surface species 3-s was independently prepared and characterized to support this hypothesis. This study highlights the importance of the synthetic methodology used for the preparation of heterobimetallic species through SOMC, and the difficulty to obtain true single-sites surface species.

Isotope exchange between mercuric [Hg(II)] chloride and Hg(II) bound to minerals and thiolate ligands: Implications for enriched isotope tracer studies

Enriched mercury (Hg) stable isotopes have been widely used as tracers in field and laboratory investigations of Hg(II) biogeochemical transformations such as methylation and demethylation. Few studies, however, have considered concurrent isotope exchange reactions between newly spiked and pre-existing Hg(II) in environmental matrices, which may alter redistribution and thus transformation of the spiked and pre-existing Hg(II). Using enriched 198Hg [as mercuric Hg(II) or HgCln species], this study investigated isotope exchange between 198Hg and pre-existing Hg(II) bound to metacinnabar (β-HgS), sediments, low-molecular-weight (LMW) thiols, and dissolved organic matter (DOM). The impact of isotope exchange on methylmercury production in the presence of organic ligands was also evaluated with an iron-reducing bacterium Geobacter sulfurreducens PCA in a phosphate buffered solution (pH 7.4). We found that spiked 198Hg readily exchanged with mineral-bound ambient Hg(II) despite concurrent Hg(II) adsorption and immobilization on the solids. Rapid exchange (<3 min) was also observed between spiked 198Hg and 200Hg pre-equilibrated with LMW thiols and DOM in solution. While the exchange did not cause net changes in Hg(II) chemical speciation, it resulted in redistribution of Hg(II) isotopes bound to the ligands and thus an apparently similar methylation rate and magnitude of the spiked 198Hg and pre-existing 200Hg by PCA cells when 198Hg and 200Hg were added at 1:1 ratio. These observations underscore the importance of isotope exchange when an enriched Hg isotope is applied in environmental matrices, as the exchange could potentially lead to biased rate calculations of Hg(II) transformation and bioaccumulation and thus risk assessments of new Hg(II) input to the natural ecosystems.

Synthesis of 18 F-radiolabeled organophosphine fluorides for thiol-chemoselective peptide conjugation.

Two 18 F-radiolabeled organofluorophosphine fluorides ([18 F]4 and [18 F]7) for chemoselective thiol-conjugation were designed and synthesized via 18 F-19 F isotopic exchange reaction. This simple and rapid radiofluorination produced both 18 F-radiolabeled fluorides in excellent radiochemical yields (>94%) and radiochemical purity. The optimal reaction conditions are 0.05-mg substrate, 0.69 mg of potassium carbonate, and dried [18 F]F- were mixed in 100-μl anhydrous acetonitrile at room temperature for 5 min. Both of [18 F]4 and [18 F]7 showed specificity for thiol-conjugation with cysteine and have been used in the radiosynthesis of c (RGDfC). The [18 F]7 with an adamantanyl-hindered substituent displayed superior in vitro and in vivo stability.

Method for obtaining radioactive methyliodide vapors under dynamic conditions

A “reagent” preparation technique for producing radioactive methyl iodide vapors applying an isotope exchange reaction has been developed. A laboratory facility for conducting heterophase iodine isotopic exchange under dynamic conditions has been created. Comparative studies of various inert carriers used in chromatography have been carried out. The dependences of the isotopic exchange efficiency on the gas flow rate and the methyliodide concentration are established.

Photoredox-Mediated Hydrogen Isotope Exchange Reactions of Amino-Acids, Peptides, and Peptide-Derived Drugs.

Hydrogen isotopically labelled compounds are essential diagnostic tools in drug research and development, as they provide vital information about the biological metabolism of drug candidates and their metabolites. Herein we report a photoredox-initiated hydrogen atom transfer (HAT) protocol which efficiently and selectively introduces deuterium or tritium at C(sp3 )-H bonds, utilizing heavy water (D2 O or T2 O) as the hydrogen isotope source, and a guanidine base. This protocol has been successfully applied to the incorporation of deuterium in several amino acids (lysine, glycine and proline) and small peptides. Finally, the method has been applied to tritium, because tritium-labelled peptides are essential for application in biological experiments, such as ligand-binding assays, or absorption, distribution, metabolism, and excretion (ADME) studies.

Mass-independent fractionation of titanium isotopes

Forty years ago, the synthesis of ozone has revealed mass-independent fractionation (MIF) of oxygen isotopes. Among the numerous published interpretations of this ozone effect, the present paper reports that a titanium MIF observed during chemical reactions in plasma can be accounted for by one of these theoretical treatments. A gaseous mixture of TiCl 4 /C 5 H 12 carried in a glass tube by a continuous flow of N 2 was submitted to a HF discharge. Carbonaceous grains, presumably resulting from homogeneous condensation, show radial variations in Ti concentration with isotopic variations ranging from −25 to +125% for all m Ti / 48 Ti isotope ratios ( m standing for masses 46, 47, 49 and 50). It is proposed that the reduction rates by carbon radicals, of the metastable molecules formed by the isotope exchange reactions between Ti and TiCl 4 are different if they involve distinguishable or indistinguishable isotopes. A numerical simulation reproduces the experimental isotope patterns defined by the m Ti / 48 Ti isotope ratios.

