Design, Synthesis and Actual Applications of the Polymers Containing Acidic P–OH Fragments: Part 2—Sidechain Phosphorus-Containing Polyacids

Macromolecules containing acidic fragments in side-groups—polyacids—occupy a special place among synthetic polymers. Properties and applications of polyacids are directly related to the chemical structure of macromolecules: the nature of the acidic groups, polymer backbone, and spacers between the main chain and acidic groups. The chemical nature of the phosphorus results in the diversity of acidic >P(O)OH fragments in sidechain phosphorus-containing polyacids (PCPAs) that can be derivatives of phosphoric or phosphinic acids. Sidechain PCPAs have many similarities with other polyacids. However, due to the relatively high acidity of –P(O)(OH)2 fragment, bone and mineral affinity, and biocompatibility, sidechain PCPAs have immense potential for diverse applications. Synthetic approaches to sidechain PCPAs also have their own specifics. All these issues are discussed in the present review.


Introduction
Polymers containing multiple acidic (-C(O)OH, S(O) 2 OH, -P(O)(OH) 2 , etc.) fragments distributed throughout the polymer backbone-polyacids, more commonly named anionic polyelectrolytes-constantly attract the researchers' attention [1][2][3]. Enhanced hydrophilicity, proton conductivity, ability to complexation with metal ions and organic bases, and biocompatibility are occasionally shown by this type of polymer-this is not a complete list of attractive properties of polyacids that determine a variety of their applications. Phosphorus-containing polyacids (PCPAs) represent a separate group of polyanionic electrolytes due to the relatively high acidity of the -P(O)(OH) 2 group, higher biocompatibility, and bone and mineral affinity of phosphates. PCPAs can be classified into main-chain PCPAs (polyphosphodiesters, discussed in Part 1 of the review) and sidechain PCPAs that represent macromolecules containing acidic phosphate or phosphonate fragments as substituents distributed throughout the polymer backbone. Sidechain PCPAs have more 'degrees of freedom' in polymer designs when compared with polyphosphodiesters; however, not all possible synthetic approaches to sidechain PCPAs have been realized to date.

Synthetic Approaches to Sidechain PCPAs: An Overview
Most of the synthetic approaches to sidechain PCPAs use (co)polymerization of the phosphorus-containing vinyl monomers (Scheme 1a,b). The alternative approach is based on the post-modification of the (co)polymers (Scheme 1c). These main approaches are article by Yamabe et al. who developed a complex and time-consuming method for th synthesis of perfuorovinyloxy-substituted perfuoroalkylphosphonic acid derivative CF2=CFO(CF2)3P(O)(OMe)2 [48].
Later, Park et al. proposed the use of Pd-catalyzed cross-coupling for the direct in troduction of one or two -P(O)(OEt)2 fragments into an aromatic ring with a formation o styryl phosphonate and bis(phosphonate) (SP and SbP, respectively) [51] (Scheme 9 Hydrolytic cleavage of the diethyl phosphonate fragments was planned and realized a ter polymerization (see Section 2.3.4). Scheme 9. Synthesis of styrenes with one or two -P(O)(OEt)2 substituents [51].
Later, Park et al. proposed the use of Pd-catalyzed cross-coupling for the direct introduction of one or two -P(O)(OEt) 2 fragments into an aromatic ring with a formation of styryl phosphonate and bis(phosphonate) (SP and SbP, respectively) [51] (Scheme 9). Hydrolytic cleavage of the diethyl phosphonate fragments was planned and realized after polymerization (see Section 2.3.4).  [48].
Later, Park et al. proposed the use of Pd-catalyzed cross-coupling for the direct introduction of one or two -P(O)(OEt)2 fragments into an aromatic ring with a formation of styryl phosphonate and bis(phosphonate) (SP and SbP, respectively) [51] (Scheme 9). Hydrolytic cleavage of the diethyl phosphonate fragments was planned and realized after polymerization (see Section 2.3.4). Scheme 9. Synthesis of styrenes with one or two -P(O)(OEt)2 substituents [51].
In the study of Hoge et al. [52], the idea of the use of styrene-derived phosphonates was further developed. Considering the high para-selectivity of nucleophilic substitution in N,N,N ,N -tetraethyl-1-(perfluorophenyl)phosphinediamine, they synthesized vinyl monomer having 1,4-perfluorophenylene linkage between styryl and -P(O)(OH) 2   Dialkyl(alkenyl)phosphates, readily available by the reaction of enolates with ClP(O)(OR)2 [53,54], can also be considered as monomers for the synthesis of sidechain PCPAs; however, their formation is complicated by the rearrangement to β-ketophosphonates [55,56].

Homopolymerization of VPA, its derivatives and analogs
Since poly(vinylphosphonic acid) (PVPA) continues to attract the researchers' attention based on new fields of PVPA can be synthesized via radical polymerization of vinylphosphonic acid in the presence of initiators and optionally chain transfer agents (CTAs) with different functionality and reactivity.
Wegner et al. [57] conducted a series of experiments on VPA polymerization in aqueous media using α,α′-azodiisobutyramidine dihydrochloride (AIBA) as an initiator. In contrast to free-radical polymerization of other polar vinyl monomers, polymerization of VPA occurred with low regioselectivity, and a probability of head-to-head and tail-to-tail links over regular head-to-tail links of 23.5% was obtained. When using AIBN as an initiator and ethyl acetate as a solvent, PVPA containing up to 17% head-to-head fragments was obtained [58]. To explain the low regioselectivity of VPA polymerization, Wegner et al. [57] suggested that the process may occur according to two different mechanisms, i.e., a classical head-to-tail radical polymerization and a cyclopolymerization of the VPA anhydride formed in situ (Scheme 11). Further studies on VPA polymerization in Ac2O media, conducted by Voit and Coll. [59], have shown that the intermediate formation of anhydride results in an acceleration of the reaction due to higher reactivity of the VPA anhydride with a formation of cyclic side-products (Scheme 11). The formation of anhydride fragments (up to 19 wt%) was also detected when the polymerization of VPA was conducted in ethyl acetate with the use of a benzoyl peroxide initiator [60]. AIBA-initiated homopolymerization of VPA was used in the preparation of PVPA samples suitable for composition with different inorganic compounds [61][62][63].  Dialkyl(alkenyl)phosphates, readily available by the reaction of enolates ClP(O)(OR)2 [53,54], can also be considered as monomers for the synthesis of sidec PCPAs; however, their formation is complicated by the rearrangement β-ketophosphonates [55,56].

Homopolymerization of VPA, its derivatives and analogs
Since poly(vinylphosphonic acid) (PVPA) continues to attract the researchers tention based on new fields of PVPA can be synthesized via radical polymerizatio vinylphosphonic acid in the presence of initiators and optionally chain transfer ag (CTAs) with different functionality and reactivity.
Wegner et al. [57] conducted a series of experiments on VPA polymerizatio aqueous media using α,α′-azodiisobutyramidine dihydrochloride (AIBA) as an initi In contrast to free-radical polymerization of other polar vinyl monomers, polymeriza of VPA occurred with low regioselectivity, and a probability of head-to-head tail-to-tail links over regular head-to-tail links of 23.5% was obtained. When using A as an initiator and ethyl acetate as a solvent, PVPA containing up to 17% head-tofragments was obtained [58]. To explain the low regioselectivity of VPA polymeriza Wegner et al. [57] suggested that the process may occur according to two diffe mechanisms, i.e., a classical head-to-tail radical polymerization and a cyclopolyme tion of the VPA anhydride formed in situ ( Scheme 11). Further studies on polymerization in Ac2O media, conducted by Voit and Coll. [59], have shown tha intermediate formation of anhydride results in an acceleration of the reaction du higher reactivity of the VPA anhydride with a formation of cyclic side-products (Sch 11). The formation of anhydride fragments (up to 19 wt%) was also detected when polymerization of VPA was conducted in ethyl acetate with the use of a benzoyl pero initiator [60]. AIBA-initiated homopolymerization of VPA was used in the preparatio Figure 1. Molecular structure of the anion of the diethyl ammonium salt of phosphinic acid with 1,4-perfluorophenylene linkage between styryl and -PO 2 H − fragments (thermal ellipsoids are set to 50% probability; cation omitted.). Reprinted with permission from [52]. Copyright (2020) Wiley-VCH GmbH.

