WO2015192175A1

WO2015192175A1 - Polymer hydrogel

Info

Publication number: WO2015192175A1
Application number: PCT/AU2015/050316
Authority: WO
Inventors: Michael John Monteiro
Original assignee: The University Of Queensland
Priority date: 2014-06-18
Filing date: 2015-06-09
Publication date: 2015-12-23

Abstract

The present invention relates to polymer hydrogel having a polymeric matrix of polymer chains, the polymer chains comprising polymerised residues of ethylenically unsaturated monomer, wherein a plurality of the polymerised monomer residues each have one or more protected and/or free thiol functional groups covalently bound thereto such that the functional groups present in pendant formation relative to the polymer chains.

Description

POLYMER HYDROGEL

Field of Invention

The present invention relates in general to polymer hydrogels and to a method for preparing the same. The polymer hydrogels are particularly suitable for use in metal atom sequestration. Accordingly, it will be convenient to describe the invention with an emphasis toward that application. The present invention therefore also relates to a process for sequestering metal atoms using the polymer hydrogel. However, it is to be understood the polymer hydrogels may be used in other applications.

Background of the Invention

Polymer hydrogels are typically characterised by a three dimensional network of polymer chains which collectively form a polymeric matrix that can absorb a hydrophilic liquid, such as water, to an extent that the polymeric matrix swells and increases in volume. A polymer hydrogel may be viewed as an open container with semi-impermeable boundaries, across which hydrophilic liquid and solute molecules can move.

Polymer hydrogels may be formed from both natural and synthetic polymer and find utility in numerous applications. For example they have been used in applications such as bio- separation, tissue engineering, sensing and molecular recognition, drug and gene delivery, control release, artificial muscles and flow control.

Polymer hydrogels have also been used in metal sequestration applications. For example, WO 2009/155643 discloses the use of polymer hydrogels for remediation of sites, such as former industrial sites and mines, contaminated with metal atoms. A variety of suitable polymer hydrogels are disclosed in the document. For example, polymer hydrogels are prepared by polymerising monomer under the control of a sulfur based Reversible Addition-Fragmentation chain Transfer (RAFT) agent. A RAFT agent residue presents at the terminus of the so formed polymer chain that is subsequently hydrolysed to form a thiol functional group. The thiol functional group provides the resulting polymer hydrogel with a site to bind with and sequester a range of metal atoms.

Although polymer hydrogels are known to provide for metal sequestration utility, there remains an opportunity to develop polymer hydrogels that can be prepared in an effective and efficient manner so as to exhibit improved metal sequestration properties.

Summary of the Invention

The present invention provides a polymer hydrogel having a polymeric matrix of polymer chains, the polymer chains comprising polymerised residues of ethylenically unsaturated monomer, wherein a plurality of the polymerised monomer residues each have one or more protected and/or free thiol functional groups covalently bound thereto such that the functional groups present in pendant formation relative to the polymer chains. The present invention further provides a method of preparing polymer hydrogel having a polymeric matrix of polymer chains, the method comprising forming the polymer chains by polymerising a monomer composition comprising ethylenically unsaturated monomer having one or more protected and/or free thiol functional groups covalently bound thereto, wherein polymerisation of the ethylenically unsaturated monomer presents the functional groups in pendant formation relative to the so formed polymer chains.

According to the present invention, it has now been found polymer hydrogels can be produced such that they comprise a high concentration of protected and/or free thiol functional groups. By forming the polymer chains that make up the polymer hydrogel using ethylenically unsaturated monomer having one or more protected and/or free thiol functional groups covalently bound thereto, the polymeric matrix of the polymer hydrogel can be decorated with many sulfur containing functional groups. The resulting polymeric matrix can not only function effectively as a polymer hydrogel, but it has been found to exhibit improved metal atom sequestering properties relative to the state of the art polymer hydrogels. The present invention therefore also provides a process for sequestering metal atoms, the process comprising contacting polymer hydrogel according to the invention with a composition comprising metal atoms, wherein (i) a hydrophilic liquid facilitates transport of metal atoms from the composition to within the polymeric matrix of the polymer hydrogel, and (ii) at least some of the transported metal atoms bind to the one or more protected and/or free thiol functional groups such that they become sequestered within the polymer hydrogel.

In one embodiment, the polymer chains of the polymeric matrix each comprise at least 10 mol%, or at least 20 mol%, or at least 30 mol%, or at least 40 mol%, at least 50 mol%, or at least 60 mol%, or at least 70 mol%, or at least 80 mol%, at least 90 mol%, or at least 100 mol% of the polymerised ethylenically unsaturated monomer residues having one or more protected and/or free thiol functional groups covalently bound thereto. In a further embodiment, the monomer composition polymerised to form the polymer chains comprises at least 10 mol%, or at least 20 mol%, or at least 30 mol%, or at least 40 mol%, at least 50 mol%, or at least 60 mol%, or at least 70 mol%, or at least 80 mol%, at least 90 mol%, or at least 100 mol% of ethylenically unsaturated monomer having one or more protected and/or free thiol functional groups covalently bound thereto.

The polymer chains that form the polymeric matrix may be a homopolymer or copolymer.

In one embodiment, the ethylenically unsaturated monomer is polymerised by a controlled radical polymerisation (CRP) technique.

In a further embodiment, according to the process for sequestering metal atoms, the composition comprising metal atoms is a soil composition.

Features of the invention are described in more detail below. Brief Description of the Drawings

The invention is described herein with reference to the following non-limiting drawings in which:

Figure 1 illustrates ¹H-NMR (CDC1₃) of S-(2-phenylethyl) 0-ethyl xanthate; Figure 2 illustrates ¹H-NMR (CDC1₃) of S-(3-hydroxypropyl) ethanethioate; and

Figure 3 illustrates ¹H-NMR (CDC1₃) of 3-(acetylthio) propyl acrylate. Detailed Description of the Invention

As used herein, the expression "polymer hydrogel" is intended to mean a three dimensional network of polymer chains which collectively form a polymeric matrix that can adsorb and be swollen by a hydrophilic liquid.

Those skilled in the art will appreciate it is inherent from the expression "polymer hydrogel" that its polymeric matrix is made up of cross-linked polymer chains. In other words, the polymer hydrogel is a three dimensional network of cross-linked polymer chains which collectively form the polymeric matrix. Without such cross-linking the polymeric matrix would become solubilised by a hydrophilic liquid and thereby could not afford, or be referred to as, a "hydrogel" structure. Those skilled in the art will also appreciate for a polymer hydrogel to be capable of absorbing hydrophilic liquid the polymeric matrix must itself be overall hydrophilic in character. In other words, there will be sufficient polymerised residues of hydrophilic ethylenically unsaturated monomer within the polymer chains to impart overall hydrophilic character to the polymeric matrix. Examples of hydrophilic liquids include water and water soluble organic liquids such as monovalent-alcohols (such as methanol and ethanol), polyvalent-alcohols (such as ethylene glycol, diethylene glycol, triethylene glycol, propylene glycol, dipropylene glycol, butylenes glycol, hexanediol, pentanediol, glycerine, hexanetriol and thiodiglycol); amines (such as ethanolamine, diethanol amine, triethanolamine, N-methyldiethanol amine, N-ethyldiethanolamine, morpholine, N-ethylmorpholine, ethylenediamine, diethylenediamine, diethylenetriamine, triethylenetetramine, tetraethylenepentanamine, polyethyleneimine, pentamethyldiethylenetriamine and tetramethylpropylenediamine); amides (such as formamide, Ν,Ν-dimethylformamide); heterocyclic compounds (such as 2-pyrrolidone, N-methyl-2-pyrrolidone, cyclohexyl-pyrrolidone, tetrahydrofuran, 2- oxazolidone and l,3-dimethyl-2-imidazolidinone); sulfoxides (such as dimethylsulfoxide); sulfones (such as sulfolane); and acetonitrile.

In one embodiment, the hydrophilic liquid is an aqueous liquid.

The polymer chains of the polymeric matrix comprise polymerised residues of ethylenically unsaturated monomer. The expression "polymerised residue" is used to define the "mer" units within the polymer chain that are formed as a result of polymerisation of the monomer. The polymerised monomer residues therefore collectively form at least the molecular backbone structure of the polymer chain. The nature of the polymerised monomer residues is outlined in more detail below.

According to the present invention, the polymer chains are formed by polymerising ethylenically unsaturated monomer. For avoidance of any doubt, this polymerisation is intended to mean polymerisation propagated through reaction of the ethylenically unsaturated functional group of the monomer. Those skilled in the art will appreciate that polymerisation of ethylenically unsaturated monomer in this way gives rise to a polymer chain having a backbone with a carbon atom based (-C-C-) molecular structure. The ethylenically unsaturated monomers are typically polymerised to form the polymer chains by free radical polymerisation. A plurality (two or more) of the polymerised monomer residues that make up the polymer chains each have one or more protected and/or free thiol functional groups covalently bound thereto. The covalently bound protected and/or free thiol functional groups are presented in pendant formation relative to the polymer chain to which they are bound.

By being presented in "pendant formation" relative to a given polymer chain is meant that the protected and/or free thiol functional groups are located at any point on the polymer backbone except at a terminal end of the polymer chain. Those skilled in the art will appreciate that a terminal end of a polymer chain refers to the position at the first or last polymerised monomer residue unit of a polymer chain length.

Accordingly, for the protected and/or free thiol functional groups to be in "pendant formation" the carbon atom of the polymerised monomer residue which forms part of the carbon atom polymer backbone to which the functional group(s) is covalently attached must have at least two other polymerised monomer residues covalently attached to it that also form part of the carbon polymer backbone. For example, Structure (i) below represents a simplified polymer backbone having a free thiol functional group covalently bound to the polymer backbone at polymerised monomer residue number 2 such that the functional group presents in pendant formation relative to the polymer chain. In contrast, Structure (ii) below represents a simplified polymer backbone with a free thiol functional group covalently bound to the polymer backbone at polymerised monomer residue number 1 such that the functional group presents in a terminal position relative to the polymer chain.

For clarity, the polymer chain depicted in Structures (i) and (ii) has been simplistically illustrated with only a carbon atom polymer backbone and a free thiol functional group covalently bound to the polymer backbone. ^■c— c— c— c— c— c

SH

Structure (i)

^■c— c— c— c— c— c

SH

Structure (ii) For avoidance of any doubt, in addition to the protected and/or free thiol functional groups presented in pendant formation, the polymer chains of the polymer matrix may also have one or more protected and/or free thiol functional groups covalently bound at the terminal position of a given polymer chain. In other words, although the polymer chains according to the present invention must present protected and/or free thiol functional groups in pendant formation relative to the polymer chain, they can also optionally have protected and/or three thiol functional groups covalently bound at a terminal position of a given polymer chain. For example a polymer chain according to the present invention may be schematically represented by Structure (iii) illustrated below.

^■c— c— c— c— c— c

SH SH

Structure (iii)

In one embodiment, the protected and/or free thiol functional groups are covalently bound to the polymerised monomer residues through a linking moiety. Suitable protected and/or free thiol functional groups and linking moieties are outlined below.

In a further embodiment, all of the protected and/or free thiol functional groups are covalently bound to the polymer chain only in pendant formation. In other words, the polymer chains do not comprise terminal protected and/or free thiol functional groups.

In another embodiment, one or more of the plurality of polymerised ethylenically unsaturated monomer residues having one or more protected and/or free thiol functional groups covalently bound thereto may independently have a structure as presented in general formula (I):

X

H₂

C P_R

PFT (I)

where:

PA and PB, which are the same or different, represent the remainder of the polymer chain and comprise one or more polymerised residues of ethylenically unsaturated monomer;

X is selected from H and optionally substituted Ci-C₆ alkyl;

A is a moiety capable of activating an ethylenically unsaturated double bond such that it will undergo polymerisation;

L is a linking moiety; and

PFT is one or more protected and/or free thiol functional groups.

Those skilled in the art will appreciate that reference to one or more of the plurality of polymerised ethylenically unsaturated monomer residues having a structure as "presented in general formula (I)" is intended to highlight a monomer residue per se shown in general formula (la):

(la)

where X, A, L, and PFT are as herein defined, and 'represents a covalent bond that is coupled to the remainder of the polymer chain which comprises one or more polymerised residues of ethylenically unsaturated monomer.

PA and P_B are presented in general formula (I) to: (a) more clearly depict the polymer backbone structure of the polymer chain, and (b) help illustrate the pendant formation of the covalently bound one or more protected and/or free thiol functional groups (PFT).

Those skilled in the art will further appreciate the polymerised monomer residue of formulae (I) / (la) will be derived from an ethylenically unsaturated monomer of general formula (II):

X

C^=CH₂

A

L

PFT (II)

where:

X is selected from H and optionally substituted Ci-C₆ alkyl;

A is a moiety capable of activating the ethylenically unsaturated double bond such that it will undergo polymerisation;

L is a linking moiety; and PFT is one or more protected and/or free thiol functional groups.

Specific examples of monomers of formula (II) include 3-(acetylthio)propyl acrylate, 3- (acetylthio)propyl methacrylate, 4-(acetylthio)butyl acrylate, and 4-(acetylthio)butyl methacrylate.

Generally, each polymer chain will comprise multiple polymerised monomer residues that each have one or more protected and/or free thiol functional groups covalently bound thereto. Each of these polymerised residues in a given polymer chain may be the same or different. For example, a polymer chain may comprise a plurality of polymerised monomer residues that each independently have a structure as presented in general formula (I).

In one embodiment, X in the general formulae herein is selected from H and optionally substituted Ci-C₆ alkyl. In a further embodiment, X is selected from H and CH₃.

The multi-valent group "A" in the general formulae herein is a moiety capable of activating an ethylenically unsaturated double bond such that it will undergo polymerisation, typically free radical polymerisation. Those skilled in the art will appreciate that in the context of general formula (I) the polymerised residue of the ethylenically unsaturated monomer is a polymerised residue of a monomer of general formula (II), and as such there no longer remains in formula (I) the ethylenically unsaturated double bond that requires activation to undergo the required polymerisation. Accordingly, the word "capable" is used in the context of formula (I) and (la) to indicate a particular property of the A group and not a requirement that the ethylenically unsaturated double bond must be present per se.

Those skilled in the art will appreciate ethylenically unsaturated double bonds typically require activation so that they are sufficiently reactive to take part in a polymerisation reaction such as free radical polymerisation. Such activation is generally achieved by covalently coupling an activating group to the double bond within suitable proximity to promote sufficient activation.

Those skilled in the art will also appreciate the range of moieties A that are capable of activating an ethylenically unsaturated double bond such that it will undergo such polymerisation. Generally, A will be selected from an aromatic- or a heteroatom containing-moiety. For example, A may be selected from a carbonyl or carbonyl containing functional group such as an ester, an anhydride, an amide or an imide, an ether functional group, or an aromatic functional group such as a phenylene group. In one embodiment, A is a multi-valent moiety selected from carbonyl, ether, ester, amide, anhydride, imide and optionally substituted arylene.

In a further embodiment, A is a multi-valent moiety selected from carbonyl (-C(O)-), ether (-0-), ester (-O-C(O)-), amide (-(R^z)N-C(0)-), anhydride (-C(O)-O-C(O)-), imide (-C(O)- (R^z)N-C(0)-) and optionally substituted arylene (-Ar-), where R^z is H or Ci-C₆ alkyl, and Ar is arylene.

A may form together with L a moiety capable of activating an ethylenically unsaturated double bond such that it will undergo polymerisation. For example, A may be a carbonyl moiety and L may be an ether group such that -A-L- form together an ester functional group. Similarly, A may be a carbonyl moiety and L may be a alkyl-(R^z)N- group (where R^z is H or Ci-C₆ alkyl) such that -A-L- form together an amide functional group.

Accordingly, A may be defined as a moiety which, alone or in combination with L is capable of activating an ethylenically unsaturated double bond such that it will undergo polymerisation.

The multi-valent moiety "L" in the general formulae herein is a linking moiety. The linking moiety couples the activating moiety (A) to the one or more protected and/or free thiol functional groups (PFT). The linking moiety may form part of the activating moiety (A). Provided the linking moiety (i) couples the activating moiety (A) to the one or more protected and/or free thiol functional groups (PFT), and (ii) the activating moiety (A), alone or in combination with the linking moiety, is capable of activating an ethylenically unsaturated double bond, then there is no particular limitation regarding the nature of the linking moiety.

