FR2935973A1 - New dipyrazol-1-yl-pyridine compounds useful for preparing complex, which is useful for e.g. the detection of metal cations in solutions, as a luminescent marker for the absorption of two-photons, and the recognition of e.g. neuravidin - Google Patents

Abstract

Dipyrazol-1-yl-pyridine compounds (I) are new. Dipyrazol-1-yl-pyridine compounds of formula (I) are new. Y 1>, Y 2>H (preferred) or 1-4C alkyl; or Y 1>+Y 2>aromatic ring; A : Ctriple boundC, CONH or COO; X : H, NH 2, halo, COOR 1>, biotin moiety (-CO-(CH 2) 4-C 5H 7N 2OS), polyheteroaromatic group or crown ether; R 1>H, alkali cation, or quaternary ammonium N(R 3>) +>4; R 3>H, alkyl, succinimide (-N-(CO-CH 2-CH 2-CO))- or pentafluorophenyl; E : linker comprising at least one of -C 6H 4-, C 10H 6-, -CO-NH-, peptide groups containing 1-4 amino acids, or 1-10C alkylene and optionally include at least one heteroatom in the carbon chain; R : H, alkali metal or a quaternary ammonium group of formula (N(R 3>) 4+>); and n : 0 or 1. Independent claims are included for: (1) preparation of (I); (2) complex of lanthanide ions from europium (Eu 3+>), terbium (Tb 3+>), dysprosium (Dy 3+>), samarium (Sm 3+>), erbium (Er 3+>), ytterbium (Yb 3+>), praseodymium (Pr 3+>) or neodymium (Nd 3+>) ions and a ligand (I); and (3) preparation of complex comprising mixing equimolar quantities of (I) and a lanthanide salt; heating and then neutralizing to a pH of 6-8 after cooling. [Image].

Description

B5006FR

The present invention relates to organic compounds useful as ligands for the preparation of complexes and to a process for their preparation. The lanthanide ion complexes have very particular spectroscopic properties that allow applications in the field of luminescence detection. These complexes have a very large Stokes shift, very thin emission lines, of the order of a few nm, which are characteristic of the lanthanide ion used. They can emit in the visible or near-infrared range, and they have an extremely long excited state of life, up to a millisecond. This last characteristic is an essential asset: it allows a time-resolved detection (which makes it possible to eliminate the parasitic fluorescence signals) and it causes a very strong increase in the detection sensitivity of the complexes by luminescence microscopy or in the analyzes fluoroimmunologiques. The luminescent complexes of lanthanide ions therefore have applications in most fields of conventional fluorescence. However, lanthanide ion complexes are generally difficult to obtain. Many properties of the complex depend on the structure of the ligand and the lanthanide ion, in particular the excitation efficiency of the complex, the degree of stability of the lanthanide complexation (which must be high to avoid the release of the cations), the luminescence quantum yield and the possibility of forming covalent bonds with the material to be labeled for the biological applications of the complexes. Adequate excitation of the complexes can be achieved when the ligand of the complex comprises heteroaromatic groups which are intended to capture light and transfer it to the lanthanide ion which will be reemitted. This phenomenon is called antenna effect. The choice of these heteroaromatic groups defines numerous spectroscopic properties of the final complex, in particular the spectral range of excitation and the luminescence quantum yield. CN-1811429-A discloses a complex of Tb3 + and a ligand which has a 2,6-dipyrazolylpyridine backbone wherein each of the pyrazolyl groups has a -CH2-N (CH2CO2H) 2 moiety. Said complex is useful for the detection of singlet oxygen. It is obtained by a process of attaching the anthracene group to a dibromoaminopyridine and then modifying the pyridyl group by reacting the bromine atoms with the appropriate reagents to replace each Br 5 with a pyrazolyl group carrying a -CH 2 -N group (CH 2 CO 2 H) 2. EP-0 770 610 discloses lanthanide ion complexes in which the ligand is a 2,6-dipyrazolylpyridine skeleton wherein each of the pyrazolyl groups carry a -CH 2 -N (CHG 2 CO 2 H) 2 group, G 2 being H, a halogen, a cyano group, a phenyl group, an alkyl group or an alkoxy group. The preparation process consists of first preparing a 2,6-dipyrazolylpyridine di bromine compound and then modifying it to obtain both end groups -CH 2 -N (CHG 2 CO 2 H) 2. This method does not make it possible to obtain compounds in which the pyridyl group carries substituents chosen to adjust the properties of the lanthanide complex in which said compounds constitute the ligand. The object of the present invention is to provide compounds useful as ligands for lanthanide complexes, and a process for their preparation, said method making it possible to obtain ligands bearing various substituents in order to confer particular properties on the complexes. A compound according to the present invention has the formula (L) COOR COOR COOR COOR wherein: each of Y 1 and Y 2 represents an H atom or an alkyl group having 1 to 4 carbon atoms, or Y 1 and Y 2 together form a biradical 2935973 B5006FR

3 forming an aromatic ring with the two carbon atoms that carry them; A is -C = C-, CO-NH-, or CO-O-; x is:

5 * H, NH 2, a halogen,

a group COOR1 in which R 'is H, an alkaline cation, a quaternary ammonium group N (R3) 4+ in which R3 is H or a linear alkyl chain preferably having from 1 to 4 carbon atoms, a succiimide group - N- (CO-CH2-CH2-CO) - or a group

Pentafluorophenyl -C6F5;

a biotin function (-CO- (CH 2) 4-C 5 H 7 N 2 OS), a polyheteroaromatic group or a crown ether,

n is 0 or 1; E is a linker consisting of at least one group selected from

-C6H4-, C10H6-, -CO-NH-, peptide groups containing from 1 to 4 amino acids, and alkylene groups which have from 1 to 10 carbon atoms and which optionally comprise at least one heteroatom in the chain. carbon,

each of R is H or an alkali metal or a N (R 3) 4+ quaternary ammonium group as defined above. The compounds L in which the Y1 and Y2 groups each represent an H atom, and the compounds L in which the Y 'and Y2 groups are part of an aromatic ring are particularly preferred. A compound L according to the present invention may be prepared from a compound of the formula wherein Y 'and Y2 have the meaning given above. and R 'is an alkyl group having 1 to 6 carbon atoms. R 'can be: a linear alkyl group, preferably having 1 to 6 carbon atoms, particularly an ethyl group; a linear alkyl group having one or more heteroatoms (especially O, N or S), preferably having 1 to 6 carbon atoms; a branched alkyl group, preferably having 3 to 6 carbon atoms, for example a t-butyl group. A compound wherein the substituents Y 'and Y2 are separate groups (hereinafter referred to as 5') may be prepared by a process comprising the following steps; i) 4-bromo-2,6-difluoropyridine 1 is reacted with an alkyl 1H-pyrazole-3-carboxylate bearing the above-defined Y 'and Y 2 groups defined above in a non-nucleophilic aprotic organic solvent, presence of an alkali metal hydride at a temperature between 0 and 60 ° C; ii) the compound 2 'obtained at the end of step i) is: reduced by a reducing agent in an aprotic organic solvent; iii) the compound 3 'obtained at the end of step ii) is reacted with a brominating agent (for example PBr3) preferably at a temperature of between 20 and 60 ° C; iv) the compound 4 'obtained at the end of step iii) is reacted with a dialkyl ester of iminodiacetic acid, in the presence of a base in an aprotic organic solvent. 4 2935973 B5006FR

The process for preparing a compound 5 'can be represented by the following reaction scheme, wherein R 2 represents an alkyl group having from 1 to 4 carbon atoms: A compound in which the substituents Y 1 and Y 2 borne by a same pyrazolyl group forms a ring (hereinafter referred to as 5 "compound) may be prepared by a process analogous to the above process, replacing the alkyl 1H-pyrazole-3-carboxylate with the alkyl ester Indazole-3-carboxylic acid 10. The process may be represented by the following reaction scheme, wherein R 2 represents an alkyl group having from 1 to 4 carbon atoms: ## STR2 ## LN ~ `F -NN COOR2 10 1 Br OH HO Br Br Br 5" 2935973 B5006EN

In the various steps of the process for preparing a compound 5, the

aprotic solvent can be THF, Et2O, Et3N, DMF, DMSO, toluene, CH2Cl2, or

one of their mixtures (for example a mixture THF, Et3N). In step i):

the alkyl 1H-pyrazole-3-carboxylate is preferably ethyl 1H-pyrazole-3-5 carboxylate for a 5 'compound, or the ethyl ester of the acid

indazole-3-carboxylic acid for a 5 "compound;

the alkali metal hydride is preferably NaH;

the temperature is preferably of the order of 0 ° C to avoid parasitic reactions. In step ii), the reducing agent may be a mixed hydride, for example LiAlH 4 or NaBH 4. In step iv), the base is a non-nucleophilic compound, for example K 2 CO 3 or Et 3 N, and the dialkyl ester of iminodiacetic acid is preferably diethyl ester or di (t-butyl) ester of iminodiacetic acid. More particularly, the process for preparing a compound L according to the invention comprises:

a first step in which the bromine of compound 5 is replaced by a group A-Z by reaction with a suitable reagent, in the presence of an organometallic catalyst, in an organic solvent;

A step in which the groups R 'are replaced by groups R, R being H, an alkaline cation or a tetralkaylammonium cation as mentioned previously;

one or more steps to replace Z by (E) n-X, when Z is different from the group (E), - X referred to. The replacement of the linear alkyl groups R 'with a K +, Na + or Li + cation can be carried out with KOH, NaOH or LiOH respectively in a polar solvent (for example a mixture CH 3 OH / H 2 O) at a temperature between 20 and 100. ° C, for example at 60 ° C. The COOK, COONa or COOLi group can then, if necessary, be modified to an acid group or an ammonium carboxylate group 2935973 B5006EN

[COON (R 3) 4+] by reaction with an acid such as HCl in water or with N (R 3) 4 OH ammonium hydroxide, respectively. H substitution of branched alkyl groups R 'can be effected by reaction with trifluoroacetic acid (TFA) in an aprotic organic solvent. The reactions intended to replace the groups R 'can be carried out either on the product obtained after replacement of the bromine, or on a product obtained after the one or one of the stages of modification of the AZ group. In the various steps of the process for preparing a compound L, the aprotic solvent may be THF, Et2O, Et3N, DMF, DMSO, toluene, CH2Cl2, or a mixture thereof (for example a THF / Et3N mixture). For the implementation of the first step of the process for preparing a compound L, the bromine atom at the 4-position on the pyridyl group of compound 5 can be subjected to various chemical reactions such as

Stille, Heck, Sonogashira or Suzuki, carboalkoxylation or carboamidation reactions. The organometallic catalyst used in the first step is preferably a complex of Pd and triphenylphosphine, for example [Pd (PPh3) 2C12] or [Pd (PPh3) 4]. The temperature is preferably between 20 and 120 ° C. The

The reagent used to react with the compound 5 depends on the nature of the group A of the compound L. In the carboamidation (or carboalkoxylation) reactions respectively, A represents CO-NH- (respectively CO-O-), the reagent used is amine (respectively an alcohol) in the presence of carbon monoxide. In Sonogashira type couplings, A represents -C = C-, the reagent used comprises a true acetylenic group, H-C = C-. When the group A of the substituent at the 4 position on the pyridyl group of the compound L is a group -C = C-, the first step of the process consists of reacting the compound 5 with a reagent which has a terminal group HCEC-. The organometallic catalyst is preferably a palladium complex and a palladium complex.

