DNA mismatch and damage patterns revealed by single-molecule sequencing.

Mutations accumulate in the genome of every cell of the body throughout life, causing cancer and other diseases1,2. Most mutations begin as nucleotide mismatches or damage in one of the two strands of the DNA before becoming double-strand mutations if unrepaired or misrepaired3,4. However, current DNA-sequencing technologies cannot accurately resolve these initial single-strand events. Here we develop a single-molecule, long-read sequencing method (Hairpin Duplex Enhanced Fidelity sequencing (HiDEF-seq)) that achieves single-molecule fidelity for base substitutions when present in either one or both DNA strands. HiDEF-seq also detects cytosine deamination-a common type of DNA damage-with single-molecule fidelity. We profiled 134 samples from diverse tissues, including from individuals with cancer predisposition syndromes, and derive from them single-strand mismatch and damage signatures. We find correspondences between these single-strand signatures and known double-strand mutational signatures, which resolves the identity of the initiating lesions. Tumours deficient in both mismatch repair and replicative polymerase proofreading show distinct single-strand mismatch patterns compared to samples that are deficient in only polymerase proofreading. We also define a single-strand damage signature for APOBEC3A. In the mitochondrial genome, our findings support a mutagenic mechanism occurring primarily during replication. As double-strand DNA mutations are only the end point of the mutation process, our approach to detect the initiating single-strand events at single-molecule resolution will enable studies of how mutations arise in a variety of contexts, especially in cancer and ageing.

From Criegee to Breslow: How π-Donors Steer the Route of Olefin Ozonolysis.

While π-bonds typically undergo cycloaddition with ozone, resulting in the release of much-noticed carbonyl O-oxide Criegee intermediates, lone-pairs of electrons tend to selectively accept a single oxygen atom from O3, producing singlet dioxygen. We questioned whether the introduction of potent electron-donating groups, akin to N-heterocyclic olefins, could influence the reactivity of double bonds - shifting from cycloaddition to oxygen atom transfer or generating lesser-known, yet stabilized, donor-substituted Criegee intermediates. Consequently, we conducted a comparative computational study using density functional theory on a series of model olefins with increasing polarity due to (asymmetric) π-donor substitution. Reaction path computations indicate that highly polarized double bonds, instead of forming primary ozonides in their reaction with O3, exhibit a preference for accepting a single oxygen atom, resulting in a zwitterionic species formally identified as a carbene-carbonyl adduct. This previously unexplored reactivity potentially introduces aldehyde umpolung chemistry (Breslow intermediate) through olefin ozonolysis. Considering solvent effects implicitly reveals that increased solvent polarity further directs the trajectories toward a single oxygen atom transfer reactivity by stabilizing the zwitterionic character of the transition state. The competing modes of chemical reactivity can be explained by a bifurcation of the reaction valley in the post-transition state region.

Conformations and Rearrangements of Collinolactone - Experiments and Theory on a Dynamic Cyclodecatriene.

Collinolactone A is a microbial specialized metabolite with a unique 6-10-7 tricyclic bislactone skeleton which was isolated from Streptomyces bacteria. The unusual cyclodecatriene motif features dynamic interconversions of two rotamers. Given the biological profiling of collinolactone A as neuroprotective agent, semisynthetic modifications represent an invaluable strategy to enhance its efficacy. Since understanding conformations and reactions of bioactive substances is crucial for rational structure-based design and synthesis of derivatives, we conducted computational studies on conformational behavior as well as experiments on thermal and acid induced rearrangements of the cyclodecatriene. Experimental conformer ratios of collinolactone A and its biosynthetic ketolactone precursor are well reproduced by computations at the PW6B95-D3/def2-QZVPP//r2 SCAN-3c level. Upon heating collinolactone A in anhydrous dioxane at 100 °C, three collinolactone B stereoisomers exhibiting enollactone structures form via Cope rearrangements. Our computations predict the energetic preference for a boat-like transition state in agreement with the stereochemical outcome of the main reaction pathway. Constriction of the ten-membered ring forms collinolactone C with four annulated rings and an exocyclic double bond. Computations and semisynthetic experiments demonstrate strong preference for an acid-catalyzed reaction pathway over an alternative Alder-ene route to collinolactone C with a prohibitive reaction barrier, again in line with stereochemical observations.

Electron-Induced Damage by UV Photolysis of DNA Attached to Gold Nanoparticles.