Examples of suitable linking moieties (L) include an optionally substituted multi-valent form of a group selected from alkyl, alkenyl, alkynyl, aryl, acyl (including -C(O)-), carbocyclyl, heterocyclyl, heteroaryl, alkyloxy, alkenyloxy, alkynyloxy, aryloxy, acyloxy, carbocyclyloxy, heterocyclyloxy, heteroaryloxy, alkylalkenyl, alkylalkynyl, alkylaryl, alkylacyl, alkylcarbocyclyl, alkylheterocyclyl, alkylheteroaryl, alkyloxyalkyl, alkenyloxyalkyl, alkynyloxyalkyl, aryloxyalkyl, alkylacyloxy, alkyloxyacylalkyl, alkylcarbocyclyloxy, alkylheterocyclyloxy, alkylheteroaryloxy, alkylalkenylalkyl, alkylalkynylalkyl, alkylarylalkyl, alkylacylalkyl, arylalkylaryl, arylalkenylaryl, arylalkynylaryl, arylacylaryl, arylacyl, arylcarbocyclyl, arylheterocyclyl, arylheteroaryl, alkenyloxyaryl, alkynyloxyaryl, aryloxyaryl, arylacyloxy, arylcarbocyclyloxy, arylheterocyclyloxy, arylheteroaryloxy, and polyoxyalkylene, wherein where present one or more -CH₂- groups in any alkyl chain may be replaced by a divalent group independently selected from -0-, -NR^a-, -C(O)-, -C(0)0-, -OC(0)0-, -OC(0)NR^a- and - C(0)NR^a-, where each R^a may be independently selected from hydrogen, alkyl, alkenyl, alkynyl, aryl, carbocyclyl, heteroaryl, heterocyclyl, arylalkyl, and acyl. Each R^a may also be independently selected from hydrogen, Ci_i₈alkyl, Ci_i₈alkenyl, Ci_i₈alkynyl, C6-i₈aryl, C₃-i₈carbocyclyl, C₃_i₈heteroaryl, C₃_i₈heterocyclyl, and C7_i₈arylalkyl.

In the list above defining groups from which the linking moiety L may be selected, each alkyl, alkenyl, alkynyl, aryl, carbocyclyl, heteroaryl, and heterocyclyl moiety may be optionally substituted. For avoidance of any doubt, where a given linking moiety L contains two or more of such moieties (e.g. alkylaryl), each of such moieties may be optionally substituted with one, two, three or more optional substituents as herein defined. In the list above defining groups from which the linking moiety L may be selected, where a given linking moiety L contains two subgroups (e.g. [group A] [group B]), the order of the subgroups is not intended to be limited to the order in which they are presented. Thus, a linking moiety L with two subgroups defined as [group A] [group B] (e.g. alkylaryl) is intended to also be a reference to a linking moiety L with two subgroups defined as [group B] [group A] (e.g. arylalkyl). Where a given linking moiety L contains three subgroups (e.g. [group A] [group B] [group C]), the order of the two end subgroups may be reversed, but the middle subgroup must remain located in between the two end subgroups. Thus, a linking moiety L such as alkyloxyaryl is intended to also be a reference to the linking moiety L aryloxyalkyl.

The term "polyoxyalkylene" used herein is intended to mean an oligomer or polymer built up from oxyalkylene units. The polyoxyalkylene may be branched or linear. When characterising a polyoxyalkylene, it can sometimes be convenient to refer to the number of oxyalkylene units that make up the polyoxyalkylene. A polyoxyalkylene used in accordance with the invention will generally comprise 2 to about 50, or from 2 to about 25 oxyalkylene units, or from 2 to about 15 oxyalkylene units. In the context of a polyoxyalkylene, the term "oxyalkylene" used herein is intended to γ γ

mean a divalent -0(CR R - group, where R and R are each independently selected from hydrogen and optionally substituted alkyl, and i is an integer ranging from 1 to 10.

X Y

Generally, R and R are each independently selected from hydrogen and optionally substituted C_1-6 alkyl, and i is an integer selected from 2, 3, and 4. When i > 1, each

X Y

(CR'R¹) may be the same or different. For example, when the oxyalkylene unit is an

X Y

oxyethylene unit, R and R are both hydrogen and i=2 (i.e. -0(CH₂)2-), and where the

X Y

oxyalkylene unit is an oxypropylene unit, i=2 and R and R of the first "i" are both hydrogen and R X and R Y of the second "i" can respectively be hydrogen and methyl (i.e. -OCH₂CH(CH₃)-).

Each oxyalkylene group or unit within the polyoxyalkylene may be the same or different. In other words, the polyoxyalkylene may be a homopolymer or a copolymer (including a random or block copolymer). The oxyalkylene units may be derived from an alkylene oxide such as ethylene oxide, propylene oxide, or butylene oxide. Further examples of a suitable linking moiety L include optionally substituted: C_1-18 alkyl, C₆_i8 aryl, CM_S alkyl -C(O)-, C₆_i₈ aryl -C(O)-, and -(-0(CR^xR^Y)i-)_r-, where R^x, R^Y, i are as herein defined and r is an integer ranging from 2-15.

The one or more protected and/or free thiol functional groups covalently attached to the polymerised monomer residues may be represented as "PFT" in the general formulae herein.

Those skilled in the art will appreciate a "free" thiol functional group is represented as -SH.

As used herein, the expression "protected" thiol functional group is intended to mean a sulfur containing moiety that can be converted from its protected form into a free thiol functional group that is covalently attached to the polymerised monomer residue. Conversion of a "protected" sulfur containing moiety into a free thiol functional group can be achieved using techniques known in the art. For example, the "protected" sulfur containing moiety may be an acetylthio group which can be converted into a free thiol group simply by subjecting it to amniolysis in the presence of primary amine (for example hexylamine) at room temperature. Examples of suitable protected thiol functional groups include -S(CO)alkyl, -S(CO)alkenyl, -S(CO)alkynyl, -S(CO)aryl, -S(CO)carbocyclyl, -S(CO)heterocyclyl, -S(CO)heteroaryl, -S(CO)alkylaryl, -S(CO)alkylcarbocyclyl, -S(CO)alkylheterocyclyl, -S(CO)alkylheteroaryl, -S(CS)alkyl, -S(CS)alkenyl, -S(CS)alkynyl, -S(CS)aryl, -S(CS)carbocyclyl, -S(CS)heterocyclyl, -S(CS)heteroaryl, -S(CS)alkylaryl, -S(CS)alkylcarbocyclyl, -S(CS)alkylheterocyclyl, -S(CS)alkylheteroaryl, -SSalkyl, -SSalkenyl, -SSalkynyl, -SSaryl, -SScarbocyclyl, -SSheterocyclyl, -SSheteroaryl, -SSalkylaryl, -SSalkylcarbocyclyl, -SSalkylheterocyclyl, and -SSalkylheteroaryl.

More than one protected and/or free thiol functional groups may be covalently attached to a given polymerised monomer residue of a polymer chain. In that case, the monomer residue will of course provide a multi-valent linking moiety (e.g. a multi-valent L) to covalently couple multiple protected and/or free thiol functional groups. For example, in the context of general formula (I), the linking moiety L may present multiple sites for coupling the protected and/or free thiol functional groups. An example of such a polymerised monomer residue is represented below by general formula (lb):

X

H₂

C P_R

A

HS- -H C- -HC- -CH 2 SH (lb)

where PA, P_B, and A are as herein defined.

The polymer chains that form the polymeric matrix of the polymer hydrogel may be a homopolymer or a co-polymer. In the case of a homopolymer, those skilled in the art will appreciate that only one type of monomer will be used to prepare the polymer chain. In the case of a copolymer, those skilled in the art will further appreciate that a combination of different monomers will be used to prepare the polymer chain. In either case, the polymer chains must comprise polymerised residues of ethylenically unsaturated monomer, where a plurality of the residues each have one or more protected and/or free thiol functional groups covalently bound thereto.

For example, the polymer chains may be a homopolymer or copolymer comprised entirely of polymerised monomer residues each having one or more protected and/or free thiol functional groups covalently bound thereto. In the case of such a copolymer, two or more different polymerised monomer residues must still be present.

The polymer chains may also be a copolymer comprised of (i) polymerised monomer residues each having one or more protected and/or free thiol functional groups covalently bound thereto, and (ii) polymerised monomer residues that do not have one or more protected and/or free thiol functional groups covalently bound thereto. For example, the polymer chains may be a homopolymer or copolymer comprised entirely of polymerised monomer residues of general formula (I). In the case of such a copolymer, two or more different polymerised monomer residues of general formula (I) will be present. Such a copolymer may be prepared, for example, by copolymerising different monomers of general formula (II).

As a further example, the polymer chains may also be a copolymer comprised of (i) polymerised monomer residues of general formula (I), and (ii) polymerised monomer residues that are not of general formula (I). Such a copolymer will be prepared, for example, by copolymerising monomer of general formula (II) with one or more other ethylenically unsaturated monomers (e.g. not of general formula (II)).

In the case of a homopolymer, it will be appreciated that PA and P_B in general formula (I) will be the same. PA and P_B in general formula (I) represent the remainder of the polymer chain and will typically be made up from multiple polymerised residues of the ethylenically unsaturated monomer.

A given polymer chain will typically comprise multiple polymerised monomer residues that each have one or more protected and/or free thiol functional groups covalently bound thereto (e.g. residues of general formula (I)). PA and/or P_B will therefore generally comprise one or more polymerised monomer residues that each have one or more protected and/or free thiol functional groups covalently bound thereto (e.g. one or more residues of general formula (I)).

The polymerised residues of ethylenically unsaturated monomer that make up a given polymer chain will typically have been formed through a free radical polymerisation process. Factors that determine the free radical (co)polymerisability of ethylenically unsaturated monomers are well documented in the art. For example, see: Greenlee, R. Z., in Polymer Handbook 3 edition (Brandup, J, and Immergut. E. H. Eds) Wiley: New York, 1989, p 11/53.

Where the polymer chains are a copolymers, in addition to the polymerised monomer residues each having one or more protected and/or free thiol functional groups covalently bound thereto (for example, derived from the polymerisation of monomer of general formula (II)), the polymer chains may also comprise the polymerised residue of one or more other ethylenically unsaturated monomers (e.g. derived from the polymerisation of monomer that is not of general formula (II)). Such "other" ethylenically unsaturated monomers may have a structure of general formula (III):

(III)

where U and W are independently selected from -C0₂H, -CO₂R¹, -COR¹, -CSR¹, -CSOR¹, -COSR¹, -CONH₂, -CONHR¹, -CONR^, hydrogen, halogen and optionally substituted Ci-C₄ alkyl or U and W form together a lactone, anhydride or imide ring that may itself be optionally substituted, where the optional substituents are independently selected from hydroxy, -C0₂H, -CO₂R¹, -COR¹, -CSR¹, -CSOR¹, -COSR¹, -CN, -CONH₂, -CONHR¹, -CONR^, -OR¹, -SR¹, -O₂CR¹,

V is selected from hydrogen, R¹, -C0₂H, -CO₂R¹, -COR¹, -CSR¹, -CSOR¹, -COSR¹, -CONH₂, -CONHR¹, -CONR^, -OR¹, -SR¹, -O₂CR¹, -SCOR¹, and -OCSR¹; where the or each R¹ is independently selected from optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, optionally substituted alkylaryl, optionally substituted alkylheteroaryl, and an optionally substituted polymer chain.

While monomers of general formula (III) may comprise a functional group comprising sulfur, those skilled in the art will appreciate that such monomers will not provide for a polymerised monomer residue having one or more protected thiol functional groups that can be converted into a free thiol group that is covalently attached to the polymerised monomer residue.

The or each R¹ may also be independently selected from optionally substituted C₁-C₂₂ alkyl, optionally substituted C₂-C₂₂ alkenyl, optionally substituted C₂-C₂₂ alkynyl, optionally substituted C₆-Ci₈ aryl, optionally substituted C₃-C₁₈ heteroaryl, optionally substituted C₃-C₁₈ carbocyclyl, optionally substituted C₂-C₁₈ heterocyclyl, optionally substituted C₇-C₂₄ arylalkyl, optionally substituted C₄-Cis heteroarylalkyl, optionally substituted C₇-C₂₄ alkylaryl, optionally substituted C₄-Ci₈ alkylheteroaryl, and an optionally substituted polymer chain.

In one embodiment, R¹ may be independently selected from optionally substituted Ci-C₆ alkyl.

Examples of optional substituents for R¹ include those selected from alkyleneoxidyl (epoxy), hydroxy, alkoxy, acyl, acyloxy, formyl, alkylcarbonyl, carboxy, sulfonic acid, alkoxy- or aryloxy-carbonyl, isocyanato, cyano, silyl, halo, amino, including salts and derivatives thereof. Examples polymer chains include those selected from polyalkylene oxide, polyarylene ether and polyalkylene ether. Examples of monomers of formula (III) include maleic anhydride, N-alkylmaleimide, N- arylmaleimide, dialkyl fumarate and cyclopolymerisable monomers, acrylate and methacrylate esters, acrylic and methacrylic acid, styrene, acrylamide, methacrylamide, and methacrylonitrile, mixtures of these monomers, and mixtures of these monomers with other monomers. Other examples of monomers of formula (III) include: methyl methacrylate, ethyl methacrylate, propyl methacrylate (all isomers), butyl methacrylate (all isomers), 2- ethylhexyl methacrylate, isobornyl methacrylate, methacrylic acid, benzyl methacrylate, phenyl methacrylate, methacrylonitrile, alpha-methylstyrene, methyl acrylate, ethyl acrylate, propyl acrylate (all isomers), butyl acrylate (all isomers), 2-ethylhexyl acrylate, isobornyl acrylate, acrylic acid, benzyl acrylate, phenyl acrylate, acrylonitrile, styrene, functional methacrylates, acrylates and styrenes selected from glycidyl methacrylate, 2- hydroxyethyl methacrylate, hydroxypropyl methacrylate (all isomers), hydroxybutyl methacrylate (all isomers), Ν,Ν-dimethylaminoethyl methacrylate, N,N-diethylaminoethyl methacrylate, triethyleneglycol methacrylate, itaconic anhydride, itaconic acid, glycidyl acrylate, 2-hydroxyethyl acrylate, hydroxypropyl acrylate (all isomers), hydroxybutyl acrylate (all isomers), Ν,Ν-dimethylaminoethyl acrylate, Ν,Ν-diethylaminoethyl acrylate, triethyleneglycol acrylate, methacrylamide, N-methylacrylamide, N,N- dimethylacrylamide, N-tert-butylmethacrylamide, N-n-butylmethacrylamide, N- methylolmethacrylamide, N-ethylolmethacrylamide, N-tert-butylacrylamide, N-n- butylacrylamide, N-methylolacrylamide, N-ethylolacrylamide, vinyl benzoic acid (all isomers), diethylamino styrene (all isomers), alpha-methylvinyl benzoic acid (all isomers), diethylamino alpha-methylstyrene (all isomers), p-vinylbenzene sulfonic acid, p- vinylbenzene sulfonic sodium salt, trimethoxysilylpropyl methacrylate, triethoxysilylpropyl methacrylate, tributoxysilylpropyl methacrylate, dimethoxymethylsilylpropyl methacrylate, diethoxymethylsilylpropyl methacrylate, dibutoxymethylsilylpropyl methacrylate, diisopropoxymethylsilylpropyl methacrylate, dimethoxysilylpropyl methacrylate, diethoxysilylpropyl methacrylate, dibutoxysilylpropyl methacrylate, diisopropoxysilylpropyl methacrylate, trimethoxysilylpropyl acrylate, triethoxysilylpropyl acrylate, tributoxysilylpropylacrylate, dimethoxymethylsilylpropyl acrylate, diethoxymethylsilylpropyl acrylate, dibutoxymethylsilylpropyl acrylate, diisopropoxymethylsilylpropyl acrylate, dimethoxysilylpropyl acrylate, diethoxysilylpropyl acrylate, dibutoxysilylpropyl acrylate, diisopropoxysilylpropyl acrylate, vinyl acetate, vinyl butyrate, vinyl benzoate, vinyl chloride, vinyl fluoride, vinyl bromide, maleic anhydride, N-phenylmaleimide, N-butylmaleimide, N-vinylpyrrolidone, N-vinylcarbazole, butadiene, ethylene and chloroprene. This list is not exhaustive.

For the polymer hydrogel to be capable of absorbing hydrophilic liquid the polymeric matrix must be overall hydrophilic in character. In other words, there will be sufficient polymerised residues of hydrophilic ethylenically unsaturated monomer within the polymer chains to impart overall hydrophilic character to the polymeric matrix.

Those skilled in the art will be able to readily selected a monomer composition that is to be polymerised to form polymer chains that impart overall hydrophilic character to the polymeric matrix. The monomer composition will of course comprise sufficient hydrophilic ethylenically unsaturated monomer to provide for polymer chains that impart overall hydrophilic character to the polymeric matrix.

Terms such as "hydrophilic" and "hydrophobic" are generally used in the art to convey interactions between one component relative to another (e.g. attractive or repulsive interactions, or solubility characteristics) and not to quantitatively define properties of a particular component relative to another.

