Infrared spectra and structures of protonated amantadine isomers: detection of ammonium and open-cage iminium ions

Abstract

The protonated form of amantadine (1-C10H15NH2, Ama), the amino derivative of adamantane (C10H16, Ada), is a wide-spread antiviral and anti-Parkinsonian drug and plays a key role in many pharmaceutical processes....

Microhydrated clusters of a pharmaceutical drug: infrared spectra and structures of amantadineH+(H2O)n

“…S4, ESI †), which differ structurally only slightly from isomer II. 49 Both isomers show similar solvation behaviour as II with nearly identical IR spectra and can thus experimentally not be distinguished (Fig. S5, ESI †).…”

“…As suggested earlier, 49 there is an alternative production route for AmaH + , in which Ama + is formed first (eqn (7)) which then reacts in an endothermic reaction with H 2 to form AmaH + (eqn (8)):…”

“…2 IRPD spectra of AmaH + (H 2 O) n=1-4 in the 2600-4000 cm À1 range recorded in the H 2 O loss channel are compared to the IRPD spectrum of AmaH + Ar. 49 The position, widths, and assignments of the transitions observed (A-Z) are listed in Table 1. The bands that can only be assigned to the iminium isomers are highlighted in red.…”

“…47 Unlike Ama + (I), which is preferentially hydrogenated at the NH 2 group (eqn ( 8)) leading to the formation of an ammonium cation AmaH + (I), Ama + (II) and Ama + (III) are hydrogenated at their radical centers, leading to the formation of iminium cations AmaH + (II-IV), 99 which have recently been detected by IRPD. 49 The produced AmaH + (H All IRPD spectra are normalized for frequency-dependent variations in the photon flux measured with a pyroelectric detector. Quantum chemical calculations are performed at the B3LYP-D3/cc-pVTZ level of theory for Ama, Ama + , AmaH + , and AmaH + (H 2 O) n hydrates to determine their structural, energetic, and spectroscopic properties.…”

“…Thus, in an alternative and strongly favoured second scenario, these bands are assigned to transitions of a minor population of the II-H 2 O(I) iminium isomer, whose monomer structure was also detected in the AmaH + Ar spectrum. 49 4) 2948 ( 20) 2948 (44) 2949 ( 16) 2948 (44) 2952 ( 17) 2949 (27) 2962 ( 19) 2951 (20) 2972 (3) 2955 (2) 2974 ( 30) 2955 (22) 2978 ( 20) Specifically, band R at 3373 cm À1 is associated with the n f NH 2 mode (predicted at 3391 cm À1 ) of II-H 2 O(I) and then the redshifted n b NH 2 mode (predicted at 3044 cm À1 ) is overlapping with band K at 3080 cm À1 with deviations of 18 and 36 cm À1 , respectively. Moreover, band B at 2821 cm À1 arises from the intense and lowfrequency n CH mode of the long C9-H bond of II-H 2 O(I) predicted at 2867 cm À1 .…”