Nitrosyl-heme and anion-arene complexes: structure, reactivity and spectroscopy

Two topics are selected and illustrated to exemplify (i) a biological and (ii) an organic ionic intermediate. The reactivity behavior of NO adducts with ferric and ferrous hemes has shown remarkable similarities when examined in the gas phase, demonstrating that the largely different NO affinity displayed in solution and in biological media is due to the different coordination environment. In fact, ferrous hemes present a vacant or highly labile axial coordination site, prone to readily bind NO. The vibrational signatures of the NO ligand have also been probed in vacuo for the first time in the nitrosyl complexes deriving from ferrous and ferric hemes under strictly comparable five-coordination at the metal center. Negatively charged sigma-adducts, from the association of anions with 1,3,5-trinitrobenzene, an exemplary pi-electron-deficient arene, have been probed by IRMPD spectroscopy and found to display variable binding motifs from a strongly covalent sigma-adduct (Meisenheimer complex) to a weakly covalent sigma-complex, depending on the anion basicity

Vibrational signatures of gaseous Meisenheimer complexes bonded at carbon and nitrogen

Anionic adducts of 1,3,5-trinitrobenzene (TNB) with deprotonated pyrrolidine (Pyr), imidazole (Im), acetone (Ac) and acetylacetone (Acac) have been delivered into the gas phase by electrospray ionization.The so-formed ions, TNB-Nu−(Nu = Pyr, Im, Ac, Acac), have been interrogated by IRMPD spectroscopy inthe fingerprint range. DFT calculations at B3LYP/6-311++G(d,p) level have been performed for a survey of candidate structures. All adducts conform to anionic sigma-complexes (Meisenheimer complexes). The symmetric stretching modes of the nitro groups yield a dominant vibrational signature at 1200–1250 cm−1,the red-shift with respect to the degenerate frequency of 1367 cm−1 in neutral TNB reflecting the extent of negative charge delocalization. The enol complexes TNB-Ac− and TNB-Acac− are largely representedby C-bonded species

Photoionization mass spectrometry of ω-phenylalkylamines: Role of radical cation-π interaction

Linear ω-phenylalkylamines of increasing alkyl chain length have been investigated employing synchrotron radiation in the photon energy range from 7 to 15 eV. These molecules have received considerable interest because they bear the skeleton of biologically relevant compounds including neurotransmitters and because of the possible interaction between the amino moiety and the phenyl ring. Recently, the contribution of this interaction has been assayed in both neutral and protonated species, pointing to a role of the polymethylene chain length. In this work, the ionization energy (IE) values of benzylamine (BA), 2-phenylethylamine (2-PEA), 3-phenylpropylamine (3-PPA), and 4-phenylbutylamine (4-PBA) were investigated in order to ascertain the impact of the different alkyl chain lengths and to verify an amino radical cation-π interaction. The IEs obtained experimentally, 8.54, 8.37, 8.29, and 8.31 eV for BA, 2-PEA, 3-PPA and 4-PBA, respectively, show a decreasing trend that is discussed employing calculations at the CBS-QB3 level. Moreover, the appearance energy values for major fragments produced by the photofragmentation process are reported

Complexation of halide ions to tyrosine: role of non-covalent interactions evidenced by IRMPD spectroscopy

The binding motifs in the halide adducts with tyrosine ([Tyr + X]-, X = Cl, Br, I) have been investigated and compared with the analogues with 3-nitrotyrosine (nitroTyr), a biomarker of protein nitration, in a solvent-free environment by mass-selected infrared multiple photon dissociation (IRMPD) spectroscopy over two IR frequency ranges, namely 950–1950 and 2800–3700 cm-1. Extensive quantum chemical calculations at B3LYP, B3LYP-D3 and MP2 levels of theory have been performed using the 6-311++G(d,p) basis set to determine the geometry, relative energy and vibrational properties of likely isomers and interpret the measured spectra. A diagnostic carbonyl stretching band at B1720 cm-1 from the intact carboxylic group characterizes the IRMPD spectra of both [Tyr + X]- and [nitroTyr + X]-, revealing that the canonical isomers (maintaining intact amino and carboxylic functions) are the prevalent structures. The spectroscopic evidence reveals the presence of multiple non-covalent forms. The halide complexes of tyrosine conform to a mixture of plane and phenol isomers. The contribution of phenol-bound isomers is sensitive to anion size, increasing from chloride to iodide, consistent with the decreasing basicity of the halide, with relative amounts depending on the relative energies of the respective structures. The stability of the most favorable phenol isomer with respect to the reference plane geometry is in fact 1.3, -2.1, -6.8 kJ mol-1, for X = Cl, Br, I, respectively. The change in p-acidity by ring nitration also stabilizes anion–p interactions yielding ring isomers for [nitroTyr + X]-, where the anion is placed above the face of the aromatic ring

IR ion spectroscopy in a combined approach with MS/MS and IM-MS to discriminate epimeric anthocyanin glycosides (cyanidin 3-O-glucoside and -galactoside)

Anthocyanins are widespread in plants and flowers, being responsible for their different colouring. Two representative members of this family have been selected, cyanidin 3-O-β-glucopyranoside and 3-O-β-galactopyranoside, and probed by mass spectrometry based methods, testing their performance in discriminating between the two epimers. The native anthocyanins, delivered into the gas phase by electrospray ionization, display a comparable drift time in ion mobility mass spectrometry (IM-MS) and a common fragment, corresponding to loss of the sugar moiety, in their collision induced dissociation (CID) pattern. However, the IR multiple photon dissociation (IRMPD) spectra in the fingerprint range show a feature particularly evident in the case of the glucoside. This signature is used to identify the presence of cyanidin 3-O-β-glucopyranoside in a natural extract of pomegranate. In an effort to increase any differentiation between the two epimers, aluminum complexes were prepared and sampled for elemental composition by FT-ICR-MS. CID experiments now display an extensive fragmentation pattern, showing few product ions peculiar to each species. More noteworthy is the IRMPD behavior in the OH stretching range showing significant differences in the spectra of the two epimers. DFT calculations allow to interpret the observed distinct bands due to a varied network of hydrogen bonding and relative conformer stability