For example, a hydrophilic component is more likely to be wetted or solvated by an aqueous medium such as water, whereas a hydrophobic component is less likely to be wetted or solvated by an aqueous medium such as water.

Provided the polymeric matrix exhibits overall hydrophilic character such that the hydrogel can absorb and be swollen by a hydrophilic liquid, the polymer chains that form the polymeric matrix may also comprise at least some polymerised residues derived from hydrophobic ethylenically unsaturated monomer. The polymerised monomer residues having one or more protected and/or free thiol functional groups covalently bound thereto may be derived from hydrophilic or hydrophobic ethylenically unsaturated monomer. Where the polymerised monomer residues having one or more protected and/or free thiol functional groups covalently bound thereto are derived from hydrophobic ethylenically unsaturated monomer, theses residues will of course be present (i) in combination with polymerised monomer residues derived from hydrophilic ethylenically unsaturated monomer, and (ii) in an amount such that polymer chains nevertheless impart overall hydrophilic character to the polymeric matrix.

In one embodiment, all polymerised monomer residues that make up the polymer chains are derived from hydrophilic ethylenically unsaturated monomers.

Hydrophilic ethylenically unsaturated monomers are known to those skilled in the art and are typically characterised by an ability to be homopolymerised to form homopolymer that can be readily wetted or solvated by an aqueous medium such as water.

Hydrophobic ethylenically unsaturated monomers are known to those skilled in the art and are typically characterised by an ability to be homopolymerised to form homopolymer that can not be readily wetted or solvated by an aqueous medium such as water. As a guide only, examples of hydrophobic ethylenically unsaturated monomers include, but are not limited to, styrene, alpha-methyl styrene, butyl acrylate, butyl methacrylate, amyl methacrylate, hexyl methacrylate, lauryl methacrylate, stearyl methacrylate, ethyl hexyl methacrylate, crotyl methacrylate, cinnamyl methacrylate, oleyl methacrylate, ricinoleyl methacrylate, cholesteryl methacrylates, cholesteryl acrylate, vinyl butyrate, vinyl tert-butyrate, vinyl stearate and vinyl laurate.

As a guide only, examples of hydrophilic ethylenically unsaturated monomers include, but are not limited to, acrylic acid, methacrylic acid, hydroxyethyl methacrylate, hydroxypropyl methacrylate, oligo(alkylene glycol)methyl ether (meth)acrylate (OAG(M)A), acrylamide and methacrylamide, hydroxyethyl acrylate, N- methylacrylamide, Ν,Ν-dimethylacrylamide and Ν,Ν-dimethylaminoethyl methacrylate, Ν,Ν-dimethylaminopropyl methacrylamide, N-hydroxypropyl methacrylamide, 4- acryloylmorpholine, phosphorylcholine methacrylate and N-vinyl pyrolidone.

In the case of the hydrophilic ethylenically unsaturated monomer OAG(M)A, the alkylene moiety will generally be a C₂-C6, for example a C₂ or C₃, alkylene moiety. Those skilled in the art will appreciate that the "oligo" nomenclature associated with the "(alkylene glycol)" refers to the presence of a plurality of alkylene glycol units. Generally, the oligo component of the OAG(M)A will comprise about 2 to about 200, for example from about 2 to about 100, or from about 2 to about 50 or from about 2 to about 20 alkylene glycol repeat units.

As a guide only, examples of hydrophilic ethylenically unsaturated monomers having one or more protected and/or free thiol functional groups covalently bound thereto include co- (acetylthio)oligo(ethylene glycol) acrylate and co-(acetylthio)oligo(ethylene glycol) methacrylate.

As a guide only, examples of hydrophobic ethylenically unsaturated monomers having one or more protected and/or free thiol functional groups covalently bound thereto include 3- (acetylthio)propyl acrylate, 3-(acetylthio)propyl methacrylate, 4-(acetylthio)butyl acrylate, and 4-(acetylthio)butyl methacrylate.

In the context of general formula (I), PA and P_B may each represent a polymer chain which may be the same or different, where each can independently comprise (i) one or more polymerised monomer residues each having one or more protected and/or free thiol functional groups covalently bound thereto, (ii) one or more other polymerised monomer residues, or (iii) combinations thereof. For example, PA and P_B may each represent part of the polymer chain which may be the same or different, where each independently comprises a polymerised residue of an ethylenically unsaturated monomer selected from general formula (II), general formula (III) and combinations thereof.

Polymer hydrogels having a polymeric matrix of polymer chains that have a structure similar to that of Structure (ii) above are known. For example, such polymer hydrogels are disclosed in WO 2009/155643. According to WO 2009/155643, ethylenically unsaturated monomers are polymerised under the control of a sulfur based RAFT agent to form the polymer chains. By virtue of the polymerisation mechanism the RAFT agent is covalently bound to a terminal end of the so formed polymer chain. The RAFT agent can be subsequently hydrolysed so as to form a free thiol functional group covalently bound to the terminal position of the polymer chain.

While methodology disclosed in WO 2009/155643 provides for polymer hydrogels having protected or free thiol functionality that can be used for sequestering metal atoms, the sequestering capacity of these hydrogels is inherently limited by the fact that each polymer chain of the polymeric matrix provides for only one protected or free thiol functional group. A unique feature of polymer hydrogels according to the present invention is that the polymeric matrix of the hydrogel can be decorated with a high concentration of the sulfur containing functional groups. This feature is provided by the polymer chains that make up the polymeric matrix which are made using ethylenically unsaturated monomer having one or more protected and/or free thiol functional groups covalently bound thereto. In this way, each polymer chain can advantageously be provided with a variable and high % of polymerised ethylenically unsaturated monomer residues that each have one or more protected and/or free thiol functional groups covalently bound thereto.

For example, polymer chains of the polymeric matrix may each comprise at least 10 mol%, or at least 20 mol%, or at least 30 mol%, or at least 40 mol%, at least 50 mol%, or at least 60 mol%, or at least 70 mol%, or at least 80 mol%, at least 90 mol%, or at least 100 mol% of polymerised ethylenically unsaturated monomer residues each having one or more protected and/or free thiol functional groups covalently bound thereto. Similarly, ethylenically unsaturated monomer composition polymerised to form the polymer chains may comprises at least 10 mol%, or at least 20 mol%, or at least 30 mol%, or at least 40 mol%, at least 50 mol%, or at least 60 mol%, or at least 70 mol%, or at least 80 mol%, at least 90 mol%, or at least 100 mol% of ethylenically unsaturated monomer having one or more protected and/or free thiol functional groups covalently bound thereto. By the polymer chains of the polymeric matrix each comprising "at least X mol%" of the specified polymerised monomer residues is meant that (i) a given polymer chain will be made up in total of 100 mol % of polymerised monomer residues, and (ii) at "at least X mol%" of this 100 mol% will be the specified polymerised monomer residues. For example, if a polymer chain of the polymeric matrix comprises 50 mol% of the polymerised ethylenically unsaturated monomer residues having one or more protected and/or free thiol functional groups covalently bound thereto, then the polymer chain will also comprise 50 mol% of other polymerised ethylenically unsaturated monomer residues. Alternatively, if a polymer chain of the polymeric matrix comprises 100 mol% of the polymerised ethylenically unsaturated monomer residues having one or more protected and/or free thiol functional groups covalently bound thereto, then this will reflect the composition of the entire polymer chain and there will be no other polymerised ethylenically unsaturated monomer residues present.

By the ethylenically unsaturated monomer composition polymerised to form the polymer chains comprising "at least X mol%" of the specified monomer is meant that (i) a given monomer composition will be made up in total of 100 mol % of monomer that is to be polymerised, and (ii) at "at least X mol%" of this 100 mol% will be the specified monomer.

For example, if the ethylenically unsaturated monomer composition polymerised to form the polymer chains comprises 50 mol% of the ethylenically unsaturated monomer having one or more protected and/or free thiol functional groups covalently bound thereto, then the remainder of the monomer composition will comprise 50 mol% of other ethylenically unsaturated monomer. Alternatively, if the ethylenically unsaturated monomer composition polymerised to form the polymer chains comprises 100 mol% of the ethylenically unsaturated monomer having one or more protected and/or free thiol functional groups covalently bound thereto, then this will reflect the entire monomer composition and there will be no other ethylenically unsaturated monomer present.

By providing an ability for the polymer chains to comprise a variable mol%, up to 100 mol%, of polymerised ethylenically unsaturated monomer residues having one or more protected and/or free thiol functional groups covalently bound thereto, the polymer hydrogels can advantageously be tailored to meet requirements of specific applications. For example, both the type and amount of the protected and/or free thiol functional groups can be readily optimized to maximise metal atom up take in metal atom sequestration applications.

The polymerisation technique used to form the polymer chains will typically be free radical polymerisation.

Polymerisation of ethylenically unsaturated monomers by free radical polymerisation may require initiation from a source of free radicals. A source of initiating radicals can be provided by any suitable means of generating free radicals, such as the thermally induced homolytic scission of suitable compound(s) (thermal initiators such as peroxides, peroxyesters, or azo compounds), the spontaneous generation from monomers (e.g. styrene), redox initiating systems, photochemical initiating systems or high energy radiation such as electron beam, X- or gamma-radiation.

Thermal initiators are generally chosen to have an appropriate half life at the temperature of polymerisation. These initiators can include one or more of the following compounds: 2,2'-azobis(isobutyronitrile), 2,2'-azobis(2-cyanobutane), dimethyl 2,2'- azobis(isobutyrate), 4,4'-azobis(4-cyanovaleric acid), 1,1'- azobis(cyclohexanecarbonitrile), 2-(t-butylazo)-2-cyanopropane, 2,2'-azobis{2- methyl-N-[l,l-bis(hydroxymethyl)-2-hydroxyethyl]propionamide}, 2,2'-azobis[2- methyl-N-(2-hydroxyethyl)propionamide] , 2,2'-azobis(N,N'- dimethyleneisobutyramidine) dihydrochloride, 2,2'-azobis(2-amidinopropane) dihydrochloride, 2,2'-azobis(N,N'-dimethyleneisobutyramidine), 2,2'-azobis{2- methyl-N- [1,1 -bis(hydroxymethyl)-2-hydroxyethyl]propionamide } , 2,2'-azobis { 2- methyl-N- [1,1 -bis(hydroxymethyl)-2-ethyl]propionamide } , 2,2'-azobis [2-methyl- N-(2-hydroxyethyl)propionamide], 2,2'-azobis(isobutyramide) dihydrate, 2,2'- azobis(2,2,4-trimethylpentane), 2,2'-azobis(2-methylpropane), t-butyl peroxyacetate, t-butyl peroxybenzoate, t-butyl peroxyneodecanoate, t-butylperoxy isobutyrate, t-amyl peroxypivalate, t-butyl peroxypivalate, diisopropyl peroxydicarbonate, dicyclohexyl peroxydicarbonate, dicumyl peroxide, dibenzoyl peroxide, dilauroyl peroxide, potassium peroxydisulfate, ammonium peroxydisulfate, di-t-butyl hyponitrite, dicumyl hyponitrite. This list is not exhaustive.

Photochemical initiator systems are generally chosen to have an appropriate quantum yield for radical production under the conditions of the polymerisation. Examples include benzoin derivatives, benzophenone, acyl phosphine oxides, and photo-redox systems.

Redox initiator systems are generally chosen to have an appropriate rate of radical production under the conditions of the polymerisation; these initiating systems can include, but are not limited to, combinations of the following oxidants and reductants: oxidants: potassium, peroxydisulfate, hydrogen peroxide, t-butyl hydroperoxide. reductants: iron (II), titanium (III), potassium thiosulfite, potassium bisulfite.

Other suitable initiating systems are described in commonly available texts. See, for example, Moad and Solomon "the Chemistry of Free Radical Polymerisation", Pergamon, London, 1995, pp 53-95. Initiators that are more readily solvated in hydrophilic media include, but are not limited to, 4,4-azobis(cyanovaleric acid), 2,2'-azobis{2-methyl-N-[l,l-bis(hydroxymethyl)-2- hydroxyethyl]propionamide}, 2,2'-azobis[2-methyl-N-(2-hydroxyethyl)propionamide], 2,2'-azobis(N,N'-dimethyleneisobutyramidine), 2,2'-azobis(N,N'- dimethyleneisobutyramidine) dihydrochloride, 2,2'-azobis(2-amidinopropane) dihydrochloride, 2,2'-azobis { 2-methyl-N- [1,1 -bis(hydroxymethyl)-2-ethyl]propionamide } , 2,2'-azobis[2-methyl-N-(2-hydroxyethyl)propionamide], 2,2'-azobis(isobutyramide) dihydrate, and derivatives thereof.

Initiators that are more readily solvated in hydrophobic media include azo compounds exemplified by the well known material 2,2'- azobisisobutyronitrile. Other suitable initiator compounds include the acyl peroxide class such as acetyl and benzoyl peroxide as well as alkyl peroxides such as cumyl and t-butyl peroxides. Hydroperoxides such as t- butyl and cumyl hydroperoxides are also widely used.

The free radical polymerisation of the monomers may proceed by conventional free radical polymerisation or by so-called living free radical polymerisation. Living polymerisation is generally considered in the art to be a form of chain polymerisation in which irreversible chain termination is substantially absent. An important feature of living polymerisation is that polymer chains will continue to grow while monomer and the reaction conditions to support polymerisation are provided.

Where free radical polymerisation of the monomers is via a living polymerisation technique, it will generally be necessary to make use of a so-called living polymerisation agent. By "living polymerisation agent" is meant a compound that can participate in and control or mediate the living polymerisation of the ethylenically unsaturated monomers so as to form a living polymer chain (i.e. a polymer chain that has been formed according to a living polymerisation technique).

Examples of free radical living polymerisation techniques include iniferter polymerisation, stable free radical mediated polymerisation (SFRP), atom transfer radical polymerisation (ATRP), and reversible addition fragmentation chain transfer (RAFT) polymerisation.

In one embodiment, the polymer chains are formed by polymerising the monomer composition by Iniferter polymerisation.

Iniferter polymerisation is generally understood to proceed by a mechanism illustrated below in Scheme 1.

a) AB ^ Α· + ·Β b) Α· + M ► "™"· c) Avwvw* + ·Β _^ A^B

d) Α^^· + AB ^ A^B + ·Α e) Α^{,ΛΛΛΛΛΛ} · + B■^AW A

B *™™A

Scheme 1: General mechanism of controlled radical polymerisation with iniferters.

With reference to Scheme 1, the iniferter agent AB dissociates chemically, thermally or photochemically to produce a reactive radical species A and generally a relatively stable radical species B (for symmetrical iniferters the radical species B will be the same as the radical species A) (step a). The radical species A can initiate polymerisation of monomer M (in step b) and may be deactivated by coupling with radical species B (in step c). Transfer to the iniferter (in step d) and/or transfer to dormant polymer (in step e) followed by termination (in step f) characterise iniferter chemistry. Suitable iniferter agents are well known to those skilled in the art, and include, but are not limited to, dithiocarbonate, disulphide, and thiuram disulphide compounds.

In a further embodiment, the polymer chains are formed by polymerising the monomer composition by SFRP.

As suggested by its name, SFRP involves the generation of a stable radical species as illustrated below in Scheme 2.

CD . C + -D

M

Scheme 2: General mechanism of controlled radical polymerisation with stable free radical mediated polymerisation.

With reference to Scheme 2, SFRP agent CD dissociates to produce an active radical species C and a stable radical species D. The active radical species C reacts with monomer M, which resulting propagating chain may recombine with the stable radical species D. Unlike iniferter agents, SFRP agents do not provide for a transfer step. Suitable agents for conducting SFRP are well known to those skilled in the art, and include, but are not limited to, moieties capable of generating phenoxy and nitroxy radicals. Where the agent generates a nitroxy radical, the polymerisation technique is more commonly known as nitroxide mediated polymerisation (NMP).

Examples of SFRP agents capable of generating phenoxy radicals include those comprising a phenoxy group substituted in the 2 and 6 positions by bulky groups such as tert-alkyl (e.g. t-butyl), phenyl or dimethylbenzyl, and optionally substituted at the 4 position by an alkyl, alkyloxy, aryl, or aryloxy group or by a heteroatom containing group (e.g. S, N or O) such dimethylamino or diphenylamino group. Thiophenoxy analogues of such phenoxy containing agents are also contemplated.

SFRP agents capable of generating nitroxy radicals include those comprising the substituent R 1 R2 N-0-, where R 1 and R2 are tertiary alkyl groups, or where R 1 and R2 together with the N atom form a cyclic structure, preferably having tertiary branching at the positions a to the N atom. Examples of such nitroxy substituents include 2,2,5,5- tetraalkylpyrrolidinoxyl, as well as those in which the 5-membered hetrocycle ring is fused to an alicyclic or aromatic ring, hindered aliphatic dialkylaminoxyl and iminoxyl substituents. A common nitroxy substituent employed in SFRP is 2,2,6, 6-tetramethyl-l - piperidinyloxy.

