2-Pyridinyl-<i>N</i>-(2,4-difluorobenzyl)aminoethyl Group As Thermocontrolled Implement for Protection of Carboxylic Acids

Brzezinska, Jolanta; Witkowska, Agnieszka; Bałabańska, Sandra; Chmielewski, Marcin K.

doi:10.1021/acs.orglett.6b01475

Cited by 9 publications

(9 citation statements)

References 27 publications

(28 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…General Procedure of the Thermal-Promoted Nucleophilic Substitutions by NRs. Probes 1 and 3 were synthesized by adapting previously reported procedures aimed to derivatize carboxylic acids with thermolabile protecting groups; 43 both compounds include either thermosensitive esters or carbamates, which are subject of deprotection in neutral conditions only by increasing temperature (∼90 °C). The thermoplasmonic properties of the NRs were used to promote the thermal reaction (nucleophilic substitution) depicted in Scheme S1, leading to the transformation of the nonfluorescent substrates (1 and 3) into the corresponding fluorescent products (2 and 4, respectively).…”

Section: Methodsmentioning

confidence: 99%

Plasmonic-Assisted Thermocyclizations in Living Cells Using Metal–Organic Framework Based Nanoreactors

et al. 2021

View full text Add to dashboard Cite

We describe a microporous plasmonic nanoreactor to carry out designed near-infrared (NIR)-driven photothermal cyclizations inside living cells. As a proof of concept, we chose an intramolecular cyclization that is based on the nucleophilic attack of a pyridine onto an electrophilic carbon, a process that requires high activation energies and is typically achieved in bulk solution by heating at ∼90 °C. The core−shell nanoreactor (NR) has been designed to include a gold nanostar core, which is embedded within a metal−organic framework (MOF) based on a polymer-stabilized zeolitic imidazole framework-8 (ZIF-8). Once accumulated inside living cells, the MOFbased cloak of NRs allows an efficient diffusion of reactants into the plasmonic chamber, where they undergo the transformation upon near-IR illumination. The photothermaldriven reaction enables the intracellular generation of cyclic fluorescent products that can be tracked using fluorescence microscopy. The strategy may find different type of applications, such as for the spatio-temporal activation of prodrugs.

show abstract

Section: Methodsmentioning

confidence: 99%

Plasmonic-Assisted Thermocyclizations in Living Cells Using Metal–Organic Framework Based Nanoreactors

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Particularly noteworthy is the 4‐oxopenthyl (Wilk et al., ) group that is removed in the thermolytic or basic conditions and it can be completely released from the protected part in a molecule within only 30 min. Moreover, in the literature the wider application of TPGs is presented: protection of phosphate (Kiuru et al., ), hydroxyl (Chmielewski et al., ), carbonyl (Brzezinska et al., ) or amine (Ohkubo et al., ) functions in chemical synthesis of nucleic acids, as well as a new concept of DNA microarray construction (Grajkowski et al., ).…”

Section: Commentarymentioning

confidence: 99%

2‐Pyridinyl Thermolabile Groups as General Protectants for Hydroxyl, Phosphate, and Carboxyl Functions

Brzezinska

Witkowska

Kaczyński

et al. 2017

CP Nucleic Acid Chemistry

Self Cite

View full text Add to dashboard Cite

Application of 2-pyridinyl thermolabile protecting groups (2-PyTPGs) for protection of hydroxyl, phosphate, and carboxyl functions is presented in this unit. Their characteristic feature is a unique removal process following the intramolecular cyclization mechanism and induced only by temperature rise. Deprotection rate of 2-PyTPGs is dependent on certain parameters, such as solvent (aqueous or non-aqueous medium), pH values, and electron distribution in a pyridine ring. The presented approach pertains not only to protecting groups but also to an advanced system of controlling certain properties of 2-pyridinyl derivatives. We improved the "chemical switch" method, allowing us to regulate the protecting group stability by inversing the electron distribution in 2-PyTPG. Together with pH values manipulation, this allows us to regulate the protecting group stability. Moreover, phosphite cyclization to oxazaphospholidine provides a very stable but easily reversible tool for phosphate protection/modifications. For all TPGs we confirmed their utility in a system of protecting groups. This concept can contribute to designing the general protecting group that could be useful in bioorganic chemistry. © 2017 by John Wiley & Sons, Inc.

show abstract

“…Moreover, protonation of 2PyTPGs can be enabled by controlling their thermolabile properties [ 10 ]. We also proved that we were able to control this deprotecting process via intramolecular cyclization and modulation of the four factors: i) temperature, ii) electron distribution in the pyridine ring by various substituents on 4 position, iii) pH levels [ 16 ], and iv) steric effect [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2018

Self Cite

View full text Add to dashboard Cite

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.

show abstract

2-Pyridinyl-N-(2,4-difluorobenzyl)aminoethyl Group As Thermocontrolled Implement for Protection of Carboxylic Acids

Cited by 9 publications

References 27 publications

Plasmonic-Assisted Thermocyclizations in Living Cells Using Metal–Organic Framework Based Nanoreactors

Plasmonic-Assisted Thermocyclizations in Living Cells Using Metal–Organic Framework Based Nanoreactors

2‐Pyridinyl Thermolabile Groups as General Protectants for Hydroxyl, Phosphate, and Carboxyl Functions

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

Contact Info

Product

Resources

About