How the nature and charge of metal cations affect vibrations in acetone solvent molecules.

Vibrational spectra of a series of gas-phase metal 1+ and 2+ ions solvated by acetone molecules are collected to investigate how the metal charge, number of solvent molecules and nature of the metal affect the acetone. The spectra of Cu+(Ace)(N2)2, Cu+(Ace)4, and M2+(Ace)4, where M = Co, Ni, Cu, and Zn are measured via photodissociation by monitoring fragment ion signal as a function of IR wavenumber. The spectra show a red shift of the CO stretch and a blue shift of the C-C antisymmetric stretch. DFT calculations are carried out to provide the simulated spectra of possible isomers to be compared with the observed vibrational spectra, and specific structures are proposed. The red shift of the CO stretch increases as the number of acetone molecules decreases. Higher charge on the metal leads to a larger red shift in the CO stretch. Although all of the M2+ complexes have very similar red shifts, they are predicted to have different geometries due to their different electron configurations. Unexpectedly, we find that the calculated red shift in the CO stretch in M+/2+(Ace) is highly linearly correlated with the ionization energy of the metal for a wide range of metal cations and dications.

Multianalytical Approach for Deciphering the Specific MS/MS Transition and Overcoming the Challenge of the Separation of a Transient Intermediate, Quinonoid Dihydrobiopterin.

Despite recent technological developments in analytical chemistry, separation and direct characterization of transient intermediates remain an analytical challenge. Among these, separation and direct characterization of quinonoid dihydrobiopterin (qH2Bip), a transient intermediate of tetrahydrobiopterin (H4Bip)-dependent hydroxylation reactions, essential in living organisms, with important and varied human pathophysiological impacts, are a clear illustration. H4Bip regeneration may be impaired by competitive nonenzymatic autoxidation reactions, such as isomerization of qH2Bip into a more stable 7,8-H2Bip (H2Bip) isomer, and subsequent nonenzymatic oxidation reactions. The quinonoid qH2Bip intermediate thus plays a key role in H4Bip-dependent hydroxylation reactions. However, only a few experimental results have indirectly confirmed this finding while revealing the difficulty of isolating qH2Bip from H4Bip-containing solutions. As a result, no current H4Bip assay method allows this isomer to be quantified even by liquid chromatography-tandem mass spectrometry (MS/MS). Here, we report isolation, structural characterization, and abundance of qH2Bip formed upon H4Bip autoxidation using three methods integrated into MS/MS. First, we characterized the structure of the two observed H2B isomers using IR photodissociation spectroscopy in conjunction with quantum chemical calculations. Then, we used differential ion mobility spectrometry to fully separate all oxidized forms of H4Bip including qH2Bip. These data are consistent and show that qH2Bip can also be unambiguously identified thanks to its specific MS/MS transition. This finding paves the way for the quantification of qH2Bip with MS/MS methods. Most importantly, the half-life value of this intermediate is nearly equivalent to that of H4Bip (tens of minutes), suggesting that an accurate method of H4Bip analysis should include the quantification of qH2Bip.

Applications of Infrared Multiple Photon Dissociation (IRMPD) to the Detection of Posttranslational Modifications.

Infrared multiple photon dissociation (IRMPD) spectroscopy allows for the derivation of the vibrational fingerprint of molecular ions under tandem mass spectrometry (MS/MS) conditions. It provides insight into the nature and localization of posttranslational modifications (PTMs) affecting single amino acids and peptides. IRMPD spectroscopy, which takes advantage of the high sensitivity and resolution of MS/MS, relies on a wavelength specific fragmentation process occurring on resonance with an IR active vibrational mode of the sampled species and is well suited to reveal the presence of a PTM and its impact in the molecular environment. IRMPD spectroscopy is clearly not a proteomics tool. It is rather a valuable source of information for fixed wavelength IRMPD exploited in dissociation protocols of peptides and proteins. Indeed, from the large variety of model PTM containing amino acids and peptides which have been characterized by IRMPD spectroscopy, specific signatures of PTMs such as phosphorylation or sulfonation can be derived. High throughput workflows relying on the selective fragmentation of modified peptides within a complex mixture have thus been proposed. Sequential fragmentations can be observed upon IR activation, which do not only give rise to rich fragmentation patterns but also overcome low mass cutoff limitations in ion trap mass analyzers. Laser-based vibrational spectroscopy of mass-selected ions holding various PTMs is an increasingly expanding field both in the variety of chemical issues coped with and in the technological advancements and implementations.