Photolysis of DNA attached to gold nanoparticles (AuNPs) with ultraviolet (UV) photons induces DNA damage. The release of nucleobases (Cyt, Gua, Ade, and Thy) from DNA was the major reaction (99%) with an approximately equal release of pyrimidines and purines. This reaction contributes to the formation of abasic sites in DNA. In addition, liquid chromatography-mass spectrometry/MS (LC-MS/MS) analysis revealed the formation of reduction products of pyrimidines (5,6-dihydrothymidine and 5,6-dihydro-2'-deoxyuridine) and eight 2',3'- and 2',5'-dideoxynucleosides. In contrast, there was no evidence of the formation of 5-hydroxymethyluracil and 8-oxo-7,8-dihydroguanine, which are common oxidation products of thymine and guanine, respectively. Using appropriate filters, the main photochemical reactions were found to involve photoelectrons ejected from AuNPs by UV photons. The contribution of "hot" conduction band electrons with energies below the photoemission threshold was minor. The mechanism for the release of free nucleobases by photoelectrons is proposed to take place by the initial formation of transient molecular anions of the nucleobases, followed by dissociative electron attachment at the C1'-N glycosidic bond connecting the nucleobase to the sugar-phosphate backbone. This mechanism is consistent with the reactivity of secondary electrons ejected by X-ray irradiation of AuNPs attached to DNA, as well as the reactions of various nucleic acid derivatives irradiated with monoenergetic very-low-energy electrons (∼2 eV). These studies should help us to understand the chemistry of nanoparticles that are exposed to UV light and that are used as scaffolds and catalysts in molecular biology, curative agents in photodynamic therapy, and components of sunscreens and cosmetics.

Synthesis of Sterically Encumbered Thiourea S-Oxides through Direct Thiourea Oxidation.

Thiourea S-oxides can be viewed as formal analogs of the currently unknown diamino-substituted Criegee intermediates (urea O-oxides). However, the preparation of such S-oxides is rather challenging, and the direct oxidation of thioureas typically only leads to formation of desulfurized products. Employing the accurate revDSD-PBEP86-D4 double hybrid density functional, it was found that the peracid mediated oxidation of thiourea S-oxides exhibits a lower reaction barrier than the oxidation of the corresponding thiourea itself in contrast to most other ordinary thioketones. The undesired overoxidation reactivity, which is associated with strong π-donation from the thiourea's nitrogen atoms, can be partially suppressed by introduction of bulky substituents and the utilization of protic solvents. In this regard, we managed to prepare two sterically encumbered thiourea S-oxides in isolated yields of 35-40 %. The S-oxides are stable in the solid state and in alcoholic solutions at room temperature for extended periods of time, but swiftly decompose in aprotic solvents by disproportionation. A dimesityl-substituted thiourea S-oxide complexed with residual mCBA could be characterized by means of X-ray crystallography, confirming the importance of hydrogen bonding in the stabilization of the amino-substituted C=S+ -O- moiety.

A Metastable Ketenyl Radical-Water Complex from UV Photolysis of the Carboxymethyl Radical.

The unpaired electron impacts the binding between radicals and ordinary closed-shell molecules in noncovalent complexes. Conversely, the complexation partner can enhance, decrease, or even control the reactivity of the interacting radical. Previously, such radical-molecule (and especially radical-water) complexes were studied by controlled assembly of the interacting partners which mostly leads to formation of the thermodynamically most stable species. Here, we show that UV photolysis of the resonance-stabilized carboxymethyl radical isolated in a cryogenic argon matrix at 4 K leads to the intermediary formation of a metastable, noncovalent complex of the ketenyl radical with a water molecule. In this complex, the ketenyl radical binds water at its terminal carbon atom, although a more stable isomer exists in which water interacts with the C-H bond of the radical. Rigorous W1 theory computations confirm that the ketenyl radical is a stronger donor in C-H···O interactions than ketene itself, while it performs comparably well as an acceptor. We propose that complex formation proceeds via an initial excited-state C-O bond breaking reaction in carboxymethyl under release of an OH radical, which is supported by multireference QD-NEVPT2 computations.

2H-Imidazol-2-one O-Oxide: A Criegee Intermediate from a σ0π2 Singlet Ground-State Carbene.

