Antonello Filippi

Gas-phase enantioselectivity

Abstract Determination of the intrinsic noncovalent interactions governing chiral recognition in diastereomeric complexes constitutes the basis for understanding information transfer between molecules in living systems as well as in synthetic supramolecular structures. The most important experimental methodologies so far employed for this task are illustrated in the present review. Emphasis is put on the principles and the applications of techniques, such as radiolysis, Fourier transform ion cyclotron resonance (FTICR) and collision-induced dissociation (CID) mass spectrometry, and resonance-enhanced multiphoton ionization time-of-flight (REMPI-TOF) spectroscopy, that allow measurement of the relative stability of diastereomeric ion/molecule and molecule/molecule complexes and quantification of the short-range forces controlling their enantioselective evolution to products.

Chiral discrimination of monofunctional alcohols and amines in the gas phase

Abstract A methodology has been developed for enantiodiscriminating chiral monoalcohols and monoamines by mass spectrometry. The approach is based on the generation of supersonically expanded complexes of these molecules with suitable chromophores, i.e. R-(+)-1-phenyl-ethanol (ER) or R-(+)-1-phenyl-1-propanol (PR). The jet-cooled diastereomeric complexes, otherwise elusive at room temperature, have been ionized by one-color resonant two-photon absorption (R2PI) and their fragmentation pattern analyzed by time-of-flight (TOF) spectrometry. Enantiodifferentiation of the chiral monoalcohols and monoamines is based on: (1) the different spectral shifts of the band origin of their molecular complexes relative to that of the bare chromophore (Δ) and (2) the different mass spectral fragmentation patterns of the jet-cooled diastereomeric adducts. Detection of stable aggregates of methane, n-butane, and other simple molecules with the selected chromophores suggests that the R2PI/TOF method can be a potential tool for enantiodifferentiating chiral hydrocarbons in the gas phase.

Cyclochiral resorcin[4]arenes as effective enantioselectors in the gas phase.

The effect of cyclochirality of rccc-2,8,14,20-tetra-n-decyl-4,10,16,22-tetra-O-methylresorcin[4]arene (C) on the enantiodiscrimination of a number of chiral bidentate and tridentate aromatic and aliphatic biomolecules (G) has been investigated by nano-electrospray ionization (nano-ESI)-Fourier transform ion cyclotron resonance mass spectrometry. The experimental approach is based on the formation of diastereomeric proton-bound [C·H·G](+) complexes by nano-ESI of solutions containing an equimolar amount of quasi-enantiomers (C) together with the chiral guest (G) and the subsequent measurement of the rate of the G substitution by the attack of several achiral and chiral amines. In general, the heterochiral complexes react faster than the homochiral ones, except when G is an aminoalcoholic neurotransmitter whose complexes, beyond that, exhibit the highest enantioselectivity. The kinetic results were further supported by both collision-induced dissociation experiments on some of the relevant [C(2) ·H·G](+) three-body species and Density functional theory (DFT) calculations performed on the most selective systems.

Gas-phase reactivity of diastereomeric acetate ion/tributylborate complexes☆

Abstract The reactivity of (CH 3 COOY) n H + ( n = 1, 2) and (CH 3 COOY)CH 3 CO + ions [Y = CH 3 , C 2 H 5 , s C 3 H 7 , ( R )- s C 4 H 9 , ( S )- s C 4 H 9 , and ( rac)- s C 4 H 9 ] toward chiral and achiral tributylborates has been measured by Fourier transform ion cyclotron resonance mass spectrometry. Proton transfer between monomeric ions (CH 3 COOY)H + and ( S , S , S )-tri-sec -butylborate competes with nucleophilic addition of the borate to the CO center of the ion followed by elimination of either a butanol molecule or the mixed borate. A similar reaction network is observed for dimeric ions (CH 3 COOY) 2 H + , although the presence of a spectator CH 3 COOY molecule in the relevant encounter complexes modifies substantially the evolution kinetics as well as the product pattern. Acetyl group transfer from (CH 3 COOY)CH 3 CO + to the borate preludes to an intracomplex CH 3 COOY-induced elimination reaction. Enantiodifferentiation between ( R )-(CH 3 COO s Bu)H + and ( S )-(CH 3 COO s Bu)H + is achieved by comparing their reactivity towards ( S , S , S )-tri- sec -butylborate.

