Chiral recognition by mass‐resolved laser spectroscopy

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 the isolated state and their spectroscopic investigation. This review deals with chiral recognition in the gas phase through the application of laser-resolved mass spectrometric techniques (R2PI-TOF and RET-MS). The measurement of the fragmentation thresholds of diastereomeric clusters by these techniques allows the determination of the nature of the intrinsic interactions, which control their formation and affect their stability and reactivity.

Chiral recognition between 1-(4-fluorophenyl)ethanol and 2-butanol: higher binding energy of homochiral complexes in the gas phase

“…The S 1 ' S 0 energy gap is higher than what was observed for similar non-fluorinated systems, namely the complexes of 1-phenylethan-1-ol (Dn homo = À121 cm À1 , Dn hetero = À132 cm À1 ), 14,28 1-phenylpropan-1-ol (Dn homo = À79 cm À1 , Dn hetero = À92 cm À1 ) 13 and 2-naphthylethan-1-ol (Dn homo = À125 cm À1 , Dn hetero = À136 cm À1 ), 29 with B R/S . The higher value of the spectral shift in [FE S ÁB R/S ] with respect to non-fluorinated analogues can be attributed to the electron-withdrawing effect of the fluorine atom with respect to the aromatic ring, which is stronger in the excited p* state than in the p ground state, due to the higher polarizability of the aromatic ring in the excited state.…”

“…It provides mass-selective electronic spectra and allows the energetic and structural characterization of neutral diastereomeric complexes and the investigation of chemical reactivity in ion complexes. 13 An important aspect of R2PI studies concerns the measure of the binding energy differences in a few adducts between chiral benzylic alcohol derivatives and chiral secondary alcohols, which is in the range of 250-400 cm À1 with the homochiral complexes always more stable than the corresponding heterochiral complexes. 13,14 Recently we have applied this methodology to fluorinated analogues 15,16 of chiral aromatic alcohols, with the aim of determining the effect of fluorine substitution on the structure and reactivity properties of their complexes and to verify the role of the fluorine substitution on the chiral recognition process.…”

“…13 An important aspect of R2PI studies concerns the measure of the binding energy differences in a few adducts between chiral benzylic alcohol derivatives and chiral secondary alcohols, which is in the range of 250-400 cm À1 with the homochiral complexes always more stable than the corresponding heterochiral complexes. 13,14 Recently we have applied this methodology to fluorinated analogues 15,16 of chiral aromatic alcohols, with the aim of determining the effect of fluorine substitution on the structure and reactivity properties of their complexes and to verify the role of the fluorine substitution on the chiral recognition process. Organofluorine compounds, although rare in nature, are increasingly applied in metabolic studies, in positron emission tomography, as antitumor agents, and as probes in studying enzyme activity, reaction mechanisms, and biomolecular binding.…”

Structural relationships in small molecule interactions governing gas-phase enantioselectivity and zwitterionic formation

“…Subsequently, other gas-phase methods have been used for determining enantiospecificity [22]. Radiolysis, Fourier-transform ion cyclotron resonance mass spectrometry (FTICR-MS), and resonance-enhanced multiphoton ionization time-of flight (REMPI-TOF) spectroscopy are techniques previously used for gas-phase chiral recognition [12,[23][24][25][26][27][28]. Cooks et al performed gas-phase chiral analysis of enantiomeric amino acid mixtures by using competitive fragmentation of trimeric transition-metalbound complexes with mass spectrometry [29 -37].…”

Diastereo-specific conformational properties of neutral, protonated and radical cation forms of (1R,2S)-cis- and (1R,2R)-trans-amino-indanol by gas phase spectroscopy

“…2 Gas-phase studies provide information on the structural differences between the diastereomers, without the complications imposed by the solvent. [3][4][5][6][7][8][9][10] The stereochemical effects observed in diastereomers isolated in the gas phase are often weak. Indeed most of the neutral systems studied so far like peptides, 11,12 polyols, 13 or amino-alcohols like neurotransmitters 14 and cinchona alkaloids 15,16 only display minor structural and spectroscopic differences.…”