Triphenylphosphine, in particular Pd (PPh3) 2C12 in the presence of Cul or [Pd (PPh3) 4]. Three embodiments can be envisaged. In a first embodiment, the compound 5 is reacted with an HC-C- (E) r, -X reagent to obtain the compound 6, and the R '5 groups are then replaced by R groups defined above, according to the indicated terms

previously to obtain a compound L. xx (E) n (E), CO2R 'CO2R' CO2R 'OZR' Nrv CO2RC O2R Y2 CO2R CO2R Brr-1 r'V ~ OZR, CO2R 'CO2R' CO2R ' The first step of the reaction scheme (which corresponds to the first step of the process) is carried out in the presence of a complex of Pd and triphenylphosphine, such as [Pd (PPh 3) 2 Cl 2] or [Pd (PPh 3) 4 ] and Cul, in an organic solvent (for example a THF / Et3N mixture), at a temperature between 20 and 80 ° C (for example at 50 ° C). In a second embodiment, the method comprises a step of modifying an AZ group different from the desired A- (E) n-X group. Compound 5 is reacted according to the following procedure: ## STR1 ## wherein R 2 is CO2R 'CO2R' CO2R 'CO2R' CO2R 'CO2R' CO2R 'CO2R' CO2R 'CO2R' CO2R 'CO2R' The different steps are carried out under the following conditions: The first step of the reaction scheme corresponds to the first step of the process in which the compound 5 is reacted with trimethylsilylacetylene (TMSacetylene). in the presence of an organometallic catalyst in a 2935973 B5006FR

Aprotic organic solvent. This step is advantageously carried out at room temperature. The organometallic catalyst may be [Pd (PPh 3) 2 Cl 2] in the presence of Cul;

The second step of the reaction scheme is to replace the TMS group with

An H atom, by reacting the compound 7 obtained at the end of the preceding step, with a deprotection reagent, for example a tetraalkylammonium fluoride (in particular tetrabutylammonium fluoride TBAF), a fluoride or a metal carbonate alkaline;

the 3rd stage of the reaction scheme (which corresponds to the modification stage

Of R '), is carried out according to one of the above-mentioned methods to obtain the compound L1 in which the group A- (E) ä-Z is a -C-CH group, depending on the choice made for R. This step could of course be done before the reaction with TBAF. The 2nd step is preferably carried out in an aprotic solvent, at a temperature of 0 to 80 ° C, for example at 0 ° C. In a third embodiment, the process comprises two steps of modifying a group AZ different from A- (E) -X group desired. The compound 8 obtained as a synthetic intermediate is reacted in the second embodiment with a compound F (r) - (E) x - X to obtain the compound 6, and the

Compound 6 as indicated above to replace R 'with R according to one of the procedures described above. The group F (r) can be 1-1, Cl, Br, 1, -O-SO2-CF3, a boronic acid group (B (OH) 2), a boronic acid ester group (B (OAlkyl) 2 ), a trialkyl stannyl group or a trialkyl silyl. The reaction scheme is given below: When the A is CO-NH- or CO-O- the first step of the process is carried out by reacting the compound with a H2N- (E) -X compound. or HO- (E) nX respectively according to the following reaction scheme: ## STR2 ## Y 2 N N N Y N N Y N IV N IV Y 2 (n NNN WH N / N CO 2 CO2R 'CO2R' CO2R 'r N In the 1st step of the reaction scheme (which corresponds to the 1st stage of the process), the compound 5 is reacted with a compound HW- (E) n X in which W is NH or O, E, n and X have the meaning given above, under a pressure of CO (for example of 1 atmosphere), in the presence of an organometallic catalyst (for example [Pd (PPh 3) 2 Cl 2]), in an aprotic solvent (for example toluene / Et 3 N, at a temperature between 60 and 120 ° C. (for example 100 ° C.) During the 2nd step of the reaction scheme, the groups R 'of the compound 9 are replaced by one of the procedures described above. 2935973 B5006FR

Some examples of ligands, to which the invention is not limited, are given below for purely illustrative purposes. Similar ligands can be obtained by replacing H or Na with one of the other R groups defined above. N L N N N N L N L CO2H CO2H L O O COZNa Na OZNa N ~ -N CO2H CO2H OH O ONA OONN II / N II N \ NO N \ ~ N ~. N rN r N- L3 CO2H CO2H CO2HC O2H L4 CO2Na 02Na CO2NaC O2Na O ONa C ONa O ~ 11 \ H Il ~ I 1 NNNNN ~ NIN ~ r L5 CO2Na CO2Na CO2Na CO2Na L6 CO2Na CO; Na CO2Na CO2Na B5006EN 2935973 12 2o o o- N r L7 CO2Na CO2Na CO2Na CO2Na L8 CO2Na CO2Na CO2Na CO2Na ONa O o fONa O ~ NH L9 CO2Na CO2Na CO2Na CO2Na L10 I CO2Na CO2Na CO2Na CO2Na ONH L13 NaO ONa ONa L12 2935973 B5006GB 13 A lanthanide complex according to the invention comprises a lanthanide ion complexed with a ligand as defined above. The lanthanide ion is selected from Eu3 +, Tb3 +, Dy3 +, Sm3 +, Er3 +, Yb3 +, Pr3 'and Nd3 +. A lanthanide complex can be obtained by mixing equimolar amounts of a compound L (preferably in salt form). of sodium) with a lanthanide salt, heating the mixture, cooling and neutralizing to pH 6 to 8, then recovery of the complex at room temperature. The lanthanide salt may be a nitrate, chloride, perchlorate or triflate Ln (CF3SO3) 3. In a particular embodiment, the compound L and the lanthanide salt are mixed in equimolar amounts in solution in water or in a MeOH / water mixture, the solution is heated for 2 to 3 hours at 60 ° C., cooled at room temperature and then neutralized if necessary to pH 7 by adding NaOH, a quaternary ammonium hydroxide or HCl diluted in water. The complexes formed are then isolated by concentration of the mother liquors and precipitation in an H 2 O / MeOH / THF / Et 2 O mixture. The complexes according to the invention have various applications, depending on the nature of the substituents of the pyridyl group of the ligand. The complexes of the invention are useful for labeling compounds which carry an amine, alcohol, thiol, carboxylic acid or activated ester group. These compounds can be monomeric molecules or polymers optionally in the form of beads. For this use, the group X of the ligand of the complex is preferably a group -COOH, a COONa group, an ester-type ester HHN ~ / N \ NN N 1 N Nz L11 or ONA NH N B5006FR 14 of NHS or pentafluorophenol ester, Br, I, or amine. For this particular application, the ligand of the complex may be selected from the compounds L3, L4, L5, L6, L9, L10, L12 and L13. When the ligand of a luminescent complex has a recognition site electronically related to the ligand complexation structure, the luminescence properties of the complex may be disrupted by the presence of an analyte that binds to the recognition site. By electronically coupling the recognition site to the central pyridine by acetylenic bonds, the interaction of the recognition site with its substrates induces electronic perturbations which result in luminescence changes of the lanthanide ion complexes. The complexes of the invention are useful for the recognition of the alkaline, alkaline earth and transition elements of the first series when the ligand bears a substituent ΔA (E) λX wherein X is a crown ether (L7) or a terpyridine (L8).

Spectroscopy and two-photon absorption microscopy are relatively recent techniques that have the advantage, particularly in microscopy, of allowing a significant improvement in the spatial resolution by using low energy photons. Almost all of the luminescent markers studied in two-photon absorption are organic fluorescent compounds of the Rhodamine type. These organic compounds have very low Stokes displacements and broad emission bands (corresponding to a half-height width greater than 50 nm). The luminescent complexes of lanthanide ions according to the present invention exhibit very high Stokes displacements and narrow emission bands. They are therefore particularly interesting compounds for marking and biphotonic microscopy and very recent work has demonstrated this possibility on Eu and Tb complexes. [See, in particular, a) Law, G.L .; et al. J. Am. Chem. Soc. 2008, 130, 3714; (b) Picot, A .; et al., J. Am. Chem. Soc. 2008, 130, 1532.] However, there is currently no two-photon lanthanide ion probe having a grafting function for covalent labeling. The complexes of the invention can be used as a two-photon probe having a grafting function for 2935973 B5006FR

Covalent labeling. For this particular application, the ligand of the complex preferably bears on the pyridyl group, a substituent A- (E) n Z wherein A is C = C, E is phenyl and Z is a terminal NaCOO- group. In particular, complexes whose ligand is L5, L6, L12 or L13 may be mentioned. The complexes of the invention wherein the X terminal group of the ligand A- (E) -X substituent is a biotin group are useful for the recognition of avidin, streptavidin and neuravidin. An example of such a complex is a complex having the compound JL11 as a ligand. The present invention is illustrated by the following examples, to which it

10 is however not limited. Examples 1 to 18 relate to the preparation of ligands. Examples 19 to 35 relate to the preparation and characterization of lanthanide complexes.