Ligation Motifs in Zinc-Bound Sulfonamide Drugs Assayed by IR Ion Spectroscopy.

The sulfonamide-zinc ion interaction, performing a key role in various biological contexts, is the focus of the present study, with the aim of elucidating ligation motifs in zinc complexes of sulfa drugs, namely sulfadiazine (SDZ) and sulfathiazole (STZ), in a perturbation-free environment. To this end, an approach is exploited based on mass spectrometry coupled with infrared multiple photon dissociation (IRMPD) spectroscopy backed by quantum chemical calculations. IR spectra of Zn(H2O+SDZ-H)+ and Zn(H2O+STZ-H)+ ions are consistent with a three-coordinate zinc complex, where ZnOH+ binds to the uncharged sulfonamide via N(heterocycle) and O(sulfonyl) donor atoms. Alternative prototropic isomers Zn(OH2)(SDZ-H)+ and Zn(OH2)(STZ-H)+ lie 63 and 26 kJ mol-1 higher in free energy, respectively, relative to the ground state Zn(OH)(SDZ)+ and Zn(OH)(STZ)+ species and do not contribute to any significant extent in the sampled population.

Binding Motifs in the Naked Complexes of Target Amino Acids with an Excerpt of Antitumor Active Biomolecule: An Ion Vibrational Spectroscopy Assay.

The structures of proton-bound complexes of 5,7-dimethoxy-4H-chromen-4-one (1) and basic amino acids (AAs), namely, histidine (His) and lysine (Lys), have been examined by means of mass spectrometry coupled with IR ion spectroscopy and quantum chemical calculations. This selection of systems is based on the fact that 1 represents a portion of glabrescione B, a natural small molecule of promising antitumor activity, while His and Lys are protein residues lining the cavity of the alleged receptor binding site. These species are thus a model of the bioactive adduct, although clearly the isolated state of the present study bears little resemblance to the complex biological environment. A common feature of [1+AA+H]+ complexes is the presence of a protonated AA bound to neutral 1, in spite of the fact that the gas-phase basicity of 1 is comparable to those of Lys and His. The carbonyl group of 1 acts as a powerful hydrogen-bond acceptor. Within [1+AA+H]+ the side-chain substituents (imidazole group for His and terminal amino group for Lys) present comparable basic properties to those of the α-amino group, taking part to a cooperative hydrogen-bond network. Structural assignment, relying on the comparative analysis of the infrared multiple photon dissociation (IRMPD) spectrum and calculated IR spectra for the candidate geometries, derives from an examination over two frequency ranges: 900-1800 and 2900-3700 cm-1 . Information gained from the latter one proved especially valuable, for example, pointing to the contribution of species characterized by an unperturbed carboxylic OH or imidazole NH stretching mode.

Infrared Multiple Photon Dissociation Spectroscopy of Protonated Cyameluric Acid.