In another embodiment, the polymer chains are formed by polymerising the monomer composition by ATRP. ATRP generally employs a transition metal catalyst to reversibly deactivate a propagating radical by transfer of a transferable atom or group such as a halogen atom to the propagating polymer chain, thereby reducing the oxidation state of the metal catalyst as illustrated below in Scheme 3.

E-X + M_t ⁿ E. + M_t ⁿX

M

]→ w>« + M_t ⁿX

Scheme 3: General mechanism of controlled radical polymerisation with atom transfer radical polymerisation.

With reference to Scheme 3, a transferable group or atom (X , e.g. halide, hydroxyl, Ci-C₆- alkoxy, cyano, cyanato, thiocyanato or azido) is transferred from the organic compound (E) to a transition metal catalyst (M_t, e.g. copper, iron, gold, silver, mercury, palladium, platinum, cobalt, manganese, ruthenium, molybdenum, niobium, or zinc) having oxidation number (n), upon which a radical species is formed that initiates polymerisation with monomer (M). As part of this process, the metal complex is oxidised (M_t ⁿ⁺¹X). A similar reaction sequence is then established between the propagating polymer chain and the dormant X end-capped polymer chains.

In a further embodiment, the polymer chains are formed by polymerising the monomer composition by RAFT polymerisation.

RAFT polymerisation is well known in the art and is believed to operate through the mechanism outlined below in Scheme 4.

Scheme 4: General mechanism of controlled radical polymerisation with reversible addition fragmentation chain transfer polymerisation.

With reference to Scheme 4, RAFT polymerisation is believed to proceed through initial reaction sequence (a) that involves reaction of a RAFT agent (1) with a propagating radical. The labile intermediate radical species (2) that is formed fragments to form a temporarily deactivated dormant polymer species (3) together a radical (R) derived from the RAFT agent. This radical can then promote polymerisation of monomer (M), thereby reinitiating polymerisation. The propagating polymer chain can then react with the dormant polymer species (3) to promote the reaction sequence (b) that is similar to reaction sequence (a). Thus, a labile intermediate radical (4) is formed and subsequently fragments to form again a dormant polymer species together with a radical which is capable of further chain growth. RAFT agents suitable for use in accordance with the invention comprise a thiocarbonylthio group (which is a divalent moiety represented by: -C(S)S-). Examples of RAFT agents are described in Moad G.; Rizzardo, E; Thang S, H. Polymer 2008, 49, 1079-1131 (the entire contents of which are incorporated herein by reference) and include xanthate, dithioester, dithiocarbonate, dithiocarbanate and trithiocarbonate compounds.

A RAFT agent suitable for use in accordance with the invention may be represented by general formula (IV) or (V):

(IV) (V) where Z and R are groups, and R* and Z* are x-valent and y-valent groups, respectively, that are independently selected such that the agent can function as a RAFT agent in the polymerisation of one or more ethylenically unsaturated monomers; x is an integer > 1; and y is an integer > 2.

In order to function as a RAFT agent in the polymerisation of one or more ethylenically unsaturated monomers, those skilled in the art will appreciate that R and R* will typically be an optionally substituted organic group that function as a free radical leaving group under the polymerisation conditions employed and yet, as a free radical leaving group, retain the ability to reinitiate polymerisation. Those skilled in the art will also appreciate that Z and Z* will typically be an optionally substituted organic group that function to give a suitably high reactivity of the C=S moiety in the RAFT agent towards free radical addition without slowing the rate of fragmentation of the RAFT-adduct radical to the extent that polymerisation is unduly retarded.

In formula (IV), R* is a x-valent group, with x being an integer > 1. Accordingly, R* may be mono-valent, di-valent, tri-valent or of higher valency. For example, R* may be an optionally substituted polymer chain, with the remainder of the RAFT agent depicted in formula (IV) presented as multiple groups pendant from the polymer chain. Generally, x will be an integer ranging from 1 to about 20, for example from about 2 to about 10, or from 1 to about 5. Similarly, in formula (V), Z* is a y-valent group, with y being an integer > 2. Accordingly, Z* may be di-valent, tri-valent or of higher valency. Generally, y will be an integer ranging from 2 to about 20, for example from about 2 to about 10, or from 2 to about 5. Examples of R in the RAFT agents used may include optionally substituted, and in the case of R* in the RAFT agents may include a x-valent form of optionally substituted, alkyl, alkenyl, alkynyl, aryl, acyl, carbocyclyl, heterocyclyl, heteroaryl, alkylthio, alkenylthio, alkynylthio, arylthio, acylthio, carbocyclylthio, heterocyclylthio, heteroarylthio, alkylalkenyl, alkylalkynyl, alkylaryl, alkylacyl, alkylcarbocyclyl, alkylheterocyclyl, alkylheteroaryl, alky loxy alkyl, alkenyloxyalkyl, alkynyloxyalkyl, aryloxyalkyl, alkylacyloxy, alkylcarbocyclyloxy, alkylheterocyclyloxy, alkylheteroaryloxy, alkylthioalkyl, alkenylthioalkyl, alkynylthioalkyl, arylthioalkyl, alkylacylthio, alkylcarbocyclylthio, alkylheterocyclylthio, alkylheteroarylthio, alkylalkenylalkyl, alkylalkynylalkyl, alkylarylalkyl, alkylacylalkyl, arylalkylaryl, arylalkenylaryl, arylalkynylaryl, arylacylaryl, arylacyl, arylcarbocyclyl, arylheterocyclyl, arylheteroaryl, alkenyloxyaryl, alkynyloxyaryl, aryloxyaryl, alkylthioaryl, alkenylthioaryl, alkynylthioaryl, arylthioaryl, arylacylthio, arylcarbocyclylthio, arylheterocyclylthio, arylheteroarylthio, and a polymer chain.

Examples of R in the RAFT agents also include optionally substituted, and in the case of R* in the RAFT agents may also include an x-valent form of optionally substituted, alkyl; saturated, unsaturated or aromatic carbocyclic or heterocyclic ring; alkylthio; dialkylamino; an organometallic species; and a polymer chain.

More specific examples of R in the RAFT agents may include optionally substituted, and in the case of R in the RAFT agents may include an x-valent form of optionally substituted, CrC₁₈ alkyl, C₂-Ci₈ alkenyl, C₂-Ci₈ alkynyl, C₆-Ci₈ aryl, Ci-Ci₈ acyl, C₃-Ci₈ carbocyclyl, C₂-Ci₈ heterocyclyl, C₃-Ci₈ heteroaryl, Ci-Ci₈ alkylthio, C₂-Ci₈ alkenylthio, C₂-Ci₈ alkynylthio, C₆-Ci₈ arylthio, Ci-Ci₈ acylthio, C₃-Ci₈ carbocyclylthio, C₂-Ci₈ heterocyclylthio, C₃-Ci₈ heteroarylthio, C₃-Ci₈ alkylalkenyl, C₃-Ci₈ alkylalkynyl, C₇-C₂₄ alkylaryl, C₂-Ci₈ alkylacyl, C₄-Ci₈ alkylcarbocyclyl, C₃-Ci₈ alkylheterocyclyl, C₄-Ci₈ alkylheteroaryl, C₂-Ci₈ alkyloxyalkyl, C₃-Ci₈ alkenyloxyalkyl, C₃-Ci₈ alkynyloxyalkyl, C₇-C₂₄ aryloxyalkyl, C₂-Ci₈ alkylacyloxy, C₂-Ci₈ alkylthioalkyl, C₃-Ci₈ alkenylthioalkyl, C₃-Ci₈ alkynylthioalkyl, C₇-C₂₄ arylthioalkyl, C₂-Ci₈ alkylacylthio, C₄-Ci₈ alkylcarbocyclylthio, C₃-Ci₈ alkylheterocyclylthio, C₄-Ci₈ alkylheteroarylthio, C₄-Ci₈ alkylalkenylalkyl, C₄-Ci₈ alkylalkynylalkyl, C₈-C₂₄ alkylarylalkyl, C₃-Ci₈ alkylacylalkyl, Ci₃-C₂₄ arylalkylaryl, Ci₄-C₂₄ arylalkenylaryl, Ci₄-C₂₄ arylalkynylaryl, Ci₃-C₂₄ arylacylaryl, C₇-Ci₈ arylacyl, C9-Ci₈ arylcarbocyclyl, C₈-Ci₈ arylheterocyclyl, C9-Ci₈ arylheteroaryl, C₈-Ci₈ alkenyloxyaryl, C₈-Ci₈ alkynyloxyaryl, Ci₂-C₂₄ aryloxyaryl, alkylthioaryl, C₈-Ci₈ alkenylthioaryl, C₈-Ci₈ alkynylthioaryl, Ci₂-C₂₄ arylthioaryl, C₇-Ci₈ arylacylthio, C9-Ci₈ arylcarbocyclylthio, C₈-Ci₈ arylheterocyclylthio, C9-Ci₈ arylheteroarylthio, and a polymer chain having a number average molecular weight in the range of about 500 to about 80,000, for example in the range of about 500 to about 30,000.

Where R in the RAFT agents include, and in the case of R* in the RAFT agents include an x-valent form of, an optionally substituted polymer chain, the polymers chain may be formed by any suitable polymerisation process such as radical, ionic, coordination, step- growth or condensation polymerisation. These polymer chains may comprise homopolymer, block polymer, multiblock polymer, gradient copolymer, or random or statistical copolymer chains and may have various architectures such as linear, star, branched, graft, or brush.

Examples of Z in the RAFT agents may include optionally substituted, and in the case of Z* in RAFT agents may include a y-valent form of optionally substituted: F, CI, Br, I, alkyl, aryl, acyl, amino, carbocyclyl, heterocyclyl, heteroaryl, alkyloxy, aryloxy, acyloxy, acylamino, carbocyclyloxy, heterocyclyloxy, heteroaryloxy, alkylthio, arylthio, acylthio, carbocyclylthio, heterocyclylthio, heteroarylthio, alkylaryl, alkylacyl, alkylcarbocyclyl, alkylheterocyclyl, alkylheteroaryl, alkyloxyalkyl, aryloxyalkyl, alkylacyloxy, alkylcarbocyclyloxy, alkylheterocyclyloxy, alkylheteroaryloxy, alkylthioalkyl, arylthioalkyl, alkylacylthio, alkylcarbocyclylthio, alkylheterocyclylthio, alkylheteroarylthio, alkylarylalkyl, alkylacylalkyl, arylalkylaryl, arylacylaryl, arylacyl, arylcarbocyclyl, arylheterocyclyl, arylheteroaryl, aryloxyaryl, arylacyloxy, arylcarbocyclyloxy, arylheterocyclyloxy, arylheteroaryloxy, alkylthioaryl, arylthioaryl, arylacylthio, arylcarbocyclylthio, arylheterocyclylthio, arylheteroarylthio, dialkyloxy- , diheterocyclyloxy- or diaryloxy- phosphinyl, dialkyl-, diheterocyclyl- or diaryl- phosphinyl, cyano (i.e. -CN), and -S-R, where R is as defined in respect of formula (V).

More specific examples of Z in the RAFT agents include optionally substituted, and in the case of Z* in the RAFT agents may include a y-valent form of optionally substituted: F, CI, Ci-Cis alkyl, C₆-Ci₈ aryl, Ci-Cis acyl, amino, C₃-C₁₈ carbocyclyl, C2-C₁₈ heterocyclyl, C3-C18 heteroaryl, Ci-Cis alkyloxy, C₆-Ci₈ aryloxy, Ci-Cis acyloxy, C3-C18 carbocyclyloxy, C₂-Ci₈ heterocyclyloxy, C₃-C₁₈ heteroaryloxy, Q-Cis alkylthio, C₆-Ci₈ arylthio, Q-Cis acylthio, C₃-C₁₈ carbocyclylthio, C₂-Ci₈ heterocyclylthio, C₃-C₁₈ heteroarylthio, C₇-C₂₄ alkylaryl, C₂-Cis alkylacyl, C₄-Ci₈ alkylcarbocyclyl, C₃-Ci₈ alkylheterocyclyl, C₄-Ci₈ alkylheteroaryl, C₂-Ci₈ alkyloxyalkyl, C₇-C₂₄ aryloxyalkyl, C₂-Ci₈ alkylacyloxy, C₄-Ci₈ alkylcarbocyclyloxy, C₃-Ci₈ alkylheterocyclyloxy, C₄-Ci₈ alkylheteroaryloxy, C₂-Ci₈ alkylthioalkyl, C₇-C₂₄ arylthioalkyl, C₂-Ci₈ alkylacylthio, C₄-Cis alkylcarbocyclylthio, C₃-Ci₈ alkylheterocyclylthio, C₄-Ci₈ alkylheteroarylthio, C₈-C₂₄ alkylarylalkyl, C₃-C18 alkylacylalkyl, Ci₃-C₂₄ arylalkylaryl, Ci₃-C₂₄ arylacylaryl, C7-C18 arylacyl, C9-C18 arylcarbocyclyl, C₈-Ci₈ arylheterocyclyl, C9-C18 arylheteroaryl, Ci₂-C₂₄ aryloxyaryl, C7-C18 arylacyloxy, C9-C18 arylcarbocyclyloxy, Cs-Cis arylheterocyclyloxy, C9-C18 arylheteroaryloxy, C7-C18 alkylthioaryl, Ci₂-C₂₄ arylthioaryl, C7-C18 arylacylthio, C9-C18 arylcarbocyclylthio, Cs-Cis arylheterocyclylthio, C9-C18 arylheteroarylthio, dialkyloxy- , diheterocyclyloxy- or diaryloxy- phosphinyl (i.e. -P(=0)OR^k ₂), dialkyl-, diheterocyclyl- or diaryl- phosphinyl (i.e. -P(=0)R^k ₂), where R^k is selected from optionally substituted Ci-Cis alkyl, optionally substituted C₆-Ci₈ aryl, optionally substituted C₂-Cis heterocyclyl, and optionally substituted C₇-C₂₄ alkylaryl, cyano (i.e. -CN), and -S-R, where R is as defined in respect of formula (V).

In one embodiment, the RAFT agent may be a trithiocarbonate RAFT agent and Z or Z* may be an optionally substituted alkylthio group. Reference herein to a x-valent, y-valent, multi-valent or di-valent "form of...." is intended to mean that the specified group is a x-valent, y-valent, multi-valent or di-valent radical, respectively. For example, where x or y is 2, the specified group is intended to be a divalent radical. In that case, a divalent alkyl group is in effect an alkylene group (e.g. - CH₂-). Similarly, the divalent form of the group alkylaryl may, for example, be represented by -(C₆H₄)-CH₂-, a divalent alkylarylalkyl group may, for example, be represented by -CH₂-(C₆H₄)-CH₂-, a divalent alkyloxy group may, for example, be represented by -CH₂-0-, and a divalent alkyloxyalkyl group may, for example, be represented by -CH₂-0-CH₂-. Where the term "optionally substituted" is used in combination with such a x-valent, y-valent, multi-valent or di-valent groups, that group may or may not be substituted or fused as herein described. Where the x-valent, y-valent, multi-valent, di-valent groups comprise two or more subgroups, for example [group A] [group B] [group C] (e.g. alkylarylalkyl), if viable one or more of such subgroups may be optionally substituted. Those skilled in the art will appreciate how to apply this rationale in providing for higher valent forms.

Techniques, equipment and reagents for undertaking free radical polymerisation of ethylenically unsaturated monomers are generally well known to those skilled in the art and can advantageously be applied in the present invention.

The network of polymer chains that form the polymeric matrix will have a degree of crosslinking so as to afford the hydrogel structure.

Those skilled in the art will appreciate that the crosslinking of polymer chains may be achieved in numerous ways. For example, crosslinking may be achieved using multi- ethylenically unsaturated monomers. In that case, crosslinking is typically derived through a free radical reaction mechanism during polymerisation.

Alternatively, crosslinking may be achieved using ethylenically unsaturated monomers which also contain a reactive functional group that is not susceptible to taking part in free radical reactions (i.e. "functionalised" unsaturated monomers). In that case, such monomers may be incorporated into the polymer backbone through polymerisation of the unsaturated group, and the resulting pendant functional group provides means through which crosslinking may occur. By utilising monomers that provide complementary pairs of reactive functional groups (i.e. groups that will react with each other), the pairs of reactive functional groups can react through non-radical reaction mechanisms to provide crosslinks. A variation on using complementary pairs of reactive functional groups is where the monomers are provided with non-complementary reactive functional groups. In that case, the functional groups will not react with each other but instead provide sites which can subsequently be reacted with a crosslinking agent to form the crosslinks. It will be appreciated that such crosslinking agents will be used in an amount to react with substantially all of the non-complementary reactive functional groups. Formation of the crosslinks under these circumstances will generally occur after polymerisation of the monomers.

