Selected physicochemical aspects of poly- and perfluoroalkylated substances relevant to performance, environment and sustainability-part one.

Chemosphere xxx (2014) xxx–xxx

Contents lists available at ScienceDirect

Chemosphere journal homepage: www.elsevier.com/locate/chemosphere

Selected physicochemical aspects of poly- and perfluoroalkylated substances relevant to performance, environment and sustainability—Part one Marie Pierre Krafft a,⇑, Jean G. Riess b a b

Institut Charles Sadron (CNRS UPR 22), Université de Strasbourg, 23 rue du Loess, 67034 Strasbourg Cedex 2, France Harangoutte Institute, 68160 Sainte Croix-aux-Mines, France

h i g h l i g h t s

g r a p h i c a l a b s t r a c t

Highly thermally and chemically

stable PFASs form sturdy, repellent protecting films. Perfluorinated chains are both extremely hydrophobic and lipophobic. Performances of PFASs decrease strongly with fluorinated chain length. Surprisingly little reliable data is available on the physical chemistry of PFASs. Such data are needed for understanding the environmental and health impact of PFASs.

a r t i c l e

i n f o

Article history: Received 11 April 2014 Received in revised form 10 August 2014 Accepted 13 August 2014 Available online xxxx Handling Editor: I. Cousins Keywords: Fluorosurfactant PFOA Self-assembled interfacial film Persistence Bioconcentration Health

a b s t r a c t The elemental characteristics of the fluorine atom tell us that replacing an alkyl chain by a perfluoroalkyl or polyfluorinated chain in a molecule or polymer is consequential. A brief reminder about perfluoroalkyl chains, fluorocarbons and fluorosurfactants is provided. The outstanding, otherwise unattainable physicochemical properties and combinations thereof of poly and perfluoroalkyl substances (PFASs) are outlined, including extreme hydrophobic and lipophobic character; thermal and chemical stability in extreme conditions; remarkable aptitude to self-assemble into sturdy thin repellent protecting films; unique spreading, dispersing, emulsifying, anti-adhesive and levelling, dielectric, piezoelectric and optical properties, leading to numerous industrial and technical uses and consumer products. It was eventually discovered, however, that PFASs with seven or more carbon-long perfluoroalkyl chains had disseminated in air, water, soil and biota worldwide, are persistent in the environment and bioaccumulative in animals and humans, raising serious health and environmental concerns. Further use of longchain PFASs is environmentally not sustainable. Most leading manufacturers have turned to shorter four to six carbon perfluoroalkyl chain products that are not considered bioaccumulative. However, many of the key performances of PFASs decrease sharply when fluorinated chains become shorter. Fluorosurfactants become less effective and less efficient, provide lesser barrier film stability, etc. On the other hand, they remain as persistent in the environment as their longer chain homologues. Surprisingly little data (with considerable discrepancies) is accessible on the physicochemical properties of the PFASs

⇑ Corresponding author. Tel.: +33 3 88 41 40 60; fax: +33 3 88 40 41 99. E-mail address: [email protected] (M.P. Krafft). URL: http://www-ics.u-strasbg.fr/ (M.P. Krafft). http://dx.doi.org/10.1016/j.chemosphere.2014.08.039 0045-6535/Ó 2014 Published by Elsevier Ltd.

Please cite this article in press as: Krafft, M.P., Riess, J.G. Selected physicochemical aspects of poly- and perfluoroalkylated substances relevant to performance, environment and sustainability—Part one. Chemosphere (2014), http://dx.doi.org/10.1016/j.chemosphere.2014.08.039

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M.P. Krafft, J.G. Riess / Chemosphere xxx (2014) xxx–xxx

under examination, a situation that requires consideration and rectification. Such data are needed for understanding the environmental and in vivo behaviour of PFASs. They should help determine which, for which uses, and to what extent, PFASs are environmentally sustainable. Ó 2014 Published by Elsevier Ltd.

1. Introduction and scope Chemistry analyses and transforms matter. It has been practiced ever since man invented beer, fired pottery and cooked his stew. Nowadays, chemistry touches essentially every facet of human life and activity. Man has created molecules and materials that do not (sometimes cannot) exist in nature and that are bestowed with properties unfound or unmatched by natural products and materials. Highly fluorinated organics are among these anthropogenic creations. The first perfluoroalkanoic acid, trifluoroacetic acid CF3COOH, was synthesized in 1920 by Swartz (Banks et al., 1994), and the first perfluorocarbon, CF4, was isolated in 1926 (Lebeau and Damien, 1926). Commercial exploitation started, with little regulation, in the early 1950’ following Plunkett’s fortuitous discovery (1938) of poly(tetrafluoroethylene) (PTFE, e.g. Teflon). Thousands of per- and polyfluoroalkyl substances (PFASs)1 (Buck et al., 2011) have since been synthesized and their outstanding properties have generated hundredths of valuable technical advances, uses and markets (Banks et al., 1994; Howe-Grant, 1995; Baasner et al., 2000; Banks, 2000; Kissa, 2001; Krafft and Riess, 2007; OECD, 2014). Then, in the late 1970’, two to three orders of magnitude higher than normal levels of organic fluorine were detected in the blood of workers at a perfluorochemical production factory. Perfluorooctanoic acid (PFOA, Table 1 compound 20) was identified in their urine (Ubel et al., 1980). PFASs were subsequently found in air, water, soil, animals and humans worldwide, and were identified as global, persistent and bioaccumulative, potentially harmful pollutants (Giesy et al., 2001; Hansen et al., 2001; Prevedouros et al., 2006; Calafat et al., 2007; Lau et al., 2007; Conder et al., 2008; Parsons et al., 2008; Olsen et al., 2009; van Leeuwen and de Boer, 2007; Pistocchi and Loos, 2009; D’Hollander et al., 2010; Frömel and Knepper, 2010; Ahrens, 2011; Houde et al., 2011; Lindstrom et al., 2011; OECD, 2014). A turning point was reached in 2000 when concerns about environmental and toxicological impact led the 3M Company, in association with the US Environmental Protection Agency (USEPA), to start phasing out its perfluorooctane sulfonates (PFOS 5), perfluorooctanoic acid (PFOA 20) and related compounds product lines. This review is Part one of a Project that examines the physicochemical properties of perfluoroalkyl chains and PFASs that underlie both their widespread usages and the environmental concerns they raise. Part Two will review the reasons why long perfluoroalkyl chain substances are now being phased out as much as technically possible; discuss their shorter chain alternatives’ performances and whether the specific functional properties of fluorosurfactants and fluoropolymers can be obtained without recourse to long perfluoroalkyl chains; outline some perspectives for future developments, and address the question whether sustainable use of highly fluorinated material is achievable.2

1 The terminology and acronyms used here (see Table 1) are those recommended by Buck et al. (2011). 2 This paper is largely based on lectures (MPK) presented at the 5th International Workshop on Per- and Polyfluorinated Alkyl Substances in Helsingør, Denmark (October 2013) and at the Society for Analytical Chemistry, Copenhagen University.

