WO2024261308A1 - Low temperature reactive aryl azides - Google Patents

Abstract

The present invention relates to a compound of formula (I) wherein R₁ is selected from the group consisting of B₁ and Y₁, R₂ is selected from the group consisting of B₂ and Y₂, R₃ is selected from the group consisting of B₃ and Y₃, R₄ is selected from the group consisting of B₄ and Y₄, and B₁ and B₃ are independently selected from the group consisting of fluoro, chloro and bromo, B₂ and B₄ are independently from the group consisting of hydrogen and fluoro, and if R₁ is Y₁, R₂ is Y₂, Y₁ being selected from the group consisting of oxygen, sulfur and selenium, and Y₂ is -CH₂CH₂- or -CH=CH- and forms together with Y₁ a 5 membered ring system; if R₃ is Y₃, R₄ is Y₄, Y₃ being selected from the group consisting of oxygen, sulfur and selenium, and Y₄ is -CH₂CH₂- or -CH=CH- and forms together with Y₃ a 5 membered ring system, X is selected from the group consisting of D-(L_p-A)_mH_1-m, wherein D is selected from the group consisting of S and O, p is 1 and m is 1, L is a linker group and A is a reactive group.

Description

Low temperature reactive aryl azides

The present invention relates to aryl azides .

Phenylazide and its derivatives are known to react via nitrogen elimination of the azide into highly reactive singlet nitrene species that can undergo a plethora of intra- or intermolecular reactions including insertion reactions into other X-Y bonds to form new covalent linkages (R-NX-Y) . This reaction is induced either by UV-light or thermally typically well above 100 ° C .

Experimental and theoretical studies have extensively investigated the stability and reactivity of nitrenes that are formed . Most of these studies have focused on the stability and reactivity of singlet nitrenes that are initially formed . It has been discovered that ortho-substituting phenylazide with a halogen ( fluorine , chlorine , or bromine ) increases the li fetime of singlet nitrene to 260 ns at 298 K . This is in contrast to the unsubstituted parent compound, which has a li fetime of less than 1 ns . A long li fetime of the produced nitrene is essential for increasing the likelihood of intermolecular insertion reactions over intramolecular rearrangement reactions .

For certain material applications such as coating of polymeric materials with low glass transition temperature or low melting point , or for the functionali zation of biomolecules it would be of great advantage to have azides that can be thermally activated below a temperature of 100 ° C . For applications where photoactivation is not possible its of great advantage i f the activation temperature is as low as possible . In a paper by Smith, P. et al (J. Org. Chem. 1985, 50 (12) , 2062-2066) , it was reported that the thermal activation temperature of unsubstituted phenylazide is significantly higher than 140°C. Additionally, Yan M. et al (Chem. Mater. 2004, 16 (9) , 1627-1632) found that the decomposition of perfluoro phenylazide begins at temperatures above 130°C, resulting in the immobilization of ultrathin polymer films.

There are only a few phenylazides with known thermal decomposition below 100°C. Those known molecules decompose in a concerted intramolecular mechanism as for example 2-nitro- phenylazide. It decomposes intramolecularly to form the ring structure benzo [c] [ 1 , 2 , 5 ] oxadiazole 1-oxide (compound A) , which is the main obtained compound in its thermal decomposition reaction.

Cardillo, P. et al (J. Therm. Anal. Calorim. 2010, 100 (1) , 191-198) found that similar concerted intramolecular mechanisms occur in other 2-substituted phenylazides, unless the substituent is a halogen. However, for unsubstituted phenylazide, the main decomposition path is intramolecular, via an azirine intermediate to azepine. As a result, these azides have very low to undetectable yields of intermolecular bonds formed via insertion reactions to nearby molecules.

Some prior art documents, such as 0. Sterner, et al. (Langmuir, 2013, 29(42) , 13031-13041) ; T. Kubo, et al. (Langmuir, 2011, 27 (15) , 9372-9378) and R.M. Bielecki, et al. (Tribology Letters, 2012, 49(1) , 273-280) disclose the preparation of modified poly (allyl amine) using the N-hydroxysuccinimidyl ester of 4-azido-perf luorobenzoic acid.

WO 2013/184796 Al discloses polymer coatings covalently attached to a surface of a substrate that is used for the detection and analysis of molecules, such as nucleic acids and proteins. The crosslinking can be carried out by UV or thermal activation. Thermal crosslinking takes place via a specific reaction of the azide with an alkene or acrylamide pre- silanized surface, without formation of a nitrene intermediate. Therefore, a pre-functionalization of the surface with such reactive groups is necessary.

The objective of the present invention was to provide substituted phenylazides having a reactive group that can be thermally activated below 100°C to generate a singlet nitrene.

The problem is solved by the compounds according to claims 1 and 7. Further preferred embodiments are subject of dependent claims 2 to 6 and 8 to 15.

Thus, the present invention relates to a compound of formula

I

wherein

R₂ is selected from the group consisting of B₂ and Y₂ ,

R₂ is selected from the group consisting of B₂ and Y₂ ,

R₃ is selected from the group consisting of B₃ and Y₃,

R₄ is selected from the group consisting of B₄ and Y₄ , and

B₂ and B₃ are independently selected from the group consisting of fluoro , chloro and bromo ,

B₂ and B₄ are independently from the group consisting of hydrogen and fluoro , and i f R₂ is Y_{l f} R₂ is Y₂ , Y₂ being selected from the group consisting of oxygen, sul fur and selenium, and Y₂ is -CH₂CH₂- or -CH=CH- and forms together with Y₂ a 5 membered ring system i f R₃ is Y_{3 f} R₄ is Y₄ , Y₃ being selected from the group consisting of oxygen, sul fur and selenium, and Y₄ is -CH₂CH₂- or -CH=CH- and forms together with Y₃ a 5 membered ring system

X is selected from the group consisting of D- ( L_p-A) _mH_2-m, wherein D is selected from the group consisting of S and 0, p is 1 and m is 1 ,

L is a linker group selected from the group consisting of an alkylene chain having 1 to 18 carbon atoms , an alkenyl chain having 1 to 18 carbon atoms, an alkynyl chain having 1 to 18 carbon atoms, an oligoethylene oxide having 2 to 20, preferably 2 to 10, repeating units, an oligo-Ch-Cs-alkyloxazoline having 2 to 20, preferably 2 to 10, repeating units, an oligo-Ch-Cs- alkyloxazine having 2 to 20, preferably 2 to 10, repeating units, peptide chains, polydimethylsiloxane, perfluoroethers, perfluoroalkyls, polyisobutene, polyethylene glycol, polydimethyl acrylamide, polyvinylpyrrolidone, polyalkyloxazolines , polyalkyloxazines, dextran, carboxymethyl dextran, poly (N-iso-propylacrylamide ) , poly(N- hydroxyethylacrylamide, poly ( 2-hydroxyethyl methacrylate) , poly-hydroxypropyl-methacrylate ) , poly- (methacryloyloxylethyl phosphorylcholine) , poly- ( sulfobetaine methacrylate) , polyalkylene residues having more than 18, preferably more than 20 carbon atoms, DNA fragments and poly- ( sulfobetaine acrylamide) ,

A is a reactive group selected from the group consisting of an active ester, amine, hydroxy, thiol, alkoxy silane, chloro silane, carboxylate, maleimide, vinylsulfone, acrylamide, bromide, iodide, iodoacetate, bromoacetate, azide, arylazide, alkyne, transcyclooctene (TCO) , tetrazine, methyltetrazine, phenyltetrazine, ring-strained alkyne, bicyclononyne (BCN) , dibenzocyclooctyne (DBCO) , biotin, 2-nitrobenzyl alcohol, 5- azido-2-nitrobenzoic acid, isothiocyanate, isocyanate, benzophenone, aldehyde, dithiopyridine, methanethiosulfonate, 3-phenyl-3- (trifluoromethyl) -3H-diazirine, hydrazide, tert- butylcarbazat , phosphoramidite, epoxide, chlorotriazine, and f luoro triaz ine .

It was found that the compounds of formula I can be thermally activated below 100°C to generate a singlet nitrene, which can react via an insertion reaction with neighboring molecules, while intramolecular reactions are suppressed. X in para position has a double function. First, it stabilizes the singlet nitrene and second it provides or allows to link a reactive group which can be utilized for attachment to other molecules, polymers or biomolecules. Regarding the stabilization of the nitrene, it has been found that the presence of group X, as defined above, provides a strong stabilization effect on the nitrene. In contrast, amide or ester groups in the para position, for instance, do not exhibit such stabilizing characteristics. Furthermore, it was shown that the electronegative and n-donating atoms in ortho position to the azide group (B_x, B₃, Y_x and Y₂) lower the activation barrier, and thus result in compounds that can be thermally activated below 100°C. Due to the fact that the generated singlet nitrene species can undergo insertion reactions into other bonds to form new covalent linkages, it is possible to functionalize surfaces that have no functional groups. Thus, pre-treatments can be avoided. Further, since the compounds according to the present invention can be activated at lower temperature, i.e. at temperatures below 100°C, the reactions are more selective and lead to less unwanted side reactions. Additionally, the possibility to activate the azide at low temperature allows to keep reactive groups with orthogonal reactivity alive. For example, it is possible to activate the azide at low temperature while other arylazides, acrylate or epoxy groups are unaffected. Such groups can then be used for selective reactions or polymerizations in a second step. Such a twostep process would not be possible at high temperature or by photoactivation. In addition, an unwanted reactivity to A can be avoided. A preferred embodiment of the present invention relates to the compound of formula II

wherein D, L, p and A have the same definition as indicated above, thus it relates to compound of formula I, wherein m is

A further preferred embodiment of the present invention refers to a compound of formula III, wherein D is 0 and p is 1, thus to a compound of formula Illa:

The presence of the linking group allows to attach a high variety of possible different A groups without influencing the reactivity of the azide. Preferably, the compound of the present invention is selected from the group consisting of compounds IV, V and VI

wherein B₂ , B₂ , B₃, B₄ , X, Y₂ and Y₂ have the same definition as above . Especially preferred are compounds selected from the group consisting of compounds IVa, Va and Via .

Preferably, in the compound of the present invention B_x and/or B₃ are fluoro , since ortho fluorinated phenylazides are excellent candidates for photoaf finity labeling of proteins and surface functionali zation, since it strongly favors the intermolecular insertion reaction .