Triplet carbenes and triplet molecular oxygen can combine to form singlet carbonyl O-oxide Criegee intermediates in an overall spin-allowed transformation. While this reaction runs at the diffusion limit in the case of triplet carbenes, singlet carbenes are commonly more reluctant to bind 3O2. In contradiction to this customarily encountered spin selectivity, the σ0π2 singlet ground-state carbene 2H-imidazol-2-ylidene 1 reacts extremely rapidly with 3O2 at temperatures as low as 30 K. The product of this cryogenic reaction is singlet 2H-imidazol-2-one O-oxide 7, an N-heterocyclic Criegee intermediate. The addition reaction becomes possible through the electrophilic activation of dioxygen in the triplet state, in which O2 binding can initially proceed without a barrier. Criegee intermediate 7 exhibits an unprecedented high O-O stretching vibration at 1105 cm-1, which can be explained by a resonance structure with an O2 double bond. Furthermore, 2H-imidazol-2-one 5 and spiro-dioxirane 6 could be identified as the photodecomposition products of the herein-reported carbonyl oxide.

Comprehensive cancer predisposition testing within the prospective MASTER trial identifies hereditary cancer patients and supports treatment decisions for rare cancers.

BACKGROUND: Germline variant evaluation in precision oncology opens new paths toward the identification of patients with genetic tumor risk syndromes and the exploration of therapeutic relevance. Here, we present the results of germline variant analysis and their clinical implications in a precision oncology study for patients with predominantly rare cancers. PATIENTS AND METHODS: Matched tumor and control genome/exome and RNA sequencing was carried out for 1485 patients with rare cancers (79%) and/or young adults (77% younger than 51 years) in the National Center for Tumor Diseases/German Cancer Consortium (NCT/DKTK) Molecularly Aided Stratification for Tumor Eradication Research (MASTER) trial, a German multicenter, prospective, observational precision oncology study. Clinical and therapeutic relevance of prospective pathogenic germline variant (PGV) evaluation was analyzed and compared to other precision oncology studies. RESULTS: Ten percent of patients (n = 157) harbored PGVs in 35 genes associated with autosomal dominant cancer predisposition, whereof up to 75% were unknown before study participation. Another 5% of patients (n = 75) were heterozygous carriers for recessive genetic tumor risk syndromes. Particularly, high PGV yields were found in patients with gastrointestinal stromal tumors (GISTs) (28%, n = 11/40), and more specifically in wild-type GISTs (50%, n = 10/20), leiomyosarcomas (21%, n = 19/89), and hepatopancreaticobiliary cancers (16%, n = 16/97). Forty-five percent of PGVs (n = 100/221) supported treatment recommendations, and its implementation led to a clinical benefit in 40% of patients (n = 10/25). A comparison of different precision oncology studies revealed variable PGV yields and considerable differences in germline variant analysis workflows. We therefore propose a detailed workflow for germline variant evaluation. CONCLUSIONS: Genetic germline testing in patients with rare cancers can identify the very first patient in a hereditary cancer family and can lead to clinical benefit in a broad range of entities. Its routine implementation in precision oncology accompanied by the harmonization of germline variant evaluation workflows will increase clinical benefit and boost research.

Coaxial laser absorption and optical emission spectroscopy of high-pressure aluminum monoxide.

This work advances laser absorption spectroscopy with measurements of aluminum monoxide (AlO) temperature and column density in extreme pressure (P > 60 bar) and temperature (T > 4000 K) environments. Measurements of the AlO A2Πi-X2Σ+ transition are made using a microelectromechanical system, tunable vertical cavity surface emitting laser (MEMS-VCSEL). Simultaneous emission measurements of the AlO B2Σ+-X2Σ+ transition are made along a line of sight that is coaxial with the laser absorption. Absorption temperature fits agree with emission spectra for a T = 3200 K, P = 9 bar case. In cases with T > 4000 K, P > 60 bar, absorption fits match the ambient temperature while emission fits over-estimate it, owing to high optical depths. These data juxtapose passive and active spectroscopic methods and demonstrate the versatility of AlO laser absorption in high-pressure and high-temperature environments where experimental data remain scarce, and engineering models will benefit from refined measurements.

The activated reaction of dichlorocarbene with triplet molecular oxygen.