The literature on the subject has become colossal, with over 400 papers published per year (Buck et al., 2011); only a limited number of references can be provided here. 2. Some fundamentals about fluorine, perfluoroalkyl chains, and fluorosurfactants Replacing hydrogen atoms by fluorine atoms in an organic molecule is not a benign operation. Fluorine, ‘‘the enabler’’ (Banks et al., 1994), has a much higher ionisation potential (1676 vs. 1312 kJ mol 1), electron affinity (328 vs. 73 kJ mol 1) and electronegativity (3.98 vs. 2.20), and lower polarisability (a = 0.557 10 24 vs. 0.667 10 24 cm3) than hydrogen (and all the other Second Row elements of the Periodic Table (Table 2)). Its covalent radius is 0.57 Å versus 0.31 Å for hydrogen. The exact value of its van der Waals radius (which reflects the atom’s space requirements) is still controversial (Schlosser and Michel, 1996). Published values range from 1.35 Å (Pauling, 1960) to 1.47 Å (vs. 1.20 Å for H), probably meaning that the space occupied by an individual fluorine atom in a molecule depends largely on its neighbourhood, which can cause some electron density anisotropy. In F-chains, the value of 1.43–1.47 Å (Bondi, 1964) appears realistic in view of the difference in cross-sections measured between F-alkyl and alkyl chains. Fluorine’s radius would then be close to that of oxygen (1.52 Å). Difluorine F2 has a much higher oxidation potential then H2 (1/2 X2 ? X : 2.87 eV) (Rosen, 1978; Tiddy, 1985; Smart, 1994; HoweGrant, 1995; Kissa, 2001). 2.1. Perfluoroalkyl chains versus alkyl chains Perfluoroalkyl chains (CnF2n+1A, F-alkyl)3 differ from alkyl chains (CnH2n+1A) in many important ways (Fig. 1) (Banks et al., 1994; Howe-Grant, 1995; Krafft and Riess, 2009). For a given number of carbon atoms, a linear F-alkyl chain has a 50% larger cross-section area than an alkyl chain (27–30 Å2, vs. 18–21 Å2). The van der Waals diameters are 5.6 Å for F-alkyl chains and 4.2 Å for alkyl chains (Barriet and Lee, 2003). F-alkyl chains are thus more space demanding than alkyl chains. Structurally, the larger size of fluorine as compared to hydrogen forces long F-chains to adopt an all-trans helical conformation rather than the trans-planar zig-zag conformation of alkyl chains (Bunn and Howells, 1954; Clark, 1999; Ellis et al., 2004b; Krafft and Riess, 2009; Zenasni et al., 2013). The volumes occupied by CF2 and CF3 groups are 38 Å3 and 92 Å3, as compared to 27 Å3 and 54 Å3 for CH2 and CH3 groups, respectively. They are also much more rigid, have lesser conformational freedom and present fewer conformational defects than hydrocarbon chains, which facilitates ordered packing of F-chain, including in one molecule-thick (1–3 nm) two-dimensional films. The helical conformation (and helical/planar interchanges) and dense electron coating also provide a smoother, streamlined dynamic molecular shape that may facilitate movement of the F-chain along its axis, a feature reflected macroscopically by lubricant properties. The standard CAF bond (av. 485 kJ mol 1, as compared to 413 kJ mol 1 for CAH bond in hydrocarbons) is the strongest sin3 The common chemist’s italized notation F- for ‘‘perfluoro’’ will be used throughout the paper; F-chains, for short, means F-alkyl chain.


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M.P. Krafft, J.G. Riess / Chemosphere xxx (2014) xxx–xxx Table 1 Principal PFASs production routes and products.

CnF2n+1SO3H (PFSA) 4

CnH2n+1SO2F EFC

P(O)(OH)2 12

(n = 8: PFOS) 5 (n = 4: PFBS) 6

-

HF, e

(FASA) 7

(PASF) 1

polyacrylates

Cn-1F2n-1COOH (PFCA) 19

CH2=CH2 (PFAI) 17 (n = 8: PFOI) 18 Telomerisation (FTI) (n = 8: 8:2 FTOI) 22

CnF2n+1CH2CH2O H (n:2 FTOH) 29

(n = 8: 8:2 FTOH) 30

Cm-2H2m-3CH=CH2

/

P(O)OH

CnF2n+1CH2CH2SO3H

(SFA) 23

(FTSA) 24 (n = 8: 8:2 FTOS) 25

C(O)

polymethacrylates

CH3

39

CH2

CH-CH

(CH2CH2O)pH (or R) 34

CH2

C(O)

C(O)CH=CH2 (FTAC) 35

CnF2n+1

CH2

NH

CH2

C(O)

CnF2n+1

O

2 (diPAP) 33

C(O)C(CH3)=CH2

CnF2n+1CmH2m+1

polyurethanes

(FTMAC) 36

C(O)NHRCH=CH2 37

CH-CH2

CF2=CH2

CH2OCH2CnF2n+1

CF3CF—CF2 O

CHF=CH2

CH2

O —CF2CF2— PTFE 41

F2 + (R)C-H Direct (surface) fluorination

40

CH2

Fluoropolymers

CF2=CF2

P(O)OH2

(monoPAP) 32

CnF2n+1CH2CH2I 21

CnF2n+1I

CnF2n+1 CH2COOH (n:2 FTCA) 31

CnF2n+1CH=CH2 (FTO) 26

(n = 7: PFOA) 20

38

CH-CH2

(n = 8: PFNA) 28

C2F5I (TFE)

C(O)NHCH=CHCH2 16

CnF2n+1COOH (PFCA) 27

Salts

Telomerisation CF2=CF2

2

Polysulfonamidoethyl

(FASE)10 (n = 8, R = Et: NEtFOSE) 11

(n = 8, R = CH3: NMeFOSA) 8 (n = 8, R = C2H5: NEtFOSA) 9

(n = 8: POSF) 2 (n = 4: PBSF) 3

P(O)OH 13

C(O)C(CH3)=CH2 (FASMAC) 15 monomers

CnF2n+1SO2N(R)CH2CH2O H

CnF2n+1SO2NHR

CnF2n+1SO2F

/

C(O)CH=CH2 (FASAC) 14

—CF2CH2—

—CHFCH2—

—CF(CF3)CF2O—

PVF 43

PVDF 42

44

CnF2n+1

—CH2C(CH3)CH2O— 45

CH2OCH2CnF2n+1 Fluoropolymers

(R)C-F + HF G25 = 433 kJ mol (inert gas control)

Table 2 Atomic characteristics of fluorine as compared to the other Second Row atoms.

Ionisation potential (kJ mol 1) Electronaffinity (kJ mol 1) Electronegativity (Pauling units) Polarizability a (10 24 cm3) Covalent radius (Å) van der Waals radius (Å)

F

H

O

N

C

1676 328 3.98 0.557 0.57 1.47

1312 72.8 2.20 0.667 0.31 1.20

1314 141 3.44 0.82 0.66 1.52

1402 -6.3 3.04 1.10 0.71 1.55

1086 153 2.55 1.76 0.76 1.75

C

F

F

a

F

F

Data from Bondi (1964) and Smart (1994) and Cambridge Structural Data Base.

gle bond known in organic chemistry. It is strongly polarised, that is, electrons are shifted from carbon to the more electronegative fluorine, thus generating a strong electric dipole. Multiple fluorine substitutions on a same carbon further increases CAF bond energy (e.g. 530 kJ mol 1 in CF3CF3 vs. 450 kJ mol 1 in CH3CH2F). Moreover, the backbone CAC bonds are significantly stronger in fluorocarbons than in hydrocarbons, (e.g. by 34 kJ mol 1 in poly(tetrafluoroethylene) vs. polyethylene), also a consequence of the electroattractive character of fluorine and polarisation of the CAF bond. The bonds between an F-chain carbon and oxygen, nitrogen, chlorine or bromine atoms are usually also strengthened (due to induced enhanced electronegative character of fluorine-bearing carbon atoms), often leading to inactivation of potential functional sites (Banks and Tatlow, 1986; Smart, 1994; Krafft and Riess, 2009). The ACF2ACH2A bond between F-alkyl and alkyl chains is strongly polarised (Tournilhac et al., 2001; Krafft and Riess, 2009). With 9 electrons and 9 protons, as compared to one electron and one proton for hydrogen, fluorine has a much denser and less polarisable electron cloud. As a result, the intermolecular (van der Waals) attraction forces are significantly weaker in fluorocarbons (CnF2n+2) than in hydrocarbons (CnH2n+2). Consequently, fluorocarbons are roughly as volatile as or more volatile than hydrocarbon

b

C

H

~ 28 Å2

C H C H

~19 Å2

Fig. 1. Comparative hard-sphere model representations of F-alkyl and alkyl chains and their cross-sections. Adapted from Krafft and Riess (2009).

analogues, in spite of over twice larger molecular weights (MW). Certain neutral fluorosurfactants are actually much more volatile than their hydrocarbon analogues. For example, the vapour pressure of fluorotelomer alcohol C8F17C2H4OH (10:2 FTOH, MW 464 g mol 1) is 1000 times higher than that of its same-length hydrocarbon analogue dodecanol C10H21OH (MW 158 g mol 1) likely as a consequence of internal hydrogen bonding (Stock et al., 2004). This facilitates fluorosurfactants entry in the atmosphere and areal transport (Ding and Peijnenburg, 2013). The more


