WO2025099154A1

WO2025099154A1 - Oily biocide compositions comprising diamine compounds

Info

Publication number: WO2025099154A1
Application number: PCT/EP2024/081503
Authority: WO
Inventors: Lothar Just; Nikolas Pietrzik; Corinna GLEISER; Gerhard Feil; Bernhard HIRT
Original assignee: Eberhard Karls Universitaet Tuebingen
Current assignee: Eberhard Karls Universitaet Tuebingen
Priority date: 2023-11-07
Filing date: 2024-11-07
Publication date: 2025-05-15
Anticipated expiration: 2026-05-07

Abstract

The invention provides stable compositions comprising a biocide component (i) comprising at least one compound of formula (I), (I), with m being an integer from 1 to 6; and R¹ being H; R² and R³ being independently selected from H, a polar protic or polar aprotic substituent independently selected from a saccharide residue, a polyalcohol residue, a polyether residue, a polyamine residue, a polyimine residue, an amino acid residue or an amino acid derivative, a peptide residue, a protein residue or a protein derivative, an organic acid residue, including a carboxylate, a sulfonate, a phosphate, or a substituent selected from Formula (a), (a), and R⁴ being selected from Formula (b), (b), with n and n' being independently selected from an integer from 1 to 25; and at least one triglyceride of formula (II), (II), with R⁵, R⁶ and R⁷ being independently selected from C₁₀-C₂₅ alkyl and C₁₀-C₂₅ alkenyl. Furthermore, a method for preparing said composition is provided, as well as the use of said compounds.

Description

Oily biocide compositions comprising diamine compounds’

The invention provides compositions comprising compounds of formula (I) and triglycerides of formula (II), a method for preparing said compositions and their use. The compositions preferably provide a long-term stability and/or a biocidal activity.

Background of the Invention

Natural fats or oils are extracted from plants or animals. Examples are soybean oil, grape seed oil, olive oil, cocoa butter, shea butter, jojoba oil, palm kernel oil, palm oil, hamp oil, soya oil, castor oil, sunflower oil, linseed oil, fish oil, beef tallow, pork fat and chicken fat. Fats and oils are used in numerous products, for example in soaps, skin products, candles, drying oils, technical oils, technical greases, paints, metal treatment products and wood treatment products.

Those natural oils or fats are complex mixtures of individual triglycerides. A triglyceride is an ester derived from glycerol and three fatty acid molecules.

The three fatty acids in triglyceride are usually different. The chain lengths of the fatty acids in naturally occurring triglycerides vary, but most contain 16, 18, or 20 carbon atoms. Fatty acids can be saturated, unsaturated or even polyunsaturated, which means, that they contain no, one or more double bonds within the fatty acid chain. (Poly)unsaturated fatty acids can easily react with oxygen, thus natural oils are susceptible to becoming rancid. Furthermore, natural oils are not protected against microbial degradation and addition of a biocidal compound would be advantageous. The disinfection, decontamination and preservation of products based on animal or plant fats or oils with biocides continues to be an important topic. Biocide compounds, such as those with a diamine backbone, especially 1 ,3-diamino propane derivatives, are important active components in formulations and dressings for microbial control.

Derivatives of N,N'-alkyl-1 ,w-diamine, especially 1 ,3-diamino propane have long been used for disinfecting purposes. Commercially available compounds with biocidal activity include “C12”, i.e., /V-dodecyl-1 ,3-diamino propane (C15H34N2; molecular weight 242.45; CAS 5538-95-4) and “Bis-C12”, i.e. /V-(3-aminopropyl)-/\/-dodecyl-1 ,3-diamino propane (C18H41N3; molecular weight 299.54; CAS 2372-82-9).

N,N'-alkyl-1 ,w-diamine, especially diamino propane derivatives are frequently used as biocides. However, these often react with triglycerides, which changes the physical and chemical properties of these biocides leading to an overall reduction or loss of the biocidal effect.

It is an object of the present invention to provide stable compositions in which N, N'-alkyl- 1 ,w-diamine, preferably diamino propane derivatives and triglycerides are present.

This problem was solved by modifying the N,N'-alkyl-1 ,w-diamine, more preferably diamino propane, derivatives or their combination with biogenic oils or fats. The respective oily compositions have the advantage of being long-term stable and/or biocidal active.

It was surprisingly found that the stability of N,N'-alkyl-1 ,w-diamine, preferably 1 ,3- diamino propane, derivatives comprising primary amine groups could be improved in the presence of triglycerides at a pH below 7. Accordingly, at an acidic pH value compositions comprising primary amines and triglycerides can be stabilized.

Furthermore, the inventors surprisingly found that N,N'-alkyl-1 ,w-diamine, especially 1 ,3-diamino propane derivatives comprising only secondary amines, especially those further comprising a pyroglutamic acid residue, are especially stable in the presence of triglycerides independent of the pH. Experiments with solutions of different structures of the 1 ,3-diamino propane derivatives at different pH, showed that addition of triglycerides yields to stable solutions without undesirable chemical reactions of the biocidal compound. This observation is unexpected.

Short Description of the Invention

The present invention provides a composition comprising:

(i) A, preferably biocide component, comprising at least one compound of formula (I), more preferably comprising a diamine, preferably a N,N'-alkyl-1 ,w-diamine, more preferably a 1 ,3-diamino propane backbone,

formula (I) with m being an integer from 1 to 6; and

R¹ being H;

R² and R³ being independently selected from H, a polar protic or polar aprotic substituent independently selected from a saccharide residue, a polyalcohol residue, a polyether residue, a polyamine residue, a polyimine residue, an amino acid residue or an amino acid derivative, a peptide residue, a protein residue or a protein derivative, an organic acid residue, including a carboxylate, a sulfonate, a phosphate, or a substituent selected from

with n and n’ being independently selected from an integer from 1 to 25; and

(ii) at least one triglyceride of formula (II)

with R⁵, R⁶ and R⁷ being independently selected from C10-C25 alkyl and C10-C25 alkenyl.