The present study reports the first structural characterization of protonated cyameluric acid ([CA + H]+) in the gas phase, which paves the way for prospective bottom-up research on the condensed-phase chemistry of CA in the protonated form. A number of [CA + H]+ keto-enol isomers can a priori be produced as a result of protonation at available N and O positions of precursor neutral CA tautomers, yet ab initio computations predict different reduced [CA + H]+ isomer populations dominating the solution and gas phases that are involved in the ion generation process (i.e., electrospray ionization). Infrared multiple photon dissociation spectra were recorded in the 990-1900 and 3300-3650 cm-1 regions and compared with theoretical [B3LYP/6-311++G(d,p)] IR absorption spectra of several [CA + H]+ isomers, providing a satisfactory agreement for the most stable monohydroxy form in the gas phase, [1358a]+, yet the contribution of its nearly isoenergetic OH rotamer, [1358b]+, cannot be neglected. This is indicative of the occurrence of [CA + H]+ isomer interconversion reactions, assisted by protic solvent molecules, during their transfer into the gas phase. The results suggest that available O positions on neutral CA are energetically favored protonation sites in the gas phase.

IRMPD Spectra of Protonated Hydroxybenzaldehydes: Evidence of Torsional Barriers in Carboxonium Ions.

Protonation at the formyl oxygen atom of benzaldehydes leading to the formation of carboxonium ions yields two distinct isomers, depending on the relative orientation of the proton either cis or trans with respect to the hydrogen atom on the adjacent carbon. In this context, the IR multiple photon dissociation (IRMPD) spectra of protonated ortho, meta, and para-hydroxybenzaldehydes (OH-BZH+ ), delivered into the gas phase by electrospray ionization of hydro-alcoholic solutions, are reported in the 3200-3700 cm-1 spectral range. This range is characteristic of O-H stretching modes and thus able to differentiate cis and trans carboxonium isomers. Comparison between IRMPD spectra and DFT calculations at the B3LYP/6-311++G(2df2p) level suggests that for both p-OH-BZH+ and m-OH-BZH+ only cis conformers are present in the ion population analyzed. For o-OH-BZH+ , IRMPD spectroscopy points to a mixture comprising one trans and more than one cis conformers. The energy barrier for cis-trans isomerization calculated for each OH-BZH+ isomer is a measure of the degree of π-electron delocalization. Furthermore, IRMPD spectra of p-OH-BZH+ , m-OH-BZH+ and protonated phenol (this last used as reference) were recorded also in the fingerprint range. Both the observed C-O and O-H stretching vibrations appear to be a measure of π-electron delocalization in the ions.

On the Interaction between Deprotonated Cytosine [C(-H) ]- and Ba2+ : Infrared Multiphoton Spectroscopy and Dynamics.

Gas-phase interactions between Ba2+ and deprotonated cytosine (C(-H) ) were studied in [C(-H) Ba]+ and [C(-H) BaC]+ complexes by IRMPD spectroscopy coupled to tandem mass-spectrometry in combination with DFT calculations. For the [C(-H) BaC]+ complex only one [C(-H) KAN1O-Ba-Canti ]+ isomer was found, although the presence of another structure cannot be excluded. This isomer features a central tetracoordinated Ba2+ that simultaneously interacts with keto-amino [C(-H) ]- deprotonated on N1 and neutral keto-amino C. Both moieties are in different planes as a consequence of an additional NH…O=C hydrogen bond between C and [C(-H) ]- . A sequential IRMPD dynamics is observed in this complex. For the [C(-H) Ba]+ complex produced by electrospray ionization two isomers ([C(-H) KAN1OBa]+ and [C(-H) KAN3OBa]+ ) were identified, in which Ba2+ interacts simultaneously with the C=O group and the N1 or N3 atom of the keto-amino [C(-H) ]- , respectively. A comparison with the related [C(-H) Pb]+ complex (J. Y. Salpin et al., Chem. Phys. Chem. 2014, 15, 2959-2971) is also presented.

Identification and quantification of amino acids and related compounds based on Differential Mobility Spectrometry.

