Chapter 1
Strategies to Bring Conjugated Polymers into Aqueous Media

Jie Liu and Bin Liu

National University of Singapore, Department of Chemical and Biomolecular Engineering, 4 Engineering Drive 4, Singapore, 117585, Singapore

1.1 Introduction

Conjugated polymers (CPs) are organic macromolecules with extended p-conjugation along the molecular backbone [1, 2]. Their unique optoelectronic properties that result from the highly delocalized p-electrons can be easily manipulated through modification of the conjugated backbones. As a result, CPs have been widely used in various research fields related to organic optoelectronic devices [3-5], chemo/biosensors [6, 7], and medical diagnosis and therapy [7-9]. For biology-related applications, the main obstacle is to render CPs water soluble or water dispersible. So far, mainly three strategies have been used to bring CPs into aqueous media, which include the design and synthesis of conjugated polyelectrolytes (CPEs) and neutral water-soluble conjugated polymers (WSCPs), as well as the fabrication of water-dispersible conjugated polymer nanoparticles (CPNPs) (Scheme 1.1).

Scheme 1.1 Illustration of typical structures of CPE (a), neutral WSCP (b), and CPNP (c). The red color represents the CP backbone.

CPEs are a kind of macromolecules characterized by p-conjugated backbones and ionic side chains [10]. Their solubility in aqueous media can be fine-tuned by modification of the ionic side chains. Although neutral WSCPs do not possess any charge, they have amphiphilic segments, for example, oligo(ethylene glycol) [11], that compensate for the hydrophobic nature of the conjugated backbones. These two strategies require the chemical modification of each polymer to bring them into water. A more general and straightforward method is to prepare for the CPNPs, which can in principle bring any organic soluble polymers into aqueous media [12]. To simplify our discussion, in this chapter, we only discuss CPNPs that are prepared from neutral CPs. The water solubility of CPNPs is largely determined by the polymer matrix used and the nanoparticle size, while their optical properties are associated with the neutral CP.

This chapter aims to provide readers with an overview of the strategies that can be used to bring CPs into aqueous media for potential biological applications. In this chapter, we will discuss the synthetic approaches for CPEs first, which is followed by the neutral WSCPs and CPNPs. The section on CPEs is organized according to the charge sign. For each type of charge, we mainly select three types of CPEs (polythiophenes, poly(phenylene)s, and polyfluorenes) as examples to describe how the conjugated backbones can be synthesized and how the charged chains can be incorporated. Similar strategies will be discussed on neutral WSCPs. For the section on CPNPs, we will mainly introduce three strategies for CPNP preparation (e.g., reprecipitation, miniemulsion, and nanoprecipitation) with specific examples. Owing to the limited space, we apologize that we cannot cover every example, and only the most representative ones are selected for discussion.

1.2 Synthesis of CPEs

In the past decades, a large number of CPEs have been successfully developed. According to their chemical structures, the synthesis of CPEs involves two aspects: construction of the conjugated backbones and incorporation of charged side chains. Many well-established polymerization methods have been employed to build the conjugated backbones (Scheme 1.2), which were typically catalyzed with organometallic complexes or bases, including Suzuki, Yamamoto, Stille coupling reaction and FeCl3-catalyzed oxidative reaction for single bond formation; Heck, Witting, Knoevenagel, and Gilch coupling reactions for double bond formation; and Sonogashira coupling reaction for triple bond formation. In addition, CpCo(CO)2-catalyzed homopolycyclotrimerization has also been used to synthesize hyperbranched CPEs [13]. Rational design of the conjugated backbones allows facile manipulation of their optical properties, such as absorption, emission, and quantum yield. The charges can be incorporated via direct polymerization of charged monomers or postfunctionalization of neutral CPs into CPEs (Scheme 1.3). According to the charge sign of the ionic side chains, CPEs can be categorized into three groups: anionic CPEs, cationic CPEs, and zwitterionic CPEs. The anionic groups generally include sulfonate [14], carboxylate [15], and phosphonate [16], while the cationic groups include quaternary ammonium [17], pyridinum [18], and phosphonium [19]. In the following section, we will use specific examples to show the synthetic approaches of CPEs with different charges. We start each section with polythiophenes, as they are commonly synthesized via electropolymerization and FeCl3-catalyzed oxidative polymerization methods. The other CPEs are generally introduced following the sequence of single, double, and triple-bonded CPEs.