In a preferred embodiment the composition is storable, preferably the concentration of component (i) based on the total amount of the composition is constant, more preferably does not decrease more than 1 weight-%, upon storage for more than two months, preferably more than four months, more preferably more than six months preferably after providing the composition, preferably the mixture, of (i) and (ii), more preferably in a closed package and/or at room temperature.

In a further aspect, the present invention provides a method for preparing a composition as described herein. The method comprises the steps of providing a, preferably biocide component, comprising a compound according to formula (I), preferably comprising a diamine, preferably a N,N'-alkyl-1 ,w-diamine, more preferably a 1 ,3-diamino propane backbone,

formula (I) with m being an integer from 1 to 6; and

R¹ being H;

R² and R³ being independently selected from H, a polar protic or polar aprotic substituent independently selected from a saccharide, a polyalcohol, a polyether, a polyamine, a polyimine, an amino acid or an amino acid derivative, a peptide, a protein or a protein derivative, an organic acid, including a carboxylate, a sulfonate, a phosphate, or a substituent selected from

with n and n’ being independently selected from an integer from 1 to 25.

Further, at least one compound of formula (II)

with R⁵, R⁶ and R⁷ being independently selected from C10-C25 alkyl and C10-C25 alkenyl is added. The present invention also provides a composition prepared by a method as described herein and the use of a composition as described herein.

Preferred embodiments are described in the dependent claims.

Short Description of the Figures

Figure 1: 5-/V-carboxamido-2-pyrrolidone-/\/’-n-dodecyl-1,3-diamino propane (Py-

C12)

Figure 2: /V-dodecyl-1 ,3-diamino propane (C12)

Figure 3: /V-(3-aminopropyl)-/\/-dodecyl-1,3-diamino propane (Bis-C12)

Figure 4: Reaction scheme of /V-dodecyl-1,3-diamino propane (C12) and linseed oil

Figure 5: LCMS-chromatograms of 5-/V-carboxamido-2-pyrrolidone-/\/’-n-dodecyl-

1,3-diamino propane (Py-C12, 1%) in linseed oil (linseed oil/FhO/EtOH (8/1/1))

Figure 6: LCMS-chromatograms of /V-dodecyl-1,3-diamino propane (C12, 1%) in linseed oil (linseed oil/FLO/EtOH (8/1/1))

Figure 7: Reaction products of /V-dodecyl-1 ,3-diamino propane (C12) in linseed oil

Figure 8: LCMS-chromatograms of /V-(3-aminopropyl)-/\/-dodecyl-1,3-diamino propane (Bis-C12, 1%) in linseed oil (linseed oil/FLO/EtOH (8/1/1)).

Detailed Description of the Invention

The invention is based on the finding that certain biocide compounds comprising a diamine backbone are stable in combination with naturally occurring triglycerides.

The invention relates to a composition comprising:

(i) a, preferably biocide component, comprising at least one compound of formula (I), preferably comprising a diamine, preferably a N,N'-alkyl-1,w-diamine, more preferably a 1,3-diamino propane backbone,

formula (I) with m being an integer from 1 to 6, preferably 3; and

R¹ being H; R² and R³ being independently selected from H, a polar protic or polar aprotic substituent independently selected from a saccharide residue, a polyalcohol residue, a polyether residue, a polyamine residue, a polyimine residue, an amino acid residue or an amino acid derivative, a peptide residue, a protein residue or a protein derivative, an organic acid residue, including a carboxylate, a sulfonate, a phosphate, or a substituent selected from

with n and n’ being independently selected from an integer from 1 to 25; and

(ii) at least one triglyceride of formula (II)

with R⁵, R⁶ and R⁷ being independently selected from C10-C25 alkyl and C -C25alkenyl.

Components (i) and (ii) are preferably present in a mixture, preferably in an emulsion, in the composition according to the invention. The composition preferably further comprises water and/ or ethanol.

The compounds of formulas (I) and (II) can be present in form of a stereoisomer, a racemic mixture, a tautomer, a solvate such as a hydrate or a salt.

According to the present invention, “m” is an integer from 1 to 6. Preferably, “m” is an integer from 2 to 4, more preferably it is an integer of 2 or 3, still more preferably “m” is 3. Compounds, wherein “m” is 3 are also referred to as “1 ,3-diamino propanes”.

Indices “n” and “n”’ are each independently selected from an integer from 1 to 25. Preferably, “n” and “n”’ are independently selected from an integer from 1 to 15, further preferred from 1 to 12, still further preferred from 3 to 12 and still more preferred from 3 to 11. In a preferred embodiment R² is selected from H, an amino acid or amino acid derivative, with R³ and R⁴ being independently selected from H or

with n and n' being an integer from 1 to 25.

The term alkenyl refers to hydrocarbon radicals with at least one C-C double bond, in particular mono-, di-, and trialkenyls at the same time, and is not limiting to alkenyls with only one double bond.

The term “protein derivative” as used herein means a natural or non-natural protein, which has been modified, but which is still functionally active despite said modification and/or has an amino acid content of at least 50 % (w/w). Likewise, amino acid derivative means a residue, which can be obtained from a natural amino acid such as by cyclization and/or that is based on a natural amino acid, which carries additional substituents and/or is cyclized.

The terms “protein” and “polypeptide” or “peptide” are used interchangeably herein.

R² can be an amino acid or an amino acid derivative, wherein any enantiomer of the amino acid or amino acid derivative is encompassed. R² may be a stereoisomer of a natural amino acid or a non-natural amino acid or derivative thereof.

R² may comprise a heterocyclic ring, in particular it can be an oxo-pyrrolidine ring or a pyrrolidine ring. A heterocyclic ring refers to a saturated or unsaturated ring that incorporates one or more heteroatoms, i.e. O, N and/or S.

In an embodiment, R² of formula (I) is selected from a polar protic or polar aprotic substituent independently selected from a saccharide, a polyalcohol, a secondary or tertiary cyclic amine, or an amino acid, which includes natural and non-natural amino acids as well as stereoisomers thereof. In particular, the amino acid is a stereoisomer of a natural amino acid or a non-natural amino acid.

