WO2016096589A1 - Synthetic enzyme mimic based on a histidine scaffold - Google Patents

Abstract

A catalytic surfactant comprising a hydrophobic moiety, preferably a C16 linear alkyl group, attached to a head group, said head group comprising a catalytic moiety incorporating multiple catalytic- functional groups, said groups comprising: (i) a carboxylate group; (ii) an imidazole group; and (iii) a nucleophilic group, preferably a hydroxy or thiol group; and wherein the catalytic-functional groups are arranged in close proximity with each other, preferably in the form of a histidine derivative.

Description

SYNTHETIC ENZYME MIMIC BASED ON A HISTIDINE SCAFFOLD

The present application claims priority benefit of EP14198189.4 (filed 16 December 2014) which is incorporated by reference herein in its entirety.

The present invention relates to synthetic enzyme mimics.

Synthetic molecules that mimic enzyme reactivity have been pursued by an active field of researchers for decades with the goals of both developing synthetically useful mimics and understanding fundamental questions with regard enzyme action as well as developing more robust catalysts that would allow them to be employed in more challenging reaction conditions required for certain industrial applications. A long standing challenge in catalysis has been to develop synthetic mimics that can perform similar chemistry inspired by biologically evolved systems. So far, man-made catalysts seem archaic in comparison with nature's elegant design of enzymes in terms of efficiency and specificity.

Publications by Breslow ei a/ (Chem. Soc. Rev. 1972, 1 , 553; Acc. Chem. Res. 1995, 28, 146; Chem. Rev. 1998, 98, 1997 and J. Biol. Chem. 2009, 284, 1337) disclose enzyme mimicry or catalysis using metal based active sties, and catalytic diads. However, no examples disclose the three functional groups of the catalytic triad, carboyxylate, imidazole and hydroxyl groups, in close proximity, as an artificial catalytic triad.

US4777250 discloses a cyclodextrin based chymotrypsin model having no amino acids but including the three functional groups (a carboxylate group, an imidazole group and a hydroxyl group) of naturally occuring chymotrpsin. However, it has since been proven that cyclodextrin itself catalyses the hydrolysis reaction faster than cyclodextrin attached to the functional groups, so the role of the functional groups in hydrolysis is not disclosed by US4777250 (Tetrahedron Letters,Vo1.30,No.33,pp 4357-4358,1989 (Zimmerman) and Tetrahedron Lett. 1989, 30, 4353 (Breslow, R.; Chung, S.).

The objective of the present invention is to provide an improved synthetic enzyme mimic and also a synthetic lipase enzyme mimic.

The synthetic enzyme mimic of the invention comprise a carboxylate group, an imidazole group, and a nucleophilic group such as a hydroxyl group. These groups arranged in close proximity. As a result, this "triad" is able to interact with substrates in a manner akin to an enzyme (in which a triad of amino acid residues is arranged to facilitate catalytic interactions). In a first aspect the invention provides a catalytic surfactant comprising a hydrophobic moiety attached to a head group, said head group comprising a catalytic moiety incorporating multiple catalytic-functional groups, said groups comprising:

(i) a carboxylate group;

(ii) an imidazole group; and

(iii) a nucleophilic group

and wherein the catalytic-functional groups are arranged in close proximity with each other.

In a second aspect the invention provides a synthetic enzyme mimic comprising a hydrophobic moiety attached to a catalytic moiety comprising multiple catalytic functional groups, said groups comprising:

(i) a carboxylate group;

(ii) an imidazole group; and

(iii) a nucleophilic group

and wherein the enzyme-functional groups are arranged in close proximity with each other.

The synthetic enzyme mimic is preferably a synthetic lipase mimic. In a third aspect the invention provides a synthetic enzyme mimic comprising a micelle, said micelle comprising a catalytic surfactant of the first aspect and/or a synthetic enzyme mimic of the second aspect.

In a fourth aspect the invention comprises an aqueous medium comprising a catalytic surfactant of the first aspect and/or a synthetic enzyme mimic of the second aspect.