EXAMPLE 1 SYNTHESIS OF A 5-ET COMPOUND A 5-Et compound was prepared according to the following reaction scheme: ## STR1 ## In a Schlenk flask containing DMF distilled (100 mL), 4-bromo-2,6-difluoropyridine 1 (2.89 g, 14.9 mmol) and ethyl 1H-pyrazole-3-carboxylate (4.17 g; 8 mmol) under argon, NaH (60% in oil, 1.32 g, 32.8 mmol) was added The mixture was stirred for 2 h at 0 ° C and the solvent was evaporated to dryness. The residue obtained is dissolved in dichloromethane (100 ml), washed with water (3 x 100 ml) and saturated NaCl solution The organic phase is dried over Na 2 SO 4, filtered and evaporated to dryness. is purified by chromatography on silica (CH 2 Cl 2 / MeOH, 100/00 to 99.5 / 0.5) to give compound 2 (3.07 g, 47%) as a white solid 1H NMR (CDCl 3 300 MHz): 8 8.55 (d, J = 2.6 Hz, 2H), 8.28 (s, 2H), 7.01 (d, J = 2.6 Hz, 2H); 4.46 (q; J = 7.1 Hz, 4H), 1.44 (t, J = 7.2 Hz; 6H). 13C {1H} NMR (CDCl3, 300 MHz):? 161.71; 149.7; 146.9; 137.4; 128.6; 114.6; 110.7; 61.5; 14.3.

IR (cm-1, ATR): ν 1774 (w); 1720 (s); 1595 (s); 1,577 (s); 1525 (m); 1458 (s); 1427 (m). Calculated for C 17H16BrN5O4 (434.25): C, 47.02; H, 3.71; N, 16.13; measured: C, 46.82; H, 3.57; N, 15.72. EI / MS (solid) m / z: 435.0 ([M + H] +, 100%); 433.0 ([M + H] +, 100%) Compound 3 In a Schlenk flask under argon containing Compound 2 (3.07 g, 7.07 mmol) and distilled THF (130 mL) cooled to -5 ° C C, is added in small portions LiAlH4 (0.54 g, 14.1 mmol). After complete addition of LiAlH 4, the mixture is stirred at -5 ° C. for 1 h and then hydrolysed with a saturated solution of NH 4 Cl until two phases are obtained. This mixture is filtered on velite and evaporated to dryness, the solid obtained is heated under reflux in THF and then filtered while hot. The solid resulting from this filtration is rinsed several times with THF. The filtrate is evaporated to dryness to give compound 3 (1.78 g). Compound 4 In a Schlenk flask under argon, containing crude Compound 3 (1.76 g, 5.03 mmol) obtained by reduction of Compound 2 and distilled DMF (100 mL) was added PBr3 (1.42 mL; , 1 mmol) at room temperature. The mixture is stirred at room temperature for 14 hours. The solvent is evaporated to dryness. The resulting residue is dissolved in H2O / CH2Cl2 and neutralized with NaHCO3. The aqueous phase is extracted with dichloromethane (4 x 200 mL), and the phases are dried.

The combined organics are washed with saturated NaCl solution, dried over Na2SO4, filtered and evaporated to dryness. The crude product is purified by chromatography on silica (CH 2 Cl 2 as eluent). Compound 4 (1.45 g, 60%) is obtained as a white solid. 1H NMR (CDCl3, 200 MHz): δ 8.45 (d, J = 2.6 Hz, 2H); 8.00 (s, 2H); 6.56 (d, J = 2.6 Hz, 2H); 4.54 (s, 4H). 13 C NMR (CDCl 3, 200 MHz): S, 152.7; 149.5; 140.0; 128.7; 113.0; 108.7; 24.5. IR (cm -1, ATR) v 1649 (w), 1608 (m), 1601 (m), 1586 (s), 1525 (s), 1467 (s), 1458 (s).

Calculated for C13H, oBr3N5 (475.97): C, 32.80; H, 2.12; N, 14.71; measured: C 32.70; H, 1.92; N, 14.45.

EI / MS (solid) m / z: 473 ([M + H] +; 30%); 475.0 ([M + H] +; 100%); 477 ([M + H] + 96%). Compound 5-In Compound 4 (0.8 g, 1.68 mmol), iminodiacetatic acid ethyl ester (0.66 ml, 3.70 mmol) and K2CO3 were mixed under argon in a flask. (0.93 g, 6.72 mmol) in a mixture of distilled THF (50 mL) / CH3CN (90 mL). The reaction medium is heated at 50 ° C. for 14 hours and then filtered. The filtrate is concentrated to dryness. The resulting oil is dissolved in dichloromethane (100 mL), washed with water (3 x 100 mL) and saturated NaCl solution. This organic phase is dried over Na 2 SO 4, filtered and evaporated to dryness. Purification by chromatography on silica (CH 2 Cl 2 / MeOH, 100: 00 to 98: 2) of the crude product afforded compound 5-Et (1.01 g, 87%) as a colorless oil. 1H NMR (CDCl3, 300 MHz): δ 8.44 (d, J = 2.6 Hz, 2H); 7.97 (s, 2H); 6.55 (d; J =

2.6 Hz; 2H); 4.18 (q, J = 7.2 Hz, 8H); 4.04 (s; 4H); 3.62 (s, 8H); 1.28 (t, J = 7.2 Hz, 12H). 13H NMR (CDCl3, 300MHz):? 171.0; 153.6; 150.3; 136.4; 128.1; 112.2; 108.8; 60.5; 54.6; 51.3; 14.2. IR (cm-1, ATR): ν 1733 (s); 1588 (s); 1575 (s); 1538 (m); 1464 (s); 1387 (s). 5 2935973 B5006FR

Calculated for C29H38BrN7O8 (692.57): C, 50.29; H, 5.53; N, 14.16; measured: C, 49.89; H, 5.28; N 13.81.

EI / MS (solid) m / z: 693.2 ([M + H] +; 100%); 691.2 ([M + H] + 100%).

EXAMPLE 2 SYNTHESIS OF THE 5-t-Bu COMPOUND

Compound 4 was prepared from compound 4 prepared according to the procedure of Example 1. In a flask under argon was mixed compound 4 (0.18 g, 0.37 g). mmol), tert-butyl ester of iminodiacetic acid (0.20 g, 0.81 mmol) and K 2 CO 3 (0.20 g, 1.47 mmol) in a mixture of THF (10 mL) / CH 3 CN The reaction medium is heated at 50 ° C. for 14 hours and then filtered The filtrate is concentrated to dryness The resulting oil is dissolved in dichloromethane (100 ml), washed with water ( 3 x 100 mL) and saturated NaCl solution This organic phase is dried over Na 2 SO 4, filtered and evaporated to dryness Purification by chromatography on silica (CH 2 Cl 2 / MeOH, 100: 00 to 99.7: 0.3) The crude product afforded the compound 5 -Bu (0.25 g, 85%) as a colorless oil.1H NMR (CDCl3, 200 MHz): S 8.42 (d, J = 2) , 5 Hz; 2 1-1); 8.00 (s; 2H); 6.55 (d; J = 2.6 Hz; 2H); 4.00 (s; 4H); 48 (s, 8H); 1.46 (s, 36H), 136.2, 127.9, 111.9; 13C {1H} NMR (CDCl3, 200 MHz): 8170.2; 153.7; 150.2; 108.7; 80.8; 55.2; 50.8; 28.0. IR (cm -1, ATR):? 1732 (s); 1589 (s); 1575 (s); 1539 (m); 1465 (s); 1391 (s); 1367 (s). Calculations calculated for C37H54BrN7O8 ( 804.78): C 55.22, H 6.76, N 12.18, measured: C 54.92, H 6.57, N 11.68, 2935973 B5006FR 19 EI / MS (solid) m / z: 805 , 2 ([M + H] +, 100%), 803.3 ([M + H] +, 100%) EXAMPLE 3 SYNTHESIS OF THE L1 COMPOUND

A compound L1 was prepared from a compound 6 according to the following reaction scheme: TMS HH Br-NN -N Na / O CO2tBu CO2tBu CO2tBu ztBu IrN r CO2tBu CO2tBu CO2tBu CO2tBu 5 -Bu 7-tBu 8- In a Schlenk tube the compound 5 - / Bu (0.20 g, 0.25 mmol), trimethylsilylacetylene (0.04 ml, 0.31 mmol), [Pd ( PPh3) 2C12] (10.5 mg, 0.02 mmol), distilled THF (20 mL) and distilled Et3N (15 mL). This mixture is degassed for 30 min, then Cul (4.80 m; 0.03 mmol) is added to the degassed solution. The reaction medium is stirred at room temperature for 14 hours. The solvent is concentrated to dryness and the resulting residue is dissolved in dichloromethane (100 mL), washed with water (3 x 100 mL), and saturated NaCl solution. This organic phase is dried over Na 2 SO 4, filtered and evaporated to dryness. Purification by chromatography on silica (CH 2 Cl 2 / MeOH, 100: 00 to 98: 2) of the crude product gives compound 7-Bu (0.15 g, 73%) as an oil. 1H NMR (CDCl3, 200 MHz): δ 8.41 (d, J = 2.6 Hz, 2H); 7.78 (s, 2H); 6.50 (d, J = 2.6 Hz, 2H); 4.00 (s, 4H); 3.45 (s, 8H); 1.43 (s; 36H); 0.23 (s, 9H). 13 C (1H) NMR (CDCl 3, 200 MHz): S, 170.3; 153.3; 150.0; 136.0; 127.7; 111.1; 108.4; 101.5; 100.6; 80.8; 55.2; 50.9; 28.1; 0.51. IR (cm-1, ATR): v 2167 (w; vc-c); 1732 (s); 1610 (s); 1553 (s); 1539 (m); 1464 (s); 1391 (s). Calculated for C42H63N7O8Si (882.1): C 61.36; H, 7.72; N, 11.93; measured: C 61.28; H, 7.64; N, 11.89. EI / MS (solid) m / z: 822.3 ([M] + 100%). Compound 8 -Bu 5 A solution of TBAF (1M in THF, 0.20 mL, 0.20 mmol) was added dropwise under argon to a solution of the compound 7-tBu (0.14 g, 0.17, 0.17 mmol). mmol) in distilled THF (4 mL) cooled to 0 ° C. The reaction medium is stirred at this temperature for 2 h and then neutralized with water. The solvent is evaporated to dryness. The resulting residue is dissolved in dichloromethane (100 mL), washed with water (3 x 100 mL) and saturated NaCl solution. This organic phase is dried over Na 2 SO 4, filtered and evaporated to dryness. The crude product is purified by chromatography on silica (CH 2 Cl 2 / MeOH, 100: 00 to 99.4: 0.6). Compound 8-Bu (0.10 g, 81%) is obtained. 1H NMR (CDCl3, 200 MHz): δ 8.43 (d, J = 2.6 Hz, 2H); 7.83 (s, 2H); 6.54 (d, J = 2.6 Hz, 2H); 4.00 (s, 4H); 3.47 (s, 8H); 3.35 (s, 1H); 1.45 (s, 36H). 13C {1H} NMR (CDCl3, 200 MHz): 8170.3; 153.6; 150.1; 135.1; 127.8; 111.4; 108.6; 82.4; 80.9; 80.6; 55.3; 51.0; 28.1. IR (cm-1, ATR): v 2112 (w; vcc); 1732 (s); 1608 (s); 1557 (s); 1536 (m); 1465 (s); 1391 (s). Calculated for C 39 H 55 N 7 O 8 (749.9): C 62.46; H, 7.39; N 13.07; measured: C, 62.19; H, 7.18; N, 12.68. EI / MS (pure) m / z: 749.3 ((Mn 100%) L1 ligand Compound 8-Bu (0.03 g, 0.04 mmol) was dissolved in dichloromethane (1 mL) and TFA (1 mL), then the mixture is stirred at room temperature for 2 h The solvent is evaporated to dryness and the resulting oil is triturated in diethyl ether The compound L1 is obtained in quantitative yield, in the form of 1H NMR (D6-DMSO, 300 MHz): δ 8.86 (d, J = 2.6 Hz, 2H), 7.67 (s, 2H), 6.57 (d.30), J = 2.6 Hz, 2H), 4.80 (s, 1H), 3.94 (s, 4H), 3.47 (s, 8H), 2935973 B5006FR 21 t3C {'H} NMR (DMSO, 300 MHz): S 172.7, 154.1, 150.3, 135.5, 129.6, 110.7, 109.3, 80.9, 80.7, 55.3, 51, 1. IR (cm -1, ATR): v 2111 (w; vc -1); 1609 (s); 1558 (s); 1534 (m); 1465 (s); 1389 (s); 1275 (w). ESIIMS (negative mode, McOH / H 2 O) m / z: 261.6 ([M-2H +] 2, 80%) EXAMPLE 4 SYNTHESIS OF COMPOUND 8-And 8-Et was prepared according to the procedure of Example 3, but using 5-Et instead of 5-Bu T MSH Br O And CO2Et 0 And CO2Et rN --- .. CO2 And CO2 And CO2 And CO2 - CO2 And CO2 And CO2 And 10 5-And 7-And 7-And 8-And in a Schlenk tube the compound 5 is mixed. And (0.70 g; 0.25 mmol), trimethylsilylacetylene (0.17 ml, 1.21 mmol), [Pd (PPh 3) 2 Cl 2) (42.5 mg, 0.06 mmol), distilled THF (20 ml) and Et3N distilled (10 mL). This mixture is degassed for 30 minutes, then Cul (19.2 mg, 0.10 mmol) is added to the degassed solution. The reaction medium is stirred at room temperature for 14 hours. The solvent is concentrated to dryness and the resulting residue is dissolved in dichloromethane (100 mL), washed with water (3 x 100 mL), and saturated NaCl solution. This organic phase is dried over Na 2 SO 4, filtered and evaporated to dryness. Purification by chromatography on silica (CH 2 Cl 2 / MeOH, 100: 00 to 98: 2) of the crude product afforded compound 7-Et (0.50 g, 70%) as an oil. 2935973 B5006FR