R² in formula (I) may comprise an oxo-pyrrolidine ring or a pyrrolidine ring, more preferably R² may comprise a heterocyclic ring. A heterocyclic ring refers to a saturated or unsaturated ring that incorporates one or more heteroatoms, i.e., O, N and/or S.

The term „polar“ refers to the presence of heteroatoms, in particular selected from one or more of N, O or S within R².

In an especially preferred embodiment R² is a pyroglutamic acid residue or a derivative thereof, namely R² is preferably:

with R⁸ and R⁹ being selected from

with p being an integer from 1 to 20 and with X being O or S.

In an especially preferred embodiment, R² in formula (I) is

both being H.

In an embodiment, the composition comprises a compound of formula (I), wherein R³ is

wherein “n” is 1 to 15, preferably, wherein “n” is 4 to 12, more preferably, wherein “n” is 6 to 11.

In an embodiment, R³ in formula (I)

with “n” being an integer from 5 to 15.

In a further preferred embodiment the compound of formula (I) is selected from the group consisting of /V-dodecyl-1 ,3-diamino propane (C12), /V-(a-Glutaminyl amido)-/V’-n- dodecyl-1 ,3-diamino propane (aGlu-012), /V-(y-Glutaminyl amido)-/V’-n-dodecyl-1 ,3- diamino propane- (yGlu-012), /V-(3-aminopropyl)-/\/-dodecyl-1 ,3-diamino propane (Bis- C12), /\/-(3-aminopropyl)-/\/-octyl-1 ,3-diamino propane (Bis-0ctyl-C12), 5-/V- carboxamido-2-pyrrolidone-/V’-n-dodecyl propane-1 , 3-diamine (Py-C12), and /V-5- carboxamido-2-pyrrolidone-/V’-acetamido-N’-n-dodecyl-1 , 3-diamine propane (Py-Acyl- C12), more preferably at least one of or a combination of /V-dodecyl-1 ,3-diamino propane (012), /V-(3-aminopropyl)-/\/-dodecyl-1 ,3-diamino propane (Bis-012), 5-/V-carboxamido- 2-pyrrolidone-/V’-n-dodecyl propane-1 , 3-diamine (Py-C12), preferably /V-dodecy 1-1 ,3- diamino propane (012), /V-(3-aminopropyl)-/\/-dodecyl-1 ,3-diamino propane (Bis-012), 5-/V-carboxamido-2-pyrrolidone-/\/’-n-dodecyl propane-1 , 3-diamine (Py-C12).

In a preferred embodiment, the compound of formula (I) is a secondary amine. A secondary amine is a compound having no NH2 residues, but at least one NH residue. In a preferred embodiment, the at least one compound of formula (I) is 5-/V-carboxamido- 2-pyrrolidone-/V’-n-dodecyl-1 ,3-diamino propane (Py-C12, CAS number 126646-23-9). The denomination 5-/V-carboxamido-2-pyrrolidone-/V’-n-dodecyl-1 ,3-diamino propane is interchangeably used herein with 2-pyrrolidinecarboxamide, /V-[3- (dodecylamino)propyl]-5-oxo-, (2S)-, or (2S)- /V-[3-(dodecylamino)propyl]-5-oxo-2- pyrrolidinecarboxamide, or 2-pyrrolidinecarboxamide or /V-[3-(dodecy!amino)propyl]-S- oxo- , (S).

Py-C12 is also one of many components of the biocidal component glucoprotamin (164907-72-6). However, glucoprotamin is by definition “reaction products of: glutamic acid and /V-(C12-14-alkyl)propylenediamine”. The latter is commonly used in form of the cocopropylene-1 ,3-diamine (CAS 61791-63-7) for glucoprotamin synthesis and is a mixture of a variety of acyclic /V-alkylpropylene-1 ,3-diamines and /V-alkylamines. It differs mainly in chain lengths of the /V-alkyl residues. Conversion with L-glutamic acid is achieved by a thermal condensation process which yields glucoprotamin as a complex mixture of diverse condensation products as well as unreacted components of the cocopropylene-1 ,3-diamine starting materials, which according to the harmonised classification and labelling (ATP01) approved by the European Union, is fatal if inhaled, causes severe skin burns and eye damage, is very toxic to aquatic life and is harmful if swallowed.

In a preferred embodiment the compound of formula (I) is the reaction product of /V- dodecyl-1 ,3-diaminopropane (CAS 5538-95-4) and 5-oxo-pyrrolidine-2(S)-carboxylic acid methyl ester. /V-dodecyl-1 , 3-diaminopropane can either be produced purely synthetically or can be purified from the cocospropylene-1-3-diamine. Pure Py-C12 as it can be obtained by the reaction of /V-dodecyl-1 ,3-diaminopropane and 5-oxo-pyrrolidine- 2(S)-carboxylic acid methyl ester is non-mutagenic, non-genotoxic non-volatile, biodegradable and in contrast to the mixture glucoprotamin and according to skin corrosivity test (SCT) (OECD 431) has been found to be non-corrosive.

In all embodiments the preferably biocide component, comprising at least one component (i) comprising a diamine backbone component preferably consists to at least 35 to 100 weight-%, more preferably 75 to 100 weight-% of at least one compound of formula (I), preferably of 5-/V-carboxamido-2-pyrrolidone-/V’-n-dodecyl-1 ,3-diamino propane (Py-C12) preferably obtained by the reaction of /V-dodecyl-1 ,3-diaminopropane (CAS 5538-95-4) and 5-oxo-pyrrolidine-2(S)-carboxylic acid methyl ester, based on the total weight of the, preferably biocide, component (i). More preferably component (i), comprising at least one component, preferably comprising a diamine backbone, consists of the at least one compound of formula (I). Meaning, that there are no other components comprising a diamine backbone present in the composition except those according to formula (I). Especially preferred is, that component (i) consists of 5-/V-carboxamido-2- pyrrolidone-/V’-n-dodecyl-1 ,3-diamino propane (Py-C12), and preferably is the reaction product of /V-dodecyl-1 , 3-diaminopropane (CAS 5538-95-4) and 5-oxo-pyrrolidine-2(S)- carboxylic acid methyl ester. Component (i), preferably the compound of formula (I) is present in the composition according to the present invention in an amount of between 0.001 weight-% to 50 weight- %, more preferably of between 0.001 weight-% to 10 weight-%, even more preferably between 0.001 weight-% to 5 weight-%, with respect to the composition.