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volatile shorter compounds may have potential for global warming (green house effect) although this effect should be negligible as compared to that due to CO2 emissions (Kirsch, 2006). Fluorosurfactants have also a strong tendency to stabilize aerosols and adsorb on sediments (Higgins and Luthy, 2006; Ding and Peijnenburg, 2013). Low polarisability of F-chains is further reflected by record low refractive indexes, close to or lower than that of water. Low intermolecular interactions also translate into enhanced aptitude to dissolve gases (e.g. Ar, O2, CO2) (Gjaldbaek and Hildebrand, 1949; Hamza et al., 1981; Patrick, 1982). On the other hand, Fchain’s aptitude for ordered packing leads to higher melting points and thus to narrower liquid phase domains (Riess, 2002). Low, ‘‘gas-like’’ intermolecular cohesion also results in very low solubility in highly structured liquids like water. All other things being equal, ionic surfactant salts have lower volatility but higher solubility in water than neutral species. Due to higher surface areas and lower intermolecular forces, Fchains are much more hydrophobic than alkyl chains of comparable length. The extreme hydrophobic interactions (Tanford, 1980) developed by F-chains cause fluorosurfactants to segregate and self-assemble when dispersed in water and also to collect in an orderly fashion at interfaces. This reflects the fact that the incremental change in free energy of adsorption, DDG0, for the transfer of each CF2 group from water to the air/water interface is almost twice as large as for a CH2 group ( 5.1 vs. 2.6 kJ mol 1) (Mukerjee and Handa, 1981; Mukerjee, 1994). In polymers, replacing part of a hydrocarbon side chain by a fluorinated one increases the hydrophobic character but also reduces chain-chain interactions (Schneider et al., 1989). It requires at least four fluorinated carbons to develop hydrophobic interactions large enough to compensate for the weaker interactions between F-chains and promote self-assembly (Riess et al., 1996). ‘‘True’’ perfluorocarbons (CnF2n+2, e.g. perfluorooctane, C8F18, and PTFE) are PFASs that are devoid of hydrophilic polar function and which, although they have very low surface energies, are not amphiphilic and are not surfactants. Fluorocarbons epitomise the essential properties of F-chains. They have the lowest surface tensions, refractive indices and dielectric constants of all liquids. They have higher density, fluidity, compressibility, gas solubilities and critical temperatures than hydrocarbons of similar length. The solubility of fluorocarbons in water is extremely low and decreases exponentially with chain length (Fig. 2). Fluorocarbons and semifluorinated alkanes (CnF2n+1CmH2m+1, SFA, 23) constitute valuable reference substances for extricating the specific roles of F-chains in a molecule and assessing the impact of F-chain length on phys-

Fig. 2. The solubility of perfluorocarbons in water (25 °C) decreases exponentially with F-chain length and molecular weight. For F-octylbromide (star, MW 499) it is 5 10 6 mol m 3 (Krafft and Riess, 2009).

ical and biological characteristics (Riess et al., 1991; Privitera et al., 1995a; Krafft and Riess, 2009; Krafft, 2012b). The remarkable biological inertness of pure fluorocarbons and closely related, essentially non-amphiphilic derivatives (e.g. C6F14, C8F17Br), is well documented subsequent to research on blood substitutes, liquid ventilation and diagnostic imaging (Fig. 3) (Leach et al., 1996; Riess, 2001; Krafft and Riess, 2007, 2008; Haiss et al., 2009). C6F14 has been used to stabilize gas microbubbles used as contrast agents in ultrasonography(Schutt et al., 2003) and C8F17Br as a contrast agent for bowel wall delineation by X-ray imaging (Mattrey et al., 1994). 2.2. Fluorosurfactants For maximum surface activity, a strongly hydrophobic, typically 8-fluorinated carbons-long F-chain is associated with an ‘‘incompatible’’ strongly hydrophilic moiety or function, such as an acid (e.g. ACOOH, ASO3H, AOP(O)(OH)2), a poly(ethylene glycol) (PEG) chain (AO(CH2CH2O)pH) or a polyol (e.g. a carbohydrate) thus forming a highly amphiphilic molecule. The resulting surfactants can be ionic or non-ionic. The F-chain strongly modifies the behaviour of the terminal hydrophilic function (e.g. diminishes the pKa of an acid). PFSAs are strong acids, fully ionised under essentially all possible environmental conditions (Ding and Peijnenburg, 2013). Diverse molecular topologies for fluorosurfactants are feasible and an alkyl spacer (e.g. (ACH2CH2A)m) can be inserted between the hydrophobic and hydrophilic moieties (Riess, 1995; Krafft and Riess, 1998) This spacer generally increases the hydrophobicity of the surfactant, but might also decrease its performances, as it introduces some lipophilic character, resulting in increasing solubility in organic solvents and fat. It also allows tuning of wetting properties of polymers (Guo et al., 2008). From a chemical reactivity standpoint, a ACH2CH2A spacer acts as a screen between the F-chain and the polar function, which essentially recovers its ‘‘normal’’ properties. Reliable data on fundamental properties of environmentally relevant PFASs are still sparse. A recent extensive compilation of experimental data and in silico predictions is available that includes aqueous solubilities, vapour pressures, pKa values for acids, partition coefficients between air and water, octanol and air, organic carbon and water, bioconcentration, bioaccumulation and biomagnification factors for environmentally relevant PFASs (Ding and Peijnenburg, 2013). These data are limited, often inaccurate and discrepancies can reach several orders of magnitude (Linkov et al., 2005; Arp et al., 2006; Goss et al., 2006; Ding and Peijnenburg, 2013). These discrepancies may originate from purity or solubility problems, colloidal aggregation or adsorption behaviour, matrix effect, unsuitable analytical methods or models, lack of standardization of procedures, inadequate validation, etc. Useful quantitative structure/property relationship (QSPR) modelling based on, and validated by experimental data have been developed for aqueous solubility, vapour pressure and critical micellar concentrations of PFASs (Bhhatarai and Gramatica, 2011). Such predictions are illustrated in Fig. 4 for PFCAs and Fig. 5 for FTOHs. Early on, it has been recognised that the phase behaviour of alkali salts of PFCAs differs considerably from that of hydrocarbon analogues (Fontell and Lindman, 1983; Tiddy, 1985; Hoffmann and Würtz, 1997; Monduzzi, 1998). Fluorinated surfactants have lower critical micellar concentrations (cmc; the concentration above which no further decrease of surface tension is seen, as the surfactant molecules start assembling into micelles in the aqueous phase) than their hydrocarbon analogues (Fig. 6). The cmc values decrease exponentially with increasing F-chain length (Fig. 7) (Lin, 1972; Shinoda et al., 1972; Kunieda and Shinoda, 1976). The cmc values of fluorosurfactants are roughly equivalent to those of hydrocarbon surfactants with a 50% longer chain (Mukerjee



5

Fig. 3. X-ray images showing (a) exquisite delineation of the bowels of an adult volunteer filled with radiopaque F-octylbromide C8F17Br; and (b) lungs of an infant with severe respiratory distress syndrome filled intratracheally with the same fluorocarbon (Leach et al., 1996). Courtesy Alliance Pharmaceutical Corp.

Fig. 4. Examples of trends in physicochemical data for a homologous series of PFCAs at 25 °C: (a) predicted (QSPR) solubilities in water (mg L 1) (Bhhatarai and Gramatica, 2011); (b) QSPR vapour pressures (Pa) (Bhhatarai and Gramatica, 2011); (c) experimental pKa values (Moroi et al., 2001), for PFOA: lower value from Igarashi and Yotsuyanagi (1992) and López-Fontán et al. (2005), higher value from López-Fontán et al. (2005); and (d) calculated air/water partition coefficient Ka/w (Arp et al., 2006).

and Handa, 1981; Mukerjee, 1994). For metal salts of PFCAs and PFSAs, the contribution of a CF2 group to micellization is roughly equivalent to 1.6 times that of a CH2 group (Mukerjee and Handa, 1981). This simple rule is not valid, however, for all type of surfactants and properties. For example, the cloud points of fluorinated poly(oxyethylene) surfactants are lower than those of hydrocarbon analogues even twice longer (Mathis et al., 1984). Short alkyl spacers do not obey the rule either, leaving control of adsorption and micellisation to the F-chain (Sadtler et al., 1998a). That fluorination drastically changes the behaviour of an alkyl chain is further illustrated by the notable fact that simply associat-

ing mutually incompatible (or phobic) F-alkyl and alkyl chains, as in SFAs, more precisely (F-alkyl)alkanes, 23), already generates marked amphiphilic character, surface activity and propensity for self-association and organisation (Gaines, 1991; Krafft and Riess, 2009; Krafft, 2012b). 2.3. Aptitude for self-assembly—interfacial film formation Introducing an F-chain in a molecule reduces not only its solubility in water but also in lipids. Consequently, F-chains tend to separate from alkyl chains as well as from hydrophilic chains, moi-