The well-known dichlorocarbene (CCl2, 1) is deemed to undergo an extremely facile addition reaction with triplet molecular oxygen (3O2) under formation of the corresponding singlet Criegee intermediate, phosgene O-oxide. This is unexpected, because the carbene possesses a singlet ground state with a large singlet-triplet gap and, typically, only triplet carbenes react swiftly with triplet dioxygen. Hence, we deployed a careful theoretical study of this reaction and computed the oxygen addition barrier at levels of electron correlation as high as CCSD(T) and BD(TQ) and basis sets as large as cc-pV5Z. Our results firmly establish the existence of a reaction barrier, and we estimate its height to amount to 8.8 kcal mol-1. Furthermore, the initially formed triplet dioxygen adduct is prone to facile O-O bond breaking rendering phosgene and triplet oxygen atoms likely products of the overall reaction. As a general conclusion, we find that carbenes are ambiphiles in oxygen additions and more electrophilic as well as that more nucleophilic carbenes show greater reactivity.

Selective cytotoxicity of ent-kaurene diterpenoids isolated from Baccharis lateralis and Baccharis retusa (Asteraceae).

This study presents the cytotoxic activity evaluation of the natural diterpenes ent-kaurenoic acid (1) and its 15ß-hydroxy (2), 15ß-senecioyloxy (3), and 15ß-tiglinoyloxy (4) derivatives, isolated from Brazilian native plants, Baccharis retusa and B. lateralis (Asteraceae). Using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) colorimetric assay, it was observed that compound 1 displayed in vitro activity towards the aggressive MDA-MB-231 adenocarcinoma cell line and reduced toxicity against MCF-10A nontumorigenic epithelial cells, indicating expressive selectivity. On the contrary, compounds 2-4 exhibited reduced toxicity and selectivity in both tested cell lines. Based on the chemical structures of compounds 1-4, it is suggested that the presence of additional functional groups at the C-15 position-a hydroxyl group in compound 2 and isomeric isoprene units in compounds 3 and 4-might be responsible for the reduction in the potential/selectivity. In silico studies show, for compounds 1-4, good predictions regarding bioavailability and ADME (absorption, distribution, metabolism, and excretion) properties as well as no alerts for PAINS (pan-assay structures interference). In conclusion, ent-kaurenoic acid (1), a common diterpenoid isolated in high amounts from different plants belonging to the Baccharis genus, has been shown to be a promising cytotoxic agent against an aggressive adenocarcinoma cell line (MDA-MB-23) and, if well exploited, could be used as a scaffold in the development of molecular prototypes for the treatment of breast cancer.

Did implementation of three ligament tenodesis improve patient outcome after chronic scapholunate instability? A retrospective study.

INTRODUCTION: Scapholunate instability frequently leads to chronic pain or even severe osteoarthritis of the wrist. Most favored reconstruction techniques of chronic SL-ligament injuries are based on the usage of a tendon, although there is still a lack of consensus which technique is superior. MATERIALS AND METHODS: In a retrospective cohort analysis we compared 9 patients who underwent SL-ligament repair according to Van den Abbeele and 12 patients who underwent modified three ligament tenodesis according to Garcia-Elias, performed at a single institution. RESULTS: Follow-up of Van den Abbeele group was 36-120 months and 13-39 months in the Garcia Elias cohort. Although both techniques showed good functional outcome in most cases, modified three ligament tenodesis seemed to be advantageous regarding wrist range of motion (162°) compared to Van den Abbeele cohort (87°). Moreover, pain score showed significant differences between the two cohorts during follow up (VAS Van den Abbeele 4.2; VAS Garcia Elias 1.7). Interestingly, DASH-score (16.1 Van den Abbeele; 16.8 Garcia Elias) and modified mayo wrist score (72 Van den Abbeele; 69 Garcia-Elias) did not show any differences between the two patient cohorts. CONCLUSIONS: Via implementation of modified three ligament tenodesis as a standard of care for our patients we could improve the functional outcome after SL-ligament injuries and effectively decrease postoperative pain.

Intramolecular London Dispersion Interactions Do Not Cancel in Solution.

We present a comprehensive experimental study of a di-t-butyl-substituted cyclooctatetraene-based molecular balance to measure the effect of 16 different solvents on the equilibrium of folded versus unfolded isomers. In the folded 1,6-isomer, the two t-butyl groups are in close proximity (H···H distance ≈ 2.5 Å), but they are far apart in the unfolded 1,4-isomer (H···H distance ≈ 7 Å). We determined the relative strengths of these noncovalent intramolecular σ-σ interactions via temperature-dependent nuclear magnetic resonance measurements. The origins of the interactions were elucidated with energy decomposition analysis at the density functional and ab initio levels of theory, pinpointing the predominance of London dispersion interactions enthalpically favoring the folded state in any solvent measured.

