PMID- 35748364
OWN - NLM
STAT- MEDLINE
DCOM- 20220708
LR  - 20220708
IS  - 1463-9084 (Electronic)
IS  - 1463-9076 (Linking)
VI  - 24
IP  - 26
DP  - 2022 Jul 6
TI  - Infrared spectra and structures of protonated amantadine isomers: detection of 
      ammonium and open-cage iminium ions.
PG  - 16101-16111
LID - 10.1039/d2cp01947g [doi]
AB  - The protonated form of amantadine (1-C(10)H(15)NH(2), Ama), the amino derivative 
      of adamantane (C(10)H(16), Ada), is a wide-spread antiviral and anti-Parkinsonian 
      drug and plays a key role in many pharmaceutical processes. Recent studies reveal 
      that the adamantyl cage (C(10)H(15)) of Ama can open upon ionization leading to 
      distonic bicyclic iminium isomers, in addition to the canonical nascent Ama(+) 
      isomer. Herein, we study protonation of Ama using infrared photodissociation 
      spectroscopy (IRPD) of Ar-tagged ions and density functional theory calculations 
      to characterize cage and open-cage isomers of AmaH(+) and the influence of the 
      electron-donating NH(2) group on the cage-opening reaction potential. In addition 
      to the canonical ammonium isomer (AmaH(+)(I)) with an intact adamantyl cage, we 
      identify at least one slightly less stable protonated bicyclic iminium ion 
      (AmaH(+)(II)). While the ammonium ion is generated by protonation of the basic 
      NH(2) group, AmaH(+)(II) is formally formed by H addition to a distonic bicyclic 
      iminium ion produced upon ionization of Ama and subsequent cage opening.
FAU - George, Martin Andreas Robert
AU  - George MAR
AUID- ORCID: 0000-0002-4718-8181
AD  - Institut fur Optik und Atomare Physik, Technische Universitat Berlin, 
      Hardenbergstr. 36, 10623 Berlin, Germany. dopfer@physik.tu-berlin.de.
FAU - Dopfer, Otto
AU  - Dopfer O
AUID- ORCID: 0000-0002-9834-4404
AD  - Institut fur Optik und Atomare Physik, Technische Universitat Berlin, 
      Hardenbergstr. 36, 10623 Berlin, Germany. dopfer@physik.tu-berlin.de.
LA  - eng
PT  - Journal Article
DEP - 20220706
PL  - England
TA  - Phys Chem Chem Phys
JT  - Physical chemistry chemical physics : PCCP
JID - 100888160
RN  - 0 (Ammonium Compounds)
RN  - 0 (Ions)
RN  - 0 (Protons)
RN  - BF4C9Z1J53 (Amantadine)
SB  - IM
MH  - Amantadine
MH  - *Ammonium Compounds
MH  - Ions
MH  - Isomerism
MH  - *Protons
MH  - Spectrophotometry, Infrared/methods
EDAT- 2022/06/25 06:00
MHDA- 2022/07/09 06:00
CRDT- 2022/06/24 06:03
PHST- 2022/06/25 06:00 [pubmed]
PHST- 2022/07/09 06:00 [medline]
PHST- 2022/06/24 06:03 [entrez]
AID - 10.1039/d2cp01947g [doi]
PST - epublish
SO  - Phys Chem Chem Phys. 2022 Jul 6;24(26):16101-16111. doi: 10.1039/d2cp01947g.