Contrary to ortho and para substituents , a substitution in meta position has a minor or opposite ef fect on the activation energy . Best results could be obtained with compounds according to the present invention, wherein B₂ and/or B₄ are hydrogen . Especially preferred are compounds of formulae Vi la, Vi l la and IXa

Preferably, the linker group L is selected from the group consisting of an alkenyl chain having 1 to 18 carbon atoms, an oligoethylene oxide having 2 to 20, preferably 2 to 10, repeating units, an oligo-C₂-C5-alkyloxazoline having 2 to 20, preferably 2 to 10, repeating units, an oligo-C₂-C5- alkyloxazine having 2 to 20, preferably 2 to 10, repeating units polydimethylsiloxane, polyethylene glycol, polyalkyloxazolines , polyalkyloxazines, dextran, and polyalkylene residues having more than 18, preferably more than 20 carbon atoms. Said linker groups can introduce flexibility into the final product and also be used to enhance the solubility and polarity.

A further embodiment of the present invention relates to a Compound of formula X

wherein D, L, R₂, R₂, R₃ and R₄ have the same definition as defined above,

G is formed by reaction of the group A as defined above, with E₂, E₂, E₃, or E₄, wherein E₂, E₂, E₃ and E₄ are selected from the group consisting of E_x is selected from the group consisting of 1 , 4-diaminobutane, 1 , 5-diaminopentane, thermospermine, caldopentamine, caldohexamine, 1 , 2-diaminocyclohexane, 4,4'- diaminodiphenylsulfone, 1, 5-diamino-2-methylpentane, diethylentriamine, hexamethylendiamine, isophorondiamine, triethylentetramine, trimethylhexamethylendiamin, spermidine, spermin, tris (2-aminoethyl) amine, tetrakis (2- aminoethyl ) amine, tris ( 3-aminopropyl ) amine, tetrakis (3- aminopropyl) ammonium, amine terminated dendrimers, amine functionalized silicones as for example the commercially available WACKER® FLUID NH polymers, polyallylamine, polyethyleneimine, polylysine or polyornithine,

E₂ is selected from the group consisting citric acid, succinic acid, glutamic acid, tartaric acid, malonic acid, maleic acid, poly (acrylic acid) , poly ( aspartic acid) , poly (maleic acid-alt- ethylene) , poly (nitrilotriacetic acid) , poly(citric acid) or esters thereof,

E₃ is selected from the group consisting of alkoxy silanes, chloro silanes, catechols, phosphates, phosphonates, anacheline, mimosine derivatives, gallols, thiols, N- heterocyclic carbenes, perfluorophenyl azides, benozophenone, di aryl di azomethane, aryltri fluoromethyl- diazomethane, organoboron, alpha lipoic acid, acrylamide, acrylate, and epoxide, and

E₄ is selected from the group consisting of a fluorescent marker, a perfluorinated alkyl, a biotin, NTA and a short peptide, preferably having 3 to 20 amino acids and q is 1 to 10'000. A skilled person is aware of the combinations of reactive groups that can undergo chemical reactions . Speci fically, they are knowledgeable about which pairs of reactive groups , labeled as A and E_x , E₂ , E₃, or E₄ , are capable of reacting with each other . Moreover, i f , for instance , A is an active ester and E₃ is 1 , 4-diaminobutane , it is evident that the value of " q" can only be 1 or 2 . However, in the case of polylysine , " q" can be as high as the degree of polymeri zation of the polylysine used . For a high molecular weight polymer q can be up to 10 ' 000 .

In a further aspect , A or G of the compounds according to the present invention comprise a terminal amino group, and most preferably a primary amine group . Said primary amine group can for example react with a reactive group on a polymer backbone or a surface-active group as a post-modi fication .

A further aspect of the present invention relates to a functional polymer comprising a polymer backbone and a plurality of side chains , wherein at least a part of said side chains comprise one or more compounds according to the present invention . For example , EP3191559A1 , EP2236524A1 , WO2018219433A1 , WO2021190766A1 and WO2019206682A1 disclose functional polymers . The contents of said applications are hereby incorporated by reference in its entirety . Preferably, the polymer backbone is a polyacrylamide .

In one embodiment of the present invention a functional polymer is a polymer wherein all side chains comprise compounds according to the present invention . Such functional polymers are highly desirable as polymeric crosslinkers and as adhesion promoters . Coatings of such polymers can be used as adhesion layer in next generation sequencing (NGS ) applications . In another embodiment of the present invention a functional polymer is a polymer that comprises at least two types of side chains , wherein at least one type of side chain comprises a compound according to the present invention . Of course , each type of side chain comprises a plurality of identical side chains .

The reactive group of the compounds according to the present invention can react with a reactive group Q on the polymer backbone , which is preferably selected from the group consisting of esters , activated esters , chloro , fluoro , acrylate , methacrylate , NHS esters , epoxides , anhydrides , azides , alkynes , and acyltri fluoroborates . Thus , the compound according to the present invention can be introduced into a functional polymer by post-modi fication of a polymer backbone carrying a reactive group . Preferably, the polymer backbone is a polyacrylamide , and polymer backbone and the side chains are linked by amide bonds .

Preferably, such a functional polymer

comprises a compound according to the present invention Z ( such as compound of formula I or compound of formula X ) as first type of side chain and at least one further type of side chain H, which is intended to reversibly bind to a substrate or has a coating function, and T₂ is an alkylene or arylene group and [ T₂ ] _r is an amide , an ester or an ether group and r is either 0 or 1 , preferably 0 ,

K is a functional group formed by a reactive group of the polymer backbone Q as defined above and the reactive group A of the compound according to the present invention . Preferably, K is selected from the group of an ester, a secondary amine , an amide , an ether, a thio ether, a thio ester, and may be the same or di f ferent for the di f ferent types of side chains . Preferably, the functional group K is an amide .

H is selected from the group consisting of a short chain side chain H₂ having a linear or branched, substituted or unsubstituted C₂ to C₁₂ alkylene group which optionally comprises heteroatoms selected from the group consisting of oxygen and nitrogen, and which carries at least one functional end or side group K₂ selected from the group consisting of amines , carboxy, poly (propylene sul fide ) , and thioethers ; a side chain H₂ having a long chain H₂ comprising more than 15 carbon or silicium atoms in the chain, wherein said long chain H₂ is selected from the group consisting of polydimethylsiloxane , perfluoroethers , perfluoroalkyls , polyisobutene , polyethylene glycol , polydimethylacrylamide , polyvinylpyrrolidone , polyalkyloxazolines , polyalkyloxazines , dextran, carboxymethyl dextran, poly (N-isopropylacrylamide ) , poly (N-hydroxyethylacrylamide , poly ( 2-hydroxyethyl methacrylate ) , poly-hydroxypropylmethacrylate ) , poly- (methacryloyloxylethyl phosphorylcholine ) , poly- ( sul fobetaine methacrylate ) , polyalkylene residues having more than 20 carbon atoms , peptide chains , DNA fragments and poly- (sulfobetaine acrylamide) , whereby H₂ has no functional end group or side group; a side chain H₃ having a long chain H₃ selected from the group consisting of a polydimethylsiloxane, perfluoroethers, perfluoroalkyls, polyisobutene, polyethylene glycol, polydimethyl acrylamide, polyvinylpyrrolidone, polyalkyloxazolines , polyalkyloxazines, dextran, carboxymethyl dextran, poly (N-isopropylacrylamide ) , poly(N- hydroxyethylacrylamide, poly ( 2-hydroxyethyl methacrylate) , poly-hydroxypropylmethacrylate ) , poly- (methacryloyloxylethyl phosphorylcholine) , poly- ( sulfobetaine methacrylate) , polyalkylene residues having more than 20 carbon atoms, peptide chains, DNA fragments and poly- ( sulfobetaine acrylamide) , whereby H₃ carries at least one functional end or side group K₃ selected from the group consisting of amines, carboxy, and nitrilotriacetic acid (NTA) , biotin, azide, terminal alkene groups, terminal alkyne groups, tetrazine.

Preferably, the functional polymer, in addition or alternatively to at least one type of side chain H, may comprise a further type of side chain J which is intended to irreversibly bind to a substrate, said side chain J having a linear or branched, substituted or unsubstituted C₂ to C₁₂ alkylene group which optionally comprises heteroatoms selected from the group consisting of oxygen and nitrogen, and which carries at least one functional end or side group K₄ selected from the group of alkoxy silanes, chloro silanes, catechols, nitrocatechols, bromocatechols, chlorocatechols, phosphates, phosphonates, mimosine derivatives, anacheline, gallols, thiols, N-heterocyclic carbenes, azides, perfluorophenyl azides , benzophenon, diaryldiazomethane , aryltri fluoromethyldiazomethane , organoboron, acrylamide , acrylate , and epoxide .

Within the context of the present invention the term side group means a group of atoms attached to a carbon atom within the side chain and an end group is a group at the end of the side chain, that is its terminal group .

In preferred embodiments of the present invention the functional polymer is selected from polymers comprising the following types of side chains

Compound of formula I

Compound of formula X

Compound of formula I and s ide chain H₂

Compound of formula X and s ide chain H₂

Compound of formula I and s ide chain H₂

Compound of formula X and side chain H₂

Compound of formula I and s ide chain H₃

Compound of formula X and s ide chain H₃

Compound of formula I and s ide chain J

Compound of formula X and s ide chain J

- Compound of formula I side chain H₂ and side chain H₂

- Compound of formula X side chain H₂ and side chain H₂

- Compound of formula I , side chain H₂ and side chain H₃

- Compound of formula X, side chain H₂ and side chain H₃

- Compound of formula I , side chain H₂ and side chain H₃

- Compound of formula X, side chain H₂ and side chain H₃ Compound of formula I side chain Hi and side chain

Compound of formula

side chain Hi and side chain J

Compound of formula I side chain H₂ and side chain J

Compound of formula

side chain H₂ and side chain J

Compound of formula I side chain H₃ and side chain J

Compound of formula

side chain H₃ and side chain J

Compound of formula I side chain HI , side chain H₂ and side chain H

Compound of formula

side chain Hi , side chain H₂ and side chain H

Compound of formula I side chain Hi , side chain H₂ and side chain J

Compound of formula

side chain Hi , side chain H₂ and side chain J

Compound of formula I side chain Hi , side chain H₃ and side chain J

Compound of formula

side chain Hi , side chain H₃ and side chain J

Compound of formula I side chain H₂ , side chain H₃ and side chain J

Compound of formula

side chain H₂ , side chain H₃ and side chain J

Compound of formula I side chain Hi , side chain H₂ , side chain H and side chain J

Compound of formula X, side chain Hi , side chain H₂ , side chain H and side chain J whereby, the order within the polymer chain is not defined by the order of the chains as listed above .