Homopolymerization and Copolymerization of the Phosphorus Containing Vinyl Monomers 2.3.1. Homopolymerization of VPA, Its Derivatives and Analogs
Since poly(vinylphosphonic acid) (PVPA) continues to attract the researchers' attention based on new fields of PVPA can be synthesized via radical polymerization of vinylphosphonic acid in the presence of initiators and optionally chain transfer agents (CTAs) with different functionality and reactivity.
Wegner et al. [57] conducted a series of experiments on VPA polymerization in aqueous media using α,α -azodiisobutyramidine dihydrochloride (AIBA) as an initiator. In contrast to free-radical polymerization of other polar vinyl monomers, polymerization of VPA occurred with low regioselectivity, and a probability of head-to-head and tail-to-tail links over regular head-to-tail links of 23.5% was obtained. When using AIBN as an initiator and ethyl acetate as a solvent, PVPA containing up to 17% head-to-head fragments was obtained [58]. To explain the low regioselectivity of VPA polymerization, Wegner et al. [57] suggested that the process may occur according to two different mechanisms, i.e., a classical head-to-tail radical polymerization and a cyclopolymerization of the VPA anhydride formed in situ (Scheme 11). Further studies on VPA polymerization in Ac 2 O media, conducted by Voit and Coll. [59], have shown that the intermediate formation of anhydride results in an acceleration of the reaction due to higher reactivity of the VPA anhydride with a formation of cyclic side-products (Scheme 11). The formation of anhydride fragments (up to 19 wt%) was also detected when the polymerization of VPA was conducted in ethyl acetate with the use of a benzoyl peroxide initiator [60]. AIBA-initiated homopolymerization of VPA was used in the preparation of PVPA samples suitable for composition with different inorganic compounds [61][62][63].
The use CTAs in the radical polymerization of VPA was reported for the first time by David and Coll. [64]. Only CBrCl3 successfully served as CTA in the synthesis of telechelic VPA oligomers with yields of ~70% and DPn = 6-60. High-MW PVPA (Mn 42.2 kDa) was obtained in aqueous media at 80 °C when using a 620:1 VPA/AIBA ratio [65].
Prospective results were received when using n-C6F13I as a CTA that exhibited CF2I functionalization of the oligomer obtained. MALDI-TOF MS and NMR analysis indicated that conventional radical initiation and termination do not occur and that the oligomers were obtained from transfer reactions [66].
The applicability of reversible addition-fragmentation chain transfer/macromolecular design via the interchange of xanthate (RAFT/MADIX) approach to radical polymerization of VPA was studied by Destarac and Coll. [67]. They demonstrated that at 65 °C in water carboxy functionalized O-ethyl xanthate reacts rapidly and quantitatively with VPA oligoradicals to yield low-MW O-ethyl xanthate-capped PVPAs (Scheme 12), and later, reversible transfer of the xanthate terminal group leads to an increase of Mn during polymerization. AIBA was used as a water-soluble initiator of radical polymerization. A follow-up study by the same group has shown that in the presence of 0.25-0.75, molar equivalents of NaOH, the rate and the final conversion of both conventional and RAFT polymerizations were increased, and the fastest rates of polymerization were obtained in the presence of 0.5 equivalents of NaOH [68]. Scheme 12. Aqueous RAFT/MADIX polymerisation of VPA mediated by a carboxy-functional xanthate [67].
The other possibility to obtain PVPA consists in the polymerization of vinylphosphonic acid derivatives CH2=CHP(O)Cl2 or CH2=CHP(O)(OR)2 followed by hydrolysis. As was demonstrated by Ellis and Wilson, PVPA can also be obtained by free-radical polymerization of CH2=CHP(O)Cl2 with the use of an AIBN initiator, followed by hydrolysis [69]. However, to provide acceptable mechanical characteristics of PVPA-based materials, the relatively low-MW polymer thus obtained was forcedly subjected to the treatment with cross-linking reagents [70].
Jin and Gonsalves reported a relatively low Mn value of 8 kDa for homopolymer formed during AIBN-initiated bulk polymerization of CH2=CHP(O)(OMe)2 [71], the microstructure of the polymer was not determined. During the study of AIBA-initiated polymerization of CH2=CHP(O)(OMe)2, Wegner et al. [57] showed higher regioselectivity of this reaction in comparison with VPA homopolymerization. For the transformation of the polymer obtained into PVPA, it reacted with an excess of aq. HBr at 110 °C for 8 h. Note that radical polymerization of CH2=CHP(O)(O i Pr)2 can be complicated by intramolecular hydrogen transfer from the backbone to the side chain [72] (Scheme 13). Scheme 11. Formation of the side products during polymerization of VPA resulting from intermediate formation of the VPA anhydrides [57,59].
The use CTAs in the radical polymerization of VPA was reported for the first time by David and Coll. [64]. Only CBrCl 3 successfully served as CTA in the synthesis of telechelic VPA oligomers with yields of~70% and DP n = 6-60. High-MW PVPA (M n 42.2 kDa) was obtained in aqueous media at 80 • C when using a 620:1 VPA/AIBA ratio [65].
Prospective results were received when using n-C 6 F 13 I as a CTA that exhibited CF 2 I functionalization of the oligomer obtained. MALDI-TOF MS and NMR analysis indicated that conventional radical initiation and termination do not occur and that the oligomers were obtained from transfer reactions [66].
The applicability of reversible addition-fragmentation chain transfer/macromolecular design via the interchange of xanthate (RAFT/MADIX) approach to radical polymerization of VPA was studied by Destarac and Coll. [67]. They demonstrated that at 65 • C in water carboxy functionalized O-ethyl xanthate reacts rapidly and quantitatively with VPA oligoradicals to yield low-MW O-ethyl xanthate-capped PVPAs (Scheme 12), and later, reversible transfer of the xanthate terminal group leads to an increase of M n during polymerization. AIBA was used as a water-soluble initiator of radical polymerization. A follow-up study by the same group has shown that in the presence of 0.25-0.75, molar equivalents of NaOH, the rate and the final conversion of both conventional and RAFT polymerizations were increased, and the fastest rates of polymerization were obtained in the presence of 0.5 equivalents of NaOH [68].
The use CTAs in the radical polymerization of VPA was reported for the first time by David and Coll. [64]. Only CBrCl3 successfully served as CTA in the synthesis of telechelic VPA oligomers with yields of ~70% and DPn = 6-60. High-MW PVPA (Mn 42.2 kDa) was obtained in aqueous media at 80 °C when using a 620:1 VPA/AIBA ratio [65].
Prospective results were received when using n-C6F13I as a CTA that exhibited CF2I functionalization of the oligomer obtained. MALDI-TOF MS and NMR analysis indicated that conventional radical initiation and termination do not occur and that the oligomers were obtained from transfer reactions [66].
The applicability of reversible addition-fragmentation chain transfer/macromolecular design via the interchange of xanthate (RAFT/MADIX) approach to radical polymerization of VPA was studied by Destarac and Coll. [67]. They demonstrated that at 65 °C in water carboxy functionalized O-ethyl xanthate reacts rapidly and quantitatively with VPA oligoradicals to yield low-MW O-ethyl xanthate-capped PVPAs (Scheme 12), and later, reversible transfer of the xanthate terminal group leads to an increase of Mn during polymerization. AIBA was used as a water-soluble initiator of radical polymerization. A follow-up study by the same group has shown that in the presence of 0.25-0.75, molar equivalents of NaOH, the rate and the final conversion of both conventional and RAFT polymerizations were increased, and the fastest rates of polymerization were obtained in the presence of 0.5 equivalents of NaOH [68]. Scheme 12. Aqueous RAFT/MADIX polymerisation of VPA mediated by a carboxy-functional xanthate [67].
The other possibility to obtain PVPA consists in the polymerization of vinylphosphonic acid derivatives CH2=CHP(O)Cl2 or CH2=CHP(O)(OR)2 followed by hydrolysis. As was demonstrated by Ellis and Wilson, PVPA can also be obtained by free-radical polymerization of CH2=CHP(O)Cl2 with the use of an AIBN initiator, followed by hydrolysis [69]. However, to provide acceptable mechanical characteristics of PVPA-based materials, the relatively low-MW polymer thus obtained was forcedly subjected to the treatment with cross-linking reagents [70].
Jin and Gonsalves reported a relatively low Mn value of 8 kDa for homopolymer formed during AIBN-initiated bulk polymerization of CH2=CHP(O)(OMe)2 [71], the microstructure of the polymer was not determined. During the study of AIBA-initiated polymerization of CH2=CHP(O)(OMe)2, Wegner et al. [57] showed higher regioselectivity of this reaction in comparison with VPA homopolymerization. For the transformation of the polymer obtained into PVPA, it reacted with an excess of aq. HBr at 110  The other possibility to obtain PVPA consists in the polymerization of vinylphosphonic acid derivatives CH 2 =CHP(O)Cl 2 or CH 2 =CHP(O)(OR) 2 followed by hydrolysis. As was demonstrated by Ellis and Wilson, PVPA can also be obtained by free-radical polymerization of CH 2 =CHP(O)Cl 2 with the use of an AIBN initiator, followed by hydrolysis [69]. However, to provide acceptable mechanical characteristics of PVPA-based materials, the relatively low-MW polymer thus obtained was forcedly subjected to the treatment with cross-linking reagents [70].
Jin and Gonsalves reported a relatively low M n value of 8 kDa for homopolymer formed during AIBN-initiated bulk polymerization of CH 2 =CHP(O)(OMe) 2 [71], the microstructure of the polymer was not determined. During the study of AIBA-initiated polymerization of CH 2 =CHP(O)(OMe) 2 , Wegner et al. [57] showed higher regioselectivity of this reaction in comparison with VPA homopolymerization. For the transformation of the polymer obtained into PVPA, it reacted with an excess of aq. HBr at 110 • C for 8 h. Note that radical polymerization of CH 2 =CHP(O)(O i Pr) 2 can be complicated by intramolecular hydrogen transfer from the backbone to the side chain [72] (Scheme 13). Scheme 13. Intramolecular hydrogen transfer from the backbone to the side chain with forma of P-O-C bonds during radical polymerization of diisopropyl vinyl phosphonate (P = polym [72]. The study of UV-induced copolymerization of VPA with CH2=CHP(O)(OMe)2 deserves to be mentioned: in the presence of 3 wt% Darocur 4265 photoinitiator (t represents a mixture of (diphenylphosphoryl)(mesityl)methanone 2-hydroxy-2-methyl-1-phenylpropan-1-one), VPA or VPA/phosphonate mixtures w laid on PTFE plates and exposed to UV irradiation. PVPA with Mn = 27.75 kDa (ÐM = 1 was obtained; for copolymers, Mn values increased from 8.78 to 16.12 kDa with an crease in the VPA/CH2=CHP(O)(OMe)2 ratio from 1:1 to 4:1. ATRP was also used in synthesis of core-shell materials with the use of oligo-(CMe2Br) substituted polyaroma and CH2=CHP(O)(OEt)2 [74].
The relatively low reactivity of CH2=CHP(O)(OR)2 in free-radical polymerization heavily conditioned the search for alternative methods of polymerization of dialkyl v phosphonates. Meyer and Coll. proposed the use of s BuLi and Ph2C=CH2 as an initiato the anionic polymerization of CH2=CHP(O)(OR)2 (R = Me, i Pr) in THF [75]. High yield the polymers were obtained when using diisopropyl vinyl phosphonate, w CH2=CHP(O)(OMe)2 gave only low yields due to the precipitation of the polymer alre in low conversions. Anionic polymerization proceeded regioselectively, but with stereoselectivity. Given that mild and quantitative hydrolysis of dialkyl phosphona can be performed via the intermediate formation of silyl esters [76], polyesters were fluxed with Me3SiBr in CH2Cl2 to yield PVPA samples of different Mw (4.2-814 kDa) ĐM of 2.1-3.9 (Scheme 14). Scheme 14. Synthesis of PVPA by anionic polymerization of dialkyl vinyl phosphonate, follow by the cleavage using Me3SiBr [75].
A similar approach to PVPA via anionic polymerization of CH2=CHP(O)(OM with subsequent hydrolysis was implemented by Takeichi et al. [77] with the use of t B or t BuLi/ n Bu3Al (1:5 mol/mol) as an initiator at the first stage (polymerization was c ducted in toluene media), and conc. HCl with 12 h of reflux at the second stage. W polymerization was initiated by t BuLi/ n Bu3Al instead of t BuLi alone, a threefold incre in monomer conversion was detected and, more significantly, ÐM decreased by half, fr 2.65 to 1.30, and isotacticity increased. The water solutions of the PVPAs were cast o glass plate and allowed to stand at room temperature for seven days. After drying, PVPA (Mn = 5.0 kDa, m = 52%), prepared through the radical polymerization, beca viscous liquids, whereas PVPA (Mn = 5.5 kDa, m = 67%), prepared through the anio process, formed self-standing transparent film. In this way, the quality of the PVPA tained at -78 °C with the use of t BuLi/ n Bu3Al initiator is clearly-in the proper sense of word-illustrated by Figure 2. Scheme 13. Intramolecular hydrogen transfer from the backbone to the side chain with formation of P-O-C bonds during radical polymerization of diisopropyl vinyl phosphonate (P = polymer) [72].
The relatively low reactivity of CH 2 =CHP(O)(OR) 2 in free-radical polymerization has heavily conditioned the search for alternative methods of polymerization of dialkyl vinyl phosphonates. Meyer and Coll. proposed the use of s BuLi and Ph 2 C=CH 2 as an initiator of the anionic polymerization of CH 2 =CHP(O)(OR) 2 (R = Me, i Pr) in THF [75]. High yields of the polymers were obtained when using diisopropyl vinyl phosphonate, while CH 2 =CHP(O)(OMe) 2 gave only low yields due to the precipitation of the polymer already in low conversions. Anionic polymerization proceeded regioselectively, but with low stereoselectivity. Given that mild and quantitative hydrolysis of dialkyl phosphonates can be performed via the intermediate formation of silyl esters [76], polyesters were refluxed with Me 3 SiBr in CH 2 Cl 2 to yield PVPA samples of different M w (4.2-814 kDa) and Ð M of 2.1-3.9 (Scheme 14). Scheme 13. Intramolecular hydrogen transfer from the backbone to the side chain with formation of P-O-C bonds during radical polymerization of diisopropyl vinyl phosphonate (P = polymer) [72].
The relatively low reactivity of CH2=CHP(O)(OR)2 in free-radical polymerization has heavily conditioned the search for alternative methods of polymerization of dialkyl vinyl phosphonates. Meyer and Coll. proposed the use of s BuLi and Ph2C=CH2 as an initiator of the anionic polymerization of CH2=CHP(O)(OR)2 (R = Me, i Pr) in THF [75]. High yields of the polymers were obtained when using diisopropyl vinyl phosphonate, while CH2=CHP(O)(OMe)2 gave only low yields due to the precipitation of the polymer already in low conversions. Anionic polymerization proceeded regioselectively, but with low stereoselectivity. Given that mild and quantitative hydrolysis of dialkyl phosphonates can be performed via the intermediate formation of silyl esters [76], polyesters were refluxed with Me3SiBr in CH2Cl2 to yield PVPA samples of different Mw (4.2-814 kDa) and ĐM of 2.1-3.9 (Scheme 14). Scheme 14. Synthesis of PVPA by anionic polymerization of dialkyl vinyl phosphonate, followed by the cleavage using Me3SiBr [75].
A similar approach to PVPA via anionic polymerization of CH2=CHP(O)(OMe)2 with subsequent hydrolysis was implemented by Takeichi et al. [77] with the use of t BuLi or t BuLi/ n Bu3Al (1:5 mol/mol) as an initiator at the first stage (polymerization was conducted in toluene media), and conc. HCl with 12 h of reflux at the second stage. When polymerization was initiated by t BuLi/ n Bu3Al instead of t BuLi alone, a threefold increase in monomer conversion was detected and, more significantly, ÐM decreased by half, from 2.65 to 1.30, and isotacticity increased. The water solutions of the PVPAs were cast on a glass plate and allowed to stand at room temperature for seven days. After drying, the PVPA (Mn = 5.0 kDa, m = 52%), prepared through the radical polymerization, became viscous liquids, whereas PVPA (Mn = 5.5 kDa, m = 67%), prepared through the anionic process, formed self-standing transparent film. In this way, the quality of the PVPA obtained at -78 °C with the use of t BuLi/ n Bu3Al initiator is clearly-in the proper sense of the word-illustrated by Figure 2. A similar approach to PVPA via anionic polymerization of CH 2 =CHP(O)(OMe) 2 with subsequent hydrolysis was implemented by Takeichi et al. [77] with the use of t BuLi or t BuLi/ n Bu 3 Al (1:5 mol/mol) as an initiator at the first stage (polymerization was conducted in toluene media), and conc. HCl with 12 h of reflux at the second stage. When polymerization was initiated by t BuLi/ n Bu 3 Al instead of t BuLi alone, a threefold increase in monomer conversion was detected and, more significantly, Ð M decreased by half, from 2.65 to 1.30, and isotacticity increased. The water solutions of the PVPAs were cast on a glass plate and allowed to stand at room temperature for seven days. After drying, the PVPA (M n = 5.0 kDa, m = 52%), prepared through the radical polymerization, became viscous liquids, whereas PVPA (M n = 5.5 kDa, m = 67%), prepared through the anionic process, formed self-standing transparent film. In this way, the quality of the PVPA obtained at −78 • C with the use of t BuLi/ n Bu 3 Al initiator is clearly-in the proper sense of the word-illustrated by Figure 2. Both free-radical and anionic polymerization of CH2=CHP(O)(OR)2 are usually not able to provide high monomer conversions and desirable molecular weight characteristics and microstructure of the polymer. In polyolefin chemistry, a similar problem was effectively solved by the use of coordination catalysis. However, conventional Ziegler-Natta and single-site catalysts, suitable for α-olefin polymerization, cannot be applied in the coordination polymerization of phosphonates due to the high electron donation ability of the oxygen atom of →P=O fragment. To date, only rare earth metal complexes were used successfully to polymerize dialkyl vinyl phosphonates.
In 2010 [78], Rabe and Coll. reported that rare earth metal amides of the formula [N(SiHMe 2 ) 2 ] 3 (THF) 2 (Ln = La, Nd, Sm) catalyze polymerization of CH 2 =CHP(O)(OEt) 2 with a formation of high-MW isotactic polymers (M n = 65-84 kDa, Ð M = 3.1-3.6, mm = 66-79%). A corresponding Y complex was found to be inactive in polymerization, forming a stable adduct [N(SiHMe 2 ) 2 ] 3 [CH 2 =CHP(O)(OEt) 2 ] 2 . In the same year, Rieger and Coll. described the first example of metallocene-catalyzed polymerization of CH 2 =CHP(O)(OEt) 2 [79]. The complexes (η 5 -C 5 H 5 ) 2 YbX (Cp 2 YbX, X = Cl, Me) have demonstrated high activities in toluene reaction media, polymerization had the 'living' character, and M w up to 1280 kDa were achieved. Already in this first work, Rieger et al. proposed a group-transfer mechanism of polymerization (Scheme 15) that was confirmed and discussed in subsequent research articles [80][81][82][83][84][85][86] and reviews [87,88] of this scientific group. Both free-radical and anionic polymerization of CH2=CHP(O)(OR)2 are usually no able to provide high monomer conversions and desirable molecular weight characteris tics and microstructure of the polymer. In polyolefin chemistry, a similar problem was effectively solved by the use of coordination catalysis. However, conventional Zieg ler-Natta and single-site catalysts, suitable for α-olefin polymerization, cannot be applied in the coordination polymerization of phosphonates due to the high electron donation ability of the oxygen atom of →P=O fragment. To date, only rare earth metal complexes were used successfully to polymerize dialkyl vinyl phosphonates.
In 2010 [78], Rabe and Coll. reported that rare earth metal amides of the formula [N(SiHMe2  [79]. The complexes (η 5 -C5H5)2YbX (Cp2YbX, X = Cl, Me) have demonstrated high activities in toluene reaction media, polymerization had the 'living character, and Mw up to 1280 kDa were achieved. Already in this first work, Rieger et al proposed a group-transfer mechanism of polymerization (Scheme 15) that was confirmed and discussed in subsequent research articles [80][81][82][83][84][85][86] and reviews [87,88] of this scientific group. When using Cp3Ln complexes (Ln = Lu, Yb, Tm, Er, Ho, Dy) as coordination cata lysts of CH2=CHP(O)(OEt)2 polymerization, C5H5 fragment acted as an initiator of the chain growth (Scheme 16) [80]. Polymerization had the 'living' character, polymers with given Mn (60-710 kDa depending on monomer-to-catalyst ratio) and ÐM = 1.05-1.36 were obtained. Corresponding PVPAs were then prepared for the reaction with Me3SiBr, fol lowed by mild hydrolysis (HCl/MeOH). Dimethyl and diisopropyl vinyl phosphonates were also polymerized. DCS studies have shown that CH2=CHP(O)(OR)2-based polymers decompose at 280-340 °C (R = Et) and 245-270 °C (R = i Pr) with olefin elimination and formation of PVPA. When using Cp3Yb catalyst, highly statistic copolymers o CH2=CHP(O)(OR)2 (R = Me, Et, n Pr) were obtained [81]. When using Cp 3 Ln complexes (Ln = Lu, Yb, Tm, Er, Ho, Dy) as coordination catalysts of CH 2 =CHP(O)(OEt) 2 polymerization, C 5 H 5 fragment acted as an initiator of the chain growth (Scheme 16) [80]. Polymerization had the 'living' character, polymers with given M n (60-710 kDa depending on monomer-to-catalyst ratio) and Ð M = 1.05-1.36 were obtained. Corresponding PVPAs were then prepared for the reaction with Me 3 SiBr, followed by mild hydrolysis (HCl/MeOH). Dimethyl and diisopropyl vinyl phosphonates were also polymerized. DCS studies have shown that CH 2 =CHP(O)(OR) 2 -based polymers decompose at 280-340 • C (R = Et) and 245-270 • C (R = i Pr) with olefin elimination and formation of PVPA. When using Cp 3 Yb catalyst, highly statistic copolymers of CH 2 =CHP(O)(OR) 2 (R = Me, Et, n Pr) were obtained [81]. Since Cp2YbX-catalyzed polymerization of acrylates and CH2=CHP(O)(OEt)2 proceed according to similar group-transfer mechanisms, a surface-initiated group transfer polymerization (SI-GTP), which allows the covalent modification of solids with dense poly(vinylphosphonate) brushes, was carried out [89]. Silicon surfaces were modified with methacrylate functionalities, either via a self-assembled monolayer of 3-(trimethoxysilyl)propyl methacrylate or via a poly(ethylene glycol dimethacrylate) film (prepared by self-initiated photografting and photopolymerization), the surfaces were treated with Cp2YbMe, and then by vinyl phosphonate monomer. After Me3SiBr and Me3SiBr treatment, hydrophilic PVPA surfaces formed. A similar approach was realized using cross-linked polystyrene microspheres [90] (Figure 3). As a result of the mechanistic studies of polymerization of CH2=CHP(O)(OR)2 [82] it was demonstrated that initiation by Cp2LnX follows a complex reaction pathway depending on the nature of X. For X = Me, CH2SiMe3 initiation occurs via the abstraction of the acidic α-CH of the vinylphosphonate, and for X = Cp, SR initiation occurs via the nucleophilic transfer of X to a coordinated monomer. For X = Cl, OR a monomer-induced ligand-exchange reaction with a formation of active Cp3Ln catalyst was observed. The further elemental steps of the reaction are presented in Figure 4 [82]. Since Cp 2 YbX-catalyzed polymerization of acrylates and CH 2 =CHP(O)(OEt) 2 proceed according to similar group-transfer mechanisms, a surface-initiated group transfer polymerization (SI-GTP), which allows the covalent modification of solids with dense poly(vinylphosphonate) brushes, was carried out [89]. Silicon surfaces were modified with methacrylate functionalities, either via a self-assembled monolayer of 3-(trimethoxysilyl)pro pyl methacrylate or via a poly(ethylene glycol dimethacrylate) film (prepared by selfinitiated photografting and photopolymerization), the surfaces were treated with Cp 2 YbMe, and then by vinyl phosphonate monomer. After Me 3 SiBr and Me 3 SiBr treatment, hydrophilic PVPA surfaces formed. A similar approach was realized using cross-linked polystyrene microspheres [90] (Figure 3). Since Cp2YbX-catalyzed polymerization of acrylates and CH2=CHP(O)(OEt)2 proceed according to similar group-transfer mechanisms, a surface-initiated group transfer polymerization (SI-GTP), which allows the covalent modification of solids with dense poly(vinylphosphonate) brushes, was carried out [89]. Silicon surfaces were modified with methacrylate functionalities, either via a self-assembled monolayer of 3-(trimethoxysilyl)propyl methacrylate or via a poly(ethylene glycol dimethacrylate) film (prepared by self-initiated photografting and photopolymerization), the surfaces were treated with Cp2YbMe, and then by vinyl phosphonate monomer. After Me3SiBr and Me3SiBr treatment, hydrophilic PVPA surfaces formed. A similar approach was realized using cross-linked polystyrene microspheres [90] (Figure 3). As a result of the mechanistic studies of polymerization of CH2=CHP(O)(OR)2 [82] it was demonstrated that initiation by Cp2LnX follows a complex reaction pathway depending on the nature of X. For X = Me, CH2SiMe3 initiation occurs via the abstraction of the acidic α-CH of the vinylphosphonate, and for X = Cp, SR initiation occurs via the nucleophilic transfer of X to a coordinated monomer. For X = Cl, OR a monomer-induced ligand-exchange reaction with a formation of active Cp3Ln catalyst was observed. The further elemental steps of the reaction are presented in Figure 4 [82]. As a result of the mechanistic studies of polymerization of CH 2 =CHP(O)(OR) 2 [82] it was demonstrated that initiation by Cp 2 LnX follows a complex reaction pathway depending on the nature of X. For X = Me, CH 2 SiMe 3 initiation occurs via the abstraction of the acidic α-CH of the vinylphosphonate, and for X = Cp, SR initiation occurs via the nucleophilic transfer of X to a coordinated monomer. For X = Cl, OR a monomer-induced ligand-exchange reaction with a formation of active Cp 3 Ln catalyst was observed. The further elemental steps of the reaction are presented in Figure 4 [82].
Since the initiation stage of Cp 2 LnX-mediated polymerization of CH 2 =CHP(O)(OR) 2 , this stage is significantly slower than propagation stages (leading to the broadening of MWD and partial loss of the polymer chain control), subsequent studies were focused on the development of highly efficient initiators. In that capacity, Cp 2 Ln derivatives of 2,4,6-trimethylpyridine were proposed [83]. The first stage of the process is presented in  Since the initiation stage of Cp2LnX-mediated polymerization of CH2=CHP(O)(OR)2, this stage is significantly slower than propagation stages (leading to the broadening of MWD and partial loss of the polymer chain control), subsequent studies were focused on the development of highly efficient initiators. In that capacity, Cp2Ln derivatives of 2,4,6-trimethylpyridine were proposed [83]. The first stage of the process is presented in Scheme 17. Polymerization experiments have demonstrated the absence of the induction period when using this new initiator. The concept of the efficient initiator of rare earth metal-mediated group transfer polymerization was beautifully realized by the example of the core-first polymer synthesis [85]. Based on 1,3-(or 1,4-bis-) and 1,3,5-tris(2,6-dimethylpyridin-4-yl)benzene, Cp2Y complexes (Scheme 18) were obtained and used as initiators of the group transfer polymerization of CH2=CHP(O)(OEt)2. When using dinuclear complexes, bimodal polymer distribution differing in molecular weight by a factor of two was detected. In the case of the trinuclear complex, trimodal molecular weight distribution was observed.  Since the initiation stage of Cp2LnX-mediated polymerization of CH2=CHP(O)(OR)2, this stage is significantly slower than propagation stages (leading to the broadening of MWD and partial loss of the polymer chain control), subsequent studies were focused on the development of highly efficient initiators. In that capacity, Cp2Ln derivatives of 2,4,6-trimethylpyridine were proposed [83]. The first stage of the process is presented in Scheme 17. Polymerization experiments have demonstrated the absence of the induction period when using this new initiator. The concept of the efficient initiator of rare earth metal-mediated group transfer polymerization was beautifully realized by the example of the core-first polymer synthesis [85]. Based on 1,3-(or 1,4-bis-) and 1,3,5-tris(2,6-dimethylpyridin-4-yl)benzene, Cp2Y complexes (Scheme 18) were obtained and used as initiators of the group transfer polymerization of CH2=CHP(O)(OEt)2. When using dinuclear complexes, bimodal polymer distribution differing in molecular weight by a factor of two was detected. In the case of the trinuclear complex, trimodal molecular weight distribution was observed. The concept of the efficient initiator of rare earth metal-mediated group transfer polymerization was beautifully realized by the example of the core-first polymer synthesis [85]. Based on 1,3-(or 1,4-bis-) and 1,3,5-tris(2,6-dimethylpyridin-4-yl)benzene, Cp 2 Y complexes (Scheme 18) were obtained and used as initiators of the group transfer polymerization of CH 2 =CHP(O)(OEt) 2 . When using dinuclear complexes, bimodal polymer distribution differing in molecular weight by a factor of two was detected. In the case of the trinuclear complex, trimodal molecular weight distribution was observed. Rieger and Coll. also drew attention to another important aspect of lanthanidocene-initiated polymerization of CH2=CHP(O)(OR)2, namely, steric factors ( Figure 5) [84]. As a result of the metal−ligand interactions, the studied catalysts varied in their properties, ranging from inert (Cp3Ln, Ln = Tb, Sm) to highly active ((C5H4Me)3Y. (C5Me4H)3Sm
Rieger and Coll. also drew attention to another important aspect of lanthanidoceneinitiated polymerization of CH 2 =CHP(O)(OR) 2 , namely, steric factors ( Figure 5) [84]. As a result of the metal−ligand interactions, the studied catalysts varied in their properties, ranging from inert (Cp 3 Ln, Ln = Tb, Sm) to highly active ((C 5 H 4 Me) 3 Y. (C 5 Me 4 H) 3 Sm was the first example of the active 'early' lanthanidocenes, and in general, the activities accelerated with decreasing cation size. Furthermore, the polymerization behaviors of (C 5 Me 4 H) 3 Ln complexes differed from unsubstituted or monosubstituted metallocenes. The pentacoordinate intermediates of these complexes exhibited lengthened metal-monomer bond lengths, resulting in a higher enthalpy ∆H = term, and are partly compensated by lower ∆S = contributions to the activation barrier. Rieger and Coll. also drew attention to another important aspect of lanthanidocene-initiated polymerization of CH2=CHP(O)(OR)2, namely, steric factors ( Figure 5) [84]. As a result of the metal−ligand interactions, the studied catalysts varied in their properties, ranging from inert (Cp3Ln, Ln = Tb, Sm) to highly active ((C5H4Me)3Y. (C5Me4H)3Sm was the first example of the active 'early' lanthanidocenes, and in general, the activities accelerated with decreasing cation size. Furthermore, the polymerization behaviors of (C5Me4H)3Ln complexes differed from unsubstituted or monosubstituted metallocenes. The pentacoordinate intermediates of these complexes exhibited lengthened metal-monomer bond lengths, resulting in a higher enthalpy ΔH ≠ term, and are partly compensated by lower ΔS ≠ contributions to the activation barrier.  In their recent publication, Rieger and Coll. described the synthesis and catalytic behavior of half-sandwich 'constrained geometry' complexes of Y and Al in the polymerization of CH2=CHP(O)(OEt)2 [86]. The complexes of Y (Scheme 20) have demonstrated high activity even at -78 °C, under these conditions highly isotactic polymer (mmm >98%) was obtained. The proposed stereocontrol mechanism is presented in Figure 6. In their recent publication, Rieger and Coll. described the synthesis and catalytic behavior of half-sandwich 'constrained geometry' complexes of Y and Al in the polymerization of CH 2 =CHP(O)(OEt) 2 [86]. The complexes of Y (Scheme 20) have demonstrated high activity even at −78 • C, under these conditions highly isotactic polymer (mmm > 98%) was obtained. The proposed stereocontrol mechanism is presented in Figure 6.
In their recent publication, Rieger and Coll. described behavior of half-sandwich 'constrained geometry' compl polymerization of CH2=CHP(O)(OEt)2 [86]. The complexe demonstrated high activity even at -78 °C, under these cond mer (mmm >98%) was obtained. The proposed stereocontrol Figure 6. Scheme 20. Efficient constrained-geometry catalysts for 'living' pol nates [86]. In conclusion, it is important to notice that the treatmen mild hydrolysis, or multi-hour reflux in HCl is not the onl poly(phosphonates) to PVPA. High efficiency of the use o cationites in 'wet' (hydrolysis) and 'dry' (olefin elimination phosphonates to phosphonic acids was demonstrated by H synthetic approaches to the hydrolysis of phosphinates and viewed very recently [94], and nothing prevents researchers f the synthesis of PVPA and other sidechain PCPAs. Scheme 20. Efficient constrained-geometry catalysts for 'living' polymerization of vinyl phosphonates [86]. Scheme 19. Six-membered initiation mechanism for 2-vinylpyridine and Y chelate complexes in polymerization of CH2=CHP(O)(OR)2 (R = Et, i Pr) [91].
In their recent publication, Rieger and Coll. described the synthesis and catalytic behavior of half-sandwich 'constrained geometry' complexes of Y and Al in the polymerization of CH2=CHP(O)(OEt)2 [86]. The complexes of Y (Scheme 20) have demonstrated high activity even at -78 °C, under these conditions highly isotactic polymer (mmm >98%) was obtained. The proposed stereocontrol mechanism is presented in Figure 6. Scheme 20. Efficient constrained-geometry catalysts for 'living' polymerization of vinyl phosphonates [86]. In conclusion, it is important to notice that the treatment with Me3SiBr, followed by mild hydrolysis, or multi-hour reflux in HCl is not the only method for transforming poly(phosphonates) to PVPA. High efficiency of the use of CF3SO3H or highly acidic cationites in 'wet' (hydrolysis) and 'dry' (olefin elimination) transformation of dialkyl phosphonates to phosphonic acids was demonstrated by Han and Coll. [93]. Different synthetic approaches to the hydrolysis of phosphinates and phosphonates have been reviewed very recently [94], and nothing prevents researchers from using these methods in the synthesis of PVPA and other sidechain PCPAs. In conclusion, it is important to notice that the treatment with Me 3 SiBr, followed by mild hydrolysis, or multi-hour reflux in HCl is not the only method for transforming poly(phosphonates) to PVPA. High efficiency of the use of CF 3 SO 3 H or highly acidic cationites in 'wet' (hydrolysis) and 'dry' (olefin elimination) transformation of dialkyl phosphonates to phosphonic acids was demonstrated by Han and Coll. [93]. Different synthetic approaches to the hydrolysis of phosphinates and phosphonates have been reviewed very recently [94], and nothing prevents researchers from using these methods in the synthesis of PVPA and other sidechain PCPAs.