1H NMR (CDCl3, 200 MHz): δ 8.45 (d, J = 2.5 Hz, 2H); 7.81 (s, 2H); 6.53 (d, -2.6 Hz, 2H); 4.18 (q, J = 7.2 Hz, 8H); 4.04 (s; 4H); 3.62 (s, 8H); 1.27 (t, J = 7.1 Hz, 12H); 0.27 (s, 9H). 13 C NMR (CDCl 3, 200 MHz): S, 171.1; 153.1; 150.0; 136.2; 128.0; 111.3; 108.5; 101.5 (2C); 60.5; 54.6; 51.4; 14.2; 0.40. IR (cm -1, ATR):? 2162 (w; C = C); 1736 (s); 1610 (s) :, 1553 (s); 1464 (s); 1389 (s); 1328 (w). EI / MS (pure) m / z: 709.2 ([M] + 100%) Compound 8-Et A solution of TBAF (1M in THF, 0.85 ml, 0.85 mmol) is added dropwise under argon to a solution of compound 7-Et (0.50 g, 0.17 mmol) in distilled THF (15 mL) cooled to 0 ° C. The reaction medium is stirred at this temperature for 2 hours, The solvent is evaporated to dryness and the resulting residue is dissolved in dichloromethane (100 mL), washed with water (3 x 100 mL) and saturated NaCl solution. The organic product is dried over Na 2 SO 4, filtered and evaporated to dryness The crude product is purified by chromatography on silica (CH 2 Cl 2 / MeOH, 100: 00 to 98: 2) to obtain the compound 8-Et (0.37 g; NMR (CDCl 3, 300 MHz): δ 8.45 (d, J = 2.6 Hz, 2H), 7.85 (s, 2H), 6.54 (d, J = 20); 2.6 Hz; 2H); 4.18 (q; J = 7.1 Hz; 8H); 4.04 (s; 4H); 3.62 (s; 8H); 3.36 (s; 1 II), 1.27 (t, J = 7.2 Hz; 12H). 13 C NMR (CDCl 3, 300 MHz): 171.0; 153.3; 150.1; 135.2; 127.9; 111.6; 108.6; 82.5; 80.6; 60.5; 54.6; 51.4; 14.2. IR (cm -1, ATR):? 2111 (w; vcc); 1734 (s); 1609 (s); 1556 (s); 1536 (m); 1465 (s); 1389 (s). Calculated Analyzes for C3H39N7O8 (637.7): C 58.39, FI 6.16, N 15.38, measured: C 58.03, H 5.95, N 15.20, EI / MS (pure) m / z: 637.2 ([M] +; 100%) EXAMPLE 5 SYNTHESIS OF THE L2 COMPOUND A L2 compound was prepared from the compound 5-and according to the following reaction scheme: ## STR2 ## CO2 and CO 2 and CO 2 were 10 rpm. 1 CO2Na CO2Na CO2Na CO2Na L2 NNr - N - I rryù.1 CO2Et CO2Et CO2Et CO2Et 5 5-Et + Compound 10 5-Et (120 mg, 0.173 mmol) and p-toluylacethylene (24.2 mg) are dissolved 0.208 mmol) in 10 ml of anhydrous THF and 6 ml of triethylamine under an argon atmosphere [Pd (PPh 3) 2 Cl 2] (7.2 mg, 0.010 mmol) is added The solution is degassed for 30 minutes then (3.2 mg, 0.017 mmol) is added The solution is heated at 50 ° C. for 24 hours The solution is concentrated under reduced pressure to give a brown oil The residual oil is dissolved in 30 ml of CH 2 Cl 2 and the organic phase is washed with 3 x 15 ml of water, dried over Na 2 SO 4 and evaporated to dryness. (80 mg, 63%) is isolated by column chromatography (SiO 2, CH 2 Cl 2 / MeOH, 99.75 / 0.25 to 99.5 / 0.5) as a clear oil. 1H NMR (CDCl3, 300 MHz): δ 1.26 (t, J = 7.2 Hz, 12H); 2.40 (s, 3H); 3.62 (s, 8H); 4.04 (s; 4H); 4.17 (q, J = 7.2 Hz, 8H); 6.5 (d, J = 2.5 Hz, 2H); 7.18 (d, J = 7.9 Hz, 2H); 7.44 (d, J = 7.9 Hz, 2H); 7.86 (s, 2H); 8.45 (d, J = 2.5 Hz, 2H). 13 C NMR (CDCl 3, 300 MHz): δ 14.1; 21.5; 51.3; 54.5; 60.4; 86.0; 95.2; 108.4; 110.8; 118.7; 127.9; 129.2; 131.9; 136.6; 139.7; 149.9; 152.9; 171.0. IR (ATR, cm-1): 3126 (w); 2981 (w); 2936 (w); 2228 (w); 2207 (w); 1738 (s); 1606 (s); 1553 (s); 1538 (m); 1513 (w); 1464 (s); 1389 (s); 1299 (w); 1259 (w); 1188 (s); 1153 (s); 1096 (w); 1028 (s). 2935973 B5006FR

24

Ligand L2 Compound 10 (80 mg, 0.11 mmol) was dissolved in 20 ml of methanol / water (1/1), and NaOH (22 mg, 0.55 mmol) was added. The mixture is heated at 60 ° C for 3 hours. The solvent is evaporated to give a pale yellow residue.

The residue is dissolved in 0.5 ml of water and 4 ml of methanol. THF is added gradually to precipitate L2 as a white powder (66.5 mg, 86%). 1 H NMR (D 2 O, 300 MHz): δ 2.15 (s, 3H); 3.01 (s; 8H); 3.62 (s, 4H); 6.39 (s; 2H);

7.02 (d, J = 7.5 Hz, 2H); 7.26 (d, J = 7.5 Hz, 2H); 7.43 (s; 2H); 8.34 (s, 2H). 13C NMR (D20, 300 MHz): δ 20.8; 25.0; 50.7; 51.3; 57.8; 85.8; 95.5; 109.3;

110.4; 117.7; 127.3; 129.2; 132.0; 136.5; 140.7; 178.9.

IR (ATR, cm-1): 3365 (br); 2926 (w); 2210 (w); 1586 (s); 1553 (s); 1532 (w); 1466 (m); 1405 (s); 1327 (s); 1258 (m); 1211 (w); 1123 (m); 1049 (m); 1021 (m). ESI / MS (negative mode, McOH / H2O) m / z: 680.1 ([M-Na +] - 70%); 211.3 ([M-

3Na +] 3-; 100%).

Calculated for C30H25N7O8Na4.4H2O: C, 46.46; H, 4.29; N, 12.64; measured: C 46.30; H, 3.85; N, 12.43.