The composition of the present invention further comprises at least one triglyceride according to formula (II)

In an embodiment, R⁵, R⁶ and R⁷ in formula (II) are independently selected from C15-C22 alkyl and C15-C22 alkenyl. In a further embodiment, R⁵, R⁶ and R⁷ in formula (II) are independently selected from C15 alkyl, C16 alkyl, C17 alkyl, C18 alkyl, C19 alkyl, C20 alkyl, C15 alkenyl, C16 alkenyl, C17 alkenyl, C18 alkenyl, C19 alkenyl, or C20 alkenyl.

In a further embodiment, R¹, R² and R³ in formula (II) are independently selected from Ci6 alkyl, C17 alkyl, Cis alkyl, C20 alkyl, C16 alkenyl, C17 alkenyl, C18 alkenyl, or C20 alkenyl.

In an embodiment, component (ii) is a mixture of at least two different triglycerides of formula (II). The residues R¹, R² and R³ of formula (II) correspond to the residues as described herein.

Preferably, the at least one triglyceride of formula (II) is a naturally occurring triglyceride. Said triglycerides are typically occurring in and extracted from plants or animals.

Mixtures of examples of triglycerides, especially of naturally occurring triglycerides, of formula (II) may correspond to soybean oil, grape seed oil, olive oil, cocoa butter, beef tallow or linseed oil.

In a preferred embodiment, component (ii) is a mixture of triglycerides, corresponding to linseed oil.

Linseed oil is a common finish for wooden items and a pigment binder in oil paints. Furthermore, linseed oil is often used to bind materials in the manufacture of the floor covering linoleum. The fatty acids in a typical linseed oil are the triply unsaturated a- linolenic acid (51.9 %-55.2 %), the monounsaturated oleic acid (18.5 %-22.6 %), the doubly unsaturated linoleic acid (14.2 %-17 %) and the saturated acids palmitic acid (about 7 %) and stearic acid (3.4 %-4.6 %).

Having a high content of di- and tri-unsaturated esters, linseed oil is susceptible to polymerization reactions and oxidation upon exposure to oxygen in air. This polymerization, which is called "drying", results in the rigidification of the material.

The drying and oxidative degradation of linseed oil have been investigated in the state of the art. The initial phase of drying consists of the autoxidation phenomenon of the unsaturated fatty acid components with the development of extensive cross-linking, together with formation of conjugated unsaturations. The following stage of slow consumption of labile cross-links gives rise to a highly stable network (see e.g., Massimo Lazzari et. al, 1999).

Typical concentrations of the at least one triglyceride of formula (II) with respect to the composition are between 0.01 weight-% and 99.999 weight-%, more preferably between 0.05 weight-% and 99.999 weight-%. In a preferred embodiment, the at least one triglyceride of formula (II) is present in the composition in an amount of between 0.1 weight-% and 99.999 weight-%.

The composition may further comprise at least one acid. The acid may be an inorganic acid, or an organic acid. The acid is preferably selected not to interfere with the compounds of formula (I), or of formula (II) as described herein.

In an embodiment, the at least one acid is an inorganic acid. The at least one acid may also be a mixture of two or more inorganic acids. Typical inorganic acids are hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid. Preferred inorganic acids for the composition of the present invention are hydrochloric acid and sulfuric acid.

In an alternative embodiment, the at least one acid of the composition of the present invention may be an organic acid. The at least one acid may also be a mixture of two or more organic acids.

Typical organic acids are formic acid, acetic acid, citric acid, lactic acid, tartaric acid, malic acid, maleic acid and succinic acid.

The at least one acid is present in an amount sufficient that the composition has an acidic pH, i.e. , a pH of at least 0 and less than 7.

The composition may further comprise a solvent, or a mixture of solvents. The solvent may be a protic or an aprotic solvent.

In exemplary embodiments, the solvent is selected from the group consisting of water, ethanol, methanol, 1-propanol, isopropanol, butanol dimethyl sulfoxide. The solvent may also be a mixture of solvents. In a preferred embodiment, the solvent is a mixture of water and ethanol or a mixture of water and isopropanol.

In an embodiment, the pH of the composition is x, x being in the range of 0<x<7. Preferably, the pH x is in the range of 1<x<6, more preferably the pH x is in the range of 4<x<6.

In an especially preferred embodiment component (i) comprises, preferably consists of, 5-/V-carboxamido-2-pyrrolidone-/\/’-n-dodecyl-1 ,3-diamino propane (Py-C12), more preferably the reaction product of /V-dodecyl-1 ,3-diaminopropane (CAS 5538-95-4) and 5-oxo-pyrrolidine-2(S)-carboxylic acid methyl ester and contains water and has a pH of 2.0 to pH 10.0, preferably 7.0 - 10.0, more preferably >7.0 to 10.0. Such compositions have been found to be stable over a long time period at any pH-value, even at basic pH- values.

The composition is preferably obtainable by mixing a, preferably biocide, component (i) preferably comprising a diamine backbone, optionally in a solvent, with a pH value of below 7 with a triglyceride of formula (II).

Alternatively, the composition is preferably obtainable by mixing 5-/V-carboxamido-2- pyrrolidone-/V’-n-dodecyl-1 ,3-diamino propane (Py-C12), more preferably the reaction product of /V-dodecyl-1 ,3-diaminopropane (CAS 5538-95-4) and 5-oxo-pyrrolidine-2(S)- carboxylic acid methyl ester, optionally in a solvent, preferably water, isopropanol, ethanol or mixtures thereof, more preferably water and/or ethanol, with a pH value of 7.0 to 10.0 with a triglyceride of formula (II).