Preferably, the functional polymer according to the present invention comprises at least 1 to 200 identical side chains per type of side chain .

Especially preferred side chains H_x are selected from the group consisting of aminobutyl , aminopentyl and aminohexyl , preferably aminohexyl .

Especially preferred side chains H₂ are selected from the group consisting of polyalkyloxazolines , polyalkyloxazines and polyethylene glycol ;

Especially preferred side chains H₃ are selected from the group consisting of biotin, NTA, a terminal alkene group and a terminal alkyne group .

Especially preferred side chains J are selected from the group consisting of alkoxy silanes , chloro silanes , especially aminopropyldimethylethoxys ilane , and catechols , especially nitrocatechol .

One embodiment relates to the use of a compound according to the present invention or the functional polymer comprising the compound according to the present invention as adhesion promoter . Due to the presence of said compounds the ability of coatings and adhesives to adhere to a variety of substrates can be strongly enhanced, including those that are di f ficult to bond to , such as plastics , metals , and composites . Furthermore , the need for extensive surface preparation can be signi ficantly reduced . Preferably, said adhesion promoter is thermally activated . This allows to use the compound or the polymer according to the present invention as adhesion promoter for materials that are sensitive to light and may degrade or undergo unwanted reactions when exposed to light or for polymers having a low glass transition temperature or low melting point . Furthermore , they can be used for light-blocking materials , that is for materials that are opaque or absorb light . Examples are coatings on the inner side of tubing, microfluidic channels or adhesives to connect opaque polymeric materials .

In another embodiment , the compounds and functional polymers according to the present invention can be used as thermally activatable crosslinking agent also called thermal crosslinker . When exposed to heat they decompose to form a singlet nitrene . Such crosslinking agents can be used for creating hydrogels , which can be used in drug delivery, tissue engineering, and wound healing applications or to modi fy the properties of di f ferent surfaces . Beside hydrogels , which start from hydrophilic water soluble compounds , also oilsoluble compounds to produce an oil or hydrocarbon containing gel can be prepared . Especially preferred is its use as a thermal crosslinker for generating a solid from a liquid polymeric precursor . Such a precursor is typically a liquid at room temperature and can be applied by various techniques such as spraying, dipping, or spin-coating to form thin films or coatings . Upon contact with the compound or the polymer according to the present invention and heat exposure the precursor hardens and generates a solid material .

Another embodiment relates to the use of the compound according to the present invention to thermally introduce functional groups , f luorescent markers , a perfluorinated alkyl , a biotin or a short peptide to a material selected from the group of a polymer, a particle , a nanoparticle and a hydrogel , wherein said material is essentially free of other functional groups . The term " functional group" means a group capable of reacting with another functional group to form a covalent bond . Examples of functional groups are hydroxyl , carbonyl , amino , carboxyl , acrylate , allyl and esters . By reacting such a material with a compound according to the present invention a functional group fluorescent markers , a perfluorinated alkyl , a biotin or a short peptide can be introduced into said material which does not contain any other functional groups . This allows for example to generate a polymer such as PVP with the attached functional groups :

The same applies for other materials such as particles , nanoparticles , hydrogels , laminin, collagen, agarose and agarose beads .

Another embodiment relates to the use of the compound or the functional polymer according to the present invention to thermally attach a coating inside a microfluidic channel . Another embodiment relates to the use of the functional polymer according to the present invention to produce layer by layer ( LbL ) multilayer films by alternating deposition of the functional polymer according to the present invention and a second polymer . Preferentially this second polymer should be oppositely charged . Such films can be deposited by alternating dipping in the two polymer solutions or by alternating spray coating . Thermal curing at low temperatures of this generated LbL films will lead to covalent bonding between the layers generating very strong f ilms and coatings .

Another embodiment relates to the use of the compound or the functional polymer according to the present invention in combination with radiation sensitive groups , preferably UV- light sensitive groups . This allows to first selectively activate the compound or the functional polymer according to the present invention by low temperature curing, while the radiation sensitive groups do not react . In a second step, the radiation sensitive groups can be activated to achieve orthogonal binding . The wavelength of the used light-source for activation should be in the range of 800 nm to 50 nm, more preferably in the range of 400 nm to 200 nm and most preferably in the range of 300 nm to 230 nm .

Another embodiment relates to the use of the compound or the functional polymer according to the present invention where not all the azide groups are activated thermally at the same time . This can be achieved using a heating method which is spatially limited, for example using a focused IR-laser or other source of locally generated heat . This allows to generate patterns or gradients by sequential attachment o f di f ferent materials selected from the group of polymers , particles , nanoparticles , hydrogels , laminin, collagen, agarose , agarose beads or hydrophobic or hydrophilic coating materials .

Another embodiment relates to the use of the compound or the functional polymer according to the present invention to thermally introduce a lubricating function to a gliding surface for winter sport equipment such as skis , snowboards , crosscountry skis , snowshoes , and bobsleds . The use of the compound or the functional polymer described in the present invention enables the achievement of a sleek gliding surface that signi ficantly improves the performance of the mentioned equipment and facilitates ef fortless movement or sliding on snow or ice .

Another embodiment relates to the use of the compound or the functional polymer according to the present invention to thermally introduce an ice-phobic function on aircraft surfaces , wind turbines , temperature and humidity sensors , fridge and freezers , photovoltaic panels , and door handles . The use of the compound described in the present invention enables the achievement of providing ice-phobic anti freeze surfaces that signi ficantly improve the performance of the mentioned equipment in ice- forming conditions and prevents ice- formation or facilitates ef fortless removal of formed ice .

Another embodiment of the compound or the functional polymer of the present invention or a formulation containing the compound or the functional polymer of the present invention, is to simultaneously apply a coating to parts during inj ection moulding . Applying a coating formulation containing the compound or the functional polymer onto an inj ection moulding tool prior inj ection, for example by dipping, stamp coating or spraying, followed by inj ection moulding of the part at a temperature bigger than the activation temperature will lead to simultaneous crosslinking of the formulation and bondforming to the inj ection moulded part , producing a coated part in a one step process . Thanks to the low activation temperature of the compound or the functional polymer of the present invention, at typical inj ection moulding temperatures bigger than 100 ° C the time needed for crosslinking is fast enough to allow fast cycle times .

The compound or the functional polymer of the present invention, or a formulation containing the compound or the functional polymer of the present invention, can also be activated by exposure to a light source , i . e . is a photoactivatable crosslinking agent . The wavelength of the used light-source for activation should be in the range of 800 nm to 50 nm, more preferably in the range of 400 nm to 200 nm and most preferably in the range of 300 nm to 230 nm .

The compound or the functional polymer of the present invention can be applied to the surface for example by dipping, spraying or in the form of a paste .

Figures :

Figure 1 : Comparative figure of coating experiments of the formulations PAA-g [ 4 ] - ( Compound 1 / Compound 2 / Compound 3/PFPA) and with PVP as top-coating layer

Figure 2 : Comparative figure of coating experiments of the formulations PAA-g [ 4 ] -compound 2 and with PVP and PDMS as top-coating layers Figure 3: Comparative figure of coating experiments of the formulations ND-2 and ND-PFPA and with PVP as topcoating layer

Examples :

Synthesis of Compounds 1 to 3

4 -Ami no -phenol (1000 mg, 9.16 mmol) was dissolved in N,N- Dimethylformamide (10 ml) and the solution was stirred until complete dissolution. Methyl 4-bromobutyrate (1272.5 pL, 10.8 mmol) was added dropwise while stirring followed by the addition of potassium hydroxide (1028.3 mg, 18.33 mmol) . The solution was allowed to stir at 60°C in a heated oil bath for 4 hours. Then, water (30 ml) was added to quench the reaction and dissolve the inorganic reagents and the reaction was extracted with diethyl ether (2 x 30 ml) . The solvent of the extract was evaporated in vacuo (40°C) to yield a dark brown/red oil. The crude methyl-4- ( 4-amino-phenoxy ) butanoate is stored in the dark below room temperature (< -10°C) and used for the next synthetic step without further purification. IH NMR (400 MHz, DMSO_d6) : 5 (ppm) , 6.65-6.58 (m, 2H, Ph-H) , 6.51-6.46 (m, 2H, Ph-H) , 4.58 (s, 2H, NH₂) , 3.82 (t, 2H, 0- CH₂-) , 3.59 (s, 3H, CH₃) , 2.43 (t, 2H, -CH₂-COO-CH₃) , 1.89 (p, 2H, — CH₂— ) . 13C NMR (100 MHz, DMSO_d6) : 5 (ppm) , 173.10,

162.31, 149.72, 142.46, 115.38, 114.90, 66.95, 51.29, 30.01, 24.43.

Methyl -4- (4 -ami no -phenoxy) butanoate (1324.27 mg, 6.33 mmol) was dissolved in trifluoroacetic acid (13 ml) in an ice bath. Sodium nitrite (526.37 mg, 7.6 mmol) was added portion wise with stirring over 5 minutes. During this time the colour changed initially to dark green followed by a change to dark red after 5 minutes. After addition of sodium azide (493.44 mg, 7.6 mmol) , production of foam was observed, explained by the release of N₂ as expected from the reaction mechanism. The solution was allowed to stir for an additional Ih at room temperature. Then, water (30 ml) was added, and the reaction mixture was extracted with ethyl acetate (3 x 30 ml) . The combined organic fractions were washed well with water and saturated aqueous NaHCO₃. The extract was dried over anhydrous magnesium sulphate and the solvent evaporated in vacuo (40°C) to yield a dark red oil. This residue was purified by column chromatography (silica gel; eluent: hexane /diethyl ether, 3:1) to obtain the desired methyl-4- ( 4-azido-phenoxy ) butanoate as a red oil (yield: 189 mg, ~13%) . The product is stored in the dark below room temperature (< -10°C) .