EXAMPLE 6 SYNTHESIS OF COMPOUND L3 Compound L3 was prepared from compound 5-and according to the following reaction scheme: ## STR3 ##

## STR3 ## To a solution of 11 (1.77 ml, 30 mmol) in 80 ml of anhydrous THF under an argon atmosphere, the reaction mixture is added to a solution of 11 (1.77 ml, 30 mmol) in 80 ml of anhydrous THF. NaH (1.32 mg, 60% in mineral oil, 33 mmol). The solution is stirred for 1 hour at room temperature. Ethyl bromoacetate (4.02 ml, 35 mmol) is added. The mixture is stirred at ambient temperature for 12 hours. The solvent is evaporated to give a yellow oil. The oil is dissolved in 40 ml of ethyl ether. The organic phase is washed with 3 × 20 ml of water, then dried over Na 2 SO 4 and concentrated. 12 is isolated as a colorless oil (2 g, 47%) after purification by column chromatography (SiO 2, petroleum ether / diethyl ether, 100/0 to 96/4), 1H NMR (CDCl 3, 300 MHz): S, 1.26 (t, J = 7.1 Hz, 3H); 2.45 (t, J = 2.4 Hz, 1H); 4.15 (s; 2H); 4.19 (q, J = 7.1 Hz, 2H); 4.27 (d, J = 2.4 Hz, 2H). 13C NMR (CDCl3, 300 MHz): S, 14.1; 58.2; 60.9; 66.2; 75.5; 78.5; 169.8. IR (ATR, cm-1): 3278 (m); 2984 (w); 2909 (w); 2118 (w); 1748 (s); 1448 (m); 1429 (m); 1382 (m); 1370 (m); 1349 (m); 1275 (m); 1249 (m); 1206 (s); 1116 (s); 1025 (s). EI / MS (pure) m / z: 142.0 (M + 100%). Calculations calculated for C7H1003: C 59.14; H, 7.09; measured: C 58.78; H, 6.84. Compound 13 5-Et (300 mg, 0.43 mmol) and 12 (148 mg, 1.04 mmol) were dissolved in 20 ml of anhydrous THF and 15 ml of triethylamine under an argon atmosphere. [Pd (PPh3) 2 Cl2] (18 mg, 0.026 mmol) is added, the solution is degassed for 5 minutes and then Cul (8.2 mg, 0.043 mmol) is added. The solution is heated at 50 ° C for 24 hours. The solution is concentrated under reduced pressure to give a brown oil. The residual oil is dissolved in 30 ml of CH 2 Cl 2 and the organic phase is washed with 3 x 15 ml of water, then dried over Na 2 SO 4 and concentrated. 13 (130 mg, 40%) is isolated by column chromatography (SiO 2, CH 2 Cl 2 / MeOH, 100/0 to 98/2) as a clear oil. 1H NMR (CDCl3, 300 MHz): δ 1.25 (t, J = 7.2 Hz, 12H); 1.29 (t, J = 7.2 Hz, 3H); 3.6 (s, 8H); 4.0 (s; 4H); 4.16 (q, J = 7.2 Hz, 8H); 4.24 (q, J = 7.2 Hz, 2H); 4.25 (s; br; 2x2H); 6.51 (d, J = 2.6 Hz, 2H); 7.8 (s, 2H); 8.43 (d, J = 2.6 Hz, 2H). 13C NMR (CDCl3, 300 MHz): b 14.1; 14.2; 51.4; 54.6; 58.7; 60.5; 61.1; 66.5; 84.4; 89.6; 108.6; 111.1; 127.9; 135.4; 150.1; 153.3; 169.7; 171.0. IR (ATR, cm-1): 3126 (w); 2982 (w); 2935 (w); 2907 (w); 1735 (s); 1610 (m); 1555 (m); 1536 (m); 1464 (m); 1388 (m); 1269 (w); 1188 (s); 1152 (s); 1118 (s); 1027 (s). EI / MS (pure) m / z: 754.2 ([M + H +], 100%). Calculations calculated for C36H47N7O11 C 57.36; H, 6.28; N 13.01; measured: C, 56.94; H, 5.67; N, 12.75. Ligand L3 Compound 13 (130 mg, 0.17 mmol) was dissolved in 20 ml of methanol. A solution of NaOH (41 mg, 1.03 mmol) in 4 ml of water is added. The mixture is heated at 60 ° C for 4 hours. The solvents are evaporated to give a brown oil. The oil is dissolved in 10 ml of water and the pH is raised to 4-5 by addition of a 0.1 M solution of HCl, resulting in the formation of a precipitate, which is isolated by centrifugation and dried for give L3 (67 mg, 64%). NMR (d 6 -DMSO, 300 MHz): δ 3.36 (s, 8H); 3.8 (s, 4H); 4.1 (s, 2H); 4.5 (s; 2H); 6.5 (s; 2H); 7.6 (s, 2H); 8.7 (s; 2H); 12.4 (s, 4H). 13 C NMR (d6-DMSO, 300 MHz): S, 54.3; 57.1; 58.7; 66.6; 86.4; 90.3; 105.3; 115.1; 130.7; 136.4; 141.8; 151.8; 173.0; 173.2. IR (ATR, cm-1): 3410 (br); 2923 (w); 2852 (w); 1729 (s); 1611 (s); 1558 (m); 1457 (s); 1388 (s); 1217 (s); 1109 (s); 1055 (s). EI / MS (neat) m / z: 614.1 ([M + H] + 100%) EXAMPLE 7 SYNTHESIS OF COMPOUND L4 Compound L4 was prepared from compound 5-And according to the following reaction scheme: BrN In a Schlenk tube, 5-Et (0.14 g, 0.20 mmol) was mixed with 5-Et 2 O (15 g). heptyno 14 (0.03 mL, 0.24 mmol), [Pd (PPh 3) 2 Cl] (8.40 mg, 0.01 mmol), distilled THF (30 mL) and distilled Et 3 N (12 mL). This mixture is degassed for 30 minutes, then Cul (3.80 mg, 0.02 mmol) is added to the degassed solution. The reaction medium is heated at 50 ° C. for 14 hours. The solvent is concentrated to dryness and the resulting residue is dissolved in dichloromethane (100 mL), washed with water (3 x 100 mL), and saturated NaCl solution. This organic phase is dried over Na 2 SO 4, filtered and evaporated to dryness. Purification by chromatography on silica (CH 2 Cl 2 / MeOH, 100: 00 to 98: 2) of the crude product afforded compound 15 (0.11 g, 77%) as an oil. 1H NMR (CDCl3, 300 MHz): δ 8.44 (d, J = 2.4 Hz, 2H); 7.77 (s, 2H); 6.51 (d, J = 2.6 Hz, 2H); 4.21 (q, J = 7.2 Hz, 8H); 4.05 (s; 4H); 3.63 (s; 8H); 2.49 (t, J = 7.2 Hz, 2H); 2.44 (t, J = 7.4 Hz, 2H); 1.90-1.81 (m; 2H); 1.75-1.65 (m; 2H); 1.27 (t, J = 7.1 Hz, 12H). 13 C NMR (CDCl 3, 300 MHz):? 171.2; 171.1; 152.8; 150.0; 137.2; 127.9; 111.3; 108.4; 96.2; 79.0; 60.6; 54.6; 51.3; 33.3; 27.5; 23.9; 19.2; 14.2. IR (cm-1, ATR): ν 2235 (w, νc = c); 1733 (s); 1610 (s); 1536 (m); 1464 (s); 1388 (s); 1261 (m). For C36H47N7O10 (737.8): C, 58.60; H, 6.42; N, 13.29; measured: C 58.42; H, 6.15; N 12.89. ESI / MS (negative mode, MeOH / H 2 O) m / z: 736.5 ([M-H]] - 100%). Ligand L4 An aqueous solution (4 mL) of NaOH (40 mg, 1.03 mmol) was added to a solution of compound 15 (0.13 g, 0.17 mmol) in methanol (20 mL). The solution is heated at 60 ° C for 3 h. The solvent is evaporated to dryness and the residue is dissolved in a minimum of water and the ligand is precipitated by addition of THF, MeOH and Et2O. The solid is isolated by centrifugation and dried under vacuum to give L4 ligand (0.11 g, 80%) as a pale brown precipitate. 1H NMR (D 2 O, 300 MII 2): δ 8.64 (br s, 2H); 7.72 (s, 2H); 6.70 (d, J = 2.5 Hz, 2H); 3.96 (brs; 4H); 3.30 (brs; 8H); 2.59 (t, J = 6.9 Hz, 2H); 2.29 (t, J = 7.1 Hz, 2H); 1.97-1.71 (m, 4H). 13 C NMR (D20, 300 MHz):? 179.4; 153.8; 150.1; 138.1; 130.2; 112.2; 109.7; 98.9; 78.3; 58.1; 50.8; 37.4; 27.8; 25.3; 19.0. IR (cm '', ATR): ν 2161 (w; vc_c); 1610 (s); 1410 (s); 1327 (m). Calculated for C28H26N7Na5O10.4H2O: C, 41.64; H, 4.24; N, 12.14; measured: C 41.52; H 4.02; N, 11.79. ESI / MS (Negative mode, MeOH / H2O) m / z: 222.2 ([M-3Na +] 3-60%). EXAMPLE 8 SYNTHESIS OF COMPOUND L5 Compound L5 was prepared according to the following reaction scheme: ## STR1 ## ## STR5 ## And CO 2 and CO 2, CO 2, CO 2, CO 2 and CO 2, CO 2 CO2Na CO2Na CO2Na 17 L5 Compound 8-Et was prepared according to the method of Example 4. Compound 17 In a Schlenk tube was mixed 8-Et (60 mg, 0.09 mmol), 4-iodobenzoate, ethyl (30 mg, 0.09 mmol), distilled THF (8 mL) and distilled Et3N (4 mL) This mixture is degassed for 30 min and [Pd (PPh 3) 4] 10 (10.5). mg, 0.01 mmol) is added to the degassed solution, the degassing is continued for 5 minutes and then the solution is heated at 60 ° C. for 14 h The solvent is evaporated to dryness and the residue obtained is dissolved in dichloromethane ( 100 ml), washed with water (3 x 100 ml) and saturated NaCl solution, this organic phase is dried over Na 2 SO 4, filtered and evaporated to dryness, purification by chromatography on silica ( CH 2 Cl 2 / MeOH, 100: 00 to 99: 1) of the crude product afforded compound 17 (40 mg; 55%) as a colorless oil. 1H NMR (CDCl3, 300 MHz): δ 8.48 (d, J = 2.6 Hz, 2H); 8.07 (d, J = 8.0 Hz, 2H); 7.91 (s, 2H); 7.63 (d, J = 8.0 Hz, 2H); 6.56 (d, J = 2.6 Hz, 2H); 4.40 (q, J = 7.2 Hz, 2H); 4.18 (q, J = 7.2 Hz, 8H); 4.06 (s; 4H); 3.64 (s, 8H); 1.41 (t, J = 7.1 Hz, 3H); 1.28 (t, J = 7.3 Hz, 12H).

B5006 13C {1H} NMR (CDCl3, 300 MHz):? 171.0; 153.2; 150.1; 135.8; 131.9; 130.9; 129.6; 128.0; 126.3; 111.0; 108.6; 89.0; 61.2; 60.5; 54.6; 51.4; 14.3; 14.2. IR (cm-1, ATR): ν 2229 (w; vc-c); 1721 (s); 1608 (s); 1553 (s); 1537 (m); 1464 (s); 1389 (s).