In a further aspect, the present invention is directed to a method for preparing a composition according to the present invention, comprising the steps of:

- providing a, preferably biocide, component comprising a compound, according to formula (I), preferably comprising a diamine, preferably a N,N'-alkyl-1 ,w-diamine, more preferably a 1 ,3-diamino propane backbone,

formula (I) with m being an integer from 1 to 6; and

R¹ being H;

with n and n’ being independently selected from an integer from 1 to 25

- adding at least one triglyceride of formula (II)

The residues R¹, R², R³, R⁴ and m of formula (I) and the residues R⁵, R⁶ and R⁷ of formula (II) for the method of the present invention, are defined as described for the composition comprising the compound of formula (I) and the triglyceride of formula (II) according to the present invention.

The method of the present invention may comprise the step of adjusting the pH value of the, preferably biocide, component (i), preferably of the compound according to formula (I), preferably comprising a diamine backbone, optionally in a solvent, preferably water or a mixture containing water and preferably ethanol or isopropanol. In the method of the present invention, an acid may be added, preferably to component (i), optionally in a solvent, to lower the pH of the composition to acidic values. The acid added corresponds to the acid as described for the composition of the present invention.

The pH value may be adjusted to a pH value x of between at least 0 and less than 7. In a preferred embodiment, the pH value x is 1<x<6, more preferably, the pH value x is 4<x<6.

In a preferred embodiment, component (i) comprises, preferably consists of 5-/V- carboxamido-2-pyrrolidone-/V’-n-dodecyl-1 ,3-diamino propane (Py-C12), more preferably the reaction product of /V-dodecyl-1 ,3-diaminopropane (CAS 5538-95-4) and 5-oxo-pyrrolidine-2(S)-carboxylic acid methyl ester and contains water and has a pH of 2.0 to pH 10.0, preferably 7.0 - 10.0, more preferably >7.0 to 10.0.

In a further aspect, the present invention is directed to a composition prepared by a method of the present invention.

A further aspect of the present invention is the use of a composition of the present invention. Compositions of the present invention may be used in wood preservatives, in cosmetics, metal treatment products such as technical oils or technical greases, preferably as preservatives in cosmetics, antimicrobial oils, etc. The compositions of the present invention may also be used in the inhibition of the activity of polypeptides and the denaturizing of proteins.

In an embodiment, the composition of the present invention can be used for modulating a polypeptide, in particular for interfering with the function and/or the structure of a polypeptide.

As used herein, “interfering with the function and/or the structure” is intended to mean a targeted change in function and/or structure of a protein; this change may include an increase, i.e. a positive change, or a decrease, i.e. a negative change. Preferably, the change in function and/or structure of a protein is a decrease, i.e. a negative change of its function and/or structure.

A polypeptide may be selected from a hormone, antibody, cytokine, enzyme, exotoxin, interferon, interleukin, chemokine, growth factor, colony stimulating factor, tumor necrosis factor, receptor, ribozyme, other disease-mediating enzymes in a targeted manner, collagen, keratin, elastin and wherein the protein is not a prion. In particular, the polypeptide is an enzyme and the decrease of its function is an inhibition of enzyme activity, i.e., an inhibition of an enzyme.

The function of proteins is linked to their three-dimensional form; this form includes secondary, tertiary and, where applicable, quaternary structures. Interfering with their structure might also be referred to as denaturation, i.e. a process in which the protein loses, at least in part, its three-dimensional form. Due to the function-structure relationship of proteins, such denaturation often leads, at least partially, to a loss of function. In case the protein is an enzyme, the relevant function might be referred to as an “activity”, and loss thereof might be referred to as “inhibiting” or “inactivating”.

A composition of the present invention may be used for inhibiting an enzyme, i.e., for inhibiting enzymatic activity.

In a particular embodiment, the inhibition of enzymatic activity may refer to a decrease in activity of at least about 0.5 %, preferably of at least about 50 %, more preferably of at least about 60 %, further preferably of at least about 80 %, still further preferably of at least about 90 % and most preferably of about 100 %, i.e. complete inhibition.

Such activities include those of oxidoreductases, such as cyclooxygenase or alcohol dehydrogenases; hydrolases, such as alkali phosphatases, endoproteases, nucleases, e.g. RNases or DNases, lipases; transferases; lyases; isomerases; and ligases.

In a preferred embodiment, the enzyme is selected from an oxidoreductase, preferably from a dioxygenase, an alcohol dehydrogenase and/or a peroxidase.

In a particular embodiment, the oxidoreductase is a cyclooxygenase.

In yet another preferred embodiment, the enzyme is selected from a hydrolase, preferably from a protease, a nuclease and/or a alkali phosphatase, wherein the protease is selected from zymogene, serine proteases, metalloproteases, collagenases, stromelysins, gelatinases, meprins, insulysin, CAAX-prenylproteases, aspartic peptidases, glutamylhydrolase, pryoglutamyl-peptidase, ubiquitinyl-hydrolase, oligopeptidase, an elastase, a carbohydrase such as driselase, and wherein the nuclease is selected from a RNase and/or DNase.

Further, it has been found that the effects of the compositions as disclosed herein on the function and/or structure of a polypeptide are dose-dependent which allows their adjustment depending on specific application purposes.

The invention will be further described in the following examples, which are not to be construed as limiting the invention.

Further Embodiments

Embodiment 1 : A composition comprising:

(i) a diamine component comprising at least one compound of formula (I)

m being an integer from 1 to 6; and

R¹ being H;

CH3 C₂H₅

and R⁴ being selected from

with n and n’ being independently selected from an integer from 1 to 25; and

(ii) a triglyceride of formula (II)

Embodiment 2: The composition according to embodiment 1 , wherein the diamine component consists at least 35 to 100 weight-%, more preferably 75 to 100 weight-% of at least one compound of formula (I), based on the total weight of the diamine component, preferably the diamine component consists of the at least one compound of formula (I). Embodiment 3: The composition according to embodiments 1 or 2, wherein the compound of formula (I) is a primary amine.

Embodiment 4: The composition according to embodiments 1 to 3, wherein the composition has a pH of below 7.

Embodiment 5: A composition according to embodiments 1 or 2, wherein the compound of formula (I) is a secondary amine, preferably 5-/V-carboxamido-2-pyrrolidone-N’-n- dodecyl propane-1 , 3-diamine.

Embodiment 6: A composition according to embodiment 5, wherein the composition has a pH of 2.0 to pH 10.0 or a free base.