Copolymerization of VPA and VPA Derivatives with Other Vinyl Monomers
Since VPA homopolymers have the prospective but limited potential of applications, valuable works on the synthesis of copolymers containing -CH 2 CHP(O)(OH) 2 -fragments were published even at the end of the last century.
The free-radical copolymerization of acrylic acid and VPA was conducted by Budd and Coll. in aqueous media (Scheme 21), AIBA was used as an initiator [95]. As the VPA content in the feed was increased, the monomer conversion and yield of the copolymers showed a general decrease. The reactivity ratios of acrylic acid (r 1 ) and VPA (r 2 ) were 4.09 and 0.042, respectively. Such a high difference in r 1 and r 2 values may give rise to composition drift, where the composition of the copolymer changes as the polymerization proceeds. Where the VPA content in the feed was below 50%, a chain transfer agent was introduced into the polymerization to restrict the molecular weight. Using this method, a range of copolymer compositions were produced with consistent molecular weights (M w = 150-200 kDa) up to a VPA content of 59 mol%. At higher VPA contents, high-MW polymers were not obtained, and the highest M w for VPA homopolymer was 29 kDa. and 0.042, respectively. Such a high difference in r1 and r2 values may give rise to composition drift, where the composition of the copolymer changes as the polymerization proceeds. Where the VPA content in the feed was below 50%, a chain transfer agent was introduced into the polymerization to restrict the molecular weight. Using this method, a range of copolymer compositions were produced with consistent molecular weights (Mw = 150-200 kDa) up to a VPA content of 59 mol %. At higher VPA contents, high-MW polymers were not obtained, and the highest Mw for VPA homopolymer was 29 kDa. Scheme 21. Free-radical copolymerization of acrylic acid and VPA [95].
RAFT/MADIX approach was used in the synthesis of poly(acrylamide)-b-PVPA copolymers (Scheme 22) [96] with a given length of poly(acrylamide) block and varied length of PVPA fragment, copolymers with Mn 5.5-11.4 kDa were obtained.
When using ethylene glycol diacrylate, cross-linked copolymers of acrylic acid and VPA were obtained [97]. Copolymers of VPA and 1-vinyl-1,2,4-triazole with 1:1, 1:2, and 2:1 comonomer ratios were obtained in DMF solution at 85 °C with AIBN initiator, the Mn values ranged from 6.0 to 8.2 kDa, the dispersity ÐM was ~2 [98]. Copolymerization of VPA and methacrylic ester of mPEG 475 was carried out in ethyl acetate with the use of AIBN as an initiator, side reactions and gel formation were detected [99].
UV-initiated copolymerization of VPA and acrylamide at the oxidized silicon surface in the presence of 2,2-dimethoxy-2-phenylacetophenone (DMPA) was described in [100], the binding of the copolymer with the surface was confirmed by photoelectron spectroscopy.
RAFT/MADIX approach was used in the synthesis of poly(acrylamide)-b-PVPA copolymers (Scheme 22) [96] with a given length of poly(acrylamide) block and varied length of PVPA fragment, copolymers with M n 5.5-11.4 kDa were obtained. position drift, where the composition of the copolymer changes as the polymerization proceeds. Where the VPA content in the feed was below 50%, a chain transfer agent was introduced into the polymerization to restrict the molecular weight. Using this method, a range of copolymer compositions were produced with consistent molecular weights (Mw = 150-200 kDa) up to a VPA content of 59 mol %. At higher VPA contents, high-MW polymers were not obtained, and the highest Mw for VPA homopolymer was 29 kDa. Scheme 21. Free-radical copolymerization of acrylic acid and VPA [95].
RAFT/MADIX approach was used in the synthesis of poly(acrylamide)-b-PVPA copolymers (Scheme 22) [96] with a given length of poly(acrylamide) block and varied length of PVPA fragment, copolymers with Mn 5.5-11.4 kDa were obtained.
When using ethylene glycol diacrylate, cross-linked copolymers of acrylic acid and VPA were obtained [97]. Copolymers of VPA and 1-vinyl-1,2,4-triazole with 1:1, 1:2, and 2:1 comonomer ratios were obtained in DMF solution at 85 °C with AIBN initiator, the Mn values ranged from 6.0 to 8.2 kDa, the dispersity ÐM was ~2 [98]. Copolymerization of VPA and methacrylic ester of mPEG 475 was carried out in ethyl acetate with the use of AIBN as an initiator, side reactions and gel formation were detected [99].
UV-initiated copolymerization of VPA and acrylamide at the oxidized silicon surface in the presence of 2,2-dimethoxy-2-phenylacetophenone (DMPA) was described in [100], the binding of the copolymer with the surface was confirmed by photoelectron spectroscopy.
UV-initiated copolymerization of VPA and acrylamide at the oxidized silicon surface in the presence of 2,2-dimethoxy-2-phenylacetophenone (DMPA) was described in [100], the binding of the copolymer with the surface was confirmed by photoelectron spectroscopy.
The syntheses of VPA copolymers with 2-deoxy-2-methacrylamido-D-glucose, 4acryloylmorpholine, or acrylamide, were the subject of the recent study of Nazarova and Coll. [102]. The reactions were conducted in DMF or MeOH (AIBN initiator) or aqueous media (AIBA initiator). VPA has demonstrated values of reactivity comparable with 4-acryloylmorpholine and acrylamide, thus confirming the preference for the use of VPA instead of VPA esters in copolymerization.
As a final note, the use of rare-earth metal complexes in the synthesis of copolymers of vinyl phosphonates was the subject of the recent review of Rieger et al. [88].

Homopolymerization and Copolymerization of Phosphorylated Acrylates
Derivatives of acrylic and methacrylic acid, containing -OP(O)(OH) 2 and -P(O)(OH) 2 fragments, have been evidently regarded as prospective monomers for the synthesis of sidechain PCPAs. There is extensive literature on this subject, and in this section, we have tried to present the most interesting and recent works in this field.
Evidently, one of the common methods of the polymerization of acrylates-anionic polymerization-is not applicable for derivatives of phosphoric and phosphinic acids, and the vast majority of research has used free-radical polymerization in one way or another. Trivial methods of free-radical polymerization (solution process, azo compounds, peroxides or UV exposure as initiators, no CTAs or other additives) are fully applicable to phosphorylated and phosphonated acrylates. This is particularly true in the case of acrylates, containing the phosphorus atom in an alkoxy fragment of the acrylate molecule (Scheme 4), due to the high reactivity of these monomers, and a number of examples of the homo-and co-polymerization of phosphorylated and phosphonated (meth)acrylates can be cited [22,23,25,26,28,30,31,[37][38][39][106][107][108]. Note that the studies of AIBN-initiated copolymerization of methyl methacrylate and CH 2 =C(Me)C(O)OCH 2 P(O)(OMe)OH showed r 1 and r 2 values of 0.98 and 1.03, respectively, thus confirming close reactivity of 'conventional' and phosphonated acrylates [30].
On the other hand, RAFT homo-and co-polymerization were successfully applied to similar acrylate monomers [29,33,109]. In particular, zwitterionic diblock copolymers were synthesized by copolymerization of the macro-RAFT agent, PMEMA (Scheme 23) with methacrylate monomers MOEP and MMPN via RAFT polymerization [29].

Homopolymerization and Copolymerization of Phosphorylated Acrylates
Derivatives of acrylic and methacrylic acid, containing -OP(O)(OH)2 and -P(O)(OH)2 fragments, have been evidently regarded as prospective monomers for the synthesis of sidechain PCPAs. There is extensive literature on this subject, and in this section, we have tried to present the most interesting and recent works in this field.
Evidently, one of the common methods of the polymerization of acrylates-anionic polymerization-is not applicable for derivatives of phosphoric and phosphinic acids, and the vast majority of research has used free-radical polymerization in one way or another. Trivial methods of free-radical polymerization (solution process, azo compounds, peroxides or UV exposure as initiators, no CTAs or other additives) are fully applicable to phosphorylated and phosphonated acrylates. This is particularly true in the case of acrylates, containing the phosphorus atom in an alkoxy fragment of the acrylate molecule (Scheme 4), due to the high reactivity of these monomers, and a number of examples of the homo-and co-polymerization of phosphorylated and phosphonated (meth)acrylates can be cited [22,23,25,26,28,30,31,[37][38][39][106][107][108]. Note that the studies of AIBN-initiated copolymerization of methyl methacrylate and CH2=C(Me)C(O)OCH2P(O)(OMe)OH showed r1 and r2 values of 0.98 and 1.03, respectively, thus confirming close reactivity of 'conventional' and phosphonated acrylates [30].

Homopolymerization and Copolymerization of Other Vinyl Monomers
Copolymers of CF2=CF2, CF2=CF(C3F7) and CF2=CFO(CF2)3P(O)(OMe)2 were obtained with the use of AIBN-initiated reaction in 1,1,2-trichloro-1,2,2-trifuoroethane (R-113) media [48]. These copolymers as such have not demonstrated outstanding characteristics, but, nevertheless, a very significant chemical aspect should be mentioned here. Whereas hydrolysis of -P(O)(OR)2-functionalized polymers is not accompanied by noteworthy side reactions, hydrolytic cleavage of the -CF2P(O)(OMe)2 fragment is not so straightforward (Scheme 27). Under basic conditions, the cleavage of the C-P bond was observed, but acidic hydrolysis resulted in the formation of the phosphinic acid.