Effects of soil moisture, needle age and leaf morphology on carbon and oxygen uptake, incorporation and allocation: a dual labeling approach with 13CO2 and H218O in foliage of a coniferous forest.

The carbon and oxygen isotopic composition of water and assimilates in plants reveals valuable information on plant responses to climatic conditions. Yet, the carbon and oxygen uptake, incorporation and allocation processes determining isotopic compositions are not fully understood. We carried out a dual-isotope labeling experiment at high humidity with 18O-enriched water (H218O) and 13C-enriched CO2 (13CO2) with attached Scots pine (Pinus sylvestris L.) branches and detached twigs of hemiparasitic mistletoes (Viscum album ssp. austriacum) in a naturally dry coniferous forest, where also a long-term irrigation takes place. After 4h of label exposure, we sampled previous- and recent-year leaves, twig phloem and twig xylem over 192h for the analysis of isotope ratios in water and assimilates. For both species, the uptake into leaf water and the incorporation of the 18O-label into leaf assimilates was not influenced by soil moisture, while the 13C-label incorporation into assimilates was significantly higher under irrigation compared with control dry conditions. Species-specific differences in leaf morphology or needle age did not affect 18O-label uptake into leaf water, but the incorporation of both tracers into assimilates was two times lower in mistletoe than in pine. The 18O-label allocation in water from pine needles to twig tissues was two times higher for phloem than for xylem under both soil moisture conditions. In contrast, the allocation of both tracers in pine assimilates were similar and not affected by soil moisture, twig tissue or needle age. Soil moisture effects on 13C-label but not on 18O-label incorporation into assimilates can be explained by the stomatal responses at high humidity, non-stomatal pathways for water and isotope exchange reactions. Our results suggest that non-photosynthetic 18O-incorporation processes may have masked prevalent photosynthetic processes. Thus, isotopic variation in leaf water could also be imprinted on assimilates when photosynthetic assimilation rates are low.

Insights into the Proton Transport Mechanism in TiO2 Simple Oxides by In Situ Raman Spectroscopy.

Understanding the mechanisms of proton conduction at the interface of materials enables the development of a new generation of protonic ceramic conductors at low temperatures (<150 °C) through water absorption and proton transport on the surface and grain boundaries. Conductivity measurements under Ar-3% H2O and Ar-3% D2O revealed a σ(H2O)/σ(D2O) ratio of approximately 2, indicating a hopping-based mechanism for proton conduction at the interface. In situ Raman spectroscopy was performed on water-saturated, porous, and nanostructured TiO2 membranes to directly observe the isotope exchange reactions over the temperature range of 25 to 175 °C. The behavior of the isotope exchange reactions suggested a Grotthuss-type proton transport and faster isotope exchange reactions at 175 °C than that at 25 °C with a corresponding activation energy of 9 kJ mol-1. The quantitative and mechanistic kinetic description of the isotope exchange process via in situ Raman spectroscopy represents a significant advance toward understanding proton transport mechanisms and aids in the development of high-performance proton conductors with rapid surface exchange coefficients of importance to contemporary energy conversion and storage material development. In addition, new material systems are proposed, which combine interface and bulk effects at low temperatures (<150 °C), resulting in enhanced proton transport through interfacial engineering at the nanoscale.

Carbon isotopic fractionation in molecular clouds

Context. Carbon fractionation has been studied from a theoretical point of view with different models of time-dependent chemistry, including both isotope-selective photodissociation and low-temperature isotopic exchange reactions. Aims. Recent chemical models predict that isotopic exchange reactions may lead to a depletion of 13C in nitrile-bearing species, with 12C/13C ratios two times higher than the elemental abundance ratio of 68 in the local interstellar medium. Since the carbon isotopic ratio is commonly used to evaluate the 14N/15N ratios with the double-isotope method, it is important to study carbon fractionation in detail to avoid incorrect assumptions. Methods. In this work, we implemented a gas-grain chemical model with new isotopic exchange reactions and investigated their introduction in the context of dense and cold molecular gas. In particular, we investigated the 12C/13C ratios of HNC, HCN, and CN using a grid of models, with temperatures and densities ranging from 10 to 50 K and 2 × 103 to 2 × 107 cm−3, respectively. Results. We suggest a possible 13C exchange through the 13C + C3 → 12C +13CC2 reaction, which does not result in dilution, but rather in 13C enhancement, for molecules that are formed starting from atomic carbon. This effect is efficient in a range of time between the formation of CO and its freeze-out on grains. Furthermore, the parameter-space exploration shows, on average, that the 12C/13C ratios of nitriles are predicted to be a factor 0.8–1.9 different from the local 12C/13C of 68 for high-mass star-forming regions. This result also affects the 14N/15N ratio: a value of 330 obtained with the double-isotope method is predicted to vary in the range 260–630, up to 1150, depending on the physical conditions. Finally, we studied the 12C/13C ratios of nitriles by varying the cosmic-ray ionisation rate, ζ: the 12C/13C ratios increase with ζ because of secondary photons and cosmic-ray reactions.