IR spectrum of the protonated neurotransmitter 2-phenylethylamine: dispersion and anharmonicity of the NH3+-pi interaction

Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG geförderten) Allianz- bzw. Nationallizenz frei zugänglich.This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.The structure and dynamics of the highly flexible side chain of (protonated) phenylethylamino neurotransmitters are essential for their function. The geometric, vibrational, and energetic properties of the protonated neutrotransmitter 2-phenylethylamine (H(+)PEA) are characterized in the N-H stretch range by infrared photodissociation (IRPD) spectroscopy of cold ions using rare gas tagging (Rg = Ne and Ar) and anharmonic calculations at the B3LYP-D3/(aug-)cc-pVTZ level including dispersion corrections. A single folded gauche conformer (G) protonated at the basic amino group and stabilized by an intramolecular NH+-pi interaction is observed. The dispersion-corrected density functional theory calculations reveal the important effects of dispersion on the cation-pi interaction and the large vibrational anharmonicity of the NH3+ group involved in the NH+-pi hydrogen bond. They allow for assigning overtone and combination bands and explain anomalous intensities observed in previous IR multiplephoton dissociation spectra. Comparison with neutral PEA reveals the large effects of protonation on the geometric and electronic structure.EC/FP7/600209/EU/International Post-Doc Initiative of the Technische Universität Berlin/IPOD

Interaction of Cisplatin with Adenine and Guanine: A Combined IRMPD, MS/MS, and Theoretical Study

International audienceInfrared multiple photon dissociation (IRMPD) spectroscopy of cis-[Pt(NH3)2(G)Cl]+ and cis-[Pt(NH3)2(A)Cl]+ ions (where A is adenine and G is guanine) has been performed in two spectral regions, 950-1900 and 2900-3700 cm-1. Quantum chemical calculations at the B3LYP/LACV3P/6-311G** level yield the optimized geometries and IR spectra for the conceivable isomers of cis-[Pt(NH3)2(G)Cl]+ and cis-[Pt(NH3)2(A)Cl]+, whereby the cisplatin residue is attached to the N7, N3, or carbonyl oxygen atom, (O6), of guanine and to the N7, N3, or N1 position of adenine, respectively. In addition to the conventional binding sites of native adenine, complexes with N7-H tautomers have also been considered. In agreement with computational results, the IR characterization of cis-[Pt(NH3)2(G)Cl]+ points to a covalent structure where Pt is bound to the N7 atom of guanine. The characterized conformer has a hydrogen-bonding interaction between a hydrogen atom of one NH3 ligand and the carbonyl group of guanine. The experimental C═O stretching feature of cis-[Pt(NH3)2(G)Cl]+ at 1718 cm-1, remarkably red-shifted with respect to an unperturbed C═O stretching mode, is indicative of a lengthened CO bond in guanine, a signature that this group is involved in hydrogen bonding. The IRMPD spectra of cis-[Pt(NH3)2(A)Cl]+ are consistent with the presence of two major isomers, PtAN3 and PtAN1, where Pt is bound to the N3 and N1 positions of native adenine, respectively

Direct healthcare costs of non-metastatic castration-resistant prostate cancer in Italy

Objectives: The management of non-metastatic castration-resistant prostate cancer (nmCRPC) is rapidly evolving; however, little is known about the direct healthcare costs of nmCRPC. We aimed to estimate the cost-of-illness (COI) of nmCRPC from the Italian National Health Service perspective. Methods: Structured, individual qualitative interviews were carried out with clinical experts to identify what healthcare resources are consumed in clinical practice. To collect quantitative estimates of healthcare resource consumption, a structured expert elicitation was performed with clinical experts using a modified version of a previously validated interactive Excel-based tool, EXPLICIT (EXPert eLICItation Tool). For each parameter, experts were asked to provide the lowest, highest, and most likely value. Deterministic and probabilistic sensitivity analyses (PSA) were carried out to test the robustness of the results. Results: Ten clinical experts were interviewed, and six of them participated in the expert elicitation exercise. According to the most likely estimate, the yearly cost per nmCRPC patient is €4,710 (range, €2,243 to €8,243). Diagnostic imaging (i.e., number/type of PET scans performed) had the highest impact on cost. The PSA showed a 50 percent chance for the yearly cost per nmCRPC patient to be within €5,048 using a triangular distribution for parameters, and similar results were found using a beta-PERT distribution. Conclusions: This study estimated the direct healthcare costs of nmCRPC in Italy based on a mixed-methods approach. Delaying metastases may be a reasonable goal also from an economic standpoint. These findings can inform decision-making abou

Intrinsic Properties of Nitric Oxide Binding to Ferrous and Ferric Hemes

Gas phase studies offer an ideal medium whereby structural and reactivity properties of charged spe-cies may be unveiled in the absence of solvent, matrix or counterion effects. In this environment NO binds to iron(II)- and iron(III)-hemes with comparable kinetics and equilibrium parameters, conclu-sively elucidating the factors determining the widely different affinity in protic solvents or in heme proteins. IRMPD spectroscopy of the isolated species provides unambiguous characterization of the gaseous nitrosyl heme complexes