Experimental eye research / short communication format characterization of DNA hydroxymethylation in the ocular choroid.

DNA methylation and hydroxymethylation represent important epigenetic modifications involved in cell differentiation. DNA hydroxymethylation can be used to classify independent biological samples by tissue type. Relatively little is known regarding the genomic abundance and function of 5-hydroxymethylcytosine (5-hmC) in ocular tissues. The choroid supplies oxygen and nutrients to the outer retina through its dense network of blood vessels. This connective tissue is mainly composed of pigmented melanocytes, and stromal fibroblasts. Since DNA hydroxymethylation level is relatively high in cutaneous melanocytes, we investigated the presence of 5-hmC in choroidal melanocytes, as well as the expression of ten-eleven translocation methylcytosine dioxygenases (TETs) and isocitrate dehydrogenases (IDHs) implicated in this DNA demethylation pathway. Immunofluorescence, DNA slot blots and liquid chromatography coupled to tandem mass spectrometry performed with choroidal tissues and melanocytes within these tissues revealed that they have a relatively high level of 5-hmC. We also examined the expression of TET1/2 and IDH1/2 in choroidal melanocytes by gene expression profiling, qPCR and Western blotting. In addition, we detected decreased levels of 5-hmC when choroidal melanocytes were exposed to a lower concentration of oxygen. Our study therefore demonstrates that DNA hydroxymethylation is present in choroidal melanocytes, and that the abundance of this epigenetic mark is impacted by hypoxia.

Ozone-Induced DNA Damage: A Pandora's Box of Oxidatively Modified DNA Bases.

Ozone is a major component of air pollution and carries potentially mutagenic and harmful affects to health. The oxidation of isolated calf thymus DNA (CT-DNA) led to the nearly quantitative loss of normal DNA 2'-deoxyribonucleosides in the following order: T > G > C ≫ A. The major modification of pyrimidines (T, C, and 5-methylcytosine (5mC)) was the corresponding 5-hydroxyhydantoin derivative after complete digestion of DNA to its component 2'-deoxyribonucleosides. The oxidation of 5mC was 2.5-fold more susceptible than C considering the relative mole fraction of 5mC to C in CT-DNA. Other common oxidation products of pyrimidines (e.g., 5,6-dihydroxy-5,6-dihydropyrimidines, the so-called pyrimidine 5,6-glycols) were formed with a lower yield than 5-hydroxyhydantoin derivatives. In addition, several common oxidation products of G were observed (e.g., 8-oxo-7,8-dihydroguanine (8oxoG)) albeit with relatively minor yields. The sum of individual products was notably less than the loss of 2'-deoxyribonucleosides from which they were derived. In a search for additional products, we discovered the formation of pyrimidine ring fragments, predominantly N-formamide and N-urea, which were measured as a dinucleotide next to a nonmodified nucleotide upon partial digestion of oxidized DNA. Interestingly, the latter fragments were also observed in dinucleotides containing 8oxoG, indicating the formation of tandem lesions during ozonolysis of DNA. The oxidation of DNA upon exposure to ozone can be explained by reactions of an intermediate ozonide. These studies underline the complexity of ozone-induced DNA damage and provide valuable information to assess the formation of this damage in cellular DNA.

σ0π2 Singlet Ground State Carbenes Undergo Least-Motion Reactions with H2 and Alkenes.

Ground state singlet carbenes commonly feature σ2π0 orbital occupations and are known for their concerted σ-bond insertion and cycloaddition reactions. Despite the facility of these transformations, orbital symmetry conservation forces them into non-least-motion π-approach reaction pathways. This situation completely changes when the singlet σ0π2 electron configuration becomes the ground state, which we show here by means of high-level CCSD(T) geometry optimizations. Carbenes like the experimentally known 2H-imidazol-2-ylidene react with H2 and ethylene with negligible or no barrier in a σ-fashion, which effectively corresponds to a least-motion reaction trajectory.

Hospital volume following major surgery for gastric cancer determines in-hospital mortality rate and failure to rescue: a nation-wide study based on German billing data (2009-2017).