The aqueous medium may comprise one or micelles of the fourth aspect.

The invention advantageously provides a catalytic-functional surfactant and a synthetic enzyme e.g. lipase mimic using the three catalytic functional groups including, but not limited to, those of the chymotrypsin model.

The activity is not limited to hydrolytic activity since enzymes may be used to catalyse product synthesis, e.g lipases may be used in chiral synthesis, esterification

(transesterification of vegetable oils for bio-diesel) and inter-esterification.

In a fifth aspect, the present invention provides a laundry composition comprising a catalytic surfactant as described herein. Definitions

As used herein "surfactant" is intended to mean the presence of a hydrophobic "head" group and a polar "tail" group.

As used herein "synthetic" is intended to mean non-naturally occurring, and excludes naturally occurring enzymes. For example, it excludes multiple amino acid formations where each amino acid residue provides a single functional group as is found in naturally occurring enzymes.

As used herein "catalytic" is intended to refer to enzyme catalytic functionality but without including natural enzyme structures i.e. without the amino acid sequences and resultant secondary, tertiary and quaternary structures which are present in naturally occurring enzymes.

As used herein the term "scaffold" includes the structure to which the multiple functional groups are carried or attached or supported or bonded but excludes the arrangement of e.g. naturally occurring enzymes whereby each functional group is provided by a different amino acid residue.

As used herein the term "close proximity with each other" means such that all the functional groups are in functional proximity, e.g. so all can together access so as to act on the relevant atom /bond/s of the substrate molecule. For example, the number of bonds linking each of the three groups (and forming the scaffold) may be 3 to 15. The number of bonds linkings is calculated as a "walk through the molecule" along the longest chain between two of the three groups, plus the number of bonds connecting the third group to that chain. In some cases, the number of bonds is 6 to 12. For example, it may be 6 to 8.

For example, in a scaffold based on 2-amino-2-(1 H-imidazol-5-yl)acetic acid and a ring opening epoxide addition:

the three functional groups are separated by 6 bonds.

For example, in a scaffold based on 2-amino-3-(1 H-imidazol-4-yl)propanoic acid and a ring opening epoxide addition:

the three functional groups are separated by 7 bonds.

For example, in a scaffold based on 2-amino-3-(1 H-imidazol-4-yl)propanoic acid and a ring opening epoxide addition to install a thiol nucleophile (the secondary alcohol is used to link with the reactive handle):

the three functional groups are separated by 8 bonds.

As used herein "histidine" is intended to include histidine derivatives and analogues including all its stereoisomeric (and racemic) forms, and also substituted imidazole derivatives.

As used herein "hydrophobic moiety" is intended to include any hydrophobic group and is preferably an alkyl group or an alkenyl group, most preferably an alkyl group. As used herein, "alkyl" is intended to include any hydrocarbon group which may be linear, cyclic, branched, aromatic, cycloaliphatic, e.g. steroids, or any combination thereof having the number of carbon atoms designated. Examples of alkyl groups include n-butyl, sec- butyl, t-butyl, cyclopropylmethyl, cyclopentyl, (cyclohexyl)methyl, etc. The alkyl group may be substituted and functionalised for example to improve hydrophobicity. Carbon chains may contain one or more oxygen atoms included at one or more positions in the main chain.

The hydrophobic moiety may comprise any suitable hydrophobic group and is preferably a hydrophobic tail.

The hydrophobic moiety may comprise any alkyl or alkenyl group with carbon chain C_n where n is greater than 4, preferably greater than 8 and more preferably≥ 16. In one example it is Ci6. Also included in the invention are hydrophobic moieties comprising fluorocarbon chains and siloxane chains. The hydrophobic moiety may be attached to the head group via an ethoxylated moiety, preferably an alkyl ethoxylate. The hydrophobic moiety may comprise polypropylene oxides to increase hydrophobicity.

