Unusually Short Chalcogen Bonds Involving Organoselenium: Insights into the Se–N Bond Cleavage Mechanism of the Antioxidant Ebselen and Analogues

Abstract

Structural studies on the polymorphs of the organoselenium antioxidant ebselen and its derivative show the potential of organic selenium to form unusually short Se⋅⋅⋅O chalcogen bonds that lead to conserved supramolecular recognition units. Se⋅⋅⋅O interactions observed in these polymorphs are the shortest such chalcogen bonds known for organoselenium compounds. The FTIR spectral evolution characteristics of this interaction from solution state to solid crystalline state further validates the robustness of this class of supramolecular recognition units. The strength and electronic nature of the Se⋅⋅⋅O chalcogen bonds were explored using high-resolution X-ray charge density analysis and atons-in-molecules (AIM) theoretical analysis. A charge density study unravels the strong electrostatic nature of Se⋅⋅⋅O chalcogen bonding and soft-metal-like behavior of organoselenium. An analysis of the charge density around Se-N and Se-C covalent bonds in conjunction with the Se⋅⋅⋅O chalcogen bonding modes in ebselen and its analogues provides insights into the mechanism of drug action in this class of organoselenium antioxidants. The potential role of the intermolecular Se⋅⋅⋅O chalcogen bonding in forming the intermediate supramolecular assembly that leads to the bond cleavage mechanism has been proposed in terms of electron density topological parameters in a series of molecular complexes of ebselen with reactive oxygen species (ROS).

Non‐Classical Synthons: Supramolecular Recognition by S⋅⋅⋅O Chalcogen Bonding in Molecular Complexes of Riluzole

“…has become a prominent topic in structural chemistry, and it has been recognized that ChB exhibits distinct directionality features compared with halogen bonds . Our recent study on the unusually short Se⋅⋅⋅O chalcogen bonds in the organoselenium antioxidant ebselen and its polymorphs by using X‐ray charge density analysis and FTIR spectral evolution (upon the formation of ChB during crystal nucleation) revealed the potential role of Se⋅⋅⋅O chalcogen bonding in the Se−N bond cleavage mechanism during the drug action of ebselen . Our results also established the occurrence of a robust and directional supramolecular synthon formed by a Se⋅⋅⋅O chalcogen bonded ring motif (analogous to the one in Figure ).…”

“…Whereas, in this report, we examine the molecular complexes of riluzole as a rare series of examples for MCCs that recurrently exhibit S⋅⋅⋅O chalcogen bonded supramolecular recognition units, with focus on their strength, nature, electronic origin, and potential implications in crystal engineering and supramolecular chemistry. Although this study is a thematic continuation of our recent work on Se⋅⋅⋅O chalcogen bonded R(5) ring motifs in organoselenium antioxidants, to our knowledge, this is the first experimental report that shows analogous sulfur chalcogen bonding forming a robust and directional intermolecular interaction motif (supramolecular synthon). As the sulfur ChBs are clearly secondary interactions compared with the strong classical HBs present in this series of crystal structures, we have also analyzed the role of S⋅⋅⋅O ChBs in the packing of crystal structures which are devoid of such HBs.…”

“…Lately, chalcogen bonding (S/Se/Te⋅⋅⋅A, where A=ChB acceptor such as O, N, F, Cl, etc.) has become a prominent topic in structural chemistry, and it has been recognized that ChB exhibits distinct directionality features compared with halogen bonds . Our recent study on the unusually short Se⋅⋅⋅O chalcogen bonds in the organoselenium antioxidant ebselen and its polymorphs by using X‐ray charge density analysis and FTIR spectral evolution (upon the formation of ChB during crystal nucleation) revealed the potential role of Se⋅⋅⋅O chalcogen bonding in the Se−N bond cleavage mechanism during the drug action of ebselen .…”

Small Organoselenium Compounds: More than just Glutathione Peroxidase Mimics

“…[8] This is shown in the structure of 4 in Scheme 2w ith average Se···O distances of 2.5 a nd CÀH···O distances of 2.35 . In GPx, nitrogen moieties of at ryptophane (Trp158) and of ag lutamine (Gln80) residue stabilize the selenium atom during the redox process.R ecent investigations on the mechanism of action of ebselen and related compounds revealed that the initial reaction of ebselen with thiols,such as GSH, leads to the formation of selenenyl sulfides,w hich are further stabilized by non-covalent selenium-oxygen interactions as shown in compound 7 in Scheme 2.…”

Tin···Oxygen Tetrel Bonding: A Combined Structural, Spectroscopic, and Computational Study

“…9,10,11,12,13,14 Over the past few years other non-conventional noncovalent interactions have gained attention, such as tetrel bonding, 15,16,17,18,19 pnictogen bonding, 20,21,22,23,24,25,26,27,28,29,30,31 chalcogenide bonding, 32,33,34,35,36,37,38,39,40,41,42,43,44 and even aerogen bonding. 45 All follow the same bonding scheme, namely a -hole, 46 which can be viewed comparably to hydrogen bonding: X-D … A, where X is any atom, D is the donor atom and A is the acceptor atom.…”