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

• Published in: Chemistry : a European journal 2015-04, Vol.21 (18), p.6793-6800
• Main Authors: Thomas, Sajesh P., Satheeshkumar, K., Mugesh, Govindasamy, Guru Row, T. N.
• Format: Article
• Language: English
• Subjects: Antioxidants; Antioxidants - chemistry; Azoles - chemistry; Bonding; chalcogen bonding; Charge density; Chemistry; Cleavage; Covalent bonds; Crystallography, X-Ray; Drugs; ebselen; Electronics; Models, Molecular; Molecular Structure; Nitrogen - chemistry; Organoselenium Compounds - chemistry; polymorphism; Recognition; selenium; Selenium - chemistry; Spectroscopy, Fourier Transform Infrared; Static Electricity
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201405998

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). Se⋅⋅⋅O supramolecular recognition units in ebselen polymorphs provide insights into the antioxidant activity of this class of organoselenium drugs. Experimental charge density analysis and atoms‐in‐molecules calculations point to the possible role of chalcogen bonding in the SeN bond cleavage mechanism.