Amino acids and related compounds constitute a class of biomarkers which is analyzed for early diagnosis of metabolic diseases (MDs). Protocols based on liquid chromatography hyphenated to tandem mass spectrometry (LC-MS/MS) are routinely used for MD diagnosis. Our ultimate objective is to evaluate the analytical performance of differential mobility spectrometry (DMS) hyphenated to MS/MS, in the perspective of using DMS-MS/MS as an alternative or complementary method for the topics of emergency in metabolic diagnosis and newborn rapid screening. The aim of the present study is to evaluate the robustness of a DMS-MS/MS protocol for the separation, identification, and quantification of amino acids and related compounds. Performance in terms of peak capacity and separation of isobaric and isomeric species is compared to those using drift tube type ion mobility spectrometry instruments. High reproducibility of the measurement of the DMS compensation voltage (CV) of metabolites shows that this CV parameter, or the corresponding electric field, could be used for application in metabolite identification. Multiple measurements show that the CV value of each AA or related compound is stable over a large period of time (6 months). Potential effects of matrix or concentration of the analytes on the DMS identifier are found to be negligible. Quantification of a selected set of metabolites in human plasmas has been carried out. The method linearity, intra-assay and inter-assay precision, detection limit, quantification limit and trueness analysis were assessed as adequate for both physiological and pathological conditions. Concentration levels of metabolites derived with our DMS-MS protocols were found to be in good agreement with those obtained with routine LC-MS/MS protocols used for the diagnosis of MDs at the Hospital Robert Debré (Paris).

Structure of Proton-Bound Methionine and Tryptophan Dimers in the Gas Phase Investigated with IRMPD Spectroscopy and Quantum Chemical Calculations.

The structures of three proton-bound dimers (Met2H+, MetTrpH+, and Trp2H+) are investigated in the gas phase with infrared multiple photon disassociation (IRMPD) spectroscopy in combination with quantum chemical calculations. Their IRMPD spectra in the range of 600-1850 cm-1 are obtained experimentally using an FT-ICR mass spectrometer and the CLIO free electron laser as an IR light source. The most abundant conformers are elucidated by comparing the IRMPD spectra with harmonic frequencies obtained at the B3LYP-GD3BJ/6-311++G** level of theory. Discrepancies between the experimental and theoretical data in the region of 1500-1700 cm-1 are attributed to the anharmonicity of the amino bending modes. We confirm the result of a previous IRMPD study that the structure of gas-phase Trp2H+ is charge-solvated but find that there are more stable structures than originally reported (Feng, R.; Yin, H.; Kong, X. Rapid Commun. Mass Spectrom. 2016, 30, 24-28). In addition, gas-phase Met2H+ and MetTrpH+ have been revealed to have charge-solvated structures. For all three dimers, the most stable conformer is found to be of type A. The spectrum of Met2H+, however, cannot be explained without some abundance of type B charge-solvated conformers as well as salt-bridged structures.

Reactions of Thiiranium and Sulfonium Ions with Alkenes in the Gas Phase.

Ion-molecule reactions between thiiranium ion 11 (m/z 213) and cyclohexene and cis-cyclooctene resulted in the formation of addition products 17a and 17b (m/z 295 and m/z 323, respectively) via an electrophilic addition pathway. Associative π-ligand exchange involving direct transfer of the PhS+ moiety, which has been observed for analogous seleniranium ions in the gas phase, did not occur despite previous solution experiments suggesting it as a valid pathway. DFT calculations at the M06-2X/def2-TZVP level of theory showed high barriers for the exchange reaction, while the addition pathway was more plausible. Further support for this pathway was provided with Hammett plots showing the rate of reaction to increase as the benzylic position of thiiranium ion derivatives became more electrophilic (ρ = +1.69; R2 = 0.974). The more reactive isomeric sulfonium ion 22 was discounted as being responsible for the observed reactivity with infrared spectroscopy and DFT calculations suggesting little possibility for isomerization. To further explore the differences in reactivity, thiiranium ion 25 and sulfonium ion 27 were formed independently, with the latter ion reacting over 260 times faster toward cis-cyclooctene than the thiiranium ion rationalized by calculations suggesting a barrierless pathway for sulfonium ion 27 to react with the cycloalkene.