Homopolymerization and Copolymerization of Other Vinyl Monomers
Copolymers of CF 2 =CF 2 , CF 2 =CF(C 3 F 7 ) and CF 2 =CFO(CF 2 ) 3 P(O)(OMe) 2 were obtained with the use of AIBN-initiated reaction in 1,1,2-trichloro-1,2,2-trifuoroethane (R-113) media [48]. These copolymers as such have not demonstrated outstanding characteristics, but, nevertheless, a very significant chemical aspect should be mentioned here. Whereas hydrolysis of -P(O)(OR) 2 -functionalized polymers is not accompanied by noteworthy side reactions, hydrolytic cleavage of the -CF 2 P(O)(OMe) 2 fragment is not so straightforward (Scheme 27). Under basic conditions, the cleavage of the C-P bond was observed, but acidic hydrolysis resulted in the formation of the phosphinic acid.
tained with the use of AIBN-initiated reaction in 1,1,2-trichloro-1,2,2-trifuoroethane (R-113) media [48]. These copolymers as such have not demonstrated outstanding characteristics, but, nevertheless, a very significant chemical aspect should be mentioned here. Whereas hydrolysis of -P(O)(OR)2-functionalized polymers is not accompanied by noteworthy side reactions, hydrolytic cleavage of the -CF2P(O)(OMe)2 fragment is not so straightforward (Scheme 27). Under basic conditions, the cleavage of the C-P bond was observed, but acidic hydrolysis resulted in the formation of the phosphinic acid. Scheme 27. Hydrolysis of perfluoroalkyl phosphonate fragment [48].
For the synthesis of homopolymers of phosphonated styrenes SP and SbP (Scheme 9) and their block copolymers with poly(isobutylene) Park and Coll. used ATRP in toluene media with CuCl/N,N,N′,N″,N″-pentamethyldiethylenetriamine catalytic system [51]. Corresponding PCPAs were obtained by treatment with Me3SiBr/CHCl3 (36 h at 40 °C) followed by 8 h of methanolysis. Alter and Hoge [50]

Cyclopolymerization
Starting from diallylamine, both linear and cross-linked PCPAs were synthesized by Al Hamouz and Ali [115] by free-radical diene cyclopolymerization approach (Scheme 28). Treatment of the polymers by NaOH resulted in anionic polyelectrolytes that have an excellent adsorption capacity for metal ions (see Section 3.3).

Cyclopolymerization
Starting from diallylamine, both linear and cross-linked PCPAs were synthesized by Al Hamouz and Ali [115] by free-radical diene cyclopolymerization approach (Scheme 28). Treatment of the polymers by NaOH resulted in anionic polyelectrolytes that have an excellent adsorption capacity for metal ions (see Section 3.3).

Direct Phosphonation of 'Saturated' Polymers
The reaction of saturated hydrocarbons with PCl3 and molecular oxygen results in the phosphonation of some of the carbon atoms in paraffin [116]. This reaction is also applicable to polyolefins [117]. To a first approximation, saturated hydrocarbons form alkylphosphonyl chlorides by the overall reaction, presented in Equation (1), and the R-P(O)Cl2 can further be hydrolyzed to the corresponding phosphonic acid. This reaction requires an excess of PCl3 and is difficult to control. Bulk phosphonation negatively affects the mechanical characteristics of the polymers [117]. Twenty years ago, Allan and Coll. reported the results of the study of surface phosphonation of low-density polyethylene. The most uniform surface treatment was achieved in the gas phase at 25 °C within 30 min [118]. Further studies in this field have not been conducted, apparently, Scheme 28. Synthesis of phosphonate-containing diene monomer and its free-radical diene cyclopolymerization [115].

Phosphonation and Phosphorylation of the Polymers 2.4.1. Direct Phosphonation of 'Saturated' Polymers
The reaction of saturated hydrocarbons with PCl 3 and molecular oxygen results in the phosphonation of some of the carbon atoms in paraffin [116]. This reaction is also applicable to polyolefins [117]. To a first approximation, saturated hydrocarbons form alkylphosphonyl chlorides by the overall reaction, presented in Equation (1), and the R-P(O)Cl 2 can further be hydrolyzed to the corresponding phosphonic acid. This reaction requires an excess of PCl 3 and is difficult to control. Bulk phosphonation neg-atively affects the mechanical characteristics of the polymers [117]. Twenty years ago, Allan and Coll. reported the results of the study of surface phosphonation of low-density polyethylene. The most uniform surface treatment was achieved in the gas phase at 25 • C within 30 min [118]. Further studies in this field have not been conducted, apparently, due to the low environmental friendliness of the process and the complexity of controlling the properties of the materials obtained.

Modification of the Reactive -OH Groups in the Polymer Backbone
Double-hydrophilic copolymers containing nonionic PEG fragments and ionic phosphorylated polyglycidol blocks were synthesized by Penczek and Coll. [119,120] by the phosphorylation of the polymer obtained previously by mPEG-initiated polymerization of CH 2 =CHOMe-protected glycidol [121,122] (Scheme 29).
the phosphonation of some of the carbon atoms in paraffin [116]. This reaction is also applicable to polyolefins [117]. To a first approximation, saturated hydrocarbons form alkylphosphonyl chlorides by the overall reaction, presented in Equation (1), (1) and the R-P(O)Cl2 can further be hydrolyzed to the corresponding phosphonic acid. This reaction requires an excess of PCl3 and is difficult to control. Bulk phosphonation negatively affects the mechanical characteristics of the polymers [117]. Twenty years ago, Allan and Coll. reported the results of the study of surface phosphonation of low-density polyethylene. The most uniform surface treatment was achieved in the gas phase at 25 °C within 30 min [118]. Further studies in this field have not been conducted, apparently, due to the low environmental friendliness of the process and the complexity of controlling the properties of the materials obtained.

Modification of the Reactive -OH Groups in the Polymer Backbone
Double-hydrophilic copolymers containing nonionic PEG fragments and ionic phosphorylated polyglycidol blocks were synthesized by Penczek and Coll. [119,120] by the phosphorylation of the polymer obtained previously by mPEG-initiated polymerization of CH2=CHOMe-protected glycidol [121,122] (Scheme 29).
The alternative method of functionalization of polyglycidol block is based on the reaction with ethyl 2-(diethoxyphosphoryl)acrylate, followed by hydrolysis (Scheme 30) [123]. The reaction of the -OH groups with ethyl 2-(diethoxyphosphoryl)acrylate did not require catalysts and was completed at 25 • C in THF or CH 2 Cl 2 after 1 day. Such an approach has an advantage due to the hydrolytic stability of the C-P bond, but the issue of the toxicity of copolymer remains open. Another example of double-hydrophilic block copolymers, containing PEG fragment and hydrocarbon chain with -CH2CH2OP(O)(OH)2 substituents, was also synthesized by Penczek's group [122] by post-modification of the block copolymer of oxirane and buta-1,3-diene (Scheme 31), obtained previously using s BuLi/phosphazene initiator [124]. Note that this strategy was reported later by Dimova and Coll. [125] who described the same method for the synthesis of block copolymers. Another example of double-hydrophilic block copolymers, containing PEG fragment and hydrocarbon chain with -CH 2 CH 2 OP(O)(OH) 2 substituents, was also synthesized by Penczek's group [122] by post-modification of the block copolymer of oxirane and buta-1,3-diene (Scheme 31), obtained previously using s BuLi/phosphazene initiator [124]. Note that this strategy was reported later by Dimova and Coll. [125] who described the same method for the synthesis of block copolymers.
However, one should not forget about an even simpler and more accessible polymer, poly(vinyl alcohol). Its phosphorylation was carried out by the reaction of poly(vinyl alcohol) (M w = 76 kDa) with~60% aq. H 3 PO 4 (1 h, reflux), the product was separated using precipitation in MeOH [126]. Degree of phosphorylation was not determined in this work.
Another example of double-hydrophilic block copolymers, containing PEG fragment and hydrocarbon chain with -CH2CH2OP(O)(OH)2 substituents, was also synthesized by Penczek's group [122] by post-modification of the block copolymer of oxirane and buta-1,3-diene (Scheme 31), obtained previously using s BuLi/phosphazene initiator [124]. Note that this strategy was reported later by Dimova and Coll. [125] who described the same method for the synthesis of block copolymers.
However, one should not forget about an even simpler and more accessible polymer, poly(vinyl alcohol). Its phosphorylation was carried out by the reaction of poly(vinyl alcohol) (Mw = 76 kDa) with ~ 60% aq. H3PO4 (1 h, reflux), the product was separated using precipitation in MeOH [126]. Degree of phosphorylation was not determined in this work.  Kieczykowski et al. in 1995 [127]. This approach was used in the syn-Scheme 31. Synthesis and hydroboration of PEG-b-poly(buta-1,3-diene) to PEG-b-poly((2hydroxyethyl)ethylene), followed by phosphorylation [122]. Original reaction scheme, presented in [122], was corrected.

Modification Based on Michaelis-Arbuzov Reaction
The copolymer of CF 2 =CFCl with 2-chloroethyl vinyl ether of the altering microstructure was obtained by free-radical copolymerization and modified with the use of the Michaelis-Arbuzov reaction [129] (Scheme 32). Five copolymers with different phosphonic acid content were thus synthesized.

Modification Based on Michaelis-Arbuzov Reaction
The copolymer of CF2=CFCl with 2-chloroethyl vinyl ether of the altering microstructure was obtained by free-radical copolymerization and modified with the use of the Michaelis-Arbuzov reaction [129] (Scheme 32). Five copolymers with different phosphonic acid content were thus synthesized. Scheme 32. Synthetic pathway to graft phosphonic acid groups onto fluorinated copolymers obtained by radical copolymerization of CF2=CFCl with 2-chloroethyl vinyl ether [129].
The reaction, presented in Scheme 33, was also used for post-modification of the complex triblock copolymer, the product of the (i) polycondensation of Bisphenol M with 4,4'-sulfonylbis(chlorobenzene); (ii) treatment with 1,4-bis(bromomethyl)benzene; (iii) ATRP with pentafluorostyrene [136]. The structural formula of the copolymer thus obtained is presented in Scheme 34. The reaction, presented in Scheme 33, was also used for post-modification of the complex triblock copolymer, the product of the (i) polycondensation of Bisphenol M with 4,4 -sulfonylbis(chlorobenzene); (ii) treatment with 1,4-bis(bromomethyl)benzene; (iii) ATRP with pentafluorostyrene [136]. The structural formula of the copolymer thus obtained is presented in Scheme 34.

Other Methods
Poly(styrene-b-methylbutylene)s were synthesized by sequential anionic polymerization of styrene and isoprene, followed by selective hydrogenation of aliphatic C=C bonds. Bromination, cross-coupling reaction with HP(O)(OEt)2, and two-stage cleavage (Scheme 35) resulted in phosphonated copolymers with different content of the -P(O)(OH)2 groups [137,138].  Cross-coupling approach was also used in the post-modification of the Bisphenol A/4,4 -sulfonylbis(chlorobenzene) polycondensation product [139]  The original approach to cross-linked copolymers, derivatives of poly(vinylidene difluoride), proposed by Sinirlioglu et al. [140], is based on dehydrofluorination of -(CH2CF2)n-with a formation of unsaturated fragments, free radical-initiated graft copolymerization with glycidyl methacrylate, and the reaction of the oxirane fragments with PVPA at the final stage. Polymer membranes were obtained by evaporation of the polymer solutions in DMF.
Two routes for grafting of the VPA on flax fabrics (81 wt% of cellulose, 13 wt% of hemicelluloses, and 2.7 wt% of lignin) were studied in [141], namely, radiation grafting and chemical modification (Figure 7). These approaches were studied in order to improve flame retardant characteristics of the fibers, qualitatively different results were obtained for the methods used (see Section 3.5.1) The original approach to cross-linked copolymers, derivatives of poly(vinylidene difluoride), proposed by Sinirlioglu et al. [140], is based on dehydrofluorination of -(CH 2 CF 2 ) nwith a formation of unsaturated fragments, free radical-initiated graft copolymerization with glycidyl methacrylate, and the reaction of the oxirane fragments with PVPA at the final stage. Polymer membranes were obtained by evaporation of the polymer solutions in DMF.
Two routes for grafting of the VPA on flax fabrics (81 wt% of cellulose, 13 wt% of hemicelluloses, and 2.7 wt% of lignin) were studied in [141], namely, radiation grafting and chemical modification (Figure 7). These approaches were studied in order to improve flame retardant characteristics of the fibers, qualitatively different results were obtained for the methods used (see Section 3.5.1). The original approach to cross-linked copolymers, derivatives of poly(vinylidene difluoride), proposed by Sinirlioglu et al. [140], is based on dehydrofluorination of -(CH2CF2)n-with a formation of unsaturated fragments, free radical-initiated graft copolymerization with glycidyl methacrylate, and the reaction of the oxirane fragments with PVPA at the final stage. Polymer membranes were obtained by evaporation of the polymer solutions in DMF.
Two routes for grafting of the VPA on flax fabrics (81 wt% of cellulose, 13 wt% of hemicelluloses, and 2.7 wt% of lignin) were studied in [141], namely, radiation grafting and chemical modification (Figure 7). These approaches were studied in order to improve flame retardant characteristics of the fibers, qualitatively different results were obtained for the methods used (see Section 3.5.1)  Hydrolyzed polyvinyl alcohols (72 and 145 kDa) were phosphorylated using reactions with H 3 PO 4 /urea, with POCl 3 and subsequent hydrolysis, and with (MeO) 3 P/I 2 [142]. In the latter case, PCPAs were obtained by the reactions with NaI in N-methyl-2-pyrrolidone or via conventional silylation/methanolysis. Efficient mechanochemical phosphorylation of cellulose, lignin, PEG, poly(vinyl alcohol), and poly(vinyl chloride) using P 2 O 5 was described in [143]. Phosphate loadings of 0.2 kg·mol −1 were achieved for PEG and lignin, whereas for cellulose, poly(vinyl alcohol), and poly(vinyl chloride) phosphate loadings were 3.3, 4.4, and 2.2 kg·mol −1 , respectively.

Metathesis Polycondensation
Polyethylene' containing one -P(O)(OH) 2 substituent in 21 carbon atoms, was synthesized in three steps by Wagener and Coll. [144] (Scheme 37). The authors noted that compared to the typical oxidative phosphorylation reactions on polyethylene [118], the proposed method offers complete control of the microstructure, which will lead to a systematic understanding of how microstructure and resulting morphology dictate particular properties. However, the properties of the material obtained were not studied in depth due to the low solubility of the -P(O)(OH) 2 substituted PE (before deprotection, the M n was 19.5 kDa, and Ð M was 1.7).
Efficient mechanochemical phosphorylation of cellulo alcohol), and poly(vinyl chloride) using P2O5 was described i of ~0.2 kg•mol -1 were achieved for PEG and lignin, whereas cohol), and poly(vinyl chloride) phosphate loadings were 3 spectively.

Metathesis Polycondensation
Polyethylene' containing one -P(O)(OH)2 substituent in thesized in three steps by Wagener and Coll. [144] (Scheme compared to the typical oxidative phosphorylation reactions proposed method offers complete control of the microstru systematic understanding of how microstructure and resulti ticular properties. However, the properties of the material o depth due to the low solubility of the -P(O)(OH)2 substituted Mn was 19.5 kDa, and ÐM was 1.7). Scheme 37. Synthetic scheme of precisely functionalized polyethy every 21st carbon [144].

Ring-Opening Metathesis Polymerization
An efficient method of the synthesis of the phosp well-defined MWD, composition, and architecture was pro [146] based on synthetically available adducts of cyclopenta-1 Scheme 37. Synthetic scheme of precisely functionalized polyethylene with phosphonic acid on every 21st carbon [144].
Later, the Wagener group expanded a range of diene monomers by varying the methylene units between phosphonate and -CH=CH 2 fragments and a number of -P(O)(OR) 2 groups at the central carbon atom [145]. As a result, a series of diethyl phosphonate substituted 'polyethylenes' with different lengths of (CH 2 ) n spacers between -CHP(O)(OEt) 2 -or -C[P(O)(OEt) 2 ] 2 -fragments were obtained, without further transformation to PCPAs.

Ring-Opening Metathesis Polymerization
An efficient method of the synthesis of the phosphonated polymers with a welldefined MWD, composition, and architecture was proposed by Bingöl and Coll. [146] based on synthetically available adducts of cyclopenta-1,3-diene with maleimide or maleic anhydride (Scheme 38). Block-and stat-copolymers were also obtained with the use of n-Bu substituted imide. Note that -P(O)(OH) 2 -functionalized polymers were obtained by treatment with Me 3 SiBr in dry CH 2 Cl 2 to yield TMS esters, followed by cleavage in a MeOH/CH 2 Cl 2 mixture.

Nucleophilic Polycondensation
The high reactivity of the C-F bond in the p-position of RC6F5 was also exhibited in the reaction of perfluoro-1,1'-biphenyl with diphosphonated hydroquinone in the presence of K2CO3 [147] (Scheme 39). Copolymer with Mn = 28.4 kDa was obtained; intermediate modification of (2,5-dihydroxy-1,4-phenylene)diphosphonic acid by the reaction with n PrNCO resulted in dicarbamate derivative, more efficient in polycondensation (milder conditions, Mn = 37.9 kDa).

Nucleophilic Polycondensation
The high reactivity of the C-F bond in the p-position of RC 6 F 5 was also exhibited in the reaction of perfluoro-1,1 -biphenyl with diphosphonated hydroquinone in the presence of K 2 CO 3 [147] (Scheme 39). Copolymer with M n = 28.4 kDa was obtained; intermediate modification of (2,5-dihydroxy-1,4-phenylene)diphosphonic acid by the reaction with n PrNCO resulted in dicarbamate derivative, more efficient in polycondensation (milder conditions, M n = 37.9 kDa).

Nucleophilic Polycondensation
The high reactivity of the C-F bond in the p-position of RC6F5 was also exhibited in the reaction of perfluoro-1,1'-biphenyl with diphosphonated hydroquinone in the presence of K2CO3 [147] (Scheme 39). Copolymer with Mn = 28.4 kDa was obtained; intermediate modification of (2,5-dihydroxy-1,4-phenylene)diphosphonic acid by the reaction with n PrNCO resulted in dicarbamate derivative, more efficient in polycondensation (milder conditions, Mn = 37.9 kDa).

