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The Huisgen thermal reaction between an organic azide and an acetylene was employed for the selective monofunctionalization of a X6 -azacryptand ligand bearing a tren coordinating unit [X6 stands for calix[6]arene and tren for tris(2-aminoethyl)amine]. Supramolecular assistance, originating from the formation of a host-guest inclusion complex between the reactants, greatly accelerates the reaction while self-inhibition affords a remarkable selectivity. The new ligand possesses a single amino-leg appended at the large rim of the calixarene core and the corresponding Zn(2+) complex was characterized both in solution and in the solid state. The coordination of Zn(2+) not only involves the tren cap but also the introverted amino-leg, which locks the metal ion in the cavity. Compared with the parent ligand deprived of the amino-leg, the affinity of the new monofunctionalized X6 tren ligand 6 for Zn(2+) is found to have a 10-fold increase in DMSO, which is a very competitive solvent, and with an enhancement of at least three orders of magnitude in CDCl3 /CD3 OD (1:1, v/v). In strong contrast with the fast binding kinetics, decoordination of Zn(2+) as well as transmetallation appeared to be very slow processes. The monofunctionalized X6 tren ligand 6 fully protects the metal ion from the external medium thanks to the combination of a cavity and a closed coordination sphere, leading to greater thermodynamic and kinetic stabilities., SCOPUS: ar.j, SCOPUS: ar.j, FLWIN, info:eu-repo/semantics/published

The selective functionalization of macrocyclic receptors remains extremely challenging because it generally requires the transformation of one and only one functional group among several identical groups. Recently, some of us described that the host-guest properties of a calix[6]arene-based Zn complex could be exploited for its selective monofunctionalization. Herein, we report on the extension of this synthetic strategy to a calix[6]arene-based receptor displaying a different recognition pattern with its guest. More precisely, a calix[6]arene tris-carboxylic acid-based receptor bearing three azido groups at the large rim was selectively monofunctionalized through an intramolecular thermal Huisgen reaction with a hexynNH3(+) ion accommodated into the cavity. This work shows that the monofunctionalization methodology can also be performed efficiently with host-guest systems involving ionic/H-bonding interactions, and it is thus not limited only to the use of metal-ligand interactions. In other words, this supramolecular methodology can be used as a general tool for the selective functionalization of molecular receptors., JOURNAL ARTICLE, SCOPUS: ar.j, info:eu-repo/semantics/published

The ipso-nitration of calix[6]arene-based molecular receptors is a important synthetic pathway for the elaboration of more sophisticated systems. This reaction has been studied for a variety of capped calixarenes, and a general trend for the regioselective nitration of three aromatic units out of six in moderate to high yield has been observed. This selectivity is, in part, attributed to the electronic connection between the protonated cap at the small rim and the reactive sites at the large rim. In addition, this work highlights the fact that subtle conformational properties can drastically influence the outcome of this reaction., Journal Article, Research Support, Non-U.S. Gov't, SCOPUS: ar.j, info:eu-repo/semantics/published

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info:eu-repo/semantics/published

SCOPUS: ar.j, info:eu-repo/semantics/published

We have previously shown that polymorphonuclear leucocytes (PMN) harvested from children with cancer and exposed to chemotherapy exhibit defective bactericidal activities against both Gram-positive and Gram-negative microorganisms as well as accelerated apoptosis. In this study, PMN from children with cancer were evaluated to compare in vitro the corrective effects of the two myeloid colony stimulating factors G-CSF and GM-CSF on these defective pathways. Both G-CSF and GM-CSF were able to increase the defective bactericidal activities against S. aureus and E. coli. However, GM-CSF was consistently superior to G-CSF in correcting PMN microbicidal activity; this correction was incomplete since it did not reach the level observed in normal PMN exposed to GM-CSF. The accelerated apoptosis of PMN was not affected by G-CSF. In contrast, GM-CSF significantly prolonged the survival of the PMN although it did not reach the level of survival observed with normal PMN exposed to GM-CSF. These observations were consistent with other studies indicating that in PMN, microbicidal activities and apoptosis are differentially sensitive to the myeloid growth factors G-CSF and GM-CSF., Journal Article, Research Support, Non-U.S. Gov't, SCOPUS: ar.j, FLWIN, info:eu-repo/semantics/published