Probing the gas-phase structure of charge-tagged intermediates of a proline catalyzed aldol reaction - vibrational spectroscopy distinguishes oxazolidinone from enamine species.

An l-proline based catalyst with a charged phenyl-pyridium substituent (1) was used to analyze intermediates of an organocatalyzed aldol reaction by infrared multi-photon dissociation (IRMPD) mass spectrometry after transfer into the gas phase via electrospray ionization (ESI). IRMPD spectra were interpreted with the aid of density functional theory (DFT) computations. A structurally restricted enamine species was used as a reference molecule for the calculated vibrational frequencies. A close correlation between theory and experiment was found for the energetically most favoured oxazolidinone structures.

Infrared multiple photon dissociation action spectroscopy of protonated glycine, histidine, lysine, and arginine complexed with 18-crown-6 ether.

Complexes of 18-crown-6 ether (18C6) with four protonated amino acids (AAs) are examined using infrared multiple photon dissociation (IRMPD) action spectroscopy utilizing light generated by the infrared free electron laser at the Centre Laser Infrarouge d'Orsay (CLIO). The AAs examined in this work include glycine (Gly) and the three basic AAs: histidine (His), lysine (Lys), and arginine (Arg). To identify the (AA)H+(18C6) conformations present in the experimental studies, the measured IRMPD spectra are compared to spectra calculated at the B3LYP/6-311+G(d,p) level of theory. Relative energies of various conformers and isomers are provided by single point energy calculations carried out at the B3LYP, B3P86, M06, and MP2(full) levels using the 6-311+G(2p,2d) basis set. The comparisons between the IRMPD and theoretical IR spectra indicate that 18C6 binds to Gly and His via the protonated backbone amino group, whereas protonated Lys prefers binding via the protonated side-chain amino group. Results for Arg are less definitive with strong evidence for binding to the protonated guanidino side chain (the calculated ground conformer at most levels of theory), but contributions from backbone binding to a zwitterionic structure are likely.

Evaluation of the Katsuki-Sharpless Epoxidation Precatalysts by ESI-FTMS, CID, and IRMPD Spectroscopy.

The Katsuki-Sharpless epoxidation reaction is one of the most recognized chiral catalytic reactions, allowing for chiral epoxides to be used as starting materials for a series of synthetic pathways. The complete understanding of this reaction mechanism depends on the identification and description of species formed from Ti(IV) alkoxides and alkyl tartrates precatalysts. Despite previous reports on the nature of a bimetallic catalyst based on IR spectroscopy and NMR analysis, some debate remains. Therefore, we carried out mass spectrometry analysis by direct extraction of the ions from the reaction media by ESI(-)-FT-ICR and evaluated the observed ions by CID and IRMPD experiments. These techniques allowed us to detect carboxylates that correlate to the species in the reaction media and to confirm the actual presence of the titanium-tartrate complexes in solution. Our IRMPD results suggest the carboxylate dimer as an asymmetric species with two tartrates coordinated to a single Ti atom, while the other Ti center is coordinated by labile alkoxydes that could be easily exchanged by the organic peroxide and the substrate, allowing the epoxidation reaction to take place.

Vibrational signatures of curcumin's chelation in copper(II) complexes: An appraisal by IRMPD spectroscopy.

Curcumin (Cur) is a natural polyphenol with a wide spectrum of biological activities and appealing therapeutic potential. Herein, it has been delivered by electrospray ionization as gaseous protonated species, [Cur + H]+, and as a Cu(ii) complex, [Cu(Cur - H)]+, a promising antioxidant and radical scavenger. The gas phase structures were assayed by infrared multiple photon dissociation (IRMPD) spectroscopy in both the fingerprint (800-2000 cm-1) and hydrogen stretching (3100-3750 cm-1) ranges. Comparison between the experimental features and linear IR spectra of the lowest energy structures computed at the B3LYP/6-311+G(d,p) level reveals that bare [Cu(Cur - H)]+ exists in a fully planar and symmetric arrangement, where the metal interacts with the two oxygens of the syn-enolate functionality of deprotonated Cur and both OCH3 groups are engaged in H-bonding with the ortho OH. The effect of protonation on the energetic and geometric determinants of Cur has been explored as well, revealing that bare [Cur + H]+ may exist as a mixture of two close-lying isomers associated with the most stable binding motifs. The additional proton is bound to either the diketo or the keto-enol configuration of Cur, in a bent or nearly planar arrangement, respectively.

