A DFT investigation of a bulky biomimetic model catalyzing the 5′-outer ring deiodination of thyroxine

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• 作者：Mariagrazia Fortino ; Tiziana Marino ; Nino Russo…
• 关键词：DFT ; Biomimetic models ; Iodothyronine deiodinase ; Thyroxine ; Selenium
• 刊名：Journal of Molecular Modeling
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：22
• 期：12
• 全文大小：659 KB
• 刊物类别：Chemistry and Materials Science
• 刊物主题：Chemistry
  Computer Applications in Chemistry
  Biomedicine
  Molecular Medicine
  Health Informatics and Administration
  Life Sciences
  Computer Application in Life Sciences
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：0948-5023
• 卷排序：22

文摘

This paper illustrates the outcomes of a density functional theory investigation aimed at unraveling mechanistic aspects of the 5′-outer ring deiodination process of thyroxine (T4) assisted by the sterically protected organoselenol compound BpqSeH. BpqSeH, which was previously synthesized and tested for its deiodinase activity, is able to afford the active hormone 3,5,3′-tetraiodothyronine (T3) by selective outer-ring deiodination of T4, and to protect the SeH moiety inside the nano-sized molecular cavity from further reactivity, allowing its isolation and characterization. Calculations were also performed including an imidazole ring that, mimicking a His residue in the active site of the original enzyme, plays an crucial role in deprotonating the selenol moiety. Both the suggested enol/keto tautomerization and the previously proven formation of an intermediate whose main characteristic is the presence of a Se⋯I⋯C halogen bond, were examined along the pathway leading to 5′-outer ring deiodination. The calculated potential energy surface showed that neither the pathway encompassing enol/keto tautomerism nor the formation of a halogen bond paving the way to C–I bond breaking and chalcogen-I bond forming is viable. The exergonic formation of the final selenenyl iodide product confirms the stabilization effect of the molecular cavity.