Physical State and Mechanical Properties
The physical state and characteristics of sidechain PCPAs can vary widely due to the diversity of the structures of macromolecules. Obviously, no one canceled the common patterns of the influence of the polymer microstructure on physicomechanical characteristics, but non-selective methods of the synthesis of sidechain PCPAs (mostly free-radical polymerization, see Section 2) make irrelevant the issue of polymer tacticity. Discussions about the influence of the polymer microstructure on polymer properties make sense only for well-researched polymers, synthesized by different methods, and PVPA is actually the only polymer in the group under consideration.
Depending on the molecular mass value, the samples of regioregular and atactic PVPA, obtained by free-radical polymerization, represent viscous liquid [77] or amorphous solid [66,149]. The sample morphology drastically changed with increasing water content. For example, for a relatively high-MW polymer (Mw = 62 kDa) up to ~45% relative humidity (RH) (~17% water sorption), the material remained a white powder. Above 45% RH, a transparent film was formed. With further increasing humidity, this film became sticky and turned into a gel at about 100% RH [149]. In the amorphous PVPA, no melting transition was detected, and a glass transition at ~220 °C was masked by dehydration with a formation of phosphonic acid anhydride [75] (on other data, for low-MW amorphous PVPA the glass temperature Tg = 141 °C [150]).
The behavior of cross-linked copolymer of HEMA, MOEP (0-100 mol% relative to HEMA), and BMEP (0.5 wt%) (see Scheme 4, obtained by γ-initiated free-radical polymerization, [108]), when immersed in water was found to be dependent on the fraction of MOEP in the polymer. The polymers with 0-20 mol % MOEP did not fracture during swelling and displayed concentration-dependent water sorption, while the copolymers with greater than 30 mol % MOEP exhibited catastrophic fracturing during swelling, resulting in the destruction of the sample geometry. In this way, with high content of acidic groups, even cross-linking does not ensure the stability of the copolymer shape (and this should be considered in developing formulations of hydrogels and composites).

Solution and Colloidal Behavior
The solution behavior of sidechain PCPAs mainly depends on the nature of the polymer backbone and the relative number of phosphonate (or phosphate) fragments. For example, PVPA is soluble in water and ethanol and can be purified by precipitation of the saturated ethanol solution in ethyl acetate [69]. Highly phosphonated PmPPA is soluble in water and water/alcohol mixtures but poorly soluble in pure methanol [148].
A high similarity of the solution behavior of poly(acrylic acid) and PVPA was demonstrated by Wegner and Coll. [151]. The results of the more recent study of the solution behavior of PVPA and random VPA/CH2=CHP(O)(OMe)2 copolymers by SEC-MALLS measurements [73] are presented in Table 1. The coefficients calculated from MHS plots were between 0.5 and 0.8 meaning that randomly coiled polymers were formed.

Physical State and Mechanical Properties
The physical state and characteristics of sidechain PCPAs can vary widely due to the diversity of the structures of macromolecules. Obviously, no one canceled the common patterns of the influence of the polymer microstructure on physicomechanical characteristics, but non-selective methods of the synthesis of sidechain PCPAs (mostly free-radical polymerization, see Section 2) make irrelevant the issue of polymer tacticity. Discussions about the influence of the polymer microstructure on polymer properties make sense only for well-researched polymers, synthesized by different methods, and PVPA is actually the only polymer in the group under consideration.
Depending on the molecular mass value, the samples of regioregular and atactic PVPA, obtained by free-radical polymerization, represent viscous liquid [77] or amorphous solid [66,149]. The sample morphology drastically changed with increasing water content. For example, for a relatively high-MW polymer (M w = 62 kDa) up to~45% relative humidity (RH) (~17% water sorption), the material remained a white powder. Above 45% RH, a transparent film was formed. With further increasing humidity, this film became sticky and turned into a gel at about 100% RH [149]. In the amorphous PVPA, no melting transition was detected, and a glass transition at~220 • C was masked by dehydration with a formation of phosphonic acid anhydride [75] (on other data, for low-MW amorphous PVPA the glass temperature T g = 141 • C [150]).
The behavior of cross-linked copolymer of HEMA, MOEP (0-100 mol% relative to HEMA), and BMEP (0.5 wt%) (see Scheme 4, obtained by γ-initiated free-radical polymerization, [108]), when immersed in water was found to be dependent on the fraction of MOEP in the polymer. The polymers with 0-20 mol% MOEP did not fracture during swelling and displayed concentration-dependent water sorption, while the copolymers with greater than 30 mol% MOEP exhibited catastrophic fracturing during swelling, resulting in the destruction of the sample geometry. In this way, with high content of acidic groups, even cross-linking does not ensure the stability of the copolymer shape (and this should be considered in developing formulations of hydrogels and composites).

Solution and Colloidal Behavior
The solution behavior of sidechain PCPAs mainly depends on the nature of the polymer backbone and the relative number of phosphonate (or phosphate) fragments. For example, PVPA is soluble in water and ethanol and can be purified by precipitation of the saturated ethanol solution in ethyl acetate [69]. Highly phosphonated PmPPA is soluble in water and water/alcohol mixtures but poorly soluble in pure methanol [148].
A high similarity of the solution behavior of poly(acrylic acid) and PVPA was demonstrated by Wegner and Coll. [151]. The results of the more recent study of the solution behavior of PVPA and random VPA/CH 2 =CHP(O)(OMe) 2 copolymers by SEC-MALLS measurements [73] are presented in Table 1. The coefficients calculated from MHS plots were between 0.5 and 0.8 meaning that randomly coiled polymers were formed. As demonstrated by Wegner et al. [57], while the VPA monomer shows the two dissociation steps expected, PVPA behaves as a monoprotic acid. The results of the study of copolymers of VPA and acrylic acid by potentiometric titration are presented in Figure 8 [95]. The nominal degrees of neutralization α of the poly(acrylic acid) (PVPA-0), copolymers containing 30 and 60 mol% of VPA (PVPA-30 and PVPA-60, respectively), poly(VPA) (PVPA-100) were calculated by taking into account elemental analysis data. The results of this study were in line with [57,65] with respect to PVPA. As opposed to the homopolymer, the titration curves of the copolymers showed two neutralization steps, which may be attributed to the contributions of VPA units with a pK a1 = 2.49 (step 1) and acrylic acid unit with a pK a2 = 7.74 (step 2).  As demonstrated by Wegner et al. [57], while the VPA monomer shows the two dissociation steps expected, PVPA behaves as a monoprotic acid. The results of the study of copolymers of VPA and acrylic acid by potentiometric titration are presented in Figure  8 [95]. The nominal degrees of neutralization α of the poly(acrylic acid) (PVPA-0), copolymers containing 30 and 60 mol% of VPA (PVPA-30 and PVPA-60, respectively), poly(VPA) (PVPA-100) were calculated by taking into account elemental analysis data. The results of this study were in line with [57,65] with respect to PVPA. As opposed to the homopolymer, the titration curves of the copolymers showed two neutralization steps, which may be attributed to the contributions of VPA units with a pKa1 = 2.49 (step 1) and acrylic acid unit with a pKa2 = 7.74 (step 2). In contrast with PVPA, for PmPPA (see Scheme 40) the pH titration curves showed distinct pH steps for the addition of one and two equivalents of base [148].
The solution behavior of polymers affects the ability to use certain methods of the preparation of polymer films and scaffolds. Among other approaches, ES molding has been successfully used in obtaining fibrous materials for different applications [152,153]. However, this method remains practically unused for sidechain PCPAs, despite their polyelectrolyte nature. Only the works of Lee [154,155] and Akar et al. [103] reported the results of the studies on the subject. In [154], ES fibrous mats with good morphology were prepared from an aqueous solution of the poly(vinyl alcohol) (PVA)/PVPA mixture. To In contrast with PVPA, for PmPPA (see Scheme 40) the pH titration curves showed distinct pH steps for the addition of one and two equivalents of base [148].
The solution behavior of polymers affects the ability to use certain methods of the preparation of polymer films and scaffolds. Among other approaches, ES molding has been successfully used in obtaining fibrous materials for different applications [152,153]. However, this method remains practically unused for sidechain PCPAs, despite their polyelectrolyte nature. Only the works of Lee [154,155] and Akar et al. [103] reported the results of the studies on the subject. In [154], ES fibrous mats with good morphology were prepared from an aqueous solution of the poly(vinyl alcohol) (PVA)/PVPA mixture. To prevent swelling, the samples were subjected to thermal treatment or chemical cross-linking (methanol/glutaraldehyde). In the next work [155], ES fibrous materials with lower content of PVPA were prepared and stabilized by heating at 150 • C for 24 h in vacuo, chemical cross-linking was not used to avoid toxicity. In [103], the preparation of the ES fibrous materials from a copolymer of VPA, acrylonitrile, and methyl acrylate is described, and copolymer solutions in DMF were used.
Amphiphilic diblock copolymers usually demonstrated complex solution behavior. For example, PMEMA-b-poly(MOEP) and PMEMA-b-poly(MMPN) (for their synthesis, see Scheme 23) in basic aqueous media formed core-shell micelles as the PMEMA block formed insoluble micelle core. It is noteworthy that PMEMA-b-poly(MMPN) diblock copolymers interacted strongly with Ca 2+ with a formation of reverse micellar structures. [29].
As was shown in [110], complex random copolymer, containing phosphorylcholine and doxorubicin fragments can self-assemble into nanoparticles with doxorubicin as the core, and hydrophilic P(MPC-co-PEGMA-BZ, see Section 3.3.4) as the shell in an aqueous solution.

Complexation of Sidechain PCPAs with Metal Ions
The reaction of PVPA with calcium tetraphosphate (Equation (2)) in 2:3 molar ratio results in the formation of Ca-PVPA and HAp [150].
2PVPA + 3Ca 4 (PO 4 ) 2 O → 2Ca-PVPA + Ca 10 (PO 4 ) 6 (OH) 2 (2) Cross-linked polymers presented in Scheme 28 demonstrated excellent adsorption of Pb 2+ and Cu 2+ ions. The values of the maximum adsorption capacity Q m were 7.19 and 17.0 mmol·g −1 , respectively [115]. Another cross-linked copolymer was obtained from a terpolymer of MOEP, HEMA and 2-hydroxypropane-1,3-diyl bis(2-methylacrylate) by radical polymerization with acrylamide and N,N -(propane-1,3-diyl)diacrylamide to mimic aquatic caddisworm silk and natural processes of Ca 2+ complexation [106]. The clear homogeneous hydrogel was formed, and in the presence of divalent metal ions, Mg 2+ , Ca 2+ , and Zn 2+ , the hydrogels shrank to about 65% of the initial volume and became translucent. Above a critical phosphate sidechain density, hydrogels equilibrated with Ca 2+ or Zn 2+ ions displayed increased initial stiffness, strain-rate dependent yield behavior, and required 100 times more work to fracture than hydrogels equilibrated with Mg 2+ or Na + ions. The toughness of the bio-inspired hydrogels exceeded the toughness of cartilage and meniscus, suggesting potential application as prosthetic biomaterials, according to the authors of the study [106]. Mg 2+ complexation by MOEP/HEMA copolymer in aqueous media was the subject of a separate study by the same research team [23].
Results of the study of VPA homopolymer and VPA copolymers with acrylamide and vinylsulfonic acid have demonstrated a high potential if the use of VPA copolymers as antiscalants for (Fe, Mg) silicates [156], the best efficiency was detected for a copolymer of VPA with vinylsulfonic acid (1:5 comonomer ratio).
The ability of the -P(O)(OH) 2 fragment to chemical binding with the metal ions largely determines the use of phosphates as anticorrosive agents. Copolymers of CF 2 =CH 2 with CH 2 =C(CF 3 )C(O)OCH 2 P(O)(OH) 2 (79-96 mol% of CF 2 =CH 2 , M n up to 10 kDa) were synthesized by tert-amyl peroxy-2-ethylhexanoate initiated free-radical copolymerization in dimethyl carbonate [36]. Steel plates, coated with the copolymer, displayed satisfactory anticorrosion properties under a simulated seawater environment. An original and efficient approach to development of anticorrosive agents was proposed by Kousar and Moratti [157], via the use of methacrylate copolymers containing -(CH 2 ) 2 (CF 2 ) 7 CH3 and -CH 2 P(O)(OH) 2 substituents. These copolymers formed monolayers at the stainless-steel surface (the contact angle >128 • ) and were stable after being submerged in water for a week. The best set of characteristics was achieved for copolymers containing phosphonated and fluorinated monomers in a 2:1 ratio.

Effects of the Sidechain PCPAs on Crystal Growth and Morphology
A number of works from the Penczek group were devoted to the study of the synthesis and morphology of CaCO 3 particles obtained in the presence of sidechain PCPAs, and an amazing diversity of the crystallite's forms was observed [119,120,122,158,159] (Figure 9). polymerization in dimethyl carbonate [36]. Steel plates, coated with the copolymer, displayed satisfactory anticorrosion properties under a simulated seawater environment. An original and efficient approach to development of anticorrosive agents was proposed by Kousar and Moratti [157], via the use of methacrylate copolymers containing -(CH2)2(CF2)7CH3 and -CH2P(O)(OH)2 substituents. These copolymers formed monolayers at the stainless-steel surface (the contact angle >128°) and were stable after being submerged in water for a week. The best set of characteristics was achieved for copolymers containing phosphonated and fluorinated monomers in a 2:1 ratio.

Effects of the Sidechain PCPAs on Crystal Growth and Morphology
A number of works from the Penczek group were devoted to the study of the synthesis and morphology of CaCO3 particles obtained in the presence of sidechain PCPAs, and an amazing diversity of the crystallite's forms was observed [119,120,122,158,159] ( Figure 9). Diblock copolymer mPEG-b-poly(EMEPN) (see Scheme 26) [114] demonstrated an interesting concentration effect on the formation of CaCO3 particles (Figure 10). Cölfen and Antonietti [160] have made a certain contribution to this issue; however, a detailed comparative analysis of their studies is complicated by the lack of detailed information on the structure of copolymers used.  Diblock copolymer mPEG-b-poly(EMEPN) (see Scheme 26) [114] demonstrated an interesting concentration effect on the formation of CaCO 3 particles (Figure 10). Cölfen and Antonietti [160] have made a certain contribution to this issue; however, a detailed comparative analysis of their studies is complicated by the lack of detailed information on the structure of copolymers used.
polymerization in dimethyl carbonate [36]. Steel plates, coated with the copolymer, displayed satisfactory anticorrosion properties under a simulated seawater environment. An original and efficient approach to development of anticorrosive agents was proposed by Kousar and Moratti [157], via the use of methacrylate copolymers containing -(CH2)2(CF2)7CH3 and -CH2P(O)(OH)2 substituents. These copolymers formed monolayers at the stainless-steel surface (the contact angle >128°) and were stable after being submerged in water for a week. The best set of characteristics was achieved for copolymers containing phosphonated and fluorinated monomers in a 2:1 ratio.

Effects of the Sidechain PCPAs on Crystal Growth and Morphology
A number of works from the Penczek group were devoted to the study of the synthesis and morphology of CaCO3 particles obtained in the presence of sidechain PCPAs, and an amazing diversity of the crystallite's forms was observed [119,120,122,158,159] ( Figure 9). Diblock copolymer mPEG-b-poly(EMEPN) (see Scheme 26) [114] demonstrated an interesting concentration effect on the formation of CaCO3 particles (Figure 10). Cölfen and Antonietti [160] have made a certain contribution to this issue; however, a detailed comparative analysis of their studies is complicated by the lack of detailed information on the structure of copolymers used.  Concentration effects, observed by the Penczek group, can be interpreted in view of the study of Dimova and Coll. [125] of the interaction of double hydrophilic block copolymers (see Scheme 31) with calcite crystals by isothermal titration calorimetry. It was shown that the interaction of copolymers with relatively large CaCO 3 crystals is an exothermic process (well fitted by a Langmuir adsorption model). In the absence of large crystals, the observed endothermic process was attributed to polymer interaction with small clusters or aggregates of calcium carbonate of the type (CaCO 3 ) x (H 2 O) y where 1 < x < 100. The formation of similar aggregates cannot but affect the crystallization process in the presence of PCPAs. Morphological control of BaSO 4 microstructure by copolymers PEG-b-PMMA and PEG-b-PMMA-PO 3 H 2 (1%) was studied by Cölfen and Coll. [128].

Hybrid Nanoparticle Formation by Sidechain PCPAs
The ability of divalent transition metal ions to induce micellization by mixing aqueous solutions of the partly ionized poly(acrylamide)-b-PVPA copolymers (see Scheme 22) and metal ions was studied as a function of the nature of the metal cation [96]. Based on DLS measurements, the authors concluded that the micellization efficiency followed the sequence: Ni 2+ , Co 2+ < Zn 2+ < Mn 2+ < Cu 2+ .
After treatment of the gold surface by HS(CH 2 ) 2 NH 2 , the self-assembled film (SAF) of the core-shell copolymer three (Figure 11a) was studied [74]. The self-assembly of a core-shell macromolecule three on gold was characterized by atomic force microscopy (AFM). As can be seen in Figure 11b, separated globular particles appear to be uniformly monodisperse with a diameter of~20 nm.
Wiley-VCH GmbH. Concentration effects, observed by the Penczek group, can be interpreted in view of the study of Dimova and Coll. [125] of the interaction of double hydrophilic block copolymers (see Scheme 31) with calcite crystals by isothermal titration calorimetry. It was shown that the interaction of copolymers with relatively large CaCO3 crystals is an exothermic process (well fitted by a Langmuir adsorption model). In the absence of large crystals, the observed endothermic process was attributed to polymer interaction with small clusters or aggregates of calcium carbonate of the type (CaCO3)x(H2O)y where 1 < x < 100. The formation of similar aggregates cannot but affect the crystallization process in the presence of PCPAs. Morphological control of BaSO4 microstructure by copolymers PEG-b-PMMA and PEG-b-PMMA-PO3H2(1%) was studied by Cölfen and Coll. [128].