Embodiment 7: The composition of any of embodiments 1 to 6, wherein the at least one triglyceride of formula (II) is a mixture of at least two different triglycerides.

Embodiment 8: The composition of any of embodiments 1 to 7, wherein the at least one triglyceride of formula (II) is a naturally occurring triglyceride.

Embodiment 9: The composition of any of embodiments 1 to 8, wherein the compound of formula (II) is a mixture of triglycerides corresponding to plant and animal oils and fats, e. g., soybean oil, grape seed oil, olive oil, cocoa butter, shea butter, jojoba oil, palm kernel oil, palm oil, hamp oil, soya oil, castor oil, sunflower oil, fish oil, beef tallow, pork fat and chicken fat or linseed oil, preferably linseed oil.

Embodiment 10: A method for preparing a composition according to any of embodiments 1 to 9, comprising the steps of:

- providing a diamine component comprising at least one compound of formula (I)

formula (I) with m being an integer from 1 to 6; and

R¹ being H;

CH₃ C₂H_5I

and R⁴ being selected from

with n and n’ being independently selected from an integer from 1 to 25;

- adding at least one

with R⁵, R⁶ and R⁷ being independently selected from C10-C25 alkyl and C10- C25 alkenyl.

Embodiment 11 : A composition prepared by a method of embodiment 10.

Embodiment 12: A use of a composition of any of embodiments 1 to 9 or 11 as a biocide or a preservative.

Embodiment 13: A use of a composition of any of embodiments 1 to 9 or 11 in a wood preservative.

Embodiment 14: A use of a composition of any of embodiments 1 to 9 or 11 as technical oils and greases for metal surfaces, preferably as corrosion protection oil and/or lubricant, such as lubricating oil or lubricating grease, preferably for lubrication of metal surfaces e.g. in metal working, or as an in-can preservative for technical oils and greases.

Embodiment 15: A use of a composition of any of embodiments 1 to 9 or 11 in a cosmetic product, preferably as a preservative in a cosmetic product or in an antimicrobial oil, in the modulation of the activity of a polypeptide, preferably in the denaturizing of a polypeptide. Embodiment 16: A use of a composition of any of embodiments 1 to 9 or 11 for modulating a polypeptide, preferably for interfering with the function and/or structure of a polypeptide, preferably an enzyme.

Examples

General

Reagents /V-dodecyl-1,3-diamino propane (C12, CAS 5538-95-4; Fig. 2) and /\/-(3- aminopropyl)-/V-dodecyl-1,3-diamino propane (Bis-C12, CAS 2372-82-9; Fig. 3) were bought from commercial sources in technical grade (> 80%) or better purity. 5-/V- carboxamido-2-pyrrolidone-/V’-n-dodecyl-1,3-diamino propane (Py-C12, CAS 126646- 23-9; Fig. 1) was prepared according to the procedure published in W02016016167A1. All experiments were carried out at ambient temperature.

The reactivity of the diamine species 5-/V-carboxamido-2-pyrrolidone-/\/’-n-dodecyl-1,3- diamino propane (Py-C12), /V-dodecyl-1,3-diamino propane (C12) and /\/-(3- aminopropyl)-/V-dodecyl-1,3-diamino propane (Bis-C12) upon treatment with linseed oil was examined. All three molecules play a major role as biocidal compounds.

Initial Experiments

Figure 4 shows the reaction scheme of C12 and the fatty carboxylic acids in linseed oil. C12 reacts via a substitution reaction with the triglyceride of formula (II) in linseed oil. The primary amine of the diamine C12 reacts with the carboxylic acid group of the fatty acids, which are bound via an ester group to the glycerol within the triglyceride.

This reaction will not take place with free fatty acids, but with the fatty acids of the triglyceride of formula (II) as the hydroxyl group is a bad leaving group. The carboxyl group needs to be activated chemically for this kind of reaction, for example by the formation of a carboxylic anhydride or -chloride or a NHS-ester. In the present case, the activation is given by binding the carboxylic acid group of the fatty acids via an ester group to glycerol within the triglyceride.

Figure 5 shows LCMS-chromatograms of 5-/V-carboxamido-2-pyrrolidone-/\/-n-dodecyl- 1 ,3-diamino propane (Py-C12, 1%) in linseed oil (linseed oil/H₂O/EtOH (8/1/1)).

Figure 5a depicts the LCMS-chromatogram of 5-/V-carboxamido-2-pyrrolidone-/\/’-n- dodecyl-1 ,3-diamino propane (Py-C12, 1%) in linseed oil (linseed oil/FhO/EtOH (8/1/1)) at pH 6 (Py-C12 stock solution was adjusted to pH 6 before dilution with linseed oil and EtOH) at day 0. It is shown that there are no reaction products. Figure 5b shows the LCMS-chromatogram of 5-/V-carboxamido-2-pyrrolidone-/\/’-n- dodecyl-1 ,3-diamino propane (Py-C12, 1%) in linseed oil (linseed oil/FhO/EtOH (8/1/1)) at pH 6 (Py-C12 stock solution was adjusted to pH 6 before dilution with linseed oil and EtOH) after 70 days. It is shown that there are no reaction products.

Figure 5c shows the LCMS-chromatogram of 5-/V-carboxamido-2-pyrrolidone-N’-n- dodecyl-1 ,3-diamino propane (Py-C12, free base, 1%) in linseed oil (linseed oil/H2O/EtOH (8/1/1)) at day 0. It can be seen that there are no reaction products.

In Figure 5d the LCMS-chromatogram of 5-/V-carboxamido-2-pyrrolidone-/\/’-n-dodecyl- 1 ,3-diamino propane (Py-C12, free base, 1%) in linseed oil (linseed oil/H2O/EtOH (8/1/1)) after 70 days is depicted. It can be seen that there are no reaction products.

No reaction/interaction of linseed oil with 5-/V-carboxamido-2-pyrrolidone-/\/-n-dodecyl propane-1 ,3-diamine (Py-C12) is detectable in Figures 5a, 5b, 5c and 5d under the given conditions.

