*1.1. Definition of Antioxidants. Their Importance in Food Preservation*

Antioxidants are a class of naturally occurring or synthetic compounds. The naturally occurring antioxidants include Vitamin C and Vitamin E (tocotrienols and tocopherols in general) [1–3]. Other classes are phenolic compounds and carotenoids [4]. Synthetic antioxidant molecules include α-lipoic acid, N-acetyl cysteine, melatonin, gallic acid, captopril, taurine, catechin, and quercetin [5]; these compounds are indispensable in the scavenging of free radical species. For example, gallic acid and poly Trolox ester polymers scavenge free radicals in the cytosolic cellular compartment [6]. In contrast, β-carotene, and vitamin E (tocopherol), are most effective against lipid peroxidation.

**Citation:** Maraveas, C.; Bayer, I.S.; Bartzanas, T. Recent Advances in Antioxidant Polymers: From Sustainable and Natural Monomers to Synthesis and Applications. *Polymers* **2021**, *13*, 2465. https:// doi.org/10.3390/polym13152465

Academic Editor: José Miguel Ferri

Received: 5 July 2021 Accepted: 23 July 2021 Published: 27 July 2021

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**Copyright:** © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

Wattamwar et al. [6] attribute the formation of reactive oxygen species to cellular processes, including inflammation—a process that results in the activation of endothelial cell macrophages, which in turn trigger the development of Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex [6]. The NADPH complex is responsible for the conversion of molecular oxygen into O2, a superoxide reactive anion, which is converted into H2O<sup>2</sup> (hydrogen peroxide) following contact with superoxide dismutase [6]. The hydrogen peroxide molecule is a potent reactant, which binds with copper and iron metal ions, releasing hydroxyl radicals. Alternatively, ONOO− (peroxynitrite) is formed if the superoxide reactive anion is formed in a NO-rich environment. The reactive oxygen and nitrogen species formed through a sequence of reactions triggered by NADPH are responsible for cellular oxidative and lipid damage—phenomena that result in the release of oxidative stress markers (4-hydroxy-2-trans-nonenal, 3-nitrotyrosine (3NT), protein carbonyl). The primary function of melatonin, gallic acid, captopril, taurine, catechin, and quercetin, vitamin C, and E analogs is to bind to the markers to prevent structural damage to cellular proteins.

The biological importance of different antioxidants in food preservation and augmentation of body defense mechanisms depends on chemical properties. Pryor et al. [3] evaluated the performance of both natural and synthetic antioxidants in sodium dodecyl sulfate micelle solutions; it was noted that hydrogen bonding on the para and ether O<sup>2</sup> atoms predicted the reactivity of the antioxidants towards peroxyl radicals. Beyond H-bonding affinity towards reactive oxygen species was predicted by the presence of bulky tert-butyl groups [3]. Even though synthetic and natural antioxidants exhibit similar potency towards ROS, the selection of the chemicals in industrial applications is predicted by regulatory standards. European Parliament and Council Directive No.1333/2008 restricts the use of synthetic antioxidants in food preservation [4], except for 2, 4-dichlorophenoxyacetic acid (2,4-DA), 2-naphthol (2NL), 4-phenyl phenol (OPP), tert-butyl hydroquinone (TBHQ), butylated hydroxytoluene (BHT), and butylated hydroxyanisole (BHA) [4]. The listed synthetic antioxidants have found broad application in the food industry, particularly in preserving fruits and vegetables, due to their low cost, stability, performance, and widespread availability [3–5,7].

Vitamin C has been proven to exhibit superior activity in the quenching of reactive oxygen species and free radicals, resulting in the formation of ascorbyl radicals. The latter is a less potent radical compared to ROS based on the potential for oxidative damage [2]. Vitamin E exhibits a similar mechanism of action as Vitamin C. However, in the former case, the main mechanism of action involves protecting biological liquid compartments and the cleavage of the lipid peroxidation chain reactions. Alternatively, tocotrienols and tocopherols, in general, have been proven to contribute to the inactivation of ROS before regeneration by ascorbate [2]. Experimental evidence has also demonstrated the practical benefits of chain-breaking tocopherols in mitigating the auto-oxidation of polyunsaturated fatty acids. This process is responsible for cancer cell growth and atherosclerosis, as well as other life-threatening conditions [3]. Other unique biological functions associated with naturally occurring antioxidants include the modulation of the activity of specific enzymes, including mitogen-activated protein kinase, protein tyrosine kinase (PTK), protein tyrosine phosphatase (PTP), protein phosphatase 2A (PP2A), and protein kinase [2].

The commercial suitability of naturally occurring antioxidants is informed by various considerations beyond regulatory standards (European Parliament and Council Directive No.1333/2008) on food preservation, encompassing antimicrobial and antifungal activities [4], lipid oxidation reactions, and chemical reactions related to anti-oxidative effects [3–5]. The synergistic impact of different considerations helps explain why phenolic antioxidants are often preferred in food preservation (see Table 1).

The extraction techniques predict the selection of natural antioxidants for food preservation. Complex extraction techniques such as microwave-assisted extraction (MAE), ultrasound-assisted extraction, pressurized liquid extraction (PLE), high hydrostatic pres-

sure (HHP), and supercritical fluid extraction (SFE) and methanol, ethanol, acetone, and water predict the cost of the extraction process and industrial application [1] (see Table 2).

**Table 1.** Active compounds, natural sources of antioxidants, and their use in different food matrices [4].


**Table 2.** Extraction techniques for different classes of naturally occurring antioxidants [4].


Natural and synthetic antioxidants are integral to reducing oxidative stress and imbalances in the cell redox reactions associated with reactive oxygen species. The formation of ROS is linked to the suppression of the innate antioxidant defense systems or the overproduction of oxygen species. Both mechanisms are common, considering that oxygen is ubiquitous in the environment, especially in biological processes involving aerobic organisms [2]. The visual illustration suggests that free radical scavenging ability is predicted by chemical structure and active components.