The Intermediates in Lewis Acid Catalysis with Lanthanide Triflates.

Lanthanide triflates are effective Lewis acid catalysts in reactions involving carbonyl compounds due to their high oxophilicity and water stability. Despite the growing interest, the identity of the catalytic species formed in lanthanide catalysed reactions is still unknown. We have therefore used mass spectrometry and ion spectroscopy to intercept and characterize the intermediates in a reaction catalysed by ytterbium and dysprosium triflates. We were able to identify a number of lanthanide intermediates formed in a simple condensation reaction between a C-acid and an aldehyde. Results show correlation between the reactivity of lanthanide complexes and their charge state and suggest that the triply charged complexes play a key role in lanthanide catalysed reactions. Spectroscopic data of the gaseous ions accompanied by theoretical calculations reveal that the difference between catalytic efficiencies of ytterbium and dysprosium ions can be explained by their different electrophilicity.

Deprotonated carbohydrate anion fragmentation chemistry: structural evidence from tandem mass spectrometry, infra-red spectroscopy, and theory.

We investigate the gas-phase structures and fragmentation chemistry of deprotonated carbohydrate anions using combined tandem mass spectrometry, infrared spectroscopy, regioselective labelling, and theory. Our model system is deprotonated, [lactose-H]-. We computationally characterize the rate-determining barriers to glycosidic bond (C1-Z1 reactions) and cross-ring cleavages, and compare these predictions to our tandem mass spectrometric and infrared spectroscopy data. The glycosidic bond cleavage product data support complex mixtures of anion structures in both the C1 and Z1 anion populations. The specific nature of these distributions is predicted to be directly affected by the nature of the anomeric configuration of the precursor anion and the distribution of energies imparted. i.e., Z1 anions produced from the ß-glucose anomeric form have a differing distribution of product ion structures than do those from the α-glucose anomeric form. The most readily formed Z1 anions ([1,4-anhydroglucose-H]- structures) are produced from the ß-glucose anomers, and do not ring-open and isomerize as the hemiacetal group is no longer present. In contrast the [3,4-anhydroglucose-H]-, Z1 anion structures, which are most readily produced from α-glucose forms, can ring-open through very low barriers (<25 kJ mol-1) to form energetically and entropically favorable aldehyde isomers assigned with a carbonyl stretch at ∼1640 cm-1. Barriers to interconversion of the pyranose [ß-galactose-H]-, C1 anions to ring-open forms were larger, but still modest (≥51 kJ mol-1) consistent with evidence of the presence of both forms in the infrared spectrum. For the cross-ring cleavage 0,2A2 anions, ring-opening at the glucose hemiacetal of [lactose-H]- is rate-limiting (>180 (α-), >197 kJ mol-1 (ß-anomers)). This finding offers an explanation for the low abundance of these product anions in our tandem mass spectra.

Insights from ion mobility-mass spectrometry, infrared spectroscopy, and molecular dynamics simulations on nicotinamide adenine dinucleotide structural dynamics: NAD+vs. NADH.