Hybrid Nanoparticle Formation by Sidechain PCPAs
The ability of divalent transition metal ions to induce micellization by mixing aqueous solutions of the partly ionized poly(acrylamide)-b-PVPA copolymers (see Scheme 22) and metal ions was studied as a function of the nature of the metal cation [96]. Based on DLS measurements, the authors concluded that the micellization efficiency followed the sequence: Ni 2+ , Co 2+ < Zn 2+ < Mn 2+ < Cu 2+ .
After treatment of the gold surface by HS(CH2)2NH2, the self-assembled film (SAF) of the core-shell copolymer three (Figure 11a) was studied [74]. The self-assembly of a core-shell macromolecule three on gold was characterized by atomic force microscopy (AFM). As can be seen in Figure 11b, separated globular particles appear to be uniformly monodisperse with a diameter of ~20 nm.  When considering and using PVPA as a biomimetic analog of matrix phosphoproteins, Tay and Coll. [60] studied mineralization of cross-linked collagen in the presence of Ca 2+ , PO 4 3− , OH − ions and poly(acrylic acid). Intrafibrillar and extrafibrillar mineralization via a bottom-up nanoparticle assembly based on the non-classical crystallization pathway were identified. Selected area electron diffraction patterns of highly mineralized collagen fibrils were nearly identical to those of natural bone, with apatite crystallites preferentially aligned along the collagen fibril axes. Conversely, only large mineral spheres with no preferred association with collagen fibrils were observed in the absence of PVPA.

Polymer-Inorganic Composites
Composites of the Ca-PVPA and HAp were prepared by warm-pressing powder mixtures of Ca 4 (PO 4 ) 2 O and PVPA at a weight ratio of 3.5:1 at temperatures of up to 300 • C and pressure up to 690 kpsi within 1 h [150]. The highest achieved values for the tensile strength and elastic modulus were 53 MPa and 32 GPa, respectively. The tensile strength values of the composites were lower than those of long bones , in the range of those reported for dentin , and higher than that reported for enamel (10.3 MPa). Elastic moduli of the composites were higher than long bones (17.2-18.6 GPa) and dentin (0.26-14.7 GPa) but lower than those of enamel . No further biomedical studies for these composites were conducted.
Attempt to prepare ferrimagnetic PVPA/BaFe 12 O 19 nanocomposite was not entirely successful due to the adsorption of PVPA anions during the preparation of the nanocomposite that strongly influenced the magnetic properties, resulting in much lower saturation magnetization values [63].
A number of composite samples were prepared from phosphorylated poly(vinyl alcohol) and nano-sized HAp (the mean crystallite size 19 nm, 0-60 wt% loaded in composite formulation) [126]. In composites, obtained by chemical methods (with the use of an aqueous polymer solution), the phosphorylated polymer has demonstrated dispersant properties. With an increase in the content of HAp in composite, the tensile strength goes through the maximum of 26.2 MPa (50 wt% of HAp), Young's modulus increases from 151 MPa (o% HAp) to 668 MPa (60% HAp), and elongation at break decreases from 39.2 to 4.8%.

Sidechain PCPAs and Cell Viability/Metabolism and Differentiation
For sidechain PCPAs, hydrolytic degradation should lead to the formation of -OH functionalized polymers with unpredictable properties. Research in this area is fragmentary; however, the results of the effect of PCPAs and their metabolites on cell adhesion and proliferation showed that sidechain PCPAs rarely demonstrate toxicity.
In particular, when studying ES mats based on PVPA/PVA, no toxicity was detected in experiments with MG-63 osteoblast-like cells for untreated materials, but cross-linked membranes (MeOH/glutaraldehyde) turned out to be toxic, the cell proliferation was also suppressed significantly [154]. In the follow-up study [155], PVPA/PVA ES mats demonstrated low cytotoxicity with respect to M3TCT3-E1 preosteoblast cells, which increased with the increase in PVPA content in the composite. At the same time, the presence of PVPA facilitated cell proliferation.
When studying osteogenic MC3T3-E1 subclone 4 cells on the surface of silicon, grafted by VPA-acrylamide copolymers, Gemeinhart and Coll. have demonstrated that cell adhesion and proliferation have a clear maximum that corresponds to 30 mol% content of VPA in the comonomer feed [100] (Figure 12). MC3T3-E1 maturation began at about the 20th day and was defined by matrix calcification and increased alkaline phosphatase activity. The mineralization of PVPA-modified surfaces was potentially due to both cellular differentiation and polymer-based calcification, but experiments in the absence of cells did not show mineralization. In this way, the cell-mediated mineralization, observed for the pVPA30grafted surface, would benefit from osteointegration, which demonstrates high prospects for the use of VPA copolymers in the further design of bone tissue engineering scaffolds.
PVPA/chitosan composites were prepared by simultaneous adsorption of PVPA and N-(3-dimethylaminopropyl)-N -ethylcarbodiimide mediated cross-linking; the porous three-dimensional matrices were prepared from the 2% aqueous solutions of chitosan (CS) or composite (PVPACS) containing 1% AcOH by thermally induced phase separation at −80 • C followed by sublimation of ice crystals [161]. MTT results for MC3T3-E1 pre-osteoblast cells have shown a higher degree of proliferation for PVPACS matrices compared with CS matrices (Figure 13). absence of cells did not show mineralization. In this way, the cell-mediated mineralization, observed for the pVPA30-grafted surface, would benefit from osteointegration, which demonstrates high prospects for the use of VPA copolymers in the further design of bone tissue engineering scaffolds. PVPA/chitosan composites were prepared by simultaneous adsorption of PVPA and N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide mediated cross-linking; the porous three-dimensional matrices were prepared from the 2% aqueous solutions of chitosan (CS) or composite (PVPACS) containing 1% AcOH by thermally induced phase separation at −80 °C followed by sublimation of ice crystals [161]. MTT results for MC3T3-E1 pre-osteoblast cells have shown a higher degree of proliferation for PVPACS matrices compared with CS matrices (Figure 13).  tion, observed for the pVPA30-grafted surface, would benefit from osteointegration, which demonstrates high prospects for the use of VPA copolymers in the further design of bone tissue engineering scaffolds. PVPA/chitosan composites were prepared by simultaneous adsorption of PVPA and N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide mediated cross-linking; the porous three-dimensional matrices were prepared from the 2% aqueous solutions of chitosan (CS) or composite (PVPACS) containing 1% AcOH by thermally induced phase separation at −80 °C followed by sublimation of ice crystals [161]. MTT results for MC3T3-E1 pre-osteoblast cells have shown a higher degree of proliferation for PVPACS matrices compared with CS matrices (Figure 13). Figure 13. (a) MTT assay of MC3T3-E1 pre-osteoblast cells proliferation on CS and PVPACS matrices after 1, 3, 5 and 7 days of incubation period, data represent the mean ± SD forfour replicates and significantly different values (***p < 0.001,**p < 0.01,*p < 0.05); (b) Confocal images of MC3T3-E1 pre-osteoblast cells cultured on CS and PVPACS matrices after 1 and 7 days of the incubation period. Reprinted with permission from [161]. Copyright (2014) Elsevier B. V. Figure 13. (a) MTT assay of MC3T3-E1 pre-osteoblast cells proliferation on CS and PVPACS matrices after 1, 3, 5 and 7 days of incubation period, data represent the mean ± SD forfour replicates and significantly different values (*** p < 0.001, ** p < 0.01, * p < 0.05); (b) Confocal images of MC3T3-E1 pre-osteoblast cells cultured on CS and PVPACS matrices after 1 and 7 days of the incubation period. Reprinted with permission from [161]. Copyright (2014) Elsevier B. V.
Copolymers of acrylic acid, VPA, and ethylene glycol diacrylate as a cross-linking agent formed hydrogel. Freeze-drying the hydrogel resulted in obtaining the mesoporous materials. The pore diameter and formation of an interconnected pore network depended on the VPA content [97]. The experiments with human osteosarcoma-derived osteoblast (SaOS-2) cells showed that an increase in the VPA content supports cell adhesion and proliferation. The authors have said that hydrogels with 30 or 50 mol% VPA are ideal for use as bone void fillers, providing high swelling and increased osteoblast-like cell attachment and proliferation.

Biocompatibility of Sidechain PCPAs and Prospects for Use in Bone Surgery
The effect of PVPA in addition to in vivo biocompatibility of PVPA/PVA ES mats was preliminarily investigated by the implantation of the PV0.1 membrane (1 wt% PVPA) in a defect compared with a defect with PV0 implanted (without PVPA) and with a defect without an implant (control) [155] (Figure 14). The results showed that the in vitro cell growth behavior on the PVPA-added membrane resulted in favorable tissue growth in vivo (confirmed by micro-CT results and histological studies). The histological observations derived from the rat skull defect implanted with PV0.1 also showed that the membrane was still intact after 4 weeks of grafting. The authors concluded that the efficiency of tissue growth is due to the phosphate groups, which facilitate the bonding process of the implant to the native host tissue. agent formed hydrogel. Freeze-drying the hydrogel resulted in obtaining the mesopo-rous materials. The pore diameter and formation of an interconnected pore network depended on the VPA content [97]. The experiments with human osteosarcoma-derived osteoblast (SaOS-2) cells showed that an increase in the VPA content supports cell adhesion and proliferation. The authors have said that hydrogels with 30 or 50 mol % VPA are ideal for use as bone void fillers, providing high swelling and increased osteoblast-like cell attachment and proliferation.

Biocompatibility of Sidechain PCPAs and Prospects for Use in Bone Surgery
The effect of PVPA in addition to in vivo biocompatibility of PVPA/PVA ES mats was preliminarily investigated by the implantation of the PV0.1 membrane (1 wt% PVPA) in a defect compared with a defect with PV0 implanted (without PVPA) and with a defect without an implant (control) [155] (Figure 14). The results showed that the in vitro cell growth behavior on the PVPA-added membrane resulted in favorable tissue growth in vivo (confirmed by micro-CT results and histological studies). The histological observations derived from the rat skull defect implanted with PV0.1 also showed that the membrane was still intact after 4 weeks of grafting. The authors concluded that the efficiency of tissue growth is due to the phosphate groups, which facilitate the bonding process of the implant to the native host tissue. Figure 14. Comparison of defects without implant (control) (a), with PV0 (b) and PV0.1 (c). Images shown were obtained during extraction after 4 weeks of implantation (1), scanned micrograph from micro-computed tomography (2) and reconstructed three-dimensional structure of the defects (3). Blood clots (black arrows) may have resulted from the trauma of the surgery because the presence in the control (a1). Percentage bone volume was also computed, showing statistically higher values obtained in defects implanted with PV0.1 compared with nonimplanted defects (***p < 0.001,**p < 0.01,*p < 0.05) (d). Reprinted with permission from [155]. Copyright (2014) Wiley-VCH GmbH.
PVPA/chitosan composite porous three-dimensional matrices were used for the implantation of full-thickness calvarial bone defects (diameter of 5 mm) in Sprague Dawley male rats [161]. Bone formation was limited by CS-treated groups, commencing only from the periphery of the host bone. However, with PVPACS treated group, bone formation was markedly higher, and some initiated in the center of the defect after 4 and Figure 14. Comparison of defects without implant (control) (a), with PV0 (b) and PV0.1 (c). Images shown were obtained during extraction after 4 weeks of implantation (1), scanned micrograph from micro-computed tomography (2) and reconstructed three-dimensional structure of the defects (3). Blood clots (black arrows) may have resulted from the trauma of the surgery because the presence in the control (a1). Percentage bone volume was also computed, showing statistically higher values obtained in defects implanted with PV0.1 compared with nonimplanted defects (*** p < 0.001, ** p < 0.01, * p < 0.05) (d). Reprinted with permission from [155]. Copyright (2014) Wiley-VCH GmbH.
PVPA/chitosan composite porous three-dimensional matrices were used for the implantation of full-thickness calvarial bone defects (diameter of 5 mm) in Sprague Dawley male rats [161]. Bone formation was limited by CS-treated groups, commencing only from the periphery of the host bone. However, with PVPACS treated group, bone formation was markedly higher, and some initiated in the center of the defect after 4 and 8 weeks of implantation ( Figure 15). The osteoinductive effect of PVPA was also confirmed by hystological studies.
A complex porous composite material, based on poly(lactic-co-glycolic acid) microspheres, the copolymer of fumaric acid and oligo(ethylene glycol), and BMEP (see Scheme 4) as a cross-linker, was studied as a bone substituent after treatment with BMP-2 [162]. It was demonstrated that it is the presence of BMEP that enhance bone formation in the context of BMP-2. 8 weeks of implantation ( Figure 15). The osteoinductive effect of PVPA was also confirmed by hystological studies. A complex porous composite material, based on poly(lactic-co-glycolic acid) microspheres, the copolymer of fumaric acid and oligo(ethylene glycol), and BMEP (see Scheme 4) as a cross-linker, was studied as a bone substituent after treatment with BMP-2 [162]. It was demonstrated that it is the presence of BMEP that enhance bone formation in the context of BMP-2.

Sidechain PCPAs and Composites for Dental Applications
Dental self-etch adhesives (SEAs) are widely employed to adhere a restorative material to a tooth. Since the functionality of SEAs is provided by polymer formation, these de facto monomeric compounds are also discussed in this section.

Sidechain PCPAs and Composites for Dental Applications
Dental self-etch adhesives (SEAs) are widely employed to adhere a restorative material to a tooth. Since the functionality of SEAs is provided by polymer formation, these de facto monomeric compounds are also discussed in this section.
Le Pluart and Coll. [34] studied three different phosphonic, bisphosphonic, and difluoromethylphosphonic acid methacrylate monomers (see Scheme 7 and structures A-C in Figure 16). A complex porous composite material, based on poly(lactic-co-glycolic acid) microspheres, the copolymer of fumaric acid and oligo(ethylene glycol), and BMEP (see Scheme 4) as a cross-linker, was studied as a bone substituent after treatment with BMP-2 [162]. It was demonstrated that it is the presence of BMEP that enhance bone formation in the context of BMP-2.

Sidechain PCPAs and Composites for Dental Applications
Dental self-etch adhesives (SEAs) are widely employed to adhere a restorative material to a tooth. Since the functionality of SEAs is provided by polymer formation, these de facto monomeric compounds are also discussed in this section.
Le Pluart and Coll. [34] studied three different phosphonic, bisphosphonic, and difluoromethylphosphonic acid methacrylate monomers (see Scheme 7 and structures A-C in Figure 16). The main objective of their study was to evaluate the influence of the nature of the acidic group on the reactivity and adhesive properties of the monomers. Photopolymerization of N,N -diethyl-1,3-bis(acrylamido)propane (DEBAAP) with monomers A-C demonstrated higher reactivity of B, the difference between A and C was minimal. Dentin shear bond strength measurements have shown that primers based on B and C are significantly more efficient than the ones based on A. The dentin shear bond strength (SBS) values were 15.4, 19.7, and 20.6 MPa for A, B, and C, respectively. Therefore, monomers B and C appear to be great candidates for light-cured adhesive formulations.
Dentin SBS measurements showed that -CF 2 P(O)(OH) 2 containing primers are significantly more efficient than the -CH 2 P(O)(OH) 2 containing methacrylates. Of particular note is the influence of the -(CH 2 ) n -spacer length: the use of the SEP containing monomer 20 (n = 10, Figure 17) resulted in an SBS value of 24.2 MPa, whereas widespread monomers 1 and 25 had values of 17.9 and 15.1 MPa, respectively, and monomer 4 (n = 4) was characterized by SBS value of 20.6 MPa. ization of N,N'-diethyl-1,3-bis(acrylamido)propane (DEBAAP) with monomers demonstrated higher reactivity of B, the difference between A and C was minimal. tin shear bond strength measurements have shown that primers based on B and C significantly more efficient than the ones based on A. The dentin shear bond stre (SBS) values were 15.4, 19.7, and 20.6 MPa for A, B, and C, respectively. There monomers B and C appear to be great candidates for light-cured adhesive formulati In further studies [35], new monomers with different spacers between methacr and -CF2P(O)(OH)2 fragments were synthesized (see Scheme 7) and used for the p ration of the primers with N,N-diethyl-1,3-bis(acrylamido)propane (10 mol%), con ing photoinitiator (camphorquinone), coinitiator (ethyl 4-(dimethylamino)benzoate stabilizer (2,6-di-tert-butyl-4-methylphenol). Primers, coupled with the AdheSE bon resin [163], were used to generate a bond between a standard Z100 A3 comp (3M/ESPE) and dentin. The results of the SBS measurements are presented in Figur

Drug Delivery and Drug Release with the Use of Sidechain PCPAs
Since zwitterionic polymers have excellent properties of hydration, anti-bacterial adhesion, long-term circulation and suppress nonspecific protein adsorption in vivo, Ni and Coll. described a novel folate-targeted and acid-labile polymeric prodrug under the microenvironment of tumor cells, based on the use MPC (Scheme 4) comonomer [110]. Functionalized copolymers containing the fragment of folic acid were able to chemical binding with doxorubicin (see Schemes 1 and 41), and the presence of phosphocholine fragments provided the delivery and release of the drug that was bonded with the neighboring fragment. The copolymers have demonstrated marked colloidal behavior with the critical aggregation concentration~50 mg·L −1 . Nanoparticles were stable at pH 7.4 and tended to aggregate at a pH of 5.0. Colloid stability correlated with the drug release rates (after 98 h, 80 and 15% of DOX released at pH 5.0 and 7.4, respectively). The DOX-free copolymer was found to be non-toxic for normal cells (L929) and cancer cells (HeLa HepG2), whereas DOXbonded copolymers have demonstrated a marked antitumor efficacy (IC 50   Given that current chemotherapies have limited effectiveness in eliminating b metastasis, Iwasaki and Coll. [40] made a separate study to provide regional che therapy for this metastatic tumor. A bone-targeting drug carrier was designed by in ducing the osteotropic bisphosphonate alendronate units into an amphiphilic phosp lipid polymer (see Scheme 24). The copolymer formed nanoparticles (d < 30 nm), diphosphonate units were exposed to the outer layer of the particles. These particles w found to be able to encapsulate a hydrophobic anticancer drug docetaxel. The com formation did not hamper the pharmacological effect of the drug against several br cancer cell lines. The fluorescence observations evaluated by an in vivo imaging sys and fluorescence microscopy showed that the addition of diphosphonate units to polymer-drug complex enhanced bone accumulation ( Figure 18). Scheme 41. Structure of MPC-based copolymer for doxorubicin delivery [110].
Given that current chemotherapies have limited effectiveness in eliminating bone metastasis, Iwasaki and Coll. [40] made a separate study to provide regional chemotherapy for this metastatic tumor. A bone-targeting drug carrier was designed by introducing the osteotropic bisphosphonate alendronate units into an amphiphilic phospholipid polymer (see Scheme 24). The copolymer formed nanoparticles (d < 30 nm), and diphosphonate units were exposed to the outer layer of the particles. These particles were found to be able to encapsulate a hydrophobic anticancer drug docetaxel. The complex formation did not hamper the pharmacological effect of the drug against several breast cancer cell lines. The fluorescence observations evaluated by an in vivo imaging system and fluorescence microscopy showed that the addition of diphosphonate units to the polymer-drug complex enhanced bone accumulation ( Figure 18).

