Trends in oxygen atom transfer to Compound I of the P450 models with an extensive test set have been studied and show a preferred regioselectivity of epoxidation over hydroxylation in the gas-phase for the first time.
A σ and not a π complex has been identified for the prototypical arenium intermediate, protonated benzene. The activation of the infrared multiphoton dissociation of C6H7+ ions (obtained by the gas‐phase protonation of benzene) by the absorption of free electron laser radiation shows a wavelength‐dependent dissociation of H2 (see spectrum) that matches the transitions calculated for the σ complex benzenium ion.
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.
Phenylalkylamines of the general formula C6H5(CH2)nNH2 (n = 1-4) have been delivered to the gas phase as protonated species using electrospray ionization. The ions thus formed have been assayed by IRMPD spectroscopy in two different spectroscopic domains, namely, the 600-1800 and the 3000-3500 cm(-1) regions using either an IR free electron laser or a tabletop OPO/OPA laser source. The interpretation of the experimental spectra is aided by density functional theory calculations of candidate species and vibrational frequency analyses. Protonated benzylamine presents a relatively straightforward instance of a single stable conformer, providing a trial case for the adopted approach. Turning to the higher homologues, C6H5(CH2)nNH3(+) (n = 2-4), more conformations become accessible. For each C6H5(CH2)nNH3(+) ion (n = 2-4), the most stable geometry is characterized by cation-π interactions between the positively charged ammonium group and the aromatic π-electronic system, permitted by the folding of the polymethylene chain. The IRMPD spectra of the sampled ions confirm the presence of the folded structures by comparison with the calculated IR spectra of the various possible conformers. An inspection of the NH stretching region is helpful in this regard.
Cytochrome P450 enzymes are heme containing monooxygenases that mainly react through oxygen atom transfer. Specific features of substrate and oxidant that determine the reaction rate constant for oxygen atom transfer are still poorly understood and, therefore, we did a systematic gas-phase study on reactions by iron(IV)-oxo porphyrin cation radical structures with arenes. We present here the first results obtained by using Fourier transform-ion cyclotron resonance mass spectrometry and provide rate constants and product distributions for the assayed reactions. Product distributions and kinetic isotope effect studies implicate a rate determining aromatic hydroxylation reaction that correlates with the ionization energy of the substrate and no evidence of aliphatic hydroxylation products is observed. To further understand the details of the reaction mechanism, a computational study on a model complex was performed. These studies confirm the experimental hypothesis of dominant aromatic over aliphatic hydroxylation and show that the lack of an axial ligand affects the aliphatic pathways. Moreover, a two parabola valence bond model is used to rationalize the rate constant and identify key properties of the oxidant and substrate that drive the reaction. In particular, the work shows that aromatic hydroxylation rates correlate with the ionization energy of the substrate as well as with the electron affinity of the oxidant.
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(+)-π interaction is observed. The dispersion-corrected density functional theory calculations reveal the important effects of dispersion on the cation-π interaction and the large vibrational anharmonicity of the NH3(+) group involved in the NH(+)-π hydrogen bond. They allow for assigning overtone and combination bands and explain anomalous intensities observed in previous IR multiple-photon dissociation spectra. Comparison with neutral PEA reveals the large effects of protonation on the geometric and electronic structure.
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.
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