The hydrophobic moiety may comprise carbon nanotubes.

The hydrophobic moiety may comprise multiple chains thereby providing multiple surfactant 'tail' groups, for example it may comprise a double-chain/tail.

Polymerized siloxanes (also known as polysiloxanes, silicones) are included in the invention, with organic side chains (R≠ H) or as polysiloxanes, e.g. [SiO(CH3)2]n (polydimethylsiloxane) and [SiO(C6H₅)2]n) (polydiphenylsiloxane). The organic side chains increasing hydrophobicity.

Preferably the nucleophilic group (Nu) is a hydroxyl group (-OH ), an amine group, or a thiol group (-SH). More preferably, it is a hydroxyl group or a thiol group. The head group is preferably hydrophilic or polar. The head group may be anionic, cationic, Zwitterionic or non-ionic.

The head group preferably comprises a scaffold and/or one or more of the catalytic functional groups are preferably carried on a scaffold. The scaffold preferably comprises histidine or is histidine-based, and more preferably based on a single histidine molecule.

The scaffold preferably comprises any one of the below structures:

CA Index Name: 1 H-lmidazole-5-acetic acid, a-amino-

2-amino-2-(1 H-imidazol-5-yl)acetic acid

CA Index Name: 1 H-lmidazole-5-propanoic acid, β-amino- 3-amino-3-(1 H-imidazol-5-yl)propanoic acid

CA Index Name: 1 H-lmidazole-5-propanoic acid, α-hydroxy-, (aS)- (2S)-2-hydroxy-3-(1 H-imidazol-5-yl)propanoic acid

CA Index Name: lmidazole-4-succinic acid, α-amino-, (+)- (8CI)

2-amino-3-(1 H-imidazol-5-yl)butanedioic acid

2 H

CA Index Name: Histidine, β-ethyl- (9CI)

2-amino-3-(1 H-imidazol-5-yl)pentanoic acid

CA Index Name: Glycine, N-(1 H-imidazol-5-ylmethyl)-

2-(1 H-imidazol-5-ylmethylamino)acetic acid

CA Index Name: Histidine, a-hydroxy- (9CI)

2-amino-3-hydroxy-3-(1 H-imidazol-5-yl)propanoic acid

CA Index Name: 1 H-lmidazole-5-hexanoic acid, α-amino-, (aS)-

2-amino-6-(1 H-imidazol-5-yl)hexanoic acid

CA Index Name: 1 H-lmidazole-5-heptanoic acid, α-amino-, (aS)- 2-amino-7-(1 H-imidazol-5-ylheptanoic acid

CA Index Name: 1 H-lmidazole-5-octanoic acid, α-amino-, (aS)- 2-amino-8-(1 H-imidazol-5-yl)octanoic acid

Formula: C6 H 10 N4 02

CA Index Name I H-lmidazole-4-propanoic acid, α-hydrazino-, (aS)

2-hydrazino-3-(1 H-imidazol-5-yl)propanoic acid

CA Index Name: 1 H-lmidazole-5-propanoic acid, β-hydroxy- 3-hydroxy-3-(1 H-imidazol-5-yl)propanoic acid

CA Index Name: 1 H-lmidazole-5-propanol, β-amino-Y-methyl- 2-amino-3-(1 H-imidazol-5-yl)butan-1-ol

CA Index Name: 1 H-lmidazole-5-butanoic acid, oarmino-

2-amino-3-(1 H-imidazol-5-yl)propan-1-ol

CA Index Name: I H-lmidazole-5-propanoic acid, ohydroxy-

2-hydroxy-3-(1 H-imidazol-5-yl)propanoic acid

CA Index Name: 1 H-lmidazole-5-butanoic acid, β-amino-, (3S)-

3-amino-4-(1 H-imidazol-5-yl)butanoic acid

H

CA Index Name: 1 H-lmidazole-5-pentanoic acid, α-amino-, (aS)-

2-amino-5-(1 H-imidazol-5-yl)pentanoic acid

Alternatively or additionally the scaffold may comprise any molecule bearing the catalytic functional groups: imidazole and a carboxylic acid group, and further includes an amino group, preferably a primary amino group.