A combination of these crosslinking techniques may be employed. The terms "multi-ethylenically unsaturated monomers" and "functionalised unsaturated monomers" mentioned above can conveniently and collectively also be referred to herein as "crosslinking ethylenically unsaturated monomers" or "crosslinking monomers". By the general term "crosslinking ethylenically unsaturated monomers" or "crosslinking monomers" it is meant an ethylenically unsaturated monomer through which a crosslink is or will be derived.

It will be appreciated that not all unsaturated monomers that contain a functional group will necessarily be used for the purpose of functioning as a crosslinking monomer. For example, acrylic acid should not be considered as a crosslinking monomer unless it is used to provide a site through which a crosslink is to be derived.

Examples of suitable multi-ethylenically unsaturated monomers that may be used to promote crosslinking include ethylene glycol di(meth)acrylate, triethylene glycol di(meth)acrylate, tetraethylene glycol di(meth)acrylate, 1,3-butylene glycol di(meth)acrylate, trimethylolpropane tri(meth)acrylate, 1,4-butanediol di(meth)acrylate, neopentyl glycol di(meth)acrylate, 1,6-hexanediol di(meth)acrylate, pentaerythritol di(meth)acrylate, pentaerythritol tri(meth)acrylate, pentaerythritol tetra(meth)acrylate, glycerol di(meth)acrylate, glycerol allyloxy di(meth)acrylate, 1, 1,1- tris(hydroxymethyl)ethane di(meth)acrylate, 1,1, 1 -tris(hydroxymethyl)ethane tri(meth)acrylate, l, l, l-tris(hydroxymethyl)propane di(meth)acrylate, 1, 1,1- tris(hydroxymethyl)propane tri(meth)acrylate, triallyl cyanurate, triallyl isocyanurate, triallyl trimellitate, diallyl phthalate, diallyl terephthalte, divinyl benzene, methylol (meth)acrylamide, triallylamine, oleyl maleate, glyceryl propoxy triacrylate, allyl methacrylate, methacrylic anhydride and methylenebis (meth) acrylamide.

Examples of suitable ethylenically unsaturated monomers which contain a reactive functional group that is not susceptible to taking part in free radical reactions include acetoacetoxyethyl methacrylate, glycidyl methacrylate, N-methylolacrylamide, (isobutoxymethyl)acrylamide, hydroxyethyl acrylate, i-butyl-carbodiimidoethyl methacrylate, acrylic acid, γ-methacryloxypropyltriisopropoxysilane, 2-isocyanoethyl methacrylate and diacetone acrylamide. Examples of suitable pairs of monomers mentioned directly above that provide complementary reactive functional groups include N-methylolacrylamide and itself, (isobutoxymethyl)acrylamide and itself, γ-methacryloxypropyltriisopropoxysilane and itself, 2-isocyanoethyl methacrylate and hydroxyethyl acrylate, and t-butyl- carbodiimidoethyl methacrylate and acrylic acid.

Examples of suitable crosslinking agents that can react with the reactive functional groups of one or more of the functionalised unsaturated monomers mentioned above include hexamethylene diamine, melamine, trimethylolpropane tris(2-methyl-l-aziridine propionate) and adipic bishydrazide. Examples of pairs of crosslinking agents and functionalised unsaturated monomers that provide complementary reactive groups include hexamethylene diamine and acetoacetoxyethyl methacrylate, hexamethylene diamine and glycidyl methacrylate, melamine and hydroxyethyl acrylate, trimethylolpropane tris(2- methyl-l-aziridine propionate) and acrylic acid, adipic bishydrazide and diacetone acrylamide.

The crosslinking monomers used may or may not also have one or more protected and/or free thiol functional groups covalently bound thereto.

Where crosslinking monomers do have one or more protected and/or free thiol functional groups covalently bound thereto, they may be a multi-ethylenically unsaturated monomer of general formula (IV):

where:

X is selected from H and optionally substituted Ci-C₆ alkyl;

n is an integer from 2-5, or is 2 or 3;

L is a linking moiety; and

PFT is one or more protected and/or free thiol functional groups. In formula (IV), L will of course have n+1 valence sites.

Crosslinking of the polymer chains may be promoted during or after formation of the polymer chains.

In one embodiment, the monomer composition polymerised to form the polymer chains also comprises multi-ethylenically unsaturated monomer. In a further embodiment, the monomer composition polymerised to form the polymer chains comprises ethylenically unsaturated monomer of general formula (II).

In another embodiment, the monomer composition polymerised to form the polymer chains comprises ethylenically unsaturated monomer of general formula (II) in combination with ethylenically unsaturated monomer of general formula (III) and/or formula (IV).

The polymer hydrogels have been found to exhibit improved metal atom sequestering properties relative to the state of the art polymer hydrogels.

According to the metal atom sequestering process, the polymer hydrogel is contacted with a composition comprising metal atoms to be sequestered. There is no particular limitation regard the form of the composition. In one embodiment, the composition comprising metal atoms is a soil composition.

In another embodiment, the composition comprising metal atoms is an aqueous composition. The polymer hydrogel may or may not be swollen with hydrophilic liquid when it is placed in contact with the composition. In either case, hydrophilic liquid will facilitate transport of metal atoms from the composition to within the polymeric matrix of the polymer hydrogel. In the case where the polymer hydrogel is not swollen with hydrophilic liquid when placed in contact with the composition, the hydrophilic liquid that facilitates transport of metal atoms will also function to swell the hydrogel.

Provided the polymer hydrogel can function as required in the metal sequestration process, there is no particular limitation on the physical form it can take. Generally, the polymer hydrogel will be in the form of discrete particles ranging in size from about 10 nm to about 1 cm.

Those skilled in the art will appreciate that sulfur-based functional groups can strongly bind with metal atoms. It is this sulfur-binding affinity that is believed to promote the metal atom sequestering function of the polymer hydrogels. By forming the polymer chains that make up the polymer hydrogel using ethylenically unsaturated monomer having one or more protected and/or free thiol functional groups covalently bound thereto, the polymeric matrix of the polymer hydrogel can be decorated with many sulfur containing functional groups. The resulting polymeric matrix can not only function effectively as a polymer hydrogel, but it has been found to exhibit improved metal atom sequestering properties relative to the state of the art polymer hydrogels.

The polymer hydrogels can be used to sequester any metal atom that binds with the protected and/or free thiol functional groups. By "metal atom" is meant an elemental metal or metalloid atom that may be in a charged or neutral state. For example, the metal atom may be a metal atom cation.

Such metal atoms include heavy and transition metal atoms. Specific examples of metal atoms include vanadium, cobalt, chromium, iron, arsenic, germanium, molybdenum, gold, antimony, tin, bismuth, zinc, copper, tungsten, rhenium, uranium, selenium, nickel, lead, mercury, cadmium, silver, manganese, palladium and platinum.

In one embodiment, the polymer hydrogels are used for remediation of sites, such as former industrial sites and mines, with soil contaminated with metal atoms. The polymer hydrogels may be applied to such a site by any convenient means. For example, the polymer hydrogel can be worked into the soil to some depth.. This can be achieved by any convenient means such as ploughing, or using a slurry or suspension of the polymer hydrogel that is applied to the site surface and soaks through the soil to a desired depth.

The polymer hydrogels can be added to the site in conjunction with plants or plant germinal material (such as seeds or spores), or added independently of the plants or their germinal material. For example, polymer hydrogel particles may comprise or be coated with one or more plant seeds or spores.

Further detail regarding the use of polymer hydrogels for remediation of sites, such as former industrial sites and mines, contaminated with metal atoms is provided in WO 2009/155643.

As used herein, the term "alkyl", used either alone or in compound words denotes straight chain, branched or cyclic alkyl, preferably Ci_₂o alkyl, e.g. Ci_io or Ci__6. Examples of straight chain and branched alkyl include methyl, ethyl, n-propyl, isopropyl, n-butyl, sec- butyl, i-butyl, n-pentyl, 1,2-dimethylpropyl, 1,1 -dimethyl-prop yl, hexyl, 4-methylpentyl, 1- methylpentyl, 2-methylpentyl, 3-methylpentyl, 1,1-dimethylbutyl, 2,2-dimethylbutyl, 3,3- dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 1,2,2-trimethylpropyl, 1, 1,2- trimethylpropyl, heptyl, 5-methylhexyl, 1-methylhexyl, 2,2-dimethylpentyl, 3,3- dimethylpentyl, 4,4-dimethylpentyl, 1,2-dimethylpentyl, 1,3-dimethylpentyl, 1,4- dimethyl-pentyl, 1,2,3-trimethylbutyl, 1, 1,2-trimethylbutyl, 1, 1,3-trimethylbutyl, octyl, 6- methylheptyl, 1-methylheptyl, 1,1,3,3-tetramethylbutyl, nonyl, 1-, 2-, 3-, 4-, 5-, 6- or 7- methyloctyl, 1-, 2-, 3-, 4- or 5-ethylheptyl, 1-, 2- or 3-propylhexyl, decyl, 1-, 2-, 3-, 4-, 5-, 6-, 7- and 8-methylnonyl, 1-, 2-, 3-, 4-, 5- or 6-ethyloctyl, 1-, 2-, 3- or 4-propylheptyl, undecyl, 1-, 2-, 3-, 4-, 5-, 6-, 7-, 8- or 9-methyldecyl, 1-, 2-, 3-, 4-, 5-, 6- or 7-ethylnonyl, 1-, 2-, 3-, 4- or 5-propyloctyl, 1-, 2- or 3-butylheptyl, 1-pentylhexyl, dodecyl, 1-, 2-, 3-, 4-, 5-, 6-, 7-, 8-, 9- or 10-methylundecyl, 1-, 2-, 3-, 4-, 5-, 6-, 7- or 8-ethyldecyl, 1-, 2-, 3-, 4-, 5- or 6-propylnonyl, 1-, 2-, 3- or 4-butyloctyl, 1-2-pentylheptyl and the like. Examples of cyclic alkyl include mono- or polycyclic alkyl groups such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl and the like. Where an alkyl group is referred to generally as "propyl", butyl" etc, it will be understood that this can refer to any of straight, branched and cyclic isomers where appropriate. An alkyl group may be optionally substituted by one or more optional substituents as herein defined.

The term "alkenyl" as used herein denotes groups formed from straight chain, branched or cyclic hydrocarbon residues containing at least one carbon to carbon double bond including ethylenically mono-, di- or polyunsaturated alkyl or cycloalkyl groups as previously defined, preferably C2-20 alkenyl (e.g. C2-10 or C₂-6)- Examples of alkenyl include vinyl, allyl, 1-methylvinyl, butenyl, iso-butenyl, 3-methyl-2-butenyl, 1-pentenyl, cyclopentenyl, 1-methyl-cyclopentenyl, 1-hexenyl, 3-hexenyl, cyclohexenyl, 1-heptenyl, 3-heptenyl, 1-octenyl, cyclooctenyl, 1-nonenyl, 2-nonenyl, 3-nonenyl, 1-decenyl, 3- decenyl, 1,3-butadienyl, 1,4-pentadienyl, 1,3-cyclopentadienyl, 1,3-hexadienyl, 1,4- hexadienyl, 1,3-cyclohexadienyl, 1,4-cyclohexadienyl, 1,3-cycloheptadienyl, 1,3,5- cycloheptatrienyl and 1,3,5,7-cyclooctatetraenyl. An alkenyl group may be optionally substituted by one or more optional substituents as herein defined. As used herein the term "alkynyl" denotes groups formed from straight chain, branched or cyclic hydrocarbon residues containing at least one carbon-carbon triple bond including ethylenically mono-, di- or polyunsaturated alkyl or cycloalkyl groups as previously defined. Unless the number of carbon atoms is specified the term preferably refers to C2-20 alkynyl (e.g. C2-10 or C₂-6)- Examples include ethynyl, 1-propynyl, 2-propynyl, and butynyl isomers, and pentynyl isomers. An alkynyl group may be optionally substituted by one or more optional substituents as herein defined.

The term "halogen" ("halo") denotes fluorine, chlorine, bromine or iodine (fluoro, chloro, bromo or iodo). The term "aryl" (or "carboaryl") denotes any of single, polynuclear, conjugated and fused residues of aromatic hydrocarbon ring systems (e.g. C₆-24 or C6-is)- · Examples of aryl include phenyl, biphenyl, terphenyl, quaterphenyl, naphthyl, tetrahydronaphthyl, anthracenyl, dihydroanthracenyl, benzanthracenyl, dibenzanthracenyl, phenanthrenyl, fluorenyl, pyrenyl, idenyl, azulenyl, chrysenyl. Preferred aryl include phenyl and naphthyl. An aryl group may or may not be optionally substituted by one or more optional substituents as herein defined. The term "arylene" is intended to denote the divalent form of aryl. The term "carbocyclyl" includes any of non-aromatic monocyclic, polycyclic, fused or conjugated hydrocarbon residues, preferably C₃-20 (e.g. C₃-10 or C₃-8). The rings may be saturated, e.g. cycloalkyl, or may possess one or more double bonds (cycloalkenyl) and/or one or more triple bonds (cycloalkynyl). Particularly preferred carbocyclyl moieties are 5- 6-membered or 9-10 membered ring systems. Suitable examples include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl, cyclopentenyl, cyclohexenyl, cyclooctenyl, cyclopentadienyl, cyclohexadienyl, cyclooctatetraenyl, indanyl, decalinyl and indenyl. A carbocyclyl group may be optionally substituted by one or more optional substituents as herein defined. The term "carbocyclylene" is intended to denote the divalent form of carbocyclyl.

The term "heteroatom" or "hetero" as used herein in its broadest sense refers to any atom other than a carbon atom which may be a member of a cyclic organic group. Particular examples of heteroatoms include nitrogen, oxygen, sulfur, phosphorous, boron, silicon, selenium and tellurium, more particularly nitrogen, oxygen and sulfur.

The term "heterocyclyl" when used alone or in compound words includes any of monocyclic, polycyclic, fused or conjugated hydrocarbon residues, preferably C₃-20 (e.g. C₃-10 or C₃-8) wherein one or more carbon atoms are replaced by a heteroatom so as to provide a non-aromatic residue. Suitable heteroatoms include O, N, S, P and Se, particularly O, N and S. Where two or more carbon atoms are replaced, this may be by two or more of the same heteroatom or by different heteroatoms. The heterocyclyl group may be saturated or partially unsaturated, i.e. possess one or more double bonds. Particularly preferred heterocyclyl are 5-6 and 9-10 membered heterocyclyl. Suitable examples of heterocyclyl groups may include azridinyl, oxiranyl, thiiranyl, azetidinyl, oxetanyl, thietanyl, 2H-pyrrolyl, pyrrolidinyl, pyrrolinyl, piperidyl, piperazinyl, morpholinyl, indolinyl, imidazolidinyl, imidazolinyl, pyrazolidinyl, thiomorpholinyl, dioxanyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydropyrrolyl, tetrahydrothiophenyl, pyrazolinyl, dioxalanyl, thiazolidinyl, isoxazolidinyl, dihydropyranyl, oxazinyl, thiazinyl, thiomorpholinyl, oxathianyl, dithianyl, trioxanyl, thiadiazinyl, dithiazinyl, trithianyl, azepinyl, oxepinyl, thiepinyl, indenyl, indanyl, 3H-indolyl, isoindolinyl, 4H-quinolazinyl, chromenyl, chromanyl, isochromanyl, pyranyl and dihydropyranyl. A heterocyclyl group may be optionally substituted by one or more optional substituents as herein defined. The term "heterocyclylene" is intended to denote the divalent form of heterocyclyl.

The term "heteroaryl" includes any of monocyclic, polycyclic, fused or conjugated hydrocarbon residues, wherein one or more carbon atoms are replaced by a heteroatom so as to provide an aromatic residue. Preferred heteroaryl have 3-20 ring atoms, e.g. 3-10. Particularly preferred heteroaryl are 5-6 and 9-10 membered bicyclic ring systems. Suitable heteroatoms include, O, N, S, P and Se, particularly O, N and S. Where two or more carbon atoms are replaced, this may be by two or more of the same heteroatom or by different heteroatoms. Suitable examples of heteroaryl groups may include pyridyl, pyrrolyl, thienyl, imidazolyl, furanyl, benzothienyl, isobenzothienyl, benzofuranyl, isobenzofuranyl, indolyl, isoindolyl, pyrazolyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolizinyl, quinolyl, isoquinolyl, phthalazinyl, 1,5-naphthyridinyl, quinozalinyl, quinazolinyl, quinolinyl, oxazolyl, thiazolyl, isothiazolyl, isoxazolyl, triazolyl, oxadialzolyl, oxatriazolyl, triazinyl, and furazanyl. A heteroaryl group may be optionally substituted by one or more optional substituents as herein defined. The term "heteroarylene" is intended to denote the divalent form of heteroaryl.

