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

Abstract

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.

Fluorescent 2-(Pyridin-2-yl)vinyl Pyridine Dyes and Their Thermocontrolled Release

“…The uniqueness of these technologies is based on the distinctive removal of N -pyridin-2-yl derivatives that occurs via intramolecular cyclization under mild conditions . The nucleophilicity of pyridine as well as the distance between endocyclic nitrogen and the aminoethanol chain provides a characteristic cyclization pathway, whereas temperature and pH accelerate or stop this process . Thermosensitive probe release is a crucial factor in many thermodependent switch on/off processes, e.g., PCR-based techniques.…”

“…31 The nucleophilicity of pyridine as well as the distance between endocyclic nitrogen and the aminoethanol chain provides a characteristic cyclization pathway, whereas temperature and pH accelerate or stop this process. 32 Thermosensitive probe release is a crucial factor in many thermodependent switch on/off processes, e.g., PCRbased techniques. A combination of time-dependent thermosensitive dye removal with fluorescence intensity level detection might be an efficient tool to quantitatively monitor the levels of labeled molecules.…”