5-(Pyridin-3-yl)-3,4-dihydro-2-furan-1-ium (NNKFI): a Computational Study of Its Physico-chemical Properties

Overview

Journal R Soc Open Sci

Specialty Science

Date 2024 Sep 12

PMID 39263456

Authors

Evan Millam

Christos Deligkaris

Edmir O Wade

Affiliations

Soon will be listed here.

Abstract

Recent work on the diazonium ion metabolite of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNKDI) suggests that 5-(pyridin-3-yl)-3,4-dihydro-2-furan-1-ium (NNKFI) may form from NNKDI via an intramolecular reaction. NNKDI is an important carcinogen whose role as an alkylating agent has received significant attention. While there is some experimental evidence supporting NNKFI's production , it has not yet been directly observed. Little is known about NNKFI's structure and reactivity. We report the first examination of this ion. Our study utilized Kohn-Sham density functional theory (B3LYP/6-311G**) and coupled cluster theory (CCSD/6-31G*) to produce energy-optimized structures, vibrational normal modes and molecular orbitals for NNKFI. To gain insight into the chemical properties of this species, we calculated electrostatic potential surfaces, natural population analysis charges and local Fukui indices. We report data and results for NNKFI's and conformers. Our work confirms C5 as the preferred site for nucleophilic attack in NNKFI. Stretching motions and predicted bond lengths near O1 are consistent with a somewhat weakened carbonyl structure in this ion. Partial charges, electrostatic potential surfaces and local Fukui indices reveal delocalization of cationic charge on the furanium moiety and notable carbocation character at C5.

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