The term "acyl" either alone or in compound words denotes a group containing the moiety C=0 (and not being a carboxylic acid, ester or amide) Preferred acyl includes C(0)-R^e, wherein R^e is hydrogen or an alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, or heterocyclyl residue. Examples of acyl include formyl, straight chain or branched alkanoyl (e.g. Ci-₂₀) such as acetyl, propanoyl, butanoyl, 2-methylpropanoyl, pentanoyl, 2,2- dimethylpropanoyl, hexanoyl, heptanoyl, octanoyl, nonanoyl, decanoyl, undecanoyl, dodecanoyl, tridecanoyl, tetradecanoyl, pentadecanoyl, hexadecanoyl, heptadecanoyl, octadecanoyl, nonadecanoyl and icosanoyl; cycloalkylcarbonyl such as cyclopropylcarbonyl cyclobutylcarbonyl, cyclopentylcarbonyl and cyclohexylcarbonyl; aroyl such as benzoyl, toluoyl and naphthoyl; aralkanoyl such as phenylalkanoyl (e.g. phenylacetyl, phenylpropanoyl, phenylbutanoyl, phenylisobutylyl, phenylpentanoyl and phenylhexanoyl) and naphthylalkanoyl (e.g. naphthylacetyl, naphthylpropanoyl and naphthylbutanoyl] ; aralkenoyl such as phenylalkenoyl (e.g. phenylpropenoyl, phenylbutenoyl, phenylmethacryloyl, phenylpentenoyl and phenylhexenoyl and naphthylalkenoyl (e.g. naphthylpropenoyl, naphthylbutenoyl and naphthylpentenoyl); aryloxyalkanoyl such as phenoxyacetyl and phenoxypropionyl; arylthiocarbamoyl such as phenylthiocarbamoyl; arylglyoxyloyl such as phenylglyoxyloyl and naphthylglyoxyloyl; arylsulfonyl such as phenylsulfonyl and napthylsulfonyl; heterocycliccarbonyl; heterocyclicalkanoyl such as thienylacetyl, thienylpropanoyl, thienylbutanoyl, thienylpentanoyl, thienylhexanoyl, thiazolylacetyl, thiadiazolylacetyl and tetrazolylacetyl; heterocyclicalkenoyl such as heterocyclicpropenoyl, heterocyclicbutenoyl, heterocyclicpentenoyl and heterocyclichexenoyl; and heterocyclicglyoxyloyl such as thiazolyglyoxyloyl and thienylglyoxyloyl. The R^e residue may be optionally substituted as described herein.

The term "sulfoxide", either alone or in a compound word, refers to a group -S(0)R wherein R is selected from hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocyclyl, carbocyclyl, and aralkyl. Examples of preferred R include Ci_₂oalkyl, phenyl and benzyl.

The term "sulfonyl", either alone or in a compound word, refers to a group S(0)₂-R , wherein R is selected from hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocyclyl, carbocyclyl and aralkyl. Examples of preferred R include Ci_₂oalkyl, phenyl and benzyl. The term "sulfonamide", either alone or in a compound word, refers to a group S(0)NR f R f wherein each R is independently selected from hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocyclyl, carbocyclyl, and aralkyl. Examples of preferred R include Ci_ ₂oalkyl, phenyl and benzyl. In one embodiment at least one R is hydrogen. In another embodiment, both R are hydrogen.

The term, "amino" is used here in its broadest sense as understood in the art and includes groups of the formula NR^aR^b wherein R^a and R^b may be any independently selected from hydrogen, alkyl, alkenyl, alkynyl, aryl, carbocyclyl, heteroaryl, heterocyclyl, arylalkyl, and acyl. R^a and R^b, together with the nitrogen to which they are attached, may also form a monocyclic, or polycyclic ring system e.g. a 3-10 membered ring, particularly, 5-6 and 9- 10 membered systems. Examples of "amino" include NH₂, NHalkyl (e.g. Ci_₂oalkyl), NHaryl (e.g. NHphenyl), NHaralkyl (e.g. NHbenzyl), NHacyl (e.g. NHC(O)Ci_₂₀alkyl, NHC(O)phenyl), Nalkylalkyl (wherein each alkyl, for example Ci_₂o, may be the same or different) and 5 or 6 membered rings, optionally containing one or more same or different heteroatoms (e.g. O, N and S).

The term "amido" is used here in its broadest sense as understood in the art and includes groups having the formula C(0)NR^aR^b, wherein R^a and R^b are as defined as above.

Examples of amido include C(0)NH₂, C(0)NHalkyl (e.g. Ci_₂₀alkyl), C(0)NHaryl (e.g.

C(O)NHphenyl), C(0)NHaralkyl (e.g. C(O)NHbenzyl), C(0)NHacyl (e.g.

C(O)NHC(O)Ci-₂₀alkyl, C(0)NHC(0)phenyl), C(0)Nalkylalkyl (wherein each alkyl, for example Ci_₂o, may be the same or different) and 5 or 6 membered rings, optionally containing one or more same or different heteroatoms (e.g. O, N and S).

The term "carboxy ester" is used here in its broadest sense as understood in the art and includes groups having the formula C0₂R^g, wherein R^g may be selected from groups including alkyl, alkenyl, alkynyl, aryl, carbocyclyl, heteroaryl, heterocyclyl, aralkyl, and acyl. Examples of carboxy ester include C0₂Ci_₂oalkyl, C0₂aryl (e.g.. C0₂phenyl), C0₂aralkyl (e.g. C0₂ benzyl). As used herein, the term "aryloxy" refers to an "aryl" group attached through an oxygen bridge. Examples of aryloxy substituents include phenoxy, biphenyloxy, naphthyloxy and the like.

As used herein, the term "acyloxy" refers to an "acyl" group wherein the "acyl" group is in turn attached through an oxygen atom. Examples of "acyloxy" include hexylcarbonyloxy (heptanoyloxy), cyclopentylcarbonyloxy, benzoyloxy, 4-chlorobenzoyloxy, decylcarbonyloxy (undecanoyloxy), propylcarbonyloxy (butanoyloxy), octylcarbonyloxy (nonanoyloxy), biphenylcarbonyloxy (eg 4-phenylbenzoyloxy), naphthylcarbonyloxy (eg 1-naphthoyloxy) and the like.

As used herein, the term "alkyloxycarbonyl" refers to an "alkyloxy" group attached through a carbonyl group. Examples of "alkyloxycarbonyl" groups include butylformate, sec-butylformate, hexylformate, octylformate, decylformate, cyclopentylformate and the like.

As used herein, the term "arylalkyl" refers to groups formed from straight or branched chain alkanes substituted with an aromatic ring. Examples of arylalkyl include phenylmethyl (benzyl), phenylethyl and phenylpropyl.

As used herein, the term "alkylaryl" refers to groups formed from aryl groups substituted with a straight chain or branched alkane. Examples of alkylaryl include methylphenyl and isopropylphenyl. In this specification "optionally substituted" is taken to mean that a group may or may not be substituted or fused (so as to form a condensed polycyclic group) with one, two, three or more of organic and inorganic groups, including those selected from: alkyl, alkenyl, alkynyl, carbocyclyl, aryl, heterocyclyl, heteroaryl, acyl, aralkyl, alkaryl, alkheterocyclyl, alkheteroaryl, alkcarbocyclyl, halo, haloalkyl, haloalkenyl, haloalkynyl, haloaryl, halocarbocyclyl, haloheterocyclyl, haloheteroaryl, haloacyl, haloaryalkyl, hydroxy, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, hydroxycarbocyclyl, hydroxyaryl, hydroxyheterocyclyl, hydroxyheteroaryl, hydroxyacyl, hydroxyaralkyl, alkoxyalkyl. alkoxyalkenyl, alkoxyalkynyl, alkoxycarbocyclyl, alkoxyaryl, alkoxyheterocyclyl. alkoxyheteroaryl, alkoxyacyl, alkoxyaralkyl, alkoxy, alkenyloxy, alkynyloxy, aryloxy. carbocyclyloxy, aralkyloxy, heteroaryloxy, heterocyclyloxy, acyloxy, haloalkoxy. haloalkenyloxy, haloalkynyloxy, haloaryloxy, halocarbocyclyloxy, haloaralkyloxy. haloheteroaryloxy, haloheterocyclyloxy, haloacyloxy, nitro, nitroalkyl, nitroalkenyl. nitroalkynyl, nitroaryl, nitroheterocyclyl, nitroheteroayl, nitrocarbocyclyl, nitroacyl. nitroaralkyl, amino (NH₂), alkylamino, dialkylamino, alkenylamino, alkynylamino. arylamino, diarylamino, aralkylamino, diaralkylamino, acylamino, diacylamino. heterocyclamino, heteroarylamino, carboxy, carboxyester, amido, alkylsulphonyloxy. arylsulphenyloxy, alkylsulphenyl, arylsulphenyl, thio, alkylthio, alkenylthio, alkynylthio. arylthio, aralkylthio, carbocyclylthio, heterocyclylthio, heteroarylthio, acylthio, sulfoxide. sulfonyl, sulfonamide, aminoalkyl, aminoalkenyl, aminoalkynyl, aminocarbocyclyl. aminoaryl, aminoheterocyclyl, aminoheteroaryl, aminoacyl, aminoaralkyl, thioalkyl. thioalkenyl, thioalkynyl, thiocarbocyclyl, thioaryl, thioheterocyclyl, thioheteroaryl. thioacyl, thioaralkyl, carboxyalkyl, carboxyalkenyl, carboxyalkynyl, carboxycarbocyclyl. carboxyaryl, carboxyheterocyclyl, carboxyheteroaryl, carboxyacyl, carboxyaralkyl. carboxyesteralkyl, carboxyesteralkenyl, carboxyesteralkynyl, carboxyestercarbocyclyl. carboxyesteraryl, carboxyesterheterocyclyl, carboxyesterheteroaryl, carboxyesteracyl. carboxyesteraralkyl, amidoalkyl, amidoalkenyl, amidoalkynyl, amidocarbocyclyl. amidoaryl, amidoheterocyclyl, amidoheteroaryl, amidoacyl, amidoaralkyl, formylalkyl. formylalkenyl, formylalkynyl, formylcarbocyclyl, formylaryl, formylheterocyclyl. formylheteroaryl, formylacyl, formylaralkyl, acylalkyl, acylalkenyl, acylalkynyl. acylcarbocyclyl, acylaryl, acylheterocyclyl, acylheteroaryl, acylacyl, acylaralkyl. sulfoxidealkyl, sulfoxidealkenyl, sulfoxidealkynyl, sulfoxidecarbocyclyl, sulfoxidearyl. sulfoxideheterocyclyl, sulfoxideheteroaryl, sulfoxideacyl, sulfoxidearalkyl, sulfonylalkyl. sulfonylalkenyl, sulfonylalkynyl, sulfonylcarbocyclyl, sulfonylaryl, sulfonylheterocyclyl. sulfonylheteroaryl, sulfonylacyl, sulfonylaralkyl, sulfonamidoalkyl, sulfonamidoalkenyl. sulfonamidoalkynyl, sulfonamidocarbocyclyl, sulfonamidoaryl, sulfonamidoheterocyclyl. sulfonamidoheteroaryl, sulfonamidoacyl, sulfonamidoaralkyl, nitroalkyl, nitroalkenyl. nitroalkynyl, nitrocarbocyclyl, nitroaryl, nitroheterocyclyl, nitroheteroaryl, nitroacyl. nitroaralkyl, cyano, sulfate, phosphate, triarylmethyl, triarylamino, oxadiazole, and carbazole groups. Optional substitution may also be taken to refer to where a -CH₂- group in a chain or ring is replaced by a group selected from -0-, -S-, -NR^a-, -C(O)- (i.e. carbonyl), -C(0)0- (i.e. ester), and -C(0)NR^a- (i.e. amide), where R^a is as defined herein.

Preferred optional substituents include alkyl, (e.g. Ci_₆ alkyl such as methyl, ethyl, propyl, butyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl), hydroxyalkyl (e.g. hydroxymethyl, hydroxyethyl, hydroxypropyl), alkoxyalkyl (e.g. methoxymethyl, methoxyethyl, methoxypropyl, ethoxymethyl, ethoxyethyl, ethoxypropyl etc) alkoxy (e.g. Ci_₆ alkoxy such as methoxy, ethoxy, propoxy, butoxy, cyclopropoxy, cyclobutoxy), halo, trifluoromethyl, trichloromethyl, tribromomethyl, hydroxy, phenyl (which itself may be further substituted e.g., by Ci_₆ alkyl, halo, hydroxy, hydroxyCi-₆ alkyl, Ci_₆ alkoxy, haloCi_₆alkyl, cyano, nitro OC(0)Ci_₆ alkyl, and amino), benzyl (wherein benzyl itself may be further substituted e.g., by Ci_₆ alkyl, halo, hydroxy, hydroxyCi_₆alkyl, Ci_₆ alkoxy, haloCi-₆ alkyl, cyano, nitro OC(0)Ci_₆ alkyl, and amino), phenoxy (wherein phenyl itself may be further substituted e.g., by Ci_₆ alkyl, halo, hydroxy, hydroxyCi-₆ alkyl, Ci_₆ alkoxy, haloCi_₆ alkyl, cyano, nitro OC(0)Ci_₆ alkyl, and amino), benzyloxy (wherein benzyl itself may be further substituted e.g., by Ci_₆ alkyl, halo, hydroxy, hydroxyCi_₆ alkyl, Ci_₆ alkoxy, haloCi-₆ alkyl, cyano, nitro OC(0)Ci_₆ alkyl, and amino), amino, alkylamino (e.g. Ci_₆ alkyl, such as methylamino, ethylamino, propylamino etc), dialkylamino (e.g. Ci_₆ alkyl, such as dimethylamino, diethylamino, dipropylamino), acylamino (e.g. NHC(0)CH₃), phenylamino (wherein phenyl itself may be further substituted e.g., by Ci_₆ alkyl, halo, hydroxy, hydroxyCi-₆ alkyl, Ci_₆ alkoxy, haloCi-₆ alkyl, cyano, nitro OC(0)Ci_₆ alkyl, and amino), nitro, formyl, -C(0)-alkyl (e.g. Ci_₆ alkyl, such as acetyl), 0-C(0)-alkyl (e.g. Ci_ ₆alkyl, such as acetyloxy), benzoyl (wherein the phenyl group itself may be further substituted e.g., by Ci_₆ alkyl, halo, hydroxy hydroxyCi_₆ alkyl, Ci_₆ alkoxy, haloCi_₆ alkyl, cyano, nitro OC(0)Ci_₆alkyl, and amino), replacement of CH₂ with C=0, C0₂H, C0₂alkyl (e.g. Ci-₆ alkyl such as methyl ester, ethyl ester, propyl ester, butyl ester), C0₂phenyl (wherein phenyl itself may be further substituted e.g., by Ci_₆ alkyl, halo, hydroxy, hydroxyl Ci_₆ alkyl, Ci_₆ alkoxy, halo Ci_₆ alkyl, cyano, nitro OC(0)Ci_₆ alkyl, and amino), CONH₂, CONHphenyl (wherein phenyl itself may be further substituted e.g., by Ci_₆ alkyl, halo, hydroxy, hydroxyl Ci_₆ alkyl, Ci_₆ alkoxy, halo Ci_₆ alkyl, cyano, nitro OC(0)Ci_₆ alkyl, and amino), CONHbenzyl (wherein benzyl itself may be further substituted e.g., by Ci-6 alkyl, halo, hydroxy hydroxyl C_1-6 alkyl, C_1-6 alkoxy, halo C_1-6 alkyl, cyano, nitro OC(0)Ci_6 alkyl, and amino), CONHalkyl (e.g. C_1-6 alkyl such as methyl ester, ethyl ester, propyl ester, butyl amide) CONHdialkyl (e.g. Ci_₆ alkyl) aminoalkyl (e.g., HN Ci_₆ alkyl-, Ci_₆alkylHN-Ci_6 alkyl- and (Ci_₆ alkyl)₂N-Ci_₆ alkyl-), thioalkyl (e.g., HS Ci_₆ alkyl-), carboxyalkyl (e.g., H0₂CCi_6 alkyl-), carboxyesteralkyl (e.g., C_1-6 alkyl0₂CCi_6 alkyl-), amidoalkyl (e.g., H₂N(0)CCi_₆ alkyl-, H(Ci_₆ alkyl)N(0)CCi_₆ alkyl-), formylalkyl (e.g., OHCCi_₆alkyl-), acylalkyl (e.g., Ci_₆ alkyl(0)CCi_₆ alkyl-), nitroalkyl (e.g., 0₂NCi_₆ alkyl-), sulfoxidealkyl (e.g., R(0)SCi_₆ alkyl, such as Ci_₆ alkyl(0)SCi_₆ alkyl-), sulfonylalkyl (e.g., R(0)₂SCi-6 alkyl- such as C_1-6 alkyl(0)₂SCi_6 alkyl-), sulfonamidoalkyl (e.g., ₂HRN(0)SCi_6 alkyl, H(Ci_₆ alkyl)N(0)SCi_₆ alkyl-), triarylmethyl, triarylamino, oxadiazole, and carbazole. The invention will now be described with reference to the following non-limiting examples.