6


Fig. 5. Examples of trends in physicochemical data for a homologous series of fluorotelomer alcohols (n:2 FTOH) at 25 °C: (a) experimental solubilities in water (mg L 1) (Liu and Lee, 2007); (b) QSPR vapour pressures (Pa) (Bhhatarai and Gramatica, 2011); (c) experimental air/water partition coefficient Ka/w (Goss et al., 2006); (d) octanol/water partition coefficient Ko/w (Carmosini and Lee, 2008); (e) experimental octanol/air partition coefficient Koa (Goss et al., 2006) and (f) experimental organic carbon/water partition coefficient Koc (Goss et al., 2006; Ding and Peijnenburg, 2013).

eties and functions, and tend to exclude both hydrophilic and lipophilic solutes. Extreme hydrophobicity, along with lipophobicity, and rod-like, rigid F-chain shape concur to endow fluorinated surfactants with a powerful driving force for segregation and self-assembly into discrete supramolecular constructs and thin interfacial films, as well as for compartmentation at the molecular level (Fig. 8) (Ringsdorf et al., 1988; Kunitake, 1992; Riess, 2002; Krafft, 2006; Krafft and Riess, 2007, 2009). These non-covalent,

‘‘super’’ hydrophobic binding interactions (alike the hydrophobic effect ubiquitous in biochemistry (Tanford, 1980), but stronger), augment markedly with F-chain length. Multiple fluorinated patches, as in non-natural CF3-sustituted aminoacids or nucleic bases, allowed molecular recognition and fluorine-driven selfassembly into non-natural proteins and nucleic acids, including in vivo! (Bilgiçer and Kumar, 2004; Jäckel et al., 2006; Montclare and Tirrell, 2006; Connor and Tirrell, 2007). A clear illustration of


7


Surface tension (mN/m)

a

b

Air, Fluorocarbon

Air, Fluorocarbon

Water Hydrocarbon cmc

c

d

Fig. 8. Fluorinated self-assembled films and colloids. (a) Monolayer of fluorosurfactant at the water/air (or water/fluorocarbon) interface; (b) illustrates the fact that F-alkyl and alkyl chains are mutually phobic: semifluorinated alkanes (CnF2n+1CmH2m+1, SFA) organise as monolayers at hydrocarbon/air (or hydrocarbon/fluorocarbon) interface; (c) bilayer of fluorosurfactant in water, as in (d) a fluorinated vesicle. Adapted from Krafft and Riess, (2007).

0

10

Critical micellar concentration (mol/L)

Water

Fig. 6. Fluorosurfactants are more effective and more efficient than their hydrogenated analogues (25 °C). Squares: ROP(O)(O )OC2H4N+(CH3)3, circles: ROP(O)[N(CH2CH2)2O]2; solid signs: R = C8F17CH2CH2A, open signs: R = C10H21A; the critical micellar concentration (cmc) is indicated in one case (Giulieri and Krafft, 1994).

Water

Concentration (mole/L)

-1

10

-2

10

-3

10

0 1 2 3 4 5 6 7 8 9 10

Perfluoroalkyl chain length Fig. 7. The cmc of fluorosurfactants (which reflects their efficiency) decreases exponentially when F-chain length increases; triangles: CnF2n+1COO K+; open circles: CnF2n+1COOH; downside triangle: H(CnF2n)COOH; closed circles: H(CnF2n)COO NH+4 (Lin, 1972).

the enhanced hydrophobic effect delivered by F-chains is that C20F42 forms stable Langmuir monolayers (with molecules standing perpendicular to the surface of water) (Li et al., 1994), whilst the shortest hydrocarbon capable of this feat is C37H76 (Kuzmenko et al., 2001). In the absence of polar head, it is solely the hydrophobic interactions that provide film cohesion. Eight or ten-carbon linear F-chain PFCAs (e.g. C8F17COOH (Zhu et al., 1999) or C10F21COOH (Kato et al., 1998), or phosphocholine and dimorpholinophosphate derivatives) can spontaneously form tightly packed, thin, insoluble films (Langmuir films) on surfaces and at interfaces. Mixtures of C8F17COOH with the hydrocarbon sulfonate C18F37SO3Na form well separated monolayers when transferred on mica. Fluorinated monolayers can be much thinner, yet more stable and less permeant than those obtained with nonfluorinated surfactants (Krafft and Goldmann, 2003). The collapse pressure of Langmuir films of fluorosurfactants, and their organisation at the interface, usually augments with F-chain length. Thus,

Fig. 9. Compression isotherms of Langmuir monolayers of [CnF2n+1(CH2)mO]2P(O)N(CH2CH2)2O (n:m = 6:2 a, 8:2 b and 9:1 c) surfactants showing markedly different behaviour. The monolayer of (c) is in a liquid expanded state throughout compression, whilst that of (a) is in a liquid condensed state. The monolayer of (b) exhibits a transition from a liquid expanded to a liquid condensed phase (Giulieri et al., 2012).

increasing F-chain length from 6 to 8 in [CnF2n+1(CH2)mO]2 P(O)N(CH2CH2)2O causes a transition from a liquid-expanded to a more ordered liquid-condensed phase to appear (Fig. 9) (Giulieri et al., 2012). For a given chain length, increasing fluorination from an 8:2 to 9:1 CF2 to CH2 ratio results in further densification and crystallinity of the monolayer and total disappearance of the liquid-expanded phase. Some fluorinated amphiphiles (e.g. PFCAs and SFAs) spontaneously form organised patterned surface films (Kato et al., 1998; Krafft, 2012b). Even single F-chain surfactants can readily form stable bilayers, as in liposomes, while hydrogenated surfactants usually require the presence of two hydrophobic chains (Krafft et al., 1993). Vesicles with bilayer membranes made from fluorinated phospholipids can resist sterilization, be less permeant, resist enzymatic hydrolysis and be less easily phagocytized then those made of hydrogenated analogues (Riess, 1994, 1995; Krafft, 2012a). Mesogens containing fluorinated chains form a wide range of liquid crystals (Kirsch, 2006; Krafft and Riess, 2009; Tschierske, 2012). Templates tailored from fluorosurfactants


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proved useful for mesoporous materials synthesis (Xiao, 2005; Hawley et al., 2011; Pottage et al., 2014). Fluorosurfactants are able to reduce both air/liquid and air/solid interfacial tensions. Two potent methods are used to study thin films of surfactants at the air/water interface, Langmuir and Gibbs monolayers. Langmuir monolayers are formed from organic solutions of insoluble surfactants spread on water, whilst Gibbs monolayers are formed by soluble surfactants spontaneously adsorbed at the interface from the bulk aqueous solution. The two approaches provide complementary tools for determination of film forming ability, thermodynamic, kinetic and structural film characteristics, such as surface adsorption rate, possible exchange between surface and bulk solution, as well as film organisation, and possible clustering at the interface, and interactions with chemicals and biological agents. It is therefore surprising that so few studies of Gibbs films of fluorosurfactants have been reported so far. The adsorption kinetics of ammonium F-nonanoate (PFNA,NH+4 salt) at the air/water interface was found to be diffusion-controlled at all concentrations below cmc (Sekine et al., 2004). Significant Marangoni effects were found to occur even when interfaces are very close to equilibrium. The adsorption of sulfosuccinate derivatives H(CF2)nCH2OC(O)CH2CH(C(O)OCH2 (CF2)nH(SO3 )Na+ (n = 4 and 6), which are fluorinated analogues of Aerosol OT, was also found to be diffusion-controlled (Valkovska et al., 2004). By contrast, the adsorption kinetics of C8F17CH2OH (8:1 FTOH) was both diffusion- and kinetically controlled (Kuo et al., 2013). Owing to the small size of their polar heads relative to the larger cross-section of their F-chains, fluorinated fatty acids and alcohols allow assessment of the effect of chain–chain interactions on the physical state and stability of Langmuir monolayers at the air/ water interface. Highly stable monolayers have been obtained from C8F17COOH (PFNA) (Zhu et al., 1999), C10F21COOH (PFUnDecA) (Kato et al., 1998), or C10F21(CH2)2OH (10:2 FTOH) (Takiue and Vollhardt, 2002). By contrast, a minimum of 13 CH2 groups are needed to obtain stable monolayers of hydrocarbon acids or alcohols. A specific feature of monolayers of F-alkylated acids, or acids and alcohols with a short, one or two CH2 aliphatic spacer, is that they undergo a direct transition from the gas (G) phase to an untilted liquid condensed (LC, semi-crystalline) phase during compression; the absence of intermediate liquid-expanded (LE) phase reflects F chain stiffness. Fluorotelomer thiols CnF2n+1(CH2)mSH are particularly apt at forming self-assembled monolayers on metal surfaces. Important examples of physiological and pharmacological effect dependence on F-chain length are provided by aptitude for bioac-