Neutrophils (PMNs) from patients with secondary iron overload have an increased iron and ferritin content as well as a phagocytosis defect. Several serum components might be incriminated in the cellular iron accumulation. We therefore compared the effects on the PMN phagocytosis of total serum as well as the ferritin and transferrin fractions of serum derived from patients with thalassemia major and healthy control subjects. An incubation system of PMNs was developed. PMN phagocytosis was measured before and after incubation. Total serum from patients with thalassemia induced a defect that was prevented by co-incubation with deferoxamine (DFO). Gel-filtration chromatography was performed to separate the serum fraction containing transferrin and albumin from that containing ferritin. The transferrin-albumin fraction had no effect on PMN phagocytosis. On the contrary, the ferritin fraction of normal serum was deleterious to PMN phagocytosis, and the same fraction from thalassemic serum decreased PMN phagocytosis even more. Co-incubation with DFO or catalase improves this defect. Moreover, a cellular increase in the L-type subunit of ferritin was observed after the incubation of PMNs with the ferritin-containing fraction from thalassemic serum. In conclusion, serum from patients with thalassemia is toxic to PMNs, and this toxicity is due to ferritin-associated iron., SCOPUS: ar.j, info:eu-repo/semantics/published

Treatment of average-risk acute lymphoblastic leukaemia (ALL) in children consists of 6 months of intensive chemotherapy followed by 18 months of maintenance therapy. Polymorphonuclear leucocyte (PMN) functions from children with ALL were studied in order to evaluate and compare the toxicity of the initial intensive treatment with the toxicity of the subsequent less intensive maintenance treatment. H2O2 and O2- production, evaluated by chemiluminescence, were significantly decreased during the intensive period but returned to normal values when maintenance therapy began. In contrast, bactericidal activity against Gram-positive and Gram-negative microorganisms remained at low levels throughout the treatment but returned to normal values in patients off chemotherapy. PMN from patients on maintenance therapy exhibited an excess of morphological changes associated with apoptosis. This was confirmed by standard two-colour flow cytometry which revealed an increase in the number of hypodiploid cells, and increased expression of membrane phosphatidylserine together with a drastic reduction in the expression of the Fcgamma receptor IIIB (CD16). These defective PMN were differentially sensitive to the effects of granulocyte colony stimulating factor (G-CSF): G-CSF induced similar increase in chemiluminescence in control and patient PMN; GSF partially corrected the defective bactericidal activity; G-CSF did not affect the accelerated PMN apoptosis. These observations indicate that ALL children undergoing chemotherapy present PMN defective functions which are partially sensitive or even resistant to G-CSF., Journal Article, SCOPUS: ar.j, FLWIN, info:eu-repo/semantics/published

To analyze the toxicity associated to chemotherapy upon granulocytes, different functional assays were performed, within days of drug exposure and at time of bone marrow recovery, on polymorphonuclear neutrophils (PMN) from children with cancer. There were no significant postchemotherapy changes in the expression of the different receptors studied nor in the phagocytosis of Staphylococcus aureus 42D. By contrast, a significant decrease was observed in H2O2 production in PMN recently exposed to chemotherapy with both cytofluorometric and chemiluminescence assays. There was also a decrease in the production of O2- and in chemotaxis; finally, the intracellular killing of S. aureus 42D and Escherichia coli was reduced. In patients having recovered from drug-induced bone marrow aplasia, PMN functions were found to be normal except for bactericidal activity which was still defective. The observations indicate that, in patients exposed to chemotherapy, some PMN functions are transiently altered, whereas microorganism cell killing is continuously impaired., In Vitro, Journal Article, Research Support, Non-U.S. Gov't, SCOPUS: ar.j, info:eu-repo/semantics/published

Granulocyte colony-stimulating factor (G-CSF) has important direct and priming effects on different functions of normal mature polymorphonuclear leukocytes (PMNL). Previous study has shown an alteration in respiratory burst and bactericidal activities of PMNL harvested from children with cancer treated with chemotherapy. The present study evaluates the possibility that recombinant human (rh) G-CSF could correct these defective functions in vitro. Free radical formation in defective PMNL was enhanced by rhG-CSF to a level similar to that found in normal PMNL primed by rhG-CSF. The defective bactericidal activity against Escherichia coli and Staphylococcus aureus was also corrected. This bactericidal activity was not different from that observed in normal PMNL primed by rhG-CSF. In conclusion, correction of the altered free radical-formation pathway by rhG-CSF in these cells contributed to the restoration of normal bactericidal activity against both gram-positive and gram-negative microorganisms., Journal Article, Research Support, Non-U.S. Gov't, SCOPUS: ar.j, info:eu-repo/semantics/published