Examples 1. Materials and Methods

Nine cross-linked micron-size polymer gels were synthesized as described in Schemes 1A and 2A. Acrylamide (MP-Biomedical), acryloyl chloride (Merck), 4,4'-azobis(4- cyanovaleric acid) (Sigma Aldrich), 1-bromoethyl benzene (Sigma Aldrich), 3- bromopropanol (Sigma Aldrich), 18-crown-6 (Sigma Aldrich), 2-(Dimethylamino) ethyl methacrylate (Sigma Aldrich), ethylenediamine (Sigma Aldrich), Ν,Ν' methylene bisacrylamide (Fluka), methyl iodide (Sigma Aldrich), potassium O-ethyl xanthate (Sigma Aldrich), potassium thioacetate (Sigma Aldrich) and triethylamine (Sigma Aldrich) were used as received. Azo-bis-isobutyrylnitrile (AIBN, Reidel-de-Haen) was recrystallized from methanol before use. Surfaee functionality and metal-binding moieties S-(2-phenylethyl) 0-ethyl xanthate (Xanthate) and 3-(acetylthio) propyl acrylate (ATA) were synthesized according to procedures reported in the literature (Hrsic et al. 20i3.PosiiKl-I.ana, Klumperman. 2009). These protected moieties were transformed into thiol groups by facile treatment with eth.ylenediam.ine (Rossato et al. 2011). DMAEMA units were qua.terneri.zed by treatment with methyl iodide (Traong et al. 2011).

1.0 Monomer synthesis 1.1 Synthesis of 5-(2-phenylethyl) O-ethyl xanthate (Xanthate)

1-Bromoethyl benzene (10.28 g, 0.055 mol) was added drop wise to a solution of potassium O-ethyl xanthate (11.58 g, 0.072 mol) in ethanol. The mixture was stirred overnight (12 h) at room temperature. The solvent was removed using rotary evaporator and diethyl ether (400 mL) was added. The filtrate was washed with distilled water (4x100 mL) and dried over anhydrous magnesium sulfate. The solvent was evaporated under vacuum and the purified product was obtained by column chromatography (Petroleum spirit 40-60) (Pound-Lana, Klumperman 2009).

Table 1: 'H-NMR (CDC1₃) 5-(2-phenylethyl) O-ethyl xanthate

1.2 Synthesis of S-(3-hydroxypropyl) ethanethioate

Potassium thioacetate (7.00 g, 0.061 mol), 3-bromopropanol (5.70 g, 0.041 mol) and 18- crown-6 (1.62 g, 0.0061 mol) were dissolved and dispersed in acetone (300 mL). The reaction was refluxed at 65 °C for 2 hr. The reaction was stopped and cooled to room temperature. The yellow salt was filtered and acetone was removed using rotary evaporator(Hrsic 2013). Table 2: ^-NMR (CDC1₃) S-(3-hydroxypropyl) ethanethioate

1.3 Synthesis of 3-(acetylthio) propyl acrylate (ATA)

A solution of acryloyl chloride(2.68 g, 0.029 mol) in dry dichloromethane (DCM) was added drop wise over a period of 30 min, to a cold mixture of S-(3-hydroxypropyl) ethanethioate(4 g, 0.029 mol) and triethylamine (3.61 g, 0.035 mol) in dry DCM. The reaction was allowed to warm up to room temperature and stirred overnight (12 h)(Hrsic 2013).

Table 3: 'H-NMR (CDC1₃) 3-(acetylthio) propyl acrylate

Synthesis of cross-linked polymer gels and binding test to heavy metal ions

Various of micron-size polymer gels were synthesized by adopting a modified procedure by Rossato et al. (2011). The following descriptions are non-limiting examples and specifically they illustrate (i) the synthesis of different micro-size polymer gels by using ATA- a monomer with protected thiol group, (ii) the capacity of gels to sequester a variety of metal ions (particularly heavy metals commonly found in toxic concentrations on contaminated mine sites) in solution. Example 1 (comparative)

Synthesis of micron-size polymer gels based on neutral, acidic and basic monomers (i) Synthesis of acrylamide based micron-size polymer gel (1)

A polymerisation stock solution was prepared in a 100 mL round bottom flask by dissolving acrylamide monomer (18 g, 0.253 mol), bisacrylamide (1.1 g, 0.0071 mol), O- ethyl xanthate (0.3 g, 0.00133 mol) and AIBN (0.04 g, 0.00024 mol) into 20 mL dry dimethyl formamide (DMF). Polymerisation was carried out at 40°C for a period of 24 h, and then allowed to continue at 60°C for a further 24 h. The cross-linked polymer was then removed and crushed to fine particles using a mortar and pestle, and washed with Milli-Q water (400 mL x 6). Each time, water was added and the mixture was stirred for 30 min and solution was decanted, finally gel was freeze dried for 72 h.

A polymerisation stock solution was prepared in a 100 mL round bottom flask by dissolving acrylic acid monomer (18 g, 0.253 mol), bisacrylamide (1.1 g, 0.0071 mol), O- ethyl xanthate (0.3 g, 0.00133 mol) and AIBN (0.04 g, 0.00024 mol) into 20 mL dry DMF. Polymerisation was carried out at 40°C for a period of 24 h, and then allowed to continue at 60°C for a further 24 h. The cross-linked polymer was then removed and crushed to fine particles in the round bottom flask using a spatula. Milli-Q water (100 mL) was added to the gel in small portions to allow the gel to swell. Then methanol (300 mL) was added to separate the gel from water and solution was decanted. This mixture was washed with methanol (400 mL x 6),each time methanol was added and the mixture was stirred for 30 min and solution was decanted, finally gel was dried under high vacuum for 24 h.

(iii) Synthesis of DMAEMA (2-(Dimethylamino) ethyl methacrylate)based micron-size polymer gel (3)

A polymerisation stock solution was prepared in a 100 mL round bottom flask by dissolving 2-(Dimethylamino) ethyl methacrylate(DMAEMA) monomer (18 g, 0.253 mol), bisacrylamide (1.1 g, 0.0071 mol), O-ethyl xanthate (0.3 g, 0.00133 mol) and AIBN (0.04 g, 0.00024 mol) into 20 mL dry DMF. Polymerisation was carried out at 40 °C for a period of 24 h, and then allowed to continue at 60 °C for a further 24 h. The cross-linked polymer was then removed and crushed to fine particles using a mortar and pestle. Methanol (100 mL) was added to the gel in small portions to allow the gel to swell. Then Milli-Q water (300 mL) was added to separate the gel from solution and solution was decanted. This mixture was then washed with Milli-Q water (5 x 300 mL),each time mixture was stirred for 30 min and water was decanted, finally gel was freeze dried for 72 h. Example 2

Synthesis of micron-size thiol functional polymer gels based on thiol protected monomer ATA (4, 5 and 6)

Three polymerisation stock solutions were prepared, each in a 100 mL round bottom flask by dissolving acrylamide monomer (18 g, 0.253 mol), bisacrylamide (1.1 g, 0.0071 mol), O-ethyl xanthate (0.3 g, 0.00133 mol) and ACVA (0.06827 g, 0.00024 mol)into 20 mL dry DMF. Increasing amounts of 3-(Acetylthio) propyl acrylate (ATA)(0.25 g, 0.0013 mol) 4a, (0.5 g, 0.0026 mol) 5a and (1.0 g, 0.00531 mol) 6a,were added to the respective solutions. Polymerisation was carried out at 40°C for a period of 24 h, and then allowed to continue at 60°C for a further 24 h. The cross-linked polymer gels were then removed and crushed to fine particles using a mortar and pestle, and each mixture was washed with Milli-Q water (400 mL x 6). Each time, water was added and the mixtures were stirred for 30 min and the water was decanted. Finally gels were freeze dried for 72 h to obtain polymer gels 4a, 5a and 6a respectively. Micron-size polymer gels (4a, 5a and 6a) were aminolyzed by adopting a modified procedure by Rossato et al. (2011). Polymer gels4a, 5aand 6a (10 g, each) were made to swell in 100 mL Milli-Q water for 1 h with continuous stirring to obtain homogeneous gels. Ethylenediamine (17 molar equivalent, to protected thiol) was added in portions to the gel and the mixture was stirred at 50°C overnight (12 h). Each resulting mixture was purged under compressed air to reduce the volume to 75 mL. Methanol (400 mL) was added to the mixture to separate gel from solution and solution was decanted. Gels were washed with methanol (400 mL x 5), each time mixtures were stirred for 30 min and solutions were decanted. Finally the gels were dried under high vacuum for 24 h to yield polymer gels 4, 5 and 6 respectively.

Example 3

Synthesis of micron-size thiol functional acrylamide and DMAEMA (2- (Dimethylamino) ethyl methacrylate)polymer gels based on thiol protected monomer ATA (7, 8 and 9)

Three polymerisation stock solutions were prepared, each in 100 mL round bottom flasks by dissolving acrylamide monomer (3 g, 0.041 mol), 2-(dimethylamino) ethyl methacrylate(DMAEMA) monomer (15 g, 0.095 mol), bisacrylamide (1.1 g, 0.0071 mol), 0-ethyl xanthate (0.3 g, 0.00133 mol) and ACVA (0.06827 g, 0.00024 mol)into 20 mL dry DMF. Increasing amounts of 3-(acetylthio) propyl acrylate (ATA)(0.25 g, 0.0013 mol) 7a, (0.5 g, 0.0026 mol) 8a and (1.0 g, 0.00531 mol) 9a, were added to the respective solutions. Polymerisation was carried out at 40°C for a period of 24 h, and then allowed to continue at 60°C for a further 24 h. The cross-linked polymer gels were then removed and crushed to fine particles using a mortar and pestle. Methanol (100 mL) was added to each gel in small portions to allow the gel to swell. Then Milli-Q water (300 mL) was added to separate the gel from water and solution was decanted. This mixture was then washed with Milli-Q water (400 mL x 6). Each time, water was added and mixture was stirred for 30 min and water was decanted. Finally gels were freeze dried for 72 h to obtain polymer gels 7a, 8a and 9a respectively.

Polymers 7a, 8a and 9a were quaternerized by adopting a modified procedure by Truong et a (2011). Polymers7a, 8a and 8a(10 g, each containing polyDMAEMA (0.047 mol))were made to swell in 400 mL methanol for 1 h with continuous stirring to obtain homogeneous gels. Iodomethane (32 g, 0.23 mol) was added dropwise over a period of 10 min to each gel and the mixture was stirred for 48 h at room temperature. Methanol (100 mL) was added to each gel in small portions to allow the gel to swell. Then Milli-Q water (300 mL) was added to separate the gel from the water and solution was decanted. This mixture was than washed with Milli-Q water (5 x 300 mL). Each time mixture was stirred for 30 min and water was decanted. Finally gels were freeze dried for 72 h to obtain polymer gels7b, 8b and 9brespectively. Micron-size polymer gels were aminolyzed by adopting a modified procedure by Rossato et al. (2011). Polymers 7b, 8b and 9b (10 g, each) were made to swell in 20 mL Milli-Q water and 200 mL methanol for 1 h with continuous stirring to obtain a homogeneous gel. Ethylenediamine (8 molar equivalent to protected thiol groups) was added in portions to each gel and the mixture was stirred overnight (12 h) at room temperature. The final products were washed with methanol (400 mL x 5), and dried under high vacuum for 24 h to yield polymer gels 7, 8 and 9 respectively.

Example 4

Determination of deionized water holding capacities and gel fractions of polymer gels Deionised water holding capacities and gel fractions of polymer gels were determined by adopting a modified procedure by Rossato et al. (2011). Known amounts of polymers were wrapped with filter paper and placed in a soxhlet extractor attached to a 500 ml round bottom flask containing 500 mL of Milli-Q water. Polymers were refluxed for 12 h, the hydrated polymer was blotted onto filter paper to remove excess water. Finally the polymers were freeze dried. The deionised water holding capacity (DWHC) was calculated as the difference between the hydrated (W_h) and (W_d) polymer weights after freeze drying, expressed as a percentage of polymer dry weight as follows:

K i t

Gel fractions were measured as follows:

^■Gel fraction (%) = x II

Where:

W_dg = Weight of dried polymer gel obtained after purification

W_sx = Weight of dried polymer gel used for soxhlet extraction

W_fd = Weight of polymer gel after soxhlet extraction followed by freeze dryin

S_m = Sum of all starting materials used for polymer gel synthesis

Table 1: Deionised water holding capacities and gel fractions of micron size polymer gels

Micron- size polymer gels

^Comparative Example 5

Determination of metal and arsenic adsorption capacity

Materials and methods: The concentrations of test solutions used in all experiments were calculated based on the molar ratio of functional groups (FG) to metals and arsenic. Due to the differences in the functional groups of polymers, the concentrations of test solution were not the same. One Molar test solutions of As, Cd, Cu, Pb and Zn were prepared from sodium arsenate [Na₂HAs0₄.7H₂0], Cadmium Nitrate [Cd(N0₃)₂.4H₂0], Copper Nitrate Hemipenta Hydrate [Cu(N0₃)₂. 2.5H₂0], Lead Nitrate [Pb(N0₃)_2], and Zinc Nitrate Hexahydrate [Zn(N0₃)₂.6H₂0, respectively. Four concentrations of test solutions with approximately 3mM, 6mM, lOmM and 20mM metals or arsenic were prepared using the 1M stock solution of As, Cd, Cu, Pb and Zn. Each test used approximately 0.2g of Polymer and 10ml or 30ml of test solution. The amount of arsenic and metals added to each test solution to react with 0.2g of polymers depended on the functional group of each polymer. In general, the molar ratio of metals to functional groups ranged from 1.4 to 2.7 to ensure there are more metals in the test solution available to bind to functional groups in the polymers. As arsenic was a secondary element tested in the experiment, lower molar ratios of arsenic to functional groups were used (ranged from 0.3 to 1). The measured molar ratio of metals and arsenic to functional groups is presented in Table 2. The ion concentrations of tested solution are listed in Table 3.

Adsorption tests: For individual metal and Arsenic adsorption experiments, 0.2g of each type of polymer was weighed into 50ml tubes. A 10ml of solution containing concentration of each metal was added into the tube. The experiment was replicated three times. The polymers mixed and shaken with 10ml of Milli-Q water were treated as blank samples. Test solutions of approximately 3mM, 6mM, lOmM and 20mM without polymer were tested concurrently with the samples. Only polymer Al to A3 (group 3) were tested in a mixture solution of As and Cu at concentration ratio of 10: 1 was used to test the binding of As and Cu to polymers in group 3 (Al to A3). For the mixture solution test, a O.lg of gel was added with 100ml test solution with a mixture of As and Cu. The test solutions with polymers and without polymers were gently shaken for 20hrs. The pH of test solutions before and after shaking was measured. Solutions were centrifuged at 3000rpm for 30min at 22°C. The supernatant was gently pipetted into 10ml tubes and acidified to the matrix of 2% nitric acid and analyzed for metals and arsenic concentrations. Metals and arsenic concentrations were analyzed by Inductively Coupled Plasma Atomic Emission Spectroscopy (ICP-OES) and Inductively Coupled Plasma Mass Spectrometry (ICP-MS) depending on solution concentration at the Analytical Services Unit, School of Agriculture and Food Sciences, the University of Queensland. The certified reference natural waters with trace elements SRM 1640a and 1643e from the National Institute of Standard and Technology (NIST), USA were used to validate the analyses made by ICPMS and ICP. Analytical accuracy in the ICPMS measurements was checked by including three replicates of the SRM 1640a and 1643e in each batch of the analysed samples.