Scheme 1.2 Polymerization methods most widely employed to construct conjugated backbones. Ar1 and Ar2 represent aromatic units.

Scheme 1.3 Representative strategies for synthesis of CPEs through incorporation of charges via direct polymerization (a) and postpolymerization (b) method.

1.2.1 Anionic CPEs

1.2.1.1 Sulfonated CPEs

Sulfonated polythiophenes are generally synthesized through electropolymerization or FeCl3-catalyzed oxidative polymerization methods. As shown in Scheme 1.4a, the first sulfonated polythiophene P2 was reported by Wudl's group in 1987 [14]. 2-(Thiophen-3-yl)ethanol 1 reacting with methanesulfonyl chloride yielded methyl 2-(thiophene-3-yl)ethanesulfonate 2. Electropolymerization of 2 led to a neutral polythiophene P1, which was subsequently treated with NaI in acetone to give sulfonated P2. Using the same electropolymerization method, another sulfonated polythiophene P3 was developed by Zotti's group (Scheme 1.4b) [20]. The key sulfonated monomer 4 was synthesized by alkylation of 4H-cyclopenta[2,1-b:3,4-b´]dithiophene 3 in the presence of 1,4-butanesultone and n-BuLi. The direct electropolymerization of 4 afforded P3. Unlike P2 prepared via postpolymerization strategy, the sulfonated groups of P3 are inherited from the key monomer 4. In addition, Leclerc's group reported a sulfonated polythiophene P4 by oxidative polymerization method (Scheme 1.4c) [21]. Briefly, the alkoxylation of 3-bromo-4-methylthiophene 5 was performed in N-methyl-2-pyrrolidone in the presence of sodium methoxide and copper bromide, leading to 3-methoxy-4-methylthiophene 6, which reacted with 2-bromoethanol and sodium sulfite in toluene to yield 3-(2-bromoethoxy)-4-methylthiophene 7. Subsequent treatment of 7 with sodium sulfite in a mixture of water/acetone led to sodium 2-(4-methyl-3-thiophenyl-1-oxy)ethanesulfonate 8, which underwent FeCl3-catalyzed oxidative polymerization to afford P4.

Scheme 1.4 Synthesis of sulfonated polythiophenes P2-P4.

To synthesize CPEs with single bonded backbones, Suzuki polymerization was often used due to its high reaction yield and good selectivity toward various functional groups [22]. As shown in Scheme 1.5a, the first sulfonated poly(p-phenylene) P6 was synthesized by Wegner's group via the Suzuki polymerization method [23]. The key monomer 10 was prepared via the chlorosulfonation of 1,4-dibromobenzene 9 with chlorosulfonic acid in dichloromethane, followed by treatment with p-cresol in the presence of pyridine. Then, Pd-catalyzed Suzuki polymerization between 10 and 2,2´-(2-dodecyl-5-methyl-1,4-phenylene)bis(1,3,2-dioxaborinane) 11 in the presence of sodium carbonate yielded a neutral poly(p-phenylene) P5. Subsequent solvolysis of P5 in a mixture of sodium butanolate/1-butanol followed by the addition of water, gave the sulfonated poly(p-phenylene) P6 in quantitative yield. Only one of the two possible positional isomeric structures of the repeated unit is shown in P5 and P6 for the sake of simplicity in illustration.

Scheme 1.5 Synthesis of sulfonated CPEs P6 and P7 with single-bonded backbones through Suzuki polymerization method.

A direct polymerization method for synthesizing sulfonated poly(p-phenylene) P7 through Suzuki polymerization was reported by Reynolds's group via three steps (Scheme 1.5b) [24]. 2,5-Dibromohydroquinone 13 was synthesized via bromination of 1,4-dimethoxybenzene 12 using bromine in tetrachloromethane, followed by the treatment with boron tribromide in anhydrous dichloromethane. Subsequent sulfonation of 13 with 1,3-propanesultone and sodium hydroxide in absolute ethanol led to the...