Fig. 11. Excretion rates of PFCAs parallel those of fluorocarbons and increase exponentially with molecular weight, but are much slower; (a) PFCAs (squares) in man; (b) perfluorocarbons (compound of data from man and rat); (c) somewhat faster excretion of slightly lipophilic fluorocarbons (circles), value for SFA C6F13C10H21 (star); and (d) PFSAs (down triangles); PFHxS presents an unexplained elevated odd point. Data from Olsen et al. (2009) and Riess (2001).

cumulation and excretion rates. The potential of PFASs for bioconcentration and bioaccumulation was determined to be directly related to F-chain length (Martin et al., 2003; Conder et al., 2008). The experimental increase of the bioconcentration factor (BCF) with fluorinated chain length in rainbow trout is shown in Fig. 10 for PFCAs (Martin et al., 2003). The trend observed for BCF (as well as for body half-lives and uptake rates) is opposite to that for aqueous solubilities and CMCs, which reflect hydrophobicity. Carboxylates with F-chain length shorter than seven were considered to have insignificant BCF. Carcass BCFs increased linearly by a factor of 8 for each carbon added to the F-chain between 8 and 12 carbons. The exponential body half-life in man versus F-chain length increase observed for PFCAs (Olsen et al., 2007) parallels that observed for fluorocarbons (Fig. 11) (Riess, 2001). There are, however, two notable differences: first, although body half-lives of fluorocarbons increase exponentially with molecular weight, they are much lower than for the surfactants of comparable F-chain length (e.g. for C8 fluorocarbons, 4 days for C8F17Br after a single intravascular dose of 2.7 g kgbw1 in man and 7 days for F-decalin, C10F18) as compared to several years for PFOA; second, human excretion data are on the same order as those collected for animals. As for the odd, out of line value reported for PFHxA, we know of no physicochemical feature that could explain it. Interestingly, the liver half-life of SFA C6F13CH@CHC10H21, 25 ± 5 days, is essentially in line with those of fluorocarbons (Zarif et al., 1994). 3. Commercial products—production and tonnages 3.1. Generic molecular structures of fluorosurfactants and fluoropolymers

Fig. 10. Bioconcentration factor (BCF) values (kg L 1) for a homologous series of PFCAs measured in the carcass (squares), blood (down triangles) and liver (up triangles) of the rainbow trout (Martin et al., 2003).

The compounds concerned here consist both of small amphiphilic molecules and of polymers (Table 1). The former include F-alkyl acids (primarily carboxylic, sulfonic or phosphoric), their salts and derivatives, as well as short telomers (e.g. telomer alcohols, amides, sulfonamides, etc.) and short F-alkylpolyether derivatives (e.g. oligomers of hexafluoropropylene oxide (CF3CFCF2(O)) such as CF3CF2CF2O[CF(CF3)CF2O]nCF(CF3)COO Na+). Perfluorinated polymers and copolymers include fluoropolymers and copolymers with a poly- or perfluorinated carbon-only



backbone (e.g. poly(tetrafluoroethylene) (PTFE) and polyvinylidene fluoride (PVDF), F-alkylpolyethers with an oxygen-containing fluorinated backbone (e.g. HOCH2CF2(CF2CF2O)p(CF2O)qCF2CH2OH), possibly with side-chain CF3 groups, as in those obtained from hexafluoropropylene oxide (e.g. HO[CF(CF3)CF2O]pH), and polymers with a hydrocarbon backbone and short appended F-alkyl side-chains such as those derived from acrylate, methacrylate or urethane monomers, or by ring-opening of oxetanes (e.g. HO[CH2C(CH3)(CH2OC3H7C4F9)CH2O]nH) (Howe-Grant, 1995; Ameduri and Boutevin, 2004). Mechanical treatment further extends the range of materials available (e.g. expanded PTFE (ePTFE) fabrics). The molecular PFASs that have raised most attention and concern, (and triggered regulation) are the long-chain F-alkane sulfonic acids (CnF2n+1SO3H, n P 6; PFSAs 4; more particularly PFOS 5 (n = 8)) and F-alkylcarboxylic acids19 (CnF2n+1COOH, n P 7 PFCAs; more particularly PFOA 20 (n = 8, of which 7 are perfluorinated).

3.2. Industrial production lines Two major approaches are used for industrial scale production of PFASs (Table 1) (Banks et al., 1994; Howe-Grant, 1995; Banks, 2000; Riess, 2001; Buck et al., 2011). One derives from electrochemical fluorination of linear alkane sulfonic fluorides in anhydrous hydrogen fluoride HF (Simons process, 1949) (Simons, 1949; Alsmeyer et al., 1994), which produces F-alkane sulfonic fluorides 1 (e. g. F-octane and F-butanesulfonyl fluorides C8F17SO2F (POSF, 2) and C4F9SO2F (PBSF, 3). The latter can be converted into sulfonic acids 4 (e.g. C8F17SO3H (PFOS 5) and C4F9SO3H (PFBS 6)) and their sulfonate salts (e.g. C8F17SO3 NH+4), sulfonamides (e.g. C8F17SO2NHCH3 (NMeFOSA) 8 and C8F17SO2NHC2H5 (NEtFOSA) 9), sulfonamidoethanol (e.g. C8F17SO2N(C2H5)C2H4OH) (NEtFOSE)11). The latter alcohol is a key intermediate for access to numerous commercial surfactants and polymers (e.g. sulfonamidoacrylate 14 and metacrylate 15 monomers). Electrochemical fluorination of octanoyl fluoride C7H17COF leads to C7F17COF from which C7F17COOH (PFOA 20) and its salts can be derived. The electrochemical process is harsh, non selective and actually leads to complex, usually poorly-defined mixtures of linear chain, branched chain and cyclic perfluorinated molecules of various chain lengths and isomeric forms, thus providing a product signature that can help track the source of a contaminant (Benskin et al., 2012). Products labelled as PFOS typically contain 70–80% of the linear molecule, and up to eleven identified isomers (Fig. 12) (Langlois et al., 2007).

Fig. 12. High-resolution gas chromatography coupled with mass spectrometry allowed identification of eleven isomers in a technical PFOS mixture. Inset: magnification (Langlois et al., 2007).