The mass balance of metals and arsenic in solution before and after the sorption test was used to calculate the ability of the polymer in binding metals and arsenic (Equation 1). metal in solutio n without gel — metal ΪΪΪ solution with; gel

% metal &&$orptien

m etal in so lution with out gel (1)

Table 2: The molar ratios of metals and arsenic to functional groups of the polymers

Functional group Molar ratios of metals/arsenic ions to functional groups of the polymers

Polymer gels

(mmol/g) As Cd²⁺ Cu²⁺ Pb²⁺ Zn²⁺

1 * 0.07 0.9 1.4 2.3 2.6 2.2

2* 0.07 0.9 1.4 2.3 2.6 2.2

3* 0.07 0.9 1.4 2.3 2.6 2.2

4 0.42 0.9 1.6 2.7 3.2 3

5 0.21 1.0 1.6 2.7 3.1 2.8

6 0.14 0.9 1.5 2.4 2.8 2.5

7 4.7 0.31 - 0.27 - -

8 4.7 0.32 - 0.21 - -

9 4.7 0.31 - 0.14 - -

^Comparative Table 3: Concentrations of metals and arsenic in test solutions

Functional group Concentrations (niM) of metals and arsenic in test solution

(mmol/g) As Cd²⁺ Cu²⁺ Pb²⁺ Zn²⁺

1 * 0.07 0.06 0.10 0.16 0.18 0.15

2* 0.07 0.06 0.10 0.16 0.18 0.15

3* 0.07 0.06 0.10 0.16 0.18 0.15

4 0.42 0.38 0.68 1.14 1.35 1.27

5 0.21 0.21 0.33 0.55 0.64 0.57

6 0.14 0.12 0.20 0.32 0.38 0.34

7 4.7 1.5 - 1.3 - -

8 4.7 1.5 - 1.0 - -

9 4.7 1.5 - 0.7 - -

Comparative

Absorption results: Table 4 presents the proportion of metals adsorbed into the polymers and reduced metals concentrations in the test solution. The results showed that none of the polymers from polymer gels 1 to 6 absorbed arsenic due to the negatively charged arsenic ions. All the 6 polymer gels with either xanthate or free thiol functional groups reduced considerable amounts of Pb²⁺ (40-90 %) and Cu²⁺ (5-73 %) in the test solutions. Polyacrylic acid Xanthate gels (2), polyacrylamide gels with free thiol made from ATA (5 and 6)reduced the concentrations of 4 tested metals Cd²⁺, Cu²⁺, Pb²⁺ and Zn²⁺ significantly. Particularly polymer gels 6 showed the highest absorption capacity of 4 tested metal ions.

Table 4: Metals adsorption in polymer gels (1 to 6) resulted from the single element test (mean + SE, n = 3)

Metals absorption (%) Metals binding to polymers (mg/g ; of gel)

Polymer gels

Cd²⁺ Cu²⁺ Pb²⁺ Zn²⁺ Cd²⁺ Cu²⁺ Pb²⁺ Zn²⁺

1* 5.0 ± 0.5 38.9 ± 0.4 4.5 ± 4.4 0.1 ± 0.01 3.1 ± 0.03 0.2 ± 0.1

2* 59.7± 1.4 58.6 ± 0.6 92.0 ± 0.2 54.6 ± 1.9 6.2 ± 0.2 1.2 ± 0.01 7.2 ± 0.02 1.2 ± 0.1

3* 73.6 ± 2.1 42.0 ± 0.5 1.6 ± 0.04 3.3 ± 0.04

4 8.2 ± 1.3 12.2 ± 0.4 52.8 ± 0.6 11.9 ± 4.2 6.0 ± 0.9 1.8 ± 0.1 30.7 ± 0.3 2.7 ± 0.6

5 14.7 ± 2.8 18.5 ± 0.1 58.9 ± 0.2 35.3 ± 18 5.5 ± 1.1 1.3 ± 0.01 16.0 ± 0.1 1.5 ± 0.1

6 56.0 ± 1.4 43.7 ± 1.5 84.5 ± 1.9 51.6 ± 2.5 12.1 ± 0.5 1.9 ± 0.1 13.7 ± 0.3 2.2 ± 0.1

Comparative

Polymer gels 7, 8 and 9 are permanent positively charged gels with thiol groups which are deprotected from ATA monomer. All 3 polymer gels reduce considerable quantities of Arsenic (29-33%) and Cu²⁺ (21-25%) in the test solutions separately (Table 5). Both As and Cu were bound to all 3 polymers with the range from 32 to 36 mg As per gram of gel and 12-13 mg Cu per gram of gels.

Further test was conducted to determine the absorption of both arsenic and Cu²⁺ in the mixed solution (Table 6). Since arsenic and Cu²⁺ generally dissolve in water at different pH values, higher concentrations for both arsenic and Cu²⁺ could not be achieved due to the precipitation during the test. This could have potentially affected the results. The test solution of the mixture of arsenic and Cu²⁺ at the concentration ratio of 10: 1 was used to ensure both arsenic and Cu²⁺ were completely dissolved in the test solution at pH 6.5. The molar ratio of arsenic to functional group was kept similar to that of single element test of -0.31. All 3 polymer gels reduced considerable quantities of arsenic (91 to 92%) and Cu²⁺ (39 to 49%) in the test solution. The mass of arsenic and Cu²⁺ bound to polymer gels 1 to 3 in the mixture test solution are lower than that of single test solution. The mass of approximate 8mg As and 0.8 mg Cu²⁺ could bind into the polymer gels 1 to 3 in the mixture test solution of arsenic and Cu 2+

Table 5: Arsenic and Cu ⁺ adsorption in polymer gels(7, 8, and 9) resulted from the single element test solution* (mean + SD, n = 3)

Polymer gels Arsenic and Cu ⁺ adsorption (%) As and Cu ⁺ binding to polymers (mg/g gel)

Arsenic Cu Ί+ Arsenic Cu

29 + 3 21 32.7 + 1.6 12.9

29 + 2 25 32.6 + 0.2 13.5

33 + 1 25 36.4 + 3.3 12.4

*Molar ratio of arsenic to functional group of 0.31

Table 6: Arsenic and Cu ⁺ adsorption in polymer gels resulted from the mixed arsenic and Cu ⁺test solution* (mean + SD, n = 3)

arsenic and Cu ⁺ binding to polymers (mg

Reduction in concentration(%) gel)

Polymer gels

Arsenic Cu^z Arsenic Cu^z

91 + 0.3 39 + 3.4 7.8 + 0.1 0.61 + 0.05 92 + 0.1 46 + 1 8.1 + 0.2 0.73 + 0.02 92 + 0.3 49 + 2.8 7.9 + 0.1 0.77 + 0.04

*Ratio of As:Cu is 10: 1 in concentrations

**Molar ratio of arsenic to functional group of 0.31 Throughout this specification and the claims which follow, unless the context requires otherwise, the word "comprise", and variations such as "comprises" and "comprising", will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of integers or steps.

The reference in this specification to any prior publication (or information derived from it), or to any matter which is known, is not, and should not be taken as an acknowledgment or admission or any form of suggestion that that prior publication (or information derived from it) or known matter forms part of the common general knowledge in the field of endeavour to which this specification relates.

Claims

1. Polymer hydrogel having a polymeric matrix of polymer chains, the polymer chains comprising polymerised residues of ethylenically unsaturated monomer, wherein a plurality of the polymerised monomer residues each have one or more protected and/or free thiol functional groups covalently bound thereto such that the functional groups present in pendant formation relative to the polymer chains.

2. The polymer hydrogel according to claim 1, wherein the polymer chains of the polymeric matrix each comprise at least 40 mol% of the polymerized ethylenically unsaturated monomer residues each having one or more protected and/or free thiol functional groups covalently bound thereto.

3. The polymer hydrogel according to claim 1 or 2, wherein one or more of the plurality of polymerised ethylenically unsaturated monomer residues having one or more protected and/or free thiol functional groups covalently bound thereto independently have a structure presented in general formula (I):

X

H₂

C P_R

PFT (I)

where:

X is selected from H and optionally substituted Ci-C₆ alkyl;

A is a moiety capable of activating an ethylenically unsaturated double bond such that it will undergo polymerisation; L is a linking moiety; and

PFT is selected from one or more of a protected thiol functional group, a free thiol functional group and a combination thereof. 3. The polymer hydrogel according to claim 2, wherein A is a multi-valent moiety selected from carbonyl (-C(O)-), ether (-0-), ester (-O-C(O)-), amide (-(R^z)N-C(0)-), anhydride (-C(O)-O-C(O)-), imide (-C(0)-(R^z)N-C(0)-) and optionally substituted arylene (-Ar-), where R^z is H or Ci-C₆ alkyl, and Ar is arylene.

4. The polymer hydrogel according to claim 2 or 3, wherein L is independently or forms together with A an optionally substituted multi-valent form of a group selected from alkyl, alkenyl, alkynyl, aryl, acyl, carbocyclyl, heterocyclyl, heteroaryl, alkyloxy, alkenyloxy, alkynyloxy, aryloxy, acyloxy, carbocyclyloxy, heterocyclyloxy, heteroaryloxy, alkylalkenyl, alkylalkynyl, alkylaryl, alkylacyl, alkylcarbocyclyl, alkylheterocyclyl, alkylheteroaryl, alkyloxyalkyl, alkenyloxyalkyl, alkynyloxyalkyl, aryloxyalkyl, alkylacyloxy, alkyloxyacylalkyl, alkylcarbocyclyloxy, alkylheterocyclyloxy, alkylheteroaryloxy, alkylalkenylalkyl, alkylalkynylalkyl, alkylarylalkyl, alkylacylalkyl, arylalkylaryl, arylalkenylaryl, arylalkynylaryl, arylacylaryl, arylacyl, arylcarbocyclyl, arylheterocyclyl, arylheteroaryl, alkenyloxyaryl, alkynyloxyaryl, aryloxyaryl, arylacyloxy, arylcarbocyclyloxy, arylheterocyclyloxy, arylheteroaryloxy, and polyoxyalkylene, wherein when present one or more -CH₂- groups in any alkyl chain is optionally replaced by a divalent group independently selected from -0-, -NR^a-, -C(O)-, -C(0)0-, -OC(0)0-, - OC(0)NR^a- and -C(0)NR^a-, where each R^a is independently selected from hydrogen, alkyl, alkenyl, alkynyl, aryl, carbocyclyl, heteroaryl, heterocyclyl, arylalkyl, and acyl.

5. The polymer hydrogel according to any one of claims 2 to 4, wherein PFT is selected from one or more of -S(CO)alkyl, -S(CO)alkenyl, -S(CO)alkynyl, -S(CO)aryl, -S(CO)carbocyclyl, -S(CO)heterocyclyl, -S(CO)heteroaryl, -S(CO)alkylaryl, -S(CO)alkylcarbocyclyl, -S(CO)alkylheterocyclyl, -S(CO)alkylheteroaryl, -S(CS)alkyl, -S(CS)alkenyl, -S(CS)alkynyl, -S(CS)aryl, -S(CS)carbocyclyl, -S(CS)heterocyclyl, -S(CS)heteroaryl, -S(CS)alkylaryl, -S(CS)alkylcarbocyclyl, -S(CS)alkylheterocyclyl, -S(CS)alkylheteroaryl, -SSalkyl, -SSalkenyl, -SSalkynyl, -SSaryl, -SScarbocyclyl, -SSheterocyclyl, -SSheteroaryl, -SSalkylaryl, -SSalkylcarbocyclyl, -SSalkylheterocyclyl, and -SSalkylheteroaryl.

6. A method of preparing polymer hydro gel having a polymeric matrix of polymer chains, the method comprising forming the polymer chains by polymerising a monomer composition comprising ethylenically unsaturated monomer having one or more protected and/or free thiol functional groups covalently bound thereto, wherein polymerisation of the ethylenically unsaturated monomer presents the functional groups in pendant formation relative to the so formed polymer chains.

7. The method according to claim 6, wherein the monomer composition polymerised to form the polymer chains comprises at least 40 mol% of ethylenically unsaturated monomer having one or more protected and/or free thiol functional groups covalently bound thereto.

8. The method according to claim 6 or 7, wherein the monomer composition comprising ethylenically unsaturated monomer is polymerised by a controlled radical polymerisation (CRP) technique.

9. The method according to any one of claims 6 to 8, wherein the monomer composition comprises ethylenically unsaturated monomer of general formula (II):

X

C^=CH₂ A

L

PFT (II)

where:

X is selected from H and optionally substituted Ci-C₆ alkyl; A is a moiety capable of activating the ethylenically unsaturated double bond such that it will undergo polymerisation;

L is a linking moiety; and

PFT is one or more protected and/or free thiol functional groups.

10. The method according to claim 9, wherein A is a multi-valent moiety selected from carbonyl (-C(O)-), ether (-0-), ester (-O-C(O)-), amide (-(R^z)N-C(0)-), anhydride (-C(O)- O-C(O)-), imide (-C(0)-(R^z)N-C(0)-) and optionally substituted arylene (-Ar-), where R^z is H or Ci-C₆ alkyl, and Ar is arylene.

11. The method according to claim 9 or 10, wherein L is independently or forms together with A an optionally substituted multi-valent form of a group selected from alkyl, alkenyl, alkynyl, aryl, acyl, carbocyclyl, heterocyclyl, heteroaryl, alkyloxy, alkenyloxy, alkynyloxy, aryloxy, acyloxy, carbocyclyloxy, heterocyclyloxy, heteroaryloxy, alkylalkenyl, alkylalkynyl, alkylaryl, alkylacyl, alkylcarbocyclyl, alkylheterocyclyl, alkylheteroaryl, alkyloxyalkyl, alkenyloxyalkyl, alkynyloxyalkyl, aryloxyalkyl, alkylacyloxy, alkyloxyacylalkyl, alkylcarbocyclyloxy, alkylheterocyclyloxy, alkylheteroaryloxy, alkylalkenylalkyl, alkylalkynylalkyl, alkylarylalkyl, alkylacylalkyl, arylalkylaryl, arylalkenylaryl, arylalkynylaryl, arylacylaryl, arylacyl, arylcarbocyclyl, arylheterocyclyl, arylheteroaryl, alkenyloxyaryl, alkynyloxyaryl, aryloxyaryl, arylacyloxy, arylcarbocyclyloxy, arylheterocyclyloxy, arylheteroaryloxy, and polyoxyalkylene, wherein when present one or more -CH₂- groups in any alkyl chain is optionally replaced by a divalent group independently selected from -0-, -NR^a-, -C(O)-, -C(0)0-, -OC(0)0-, - OC(0)NR^a- and -C(0)NR^a-, where each R^a is independently selected from hydrogen, alkyl, alkenyl, alkynyl, aryl, carbocyclyl, heteroaryl, heterocyclyl, arylalkyl, and acyl.

12. The method according to any one of claims 9 to 11, wherein PFT is selected from one or more of -S(CO)alkyl, -S(CO)alkenyl, -S(CO)alkynyl, -S(CO)aryl, -S(CO)carbocyclyl, -S(CO)heterocyclyl, -S(CO)heteroaryl, -S(CO)alkylaryl, -S(CO)alkylcarbocyclyl, -S(CO)alkylheterocyclyl, -S(CO)alkylheteroaryl, -S(CS)alkyl, -S(CS)alkenyl, -S(CS)alkynyl, -S(CS)aryl, -S(CS)carbocyclyl, -S(CS)heterocyclyl, -S(CS)heteroaryl, -S(CS)alkylaryl, -S(CS)alkylcarbocyclyl, -S(CS)alkylheterocyclyl, -S(CS)alkylheteroaryl, -SSalkyl, -SSalkenyl, -SSalkynyl, -SSaryl, -SScarbocyclyl, -SSheterocyclyl, -SSheteroaryl, -SSalkylaryl, -SSalkylcarbocyclyl, -SSalkylheterocyclyl, and -SSalkylheteroaryl.

13. The method according to any one of claims 6 to 12, wherein the monomer composition comprises one or more monomers selected from 3-(acetylthio)propyl acrylate, 3-(acetylthio)propyl methacrylate, 4-(acetylthio)butyl acrylate, and 4-(acetylthio)butyl methacrylate.

14. The method according to any one of claims 6 to 13, wherein the monomer composition comprises one or more multi-ethylenically unsaturated monomers.

15. A process for sequestering metal atoms, the process comprising contacting polymer hydrogel according to any one of claims 1 to 5 with a composition comprising metal atoms, wherein (i) a hydrophilic liquid facilitates transport of metal atoms from the composition to within the polymeric matrix of the polymer hydrogel, and (ii) at least some of the transported metal atoms bind to the one or more protected and/or free thiol functional groups such that they become sequestered within the polymer hydrogel.

16. The process according to claim 15, wherein the composition comprising metal atoms is a soil composition.

17. The process according to claim 16, wherein polymer hydrogel is contacted with the soil composition by ploughing the hydrogel into the soil or by applying a slurry or suspension of the hydrogel to the soil.

18. The process according to any one of claims 15 to 17, wherein the metal atoms are selected from one or more of vanadium, cobalt, chromium, iron, arsenic, germanium, molybdenum, gold, antimony, tin, bismuth, zinc, copper, tungsten, rhenium, uranium, selenium, nickel, lead, mercury, cadmium, silver, manganese, palladium and platinum.