One or more functional groups may be carried on the hydrophobic moiety. According to a further aspect of the invention, a catalytic surfactant or an enzyme is provided, having the following structure:

Wherein:

Ri is a hydrophobic group as defined above;

The hydrophobic group is a hydrophobic moiety, e.g. linear, branched, cyclic alkyl or alkenyl chain, aromatic group, cycloaliphatic, e.g. steroids; For example, Ri may be C4-3oalkyl, C4-3oalkenyl, C5-3ocycloalkyl, C5-3ocycloalkenyl, Cs-2oaryl or combinations therefore. For example, Ri may be C5-3ocycloalkyl-C4-3oalkyl etc. For example. Ri may be a steroid group. These groups may be unsubstituted or optionally substituted. Preferably, Ri is C4-3oalkyl, C4-3oalkenyl or a steroid group. For example, Ri may be Ce-25-, Cs-25-, C10-25-, C14-25-, C16-25-, Cis-25-alkyl or alkenyl. R2 preferably comprises B substituents. For example, R2 may be H and/or may be linear or cyclic and may be a short or long alkyl group, e.g. methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, hexadecyl,

cyclohexane, etc. aryl, e.g. phenyl, naphthyl, arylalky, e.g. benzyl, oxyethylene, oxypropylene, polyoxyethylene, polyoxypropylene, or any combination thereof, etc;

R2 may be selected from H , Ci-2oalkyl, C2-2oalkenyl, C2-2oalkynyl, C3-8cycloalkyl,

C38heterocycyl, C6-ioaryl, Cs-ioheteroaryl, Ci-2oalkoxy, C3-2oalkenoxy, and Ci-5alkyl-C6- ioaryl. These groups may be unsubstituted or optionally substituted,

For example, R2 may be selected from H, Ci-isalkyl, C2-isalkenyl, C3-8cycloalkyl, phenyl and benzyl. These groups may be unsubstituted or optionally substituted Preferably, R2 is H. In these cases, the imidazole moiety may be considered amphoteric.

X is preferably a divalent atom, for example an O or S atom;

Y preferably comprises a nucleophilic functional group, for example -OH, -SH, -IMH2 or - CO2H functional groups. Preferably, Y comprises -OH, -SH, or -IMH2. Preferably, Y is (CR3R4)n-Nu, wherein Nu is the nucleophilic functional group and n is an integer (e.g. 0,1 ,2,3,4). Preferably, n is O or 1. Most preferably Y is -OH, -SH, CH₂OH or -CH₂SH. For example, Y may be -OH or -CH₂SH;

Z is preferably a cationic counterion of the carboxylate functional group. For example, Z may be H, or any metal ion such as Cs, Na, K, ammonium, sulphonium or phosphonium salts, e.g. tetraalkylammonium, tetraalkylsulphonium or tertaalkylphosphonium salts;

B, C, and D and E are preferably independently selected connecting groups denoted by - (CR3R4)n; where R3 & R4 may be H, a linear and cyclic alkyl, aryl, arylalkyl groups as defined for R2 above and n is an integer e.g. 0,1 ,2,3. For B, C, and D, n is preferably 1 , 2 or 3. For E, n is preferably, 0, 1 , 2, or 3.

For example, R3 and R₄ may be independently H, OH, halogen, Ci-4alkyl or Ci_-4alkoxy.

Preferably, R3 and R₄ are both H.

B forms part of a linker attaching the scaffold (the moiety bearing functional groups (i), (ii), and (iii) as described herein) and the hydrophobic group. B may, in some cases, be (CR3R₄)i-6, for example (CH3H₄)i-6, preferably (CH3H₄)i-3. Preferably, B is CH2. In the case of C and D, n is preferably selected such that the functional groups are maintained in close proximity to each other;

For example, in some cases, both C and D are (CR3R₄)i-6, preferably both (CH2)i-₄.