BACKGROUND: For many cancer resections, a hospital volume-outcome relationship exists. The data regarding gastric cancer resection-especially in the western hemisphere-are ambiguous. This study analyzes the impact of gastric cancer surgery caseload per hospital on postoperative mortality and failure to rescue in Germany. METHODS: All patients diagnosed with gastric cancer from 2009 to 2017 who underwent gastric resection were identified from nation-wide administrative data. Hospitals were grouped into five equal caseload quintiles (I-V in ascending caseload order). Postoperative deaths and failure to rescue were determined. RESULTS: Forty-six thousand one hundred eighty-seven patients were identified. There was a significant shift from partial resections in low-volume hospitals to more extended resections in high-volume centers. The overall in-house mortality rate was 6.2%. The crude in-hospital mortality rate ranged from 7.9% in quintile I to 4.4% in quintile V, with a significant trend between volume categories (p < 0.001). In the multivariable logistic regression analysis, quintile V hospitals (average of 29 interventions/year) had a risk-adjusted odds ratio of 0.50 (95% CI 0.39-0.65), compared to the baseline in-house mortality rate in quintile I (on average 1.5 interventions/year) (p < 0.001). In an analysis only evaluating hospitals with more than 30 resections per year mortality dropped below 4%. The overall postoperative complication rate was comparable between different volume quintiles, but failure to rescue (FtR) decreased significantly with increasing caseload. CONCLUSION: Patients who had gastric cancer surgery in hospitals with higher volume had better outcomes and a reduced failure to rescue rates for severe complications.

Criegee Intermediates in Autoxidation Reactions: Mechanistic Considerations.

Products of Criegee intermediate (CI) chemistry were recently detected in radical chain autoxidation reactions involving ß-hydroxyperoxy radicals. Here, we demonstrate by means of accurate G4 computations that direct scission of the latter to CIs and radical byproducts is thermodynamically highly unfavorable. Instead, the reaction becomes possible through a hydrogen abstraction reaction that could proceed by reversible formation of a dimeric tetroxide and a subsequent [1,6] hydrogen shift of the hydroxy hydrogen.

D-Galacturonic acid reduction by S. cerevisiae for L-galactonate production from extracted sugar beet press pulp hydrolysate.

Pectin-rich residues are considered as promising feedstocks for sustainable production of platform chemicals. Enzymatic hydrolysis of extracted sugar beet press pulp (SBPP) releases the main constituent of pectin, D-galacturonic acid (D-GalA). Using engineered Saccharomyces cerevisiae, D-GalA is then reduced to L-galactonate (L-GalOA) with sorbitol as co-substrate. The current work addresses the combination of enzymatic hydrolysis of pectin in SBPP with a consecutive optimized biotransformation of the released D-GalA to L-GalOA in simple batch processes in stirred-tank bioreactors. Process conditions were first identified with synthetic media, where a product concentration of 9.9 g L-1 L-GalOA was obtained with a product selectivity of 99% (L-GalOA D-GalA-1) at pH 5 with 4% (w/v) sorbitol within 48 h. A very similar batch process performance with a product selectivity of 97% was achieved with potassium citrate buffered SBPP hydrolysate, demonstrating for the first time direct production of L-GalOA from hydrolyzed biomass using engineered S. cerevisiae. Combining the hydrolysis process of extracted SBPP and the biotransformation process with engineered S. cerevisiae paves the way towards repurposing pectin-rich residues as substrates for value-added chemicals. KEY POINTS: • Efficient bioreduction of D-GalA with S. cerevisiae in stirred-tank reactors • Batch production of L-GalOA by engineered S. cerevisiae with high selectivity • Direct L-GalOA production from hydrolyzed sugar beet press pulp Bioreduction of D-galacturonic acid to L-galactonate with recombinant Saccharomyces cerevisiae enables for the first time the valorization of hydrolysates from extracted sugar beet press pulp for the sustainable production of value-added chemicals.

Infrared spectroscopy of the protonated HCl dimer and trimer.

The protonated HCl dimer and trimer complexes were prepared by pulsed discharges in supersonic expansions of helium or argon doped with HCl and hydrogen. The ions were mass selected in a reflectron time-of-flight spectrometer and investigated with photodissociation spectroscopy in the IR and near-IR regions. Anharmonic vibrational frequencies were computed with VPT2 at the MP2/cc-pVTZ level of theory. The Cl-H stretching fundamentals and overtones were measured in addition to stretch-torsion combinations. VPT2 theory at this level confirms the proton-bound structure of the dimer complex and provides a reasonably good description of the anharmonic vibrations in this system. The trimer has a HCl-HClH+-ClH structure in which a central chloronium ion is solvated by two HCl molecules via hydrogen bonding. VPT2 reproduces anharmonic frequencies for this system, including several combinations involving core ion Cl-H stretches, but fails to describe the relative band intensities.