IH NMR (400 MHz, DMSO_d6) : 5 (ppm) , 7.6-6.82 (m, 2H, Ph-H) , 6.99-6.93 (m, 2H, Ph-H) , 3.96 (t, 2H, O-CH₂-) , 3.59 (s, 3H, CH₃) , 2.46 (t, 2H, -CH₂-COO-CH₃) , 1.95 (p, 2H, -CH₂-) . 13C NMR (100 MHz, DMSO_d6) : 5 (ppm) , 172.99, 155.96, 131.46, 120.16, 115.90, 66.85, 51.32, 29.88, 24.15. Methyl-4- (4 -azido -phenoxy) butanoate (155 mg, 0.66 mmol) was dissolved in methanol (2 ml) . Sodium hydroxide (46.4 mg, 1.16 mmol) was dissolved in 0.5 ml water and added dropwise until pH~10. The mixture was let to react by stirring overnight at room temperature, capped and in dark. The following day, HC1 (2N) was added until pH~l. The solvent methanol was evaporated in vacuo (50°C) . Then, water (10 ml) was added, and the reaction mixture was extracted with chloroform (3 x 10 ml) . The extract was dried over anhydrous magnesium sulphate and the solvent evaporated in vacuo (50°C) to obtain the desired ( 4-azido-phenoxy ) butanoic acid as a red solid (yield: 97 mg, 67%) . The product is stored in the dark below room temperature (< - 10°C) to minimize its decomposition.

1H NMR (400 MHz, DMSO_d6) : 5 (ppm) , 7.06-7 (m, 2H, Ph-H) , 7- 6.94 (m, 2H, Ph-H) , 3.96 (t, 2H, O-CH₂-) , 2.37 (t, 2H, -CH₂- COO-CH3) , 1.91 (p, 2H, — CH₂— ) . 13C NMR (100 MHz, DMSO_d6) : 5 (ppm) , 174.05, 156.02, 131.42, 120.16, 115.90, 66.95, 30.05, 24.18.

(4-azido-phenoxy) butanoic acid (97 mg, 0.44 mmol) was dissolved in dichloromethane (1.5 ml) . N-Hydroxysuccinimide (50.5 mg, 0.44 mmol) was added. N, N ' -dicyclohexylcarbodiimide (92.3 mg, 0.45 mmol) after dissolved in 0.5 ml dichloromethane, was added dropwise to the above mixture. The mixture was let to react by stirring overnight at room temperature, capped and in dark. The following day, dicyclohexylurea produced during the overnight reaction was filtered out the mixture, and the filtrate solution was then filtered over celite. The solvent of the final filtrate solution was evaporated in vacuo (50°C) to obtain the desired (4-azido-phenoxy) butanoic acid - N- hydroxysuccinimide ester 1 as a red solid (yield: 138 mg, 100%) . Exposure to light or keeping the product at room temperature may results in degradation and, therefore, it should be stored in the dark below room temperature (< -10 °C) to minimize its decomposition.

1H NMR (400 MHz, DMSO_d6) : 5 (ppm) , 7.07-7.02 (m, 2H, Ph-H) , 7.02-6.97 (m, 2H, Ph-H) , 4.03 (t, 2H, O-CH₂-) , 2.84 (t, 2H, - CH₂-COO-) , 2.81 (s, 4H, C4H4NO2) , 2.06 (p, 2H, -CH₂-) . 13C NMR (100 MHz, DMSO_d6) : 5 (ppm) , 170.20, 168.73, 155.85, 131.59, 120.16, 115.96, 66.21, 27.04, 25.43, 23.98. IR (ATR diamond crystal) wavenumber (cur¹) : 825 (s) , 889 (s) , 944 (w) ,

1049/1068 (mbr) , 1196 (s, as stretch N3) , 1247 (s) , 1276 (w) , 1378 (w) , 1431 (w) , 1505 (s) , 1196 (s) , 1780 (w) , 1814 (w) , 2114 (s, as stretch N₃) and 2954 (b) .

4-Amino-3 , 5 -di fluorophenol (1000 mg, 6.89 mmol) was dissolved in N, N-Dimethylformamide (10 ml) and the solution was stirred until complete dissolution. Methyl 4-bromobutyrate (957 pL, 7.58 mmol) was added dropwise while stirring followed by the addition of potassium carbonate (1905 mg, 13.78 mmol) . The solution was allowed to stir at 85°C heated oil bath for 4 hours. Then, water (30 ml) was added to quench the reaction and dissolve the inorganic reagents and the reaction was extracted with ethyl acetate (2 x 30 ml) . The solvent of the extract was evaporated in vacuo (40°C) to yield a dark brown/red oil. The crude methyl-4- ( 4-amino-3 , 5- dif luorophenoxy) butanoate is stored in the dark below room temperature (< -10°C) and used for the next synthetic step without further purification.

IH NMR (400 MHz, DMSO_d6) : 5 (ppm) , 6.65-6.52 (m, 2H, Ph-H) , 4.6 (s, 2H, NH₂) , 3.87 (t, 2H, O-CH₂-) , 3.59 (s, 3H, CH₃) , 2.42 (t, 2H, -CH₂-COO-CH₃) , 1.9 (p, 2H, — CH₂— ) . 19F NMR (376.5 MHz, DMSO_d6) : 5 (ppm) , -129.7 (s, 2F) . 13C NMR (100 MHz, DMSO_d6) : 5 (ppm) , 172.96, 152.69 (d, J = 11.5 Hz) , 150.33 (d, J = 11.5 Hz) , 148.53 (t, J = 12.8 Hz) , 118.76 (t, J = 17.3 Hz) , 99.36 - 98.17 (m) , 67.31, 51.29, 29.83, 24.05.

Methyl-4- (4-amino-3 , 5-difluorophenoxy) butanoate (1690 mg, 6.89 mmol) was dissolved in trifluoroacetic acid (10 ml) in an ice bath. Sodium nitrite (570.6 mg, 8.27 mmol) was added portion wise with stirring over 5 minutes. During this time the colour changed initially to dark green followed by a change to dark red after 5 minutes. After addition of sodium azide (537 mg, 8.27 mmol) , production of foam was observed, explained by the release of N₂ as expected from the reaction mechanism. The solution was allowed to stir for an additional Ih at room temperature. Then, water (30 ml) was added, and the reaction mixture was extracted with diethyl ether (3 x 30 ml) , washed well with water and saturated aqueous NaHCO₃. The extract was dried over anhydrous magnesium sulphate and the solvent evaporated in vacuo (40°C) to yield dark red/brown oil. This residue was purified by column chromatography (silica gel; eluent: hexane /diethyl ether, 3:1) to obtain the desired methyl-4- ( 4-azido-3 , 5-di fluorophenoxy ) butanoate as a dark orange oil (yield: 700 mg, ~40%) . The product is stored in the dark below room temperature (< -10°C) .

1H NMR (400 MHz, DMSO_d6) : 5 (ppm) , 6.9-6.82 (m, 2H, Ph-H) , 3.99 (t, 2H, O-CH₂-) , 3.59 (s, 3H, CH₃) , 2.44 (t, 2H, -CH₂-COO- CH₃) , 1.94 (p, 2H, — CH₂— ) . 19F NMR (376.5 MHz, DMSO_d6) : 5

(ppm) , -122.4 (s, 2F) . 13C NMR (100 MHz, DMSO_d6) : 5 (ppm) , 172.86, 156.74 (d, J = 7.6 Hz) , 156.17 (t, J = 13.4 Hz) , 154.30 (d, J = 7.6 Hz) , 108.73 (t, J = 15.1 Hz) , 100.18 - 99.31 (m) , 67.72, 51.33, 29.69, 23.82.

Methyl -4- (4-azido-3 , 5 -di fluorophenoxy) butanoate (700 mg, 2.58 mmol) was dissolved in methanol (7 ml) . Sodium hydroxide (181.7 mg, 4.54 mmol) was dissolved in 2ml water and added dropwise until pH~10. The mixture was let to react by stirring overnight at room temperature, capped and in dark. The following day, HC1 (2N) was added until pH~l. The solvent methanol was evaporated in vacuo (50°C) . Then, water (8 ml) was added, and the reaction mixture was extracted with chloroform (3 x 10 ml) . The extract was dried over anhydrous magnesium sulphate and the solvent evaporated in vacuo (50°C) to obtain the desired (4-azido-3, 5-dif luorophenoxy) butanoic acid as a dark red solid (yield: 538 mg, 81%) . The product is stored in the dark below room temperature (< -10°C) to minimize its decomposition .

1H NMR (400 MHz, DMSO_d6) : 5 (ppm) , 12.15 (s, 1H, OH) , 6.92- 6.83 (m, 2H, Ph-H) , 3.99 (t, 2H, O-CH₂-) , 2.35 (t, 2H, -CH₂- COO-CH3) , 1.9 (p, 2H, — CH₂— ) . 19F NMR (376.5 MHz, DMSO_d6) : 5 (ppm) , -122.4 (s, 2F) . 13C NMR (100 MHz, DMSO_d6) : 5 (ppm) , 173.94, 156.75 (d, J = 7.6 Hz) , 156.23 (t, J = 13.4 Hz) , 154.30 (d, J = 7.6 Hz) , 108.7 (t, J = 15.1 Hz) , 101.12 - 98.80 (m) , 67.84, 29.87, 23.84.

(4-azido-3 , 5 -di fluorophenoxy) butanoic acid (530 mg, 2.06 mmol) was dissolved in dichloromethane (6 ml) . N- Hydroxysuccinimide (249 mg, 2.16 mmol) was added. N,N'- Dicyclohexylcarbodiimide (446.4 mg, 2.16 mmol) after dissolved in 2ml dichloromethane, was added dropwise to the above mixture. The mixture was let to react by stirring overnight at room temperature, capped and in dark. The following day, dicyclohexylurea produced during the overnight reaction was filtered out the mixture, and the filtrate solution was then filtered over celite. The solvent of the final filtrate solution was evaporated in vacuo (50°C) to obtain the desired (4-azido-3, 5-dif luorophenoxy) butanoic acid - N- hydroxysuccinimide ester 2 as a brown solid (yield: 704 mg, 96%) . Exposure to light or keeping the product at room temperature may results in degradation and, therefore, it should be stored in the dark below room temperature (< -10°C) to minimize its decomposition.

