Experimental/Computational Study on the Impact of Fluorine on the Structure and Noncovalent Interactions in the Monohydrated Cluster of ortho-Fluorinated 2-Phenylethylamine.

Fluorine-containing medicinal compounds frequently allow modulation of physical-chemical properties. Here, we address the effect of fluorine, near the ethylamino side chain, on conformational flexibility and noncovalent interactions (NCIs) of the selected jet-cooled monohydrated cluster of 2-(2-fluoro-phenyl)-ethylamine (2-FPEA) by mass-selected resonance-enhanced two-photon ionization and ionization-loss stimulated Raman spectroscopies. Our results show that Raman spectral signatures of the 2-FPEA-H2O cluster match the scaled harmonic vibrational Raman frequencies, resulting from density functional theory calculations of the most stable 2-FPEA gauche conformer hydrogen-bonded (HB) to water, confirming the three-dimensional cluster structure. This predicted electronic structure, together with NCI analysis, allows visualization and assessment of the attractive and repulsive interactions. The comparison of the NCIs and revealed red (O-H and N-H stretches) and blue shifts (C-H stretches and CH2 out-of-plane bends) of the cluster to other class members confirm O-H···N, N-H···π, C-H···O, and C-H···F HB formation and their contribution to structure stabilization, uncovering the potential of the approach.