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The second major commercial production line involves free radical telomerization of tetrafluoroethene, CF2@CF2 (TFE, the taxogen), with a F-alkyl iodide (the telogen), most generally CF3CF2I, occasionally CF3CF2CF2I, leading to a distribution of homologous even carbon-numbered linear F-alkyl iodide telomers, CF3CF2(CF2 CF2)nI 17 (PFAI) (Haszeldine, 1953; Banks et al., 1994). Adjustment of reactant ratio allows maximising the proportion of telomer with a desired chain length n. Distillation allows easy isolation (in view of the 100 molecular weight unit difference between consecutive telomers n and n + 1) of pure homologues within the series. The F-alkyl iodides (PFAI) 17 can subsequently be converted into Falkylcarboxylic acids (PFCAs 19, e.g. PFOA 20) or reacted with olefins (e.g. ethylene) to form (F-alkyl)alkyl iodides CF3CF2(CF2CF2)n-2CH2CH2I (n:2 FTI 21) from which fluorotelomer alcohols 29 (e.g. C8F17CH2CH2OH (8:2 FTOH 30)), carboxylic acids (CnF2n+1CH2COOH 31), thiols, sulfonyl chlorides, sulfonic acids, sulfonamides, phosphates (mono and diPAP, 32 and 33), phosphonates, etc., as well as acrylate C8F17CH2CH2OC(O)CH@CH2) 35, metacrylate (C8F17CH2CH2OC(O)C(CH3)@CH2) 36 and other monomers, from which a range of polymers and copolymers can be derived. Phosphate, phosphonate, phosphoramidate, etc. functions provide the opportunity for having two hydrophobic F-chains on a same hydrophilic head group. Nonionic phosphates are represented by poly(ethylene glycol) (PEG) esters CnF2n+1OP(O)(O(CH2CH2O)pOH)2 (Privitera et al., 1995b; Sadtler et al., 1998b) or dimorpholinophosphate (CnF2n+1O)2P(O)N(CH2CH2)2O (Privitera et al., 1995b; Sadtler et al., 1998b). Nonionic surfactants with a poly(ethylene glycol) (PEG) hydrophilic chain (e.g., ACH2CH2(CH2CH2O)nH), a sugar function (e.g. glucose, saccharose) or a polyol can easily be derived from telomer alcohols (Riess and Greiner, 2000; Kaplánek et al., 2009). A further approach to fluorinated surface coating relies on direct fluorination of organic material using inert gas-controlled reaction of elemental fluorine (difluorine, F2; the LaMar process) (Lagow and Margrave, 1974, 1979; Lagow, 1995; Kharitonov et al., 2005; Tressaud et al., 2007). This process is reserved for specialty products or, on a large scale, for surface fluorination of preformed objects made from non-fluorinated organic materials. 3.3. Amounts produced A 2005 estimate of total global amounts of PFCAs produced was 3200–7300 tons, mostly (80%) for fluoropolymer manufacture and use (Prevedouros et al., 2006). For POSF, the global production between 1970 and 2002 was estimated to be 96 000 tons (122 500 tons when including unusable manufacturing wastes), and the global release to the environment was estimated to about 45 250 tons (Paul et al., 2009). Post-2002 global annual production of POSF was then estimated to 1000 tons (Paul et al., 2009). Fluorotelomer production has increased steeply between 1995 and 2004, reaching 5000 tons year 1 (Ellis et al., 2004a). A recent thorough inventory of the global emissions of C4–C14 PFCAs from quantifiable sources originating from products based on PFOA, PFNA, POSF and fluorotelomer compounds, estimated these emissions to 2610 to 21 400 tons in the 1951–2015 period (Wang et al., 2014a). These emissions (particularly from fluoropolymer production) increased continuously from 1951 to 2002, underwent a marked but only temporary decrease around 2002, and increased again thereafter. The temporary relapse is assigned to a geographical shift of the industrial sources from North America, Europe and Japan to emerging economies, particularly China, but also Russia, India and Poland, and manufacturers that are not committed to the USEPA Stewardship Programs. The increase in PFCA emissions in the latter countries appears to be much faster than the decrease achieved through technical progress (reduction of losses, recovery, alternative polymerisation processes) at the historical sites. Projections for the 2016–2030 period range from


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20 tons, for a probably overoptimistic lower emission scenario, to 6420 tons (primarily from fluoropolymer production and fluorotelomer product degradation). In spite of thorough research and analysis of the available information, the uncertainty about global PFASs emissions remains amazing (Wang et al., 2014a). Information about sources that are known to exist but cannot be quantified is provided in a companion paper (Wang et al., 2014b). 4. Functional properties and uses Fluorinated chains endow surfactants and coatings with a unique combination of largely interrelated physical and chemical properties, generally unmatched by standard, non-fluorinated products. Many of these key performances diminish, however, rapidly, often exponentially, when F-chain length decreases (e.g. Fig. 7). These properties led to scores of applications in both industrial processes and consumer products, fuelling huge, highly diverse and diffuse markets. The actual technical products often consist of blends (of largely unknown or unpublicized composition) of several surfactants and/or polymers. There is a definite need for better defined pure test material and standards for research, determination of such parameters as partition coefficients, critical solution temperatures, lipid solubilities that are essential for environmental monitoring and environmental processes understanding (Lehmler, 2005). 4.1. Unmatchable properties Fluorosurfactants and fluoropolymers provide extreme hydrophobicity and, simultaneously, high lipophobicity, leading to outstanding surface properties. Extreme thermal stability and chemical inertness, and resilience, allow performance under extremely harsh conditions. Aptitude for segregation and self-assembly provide sturdy thin films. Numerous other technically important ‘‘extreme’’ characteristics related to unique mechanical, electrical, electronic, optical behaviour are implemented in high-tech products. 4.1.1. Hydrophobic and lipophobic F-chains are both highly hydrophobic and lipophobic, a unique feature for organic moieties. These characters decrease, however, strongly with F-chain length. Thus, for n:2 fluorotelomer alcohols 29 (n = 4–10), water solubility decreases by 0.78 log units for each single CF2 added to the chain (Liu and Lee, 2007). A great many applications rely on this aptitude for F-chains to repel essentially everything non-fluorinated: water, fat, grease and dirt, and microorganisms, against which they erect effective protective barrier films. 4.1.2. Unmatched surface activity—effective and efficient Associating F-chains with highly hydrophilic polar functional groups (e.g. acids, alcohols or PEG chains) leads to outstanding surface activity. Significantly lower surface tensions (i.e. greater effectiveness) than with hydrocarbon chains can be achieved (Fig. 6). And this with lesser amounts of surfactant (i.e. greater efficiency), which mitigates the higher cost of fluorinated surfactants. Both features are illustrated in Fig. 6 for F-alkylated derivatives of phosphocholine and dimorpholinophosphate surfactants. Fluorosurfactants can typically lower the surface tension of water, c, from 72 to 15–20 mN m 1 (e.g. 15 mN m 1 for C7F15COO NH+4 (Kissa, 2001); 14 mN m 1 for C8 gemini surfactants (Yoshimura et al., 2006)), as compared to 30–40 mN m 1 for hydrocarbon analogues. Greater efficiency as compared to related non-fluorinated analogues is reflected by lower cmc values (Fig. 6). As little as 10 ppm of a fluorosurfactant may suffice to

reduce the surface tension of water significantly. In many applications the amount of F-surfactant required can thus be as low as 0.001 wt%. It is noteworthy that fluorosurfactants can also be surface active in organic solvents, fuels and supercritical carbon dioxide (Katritzky et al., 1988; Hoefling et al., 1991). By reducing surface and interfacial tension, fluorosurfactants facilitate spreading, dispersion, emulsification, adsorption on solid or liquid particles. Efficiency (cmc) decreases exponentially when F-chain length increases (Fig. 7). Surface activity depends also strongly on structure of the hydrophilic group, counter ion and temperature (Shinoda et al., 1972; Kissa, 2001). Optimal performance/convenience/cost ratio considerations led historically to selection of C8F17 chains for general use; this is no longer possible. 4.1.3. Extreme thermal stability and unmatched kinetic inertness Perfluorosurfactants are extremely enduring. Heat resistance is related to the stability of the CAF and backbone CAC bonds in Fchains. Fluorocarbons are not inflammable. Typical F-alkylcarboxylic and F-alkane sulfonic acids can be heated to 400 °C without significant decomposition (Kissa, 2001). Most importantly, fluorosurfactants and polymers (e.g. fluoroelastomers) generally retain their properties at both high and low temperatures and resist to UV radiation as well, allowing them to perform in extreme temperature conditions. The much lower glass transition temperatures of fluoroelastomers as compared to hydrocarbon analogues has made their use compulsory in aeronautics (e.g. o-rings) after the disaster of the Challenger space shuttle. In addition to thermal stability, fluorosurfactants and polymers can display outstanding resistance to chemical reaction with strong acids and bases, oxidising and reducing agents, including at elevated temperatures, thereby preserving their surface activity, film-forming ability, elasticity, etc. in extremely tough environments, in which no other organic materials resists. This kinetic inertness is essentially due to the large size of the fluorine atoms and compact, repellent electronic sheath that covers them (a scotchguard effect at the molecular level), which shields the molecule’s carbon backbone against chemical attack. For example, PFOS resists heating in concentrated nitric acid at 160 °C for 8 h (Kissa, 2001). Some anionic perfluorinated surfactants have been stored in 98% sulfuric acid containing 10 g L 1 of highly oxidising chromic oxide at 90 °C for 28 days or with saturated aqueous sodium hydroxide for 100 days, with little loss of surface activity (Glockner et al., 1989). Fluorotelomer alcohol derivatives were shown to preserve their surface activity in 10% potassium hydroxide, 25% sulfuric acid, 37% hydrochloric acid, or 70% nitric acid. 4.1.4. Aptitude for film formation Taken together, the specific bulky and rigid, almost defect-free rod-like structure of linear F-chains, in combination with extreme hydrophobic and strong lipophobic characters, concur to induce segregation at the molecular level and self-assembly into sturdy, ordered surface and interfacial films (Fig. 8). Such films play a critical role in emulsion polymerization, metal plating, fire fighting, repellent fabrics (copolymers), etc. Their stability, insolubility, elasticity depend again strongly on F-chain length. 4.1.5. Further invaluable properties PFASs can lower friction (photographic industry, ski waxing), facilitate levelling, provide lubrication and readily adsorb on solids, and modulate wetting properties. They have outstanding dielectric, piezoelectric and pyroelectric properties. For example, PTFE has the lowest dielectric constant (e = 2.1) of all known polymers, thus offering optimal isolation for high-tension currents. Also remarkable are their optical properties, with the lowest refraction indices