1H NMR (400 MHz, DMSO_d6) : 5 (ppm) , 6.96-6.86 (m, 2H, Ph-H) , 4.06 (t, 2H, O-CH₂-) , 2.82 (t, 2H, -CH₂-COO-) , 2.81 (s, 4H, C4H4NO2) , 2.05 (p, 2H, — CH₂— ) . 19F NMR (376.5 MHz, DMSO_d6) : 5 (ppm) , -122.3 (s, 2F) . 13C NMR (100 MHz, DMSO_d6) : 5 (ppm) , 170.23, 168.68, 156.71 (d, J = 7.7 Hz) , 156.04 (s) , 154.27 (d, J = 7.5 Hz) , 100.34 - 99.31 (m) , 67.15, 26.99, 25.44, 23.63. IR (ATR diamond crystal) wavenumber (cur¹) : 642 (w) , 809 (s) , 840 (s) , 875 (s) , 911 (w) , 1048/1073 (sbr) , 1159 (s) , 1208 (s) , 1302 (w) , 1361 (w) , 1508 (w) , 1579 (w) , 1639 (w) , 1735 (s) , 1783 (w) , 2100 (w) , 2135 (s, as stretch N₃) and 2937 (m) .

4 -Amino-2 , 3 , 5 , 6- tetrafluorophenol (700 mg, 3.87 mmol) was dissolved in N, N-Dimethylformamide (7 ml) and the solution was stirred until complete dissolution. Methyl 4-bromobutyrate (536.8 pL, 4.25 mmol) was added dropwise while stirring followed by the addition of potassium carbonate (1068.5 mg, 7.73 mmol) . The solution was allowed to stir at 100°C heated oil bath for 4 hours. Then, water (30 ml) was added to quench the reaction and dissolve the inorganic reagents and the reaction was extracted with diethyl ether (2 x 30 ml) . The solvent of the extract was evaporated in vacuo (40°C) to yield a dark brown oil. The crude methyl-4- (4-amino-2, 3, 5, 6- tetraf luorophenoxy ) butanoate is stored in the dark below room temperature (< -10°C) and used for the next synthetic step without further purification.

1H NMR (400 MHz, DMSO_d6) : 5 (ppm) , 5.64 (s, 2H, NH₂) , 4.01 (t, 2H, O-CH₂-) , 3.59 (s, 3H, CH₃) , 2.47 (t, 2H, -CH₂-COO-CH₃) , 1.9 (p, 2H, — CH₂— ) . 19F NMR (376.5 MHz, DMSO_d6) : 5 (ppm) , - 160.25 (d, 2F) , -162.4 (d, 2F) . 13C NMR (100 MHz, DMSO_d6) : 5 (ppm) , 172.85, 142.87 (m) , 140.51 (m) , 137.11 (m) , 134.77 (m) , 126.54 - 121.95 (m) , 74.31, 51.32, 29.40, 24.68.

Methyl-4- (4-amino-2 , 3 , 5 , 6 -tetrafluorophenoxy) butanoate (1087 mg, 3.87 mmol) was dissolved in trifluoroacetic acid (10 ml) in an ice bath. Sodium nitrite (320 mg, 4.64 mmol) was added portion wise with stirring over 5 minutes. During this time the colour changed initially to dark green followed by a change to dark red after 5 minutes. After addition of sodium azide (301.6 mg, 4.64 mmol) , production of foam was observed, explained by the release of N₂ as expected from the reaction mechanism. The solution was allowed to stir for an additional Ih at room temperature. Then, water (30 ml) was added, and the reaction mixture was extracted with diethyl ether (3 x 30 ml) , washed well with water and saturated aqueous NaHCO₃. The extract was dried over anhydrous magnesium sulphate and the solvent evaporated in vacuo (40°C) to yield a dark red oil. This residue was purified by column chromatography (silica gel; eluent: hexane /diethyl ether, 3:1) to obtain the desired methyl-4- (4-azido-2, 3, 5, 6- tetrafluorophenoxy) butanoate as an orange/red oil (yield: 737 mg, 62%) . The product is stored in the dark below room temperature (< -10°C) .

1H NMR (400 MHz, DMSO_d6) : 5 (ppm) , 4.2 (t, 2H, O-CH₂-) , 3.6 (s, 3H, CH₃) , 2.48 (t, 2H, -CH₂-COO-CH₃) , 1.95 (p, 2H, -CH₂-) . 19F NMR (376.5 MHz, DMSO_d6) : 5 (ppm) , -153.35 (d, 2F) , -157.61 (d, 2F) .

Methyl-4- (4-azido-2 , 3 , 5 , 6 -tetrafluorophenoxy) butanoate (737 mg, 2.4 mmol) was dissolved in methanol (7 ml) . Sodium hydroxide (168.9 mg, 4.22 mmol) was dissolved in 1 ml water and added dropwise until pH~10. The mixture was let to react by stirring overnight at room temperature, capped and in dark. The following day, HC1 (2N) was added until pH~l. The solvent methanol was evaporated in vacuo (50°C) . Then, water (10 ml) was added, and the reaction mixture was extracted with chloroform (3 x 10 ml) . The extract was dried over anhydrous magnesium sulphate and the solvent evaporated in vacuo (50°C) to obtain the desired (4-azido-2, 3, 5, 6-tetraf luorophenoxy ) butanoic acid as a yellow/orange solid (yield: 690 mg, 98%) . The product is stored in the dark below room temperature (< - 10°C) to minimize its decomposition.

1H NMR (400 MHz, DMSO_d6) : 5 (ppm) , 12.16 (s, 1H, OH) , 4.2 (t, 2H, O-CH₂-) , 2.38 (t, 2H, -CH₂-COO-CH₃) , 1.91 (p, 2H, -CH₂-) . 19F NMR (376.5 MHz, DMSO_d6) : 5 (ppm) , -153.32 (d, 2F) , -157.53

(d, 2F) .

(4-azido-2 , 3 , 5 , 6 -tetrafluorophenoxy) butanoic acid (680 mg, 2.32 mmol) was dissolved in dichloromethane (6 ml) . N- Hydroxysuccinimide (267.2 mg, 2.32 mmol) was added. N,N'- Dicyclohexylcarbodiimide (488.7 mg, 2.37 mmol) after dissolved in 1 ml dichloromethane, was added dropwise to the mixture. The mixture was let to react by stirring overnight at room temperature, capped and in dark. The following day, dicyclohexylurea produced during the overnight reaction was filtered out the mixture, and the filtrate solution was then filtered over celite. The solvent of the final filtrate solution was evaporated in vacuo (50°C) to obtain the desired (4-azido-2, 3, 5, 6-tetraf luorophenoxy ) butanoic acid - N- hydroxysuccinimide ester 3 as a brown solid (yield: 862 mg, 96%) . Exposure to light or keeping the product at room temperature may results in degradation and, therefore, it should be stored in the dark below room temperature (< -10°C) to minimize its decomposition.

1H NMR (400 MHz, DMSO_d6) : 5 (ppm) , 4.26 (t, 2H, O-CH₂-) , 2.86 (t, 2H, -CH₂-COO-) , 2.81 (s, 4H, C₄H₄NO₂) , 2.06 (p, 2H, -CH₂-) . 19F NMR (376.5 MHz, DMSO_d6) : 5 (ppm) , -153.3 (d, 2F) , -157.39 (d, 2F) . 13C NMR (100 MHz, DMSO_d6) : 5 (ppm) , 170.20, 168.73, 155.85, 131.59, 120.16, 115.96, 66.21, 27.04, 25.43, 23.98. IR (ATR diamond crystal) wavenumber (cur¹) : 897 (w) , 966 (w) , 1000 (w) , 1075 (w) , 1107 (w) , 1207 (s) , 1314 (w) , 1374 (w) 1498 (s) , 1728 (s) , 1781 (w) , 1808 (w) , 2129 (s, as stretch N₃) and 2954 (m) .

Thermal characterization of molecules

Thermal characterization by Thermogravimetric analysis (TGA)

Thermogravimetric analysis (TGA) is a method of thermal analysis in which the mass of a sample is measured over time as the temperature increases. This measurement provides information about physical and chemical phenomena.

This technique is used to determine the reactivity of the aryl azides upon thermal decomposition and to specify the temperature that this occurs. The results indicate that all synthesized molecules exhibit thermal decomposition taking place at lower temperatures when compared to 4-azido-2, 3, 5, 6- tetraf luorobenzoic acid-NHS ester (PFPA-NHS) , in the order of Compound 2 < Compound 3 < Compound 1 < PFPA-NHS .

Surface characterization

Example 1: Preparation of polyallylamine-graf ted-synthesized molecule (1/2/3) ( PAA-g-1/2/3 ) stock solutions with grafting ratio g of about 4: 3 mg (0.032 mmol) of PAAm-HCl and 7.53 mg K₂CO₃ were dissolved in 598.5 ml of water. A solution of 2.55/2.84/3.13 mg of synthesized molecule in 970.9 pl Ethanol were added and the mixture was vigorously stirred overnight.

Example 2: Preparation of composition comprising of PAA-g- 1/2/3 with a grafting ratio of about 4

1.4/1.29/1.2 ml of 1/2/3 of the stock solutions respectively, described in example 1 was added to 28.6/28.71/28.8 ml of a 1:2 mixture of ethanol and buffered water (HEPES (2— (4— (2— hydroxyethyl ) -1-piperazinyl ) -ethanesulfonic acid) 10 mM, pH 7.4) .

Example 3: Use of a composition comprising PAAm-g-1/2/3 as an adhesion promoter for a hydrophilic non-fouling coating on silicon substrates with a natural oxide layer

Several silicon wafers with a natural oxide layer (10x9 mm, 5.65 nm thick layer of SiO₂) were cleaned in an ultrasonic bath of toluene (20 min) and subsequently 2-propanol (20 min) and then dried in a nitrogen stream. The surfaces were then plasma treated in an oxygen atmosphere for 4 minutes.

The treated samples were immersed in the composition comprising of PAAm-g-1/2/3 respectively (example 2, g =4) for 30 minutes at room temperature and then rinsed extensively with a 1:2 mixture of ethanol and buffered water.

A polyvinylpyrrolidone (PVP) solution (1300kDa, 25 mg/ml in chloroform) was spin-coated onto the treated surface.

Activation by thermolysis (30 min, at different temperatures) was performed. The modified surfaces were then rinsed in an ultrasonic bath of chloroform (5 min) and subsequently in ultrapure water (5 min) and then were immersed overnight in ultrapure water until complete removal of the non-bound polymer chains . The layer thickness was measured after each of the above steps, using a variable angle spectroscopic ellipsometer (M-2000F ESM-300, J. A. Wollam Inc., Lincoln, USA) and the data was evaluated using the software CompleteEASE (J. A. Wollam Inc., Lincoln, USA) .