EI / MS (solid) m / z: 785.2 ([M] +: 100%). Ligand L5 An aqueous solution (2 mL) of NaOH (10 mg, 0.28 mmol) is added to a solution of compound 17 (40 mg, 0.05 mmol) in methanol (5 mL). The reaction medium is heated at 60 ° C. for 3 h. The solvent is evaporated to dryness and the residue is dissolved in a minimum of water and L5 is precipitated by addition of THF, MeOH and Et2O. The precipitate is isolated by centrifugation and dried under vacuum to obtain L5 (0.03 g, 86%). 1H NMR (D 2 O, 300 MHz): δ 8.58 (br s, 2H); 7.92-7.65 (m, 6H); 6.63 (br s, 2H); 3.88 (s, 4H); 3.28 (s, 8H). 13 C NMR (D20, 300 MHz): 178.98; 174.5; 153.1; 149.3; 137.2; 136.2; 132.0; 129.6; 128.9; 123.5; 110.7; 109.5; 94.7; 87.5; 58.0; 48.9. IR (cm -1, ATR):? 2220? (W; vc?) 1582 (s); 1550 (s); 1534 (w); 1465 (m); 1384 (s); 1327 (m); w) ESI / MS (negative mode, MeOH / H2O) m / z: 354.4 ([M-2Na +] 2-; 80%); 228.5 ([M-20 3Na +] 3 25%) EXAMPLE Compound L6 was prepared according to a procedure corresponding to the following reaction scheme: ## STR5 ## CO2Na 22 L6 TMS OH OH O ~ OEt 1 18 TMS

Compound 19 In a Schlenk tube 4-iodophenol 18 (0.5 g, 2.27 mmol), trimethylsilylacetylene (0.4 ml, 2.72 mmol), Pd (PPh 3) 2 Cl 2 (95, 5 mg, 0.14 mmol), distilled THF (15 mL) and distilled Et3N (8 mL). The mixture is degassed for 30 min and Cul (43.2 mg, 0.23 mmol) added to the degassed solution. The reaction medium is stirred at room temperature for 14 hours. The solvent is concentrated to dryness and the resulting residue is dissolved in dichloromethane (100 mL), washed with water (3 x 100 mL), and saturated NaCl solution. This organic phase is dried over Na 2 SO 4, filtered and evaporated to dryness. Purification by silica chromatography (petroleum ether / CH 2 Cl 2, mp = 0.005 to 0.001) of the crude product afforded compound 19 (0.34 g, 78%) as a brown solid. 1H NMR (CDCl3, 300 MHz): δ 7.39-7.34 (in; 2H); 5.78-6.73 (m, 2H); 6.15 (s, 1H); 0.27 (s, 9H). 13C {1H} NMR (CDCl3, 300 MHz): S, 155.6; 133.7; 115.4; 115.3; 105.5; 92.9; 0.05. IR (cm-1, ATR): v 2161 (s; vc-c); 1882 (s); 1608 (s); 1590 (m); 1545 (w); 1507 (s); 1434 (m). Calculations calculated for C11H14OSi.4H2O: C, 69.42; H, 7.41; measured: C 69.13; H 7.22.

EI / MS (solid) m / z: 190.1 ([M] +; 100%). Compound 20 To a suspension of NaH (60% in oil, 0.07 g, 1.87 mmol) in distilled THF (10 mL) cooled to 0 ° C was added under argon Compound 19 ( 0.32 g, 1.70 mmol). To this mixture is added at room temperature ethyl 4-bromobutyrate (0.49 ml, 3.40 mmol) and a catalytic amount of NaI. The solution is brought to 50 ° C for two nights. The solvent is evaporated to dryness and the resulting residue is dissolved in dichloromethane (100 mL), washed with water (3 x 100 mL), and saturated NaCl solution. This organic phase is dried over Na 2 SO 4, filtered and evaporated to dryness. Purification by silica chromatography (petroleum ether / CH2Cl2, 90:10 to 00: 100) from the crude product afforded compound 20 (0.19 g, 37%) as a colorless oil. 1H NMR (CDCl3, 300 MHz): δ 7.37 (d, J = 8.8 Hz, 2H); 6.77 (d, J = 8.8 Hz, 2H); 4.12 (q, J = 7.1 Hz, 2H); 3.96 (t, J = 6.0 Hz, 2H); 2.48 (t, J = 7.3 Hz, 2H); 2.07 (q, J = 6.7 Hz, 2H); 1.23 (t, J = 7.1 Hz, 3H); 0.23 (s, 9H). 13C {1H} NMR (CDCl3, 300 MHz): δ 172.9; 158.9; 133.4; 115.2; 114.2; 105.1; 92.3; 66.6; 60.3; 30.6; 24.4; 14.1; 0.03. IR (cm -1, ATR):? 2155 (s; vc-c); 1893 (w); 1733 (s); 1605 (s); 1569 (w); 1506 (s); 1473 (m). Analyzes Calculated for C 17 H 24 O 3 Si: C 67.06, H 7.95, C 66.75, H 7.78, 20 EI / MS (solid) m / z: 305.1 ([M + H] +; Compound 21 A solution of TBAF (1M in THF) (0.67 mL, 0.67 mmol) was added dropwise under argon to a solution of compound 20 (0.17 g, 0.56 mmol) in distilled THF (5 mL) cooled to 0 ° C. The reaction medium is stirred for 1 h at 0 ° C. and then for 2 h at room temperature, then neutralized with water The solvent is evaporated to dryness. The residue obtained is dissolved in dichloromethane (100 mL), washed with water (3 x 100 mL) and saturated NaCl solution This organic phase is dried over Na 2 SO 4, filtered and evaporated to dryness The crude product is purified by chromatography on silica (petroleum ether / CH2Cl2, 2935973 B5006FR

50:50 to 00: 100) to obtain compound 21 (0.13 g) in quantitative yield as a white solid.

1H NMR (CDCl3, 300 MHz): δ 7.39 (d, J = 8.8 Hz, 2H); 6.80 (d, J = 8.8 Hz, 2H); 4.13 (q, J = 7.2 Hz, 2H); 3.97 (t, J = 6, Hz, 2H); 3.00 (s; 1H); 2.49 (t, J = 7.1 Hz, 5H); 2.08 (q, J = 6.7 Hz, 2H); 1.24 (t, J = 7, 1 Hz, 3H). 13C {1H} NMR (CDCl3, 300 MHz): b 172.9; 159.1; 133.4; 114.3; 114.1; 83.5; 75.8; 66.6; 60.3; 30.6; 24.4; 14.1. IR (cm-1, ATR): v 2107 (w; vc-c); 1722 (s); 1607 (s); 1572 (m); 1511 (s); 1470 (s); 1440 (m).

Calculated for C14H16O3: C, 72.39; H, 6.94. Measured C 72.20; H, 6.73. EI / MS (solid) m / z: 233.1 ([M + H] +; 100%). Compound 22 In a Schlenk tube is compound 5-Et (0.19 g, 0.27 mmol), compound 21 (0.08 g, 0.33 mmol), [Pd (PPh 3) 2 Cl 2) (11 , 4 mg, 0.02 mmol), THF

Distilled (10 mL) and distilled Et3N (5 mL). This mixture is degassed for 30 minutes, then Cul (5.20 mg, 0.03 mmol) is added to the degassed solution. The reaction medium is brought to 50 ° C throughout the 14 hours. The solvent is concentrated to dryness and the resulting residue is dissolved in dichloromethane (100 mL), washed with water (3 x 100 mL), and saturated NaCl solution. This organic phase is dried over Na 2 SO 4, filtered and evaporated to dryness. Purification of the crude product by chromatography on silica (CH 2 Cl 2 / MeOH, 100: 00 to 98: 2) afforded compound 22 (0.12 g, 53%) as an oil. 1H NMR (CDCl3, 300 MHz): δ 8.45 (d, J = 2.6 Hz, 2H); 7.83 (s, 2H); 7.47 (d, J = 8.4 Hz, 2H); 6.87 (d, J = 8.8 Hz, 2H); 6.52 (d, J = 2.6 Hz, 2H); 4.21-3.99 (m; 16

