Intramolecular Direct Oxygen Transfer from Oxoferryl Porphyrin to a Sulfide Bond

A 1:1 supramolecular complex (met-hemoCD) of 5,10,15,20-tetrakis­(4-sulfonatophenyl)­porphyrinatoiron­(III) (Fe^IIITPPS) with a per-<i>O</i>-methylated β-cyclodextrin dimer having a −SCH₂PyCH₂S– (Py = pyridin-3,5-diyl) linker (Py3CD) reacted rapidly with hydrogen peroxide or cumene hydroperoxide in an aqueous solution forming two types of hydroperoxo or alkylperoxo intermediates, ROO-Fe^III(OH^–)­PCD and ROO-Fe^III(Py)­PCD, which underwent rapid homolysis to the corresponding ferryloxo species, namely, OFe^IV(OH^–)­PCD and OFe^IV(Py)­PCD, respectively. For the OFe^IV(OH^–)­PCD species, the iron-oxo oxygen facing the linker gradually transferred to the nearby sulfide bond on the linker, forming the sulfoxidized Py3CD (Py3CD-O)/Fe^IITPPS complex, which then bound dioxygen in air forming an oxy-ferrous complex, O₂-Fe^IITPPS/Py3CD-O. In contrast, the OFe^IV(Py)­PCD species, in which the iron-oxo oxygen was located on the opposite side of the sulfide bond on the linker across the porphyrin ring, was reduced to the resting state (met-hemoCD) by the surroundings without any oxidation of the Py3CD linker

Supramolecular Ferric Porphyrins as Cyanide Receptors in Aqueous Solution

All fundamental data about binding of the cyanide to a supramolecular complex composed of a per-<i>O</i>-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

Glycan-Targeted Virus-like Nanoparticles for Photodynamic Therapy

Virus-like particles (VLPs) have proven to be versatile platforms for chemical and genetic functionalization for a variety of purposes in biomedicine, catalysis, and materials science. We describe here the simultaneous modification of the bacteriophage Qβ VLP with a metalloporphyrin derivative for photodynamic therapy and a glycan ligand for specific targeting of cells bearing the CD22 receptor. This application benefits from the presence of the targeting function and the delivery of a high local concentration of singlet oxygen-generating payload

Detection and Removal of Endogenous Carbon Monoxide by Selective and Cell-Permeable Hemoprotein Model Complexes

Carbon monoxide (CO) is produced in mammalian cells during heme metabolism and serves as an important signaling messenger. Here we report the bioactive properties of selective CO scavengers, hemoCD1 and its derivative R8-hemoCD1, which have the ability to detect and remove endogenous CO in cells. HemoCD1 is a supramolecular hemoprotein-model complex composed of 5,10,15,20-tetrakis­(4-sulfonatophenyl)­porphinatoiron­(II) and a per-<i>O</i>-methylated β-cyclodextrin dimer having an pyridine linker. We demonstrate that hemoCD1 can be used effectively to quantify endogenous CO in cell lysates by a simple spectrophotometric method. The hemoCD1 assay detected ca. 260 pmol of CO in 10⁶ hepatocytes, which was well-correlated with the amount of intracellular bilirubin, the final breakdown product of heme metabolism. We then covalently attached an octaarginine peptide to a maleimide-appended hemoCD1 to synthesize R8-hemoCD1, a cell-permeable CO scavenger. Indeed, R8-hemoCD1 was taken up by intact cells and captured intracellular CO with high efficiency. Moreover, we revealed that removal of endogenous CO by R8-hemoCD1 in cultured macrophages led to a significant increase (ca. 2.5-fold) in reactive oxygen species production and exacerbation of inflammation after challenge with lipopolysaccharide. Thus, R8-hemoCD1 represents a powerful expedient for exploring specific and still unidentified biological functions of CO in cells

Feedback Response to Selective Depletion of Endogenous Carbon Monoxide in the Blood

The physiological roles of endogenous carbon monoxide (CO) have not been fully understood because of the difficulty in preparing a loss-of-function phenotype of this molecule. Here, we have utilized in vivo CO receptors, hemoCDs, which are the supramolecular 1:1 inclusion complexes of <i>meso</i>-tetrakis­(4-sulfonatophenyl)­porphinatoiron­(II) with per-<i>O</i>-methylated β-cyclodextrin dimers. Three types of hemoCDs (hemoCD1, hemoCD2, and hemoCD3) that exhibit different CO-affinities have been tested as CO-depleting agents in vivo. Intraperitoneally administered hemoCD bound endogenous CO within the murine circulation, and was excreted in the urine along with CO in an affinity-dependent manner. The sufficient administration of hemoCD that has higher CO-affinity than hemoglobin (Hb) produced a pseudoknockdown state of CO in the mouse in which heme oxygenase-1 (HO-1) was markedly induced in the liver, causing the acceleration of endogenous CO production to maintain constant CO-Hb levels in the blood. The contents of free hemin and bilirubin in the blood plasma of the treated mice significantly increased upon removal of endogenous CO by hemoCD. Thus, a homeostatic feedback model for the CO/HO-1 system was proposed as follows: HemoCD primarily removes CO from cell-free CO-Hb. The resulting oxy-Hb is quickly oxidized to met-Hb by oxidant(s) such as hydrogen peroxide in the blood plasma. The met-Hb readily releases free hemin that directly induces HO-1 in the liver, which metabolizes the hemin into iron, biliverdin, and CO. The newly produced CO binds to ferrous Hb to form CO-Hb as an oxidation-resistant state. Overall, the present system revealed the regulatory role of CO for maintaining the ferrous/ferric balance of Hb in the blood