Gas-phase complexes: noncovalent interactions and stereospecificity

Abstract Chiral recognition is a fundamental phenomenon in life sciences based on the enantioselective complexation of a chiral molecule with a chiral selector. The diastereomeric aggregates, formed by complexation, are held together by a different combination of intermolecular forces and are, therefore, endowed with different stability and reactivity. Determination of these forces, which are normally affected in the condensed phase by solvent and supramolecular interactions, requires the generation of the diastereomeric complexes in an isolated state and their kinetic and spectroscopic investigation. This paper concerns enantiodiscrimination of chiral molecules in the gas phase through the application of various ESI-MS n -CID and REMPI-TOF methodologies. The measurement of the fragmentation thresholds of diastereomeric clusters by these techniques allowed to shed light upon the nature and the magnitude of the intrinsic interactions which control their formation and which affect their stability and reactivity.

Chiral recognition of diols by complexation with (R)-(+)-1-phenyl-1-propanol: a R2PI approach in supersonic beam

Wavelength and mass resolved resonance-enhanced multiphoton ionization (REMPI) excitation spectra of (R)-(+)-1-phenyl-1-propanol (PR) and its complexes with some chiral diols, i.e. 1,2-propanediols, 2,3-butanediols, and 2,4-pentanediols, have been recorded after a supersonic molecular beam expansion and interpreted in the light of molecular dynamic (MD) conformational minima searches. The spectral features of the selected complexes were found to depend on cooperative hydrogen-bond interactions between the two components, whose intensity depends upon the specific configuration of the diol moiety and the relative position of its hydroxy groups. The study further confirms resonant two-photon ionization spectroscopy, coupled with time-of-flight mass resolution (R2PI-TOF), as an excellent tool for gathering valuable information on the interactive forces in molecular clusters and for enantiodiscrimination of chiral molecules in the gas phase.

Enantioselective supramolecular devices in the gas phase. Resorcin[4]arene as a model system

Summary This review describes the state-of-art in the field of the gas-phase reactivity of diastereomeric complexes formed between a chiral artificial receptor and a biologically active molecule. The presented experimental approach is a ligand-displacement reaction carried out in a nano ESI-FT-ICR instrument, supported by a thermodynamic MS-study and molecular-mechanics and molecular-dynamics (MM/MD) computational techniques. The noncovalent ion–molecule complexes are ideal for the study of chiral recognition in the absence of complicating solvent and counterion effects.

Wagner–Meerwein Rearrangements in the Gas Phase: Anchimeric Assistance to Acid-Induced Dissociation of Optically Active Phenylpropanols

Activation entropy, rather than enthalpy, governs anchimeric assistance in gas-phase water loss from O-protonated (S)-1-phenyl-2-propanol and (S)-2-phenyl-1-propanol. Conformational factors and electrostatic interactions are responsible for a gas-phase frontside phenyl-group participation, with an activation energy lower than that of the competing backside participation (see diagram).

Chiral ions in the gas phase. 5. Acid-induced methanolysis of optically active styrene oxide

Abstract The acid induced ring opening of (R)-(+) styrene oxide ( 1R ) or (S)-(−) styrene oxide ( 1S ) is investigated in the gas phase, at a temperature of 25 °C and in the presence of a labeled nucleophile (CH 3 18 OH, CD 3 OH, or H 2 18 O). Various acid catalysts are generated in situ by γ radiolysis of the bulk gas (720 Torr of CH 4 or CH 3 F). The mechanisms of the ring-opening reaction are assessed by modulating the composition of the gaseous mixture. Two reaction pathways are operative in the gas phase, both proceeding with the same regio- (100% at C α ) and stereochemistry (55–67% inversion of the C α configuration). In the CH 3 F/H 2 18 O systems, a slow reaction takes place within a persistent proton-bound complex between the epoxide and the CH 3 18 OH 2 + ion, formed by (CH 3 ) 2 F + -methylation of H 2 18 O (the intracomplex pathway). When methanol is present in the gaseous mixtures, the intracomplex process is superseded by a faster extracomplex reaction, involving the attack of an external methanol molecule on the O-protonated epoxide. The present results are discussed in the light of related gas-phase and solution data.

Wagner–Meerwein Rearrangements in the Gas Phase: Deuterium Isotope Effects on Acid‐Induced Dissociation of Optically Active Phenylpropanols

The combined analysis of the primary and secondary deuterium kinetic effects and of the activation parameters for water loss from O-protonated (S)-1-phenyl-2-propanol and (S)-2-phenyl-1-propanol in the gas phase provides detailed information on the relevant transition states.