Polyelectrolytes Based on Sidechain PCPAs
Proton conduction in solid-state polyelectrolytes has aroused considerable interest in recent years in connection with the development of fuel cells, batteries, and water electrolyzers [164]. Sidechain PCPAs are regarded as prospective materials due to the presence of acid groups and the stable polymer backbone. Over the past decades, the number of research papers on the issue of sidechain PCPAs-based polyelectrolytes has significantly increased, and in this section we will look at some representative examples, taking into account the molecular structure of the polymers.
For polymer electrolytes, the critical structural variable is the concentration of the ionic functional groups that affect the water uptake and ion conductivity, expressed by the ion exchange capacity (IEC, molar equivalents of ion exchange group per g of dry polymer (mequiv•g -1 or mmol•g -1 ). Because -P(O)(OH)2-functionalized compounds are weaker acids than -SO3H-substituted polymers, phosphonic acids have lower conductivity in the presence of water. As a result, low-temperature electrochemical devices typically use sulfonated polymer electrolytes. However, for electrochemical devices operating at 100 °C and higher temperatures, phosphonic/phosphoric acid systems have an advantage because of their ability to provide proton conductivity in the absence of water. So in addition to proton conductivity, the high thermal stability of the polymers is desirable.

PVPA-based Polyelectrolytes
In water-free proton-conducting solid polyelectrolytes, proton transfer can be carried out only by hydrogen bond breaking and forming due to the absence of mobile species other than protons. The mechanism of the complex proton motion in solid PVPA was studied by Spiess and Coll. by solid-state NMR [165,166]. They confirmed the mobility of the P-OH protons but found that the formation of anhydride fragments leads to a decrease in proton conductivity through the decrease in the number of charge carriers and blockage of charge transport through immobilization of charge carriers together with a hindered reorientation of the anhydride groups. The 1 H chemical shift of the P-OH protons provided evidence for the presence of a hydrogen-bond network (Figure 19), which allows for proton transport via a Grotthus-type mechanism [165]. Combined 2 H line shape analysis and ab initio MD calculations [166] characterized the dynamical proton motion via the rearrangement of the H-bonding network, which involves both intra-and inter-chain transfers.

Polyelectrolytes Based on Sidechain PCPAs
Proton conduction in solid-state polyelectrolytes has aroused considerable interest in recent years in connection with the development of fuel cells, batteries, and water electrolyzers [164]. Sidechain PCPAs are regarded as prospective materials due to the presence of acid groups and the stable polymer backbone. Over the past decades, the number of research papers on the issue of sidechain PCPAs-based polyelectrolytes has significantly increased, and in this section we will look at some representative examples, taking into account the molecular structure of the polymers.
For polymer electrolytes, the critical structural variable is the concentration of the ionic functional groups that affect the water uptake and ion conductivity, expressed by the ion exchange capacity (IEC, molar equivalents of ion exchange group per g of dry polymer (mequiv·g −1 or mmol·g −1 ). Because -P(O)(OH) 2 -functionalized compounds are weaker acids than -SO 3 H-substituted polymers, phosphonic acids have lower conductivity in the presence of water. As a result, low-temperature electrochemical devices typically use sulfonated polymer electrolytes. However, for electrochemical devices operating at 100 • C and higher temperatures, phosphonic/phosphoric acid systems have an advantage because of their ability to provide proton conductivity in the absence of water. So in addition to proton conductivity, the high thermal stability of the polymers is desirable.

PVPA-Based Polyelectrolytes
In water-free proton-conducting solid polyelectrolytes, proton transfer can be carried out only by hydrogen bond breaking and forming due to the absence of mobile species other than protons. The mechanism of the complex proton motion in solid PVPA was studied by Spiess and Coll. by solid-state NMR [165,166]. They confirmed the mobility of the P-OH protons but found that the formation of anhydride fragments leads to a decrease in proton conductivity through the decrease in the number of charge carriers and blockage of charge transport through immobilization of charge carriers together with a hindered reorientation of the anhydride groups. The 1 H chemical shift of the P-OH protons provided evidence for the presence of a hydrogen-bond network (Figure 19), which allows for proton transport via a Grotthus-type mechanism [165]. Combined 2 H line shape analysis and ab initio MD calculations [166] characterized the dynamical proton motion via the rearrangement of the H-bonding network, which involves both intra-and inter-chain transfers.
The proton conductivity of PVPA was not as high as expected (~0.8 mS·cm −1 at 140 • C in dry conditions [167]), and the activation energy was around 60 kJ·mol −1 [168]. Since poly(ethylene oxide) (PEO) has a low glass transition temperature (210 K) and contains a huge number of oxygen atoms in the backbone which can form hydrogen bonds with phosphonic acid groups, Meyer and Coll. [167] proposed to build a dynamic hydrogen bond network in PVPA/PEO blends. However, even in homogeneous PVPA/PEO blends although the fast mobility of PEO chains, the proton conductivity decreased with increasing PEO content. The proton conductivity of PVPA was not as high as expected (~0.8 mS•cm -1 at 140 °C in dry conditions [167]), and the activation energy was around 60 kJ•mol -1 [168]. Since poly(ethylene oxide) (PEO) has a low glass transition temperature (210 K) and contains a huge number of oxygen atoms in the backbone which can form hydrogen bonds with phosphonic acid groups, Meyer and Coll. [167] proposed to build a dynamic hydrogen bond network in PVPA/PEO blends. However, even in homogeneous PVPA/PEO blends although the fast mobility of PEO chains, the proton conductivity decreased with increasing PEO content.
In further studies of the same scientific group, the influence of water sorption on the proton conductivity of PVPA was assessed [149]. High-MW almost atactic polymer (Mw = 62 kDa) was selected for experiments upon annealing and drying; it was demonstrated that H2O and self-condensation products coexist in the sample.
To improve the characteristics of PVPA-based membranes, Sen and Coll. have studied blends of PVPA and Nafion (Scheme 42), and polymer membranes were prepared by means of film casting from Nafion/PVPA solutions [169]. Nafion/PVPA electrolyte with S/P molar ratio of 1:1 was thermally stable up to 400 °C, the presence of -SO3H groups blocked the formation of a phosphonic acid anhydride. The proton conductivity of the Nafion/PVPA blend membrane at 130 °C in an anhydrous state was 1.1•10 −5 S•cm -1 . Under humidified conditions, the conductivities of the blends increased by four orders of magnitude, up to 1.2•10 −2 S•cm -1 .
The effect of the basic polymeric component in the composite with PVPA was studied by Zhang and Coll. on the example of PVPA-treated SiO2/poly(4-vinylpyridine) (PVP, Scheme 42) nanocomposite [170]. PVP-decorated SiO2 nanoparticles (diameter of the silica core 7-10 nm), containing 94 wt% of PVP, were treated by aq. PVPA solution in different N/P molar ratios, and freeze-dried. The proton conductivity of the membranes obtained was up to 10 mS•cm -1 under humidified conditions (for 80 wt% PVPA composite) and inferior to PVPA-based membrane.
PVPA/mPBI (Scheme 42) blend membranes were prepared using DMSO polymer solutions and studied by Sharif and Coll. in 2021 [171]. The activation energies of proton transport were calculated in the ranges of 7.1-40.8 kJ•mol -1 and 37.4-49.7 kJ•mol -1 at RH = 100 and 0%, respectively. H3PO4-doped PVPA/mPBI (1:1 mol/mol) have demonstrated the highest proton conductivity of 79.6 mS•cm -1 at 150 °C, which is comparable to Nafion In further studies of the same scientific group, the influence of water sorption on the proton conductivity of PVPA was assessed [149]. High-MW almost atactic polymer (M w = 62 kDa) was selected for experiments upon annealing and drying; it was demonstrated that H 2 O and self-condensation products coexist in the sample.
To improve the characteristics of PVPA-based membranes, Sen and Coll. have studied blends of PVPA and Nafion (Scheme 42), and polymer membranes were prepared by means of film casting from Nafion/PVPA solutions [169]. Nafion/PVPA electrolyte with S/P molar ratio of 1:1 was thermally stable up to 400 • C, the presence of -SO 3 H groups blocked the formation of a phosphonic acid anhydride. The proton conductivity of the Nafion/PVPA blend membrane at 130 • C in an anhydrous state was 1.1 × 10 −5 S·cm −1 . Under humidified conditions, the conductivities of the blends increased by four orders of magnitude, up to 1.2 × 10 −2 S·cm −1 . The complex character of the proton conductivity of PVPA (as well as evident problems arising from the formation of anhydrides at elevated temperatures) prompted the researchers to synthesize and study VPA copolymers. So, for example, free-standing films were obtained from copolymers of VPA and 1-vinyl-1,2,4-triazole (49-67 mol% of The effect of the basic polymeric component in the composite with PVPA was studied by Zhang and Coll. on the example of PVPA-treated SiO 2 /poly(4-vinylpyridine) (PVP, Scheme 42) nanocomposite [170]. PVP-decorated SiO 2 nanoparticles (diameter of the silica core 7-10 nm), containing 94 wt% of PVP, were treated by aq. PVPA solution in different N/P molar ratios, and freeze-dried. The proton conductivity of the membranes obtained was up to 10 mS·cm −1 under humidified conditions (for 80 wt% PVPA composite) and inferior to PVPA-based membrane.
PVPA/mPBI (Scheme 42) blend membranes were prepared using DMSO polymer solutions and studied by Sharif and Coll. in 2021 [171]. The activation energies of proton transport were calculated in the ranges of 7.1-40.8 kJ·mol −1 and 37.4-49.7 kJ·mol −1 at RH = 100 and 0%, respectively. H 3 PO 4 -doped PVPA/mPBI (1:1 mol/mol) have demonstrated the highest proton conductivity of 79.6 mS·cm −1 at 150 • C, which is comparable to Nafion membrane conductivity (mS·cm −1 ) under humidified condition at 80 • C. The methanol permeabilities of the blend membranes were about 1000 times lower than that of Nafion.
The complex character of the proton conductivity of PVPA (as well as evident problems arising from the formation of anhydrides at elevated temperatures) prompted the researchers to synthesize and study VPA copolymers. So, for example, free-standing films were obtained from copolymers of VPA and 1-vinyl-1,2,4-triazole (49-67 mol% of VPA) by evaporation of the aqueous solutions and studied [98]. Suddenly, the formation of phosphonic acid anhydride in copolymers was comparable to that in pure PVPA (~30-40% before and~60% after annealing at 160 • C, 31 [105]. The copolymer of VPA and styrene was studied in mixing with 1-propylimidazole [172], but the results have been mediocre (good thermal stability but very low conductivity even in the presence of water).
PVPA-grafted poly(vinylidene fluoride) (see Section 2.4.5) membranes were prepared from the DMF solutions [140], and the maximum proton conductivity of 2.3 mS·cm −1 was detected at 150 • C for copolymer with 20 wt% PVPA content.
The idea of the use of PVPA/inorganic composites as electrolyte membranes was tested in the study of Aslan and Bozkurt [62] who prepared PVPA/TiO 2 composites containing 5, 10, 15, or 20 wt% of TiO 2 . The maximum proton conductivity under water-free conditions was detected for 10% TiO 2 composite at 120 • C and found to be 4 mS·cm −1 . For PVPA/BN composites (3, 5, 10, and 15 wt% of the hexagonal BN) high thermal stability was detected (up to 200 • C), and maximum proton conductivity was measured for PVPA-15%HBN as 6.51 mS·cm −1 at 150 • C in anhydrous conditions [61].

Polyelectrolytes Based on Other Non-Fluorinated Polymers
PmPPA (see Scheme 40) [148] has demonstrated high thermal stability (up to 300 • C) without softening before decomposition. Temperature-dependent conductivity measurements under 1 atm water vapor pressure revealed that the conductivity of PmPPA amounted to 6 mS·cm −1 at 115 • C and decreased to 2 mS·cm −1 at a higher temperature. Without humidification, no reproducible results were obtained, which was attributed by the authors to irreversible condensation reactions, so PmPPA can be used as a proton conductor in the presence of water, but not in the dry state.
AIBA-initiated free-radical polymerization of styryl phosphonic acids with -CH 2 O(CH 2 ) n -(n = 2, 6) spacers between the aromatic ring and P atom (Scheme 8) resulted in the formation of PCPAs with relatively high thermal stability (no anhydride formation up to 140 • C) [49]. The proton conductivities were found to be~0.26 mS·cm −1 at 140 • C under nominally anhydrous conditions, and the length of the alkanediyl spacer did not affect the conductivity. Functionalized poly(styrene-ethylene/butylene-styrene) block copolymers of an even more simple structure (-CH 2 -spacers between the aromatic ring and -P(O)(OH) 2 , see Section 2.4.3) have demonstrated a lowering of the tensile strength and an increase in proton conductivity. With an increase in the degree of phosphonation [130], the maximum value of protonic conductivity at 140 • C was 5.82 mS·cm −1 .
Although fluorinated polymers as polyelectrolytes are discussed in the next section, we felt it more appropriate to consider -CH 2 CF 2 P(O)(OH) 2 -functionalized polystyrene [50] just after non-fluorinated analogs. The IEC of this polymer was 7.3 mmol·g −1 , and the conductivity of the dried sample at 120 • C reached 0.018 mS·cm −1 .
A similar study with a variation of the length of -(CH 2 ) n -spacers between 'PE' backbone and -P(O)(OH) 2 groups was conducted by Ueda and Coll. [45]. Phosphonated poly(acrylates) were obtained via free-radical polymerization of CH 2 =CHC(O)O(CH 2 ) n P(O) (OEt) 2 (n = 2, 4, 6) followed by hydrolytic cleavage, polymer membranes were prepared by cross-linking with the use of 5 wt% of benzoyl peroxide. The IEC values were 5.44, 4.76, and 4.09 mequiv·g −1 , respectively. These membranes have demonstrated high proton conductivity under humidification at 80 • C, and the sample based on acrylate with the longest -(CH 2 ) 6 -spacer was not inferior to Nafion 117 (Scheme 42) in conductivity.
In the development of proton-exchange membranes, star polymers may have some advantages compared to linear analogs owing to the compact and branched architecture of star polymers. An original approach to similar polymers was proposed by Müllen and Coll. [74], core-shell macromolecule containing polyaromatic core and polystyrene with -CH 2 P(O)(OH) 2 groups in the position para (Figure 11a) was synthesized and studied. The polymer showed relatively high thermal stability (up to 180 • C), and no anhydride formation was detected by 31 P MAS NMR. The maximum conductivity of 3.9 mS·cm −1 was detected in a humidified atmosphere at 115 • C.
Phosphonated poly(styrene-b-methylbutylene)s (see Scheme 35) were used in the preparation of membranes, containing ionic liquids (obtained from imidazole (Im), 2methylimidazole (2MIm) or 2-ethyl-4-methylimidazole (2E4MIm) and bis(trifluoromethane) sulfonimide (TFSI)) [137]. The introduction of alkyl substituents in imidazole resulted in increase of the proton conductivity in the temperature range of 60−150 • C, the maximum value of 2 mS·cm −1 was reached at 150 • C. The studies of the composites with ionic liquids were continued [138] mostly in view of self-assembled morphologies. It was demonstrated that with minimal changes in the numbers of comonomer units in copolymer, and depending on the type of the ionic liquid and thermal history, well-defined lamellae, gyroid, hexagonal cylinder (HEX), body-centered cubic, and A15 lattice morphologies are formed. The samples having the A15 lattice showed higher morphology factors (0.83-0.96) than those with the HEX phases (0.42-0.69), this structural advantage of the A15 lattice over the HEX for constructing less tortuous ion-conduction pathways resulted in higher proton conductivity (Figure 20).
Block copolymers of diethyl styryl phosphonate or diethyl styryl bis(phosphonate) (SP and SbP, respectively, see Scheme 9) were synthesized by ATRP, -OC(O)CMe2Br-functionalized poly(isobutylene) (pIB) was used as a macroinitiator; homopolymers were also obtained [51]. After hydrolytic cleavage (see Section 2.3.4), poly(phosphonic acid)s were dissolved in THF/MeOH or mixed with Im, 2MIm, or 2E4MIm / TFSI-based ionic liquids in THF/MeOH media, polyelectrolite membranes were obtained by solvent casting and subsequent vacuum drying. Wide-angle X-ray scattering (WAXS) profiles of the membrane samples (pSP, pSbP, pIB66-b-pSP30, pIB66-b-pSbP16, pIB66-b-pSbP28 without and with ionic liquids, Figure 21) and results of the small-angle X-ray scattering (SAXS) studies showed that block copolymers display long-range ordered self-assembled morphologies, in pSbP-based polymers ion aggregation was avoided featuring the confinement of polymer chains to few-nanometer domains.  In the presence of ionic liquids, virtually homogeneous ionic phases with suppressed ion clustering were detected for pSbP-based block copolymer. pIB 66 -b-pSbP 16 -based membranes have demonstrated the highest conductivity despite lower IEC presumably due to a narrow polymer domain with excluded ion aggregation ( Figure 22). Given that the T g of pSbP is more than 20 • C higher than the T g of pSP, the use of pSbP-based membranes appears a promising way for improving both the conductivity and mechanical strength of solid-state polyelectrolytes.
pIB66-b-pSbP16-based membranes have demonstrated the highest condu lower IEC presumably due to a narrow polymer domain with excluded io (Figure 22). Given that the Tg of pSbP is more than 20 °C higher than the Tg of pSbP-based membranes appears a promising way for improving both th and mechanical strength of solid-state polyelectrolytes.

