Poly(3,4-ethylenedioxythiophene) (PEDOT) Derivatives: Innovative Conductive Polymers for Bioelectronics

Abstract

Poly(3,4-ethylenedioxythiophene)s are the conducting polymers (CP) with the biggest prospects in the field of bioelectronics due to their combination of characteristics (conductivity, stability, transparency and biocompatibility). The gold standard material is the commercially available poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS). However, in order to well connect the two fields of biology and electronics, PEDOT:PSS presents some limitations associated with its low (bio)functionality. In this review, we provide an insight into the synthesis and applications of innovative poly(ethylenedioxythiophene)-type materials for bioelectronics. First, we present a detailed analysis of the different synthetic routes to (bio)functional dioxythiophene monomer/polymer derivatives. Second, we focus on the preparation of PEDOT dispersions using different biopolymers and biomolecules as dopants and stabilizers. To finish, we review the applications of innovative PEDOT-type materials such as biocompatible conducting polymer layers, conducting hydrogels, biosensors, selective detachment of cells, scaffolds for tissue engineering, electrodes for electrophysiology, implantable electrodes, stimulation of neuronal cells or pan-bio electronics.

Keywords: PEDOT; bioelectronics; biopolymers; conducting polymers.

Figure 1

Graphical representation of alternative materials to PEDOT:PSS described in this review.

Figure 2

The two most used synthetic pathways for the synthesis of EDOT and ProDOT monomers.

Figure 3

The most used functional EDOT derivatives.

Figure 4

The most representative functional EDOT monomers synthesized from hydroxymethyl-EDOT. On the left side, the synthetic pathway is shown using alkylbromides to connect an (a) aromatic acid [18], (b) aliphatic bromine [19], (c) aliphatic acid [20,21,22,23], (d) aliphatic chains [24,25], (e) alkene [26], (f) halogenated aliphatic [27,28], (g) alkyne [29,30], and (h) aliphatic sulfonate [31] moieties. On the right side, the pathway is shown using carboxylic acid derivatives to connect an (i) aliphatic acid [23], (j) protected amino acid [32], (k) fluorinated aliphatic chain [24,33,34], (l) TEMPO ((2,2,6,6-Tetramethylpiperidin-1-yl)oxyl) [35], (m) pyridinium [36], (n) alkene [37], (o) tertiary bromide [38], (p) secondary bromide [39], and (q) quaternized ammonium salt moieties [40].

Figure 5

Most representative functional EDOT monomers synthesized from chloromethyl-EDOT. Substituted with: (a) imidazolium salts [44,45], (b) methacrylate [46], (c) pyrimidine bases [47], (d) thiole [26,48], (e) azide [49,50,51,52,53], and (f) amino moieties [54,55].

Figure 6

Most representative functional EDOT monomers synthesized from azidomethyl-EDOT using click chemistry: (a) aliphatic, ferrocene phtalamide [50,52], (b) fluorinated ester, substituted xantene [51], (c) sugar, bipyridine, naphtalenediimide, substituted fullerene [63], (d) plain aliphatic chains [49,64], (e) plain aromatic groups [65], (f) fluorinated ester [64], (g) fluorinated aromatic, primary alcohol [53], and (h) sulfonate salt, have all been connected to the EDOT scaffold via a triazole spacer [66].

Figure 7

ProDOT main synthetic pathway and derivatives: (a) primary alcohols and diol [24,81,82,83,84,85,86,87,88], (b) primary mono- and di-bromide [71,72,73,74,75,76,77], (c) mono- and di-azide [30,71,72,73,74,75,76,77,80], (d) mono- and di-aliphatic chains [58,81,89,90,91,92,93,94,95,96,97,98,99], (e) mono- and di-aromatic groups [67,68,69,70], (f) di-cyano [78], (g) di-alkene [79], (h) di-carboxylic acid [78], (i) carboxylic acid [100].

Figure 8

Synthetic route to PEDOT:Hyaluronic acid aqueous dispersions [113].

Figure 9

PEDOT:biopolymer dispersions employing hyaluronic acid, heparin, chondroitin sulfate [113], dextran sulfate [112], DNA [110], sulfated cellulose [111], pectin [114], and guar gum [115].

Figure 10

Different applications of functional EDOT monomers. (a) adhesion properties [120], (b) electronic-plants [121], (c) selective detachment of cells [122], (d) hydrogels [22].

Figure 11

Different applications of functional EDOT monomers II. (a) virus recognition [125], (b) vitamin C detection [32], (c) specific recognition [47], (d) switchable wettability [126].

Figure 12

Different applications of PEDOT:biopolymer dispersions. (a) PEDOT ion gel [115], (b) recording/stimulating devices [113], (c) inkjet printing [112], (d) preparation of scaffolds [127].