Vasorelaxing effects and inhibition of nitric oxide in macrophages by new iron-containing carbon monoxide-releasing molecules (CO-RMs)

Roberto Motterlini, Philip Sawle, Jehad Hammad, Brian E Mann, Tony R Johnson, Colin J Green, Roberta Foresti

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)


Carbon monoxide-releasing molecules (CO-RMs) are a class of organometallo carbonyl complexes capable of delivering controlled quantities of CO gas to cells and tissues thus exerting a broad spectrum of pharmacological effects. Here we report on the chemical synthesis, CO releasing properties, cytotoxicity profile and pharmacological activities of four novel structurally related iron-allyl carbonyls. The major difference among the new CO-RMs tested was that three compounds (CORM-307, CORM-308 and CORM-314) were soluble in dimethylsulfoxide (DMSO), whereas a fourth one (CORM-319) was rendered water-soluble by reacting the iron-carbonyl with hydrogen tetrafluoroborate. We found that despite the fact all compounds liberated CO, CO-RMs soluble in DMSO caused a more pronounced toxic effect both in vascular and inflammatory cells as well as in isolated vessels. More specifically, iron carbonyls soluble in DMSO released CO with a fast kinetic and displayed a marked cytotoxic effect in smooth muscle cells and RAW 247.6 macrophages despite exerting a rapid and pronounced vasorelaxation ex vivo. In contrast, CORM-319 that is soluble in water and liberated CO with a slower rate, preserved smooth muscle cell viability, relaxed aortic tissue and exerted a significant anti-inflammatory effect in macrophages challenged with endotoxin. These data suggest that iron carbonyls can be used as scaffolds for the design and synthesis of pharmacologically active CO-RMs and indicate that increasing water solubility and controlling the rate of CO release are important parameters for limiting their potential toxic effects.

Original languageEnglish
Pages (from-to)108-17
Number of pages10
JournalPharmacological Research
Issue number1
Early online date17 Dec 2012
Publication statusPublished - Feb 2013


  • Animals
  • Aorta, Thoracic
  • Carbon Monoxide
  • Cell Line
  • In Vitro Techniques
  • Iron
  • Macrophages
  • Male
  • Mice
  • Nitric Oxide
  • Organometallic Compounds
  • Rats
  • Rats, Sprague-Dawley
  • Vasodilation
  • Vasodilator Agents
  • Journal Article
  • Research Support, Non-U.S. Gov't


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