Figure 6 shows the LCMS-chromatograms of /V-Dodecyl-1 ,3-diamino propane (C12, 1%) in linseed oil (linseed oil/H2O/EtOH (8/1/1)).

Figure 6a shows the LCMS-chromatogram of /V-Dodecyl-1 ,3-diamino propane (C12, 1 %) in linseed oil (linseed oil/H2O/EtOH (8/1/1)) at pH 6 (C12 stock solution was adjusted to pH 6 before dilution with linseed oil and EtOH) at day 0. No reaction products can be detected in the chromatogram.

Figure 6b shows the LCMS-chromatogram of /V-dodecyl-1 ,3-diamino propane (C12, 1%) in linseed oil (linseed oil/H2O/EtOH (8/1/1)) at pH 6 (C12 stock solution was adjusted to pH 6 before dilution with linseed oil and EtOH) after 70 days. No reaction products can be detected in the chromatogram.

Figure 6c shows the LCMS-chromatogram of /V-dodecyl-1 ,3-diamino propane (C12, free base, 1%) in linseed oil (linseed oil/H2O/EtOH (8/1/1)) at day 0.

Figure 6d shows the LCMS-chromatogram of /V-dodecyl-1 ,3-diamino propane (C12, free base, 1%) in linseed oil (linseed oil/H2O/EtOH (8/1/1)) after 70 days. Reaction products of C12 with the fatty acids (oleic acid, linoleic acid, a -linolenic acid, palmitic acid and stearic acid) in linseed oil are encircled. No left C12 is detectable.

No degradation or reaction of /V-dodecyl-1 ,3-diamino propane (C12) is detectable under the given conditions in Figure 6a and 6b at pH 6 (C12 stock solution was adjusted to pH 6 before dilution with linseed oil and EtOH). Under alkaline conditions, C12 (free base) is not detectable after 70 days as is shown in Figure 6d. C12 reacts completely with the fatty acids of linseed oil, which are oleic acid, linoleic acid, a -linolenic acid, palmitic acid and stearic acid. The amine of C12 forms an amide with the carboxylic acid group of the fatty acids. The resulting five C12-fatty acid-components are encircled in Figure 6d.

Figure 7 shows exemplary reaction products of C12 after incubation of C12 as free base in linseed oil for 70 days (detected via HPLC-MS/MS).

Figure 8 shows the LCMS-chromatograms of /V-(3-aminopropyl)-/\/-dodecyl-1 ,3-diamino propane (Bis-C12, 1%) in linseed oil (linseed oil/FhO/EtOH (8/1/1)).

Figure 8a shows the LCMS-chromatogram of /V-(3-aminopropyl)-/\/-dodecyl-1 ,3-diamino propane (Bis-C12, 1 %) in linseed oil (linseed oil/H₂O/EtOH (8/1/1)) at pH 6 (Bis-C12 stock solution was adjusted to pH 6 before dilution with linseed oil and EtOH) at day 0 (Peak 1 and Peak 2: Bis-C12, Peak 4: C12 impurity). No reaction products are detectable.

Figure 8b shows the LCMS-chromatogram of /V-(3-aminopropyl)-/\/-dodecyl-1 ,3-diamino propane (Bis-C12, 1 %) in linseed oil (linseed oil/H2O/EtOH (8/1/1)) at pH 6 (Bis-C12 stock solution was adjusted to pH 6 before dilution with linseed oil and EtOH) after 70 days (Peak 1 and Peak 2: Bis-C12, Peak 4: C12 impurity). No reaction products are detectable.

Figure 8c shows the LCMS-chromatogram of /V-(3-aminopropyl)-/\/-dodecyl-1 ,3-diamino propane (Bis-C12, free base, 1%) in linseed oil (linseed oil/H2O/EtOH (8/1/1)) at day 0 (Peak 1 and Peak 2: Bis-C12, Peak 4: C12 impurity).

Figure 8d shows the LCMS-chromatogram of /V-(3-aminopropyl)-/\/-dodecyl-1 ,3-diamino propane (Bis-C12, free base, 1%) in linseed oil (linseed oil/H2O/EtOH (8/1/1)) after 70 days. Reaction products of Bis-C12 and the impurity /V-Dodecyl-1 ,3-diamino propane (C12) with the fatty acids (oleic acid, linoleic acid, a-linolenic acid, palmitic acid and stearic acid) in linseed oil are encircled. No left Bis-C12 or C12 is detectable.

No degradation or reaction of /V-(3-aminopropyl)-/\/-dodecyl-1 ,3-diamino propane (BisCi 2) is detectable under the given conditions at pH 6 (Bis-C12 stock solution was adjusted to pH 6 before dilution with linseed oil and EtOH). Under alkaline conditions, Bis-C12 (free base) is not detectable after 70 days (Figure 8d). Bis-C12 reacts completely with the fatty acids of linseed oil, which are oleic acid, linoleic acid, a -linolenic acid, palmitic acid and stearic acid. The amine(s) of Bis-C12 react(s) with the carboxylic acid group of the fatty acids to form an amide. The resulting Bis-C12-fatty acidcomponents are encircled in figure 8d.

In conclusion it can be noticed that at acidic pH neither Py-C12 nor (Bis-)C12 react with linseed oil. At basic pH the primary amino group(s) of C12 and Bis-C12 react with linseed oil, more exactly with the fatty acids under formation of amides. Py-C12 does not react. This is advantageous, as Py-C12 is structurally unchanged in linseed oil at basic (free base) pH and therefore is stable and remains its biocidal activity.

Claims

1. A composition comprising:

(i) a biocide component comprising at least one compound of formula (I)

formula (I) with m being an integer from 1 to 6; and

R¹ being H and with R³ and R⁴ being independently selected from

with R⁸ and R⁹ being selected from

with p being an integer from 1 to 20 and with X being O or S; and

(ii) at least one triglyceride of formula (II)

2. The composition according to claim 1 , wherein R³

, wherein “n” is 1 to 15, preferably, wherein “n” is 4 to 12, more preferably, wherein “n” is 6 to 11 , alternatively 5 to 15 and preferably R⁴ is H.