of all organic compounds, comparable to water, sometimes even lower. 4.2. Scores of uses PFASs have found multiple usages in a range of industrial processes, formulations and consumer products (Banks, 2000; Kissa, 2001; Prevedouros et al., 2006; OECD, 2014). They are also involved in the areas of safety, energy sparing, high technology devices, health and research. Only a brief summary of uses and potential is provided here. Some of the high-tech, safety-related, medical and research applications raise little environmental concerns, if only because of the small amounts of materials usually involved and high benefit acquired. 4.2.1. Industrial/technical applications and consumer products PFOA‘s ammonium salt and, to a lesser extent, that of its C9 homolog C8F17COOH (PFNA), were used as highly effective processing aids, emulsifiers and levelling agents for fluoropolymers (e.g. PTFE, PVDF, PFA) manufacturing. They are now generally replaced by salts of shorter chain acids (e.g. PFHxA) or by F-alkyl ether acids with ether oxygen atoms located in various positions along the Fchain (e.g. CF3OCF2CF2CF2OCF2CF2COO ) (Wang et al., 2013). More generally, PFASs provide effective detergents and wetting agents; spreading and levelling agents; repellents; dispersing agents, emulsifiers and foaming agents; lubricants, etc. They are used in the formulation of flux and releasing agents for moulding, in particular of plastic products; for metal cleaning, wetting and mist suppressing agents for electroplating; fluxing agents for soldering. They intervene in the formulation of impregnating agents for textile, fabrics, leather; paints, varnishes, and lacquers; glues; herbicides and pesticides; reprographic agents and printing inks; fabrication of low-friction bearings and seals; cables, wires for high frequency electronics, etc. (Kissa, 2001; Prevedouros et al., 2006; Krafft and Riess, 2007; Riess, 2009; OECD, 2014). Everyday life consumes impregnating agents, usually polymers, for repelling water and oil, soil and stain, from carpets (thus creating a primary reservoir for delayed PFASs release) and furniture, clothes and leather, in particular for water- and grease-proofing all-weather clothing, sunshades, tents and sails, car interiors, table clothes, shower curtains, bags, paper and cardboard for food wrapping. They are found in the formulation of cosmetics; polishes and waxes for shoe care, floor and cars; ski gliding waxes; non-stick cookware, etc. Special ‘‘breathable’’ fabrics (e.g. expanded PTFE) that prevent water drops from traversing, but not vapour, are omnipresent in all-weather waterproof garments and footwear. Direct surface fluorination of preformed materials imparts barrier and surface properties and resistance to chemicals and environment, thus extending product life and safety. It concerns a variety of pipes, tubings, fuel tanks, bottles, containers, toys, films, medical and dental parts, etc. and regards millions of articles (Kharitonov et al., 2005; Tressaud et al., 2007). 4.2.2. Safety—energy and resources sparing PFASs play a critical role in the safe operation of aircrafts and spacecrafts by providing high performance, temperature resistant hydraulic fluids, lubricants, resilient seals (e.g. o-rings), etc. Exemptions have been granted for use of long-chain PFASs in these applications (OECD, 2014). PFASs also provide flame retardants (as in polycarbonate resins) and effective foams for fighting fuel fires as in airports (USPA). These foams are formulated with fluorosurfactants blended with hydrocarbon surfactants, hydrolyzed proteins and/or polymers. PFASs are also important for the safety and protection of factory workers. Thin films of fluorosurfactants can prevent emission of toxic corrosive mist and spatter during lithographic, electroplating

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and other processes involving extremely acidic and/or oxidising media and toxic metals in high oxidation states. They are also present in protective clothes for workers and fire fighters. Less spectacular (and hardly quantifiable) everyday safetyrelated uses include anti-reflective and antifogging formulations for windshields and mirrors. Water proofing of clothes may be argued to reduce the incidence and spread of flu. Even grease-proof paper wrapping, etc. could be claimed to participate to public safety by hindering pathogen proliferation and transmission. PFSAs are also used for waterproofing surgical items and surgical wear. Examples of applications that provide environmental benefit in terms of energy and resource conservation include many uses for moulding, lubrication, flow-enhancement; erosion and rusting inhibition; anti-fouling coatings; ore floatation; oil drilling, oil well stimulation and gas extraction aids; prolongation of the life of consumer goods; coatings for long-lasting weathering and flame resistance (e.g. protection of solar panels); conservation of monuments and cultural heritage. 4.2.3. High-tech applications The high-tech industry uses emulsifiers, antifoaming agents and lubricants for the photographic and photolithographic, electronic, semi-conductor and optoelectronic industries (as during photolithographic fabrication of computer chips); for printing electronic circuit boards; liquid crystal displays; use for piezoelectric and pyroelectric properties, PVDF films are used in speakers and transducers to convert mechanical or thermal signals in an electrical signal, or inversely, or mechanical motion or a change in heat content in response to an applied electrical field (Banks et al., 1994; OECD, 2014). The unique combination of high polarity, low polarisability, and steric and conformational effects of F-chains allows formation of liquid crystal phases with unique characteristic (Kirsch, 2006; Hird, 2007; Tschierske, 2012). F-alkyl segments stabilize all positionally ordered liquid–crystal phases, owing to reduced cohesive energy density, as compared to hydrocarbon segments. Polyphilic molecules with fluorinated segments form multilayered, core– shell structures and new types of liquid–crystals (Tschierske, 2012). F-chains provide insulating layers for separating charge carrier pathways, thus enhancing the efficiency of devices based on ion conduction or electron/hole transportation. Rod-like mesogens with short F-chains lead to de Vries phases and to 90°-tilted antiferroelectric smectic chiral phases that have potential for orthoconic switching in display applications (Tschierske, 2012). Fluorination also leads to enhanced polarisation in ferroelectric and antiferroelectric liquid–crystal phases. Fluorinated liquid– crystal materials display low surface energy density, leading to distinct surface and alignment properties. They can form regular arrays of defects that can be used for soft lithography as optically addressable photo masks and microlenses (Kim et al., 2010). A large variety of fluorinated materials (e.g., fluorinated carbon materials, electrodes, ionic liquid electrolytes, polymeric membranes) are being developed for energy conversion in lithium batteries, fuel and solar cells, etc. Polyelectrolyte membranes such as Nafion are essential for more environmentally friendly fuel cell vehicles (Nakajima and Groult, 2005; Morohoshi and Hayashi, 2013). 4.2.4. Research tools PBSF n is an effective and thermally stable fluorinating agent in organic synthesis (Zhao et al., 2009). Fluorinated reverse-phase chromatographic columns are well known to analysts for effectively separating fluorinated surfactants, metabolites, etc. and fluorine-tagged compounds (Krafft et al., 1988; Gladysz et al., 2004; Glatz et al., 2004). Fluorocarbons (e.g. a mixture of F-alkylamines) are being used as inert carrier fluids in lab-on-a-chip assays using


