PLoS ONE (2018-01-01)

Experimental and computational studies on a protonated 2-pyridinyl moiety and its switchable effect for the design of thermolytic devices.

  • Jolanta Brzezinska,
  • Jacek Kujawski,
  • Agnieszka Witkowska,
  • Kornelia Czaja,
  • Marek K Bernard,
  • Marcin K Chmielewski,
  • Marcin K Chmielewski

DOI
https://doi.org/10.1371/journal.pone.0203604
Journal volume & issue
Vol. 13, no. 9
p. e0203604

Abstract

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1D and 2D NMR investigations as well as computational studies, including static quantum-mechanics calculations, density function theory formalism, and classical molecular dynamics, were applied to determine the protonation sites in the thermolabile protecting group (TPG) containing a 2-pyridynyl moiety within its structure. This protecting group has three possible sites for protonation: an azomethine (pyridinic) atom (N1), 2-aminoethanol residue (N2), and 4-amino substituent (N4). Our investigations showed that the protonation mainly occurs on the N1 atom. Such protonation seems to be a major inhibitory factor in the thermal removal of 2-pyridynyl TPG by the "chemical switch" approach and decreases the aromaticity of the pyridine ring. We also discussed possible participation of N2 nitrogen in irreversible intramolecular cyclization under acidic conditions.