Interaction of CORM-2 with hydrophobic sites: Beyond CO

Elena A. Sher, Mati Shaklai, Nurith Shaklai

Departments of Hematology, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel.
Departments of Human Genetics & Biochemistry, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel.

DOI: 10.4236/abc.2012.22023                

Abstract

Carbon monoxide releasing molecules (CORMs) have been recently developed for research and pharmacological purposes. A considerable amount of studies demonstrated a wide spectrum of biological activities for lipophilic CORM-2 (tricarbonyldichlororuthenium (II) dimer). It is generally accepted that the liberated gas provides the specific activities to CORMs, with a little attention paid to any possible effect of complementary core molecules. However, the versatile repertoire of actions attributed to CORM-2 is surprisingly wide for CO, a molecule with the sole chemical activity of binding to ferrous iron in protein prosthetic groups. The study was designed to analyze CORM-2 and its core molecule (“i”CORM) activities at a molecular level. With respect to the hydrophobic nature of the compounds, we followed their interactions with several amphipathic entities: the heme sites of hemoproteins, heme binding proteins and cell membranes. CORM-2/“i”CORM decreased the Soret optical density of hemoglobin and myoglobin, indicating that both compounds interact with the protein amphipathic site in the heme pocket. Pre-addition of CORM-2/“i”CORM to the apo-forms of the plasma heme binding proteins, hemopexin and albumin, partially abolished their heme binding capacity. In contrast, the compounds had no effect on the preformed heme-protein complexes. Addition of CORM-2/“i”- CORM to blood or isolated erythrocytes revealed aggregation of the cells or lysis, depending on the rea-gent-to-cells ratio. It was concluded that the ruthenium containing core molecule of CORM-2 may be physiologically active due to non-specific hydrophobic interactions. As each type of CORMs is expected to have a different mode of action beyond CO activity, their potential therapeutic uses will require clarification.

Keywords

Carbon Monoxide; CO-Releasing Molecules; Heme; Ruthenium Complexes; Hemoproteins; Hemopexin; Albumin; Red Cell Membranes; Hydrophobic Interactions

Conflicts of Interest

The authors declare no conflicts of interest.

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