5 research outputs found
Intramolecular Direct Oxygen Transfer from Oxoferryl Porphyrin to a Sulfide Bond
A 1:1 supramolecular complex (met-hemoCD)
of 5,10,15,20-tetrakisÂ(4-sulfonatophenyl)ÂporphyrinatoironÂ(III)
(Fe<sup>III</sup>TPPS) with a per-<i>O</i>-methylated β-cyclodextrin
dimer having a âSCH<sub>2</sub>PyCH<sub>2</sub>Sâ (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<sup>III</sup>(OH<sup>â</sup>)ÂPCD and ROO-Fe<sup>III</sup>(Py)ÂPCD, which underwent
rapid homolysis to the corresponding ferryloxo species, namely, OîťFe<sup>IV</sup>(OH<sup>â</sup>)ÂPCD and OîťFe<sup>IV</sup>(Py)ÂPCD,
respectively. For the OîťFe<sup>IV</sup>(OH<sup>â</sup>)ÂPCD 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<sup>II</sup>TPPS complex, which then bound dioxygen
in air forming an oxy-ferrous complex, O<sub>2</sub>-Fe<sup>II</sup>TPPS/Py3CD-O. In contrast, the OîťFe<sup>IV</sup>(Py)ÂPCD 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<sup>(III)</sup>TPPS) indicate that the Fe<sup>(III)</sup>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-tetrakisÂ(4-sulfonatophenyl)ÂporphinatoironÂ(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 10<sup>6</sup> 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>-tetrakisÂ(4-sulfonatophenyl)ÂporphinatoironÂ(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