Preferably, at least one of C and D is CH2. In some cases, both C and D are CH2. In the case of E, n is preferably selected such that the functional groups are maintained in close proximity to each other;

For example, n may be zero (in other words, E may be a bond) or n may be 1 (in other words, E may be Chb.

F preferably comprises an amino group (-NH-) or an amino group linked by an alkyl group e.g. F may be CH-NH₂ or (CH)- (CH2)_n - NH₂ where n is an integer 0,1 ,2,3 etc. limited such that the resultant structure has the functional groups in close proximity to each other. Accordingly, it will be understood that F may comprise a primary amine or a secondary amine. The alkyl group or groups may be modified. In one example F is - NH- providing a histidine-based scaffold as shown in the following structure:

another example, F is CH-Nhb and the synthetic enzyme mimic has the structure:

where groups are as defined above.

In some embodiments, the present invention provides a catalytic surfactant or enzyme mimic according to the first or second aspect, with the proviso that said catalytic surfactant or enzyme mimic does not have the structure:

wherein Ri is C10H21 , C12H25, C14H29 or C16H33.

Where appropriate, groups as described herein may be optionally substituted. For example, and not by way of limitation, Suitable substituents may include halogen (F, CI, Br, I . preferably F or CI), OH,

Ci-4alkoxy, or C6-ioaryl.

PROCESS In a further aspect the invention provides a process for making a catalytic surfactant of the first aspect or synthetic enzyme mimic of the second aspect, as follows:

Wherein:

R1 = A hydrophobic moiety, e.g. linear, branched, cyclic alkyl or alkenyl chain, aromatic group, cycloaliphatic, e.g. steroids;

For example, Ri may be C4-3oalkyl, C4-3oalkenyl, C5-3ocycloalkyl, C5-3ocycloalkenyl, Cs-2oaryl or combinations therefore. For example, Ri may be C5-3ocycloalkyl-C4-3oalkyl etc. For example. Ri may be a steroid group. These groups may be unsubstituted or optionally substituted.

Preferably, Ri is C4-3oalkyl, C4-3oalkenyl or a steroid group.

R2 =A substituents. For example, but not limited to H, linear or cyclic short or long alkyl group, e.g. methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, hexadecyl, cyclohexane, etc. aryl, e.g. phenyl, naphthyl, arylalky, e.g. benzyl, oxyethylene, oxypropylene, polyoxyethylene, polyoxypropylene, and combination thereof, etc;

For example, R2 may be selected from H, Ci-2oalkyl, C2-2oalkenyl, C2-2oalkynyl, C3- scycloalkyl, Cs sheterocycyl, C6-ioaryl, Cs-ioheteroaryl, Ci-2oalkoxy, C3-2oalkenoxy, and Ci- ₅alkyl-C6-ioaryl. These groups may be unsubstituted or optionally substituted,

For example, R2 may be selected from H, Ci-isalkyl, C2-isalkenyl, C3-8cycloalkyl, phenyl and benzyl. For example, R2 may be selected from H, Ci-i6alkyl, C2-6alkenyl,

C5-8cycloalkyl, phenyl and benzyl. These groups may be unsubstituted or optionally substituted

Preferably, R2 is H. In these cases, the imidazole moiety may be considered amphoteric. Each A is a divalent atom. For example, but not limited to O or S atoms. Each A may be the same or different. For example, the left-hand starting material may be an alkyl glycidol (both A are O). Ring opening addition affords a secondary alcohol (labelled Y) and an ether moiety (labelled A in this scheme, elsewhere also referred to as X).

