Simonetta Fornarini

Probing the Compound I-like reactivity of a bare high-valent oxo iron porphyrin complex: the oxidation of tertiary amines.

The mechanisms of oxidative N-dealkylation of amines by heme enzymes including peroxidases and cytochromes P450 and by functional models for the active Compound I species have long been studied. A debated issue has concerned in particular the character of the primary step initiating the oxidation sequence, either a hydrogen atom transfer (HAT) or an electron transfer (ET) event, facing problems such as the possible contribution of multiple oxidants and complex environmental effects. In the present study, an oxo iron(IV) porphyrin radical cation intermediate 1, [(TPFPP)*+ Fe(IV)=O]+ (TPFPP = meso-tetrakis (pentafluorophenyl)porphinato dianion), functional model of Compound I, has been produced as a bare species. The gas-phase reaction with amines (A) studied by ESI-FT-ICR mass spectrometry has revealed for the first time the elementary steps and the ionic intermediates involved in the oxidative activation. Ionic products are formed involving ET (A*+, the amine radical cation), formal hydride transfer (HT) from the amine ([A(-H)]+, an iminium ion), and oxygen atom transfer (OAT) to the amine (A(O), likely a carbinolamine product), whereas an ionic product involving a net initial HAT event is never observed. The reaction appears to be initiated by an ET event for the majority of the tested amines which included tertiary aliphatic and aromatic amines as well as a cyclic and a secondary amine. For a series of N,N-dimethylanilines the reaction efficiency for the ET activated pathways was found to correlate with the ionization energy of the amine. A stepwise pathway accounts for the C-H bond activation resulting in the formal HT product, namely a primary ET process forming A*+, which is deprotonated at the alpha-C-H bond forming an N-methyl-N-arylaminomethyl radical, A(-H)*, readily oxidized to the iminium ion, [A(-H)]+. The kinetic isotope effect (KIE) for proton transfer (PT) increases as the acidity of the amine radical cation increases and the PT reaction to the base, the ferryl group of (TPFPP)Fe(IV)=O, approaches thermoneutrality. The ET reaction displayed by 1 with gaseous N,N-dimethylaniline finds a counterpart in the ET reactivity of FeO+, reportedly a potent oxidant in the gas phase, and with the barrierless ET process for a model (P)*+ Fe(IV)=O species (where P is the porphine dianion) as found by theoretical calculations. Finally, the remarkable OAT reactivity of 1 with C6F5N(CH3)2 may hint to a mechanism along a route of diverse spin multiplicity.

Determination of sulfonamide antibiotics by gas chromatography coupled with atomic emission detection

The paper describes the analysis of nine sulfonamides, chosen as the most widely used representatives of an important class of antibacterial drugs. Atomic emission detection has been found to allow simultaneous quantification and identification of the N1-methylated derivatives, which are resolved efficiently by conventional capillary gas chromatography. Results are given concerning the linearity of the response and the characterization of the individual compounds by the elemental ratio of their carbon, nitrogen and sulfur content. The method looks promising for the quantitative analysis and confirmation of sulfonamide residues in complex mixtures.

Interaction of cisplatin with adenine and guanine: a combined IRMPD, MS/MS, and theoretical study.

Infrared multiple photon dissociation (IRMPD) spectroscopy of cis-[Pt(NH(3))(2)(G)Cl](+) and cis-[Pt(NH(3))(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(NH(3))(2)(G)Cl](+) and cis-[Pt(NH(3))(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(NH(3))(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 NH(3) ligand and the carbonyl group of guanine. The experimental C═O stretching feature of cis-[Pt(NH(3))(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(NH(3))(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.

Molecular complexes of simple anions with electron-deficient arenes: spectroscopic evidence for two types of structural motifs for anion-arene interactions.

Anion-pi interactions between a pi-acidic aromatic system and an anion are gaining increasing recognition in chemistry and biology. Herein, the binding features of an electron-deficient aromatic system (1,3,5-trinitrobenzene (TNB)) and selected anions (OH-, Br-, and I-) are examined in the gas phase by using the combined information derived from collision-induced dissociation experiments at variable energy, infrared multiple-photon dissociation spectroscopy, and quantum chemical calculations. We provide spectroscopic evidence for two different structural motifs of anion-arene complexes depending on the nature of the anion. The TNB-OR- complexes (R=H, or alkyl groups which were studied earlier) adopt an anionic sigma-complex structure whereby RO- attacks the aromatic ring with covalent bond formation, and develops a tetrahedral ring carbon bound to H and OR. The halide complexes rather conform to a structure in which the TNB moiety is hardly altered, and the halogen is placed on an unsubstituted carbon atom over the periphery of the ring at a C-X distance that is appreciably longer than a typical covalent bond length. The ensuing structural motif, previously characterized in the solid state and named weak sigma interaction, is now confirmed by an IR spectroscopic assay in the gas phase, in which the sampled species are unperturbed by crystal packing or solvation effects.

Oxygen-atom transfer by a naked manganese(V)-oxo-porphyrin complex reveals axial ligand effect.

Manganese(V)–oxo speciesare suggested to be crucial intermediates in the epoxidationof a wide range of alkenes and they provide useful function-al models for the active species of heme-containing monoox-ygenases, including cytochrome P450 enzymes. Manganese–oxo units are also found at the core of photoACHTUNGREsystem II, per-forming oxidation of water to oxygen.