Polyelectrolytes Based on Fluorinated Polymers
For phosphonated copolymers (CF2CFClCH2CH(OCH2CH2X))n P(O)(OH)2) with different degrees of phosphonation, the dependence of th on ionic exchange capacity (IEC) was investigated at 20 °C and 95% rel [129]. The level of conductivity was in the range of 0.02-20 mS•cm -1 , which to the Nafion 115 (up to ~50 mS•cm -1 ). The conductivity was strongly dep IEC: the conductivities of the copolymer with 36% phosphonate functiona 2.9 mequiv•g -1 ) and 93% phosphonate functionalization (IEC of 7.0 mequ by almost 3 orders of magnitude. When decreasing relative humidity from conductivity values decreased tenfold. An increase in the temperature fro resulted in an increase of the proton conductivity by twice. This result water molecules and phosphonic acid hydrogen bonding are involved conduction mechanism.

Polyelectrolytes Based on Fluorinated Polymers
For phosphonated copolymers (CF 2 CFClCH 2 CH(OCH 2 CH 2 X)) n (X = Cl, H, P(O)(OH) 2 ) with different degrees of phosphonation, the dependence of the conductivity on ionic exchange capacity (IEC) was investigated at 20 • C and 95% relative humidity [129]. The level of conductivity was in the range of 0.02-20 mS·cm −1 , which is comparable to the Nafion 115 (up to~50 mS·cm −1 ). The conductivity was strongly dependent on the IEC: the conductivities of the copolymer with 36% phosphonate functionalization (IEC of 2.9 mequiv·g −1 ) and 93% phosphonate functionalization (IEC of 7.0 mequiv·g −1 ) differed by almost 3 orders of magnitude. When decreasing relative humidity from 95 to 25%, the conductivity values decreased tenfold. An increase in the temperature from 90 to 120 • C resulted in an increase of the proton conductivity by twice. This result indicates that water molecules and phosphonic acid hydrogen bonding are involved in the proton conduction mechanism.
Around the same time, one first and promising step toward the development of efficient solid-state polyelectrolytes has been made by Atanasov and Kerres [131]. Poly(4vinyl-2,3,5,6-tetrafluorophenylphosphonic acid) (PWN2010) (see Scheme 33) with a degree of phosphonation~90% and IEC = 7 mmol·g −1 was found to be thermally stable up to 349 • C, and has not T g . The water uptake of PWN largely exceeded the one of Nafion 117, whereas the numbers of the water molecules per functional group (λ) of PWN2010 and Nafion 117 were similar. The conductivity of PWN2010, measured at 1 atm water vapor pressure (see Figure 23), was found to be by a factor of 4-10 higher than similar phosphonated polymers such as PVPA and PmPPA. It was even higher than the conductivity of Nafion 117 (Scheme 42), being up to two times larger at T = 155 • C. Similar to PmPPA, PWN2010 showed reduced dependence on the conductivity from the water content at higher temperatures (T = 135-155 • C). The absence of conductivity hysteresis indicated the absence of the anhydride formation in stark contrast to PVPA and PmPPA.
Poly(4-vinyl-2,3,5,6-tetrafluorophenylphosphonic acid) (PWN2010) (see Scheme 33) with a degree of phosphonation ~90% and IEC = 7 mmol•g -1 was found to be thermally stable up to 349 °C, and has not Tg. The water uptake of PWN largely exceeded the one of Nafion 117, whereas the numbers of the water molecules per functional group (λ) of PWN2010 and Nafion 117 were similar. The conductivity of PWN2010, measured at 1 atm water vapor pressure (see Figure 23), was found to be by a factor of 4-10 higher than similar phosphonated polymers such as PVPA and PmPPA. It was even higher than the conductivity of Nafion 117 (Scheme 42), being up to two times larger at T = 155 °C. Similar to PmPPA, PWN2010 showed reduced dependence on the conductivity from the water content at higher temperatures (T = 135-155 °C). The absence of conductivity hysteresis indicated the absence of the anhydride formation in stark contrast to PVPA and PmPPA. Figure 23. The conductivity of PWN2010 as a function of temperature at water partial pressure of p(H2O) = 1 atm. Conductivities of Nafion 117, PVPA, and PmPPA, measured at the same conditions and setup, are given as a comparison. Reprinted with permission from [131]. Copyright (2011) American Chemical Society.
In [133], Atanasov and Coll. reported the results of further studies of PWN. They convincingly showed that PWN really does not form anhydride at moderately elevated temperatures. Even at 250 °C 48% dehydration required annealing within 5 h! At 150 °C in dry N2, the proton conductivity was 0.4 mS•cm -1 . Stable polymer films were prepared by blending PWN with poly(benzimidazole) PBIOO (Scheme 42), which after doping with PA reached a peak power density of about 230 mW•cm -2 at 150 °C. Another important aspect in the potential use of PWN is its poor mechanical properties at high degrees of the phosphonation, and in [132] the synthesis and studies of poly(pentafluorostyrene)s with controlled phosphonation degrees (17-66%) were presented. Ion conductivity was found to increase with both temperature and phosphonation degree reaching 57 mS•cm -1 at 120 °C (RH ~90%). In the fuel cell, the blend showed the best peak power density of 400 mW•cm -2 against 350 mW•cm -2 for Nafion 212. A blend membrane consisting of 82 wt% PWN and 18 wt% benzimidazole copolymer F6PBI (Scheme 42) with IEC ~ 2.1 mmol•g -1 was produced and showed better thermal and radical resistance, lower water uptake but similar ion-conductivity. With the use of these blends, full-featured prototypes of the fuel cells were developed and tested.
In trying to improve PWN characteristics, triblock copolymers with poly(diaryl sulfone) were synthesized (see Scheme 34) and studied [136]. Copolymer membranes Figure 23. The conductivity of PWN2010 as a function of temperature at water partial pressure of p(H 2 O) = 1 atm. Conductivities of Nafion 117, PVPA, and PmPPA, measured at the same conditions and setup, are given as a comparison. Reprinted with permission from [131]. Copyright (2011) American Chemical Society.
In [133], Atanasov and Coll. reported the results of further studies of PWN. They convincingly showed that PWN really does not form anhydride at moderately elevated temperatures. Even at 250 • C 48% dehydration required annealing within 5 h! At 150 • C in dry N 2, the proton conductivity was 0.4 mS·cm −1 . Stable polymer films were prepared by blending PWN with poly(benzimidazole) PBIOO (Scheme 42), which after doping with PA reached a peak power density of about 230 mW·cm −2 at 150 • C. Another important aspect in the potential use of PWN is its poor mechanical properties at high degrees of the phosphonation, and in [132] the synthesis and studies of poly(pentafluorostyrene)s with controlled phosphonation degrees (17-66%) were presented. Ion conductivity was found to increase with both temperature and phosphonation degree reaching 57 mS·cm −1 at 120 • C (RH~90%). In the fuel cell, the blend showed the best peak power density of 400 mW·cm −2 against 350 mW·cm −2 for Nafion 212. A blend membrane consisting of 82 wt% PWN and 18 wt% benzimidazole copolymer F6PBI (Scheme 42) with IEC~2.1 mmol·g −1 was produced and showed better thermal and radical resistance, lower water uptake but similar ion-conductivity. With the use of these blends, full-featured prototypes of the fuel cells were developed and tested.
In [134], the most promising results of the studies of PWN-based polyme branes were discussed and summarized, and the advantages (film processing conductivity, acid retention with water) and disadvantages (hydrophobicity, stability) of these polymers in comparison with Nafion were demonstrated.
The high efficiency of the synergy of PWN-type polymer and Nafion was strated in the very recent work of Kin and Coll. [135]. They proposed that the pre highly acidic -SO3H groups could enhance the anhydrous proton conduction of electrodes due to proton transfer to the phosphonic acid groups. The fuel cell, ex a rated power density of 780 mW•cm -2 at 160 °C, with minimal degradation durin of operation and 700 thermal cycles from 40 to 160 °C under load, was develope results of the study.

Sidechain PCPAs as Flame Retardants
The phosphorus-containing FRs surpass halogen-based FRs in safety and a intensively researched [12]. In a recent review of Ö zer and Gaan, devoted to p rus-based flame retardant coatings for textiles [174], low-MW compounds have been described.
As with main-chain PCPAs, sidechain polyacids have been little studied as 2013 Fang and Coll. reported on a study of the construction of Zn 2+ -and Cu 2+ -do coatings on the surface of ramie fabrics [175]. PVPA and branched polyethylenim were used in the layer-by-layer assembly technique. As a result, the thermal stability of the coated fabric was improved, e.g., a significant residue (up to 25. was left (<1% for the control). The results of this study were somewhat expand The conductivity value for copolymer membrane, based on perfluoro-1,1 -biphenyl and diphosphonated hydroquinone (see Scheme 39), reached 92 mS·cm −1 when fully hydrated at ambient temperature [147] which is comparable with standard Nafion membranes [173] and substantially higher than reported for certain other phosphonated polymers [44,129,139].
In [134], the most promising results of the studies of PWN-based polymer membranes were discussed and summarized, and the advantages (film processing, proton conductivity, acid retention with water) and disadvantages (hydrophobicity, thermal stability) of these polymers in comparison with Nafion were demonstrated.
The high efficiency of the synergy of PWN-type polymer and Nafion was demonstrated in the very recent work of Kin and Coll. [135]. They proposed that the presence of highly acidic -SO 3 H groups could enhance the anhydrous proton conduction of fuel cell electrodes due to proton transfer to the phosphonic acid groups. The fuel cell, exhibiting a rated power density of 780 mW·cm −2 at 160 • C, with minimal degradation during 2500 h of operation and 700 thermal cycles from 40 to 160 • C under load, was developed by the results of the study.

Sidechain PCPAs as Flame Retardants
The phosphorus-containing FRs surpass halogen-based FRs in safety and are being intensively researched [12]. In a recent review of Özer and Gaan, devoted to phosphorusbased flame retardant coatings for textiles [174], low-MW compounds have mainly been described.
As with main-chain PCPAs, sidechain polyacids have been little studied as FRs. In 2013 Fang and Coll. reported on a study of the construction of Zn 2+ -and Cu 2+ -doped FR coatings on the surface of ramie fabrics [175]. PVPA and branched polyethylenimine/M 2+ were used in the layer-by-layer assembly technique. As a result, the thermal and fire stability of the coated fabric was improved, e.g., a significant residue (up to 25.2 wt %) was left (<1% for the control). The results of this study were somewhat expanded and corrected one year later [176].
El Hage and Coll. had chosen not to use metal salts, and studied different methods of VPA grafting [141] (Figure 7). Flame retardant properties of VPA-grafted flax fabrics can be explicitly illustrated by Figure 25, thus confirming the correctness of a chosen way.
El Hage and Coll. had chosen not to use metal salts, and studied different methods of VPA grafting [141] (Figure 7). Flame retardant properties of VPA-grafted flax fabrics can be explicitly illustrated by Figure 25, thus confirming the correctness of a chosen way. As was shown in [103], even small amounts of VPA in copolymer with acrylonitrile or acrylonitrile/methyl methacrylate reduces significantly the flammability of the materials. The authors assumed that the presence of -P(O)(OH)2 groups in acrylonitrile-based polymers accelerates intramolecular cyclization of the nitrile units (Scheme 43). Scheme 43. The proposed mechanism, and the effect of phosphonate and phosphonic acid on cyclization during heat treatment of acrylonitrile copolymers. [103].
Copolymers of methyl methacrylate and the most synthetically available phosphate-containing acrylate-type monomer MEPN (see Scheme 7) were studied by Marić and Coll. in 2020 [109]. They showed that the char yield content increased from 1.2 to 24.4 As was shown in [103], even small amounts of VPA in copolymer with acrylonitrile or acrylonitrile/methyl methacrylate reduces significantly the flammability of the materials. The authors assumed that the presence of -P(O)(OH) 2 groups in acrylonitrile-based polymers accelerates intramolecular cyclization of the nitrile units (Scheme 43). El Hage and Coll. had chosen not to use metal salts, and studied different methods of VPA grafting [141] (Figure 7). Flame retardant properties of VPA-grafted flax fabrics can be explicitly illustrated by Figure 25, thus confirming the correctness of a chosen way. As was shown in [103], even small amounts of VPA in copolymer with acrylonitrile or acrylonitrile/methyl methacrylate reduces significantly the flammability of the materials. The authors assumed that the presence of -P(O)(OH)2 groups in acrylonitrile-based polymers accelerates intramolecular cyclization of the nitrile units (Scheme 43). Scheme 43. The proposed mechanism, and the effect of phosphonate and phosphonic acid on cyclization during heat treatment of acrylonitrile copolymers. [103].
Copolymers of methyl methacrylate and the most synthetically available phosphate-containing acrylate-type monomer MEPN (see Scheme 7) were studied by Marić and Coll. in 2020 [109]. They showed that the char yield content increased from 1.2 to 24.4 Scheme 43. The proposed mechanism, and the effect of phosphonate and phosphonic acid on cyclization during heat treatment of acrylonitrile copolymers [103].
Copolymers of methyl methacrylate and the most synthetically available phosphatecontaining acrylate-type monomer MEPN (see Scheme 7) were studied by Marić and Coll. in 2020 [109]. They showed that the char yield content increased from 1.2 to 24.4 wt% for copolymers containing 6 to 28 mol% of MEPN. The limiting oxygen index (LOI) value (the minimum fraction of oxygen in an O 2 /N 2 mixture supporting the burning of a vertical sample) was estimated by Van Krevelen empirical Equation (3) for halogen-free polymers [177]: where CY is char yield. The LOI of pure poly(methyl methacrylate) and copolymer with 28 mol% MEPN content were 17.8 and 27.3 respectively. Note that the LOI of pure poly(MEPN) was 34.1.

Sidechain PCPA-Based Polymer Networks for Enzyme Immobilization
In the study of Toppare and Coll. [178], proton conducting polymer blend was prepared by mixing PVPA with poly(1-vinylimidazole) at various ratios (Scheme 44). The polymer network having the most suitable stoichiometric ratio for substantial proton conductivity was used for the immobilization of invertase. Despite the fact that the value of the Michaelis-Menten constant (K M ) for immobilized invertase was 3.5 times lower than the K M of the free enzyme (6.8 vs. 24.3 mM), the use of polymer matrix allowed to have the activity of the enzyme kept constant after 25 repetitive usages. wt% for copolymers containing 6 to 28 mol% of MEPN. The limiting oxygen index (LOI) value (the minimum fraction of oxygen in an O2/N2 mixture supporting the burning of a vertical sample) was estimated by Van Krevelen empirical Equation (3) for halogen-free polymers [177]: where CY is char yield. The LOI of pure poly(methyl methacrylate) and copolymer with 28 mol% MEPN content were 17.8 and 27.3 respectively. Note that the LOI of pure poly(MEPN) was 34.1.

Sidechain PCPA-based Polymer Networks for Enzyme Immobilization
In the study of Toppare and Coll. [178], proton conducting polymer blend was prepared by mixing PVPA with poly(1-vinylimidazole) at various ratios (Scheme 44). The polymer network having the most suitable stoichiometric ratio for substantial proton conductivity was used for the immobilization of invertase. Despite the fact that the value of the Michaelis-Menten constant (KM) for immobilized invertase was 3.5 times lower than the KM of the free enzyme (6.8 vs. 24.3 mM), the use of polymer matrix allowed to have the activity of the enzyme kept constant after 25 repetitive usages. Scheme 44. Protonation of PVPA and poly(1-vinylimidazole) with a formation of polyelectrolyte network [178].

Conclusions
In our review, we tried to show all the diversity of the synthetic approaches to sidechain PCPAs and the great potential of their applications. Sidechain PCPAs are different from other organic polyacids by higher acidity and, more significantly, by the ability to participate in biomineralization processes. The high chemical stability of the backbone of the sidechain PCPAs is a clear advantage in the development of the solid-state polyelectrolytes but is a serious obstacle to their use in tissue engineering and bone surgery.
Both for main-chain and sidechain PCPAs, the potential of the current polymer chemistry and science of catalysis remains largely unexploited. The very idea to combine polyester (or other) biodegradable backbone with -P(O)(OH)2-functionalized substituents has not yet been implemented despite its apparent promise.

Conclusions
In our review, we tried to show all the diversity of the synthetic approaches to sidechain PCPAs and the great potential of their applications. Sidechain PCPAs are different from other organic polyacids by higher acidity and, more significantly, by the ability to participate in biomineralization processes. The high chemical stability of the backbone of the sidechain PCPAs is a clear advantage in the development of the solid-state polyelectrolytes but is a serious obstacle to their use in tissue engineering and bone surgery.
Both for main-chain and sidechain PCPAs, the potential of the current polymer chemistry and science of catalysis remains largely unexploited. The very idea to combine polyester (or other) biodegradable backbone with -P(O)(OH) 2 -functionalized substituents has not yet been implemented despite its apparent promise.