Benzimidazole- and Imidazole-Fused Selenazolium and Selenazinium Selenocyanates: Ionic Organoselenium Compounds with Efficient Peroxide Scavenging Activities

Abstract

Three new classes of ionic organoselenium compounds containing cationic benzimidazolium and imidazolium ring systems with selenocyanates as counterions are described. The cyclization of N,N'-disubstituted benzimidazolium and imidazolium bromides having <i>N</i>-(CH₂)₂-Br and <i>N</i>-(CH₂)₃-Br groups in the presence of potassium selenocyanate (KSeCN) led to formation of the corresponding selenazolium selenocyanates (<b>21a</b>, <b>21b</b>, <b>22a</b>, and <b>22b</b>) and selenazinium selenocyanates (<b>21c</b>, <b>21d</b>, <b>22c</b>, and <b>22d</b>). However, the open-chain selenocyanates with additional selenocyanate counterions (<b>21e</b>, <b>21f</b>, <b>22e</b>, and <b>22f</b>) were formed from the N,N'-disubstituted benzimidazolium and imidazolium bromides having <i>N</i>-(CH₂)₆-Br groups. Mechanistic studies were carried out to understand the feasibility of such cyclization processes in the presence of KSeCN. The compounds were studied further for their potencies to catalytically reduce H₂O₂ in the presence of thiols. Interestingly, the cyclic selenazolium (<b>21a</b>, <b>21b</b>, <b>22a</b>, and <b>22b</b>) and selenazinium compounds (<b>21c</b>, <b>21d</b>, <b>22c</b>, and <b>22d</b>) exhibited significantly higher antioxidant activities than the corresponding acyclic selenocyanates (<b>21f</b>, <b>22e</b>, and <b>22f</b>). Selected compounds (<b>22d</b> and <b>22e</b>) were further evaluated for their potencies in modulating the intracellular level of reactive oxygen species (ROS) in a representative macrophage cell line (RAW 264.7). Owing to the cationic nature of compounds, they may target and scavenge mitochondrial ROS in the cellular medium.