Mechanistic views on aromatic substitution reactions by gaseous cations

Recent advances in the understanding of the gas-phase reaction of aromatics with cationic electrophiles in a thermally equilibrated domain are described. The overall substitution reaction is analyzed in terms of its elementary steps. Their contribution to the overall reactivity pattern is dissected by the use of selected systems, which allowed one to highlight the kinetic role of single elementary events. Mechanistic studies have focused on the structure and reactivity of covalent and non-covalent ionic intermediates, which display a rich chemistry and provide benchmark reactivity models. Particular interest has been devoted to proton transfer reactions, which may occur in either an intra- or intermolecular fashion in arenium intermediates. A quantitative study of their rates and associated kinetic isotope effects is reported.

Benzylium versus Tropylium Ion Dichotomy: Vibrational Spectroscopy of Gaseous C8H9+ Ions†

Definitely different: the path towards sorting out a long-standing dichotomy in carbocation chemistry is disclosed by infrared multiple photon dissociation spectroscopy of tropylium and benzylium isomers of C(8)H(9)(+) ions.

Naked Five-Coordinate FeIII(NO) Porphyrin Complexes: Vibrational and Reactivity Features

Model ferric heme nitrosyl complexes, [Fe(TPP)(NO)](+) and [Fe(TPFPP)(NO)](+), where TPP is the dianion of 5,10,15,20-tetrakis-phenyl-porphyrin and TPFPP is the dianion of 5,10,15,20-tetrakis-pentafluorophenyl-porphyrin, have been obtained as isolated species by the gas phase reaction of NO with [Fe(III)(TPP)](+) and [Fe(III) (TPFPP)](+) ions delivered in the gas phase by electrospray ionization, respectively. The so-formed nitrosyl complexes have been characterized by vibrational spectroscopy also exploiting (15)N-isotope substitution in the NO ligand. The characteristic NO stretching frequency is observed at 1825 and 1859 cm(-1) for [Fe(III)(TPP)(NO)](+) and [Fe(III)(TPFPP)(NO)](+) ions, respectively, providing reference values for genuine five-coordinate Fe(III)(NO) porphyrin complexes differing only for the presence of either phenyl or pentafluorophenyl substituents on the meso positions of the porphyrin ligand. The vibrational assignment is aided by hybrid density functional theory (DFT) calculations of geometry and electronic structure and frequency analysis which clearly support a singlet spin electronic state for both [Fe(TPP)(NO)](+) and [Fe(TPFPP)(NO)](+) complexes. Both TD-DFT and CASSCF calculations suggest that the singlet ground state is best described as Fe(II)(NO(+)) and that the open-shell AFC bonding scheme contribute for a high-energy excited state. The kinetics of the NO addition reaction in the gas phase are faster for [Fe(III)(TPFPP)](+) ions by a relatively small factor, though highly reliable because of a direct comparative evaluation. The study was aimed at gaining vibrational and reactivity data on five-coordinate Fe(III)(NO) porphyrin complexes, typically transient species in solution, ultimately to provide insights into the nature of the Fe(NO) interaction in heme proteins.

Gas-Phase Dioxygen Activation by Binuclear Manganese Clusters

Binuclear manganese oxide cations, Mn2O2+ (1) and Mn2O+ (2), have been prepared in the gas phase by a chemical route by using the reaction of O2 with the ions formed from the ionization of [Mn2(CO)10]. Their reactivity towards selected neutrals has been probed by Fourier Transform Ion Cyclotron Resonance spectrometry (FT-ICR), and insights into the structure of the reagent ions and of ionic reaction intermediates have been obtained by collision-induced dissociation and by the outcome of ion-molecule reactions. Whereas dihydrogen proved to be unreactive, the hydrides H2O, H2S, and NH3 react by exchange, addition, and oxidation pathways. Oxidative features are displayed also in the reactions of 1 and 2 with model organic molecules, such as methanol, acetaldehyde, and unsaturated hydrocarbons, which undergo dehydrogenation, O-atom transfer, and homolytic cleavage processes. Potentially catalytic cycles are indicated, based on the regeneration of 1 by ligand exchange of end product ions with O2.

Discrimination of 4-hydroxyproline diastereomers by vibrational spectroscopy of the gaseous protonated species.

Hydroxylation of proline is a prominent oxidative post-translational modification (oxPTM) in animals, characterized by site specificity and stereochemical control. The presence of this irreversible modification and the ensuing generation of a chiral center have been assayed in (2S,4R)-4-hydroxyproline and (2S,4S)-4-hydroxyproline forming the protonated species by electrospray ionization and sampling them by infrared multiple photon dissociation (IRMPD) spectroscopy. IRMPD spectra, recorded both in the 950-1950 cm(-1) (using the CLIO free electron laser) and in the 3200-3700 cm(-1) [using a tabletop parametric oscillator/amplifier (OPO/OPA) laser] regions, have been interpreted by comparison with the absorbance spectra of the lowest energy structures calculated at MP2/6-311+G** level of theory. Remarkable spectral differences have emerged in the fingerprint region, pointing to the unambiguous discrimination between S,R and S,S diastereomers. The main differences arise from the position of the carbonyl stretching mode, a signature of nonzwitterionic structures, moving from 1750 cm(-1) for the S,R form to 1770 cm(-1) for the S,S diastereomer. Furthermore, a well-defined band associated with the NH(2) wagging mode at 1333 cm(-1) is a distinct mark of the S,S isomer. Each gaseous protonated epimer comprises a population of at least three conformers, stabilized by intramolecular hydrogen bonds linking the two hydrogens of protonated secondary amine group with the 4-hydroxy substituent and with an oxygen atom of the carboxylic group, respectively. Interestingly, a tendency to adopt either C(4)-exo (up) or C(4)-endo (down) pyrrolidine puckering upon proline 4(R)- or 4(S)-hydroxylation, respectively, is observed here. The same bias is found in neutral hydroxyprolines and in collagen model peptides. In the protonated species under examination, this bias originates chirality-induced vibrational features revealed by IRMPD spectroscopy.