High-resolution structural study on pyridin-3-yl ebselen and its N-methylated tosylate and iodide derivatives

Abstract

The crystal structure of the pyridine-substituted benzisoselenazolinone 2-(pyridin-3-yl)-2,3-dihydro-1,2-benzoselenazol-3-one (C12H8N2OSe, 2), related to the antioxidant ebselen [systematic name: 2-phenyl-1,2-benzoselenazol-3(2H)-one, 1], is characterized by strong intermolecular N...Se(—N) chalcogen bonding, where the N...Se distance of 2.3831 (6) Å is well within the sum of the van der Waals radii for N and Se (3.34 Å). This strong interaction results in significant lengthening of the internal N—Se distance, consistent with significant population of the Se—N σ* antibonding orbital. Much weaker intermolecular O...Se chalcogen bonding occurs between the amide-like O atom in 2 and the less polarized C—Se bond in this structure. Charge density analysis of 2 using multipole refinement of high-resolution data allowed the electrostatic surface potential for 2 to be mapped, and clearly reveals the σ-hole at the extension of the Se—N bond as an area of positive electrostatic potential. Topological analysis of the electron-density distribution in 2 was carried out within the Quantum Theory of Atoms in Molecules (QTAIM) framework and revealed bond paths and (3,−1) bond critical points (BCPs) for the N...Se—N moiety consistent with a closed-shell interaction; however, the potential energy term is suggestive of electron sharing. Analysis of the electron localization function (ELF) for the strong N...Se and the weak O...Se chalcogen-bonding interactions in the structure of 2 suggest significant electron sharing in the former interaction, and a largely electrostatic interaction in the latter. Conversion of 2 to its N-methylated derivatives by reaction with methyl iodide [1-methyl-3-(3-oxo-2,3-dihydro-1,2-benzoselenazol-2-yl)pyridin-1-ium iodide, C13H11N2OSe+·I−] and methyl tosylate [1-methyl-3-(3-oxo-2,3-dihydro-1,2-benzoselenazol-2-yl)pyridin-1-ium toluenesulfonate trihydrate, C13H11N2OSe+·C7H7O3S−·3H2O] removes the possibility of N...Se chalcogen bonding and instead structures are obtained where the iodide and tosylate counter-ions fulfill the role of chalcogen-bond acceptors, with a strong I−...Se interaction in the iodide salt and a weaker p-Tol-SO3 −...Se interaction in the tosylate salt.

Halogen bonds, chalcogen bonds, pnictogen bonds, tetrel bonds and other σ-hole interactions: a snapshot of current progress

“…The crystallographic studies are complemented by DFT calculations of molecular electrostatic potentials. White and co-workers report a study of the pyridin-3-yl derivative of the selenium-containing drug ebselen, 1 (Xu et al, 2023), and its methylpyridinium iodide salt (1-Me + I À ) and tosylate salt (1-Me + CH 3 C 6 H 4 SO 3 À •3H 2 O). The crystal structure of the parent drug (Dupont et al, 1990) and a subsequent charge-density study (Thomas et al, 2015) revealed a short and strong C-Se� � �O C chalcogen bond [Se� � �O = 2.522 (1) A ˚] accompanied by an IR stretching frequency shift [��(CO) ' 71 cm À 1 ].…”

Hammett Structural Relationships Revealed in Chalcogen-Bonded Co-Crystals of Electron-Rich Pyridines with 4′-Substituted Ebselen Derivatives

“…We were fortunate that these high-quality co-crystals spanned the range of electron demand ( 1NO 2 · 2b as the electron-poor derivative, 1 · 2b as a neutral derivative, and 1Me · 2b as an electron-rich derivative), giving us the opportunity to examine differences in the experimental charge density in weakly and strongly bonded systems. We were also able to compare these co-crystals with previously reported charge-density studies of single-component crystals of ebselen itself ( 1 ), and a meta -pyridyl derivative ( 1Py ). , The BCPs in the vicinity of the selenium were first inspected, and the values of ρ BCP and ∇ 2 ρ BCP for the Ch-bond (Se···A) and endocyclic Se–N and Se–C bonds are given in Table .…”

“…We were also able to compare these co-crystals with previously reported charge-density studies of single-component crystals of ebselen itself (1), and a meta-pyridyl derivative (1Py). 54,55 The BCPs in the vicinity of the selenium were first inspected, and the values of ρ BCP and ∇ 2 ρ BCP for the Ch-bond (Se•••A) and endocyclic Se−N and Se−C bonds are given in Table 4.…”

Hammett Structural Relationships Revealed in Chalcogen Bonded Co-crystals of Electron Rich Pyridines with 4′-Substituted Ebselen Derivatives

“…We were also able to compare these co-crystals with previously reported charge-density studies of single component crystals of ebselen itself (1), and a meta-pyridyl derivative (1Py). 54,55 The BCPs in the vicinity of the selenium were first inspected, and the values of 𝜌 BCP and ∇ 2 𝜌 BCP for the Ch-bond (Se • • • A) and endocyclic Se−N and Se−C bonds are given in table 4. Table 4: QTAIM parameters of Ch-bonded complexes.…”