B, C, D and E = Independently selected connecting groups denoted by -(CR3R4)n- where R3 & R4 represent but are not limited to H, linear and cyclic alkyl, aryl, arylalkyi groups as defined for R2; n = An integer, e.g. 0, 1 , 2, 3, 4... Y = A proton donor functional group. For example, but not limited to -OH, -SH, -IMH2, - CO2H, functional groups. Preferably -OH, -SH functional groups;

Z = A cationic counterion. For example, but not limited to H, metal ions such as Cs, Na, K, ammonium and sulphonium, phosphonium salts, e.g. tetraalkylammonium,

tetraalkylsulphonium and tetraalkylphosphonium salts;

F preferably comprises an amino group (-IMH2) or an amino group linked by an alkyl groups e.g. F may be CH-NH2 or (CH)- (CH2)_n - NH2 where n is an integer 0,1 ,2,3 etc. limited such that the resultant structure has the functional groups in close proximity to each other. The alkyl group or groups may be modified. In one example F is -IMH2 providing a histidine-based scaffold.

This may also be depicted

It will be appreciated that, in the above scheme, Y is typically AH (protonated A).

In a further aspect the invention provides a process for making a surfactant-enzyme mimic of the first aspect or the synthetic enzyme mimic of the second aspect or the synthetic lipase mimic of the third aspect or the molecules of the aspects of the invention as above described, the method comprising the steps of:

(i) construction of a catalytic moiety comprising one or more functional groups, and

(ii) attachment of the catalytic moiety to a hydrophobic moiety.

Preferably the step (ii) of attachment of the catalytic moiety to a hydrophobic moiety also introduces further functional groups. Preferably the hydrophobic moiety of the process is an ethoxide-functionalised group, and more preferably it bears a terminal epoxide and more preferably it bears a terminal glycidyl epoxy group (also known as glycidyl ether). Preferably the catalytic moiety comprises a scaffold as defined above. Preferably the catalytic moiety further comprises an amino group, which is preferably a primary amino group. Preferably it comprises a histidine-based scaffold.

Preferably the step (ii) of attachment of the catalytic moiety to a hydrophobic group comprises a ring-opening reaction of the epoxide-functionalised hydrophobic moiety.

Preferably the ring-opening reaction introduces the further functional group being a nucleophilic group. e.g. a hydroxyl group or thiol group (Y in the above structures). Preferably the step (ii) of attachment of the catalytic moiety to a hydrophobic moiety comprises a ring-opening reaction of the ethoxide-functionalised hydrophobic moiety with the amino group, preferably the primary amino group of the catalytic moiety.

There are a large range of suitable epoxide functionalized compounds commercially available. For example: 3-(4-chlorobenzoyl)-N-(2-propynyl)-2-oxiranecarboxamid, 3,4- Epoxy-1-butene, Neopentyl glycol diglycidyl ether, Allyl glycidyl ether, Glycidyl acrylate, Glycidyl methacrylate, Resorcinol diglycidyl ether, (3-Glycidyloxypropyl)trimethoxysilane, 4-Vinyl-1 -cyclohexene 1 ,2-epoxide, mixture of isomers, (+)-Limonene 1 ,2-epoxide. A preferred epoxide functionalised hydrophobic molecule is an alkyl glyceryl epoxides (also known as AGE also known as an alkyl glycidyl ether being, an ether and epoxide) and most preferably bearing a terminal glycidate epoxy group:

O

w c may a so e expresse as: O

In one example the glycidate epoxy hydrophobe is a Ci6 alkyl glycidate epoxide:

This process advantageously does not require protection of the functional groups by any p re-step.

The present invention provides a catalytic surfactant. As described herein, the catalytic surfactant has a fatty "tail" group (the hydrophobic group) and a "head group" featuring three functional groups in close proximity that together mimic the catalytic triad of certain enzymes.

It will be appreciated that the catalytic surfactants of the present invention may have utility in laundry compositions (both powders and liquids).

Accordingly, in a further aspect, the present invention provides a laundry composition comprising a catalytic surfactant / synthetic enzyme mimic as described herein. It will be appreciated that the laundry composition may further comprise any of other surfactants, for example, non-ionic surfactants; builders, perfumes, dye transfer inhibitors,

antiredeposition agents, optical brighteners, hydrotropes, preservatives, processing aids and foam regulators.

