Synthesis and characterization of polyampholytic aryl-sulfonated chitosans and their in vitro anticoagulant activity

Safa Ouerghemmi (1) , Syrine Dimassi , Nicolas Tabary (1) , Laurent Leclercq (2, 3) , Stephanie Degoutin (1) , Feng Chai (4) , Christel Pierlot (5) , Fréderic Cazaux (1) , Alexandre Ung (6) , Jean-Noel Staelens (1) , Nicolas Blanchemain (4) , Bernard Martel (7)

1 UMET - Unité Matériaux et Transformations - UMR 8207
2 UM - Université de Montpellier
3 IBMM - Institut des Biomolécules Max Mousseron [Pôle Chimie Balard]
4 MBLC - ADDS - Médicaments et biomatériaux à libération contrôlée: mécanismes et optimisation - Advanced Drug Delivery Systems - U 1008
5 UCCS - Unité de Catalyse et Chimie du Solide - UMR 8181
6 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
7 UMR CNRS 8009 - Laboratoire de Chimie Organique et Macromoleculaire

This work firstly aimed to synthesize mono-and di-sulfonic derivatives of chitosan by reductive amination reaction using respectively 2-formyl benzene sulfonic acid and 2,4 formyl benzene sulfonic acid sodium salts. The influence of the reactants molar ratio (R), aryl - substituted amino groups versus chitosan free amino groups, on the degree of substitution (DS) of both sulfonated chitosans was assessed by H-1 NMR, elemental analysis, coupled conductometry-potentiometry analysis and UV spectrometry and FTIR. The influence of pH on sulfonated chitosans' properties in solution were investigated by solubility and zeta potential (ZP) studies, size exclusion chromatography equipped with MALLS detection (SEC-MALLS) and Taylor dispersion analysis (TDA). The polyampholytic character of both series was evidenced and strongly modified the solutions properties compared to chitosan. Then, the anticoagulant properties of mono-and di-sulfonic polymers were investigated by the measurement of the activated partial thromboplastin time (aPTT), Prothrombin-time (PT) and anti-(factor Xa).

Mots clés: Sulfonated chitosan; Chitosan; Reductive amination; Polyampholyte; Anticoagulant

Domaines: Polymères; Chimie thérapeutique

Safa Ouerghemmi, Syrine Dimassi, Nicolas Tabary, Laurent Leclercq, Stephanie Degoutin, et al.. Synthesis and characterization of polyampholytic aryl-sulfonated chitosans and their in vitro anticoagulant activity. Carbohydrate Polymers, 2018, 196, pp.8-17. ⟨10.1016/j.carbpol.2018.05.025⟩. ⟨hal-02322537⟩