Table 1: Layer thickness after immersion in the composition PAAm-g [4] -1/2/3.

The more of the azide group (-N₃) material is reacted at a certain temperature during the 30 minutes thermolysis step, the higher the PVP layer thickness will be. An increasing number of nitrene radicals is generated and will attack carbon bonds, forming increasing number of covalent bonds with the top-coating comprising of PVP (see Figure 1 showing coating experiments of the formulations PAA-g [ 4 ]- ( compound 1/ compound 2/ compound 3/PFPA) and with PVP as top-coating layer) . Example 4: Use of a composition comprising PAAm-g-2 as an adhesion promoter, comparing the binding capability of a hydrophilic and a hydrophobic coating respectively, on silicon substrates with a natural oxide layer

Several silicon wafers with a natural oxide layer (10x9 mm, 6.33 nm thick layer of SiO₂) were cleaned in an ultrasonic bath of toluene (20 min) and subsequently 2-propanol (20 min) and then dried in a nitrogen stream. The surfaces were then plasma treated in an oxygen atmosphere for 4 minutes.

The treated samples were immersed in the composition comprising of PAAm-g-2 (example 2, g =4) for 30 minutes at room temperature and then rinsed extensively with a 1:2 mixture of ethanol and buffered water.

A polyvinylpyrrolidone (PVP) solution (1300kDa, 25 mg/ml in chloroform) was spin-coated onto some of the treated surface.

A Polydimethylsiloxane (PDMS) solution (330kDa, 25mg/ml in heptane) was spin-coated onto some of the treated surface.

Activation by UV-C light (254nm for 2 min) was performed. The PVP modified surfaces were then rinsed in an ultrasonic bath of chloroform (5 min) and subsequently in ultrapure water (5 min) and then were immersed overnight in ultrapure water until complete removal of the non-bound polymer chains. The PDMS modified surfaces were then rinsed in an ultrasonic bath of heptane (5 min) twice and then were immersed overnight in heptane until complete removal of the non-bound polymer chains.

The layer thickness was measured after each of the above steps, using a variable angle spectroscopic ellipsometer (M-2000F ESM-300, J. A. Wollam Inc., Lincoln, USA) and the data was evaluated using the software CompleteEASE (J. A. Wollam Inc., Lincoln, USA) .

Table 2: Layer thickness after immersion in the composition PAAm-g[4]-2 and after activation of the coated PVP and PDMS .

It is clear that effective binding of the adhesion promoter comprising PAAm-g-2, occurs both when activated with temperature (example 3) or UV-C light and also with hydrophilic (PVP) and hydrophobic (PDMS) top-coatings. The energy given, should be enough to photolyze the majority of the azide groups (-N₃) and the generated nitrene radicals will attack carbon bonds, forming increasing number of covalent bonds with the top-coating comprising of PVP or PDMS (see Figure 2 showing coating experiments of the formulations PAA-g [ 4 ] -compound 2 and with PVP and PDMS as top-coating layers) . The difference on the thickness value of the attached PVP or PDMS layer, can be explained by the difference on the molecular weight of the polymers and the molecular structure.

Example 5: Preparation of polyethylenimine-graf ted-synthesized molecule 1/2/3 ( PEI-g-1/2/3 ) stock solution with grafting ratio g of about 6

65/59.7/54.22 mg of PEI stock solution (100 mg/ml) were weighed in a vial. 8/10/10 mg (0.0256/0.0251/0.0282 mmol) of 1/2/3 were dissolved in 1.13/1.27/1.15 ml ethanol. The mixture was then added dropwise to the PEI while vigorously stirring and was let to stir overnight.

Example 6: Preparation of composition comprising of PEI-g-

1/2/3 with a grafting ratio of about 6 and PVP in ethanol

0.1 ml of PVP solution in ethanol (200 mg/ml) was mixed with 0.41/0.38/0.36 ml of PEI-g-l/2/3_stock solutions described in example 4, in a 4:1 ratio and ethanol was added to a final volume of 1 ml.

Example 7: Use of a composition described in example 5 as a crosslinking agent between PEI-g-l/2/3/PFPA and PVP on contact lens cartridge

Several polymeric PP contact lens cartridges were used as received. 250pl of solutions from the compositions described in the example 5 were used to fill completely the volume area of the contact lens cartridge.

The samples were left to dry overnight, and the system was activated by thermolysis (30 min, at different temperatures) . When the system gets crosslinked, a film should be deposited on the surface.

The modified contact lens cartridges were then filled with water. If the system was crosslinked, water should be absorbed forming a hydrogel, if not, traces left on the surface would be dissolved.

Table 3: Gel formation results of example 6 at different temperatures

n/a: not tested

Example 8: Preparation of nitrodopamine-synthesized molecule

2 (ND-2) one step synthesis

ND-2

35 mg of Nitrodopamine (0.12 mmol) were dissolved in 1 ml N,N- Dimethylformamide . 54.5 pl N-Methylmorpholine (0.49 mmol) and 52.7 mg of synthesized molecule 2 (0.15 mmol) were added. The mixture was let to react by stirring overnight at room temperature, capped and in dark. Followed a thorough work up procedure and freeze drying, resulting the desired synthesized material ND-2 (52mg, 100% yield) .

Example 9: Use of a composition comprising nitrodopamine - synthesized molecule 2 (ND-2) as an adhesion promoter for a hydrophilic non-fouling coating on titanium substrates with a natural oxide layer

A solution comprising of 0.7 mg ND-2 (0.1 mg/ml) in 7 ml of a 1:1 mixture of ethanol and ultrapure water was prepared. ND-2 was dissolved in the appropriate volume of ethanol and then ultrapure water was added to reach the final volume.

Several titanium wafers with a natural oxide layer (10x9 mm, 18.23 nm thick layer of TiO₂) were cleaned in an ultrasonic bath of toluene (20 min) and subsequently 2-propanol (20 min) and then dried in a nitrogen stream. The surfaces were then plasma treated in an oxygen atmosphere for 4 minutes.

The treated samples were immersed in the composition comprising of ND-2 (Example 8) for four hours at room temperature and then rinsed extensively with ethanol and followed by ultrapure water .

A PVP solution (1300kDa, 25 mg/ml in chloroform) was spincoated onto the treated surface.

Activation by thermolysis (30 min, at different temperatures) was performed. The modified surfaces were then rinsed by immersion in ethanol overnight, until complete removal of the non-bound polymer chains, and then dried over a nitrogen stream.

The layer thickness was measured after each of the above steps, using a variable angle spectroscopic ellipsometer (M-2000F ESM-300, J. A. Wollam Inc., Lincoln, USA) and the data was evaluated using the software CompleteEASE (J. A. Wollam Inc., Lincoln, USA) . Figure 3 shows the comparative data of coating experiments of the formulations ND-2 and ND-PFPA and with PVP as top-coating layer. In case of ND-2, a thicker PVP film was formed already at 80°C, while for ND-PFPA even at 120°C the PVP film thickness did not reach the thickness obtained for

ND-2.

Example 10: Synthesis of compound 4

8-Amino-l , 7-dioxa-2 , 3 , 5 , 6-tetrahydro-s-indacen-4-ol (1000 mg, 5.17 mmol) was dissolved in N, N-Dimethylformamide (10 ml) and the solution was stirred until complete dissolution. Methyl 4- bromobutyrate (717 pL, 5.68 mmol) was added dropwise while stirring followed by the addition of potassium carbonate (1570 mg, 11.36 mmol) . The solution was allowed to stir at 85°C heated oil bath for 4 hours. Then, water (30 ml) was added to quench the reaction and dissolve the inorganic reagents and the reaction was extracted with ethyl acetate (2 x 30 ml) . The solvent of the extract was evaporated in vacuo (40°C) to yield a dark oil. The crude methyl 4- ( 8-amino-l , 7-dioxa-2 , 3 , 5, 6- tetrahydro-s-indacen-4-yloxy) butyrate is stored in the dark below room temperature (< -10°C) and used for the next synthetic step without further purification.

1H NMR (400 MHz, DMSO_d6) : 5 (ppm) , 5.63 (s, 2H, NH2 ) , 4.14 (t, 4H, -O-CH₂- ring) , 3.55 (t, 2H, -O-CH₂- chain) , 3.44 (s, 3H,-O-CH₃) , 2.95 (t, -O-CH₂-CH₂- ring) , 2.14 (t, 2H, -CH₂-COO- CH₃) , 1.64 (p, 2H, — CH₂— ) .

Methyl 4- (8-amino-l , 7-dioxa-2 ,3,5, 6-tetrahydro-s-indacen-4- yl oxy) butyrate (1516 mg, 5.17 mmol) was dissolved in trifluoroacetic acid (10 ml) in an ice bath. Sodium nitrite (428.0 mg, 6.2 mmol) was added portion wise with stirring over 5 minutes. After addition of sodium azide (403 mg, 6.2 mmol) , production of foam was observed, explained by the release of N₂ as expected from the reaction mechanism. The solution was allowed to stir for an additional Ih at room temperature. Then, water (30 ml) was added, and the reaction mixture was extracted with diethyl ether (3 x 30 ml) , washed well with water and saturated aqueous NaHCO₃. The extract was dried over anhydrous magnesium sulphate and the solvent evaporated in vacuo (40°C) to yield dark oil. This residue was purified by plug filtration over silica gel to obtain the desired methyl 4- (8-azido-l,7- dioxa-2, 3, 5, 6-tetrahydro-s-indacen-4-yloxy) butyrate as a dark oil. The product is stored in the dark below room temperature (< -10°C) .

IH NMR (400 MHz, DMSO_d6) : 5 (ppm) , 4.25 (t, 4H, -O-CH₂- ring) , 3.67 (t, 2H, -O-CH₂- chain) , 3.56 (s, 3H,-O-CH₃) , 3.01 (t, -0- CH₂-CH₂- ring) , 2.16 (t, 2H, -CH₂-COO-CH₃) , 1.65 (p, 2H, -CH₂- Methyl 4- (8-azido-l , 7-dioxa-2 ,3,5, 6-tetrahydro-s-indacen-4- yl oxy) butyrate (900 mg, 2.81 mmol) was dissolved in methanol (9 ml) . Sodium hydroxide (224 mg, 5.62 mmol) was dissolved in 2ml water and added dropwise until pH~10. The mixture was let to react by stirring overnight at room temperature, capped and in dark. The following day, HC1 (2N) was added until pH~l. Methanol was evaporated in vacuo (50°C) . Then, water (8 ml) was added, and the reaction mixture was extracted with chloroform (3 x 10 ml) . The extract was dried over anhydrous magnesium sulphate and the solvent evaporated in vacuo (40°C) to obtain the desired 4- ( 8-Azido-l , 7-dioxa-2 , 3 , 5, 6-tetrahydro- s-indacen-4-yloxy) butyric acid as a dark solid. The product is stored in the dark below room temperature (< -10 °C) to minimize its decomposition.