Advantageously, the catalytic triad may mimic the behaviour of enzymes that are often added to conventional laundry compositions. This may mean that less enzyme may be required, with clear economic and environmental benefits. Catalytic surfactants as described herein have been shown to exhibit lipase activity. Accordingly, said catalytic surfactants may be used to replace a lipase in laundry compositions. In some

embodiments therefore, the laundry composition does not comprise a lipase. In osme embodiments, the laundry composition does not comprise an enzyme.

It will be appreciated that the catalytic surfactants of the invention may therefore be useful where both protease and lipase activity is desired from a single composition (as the catalytic surfactant of the present invention does not include peptide bonds, the two can be combined). Accordingly, in some embodiments, the laundry composition comprises a protease. For the avoidance of doubt the preferred features of any one aspect are also preferred features of all other aspects and vice versa.

Example of Non Limiting Embodiments of the Invention The following is a non-limiting example of an embodiment of the invention in which

Figures 1 - 3 show the NMR and mass spectrometry data of the invention compounds; and

Figures 4 - 7 show colourmetric assay analysis using the 4- nitrophenyl palmitate assay, and illustrating enzymatic, in this case lipolytic performance. Example 1 : Synthesis of an exemplary synthetic enzyme

In this example, the enzyme functionalized surfactant is synthesized by reacting unprotected histidine with an alkyl epoxide.

Experimental method

Starting materials for the following example are unprotected histadine in the form of L- histidine (CAS Number 71 -00-1 ; product code H6034, ex Sigma Aldrich) and an hydrophobic group being an epoxide glycidyl alkyl (Ci6) group in the form of: Glycidyl hexadecyl ether (2,3-Epoxypropyl hexadecyl ether) having CAS Numberl 5965-99-8 (product code 473642 ex Sigma Aldrich):

Glycidyl hexadecyl ether (1.24 g, 4.2mmol), histidine (1 .01 g, 6.5 mmol) and NaOH (0.5g, 12mmol) was dissolved in methanol and refluxed for 18 h. The product was isolated by titration with HCI until precipitation formed at pH 5. The solid was filtered and dried to yield 3 as a white solid (1.5g, 78%). This process advantageously does not require protection of the functional groups by any pre-step.

Characterisation and colourmetric assays were carried out, the latter 4-nitrophenyl palmitate.

Figures 1 - 3 show the NMR and mass spectrometry data of the invention compounds and Figures 4 - 7 show colourmetric assay analysis using the 4- nitrophenyl palmitate assay, and illustrating enzymatic, in this case lipolytic performance.

It is of course to be understood that the invention is not intended to be restricted to the details of the above embodiment which are described by way of example only.

Claims

A synthetic enzyme mimic or catalytic surfactant comprising a hydrophobic moiety attached to a head group, said head group comprising a catalytic moiety incorporating:

(i) a carboxylate group;

(ii) an imidazole group; and

(iii) a nucleophilic group

and wherein the catalytic-functional groups are arranged in close proximity with each other.

A synthetic enzyme mimic or catalytic surfactant according to claim 1 wherein the hydrophobic moiety comprises a C_n alkyl or alkenyl group, where n is greater than 4, preferably greater than 8 and more preferably≥ 16.

A synthetic enzyme mimic or catalytic surfactant according to any preceding claim wherein the nucleophilic group is a hydroxyl group (-OH) or thiol group (-SH).

A synthetic enzyme mimic or catalytic surfactant according to any preceding claim wherein the carboxylate group, the imidazole group and the nucleophilic groups are separated by between 6 and 12 bonds.

A synthetic enzyme mimic or catalytic surfactant according to any preceding claim wherein the head group comprises a histidine-based moiety.