H); 3.61 (s, 8H); 2.50 (t, J = 7.2 Hz, 2H); 2.10 (q, J = 6.7 Hz, 2H); 1.28-1.20 (m, 15H). 13C {1H} NMR (CDCl3, 300 MHz): S, 173.0; 171.0; 159.7; 152.9; 149.9; 136.7; 133.6; 127.9; 114.6; 113.9; 110.7; 108.3; 95.2; 85.6; 66.8; 60.4; 60.3; 54.5; 51.3; 30.6; 24.4; 14.1. IR (cm-1, ATR): v2204 (m; vc-c); 1731 (s); 1599 (s) :, 1552 (s); 1538 (m); 1512 (m); 1464 (s). EI / MS (solid) m / z: 843.2 ([M] + 100%). Ligand L6 An aqueous solution (2 mL) of NaOH (30.7 mg, 0.77 mmol) is added to a solution of compound 22 (0.11 g, 0.13 mmol) in methanol (5 mL). The reaction medium is heated at 60 ° C. for 3 h. The solvent is evaporated to dryness and the residue is dissolved in the minimum of H2O. Addition of THF, MeOH and Et 2 O affords a precipitate which is isolated by centrifugation and dried under vacuum to give L6 (90.1 mg, 87%) as a precipitate. 1H NMR (D 2 O, 300 MHz): δ 8.37 (br s, 2H); 7.37 (s, 2H); 7.31 (d, J = 7.9 Hz, 2H); 6.75 (d, J = 7.9 Hz, 2H); 6.52 (br s, 2H); 3.74 (s; 4H); 3.19 (s, 8H); 2.36 (t, J = 7.4 Hz, 2H); 2.05-2.00 (m, 2H); 1.86-1.84 (m, 2H). 13 C NMR (D20, 300 MHz): S, 183.2; 179.6; 159.9; 153.7; 149.6; 137.2; 134.5; 130.0; 115.2; 113.9; 110.7; 109.9; 96.3; 86.2; 68.4; 58.6; 51.4; 34.5; 26.1. IR (cm-1, ATR):? 2201 (s; vc-c); 1590 (s); 1554 (w); 1511 (m); 1408 (s); 1336 (m); 1248 (m). Calculated for C33H34N7Na5O14.3H2O: C, 45.68; H, 3.95; N 11.30. Measured: C, 45.62; H, 3.75; N, 11.20. ESI / MS (negative mode, MeOH / H 2 O) m / z: 248.0 ([M-3Na] 3 100%); 180.0 ([M-4Na] 4 - 20%) EXAMPLE 10 SYNTHESIS OF COMPOUND L7 Compound L7 was prepared from compound 8-And according to the following reaction scheme: B5006FR NO and 02 and CO2 and CO2 r CO2Na CO2Na CO2Na CO2Na NC Ett O2Et CO and CO2Et 8-And Br 23 Compound 24 24 L7 In a Schlenk tube 8-Et (0.08 g, 0.13 mmol), 23 (0.06 g; 14 mmol), distilled toluene (10 mL) and distilled Et3N (5 mL) were degassed for 30 min and [Pd (PPh3) 4] (14.4 mg, 0.01 mmol) was added The solution is degassed for 5 minutes and then heated at 60 ° C. for 14 hours The solvent is evaporated to dryness and the residue obtained is dissolved in dichloromethane (100 ml), washed with water (3 ml). x 100 mL) and a saturated solution of NaCl This organic phase is dried over Na 2 SO 4, filtered and evaporated to dryness Purification of the crude by chromatography on silica (CH 2 Cl 2 / MeOH, 99: 1 to 95: 5) and then on alumina ( CH 2 Cl 2 / MeOH, 100: 00 to 99.5: 0, 5) provides compound 24 (13.2 mg; 11%), in the form of an oil. 1H NMR (CDCl3, 300 MHz): δ 8.47 (d, J = 2.5 Hz, 2H); 7.87 (s, 2H); 7.16 (d, J = 7.7 Hz, 1H); 7.08 (s; 1H); 6.86 (d, J = 8.2 Hz, 1H); 6.54 (d, J = 2.4 Hz, 2H); 4.22-3.64 (m, 40H); 1.27 (t, J = 7.1 Hz, 12H). NMR (CDCl3, 300 MHz): δ 171.0; 153.0; 150.4; 150.0; 148.6; 136.7; 127.9; 126.0; 117.0; 114.3; 113.3; 110.8; 108.4; 95.4; 85.6; 71.0; 70.8; 70.7; 69.5; 69.1; 69.0; 60.5; 54.5; 53.4; 51.4; 14.2. EI / MS (solid) m / z: 948.2 ([M] + 100%). IR (cm -1, ATR): 1737 (s); 1608 (s); 1596 (s); 1551 (s); 1535 (m); 1515 (s). B5006EN 2935973 36 Ligand L7 An aqueous solution (2 mL) of NaOH (5.2 mg, 0.13 mmol) is added to a solution of 24 (24.7 mg, 0.03 mmol) in methanol (7 mL). . The reaction medium is heated at 60 ° C. for 3 h. The solvent is evaporated to dryness and the residue is dissolved in a minimum of water and precipitated by addition of THF, MeOH and Et2O. The solid is isolated by centrifugation and then dried to give L7 (0.02 g, 83%) as a yellow precipitate. 1 H NMR (D 2 O, 400 MHz, all peaks are broad): S 8.47 (s, 2H); 7.49-6.60 (m, 7H); 3.95 (m, 32H). ESI / MS (Negative Mode, MeOH / H 2 O) m / z: 285.0 ([M-3Na] 3 -> 100%) IR (cm-1, ATR): 2208 (w); 1594 (s); 1552 (m); 1515 (m); 1463 (s); 1433 (s) EXAMPLE 11 SYNTHESIS OF COMPOUND L8 Compound L8 was prepared according to the following reaction scheme: Br N IN Ett 02At CO and CO2Et 5-And 25 + CO2Na CO2Na CO2Na CO2Na L8 rN N rv ru COZEt lr And COZEt r 26 Compound 26 In a Schlenk tube 5-Et (0.29 g, 0.43 mmol) is mixed on the 4- ethynyl-2,2'-6,2 "-terpyridine (0.13 g, 0.05 mmol), [Pd (PPh 3) 2 Cl 2) (17.9 mg, 0.03 mmol), distilled THF ( mL) and distilled Et3N (6 mL). The mixture is degassed by bubbling argon for 30 minutes and Cul (8.10 mg, 0.43 mmol) is added to the degassed solution. The reaction medium is heated at 50 ° C. for 14 hours. The solvent is concentrated to dryness and the resulting residue is dissolved in dichloromethane (100 mL), washed with water (3 x 100 mL), and saturated NaCl solution. This organic phase is dried over Na 2 SO 4, filtered and evaporated to dryness. Purification by chromatography on silica (CH 2 Cl 2 / MeOH, 100: 00 to 97: 3) of the crude product afforded compound 26 (0.12 g, 32%) as an oil. 1H NMR (CDCl3, 300 MHz): δ 8.74 (d, J = 3.9 Hz, 2H); 8.63-8.61 (m, 4H); 8.48 (d, J = 2.5 Hz, 2H); 7.95 (s, 2H); 7.88 (td, J = 7.7 Hz, J = 1.6 Hz, 2H); 7.39-7.35 (m, 2H); 6.57 (d, J = 2.6 Hz, 2H); 4.20 (q, J = 7.2 Hz, 8H); 4.08 (s; 4H); 3.66 (s, 8H); 1.29 (t, J = 7.2 Hz, 12H). NMR (CDCl3, 400 MHz): 8170.9; 155.6; 155.2; 153.1; 150.1; 149.1; 136.8; 135.2; 131.7; 127.8; 124.0; 122.9; 121.1; 111.1; 108.5; 92.1; 90.0; 60.4; 54.5; 51.3; 14.1. EI / MS m / z: 869.5 ([M + H] + - 100%) IR (cm-1, ATR): 2221 (w) 1736 (s); 1607 (s); 1583 (s); 1567 (m); 1553 (s); 1538 (m). Ligand L8 An aqueous solution (2 mL) of NaOH (24.6 mg, 0.62 mmol) is added to a solution of 26 (0, 11 g, 0.12 mmol) in methanol (7 mL) The reaction mixture is heated at 60 ° C. for 3 h The solvent is evaporated to dryness and the residue is dissolved in a minimum of H 2 O and L 8 is obtained by precipitation by addition of THF, MeOH and Et2O The solid is isolated by centrifugation and then dried under vacuum, affording L8 (0.07 g, 65%) as a beige precipitate. D20, 400MHz): δ 8.43 (br s, 2H), 8.17-7.37 (m, 8H), 7.28 (br s, 4H), 6.47 (br s; 2H), 3.76 (brs; 4H), 3.22 (brs; 8H), ESI / MS (negative mode, MeOH / H 2 O) m / z: 399.1 ([M-2Na] 2 100%) 258.5 ([M-25 3Na] 3, 20%) IR (cm-1, ATR): 2163 (w); 1583 (s); 1554 (s); 1428 (s); 1390 (s); 1325 (m); 1263 (m). EXAMPLE 12 SYNTHESIS OF THE COMPOUND L9 was prepared according to the following reaction scheme: ## EQU1 ## 0.30 g; 0.43 mmol), glycyl ethyl ester hydrochloride (0.18 g, 1.30 mmol), [Pd (PPh 3) 2 Cl 2) (60.8 mg, 0.09 mmol), distilled Et 3 N (10 mL). ) and distilled toluene (15mL) is heated at 100 ° C for 14 hours with a continuous flow of CO at atmospheric pressure. The precipitate formed is filtered. The filtrate is evaporated to dryness and the residue is dissolved in dichloromethane (100 mL), washed with water (3 x 100 mL) and saturated NaCl solution. This organic phase is dried over Na 2 SO 4, filtered and evaporated to dryness. The crude product is purified by silica chromatography (CH 2 Cl 2 / MeOH, 100: 00 to 95: 5) to afford compound 27 (0.26 g, 81%). 1H NMR (CDCl3, 300 MHz): δ 8.45 (d, J = 2.6 Hz, 2H); 8.12 (s, 2H); 7.07 (t, J = 4.9 Hz, 1H); 6.55 (d, J = 2.6 Hz, 2H); 4.304.14 (m, 12H); 4.04 (s; 4H); 3.62 (s, 8H); 1.34 ± 1.2 (m, 15H). 13 C NMR (CDCl 3, 300 MHz):? 171.0; 169.4; 164.7; 153.5; 150.7; 146.7; 128.0; 108.7; 106.8; 61.7; 60.5; 54.6; 51.4; 41.9; 14.2; 14.1. IR (cm-1, ATR):? 1732 (s); 1674 (m); 1618 (m); 1571 (s); 1534 (s); 1463 (s). Calculated for C34H46N8O11 (742.8): C 54 , 98, H 6.24, N 15.09, measured: C 54.70, H 5.95, N 14.65, EI / MS (solid) m / z: 743.0 ([M + H]) + 100%) Ligand L9 An aqueous solution (4 mL) of NaOH (0.09 g, 2.29 mmol) is added to a solution of 27 (0.28 g, 0.38 mmol) in methanol ( 20 mL) The reaction medium is heated at 60 ° C. for 3 h The solvent is evaporated to dryness and the residue is dissolved in a minimum of water This aqueous phase is washed with dichloromethane (3 × 100) The addition of THF, MeOH and Et2O resulted in the formation of a precipitate which was isolated by centrifugation and dried to give L9 (0.26 g, 94%) as a yellow precipitate. 1H NMR (D 2 O, 300 MHz): δ 8.70 (br s, 2H), 8.01 (br s, 2H), 6.71 (br s, 2H), 4.01 (brs; brs; 2H); 3.95 (brs; 4H); 3.29 (brs; 8H). 13C (1H NMR (D20, 300MHz): S, 179.9; 177.0; 167.7, 154.4; 150.9, 148.1, 130.6, 110.2; 108.1; 58.6; 51.2; 44.7. IR (cm '', ATR): ν 1570 (s); 1531 (s); 1463 (s); 1389 (s); 1326 (s); 1255 (s). Calculated for C24H21N8Na5O11.3H2O (766.5): C, 37.61; H, 3.55; N, 14.62; measured: C 37.42; H, 3.25; N, 14.41. ESI / MS (negative mode, MeOH / H 2 O) m / z: 214.2 ([M-3Na +] 3 80%). EXAMPLE 13 Synthesis of compound L10 Compound L10 was prepared according to the following reaction scheme: ## STR1 ## And 28 Compound 28 Compound 5-Et (200 mg, 0.29 mmol) and hydrochlorinated ethyl 4-aminobutyrate (97 mg, 0.58 mmol) were dissolved in 10 ml of distilled toluene and 10 ml of triethylamine. [Pd (PPh 3) 2 Cl 2] (20 mg, 0.029 mmol) is added. The solution is placed at 100 ° C under a continuous flow of CO at atmospheric pressure for 12 hours. 2935973 B5006FR