1H NMR (400 MHz, DMSO_d6) : 5 (ppm) , 11.53 (s, 1H, OH) , 4.23 (t, 4H, -O-CH₂- ring) , 3.69 (t, 2H, -O-CH₂- chain) , 3.55 (s, 3H,-O-CH₃) , 3.02 (t, -O-CH₂-CH₂- ring) , 2.24 (t, 2H, -CH₂-COOH) , 1.64 (p, 2H, - CH₂- ) .

4- (8-Azido-l , 7-dioxa-2 ,3,5, 6-tetrahydro-s-indacen-4- yloxy) butyric acid (500 mg, 1.63 mmol) was dissolved in dichloromethane (5 ml) . N-hydroxy succinimide (195 mg, 1.69 mmol) was added. N, N ' -dicyclohexyl carbodiimide (348.7 mg, 1.69 mmol) after dissolved in 2ml dichloromethane, was added dropwise to the above mixture. The mixture was let to react by stirring overnight at room temperature, capped and in dark. The following day, dicyclohexylurea produced during the overnight reaction was filtered off, and the solution was then filtered a second time over celite. The solvent of the final filtrate solution was evaporated in vacuo (40°C) to obtain the desired 4- (8-Azido-l, 7-dioxa-2, 3, 5, 6-tetrahydro-s-indacen-4- yloxy) butyric acid- N-hydroxy succinimide ester 4 as a dark solid. Exposure to light or keeping the product at room temperature may results in degradation and, therefore, it should be stored in the dark below room temperature (< -10°C) to minimize its decomposition.

1H NMR (400 MHz, DMSO_d6) : 5 (ppm) , 4.20 (t, 4H, -O-CH₂- ring) , 3.67 (t, 2H, -O-CH₂- chain) , 3.53 (s, 3H,-O-CH₃) , 3.00 (t, -0- CH₂-CH₂- ring) , 2.79 (s, 4H, NHS) 2.24 (t, 2H, -CH₂-COO) , 1.64 (p, 2H, -CH₂-) .

Example 11: Synthesis of compound 5

Starting from 8-Amino-l , 7-dioxa-s-indacen-4-ol, following the same protocol as for compound 4, 4- ( 8-Azido-l , 7-dioxa-s- indacen-4-yloxy ) butyric acid- N-hydroxy succinimide ester 5 was synthesized.

Example 12: Synthesis of compound 6

Starting from 7-amino-6-fluoro-2 , 3-dihydro-l-benzofuran-4-ol following the same protocol as for compound 4, 4- ( 7-Azido- 6- f luoro-2 , 3-dihydro-l-benzofuran-4-yloxy) butyric acid- N- hydroxysuccinimide ester 6 was synthesized.

Example 13: Synthesis of compound 7

Starting from 7-Amino-6-fluoro-l-benzofuran-4-ol following the same protocol as for compound 4, 4- (7-Azido-6-fluoro-l- benzofuran-4-yloxy ) butyric acid- N-hydroxy succinimide ester 7 was synthesized.

Example 14 : Conversion of N-hydroxy succinimide ester to an amine compound 8 :

(4-azido-3 , 5 -di fluorophenoxy) butanoic acid - N- hydroxysuccinimide ester 2 (300.61 mg, 0.85 mmol) was dissolved in 3.5 mL DMF. N-Boc- 1 , 6-hexanediamine hydrochloride (215.91mg, 0.85 mmol) was added, followed by the addition of triethylamine (117.6 pL, 0.85 mmol) . The reaction mixture was warmed to 40 °C and stirred for 16h in the dark. A white solid precipitated and the mixture was filtered and vacuum evaporated to dryness at 43°C. The crude 6- [ 4- ( 4-Azido-3 , 5- difluorophenoxy) butyrylamino] hexyl 2-methyl-2- propanecarbamate was dissolved in dichloromethane (3 mL) and 4 molar hydrochloric acid in dioxane (3.5 mL, 14 mmol) was added. The mixture was stirred for 15 min and vacuum evaporated to dryness. The material was dissolved in water (2.5 mL) , frozen and lyophilized to obtain 468 mg of N- 6-Aminohexyl 4- (4-azido-3, 5-dif luorophenoxy) butyramide hydrochloride salt 8 as a brown-red solid. Example 15: Synthesis of compounds 9, 10, 11 and 12

Compound 9: ( N- 6-Aminohexyl4- ( 8-azido-l , 7-dioxa-s-indacen-4- yloxy) butyramide hydrochloride salt) , Compound 10: ( N- 6-Aminohexyl4- ( 8-azido-l , 7-dioxa-2 , 3 , 5, 6- tetrahydro-s-indacen-4-yloxy) butyramide hydrochloride salt) , Compound 11: ( -6-Aminohexyl4- (7-azido-6-fluoro-l-benzofuran- 4-yloxy) butyramide hydrochloride salt) , and

Compound 12: ( -6-Aminohexyl4- (7-azido-6-fluoro-2, 3-dihydro- l-benzofuran-4-yloxy) butyramide hydrochloride salt) were prepared following the same procedure as for 8 starting from the corresponding N-hydroxy succinimide ester.

As for the amine compound 8, the following functionalities were obtained by conversion of the corresponding NHS ester with a correctly functionalized amine: Hydroxy from amino- alkyl-hydroxide, thiol from amino-alkyl-thiol , maleimide from amino-alkyl-maleimide and alkyne from propargylamine. Example 16: Conversion of N-hydroxy succinimide ester to an alkoxysilane compound 13:

(4-azido-3 , 5 -di fluorophenoxy) butanoic acid - N-hydroxy succinimide ester 2 (300.61 mg, 0.85 mmol) was dissolved in anhydrous dichloromethane (10 mL) in a dry inert nitrogen atmosphere. Aminopropyl triethoxy silane (APTES) (188 mg, 0.85 mmol) was added and the mixture stirred at room temperature for 16h. The solvent is evaporated, the crude material dissolved in anhydrous toluene (33.4 mL) and filtered to obtain a red toluene solution of N-3- ( Triethoxysilyl ) propyl4- ( 4- azido-3, 5-dif luorophenoxy) but yr amide 13.

Example 17 : Synthesis of compound 14

4-Amino-3 , 5-difluorophenol (1000 mg, 6.89 mmol) was dissolved in N, N-Dimethylformamide (10 ml) and the solution was stirred until complete dissolution. 2- ( 3-Bromopropyl ) -1 , 3- isoindolinedione (2034 mg, 7.59 mmol) was added followed by the addition of potassium carbonate (2095 mg, 15.18 mmol) . The solution was allowed to stir at 85°C heated oil bath overnight. Then, water (30 ml) was added to quench the reaction and dissolve the inorganic reagents and the reaction was extracted with dichloromethane (2 x 30 ml) . The solvent of the extract was evaporated in vacuo (50°C) to yield a dark solid. The crude 2- [3- (4-Amino-3, 5-dif luorophenoxy) propyl] -1, 3- isoindolinedione is stored in the dark below room temperature (< - 10°C) and used for the next synthetic step without further purification .

1H NMR (400 MHz, CDC1₃) : 5 (ppm) , 7.38 (m, 4H, phtalimide) , 6.19 (s, 2H, arom) , 3.44 (t, 4H, -O-CH₂- CH₂-) , 3.34 (p, 2H, O-CH2-CH₂-CH₂-) , 1.24 (t, 2H O-CH2-CH₂-CH₂- ) .

2- [3- (4-Amino-3 , 5 -di fluorophenoxy) propyl ] -1 , 3- isoindolinedione (927 mg, 2.79 mmol) was dissolved in trifluoroacetic acid (10 ml) in an ice bath. Sodium nitrite (231.2 mg, 3.3 mmol) was added portion wise with stirring over 5 minutes. After addition of sodium azide (214 mg, 3.3 mmol) , production of foam was observed, explained by the release of N₂ as expected from the reaction mechanism. The solution was allowed to stir for an additional Ih at room temperature. Then, water (30 ml) was added, and the reaction mixture was extracted dichloromethane (3 x 30 ml) , washed well with water and saturated aqueous NaHCO₃. The extract was dried over anhydrous magnesium sulphate and the solvent evaporated in vacuo (40°C) to yield a dark solid. This residue was recrystallized to obtain the desired 2- [3- (4-Azido-3, 5-dif luorophenoxy) propyl] - 1 , 3-isoindolinedione . The product is stored in the dark below room temperature (< -10°C) .

IH NMR (400 MHz, CDC1₃) : 5 (ppm) , 7.40 (m, 4H, phtalimide) , 6.43 (s, 2H, arom) , 3.44 (t, 4H, -O-CH₂- CH₂-) , 3.34 (p, 2H, O-CH2-CH₂-CH₂-) , 1.24 (t, 2H O-CH2-CH₂-CH₂- ) .

2- [3- (4-Azido-3 , 5 -di fluorophenoxy) propyl ] -1 , 3- isoindolinedione (716 mg, 2.0 mmol) was dissolved in methanolic hydrazine hydrate (22 mL, 0.3M, 6.6 mmol) and stirred for 30 minutes at room temperature. Hydrochloric acid (9 mL, 5%) was added and the mixture stirred for additional 18h at room temperature. Water (30 mL) was added, acidified (pH<2) and the solution extracted with diethyl ether. The organic phase was discarded and the aqueous phase was basified with solid KOH (pH>10) . This basic aqueous phase is extracted with dichloromethane, and the combined dichloromethane fractions, dried with MgSO₄ and evaporated to dryness to obtain the desired 3- (4-Azido-3, 5-dif luorophenoxy) -1-propanamine 14 as a dark oil. The product is stored in the dark below room temperature (< -10°C) to minimize its decomposition. 1H NMR (400 MHz, CDC1₃) : 5 (ppm) , 6.40 (s, 2H, arom) , 3.54 (t, 4H, -O-CH2- CH₂-) , 2.62 (broad s, -NH₂) , 2.54 (t, 2H O-CH₂-CH₂- CH₂-NH₂) , 1.54 (p, 2H, O-CH₂-CH₂-CH₂-) . Example 18: Synthesis of compounds 15, 16, 17 and 18

Compound 15 : (3- (8-Azido-l, 7-dioxa-s-indacen-4-yloxy) -1- propanamine) ,

Compound 16 : (3- (8-Azido-l, 7-dioxa-2, 3, 5, 6-tetrahydro-s- indacen-4-yloxy ) -1-propanamine) ,

Compound 17: (3- (7-Azido-6-fluoro-l-benzofuran-4-yloxy) -1- propanamine) and

Compound 18: (3- (7-azido-6-fluoro-2, 3-dihydro-l-benzofuran-4- yloxy) propan-l-amine) were prepared following the same procedure as for compound 14.

