Effect of carboxymethylcellulose main chain structure on the result of its periodate oxidation under Malaprade reaction

Abstract

Carboxymethylcellulose (CMC) and dialdehyde carboxymethylcellulose (DACMC) are used in pharmacology as polymer carriers of physiologically active compounds. The chemical structure of these polymers determines their specific areas and modes of application [1,2,3,4]. The aim of the study was to investigate the influence of carboxymethylation regioselectivity and the number of carboxymethyl substituents on the ability of CMC to form covalent drug binding sites and on the molecular weight after its periodate oxidation followed DACMC formation. It were studied CMC samples having molecular weights ranging from M_w=90–725 kDa, containing from 40 (γ_carb = 42) up to 120 (γ_carb = 119) carboxymethyl substituents per 100 averaged anhydroglucose units (AGU). 2D NMR spectroscopy confirmed that partial ester substituents formed during the carboxymethylation of cellulose with chloroacetic acid. The reactive sites within the AGUs and the ratio of oxidation-susceptible to oxidation-resistant rings were identified. The proportion of C6, C2, and C3 substituted units ranges from 1.5:1.2:1.0 to 3.0:2.0:1.0 respectively. The maximum content of oxidized units increases as the degree of carboxymethylation decreases. Periodate oxidation produces DACMC, containing from 8 to 30 oxidized units per 100 averaged AGU. Unsubstituted AGU are oxidized first, while rings substituted at positions 2 and 3 do not react. The oxidized units form seven-membered hemiacetal cycles and do not contain free aldehyde groups. The Malaprade reaction is accompanied by hydrolysis, resulting in a decrease in dynamic viscosity and molecular weight of the resulting polymer. The reaction rate is significantly lower compared to 1,6-polysaccharides.