Supramolecular Ferric Porphyrins as Cyanide Receptors in Aqueous Solution

Abstract

All fundamental data about binding of the cyanide to a supramolecular complex composed of a per-O-methylated β-cyclodextrin dimer having an imidazole linker (Im3CD) and an anionic ferric porphyrin (Fe((III))TPPS) indicate that the Fe((III))TPPS/Im3CD complex is much better as an cyanide receptor in vivo than hydroxocobalamin, whose cyanide binding ability is lowered by its strong binding to serum proteins in the blood.

Supramolecular Iron Porphyrin/Cyclodextrin Dimer Complex that Mimics the Functions of Hemoglobin and Methemoglobin

“…Such an assumption is based on the idea that an axial H 2 O exchanges more easily with CN − than OH − . The spectroscopic pH titration of met‐hemoCD3 provided a p K a of 8.0, which is close to the p K a values of metHb (8.33) and HOCbl (8.1) and is slightly larger than that of the H 2 O‐Fe III TPPS/Im3CD complex (7.7) 3. Under physiological conditions, the axial ligand of the met‐hemoCD3 is mostly H 2 O, not OH − .…”

“…Our previous studies on a porphinato iron/per‐ O ‐methylated β‐cyclodextrin dimer supramolecular system revealed that 5,10,15,20‐tetrakis(4‐sulfonatophenyl)porphinato iron (FeTPPS), encapsulated by two cyclodextrin units and ligated by a nitrogenous axial ligand at a linker position of the cyclodextrin dimer, captures molecular oxygen,1 carbon monoxide,1, 2 nitrogen monoxide,1d or a cyanide anion3 in aqueous solution. Because these functions of the supramolecular system are similar to those of hemoglobin (Hb), myoglobin (Mb), and their ferric derivatives, the FeTPPS/cyclodextrin dimer complexes have potential for use in basic research and practical applications.…”

“…For example, the complex of Fe II TPPS and Py3CD (hemoCD1, Scheme ) is a powerful candidate to remove CO from the blood stream 2. The Fe III TPPS/Im3CD complex is expected to function as an effective and safe cyanide antidote 3. However, synthesis of the per‐ O ‐methylated β‐cyclodextrin dimers (Py3CD,1a Py2CD,1d and Im3CD1c) shown in Scheme is time consuming, because of the multiple steps involved.…”

“…A recent treatment for cyanide poisoning is the capture of CN − ions by hydroxocobalamin (HOCbl) 7. However, the greatest disadvantage of using HOCbl is its poor ability to bind CN − in blood, because serum albumin strongly incorporates HOCbl in its pockets to cause marked reduction in the binding ( K CN ) and rate constants ( k on CN ) of CN − 3. 8 We previously reported that the 1:1 complex of Fe III TPPS with Im3CD (Scheme ) shows good capture of CN − in the blood 3.…”

“…However, the greatest disadvantage of using HOCbl is its poor ability to bind CN − in blood, because serum albumin strongly incorporates HOCbl in its pockets to cause marked reduction in the binding ( K CN ) and rate constants ( k on CN ) of CN − 3. 8 We previously reported that the 1:1 complex of Fe III TPPS with Im3CD (Scheme ) shows good capture of CN − in the blood 3. However, k on CN (193 M −1 s −1 ; Table 1) of the Fe III TPPS/Im3CD complex is not high enough when compared with that of metHb (320 M −1 s −1 ) and metMb (305 M −1 s −1 ).…”