Claims

Claims

1. Compound of formula I

wherein

R₂ is selected from the group consisting of B₂ and Y₂,

R₂ is selected from the group consisting of B₂ and Y₂,

R₃ is selected from the group consisting of B₃ and Y₃,

R₄ is selected from the group consisting of B₄ and Y₄, and

B₂ and B₃ are independently selected from the group consisting of fluoro, chloro and bromo,

B₂ and B₄ are independently from the group consisting of hydrogen and fluoro, and if R₂ is Y_lf R₂ is Y₂, Y₂ being selected from the group consisting of oxygen, sulfur and selenium, and Y₂ is - CH₂CH₂- or -CH=CH- and forms together with Y₂ a 5 membered ring system, if R₃ is Y_3f R₄ is Y₄, Y₃ being selected from the group consisting of oxygen, sulfur and selenium, and Y₄ is - CH₂CH₂- or -CH=CH- and forms together with Y₃ a 5 membered ring system,

X is selected from the group consisting of D- (Lp-A)_mH₂_ m, wherein D is selected from the group consisting of S p is 1 and m is 1, L is a linker group selected from the group consisting of an alkylene chain having 1 to 18 carbon atoms, an alkenyl chain having 1 to 18 carbon atoms, an alkynyl chain having 1 to 18 carbon atoms, an oligoethylene oxide having 2 to 10 repeating units, an oligo-Ch-Cs- alkyloxazoline having 2 to 10 repeating units, an oligo- Ch-Cs-alkyloxazine having 2 to 10 repeating units, peptide chains, polydimethylsiloxane, perfluoroethers, perfluoroalkyls, polyisobutene, polyethylene glycol, poly- dimethyl acrylamide, polyvinylpyrrolidone, polyalkyloxazolines , polyalkyloxazines, dextran, carboxymethyl dextran, poly (N-iso-propylacrylamide ) , poly (N-hydroxyethylacrylamide, poly ( 2-hydroxyethyl methacrylate) , poly-hydroxypropyl-methacrylate ) , poly- (methacryloyloxylethyl phosphorylcholine) , poly- ( sulfobetaine methacrylate) , polyalkylene residues having more than 20 carbon atoms, DNA fragments and poly- ( sulfobetaine acrylamide) ,

A is a reactive group selected from the group consisting of an active ester, amine, hydroxy, thiol, alkoxy silane, chloro silane, carboxylate, maleimide, vinylsulfone, acrylamide, bromide, iodide, iodoacetate, bromoacetate, azide, arylazide, alkyne, transcyclooctene (TCO) , tetrazine, methyltetrazine, phenyltetrazine, ring-strained alkyne, bicyclononyne (BCN) , dibenzocyclooctyne (DBCO) , biotin, 2-nitrobenzyl alcohol, 5-azido-2-nitrobenzoic acid, isothiocyanate, isocyanate, benzophenone, aldehyde, dithiopyridine, methanethiosulfonate, 3-phenyl-3- (trifluoromethyl) -3H- diazirine, hydrazide, tert-butylcarbazat , phosphoramidite , epoxide , chlorotriazine , and f luoro triaz ine .

2 . Compound according to claim 1 , wherein the compound of formula I is compound I I

3 . Compound according to any of the preceding claims , wherein D is

0 and p is 1 .

Compound according to any of the preceding claims , wherein the compound of formula I is selected from the

5. Compound according to any of the preceding claims, wherein the compound of formula I is selected from the group consisting of compounds IV, V and VI

6. Compound according to any of the preceding claims wherein

B₂ and/or B₃ are fluoro, or B₂ and/or B₄ are hydrogen.

7. Compound of formula X

wherein D, L, R₂, R₂, R3 and R₄ have the same definition as in any of claims 1 to 6,

G is formed by reaction of the group A as defined in any of claims 1 to 6 with E₂, E₂, E₃, or E₄, wherein E₂, E₂, E₃ and E₄ are selected from the group consisting of E_x is selected from the group consisting of 1,4- diaminobutane, 1 , 5-diaminopentane, thermospermine, caldopentamine, caldohexamine, 1 , 2-diaminocyclohexane, 4, 4 '-diaminodiphenylsulfone, 1, 5-diamino-2- methylpentane, diethylentriamine, hexamethylendiamine, isophorondi amine, triethylentetramine, trimethylhexamethylendiamin, spermidine, spermin, tris ( 2-aminoethyl ) amine, tetrakis ( 2-aminoethyl ) amine, tris ( 3-aminopropyl ) amine, tetrakis ( 3-aminopropyl ) ammonium, amine terminated dendrimers, amine functionalized silicones, polyallylamine, polyethyleneimine, polylysine or polyornithine,

E₂ is selected from the group consisting citric acid, succinic acid, glutamic acid, tartaric acid, malonic acid, maleic acid, poly (acrylic acid) , poly ( aspartic acid) , poly (maleic acid-alt-ethylene) , poly (nitrilotriacetic acid) , poly(citric acid) or esters thereof,

E₃ is selected from the group consisting of alkoxy silanes, chloro silanes, catechols, phosphates, phosphonates, anacheline, mimosine derivatives, gallols, thiols, N- heterocyclic carbenes, perfluorophenyl azides, benozophenone, di aryl di azomethane, aryltrif luoromethyl-diazomethane, organoboron, alpha lipoic acid, acrylamide, acrylate and epoxide, and

E₄ is selected from the group consisting of a fluorescent marker, a perfluorinated alkyl, a biotin, NTA and a short peptide and q is 1 to 1000.

8. Compound according to any of the preceding claims, wherein either A or G comprises a terminal amino group .

9 . Functional polymer comprising a polymer backbone and a plurality of side chains , characteri zed in that at least a part of said side chains comprise compounds according to any of claims 1 to 8 .

10 . Functional polymer according to claim 9 , wherein all side chains are copolymers according to any of claims 1 to 8 .

11 . Functional polymer according to claim 9 , wherein said functional polymer comprises at least two di f ferent types of side chains , and wherein at least one type of side chain is a compound according to any of claims 1 to 8 .

12 . Functional polymer according to claim 11 , wherein said functional polymer comprises a further type of side chain H which is intended to reversibly bind to a substrate or has a coating function, and H is selected from the group consisting of a short chain side chain H₂ having a linear or branched, substituted or unsubstituted C₂ to C₂₂ alkylene group which optionally comprises heteroatoms selected from the group consisting of oxygen and nitrogen, and which carries at least one functional end or side group KI selected from the group consisting of amines , carboxy, poly (propylene sul fide ) , and thioethers ; a side chain H₂ having a long chain H₂ comprising more than 15 carbon or silicium atoms in the chain, wherein said long chain H₂ is selected from the group consisting of polydimethylsiloxane, perfluoroethers, perfluoroalkyls, polyisobutene, polyethylene glycol, polydimethyl acrylamide, polyvinylpyrrolidone, polyalkyloxazolines , polyalkyloxazines, dextran, carboxymethyl dextran, poly (N-isopropylacrylamide ) , poly (N-hydroxyethylacrylamide, poly (2-hydroxyethyl methacrylate) , poly-hydroxypropylmethacrylate) , poly- (methacryloyloxylethyl phosphorylcholine) , poly- ( sulfobetaine methacrylate) , polyalkylene residues having more than 20 carbon atoms, peptide chains, DNA fragements and poly- ( sulfobetaine acrylamide) , whereby H₂ has no functional end group or side group; a side chain H₃ having a long chain H₃ selected from the group consisting of a polydimethylsiloxane, perfluoroethers, perfluoroalkyls, polyisobutene, polyethylene glycol, polydimethylacrylamide, polyvinylpyrrolidone, polyalkyloxazo lines , polyalkyloxazines, dextran, carboxymethyl dextran, poly (N-isopropylacrylamide ) , poly(N- hydroxyethylacrylamide, poly ( 2-hydroxyethyl methacrylate) , poly-hydroxypropylmethacrylate ) , poly- (methacryloyloxylethyl phosphorylcholine) , poly- ( sulfobetaine methacrylate) , polyalkylene residues having more than 20 carbon atoms, peptide chains, DNA fragments and poly- ( sulfobetaine acrylamide) , whereby H₃ carries at least one functional end or side group K₃ selected from the group consisting of amines, carboxy, and nitrilotriacetic acid (NTA) , biotin, azide, terminal alkene groups, terminal alkyne groups, tetrazine .

13. Functional polymer according to any of claims 11 or 12, wherein said functional polymer comprises a further type of side chain J which is intended to irreversibly bind to a substrate, said side chain J having a linear or branched, substituted or unsubstituted C₂ to C_i2 alkylene group which optionally comprises heteroatoms selected from the group consisting of oxygen and nitrogen, and which carries at least one functional end or side group K₄ selected from the group of alkoxy silanes, chloro silanes, catechols, nitrocatechols, bromocatechols, chlorocatechols, phosphates, phosphonates, mimosine derivatives, anacheline, gallols, thiols, N-heterocyclic carbenes, azides, perfluorophenyl azides, benzophenon, di aryl di azomethane, aryltri fluoromethyl diazomethane, organoboron, acrylamide, acrylate and epoxide.

14. Use of a compound according to any of claims 1 to 8 or a polymer according to any of claims 9 to 13 as adhesion promoter, as thermally activatable crosslinking agent, as photoactivatable crosslinking agent, as a hardener compound in a two-component adhesive.

15. Use of a compound according to claims 1 to 7 to thermally introduce functional groups or fluorescent markers to material selected from the group of a polymer, a particle, a nanoparticle and a hydrogel, wherein said material is essentially free of other functional groups.