3. The composition according to claims 1 or 2, wherein R⁸ and R⁹ both being H.

4. The composition according to any of the preceding claims, wherein the compound of formula (I) is the reaction product of N-dodecyl-1 ,3-diaminopropane (CAS 5538- 95-4) and 5-oxo-pyrrolidine-2(S)-carboxylic acid methyl ester.

5. The composition according to any of the preceding claims, wherein the compound of formula (I) is 5-/V-carboxamido-2-pyrrolidone-/\/-n-dodecyl propane-1 , 3-diamine.

6. The composition according to any of the preceding claims, wherein the biocide component (i) comprising at least one compound of formula (I) consists of at least 35 to 100 weight-%, more preferably 75 to 100 weight-% of at least one compound of formula (I), based on the total weight of the biocide component (i), preferably the component consists of the at least one compound of formula (I).

7. The composition according to any of the preceding claims, wherein the biocide component (i) comprising at least one compound of formula (I), consists of at least 35 to 100 weight-%, more preferably 75 to 100 weight-%, of 5-/V-carboxamido-2- pyrrolidone-/V-n-dodecyl propane-1 , 3-diamine, most preferably consists of 5-/V- carboxamido-2-pyrrolidone-/V-n-dodecyl propane-1 , 3-diamine based on the total weight of the component (i).

8. The composition according to any of the preceding claims, wherein the composition contains water and has a pH of 2.0 to pH 10.0, preferably 7.0 - 10.0, more preferably >7.0 to 10.0.

9. The composition of any of the preceding claims, wherein component (ii) is a mixture of at least two different triglycerides.

10. The composition of any of the preceding claims, wherein the at least one triglyceride of formula (II) is a naturally occurring triglyceride.

11. The composition of any of claims 1 to 8, wherein component (ii) is a mixture of triglycerides corresponding to plant and animal oils and fats, e. g., soybean oil, grape seed oil, olive oil, cocoa butter, shea butter, jojoba oil, palm kernel oil, palm oil, hamp oil, soya oil, castor oil, sunflower oil, fish oil, beef tallow, pork fat and chicken fat or linseed oil, preferably linseed oil.

12. A method for preparing a composition according to any of claims 1 to 9, comprising the steps of: - providing a biocide component (i) comprising at least one compound of formula (I)

formula (I) with m being an integer from 1 to 6; and

R¹ being H and with R³ and R⁴ being independently selected from

with n and n' being an integer from 1 to 25, and

R² being

with R⁸ and R⁹ being selected from

with p being an integer from 1 to 20 and with X being O or S; and

- adding at least one triglyceride of formula (II)

13. Method according to claim 12, wherein the at least one compound according to formula (I) is provided in solvent.

14. Method according to claim 13, wherein the solvent is selected from the group consisting of water, ethanol, methanol, 1-propanol, isopropanol, butanol dimethyl sulfoxide and mixtures thereof.

15. Method according to claims 13 to 14, wherein the solvent comprises water and the pH of component (i) comprising at least one compound of formula (I) is adjusted to pH 2.0 to 10.0, preferably 7.0 - 10.0, more preferably >7.0 to 10.0, before addition of (ii) the at least on triglyceride.

16. Method according to claims 12 to 15, wherein R³

wherein “n” is 1 to 15, preferably, wherein “n” is 4 to 12, more preferably, wherein “n” is 6 to 11 , alternatively 5 to 15 and preferably R⁴ is H.

17. Method according to claims 12 to 16, wherein R⁸ and R⁹ both being H.

18. Method according to claims 12 to 17, wherein the compound of formula (I) is 5-/V- carboxamido-2-pyrrolidone-/V’-n-dodecyl propane-1 ,3-diamine.

19. Method according to claims 12 to 18, wherein the compound of formula (I) is the reaction product of /V-dodecyl-1 ,3-diaminopropane (CAS 5538-95-4) and 5-oxo- pyrrolidine-2(S)-carboxylic acid methyl ester.

20. Method according to claims 12 to 19, wherein the biocide component (i) comprising at least one compound of formula (I) consists of at least 35 to 100 weight-%, more preferably 75 to 100 weight-% of at least one compound of formula (I), based on the total weight of the biocide component (i), preferably the component consists of the at least one compound of formula (I).

21. Method according to claims 12 to 20, wherein the biocide component (i) consists of at least 35 to 100 weight-%, more preferably 75 to 100 weight-%, of 5-/V- carboxamido-2-pyrrolidone-/V-n-dodecyl propane-1 , 3-diamine, most preferably consists of 5-/V-carboxamido-2-pyrrolidone-/\/-n-dodecyl propane-1 , 3-diamine based on the total weight of the component.

22. A composition prepared by a method of claims 12 to 21.

23. A composition according to claims 1 to 11 or 22, wherein the composition is storable, preferably the concentration of the compound according to formula (I) in the composition is essentially constant, more preferably the amount of the compound according to formula (I) does not decrease more than 3 weight-%, preferably more than 1 weight-%, upon storage for more than two months, preferably more than four months, more preferably more than six months preferably after providing the composition, preferably the mixture, of (i) and (ii), more preferably in a closed package and/or at room temperature.

24. Use of a composition of any of claims 1 to 11 , 22 or 23 as a biocide or a preservative.

25. Use of a composition of any of claims 1 to 11 , 22 or 23 in a wood preservative, preferably as a wood preservative.

26. Use of a composition of any of claims 1 to 11 , 22 or 23 as technical oil or technical grease, preferably for metal surfaces, more preferably as corrosion protection oil and/or lubricant, such as lubricating oil or lubricating grease, preferably for lubrication of metal surfaces e.g. in metal working,

27. Use of a composition of any of claims 1 to 11 , 22 or 23 as in-can preservative for technical oil or technical grease.

28. Use of a composition of any of claims 1 to 11 , 22 or 23 in a cosmetic product, preferably as a preservative.

29. Use of a composition of any of claims 1 to 11 , 22 or 23 as an antimicrobial oil.

30. Use of a composition of any of claims 1 to 11 or 22 or 23 for modulating a polypeptide, preferably for interfering with the function and/or structure of a polypeptide, preferably an enzyme.