Rachid Baati

Tailoring carbon nanotube surfaces with glyconanorings: new bionanomaterials with specific lectin affinity

Remarkably stable, water-soluble glyconanoring-coated SWCNTs were prepared by self organization and photopolymerization of neutral diacetylene-based glycolipids on the nanotube surface; the nanoconstructs are able to engage in specific ligand-lectin interactions in a similar way to glycoconjugates on cell membranes.

Selective Irreversible Chemical Tagging of Cysteine with 3-Arylpropiolonitriles

Exquisite chemoselectivity for cysteine has been found for a novel class of remarkably hydrolytically stable reagents, 3-arylpropiolonitriles (APN). The efficacy of the APN-mediated tagging was benchmarked against other cysteine-selective methodologies in a model study on a series of traceable amino acid derivatives. The selectivity of the methodology was further explored on peptide mixtures obtained by trypsin digestion of lysozyme. Additionally, the superior stability of APN-cysteine conjugates in aqueous media, human plasma, and living cells makes this new thiol-click reaction a promising methodology for applications in bioconjugation.

Regioselective de-O-benzylation of monosaccharides

Abstract Poly- O -benzylated sugars are regioselectively debenzylated using CrCl 2 /LiI in moist EtOAc. A predictive, three-point coordination model is proposed.

Non-covalent functionalization of carbon nanotubes with glycolipids: glyconanomaterials with specific lectin-affinity

A strategy based on the utilization of neutral pyrene functionalized neoglycolipids I that interact with a CNT’s surface giving rise to biocompatible nanomaterials which are able to engage specific ligand-lectin interactions similar to glycoconjugates on the cell membrane is reported.

Phenyltetrahydroisoquinoline-pyridinaldoxime conjugates as efficient uncharged reactivators for the dephosphylation of inhibited human acetylcholinesterase.

Pyridinium and bis-pyridinium aldoximes are used as antidotes to reactivate acetylcholinesterase (AChE) inhibited by organophosphorus nerve agents. Herein, we described a series of nine nonquaternary phenyltetrahydroisoquinoline-pyridinaldoxime conjugates more efficient than or as efficient as pyridinium oximes to reactivate VX-, tabun- and ethyl paraoxon-inhibited human AChE. This study explores the structure-activity relationships of this new family of reactivators and shows that 1b-d are uncharged hAChE reactivators with a broad spectrum.

Theoretical mechanistic study of the TBD-catalyzed intramolecular aldol reaction of ketoaldehydes.

The intramolecular aldol reaction of acyclic ketoaldehydes catalyzed by 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) is investigated using density functional theory calculations. Compared to the proline-catalyzed aldol reaction, the use of TBD provides a unique and unusual complete switch of product selectivity. Three mechanistic pathways are proposed and evaluated. The calculations provide new insights into the activation mode of bifunctional guanidine catalysts. In the favored mechanism, TBD first catalyzes the enolization of the substrate and then the C-C bond formation through two concerted proton transfers. In addition, the computationally predicted stereochemical outcome of the reaction is in agreement with the experimental findings.

A convenient synthesis of (Z)-1-chloro-1-alkenes and (Z)-1-chloro-2-alkoxy-1-alkenes

Abstract Mild, room temperature CrCl 2 reduction of 1,1,1-trichloroalkanes stereoselectively generates ( Z )-1-chloro-2-substituted-1-alkenes in excellent yields.

Syntheses and in vitro evaluations of uncharged reactivators for human acetylcholinesterase inhibited by organophosphorus nerve agents

Organophosphorus nerve agents (OPNAs) are highly toxic compounds that represent a threat to both military and civilian populations. They cause an irreversible inhibition of acetylcholinesterase (AChE), by the formation of a covalent P-O bond with the catalytic serine. Among the present treatment of nerve agents poisoning, pyridinium and bis-pyridinium aldoximes are used to reactivate this inhibited enzyme but these compounds do not readily cross the blood brain barrier (BBB) due to their permanent cationic charge and thus cannot efficiently reactivate cholinesterases in the central nervous system (CNS). In this study, a series of seven new uncharged oximes reactivators have been synthesized and their in vitro ability to reactivate VX and tabun-inhibited human acetylcholinesterase (hAChE) has been evaluated. The dissociation constant K(D) of inhibited enzyme-oxime complex, the reactivity rate constant kr and the second order reactivation rate constant k(r2) have been determined and have been compared to reference oximes HI-6, Obidoxime and 2-Pralidoxime (2-PAM). Regarding the reactivation of VX-inhibited hAChE, all compounds show a better reactivation potency than those of 2-PAM, nevertheless they are less efficient than obidoxime and HI-6. Moreover, one of seven described compounds presents an ability to reactivate tabun-inhibited hAChE equivalent to those of 2-PAM.

Semi-Covalent Surface Molecular Imprinting of Polymers by One-Stage Mini-emulsion Polymerization: Glucopyranoside as a Model Analyte†

This paper describes a new type of surface imprinting technique that combines the advantages of both the semi-covalent approach and one-stage miniemulsion polymerization. This process has been successfully applied for the preparation of glucose surface-imprinted nanoparticles. The selective artificial receptors for glucopyranoside were fully characterized by IR, TEM and BET analyses, and their molecular recognition abilities by binding experiments carried out in batch processes. The molecular affinity and selectivity of the glucose molecularly imprinted polymers were accurately quantified. These characteristics are essential for verification of the efficiency of the developed surface imprinting process. The imprinting effect was clearly demonstrated using the batch rebinding method. We have found that the glucose imprinted polymers produced using the optimized one-stage mini-emulsion exhibited quite fast kinetics of binding and equilibration with glucopyranoside templates, compared to polymers prepared by bulk polymerization technique, as well as extremely low levels of unspecific bindings. We also demonstrated that glucose molecular imprinted polymer (MIP) exhibited very good selectivity for its original template compared to other glycopyranoside derivatives, such as galactose. Finally, the extraction of the binding properties from isotherms of binding by fitting to the bi-Langmuir and Freundlich models allowed the determination of the affinity constant distribution of the binding sites. This imprinting protocol allowed the determination of an affinity constant (K(D)), involving exclusively H-bonding interactions, for the glucose MIP (P2C) with the best template 1, in CH3CN as the solvent system.

Total Synthesis of (±)-Halomon by a Johnson–Claisen Rearrangement

The total synthesis of the polyhalogenated antitumour agent halomon (1) was accomplished with two novel transformations as key steps: a Johnson-Claisen rearrangement of a dichlorinated alkene for the preparation of the tertiary chlorinated C3 and a new rearrangement of bromohydrins for the regiospecific introduction of the bromine and chlorine atoms on C6 and C7, respectively.