A synthetic enzyme mimic or catalytic surfactant comprising the following structure:

Wherein Ri is a hydrophobic moiety selected from linear, cyclic, branched, aromatic, cycloaliphatic, e.g. steroids, hydrocarbons or any combination thereof ;

R2 is selected from the group consisting of H, linear , cyclic, branched alkyl groups such as butyl, pentyl, hexyl, heptyl, octyl, hexadecyl, cyclohexane, etc.; aryl, e.g. phenyl, naphthyl, arylalky, e.g. benzyll, oxyethylene, oxypropylene,

polyoxyethylene, polyoxypropylene, or any combination thereof,

X is a divalent atom selected from the group consisting of O or S atoms;

Y comprises a nucleophilic functional group selected from the group consisting of - OH, -SH, -IMH2 or -C02H functional groups;

Z is a cationic counterion of the carboxylate functional group selected from the group consisting of: H, or any metal ion such as Cs, Na, K; ammonium, sulphonium or phosphonium salts, e.g. tetraalkylammonium, tetraalkylsulphonium or tertaalkylphosphonium salts;

B, C, and D and E are independently selected connecting groups selected from the group denoted by -(CR3R₄)_n; where R3 & R₄ are independently selected from the group consisting of H, a linear and cyclic alkyl, aryl, arylalkyl groups as defined for R2 above and n is an integer e.g. 0,1 ,2,3 and and wherein for C and D, n is preferably selected such that the functional groups are maintained in close proximity to each other; F is -NH-, CH-NH2 or (CH)-(CH2)_n- NH₂ where n is an integer 0,1 ,2,3 etc. limited such that the resultant structure has the functional groups in close proximity to each other. 7. The synthetic enzyme mimic or catalytic surfactant of claim 6, wherein Y is -OH,

8. The synthetic enzyme mimic or catalytic surfactant of claim 6 or claim 7, wherein Ri is C4-3oalkyl, C4-3oalkenyl, C5-3ocycloalkyl, C5-3ocycloalkenyl, Cs-2oaryl or a

combinations therefore.

9. The synthetic enzyme mimic or catalytic surfactant of claim 8, wherein Ri is

C4-3oalkyl, C4-3oalkenyl, or a steroid group. 10. The synthetic enzyme mimic or catalytic surfactant of any one of claims 6 to 9, wherein R2 is H.

11. The synthetic enzyme mimic of any one of claims 6 to 10, wherein R3 and R4 are independently H, OH, halogen, Ci-4alkyl or Ci-4alkoxy.

12. A process for making a catalytic surfactant or a synthetic enzyme mimic of any of claims 1 to 11 , the rocess comprising the following reaction step:

wherein each A is -O- or -S- and all other groups are as defined in claim 6.

13. A process for making a catalytic surfactant or a synthetic enzyme mimic of any of claims 1 to 12, the method comprising the steps of : (i) construction of a catalytic moiety comprising one or more functional groups, and

(ii) attachment of the catalytic moiety to a hydrophobic moiety.

14. A process according to claim 13 wherein the step of attachment of the catalytic unit to a hydrophobic moiety also introduces further functional groups.

A process according to claim 13 or claim 14 wherein the hydrophobic moiety is an epoxide-functionalised group e.g. epoxide-functionalised alkyl group; optionally wherein the hydrophobic moiety bears a terminal epoxidel, preferably a terminal glycidyl epoxide.

A process according to any of claims 13-15 wherein the step (ii) of attachment of the catalytic moiety to a hydrophobic moiety comprises a ring-opening reaction of the epoxide group.

A process according to claim 16 wherein the ring-opening reaction introduces the further functional group being a nucleophilic group. e.g. a hydroxyl group or thiol group.

18. A process according to claim 17 wherein the step (ii) of attachment via a ring- opening reaction of the ethoxide is by the amino group, preferably a primary amino group of the catalytic moiety.

19. A laundry composition comprising a catalytic surfactant according to any one of claims 1 to 1 1.

20. The laundry composition of claim 19, wherein the composition does not comprise a lipase, optionally wherein the composition comprises a protease.