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microfluidic technologies (Chen and Ismagilov, 2006; Holtze et al., 2008). Fluorosurfactants obtained by coupling oligomeric perfluorinated polyethers with poly(ethyleneglycol) allowed stabilizing water-in-fluorocarbon emulsions in microfluidic channels. The aqueous drops stabilized with these surfactants were used to encapsulate and incubate single cells. Temperature-driven segregation and partition of F-chains is the basis for ‘‘fluorous’’ technologies that have proved effective in numerous synthesis and separation procedures (Krafft et al., 1988; Gladysz et al., 2004). Reactants or catalyzers are temporarily tagged with F-chains (e.g. using tagging reagents such as C8F17C2H4SO2Cl) (Bejot et al., 2012), allowing preferential partition in fluorous media (e.g. a fluorocarbon) or on highly fluorinated substrates (Dinh and Gladysz, 2005). These technologies are presently moving towards use of lesser amounts of fluorinated material and shorter F-chains. Fluorosurfactants and fluorocarbons are key compounds in three of the most developed solvent replacement strategies currently used or under investigation for synthetic chemistry: Ionic liquids, fluorous phase techniques, and supercritical carbon dioxide (Wells and DeSimone, 2001; Eastoe et al., 2003; Clarke et al., 2004; Gladysz et al., 2004; Livi et al., 2014). These are fascinating reaction media, with considerable potential for pharmaceutical synthesis, and for activation and manipulation of carbon nanoforms (e.g. fullerenes, nanotubes, graphene, etc.) (Vazquez et al., 2014). Fluorosurfactants are highly effective for stabilizing microemulsions of water in supercritical CO2 for decaffeination of coffee, supercritical fluid chromatography and as reaction media, e.g. for fluoropolymer synthesis (DeSimone et al., 1992; Eckert et al., 1996; Smith, 1999). In the materials science, fluorinated compounds, films and selfassemblies can provide templates, surface patterning, piezoelectric sensors, biosensors, liquid crystals, non-linear optical devices, magnetic bubbles, targeted emulsions. a,x-diiodoperfluoroalkanes have been reversibly encapsulated in organic salts, (e.g. bis(trimethylammonium)alkane diiodides), through intermolecular halogen bonding interactions, and isolated from mixtures by crystallisation from solution upon addition of the size-matched ionic salt (Metrangolo et al., 2009). This new purification method was applied to a,x diiodo-F-polyethers, which are important intermediates for the synthesis of fluororesins, elastomers, and surfactants. Partially fluorinated thiols (CnF2n+1(CH2)mSH, typically n = 6–10; m = 2–17) are important components for self-assembled monolayers (SAMs) adsorbed at the surface of coinage metals or oxide surfaces for nanomaterials fabrication, including nanoscale surface coatings that inhibit corrosion of microelectromechanical systems (Zenasni et al., 2013). Wettability can be modulated by varying Fchain length. Increasing F-chain length augments the stability and barrier properties of the monolayers. Fluorinated monolayers also provide coatings for biomaterial that hinder colonisation by microorganisms. For example, the affinity interaction between biotin molecules tagged with C8F17 chains and a glass surface grafted with C8F17 chains facilitates detection of avidin–ligand binding interactions for the fabrication and screening of small molecule microarrays (Nicholson et al., 2007). High yield functionalization via ‘‘click’’ chemistry of thin F-chain-bearing films non-covalently immobilised by F-chain/F-chain interactions on a fluorinated surface has also been achieved (Santos et al., 2009). A variety of fluorinated conjugated systems, either polymeric (e.g. poly(phenyleneethynylene)s, oligo- and polythiophene), are used for electronic and optoelectronic applications in devices such as electroluminescent diodes or field effect transistors (Babudri et al., 2007). Teflon AF 2400, an amorphous fluoropolymer with a refractive index of 1.29 (water 1.33; 20 °C), allowed preparation

of liquid-core optical fibres that achieve light transmission by total internal reflection (Altkorn et al., 1997). 4.2.5. Uses and potential in theranostics Short volatile 3–6 carbon F-alkanes are being used in commercial diagnostic contrast agents for ultrasound imaging (Schutt et al., 2003; Lindner, 2004; Unger et al., 2004). Various F-alkanes and (F-alkyl)alkanes (SFAs) serve as intraocular tamponades during retinal detachment surgery (Kirchhof et al., 2002; Rico-Lattes et al., 2008). Some of the most commonly used anaesthetics are substantially fluorinated (e.g. isoflurane (CF3CHClOCHF2), desflurane (CF3CHFOCHF2), sevoflurane ((CF3)2CHOCH2F)). Use of fluorine-containing drugs and contrast agents is steadily increasing (Müller et al., 2007; Purser et al., 2008). A few isolated fluorine atoms or CF3 groups help control a drug’s binding affinity to receptor, bioavailability, metabolism, half-life, pharmacokinetics, and increase efficacy/side effect ratios. A C2F5 group is present in the anticancer agent Fulvestran (Faslodex). C2F5-nitrosoimidazole is one of the most potent radiopharmaceutical thus far identified for positron emission tomography (PET) (Mees et al., 2009). PET uses short-lived radionuclides, among which 18F (half-life 110 min) is one of the most convenient. Numerous pharmaceuticals with longer F-chains are being investigated for treatment of a wide range of conditions. Fluorocarbons (e.g. C6F14, C8F17Br) show potential as lung surfactant substitutes (Gerber et al., 2005, 2006) Fluorocarbons and fluorosurfactants (e.g. C8F17C2H4OP(O)(OH)2), and colloids comprising fluorinated components (e.g. microbubbles, emulsions, vesicles, etc.) show promise in molecular imaging, 19 F MRI, oxygen, drug and gene delivery (Krafft and Riess, 2007, 2008; Jacoby et al., 2014). Microporous expanded PTFE (ePTFE) is used for reconstructive surgery, in particular intravascular bypass grafts. F-alkyl moieties can modify the surface of polymer, including ePTFE, reduce thrombonicity and friction, protect from enzymatic degradation, and promote attachment and growth of specific cells (Ernsting et al., 2005; Larsen et al., 2006). PFASs for diagnosis and therapy demand obviously special attention concerning product definition and purity. From an environmental standpoint, they can reasonably be considered apart in view of the important potential health benefits and small doses involved. For example, an effective diagnostic dose of contrast agent for ultrasound imaging, contains only milligrams of fluorocarbon. A few mL of a perfluorocarbon is needed for retinal surgery tamponade. The diagnostic dose for PET is minuscule and 18F decays into non-radioactive, non toxic 18O. 5. Conclusions and prospects As a result of extensive use of long-chain PFASs (PC6 for PFSAand PC8 for PFCA-related compounds), these substances have disseminated all over the world. They were found to bioaccumulate and biomagnify in animals and humans. Their outstanding inertness makes them highly persistent in the environment and biota. Their half-life in humans attains several years. Toxicity studies in animals and disturbing observations in humans raise health concerns. The very extensively produced, most accumulating PFOS and PFOA and higher homologues have now joined the list of Persistent Organic Pollutants of the Stockholm Convention and the List of Substances of Very High Concern under the European REACH regulation. Efforts from American and European Agencies, voluntary industrial phase-out, and Stewardship programs have generated strict regulations that now limit their production and uses in Europe, the United States and Japan. The shorter, alternative compounds (6C4 for PFSA- and 6C6 for PFCA-related compounds) that are now being used have biocon-



centration factors far below the upper limits set by the EU (BCF < 1000) or USEPA (BCF < 2000) and are not considered bioaccumulative. These compounds are, however, as persistent in the environment as their higher homologues. Many of the most valuable and unique physical characteristics of PFASs decrease sharply when F-chains become shorter. The shorter-chain alternatives have therefore much lower performances. Lesser performance appears sufficient for most standard uses, possibly meaning that pollution by long-chain PFAS was, at least in part, technically unfounded. On the other hand, specific exemptions for use of high performance long-chain PFASs had to be recognised for a number of applications (e.g. aviation hydraulic fluids, metal plating aids, certain medical devices, etc.). For some demanding applications, the alternatives consist actually of long-chain polyether analogues closely related to the now banished long-chain products. New high-tech developments may plea for further exemptions. In view of the magnitude of the issues they raise, it is surprising how little is known about the physicochemical characteristics of the compounds concerned. The scarce data publicly accessible are often uncertain, due to poor product definition and purity, trade secrets, complexity and diversity of environmental matrices or else. Little reliable data is available on such matters as simply the effect of F-chain length on colloidal and interfacial chemistry, self-association, surface film formation ability and characteristics, not to speak of effects on physiology and pharmacokinetics. The important film formation, stability and elasticity properties of defined individual compounds, relevant to emulsification, aerosol formation, adsorption on solids, coating, partitioning, etc. are barely documented. Among the likely reasons for this situation are insufficient communication and exchanges between the physical chemist and environmental chemist communities; the difficulty for the former to obtain sufficiently pure and well-defined test material; the fact that such systematic studies may not be considered sufficiently gratifying in the physical chemistry community in its race for novelty; and scarcity of specific funding. The paucity of public data could raise the question whether some products have been fully investigated and tested prior to commercialization. We insist that there is a blatant need for reliable, independent systematic experimental determination of the physicochemical behaviour of homologous series of pure PFASs, including longand short-chain compounds, their precursors, metabolites, and alternatives. These data are, in particular, essential in order to adjust PFASs’ chain length/fluorine content/structure/performance to specific technical needs. They should help substantiate relationships between structure, physical properties, physiological behaviour and possible untoward effects. The second part of this review will assess the evidence that led to forsake long-chain PFASs; analyze the performances and environmental behaviour of their shorter chain replacement products; discuss further alternative products, research and options for reducing environmental and health concerns, while still answering the ever increasing world-wide demand for high performance materials; and question whether and to which extent use of PFASs is sustainable. References

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