Nicotinamide adenine dinucleotide (NAD) is found in all living cells where the oxidized (NAD+) and reduced (NADH) forms play important roles in many enzymatic reactions. However, little is known about NAD+ and NADH conformational changes and kinetics as a function of the cell environment. In the present work, an analytical workflow is utilized to study NAD+ and NADH dynamics as a function of the organic content in solution using fluorescence lifetime spectroscopy and in the gas-phase using trapped ion mobility spectrometry coupled to mass spectrometry (TIMS-MS) and infrared multiple photon dissociation (IRMPD) spectroscopy. NAD solution time decay studies showed a two-component distribution, assigned to changes from a "close" to "open" conformation with the increase of the organic content. NAD gas-phase studies using nESI-TIMS-MS displayed two ion mobility bands for NAD+ protonated and sodiated species, while four and two ion mobility bands were observed for NADH protonated and sodiated species, respectively. Changes in the mobility profiles were observed for NADH as a function of the starting solution conditions and the time after desolvation, while NAD+ profiles showed no dependence. IRMPD spectroscopy of NAD+ and NADH protonated species in the 800-1800 and 3200-3700 cm-1 spectral regions showed common and signature bands between the NAD forms. Candidate structures were proposed for NAD+ and NADH kinetically trapped intermediates of the protonated and sodiated species, based on their collision cross sections and IR profiles. Results showed that NAD+ and NADH species exist in open, stack, and closed conformations and that the driving force for conformational dynamics is hydrogen bonding of the N-H-O and O-H-O forms with ribose rings.

Mimicking the Regulation Step of Fe-Monooxygenases: Allosteric Modulation of FeIV -Oxo Formation by Guest Binding in a Dinuclear ZnII -FeII Calix[6]arene-Based Funnel Complex.

A heteroditopic ligand associated with a calix[6]arene scaffold bearing a tris(imidazole) coordinating site at its small rim and an amine/pyridine ligand at its large rim has been prepared, and its regioselective coordination to ZnII at the small rim and FeII in the amine/pyridine ligand has been achieved. The heterodinuclear complex obtained displays an overall cone conformation capped by the tris(imidazole)ZnII moiety and bears a non-heme FeII complex at its base. Each of the metal centers exhibits one labile position, allowing the coordination inside the cavity of a guest alkylamine at ZnII and the generation of reaction intermediates (FeIII (OOH) and FeIV O) at the large rim. A dependence between the chain length of the encapsulated alkylamine and the distribution of FeIII (OOH) intermediates and FeIII (OMe) is observed. In addition, it is shown that the generation of the FeIV O intermediate is enhanced by addition of the alkylamine guest. Hence, this supramolecular system gathers the three levels of reactivity control encountered in oxidoreductases: i) control of the FeII redox properties through its first coordination sphere, allowing us to generate high valent reactive species; ii) control of guest binding through a hydrophobic funnel that drives its alkyl chain next to the reactive iron complex, thus mimicking the binding pocket of natural systems; iii) guest-modulated reactivity of the FeII center towards oxidants.

Cytosine Radical Cations: A Gas-Phase Study Combining IRMPD Spectroscopy, UVPD Spectroscopy, Ion-Molecule Reactions, and Theoretical Calculations.

The radical cation of cytosine (Cyt.+ ) is generated by dissociative oxidation from a ternary CuII complex in the gas phase. The radical cation is characterized by infrared multiple photon dissociation (IRMPD) spectroscopy in the fingerprint region, UV/Vis photodissociation (UVPD) spectroscopy, ion-molecule reactions, and theoretical calculations (density functional theory and ab initio). The experimental IRMPD spectrum features diagnostic bands for two enol-amino and two keto-amino tautomers of Cyt.+ that are calculated to be among the lowest energy isomers, in agreement with a previous study. Although the UVPD action spectrum can also be matched to a combination of the four lowest energy tautomers, the presence of a nonclassical distonic radical cation cannot be ruled out. Its formation is, however, unlikely due to the high energy of this isomer and the respective ternary CuII complex. Gas-phase ion-molecule reactions showed that Cyt.+ undergoes hydrogen-atom abstraction from 1-propanethiol, radical recombination reactions with nitric oxide, and electron transfer from dimethyl disulfide.