Hydrogen bond directed molecular recognition in water in a strapped-porphyrin-cyclodextrin assembly

A water soluble, phenanthroline-strapped zinc porphyrin bearing four arylsulfonate groups formed a stable host–guest complex with two per-O-methylated β-cyclodextrin cavities. In the host–guest assembly, the zinc porphyrin was capable of binding imidazole within the cavity between the zinc(II) ion and the phenanthroline strap in an aqueous medium. The formation of a hydrogen bond between the imidazole NH and the nitrogen atoms of the phenanthroline was an essential element of the binding event, as shown by comparative binding studies with a non-strapped tetrasulfonated zinc porphyrin and with N-methylimidazole. This hydrogen bonding in an aqueous medium was possible due to the protected hydrophobic environment created by the cyclodextrins around the phenanthroline strap. This type of binding event may provide a biomimetic approach to study water soluble heme protein models

FRET‐Based In‐Cell Detection of Highly Selective Supramolecular Complexes of <i>meso</i> ‐Tetraarylporphyrin with Peptide/BODIPY‐Modified Per‐ <i>O</i> ‐Methyl‐β‐Cyclodextrins

Artificial supramolecular systems capable of self-assembly and that precisely function in biological media are in high demand. Herein, we demonstrate a highly specific host-guest-pair system that functions in living cells. A per-O-methyl-β-cyclodextrin derivative (R8-B-CD Me) bearing both an octaarginine peptide chain and a BODIPY dye was synthesized as a fluorescent intracellular delivery tool. R8-B-CD Me was efficiently taken up by HeLa cells through both endocytosis and direct transmembrane pathways. R8-B-CD Me formed a 2 : 1 inclusion complex with tetrakis(4-sulfonatophenyl)porphyrin (TPPS) as a guest molecule in water, from which fluorescence resonance energy transfer (FRET) from R8-B-CD Me to TPPS was observed. The FRET phenomenon was clearly detected in living cells using confocal microscopy techniques, which revealed that the formed supramolecular R8-B-CD Me /TPPS complex was maintained within the cells. The R8-B-CD Me cytotoxicity assay revealed that the addition of TPPS counteracts the strong cytotoxicity (IC 50 = 16 μM) of the CD cavity due to complexation within the cells. A series of experiments demonstrated the bio-orthogonality of the supramolecular per-O-methyl-β-CD/tetraarylporphyrin hostguest pair in living cells

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

Sensitive quantification of carbon monoxide in vivo reveals a protective role of circulating hemoglobin in CO intoxication

International audienceAbstract Carbon monoxide (CO) is a gaseous molecule known as the silent killer. It is widely believed that an increase in blood carboxyhemoglobin (CO-Hb) is the best biomarker to define CO intoxication, while the fact that CO accumulation in tissues is the most likely direct cause of mortality is less investigated. There is no reliable method other than gas chromatography to accurately determine CO content in tissues. Here we report the properties and usage of hemoCD1, a synthetic supramolecular compound composed of an iron(II)porphyrin and a cyclodextrin dimer, as an accessible reagent for a simple colorimetric assay to quantify CO in biological samples. The assay was validated in various organ tissues collected from rats under normal conditions and after exposure to CO. The kinetic profile of CO in blood and tissues after CO treatment suggested that CO accumulation in tissues is prevented by circulating Hb, revealing a protective role of Hb in CO intoxication. Furthermore, hemoCD1 was used in vivo as a CO removal agent, showing that it acts as an effective adjuvant to O 2 ventilation to eliminate residual CO accumulated in organs, including the brain. These findings open new therapeutic perspectives to counteract the toxicity associated with CO poisoning

Design and Biological Evaluation of Manganese‐ and Ruthenium‐Based Hybrid CO‐RMs (HYCOs)

International audienc

Design and Biological Evaluation of Manganese‐ and Ruthenium‐Based Hybrid CO‐RMs (HYCOs)

International audienc

Functional Myoglobin Model Composed of a Strapped Porphyrin/Cyclodextrin Supramolecular Complex with an Overhanging COOH That Increases O(2)/CO Binding Selectivity in Aqueous Solution

International audienceA water-soluble strapped iron(III)tetraarylporphyrin () bearing two propylpyridinium groups at the side chains and a carboxylic acid group at the overhanging position of the strap was synthesized to mimic the function of myoglobin with the distal polar functionality in aqueous solution. forms a stable 1:1 inclusion complex with a per--methylated β-cyclodextrin dimer having a pyridine linker (), providing a hydrophobic environment and a proximal fifth ligand to stabilize the O-complex. The ferrous complex () binds both O and CO in aqueous solution. The O and CO binding affinities ( and ) and half-life time () of the O complex of are 6.3 and 0.021 Torr, and 7 h, respectively, at pH 7 and 25 °C. The control compound without the strap structure () has similar oxygen binding characteristics ( = 8.0 Torr), but much higher CO binding affinity ( = 3.8 × 10 Torr), and longer (30 h). The O and CO kinetics indicate that the strapped structure in inhibits the entrance of these gaseous ligands into the iron(II) center, as evidenced by lower and values. Interestingly, the CO complex of is significantly destabilized (relatively larger ), while the value is much smaller than that of , resulting in significantly increased O/CO selectivity (reduced value, where = / = 320) in compared to ( = 21000)

Development of carbon monoxide-releasing molecules conjugated to polysaccharides (glyco-CORMs) for delivering CO during obesity

Metal carbonyls have been developed as carbon monoxide-releasing molecules (CO-RMs) to deliver CO for therapeutic purposes. The manganese-based CORM-401 has been recently reported to exert beneficial effects in obese animals by reducing body weight gain, improving glucose metabolism and reprogramming adipose tissue towards a healthy phenotype. Here, we report on the synthesis and characterization of glyco-CORMs, obtained by grafting manganese carbonyls on dextrans (70 and 40 kDa), based on the fact that polysaccharides facilitate the targeting of drugs to adipose tissue. We found that glyco-CORMs efficiently deliver CO to cells in vitro with higher CO accumulation in adipocytes compared to other cell types. Oral administration of two selected glyco-CORMs (5b and 6b) resulted in CO accumulation in various organs, including adipose tissue. In addition, glyco-CORM 6b administered for eight weeks elicited anti-obesity and positive metabolic effects in mice fed a high fat diet. Our study highlights the feasibility of creating carriers with multiple functionalized CO-RMs