Non-radical synthesis of chitosan-quercetin polysaccharide: Properties, bioactivity and applications
Graphical abstract
Introduction
One of the common reasons for food deterioration is the contamination by spoilage microorganisms. Oxidative reactions also affect the quality and safety of food products (Azad et al., 2019; Dilmaçünal & Kuleaşan, 2018). Synthetic antimicrobials and antioxidants have been used to prevent this damage, but there is a growing awareness of the health risks and environmental impact of these compounds. As a result, numerous attempts have been made to develop green, safe, nature-sourced alternatives for the effective protection of food products (Liqing et al., 2019; Mahdieh et al., 2020).
Modified polysaccharides with covalently attached bioactive agents have been successfully applied as active packages delivery systems and edible coatings (Arnon et al., 2021; Liu et al., 2018, Liu et al., 2018; Oria et al., 2019; Qiaobin & Yangchao, 2016; Shu et al., 2011). The nature-sourced biodegradable polysaccharide chitosan (CS) is known for its intrinsic antimicrobial activity; it is widely used in food, medicine, cosmetics, agriculture, and more (Bakshi et al., 2020). Modifications of CS with various substituents aimed at enhancing its bioactivity and physico-mechanical properties are of high scientific and applied interest (Zhang et al., 2010). The attachment of natural bioactive compounds, such as phenolic and terpenic agents, to CS polymer is one recent direction for such modifications (Qiaobin & Yangchao, 2016; Rajendran et al., 2019).
Quercetin is a natural flavonoid commonly found in fruit and vegetables, which possesses antioxidative, antimicrobial and therapeutic properties (Parvez et al., 2004; Rodov et al., 2010; Victor et al., 2016). Quercetin is considered as one of the most powerful antioxidants among flavonoids, and it was found to inhibit Botrytis cinerea and blue mold, harmful plant pathogens that cause deterioration of numerous fruits and vegetables (Mendoza et al., 2013; Zhang et al., 2018). Therefore, quercetin has good a potential to be used as natural agent for postharvest protection of fresh produce. However, application of quercetin has two main drawbacks: poor solubility in water that limits its applicability and low high tendency toward oxidation (Cai et al., 2013). Covalent linkage to water-soluble polysaccharides may improve applicability and increase stability of active agent; however, preserving bioactivity upon linkage is challenging.
Linkage of flavonoid compounds to polysaccharides can be done through oxidative radical grafting (Curcio et al., 2009; Qiaobin & Yangchao, 2016; Torres et al., 2012). However, such reactions cause the formation of free radicals at various positions of polyphenol, resulting in uncontrolled mixtures of products. These radical reaction products are formed rather randomly and vary in different reaction stocks. Therefore, it is problematic to control bioactivity of radical reaction products (Qiaobin & Yangchao, 2016).
In this work, we present the covalent linkage of quercetin to a CS polymeric scaffold, without using oxidative radical grafting. The quercetin-chitosan (QCS) polysaccharide was synthesized by reaction with the L-valine-quercetin precursor. We hypothesized that the linkage would improve antimicrobial and antioxidant properties of the original CS, resulting in a nature-sourced biocompatible polysaccharide that benefits from advanced bioactivity and does not involve radical synthesis during its preparation. Such a polysaccharide has good potential for use as an active material in food and other safety-sensitive applications. The prepared modified polymer was systematically characterized, and its antimicrobial and antioxidant properties were examined in vitro and then on fresh-cut produce, which is highly prone to deterioration (Basharat et al., 2018). The effect of QCS on physiological quality and microbial content of fresh-cut melon/apple was examined.
Section snippets
Materials
Chitosan (min. deacetylation degree of 90% and molar mass of approx. 890,000 g/mol) was purchased from Glentham Life Sciences (Wiltshire, UK). L-valine tert-butyl ester hydrochloride (99%) was purchased from Chem-Impex INT'L INC (Wood Dale, USA). N,N-Diisopropylethylamine (DIPEA) (99%) and molecular sieves beads (4 Å, −8 + 12, 2 mm) were purchased from Alfa Aesar (Heysham, England). Bis(4-nitrophenyl) carbonate (97%), quercetin hydrate (95%), trifluoroacetic acid (99%),
Synthesis and characterization
Quercetin-tert-butyl-L-valine carbamate regioisomers were prepared using modified method of Kim et al. (2009). The quercetin-tert-butyl–L-valine carbamate was coupled with chitosan (CS) by amidation reaction in presence of EDC, resulting in the modified quercetin-chitosan polymer, QCS (Scheme 1).
ATR-FTIR spectrum of the quercetin-tert-butyl-L-valine carbamate shows two new peaks at 1644 cm−1 and 1636 cm−1 for CO bonds of secondary amide newly formed upon covalent bonding L-valine tert-butyl
Conclusions
The modified QCS polysaccharide was synthesized by a non-radical grafting method using quercetin-ter-butyl-L-valine-carbomate as the precursor. The prepared QCS polymer had amphiphilic properties that allowed spontaneous self-assembly, and antimicrobial and antioxidant activity. QCS-based active coatings were applied on fresh-cut fruit and successfully reduced microbial spoilage, oxidative browning and moisture loss of the coated produce, supporting the initial research hypothesis. The prepared
Funding
This research was funded by the Israeli Ministry of Science and Technology, grant no. 421034517.
CRediT authorship contribution statement
Yevgenia Shebis
Conceptualization, methodology, software, paper writing, data curation, conducting the research and investigation process, formal analysis.
Alexander Laskavy
Conceptualization, methodology, software, paper writing, data curation, conducting the research and investigation process, formal analysis.
Anat Molad-Filossof
Methodology, software, paper writing, conducting the research and investigation process, formal analysis.
Hadar Arnon-Rips
Methodology, investigation process.
Michal
Declaration of competing interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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These authors contributed equally to this work.