The solution is filtered through Celite and then evaporated to dryness to give a pale yellow oil. The residual oil is dissolved in 30 ml of CH 2 Cl 2 and the organic phase is washed with 3 x 15 ml of water, then dried over Na 2 SO 4 and evaporated to dryness. 28 (126 mg, 57%) is isolated by column chromatography (SiO 2, CH 2 Cl 2 / MeOH, 100/0 to

98/2) as a colorless oil. 1 H NMR (CDCl 3, 300 MHz): δ 1.21 (t, J = 7.2 Hz, 3H); 1.22 (t, J = 7.2 Hz, 12H); 1.96 (qt; J = 7.1 Hz; 2H); 2.44 (t, J = 7.1, 2H); 3.50 (q, J = 7.0 Hz, 2H); 3.58 (s; 8H); 3.99 (s; 4H); 4.10 (q, J = 7.2 Hz, 2H); 4.13 (q, J = 7.2 Hz, 8H); 6.48 (d, J = 2.6 Hz, 2H); 8.04 (s; 2H); 8.40 (d, J = 2.6 Hz, 2H). 13C NMR (CDCl3, 300 MHz): δ 14.1 (2C); 24.3; 31.7: 39.7; 51.3; 54.4; 60.4; 60.5; 106.7; 108.5; 127.9; 147.5; 150.4; 153.2; 164.6; 170.9; 173.2. IR (ATR, cm-1): ν 3330 (br); 3126 (w); 2981 (w); 2936 (w); 1731 (s); 1671 (m); 1617 (m); 1569 (m); 1534 (m); 1463 (s); 1388 (s); 1304 (w); 1259 (w); 1187 (s); 1154 (s); 1096 (w); 1027 (s). Ligand L10 28 (126 mg, 0.16 mmol) was dissolved in 40 ml of a methanol (1/1) mixture. NaOH (39 mg, 0.98 mmol) is added. The mixture is left at 60 ° C for 3 hours. The solvent is evaporated and the residue is solubilized in 20 ml of water, the aqueous phase is washed with 3 x 10 ml of DCM and then evaporated to dryness to give

Pale yellow residue. The residue is dissolved in 0.5 ml of water. Methanol, THF and dicthylether are added gradually leading to the formation of a precipitate. The mixture is triturated, the solid is isolated by centrifugation and dried to obtain L10 as a very fine pale yellow powder (113 mg, 95%). 1H NMR (D 2 O, 300 MHz):? 1.91 (qt; J = 7.2Hz; 2H); 2.29 (t, J = 7.2 Hz, 2H); 3.27 (s, 8H); 3.45 (t, J = 7.2 Hz, 2H); 3.91 (s, 4H); 6.66 (s; 2H); 7.94 (s; 2H); 8.64 (s, 2H). 40.5; 51.3; 58.7; 68.3; 107.3; 110.0; 13 C NMR (D 2 O, 300 MHz): S, 25.8; 35.4; 130.0; 150.2; 165.0; 167.1; 179.4; 183.1. IR (ATR cm -1):? 3276 (br); 2934 (w); 1568 (s); 1462 (m); 1403 (s); 1327 (m); 1123 (m); 1051 (m). Calculated for C26H25N3Na5O11.5H2O: C 37.43, H 3.96, N 13.24, measured: C 37.60, H 4.25, N 13.49, ESI (negative mode, MeOH / H 2 O). MS / ml: 347.1 ([M-2Na +] 2-; 80%); 223.6 ([M-3Na +] 3 80%) EXAMPLE 14 SYNTHESIS OF L11 COMPOUND Synthesis of an L11 ligand is carried out according to the following reaction scheme: ## STR1 ## 5-Et (100 mg, 0.14 mmol) and 29 (50.3 mg, 0.29 mmol, obtained according to WS Sarari, JE Schwering, PA Lyle, SJ Smith, Engelhardt EL, J. Med Chem, 1990, 33, 97) are dissolved in 10 mL of distilled toluene and 10 mL of distilled triethylamine [Pd (PPh 3 2C12] (9.8 mg, 0.014 mmol) is added The solution is heated at 100 ° C. under a continuous flow of CO at atmospheric pressure for 12 hours The solution is filtered on celite and then evaporated to dryness to give A pale yellow oil The residual oil is dissolved in 30 ml of CH 2 Cl 2 and the organic phase is washed with 3 x 15 ml of water, dried over Na 2 SO 4 and evaporated to dryness. (70 mg, 60%) is isolated by column chromatography (SiO2, CH2Cl2 / MeOH, 100/0 to 95/5) as a colorless oil. 1 H NMR (CDCl 3, 300 MHz): δ 1.25 (t, J = 7.2 Hz, 12H); 1.44 (s, 9H); 1.76 (t, J = 7.0 Hz, 2H); 2.16 (broad s, 1H); 3.24 (t, J = 7.0 Hz, 2H); 3.54 (q, J = 7.0 Hz, 2H); 3.61 (s, 8H); 4.02 (s, 4H); 4.16 (q, J = 7.2 Hz, 8H); 6.52 (d, J = 2.6 Hz, 2H); 8.13 (s, 15H); 8.45 (d, J = 2.6 Hz, 2H). 13C NMR (CDCl3, 300 MHz): δ14.2; 28.4; 30.0; 37.0; 51.5; 53.4; 54.6; 60.6; 79.6; 106.8; 108.6; 128.1; 147.5; 150.6; 153.3; 156.8; 164.8; 171.1. IR (ATR, cm-1): v 3341 (br); 3126 (w); 3060 (w); 2980 (m); 2934 (m); 1737 (s); 1671 (ni); 1618 (m); 1570 (s); 1533 (s); 1462 (s); 1389 (s); 1366 (s); 1303 (m); 1270 (s); 1251 (s); 1188 (s); 1155 (s); 1096 (m); 1027 (s). Calculations calculated for C38H55N9011 (813.9): C 56.08: H, 6.81; N, 15.49. Measured: C 55.73; H, 6.51; N, 15.58. EI / MS (solid) m / z: 814.2 ([M + H] +, 100%), 712.3 ([(M-05H9O2) + H] +, 35%). Compound 31 Compound 30 (35 mg, 43 mol) is dissolved in 10 mL of CH2Cl2. TFA (20 L, 0.26 mmol) is added. The solution is stirred at ambient temperature for 12 hours. The solvent is evaporated. The residual oil is dissolved in 10 mL of CH 2 Cl 2, washed with 3 x 10 mL of water. The organic phase is dried over Na2SO4, filtered and concentrated to give 31 (26 mg, 85%). H NMR (CD3OD, 300 MHz): S 1.18 (t, J = 7.2 Hz, 12H); 2.06 (t, J = 7.0 Hz, 2H); 3.06 (t, J = 7.0 Hz, 2H); 3.54 (t, J = 7.0 Hz, 2H); 4.18 (s, 8H); 4.25 (q, J = 7.2 Hz, 8H); 4.56 (s, 4H); 6.75 (d, J = 2.0 Hz, 2H); 8.24 (s, 2H); 8.81 (d, J = 2.0 Hz, 2H). 13C NMR (CD3OD, 300 MHz): S 13.0; 27.3; 29.5; 36.6; 37.0; 51.5; 53.8; 61.6; 107.3; 109.9; 129.2; 147.6; 148.2; 150.3; 168.0. IR (ATR, cm -1):? 3271 (br); 3060 (br); 2987 (m); 1744 (s); 1672 (s); 1620 (m); 1571 (m); 1531 (m); 1460 (m); 1385 (m); 1301 (w); 1196 (s); 1179 (s); 1132 (s); 1052 (m); 1018 (m). EI / MS (solid) m / z: 714.2 ([M + H] +, 100%) Compound 33 Biotin 32 (100 mg, 0.41 mmol) and 10 mL distilled DMF are added to a Schlenk tube under argon. at 50 ° C. until complete dissolution of the biotin After cooling to room temperature, the NHS (57 mg, 0.50 mmol) and EDCI-HCl (94 mg, 0.50 mmol) are added. stirred at room temperature under an inert atmosphere for 12 hours The solvent is evaporated to give a white solid The residue is dissolved in 20 ml of CH 2 Cl 2 The organic phase is washed with 3 × 10 ml of water and then dried over Na 2 SO 4. filtered and concentrated to give 33 (98 mg, 70%) as a white solid 1H NMR (d6-DMSO, 300MHz): b 1.3-1.8 (m, 6H); (s, 2H); 2.50-2.77 (m, 2H); 2.8.5 (s, 4H); 3.09; (m, 1H); 4.14 (m, 1H); 4.30 (m, 1H); 6.36 (s, 1H); 6.42 (s, 1H). 13C NMR (d6-DMSO, 300MHz): S, 24.8; 25.9; 28.0; 28.3; 30.4; 55.4; 55.7; 59.6; 61.4; 163.1; 169.4; 170.7. IR (ATR, cm -1): v 3341 (br); 3226 (br); 3117 (w); 2940 (w); 2918 (w); 2877 (w); 1818 (m); 1787 (m); 1746 (m); 1728 (s); 1697 (s); 1553 (w); 1464 (m); 1435 (m); 1422 (m); 1368 (m); 1209 (s); 1070 (s); 1061 (s); 1047 (s). EI / MS (solid) m / z: 244.32 ([(M-C4H4O2) + H] +, 100%, 341.1 ([M + H] +, 20%) B5006FR 2935973 44 Compound 34 The compound 31 (26 mg, 36 mol) is dissolved in 10 mL of DMF and 30 L of triethylamine 33 (15 mg, 44 mol) is added The solution is stirred at room temperature for 12 hours The solvent is evaporated to give a The residue is dissolved in 20 mL of CH 2 Cl 2, washed with 3 x 10 mL of water The organic phase is dried over Na 2 SO 4, filtered and concentrated The purification by chromatography on silica (DCM / VELOH, 99: 1 95: 5) afforded 34 (15mg, 45%) as a pale yellow oil Ligand L11 Compound 34 (12.6mg, 0.16mmol) was dissolved in 40mL of MeOH solution Water (1: 1) and NaOH (39 mg, 0.98 mmol) are added The solution is stirred at 60 ° C. for 3 hours The solvents are evaporated and the residue is dissolved in 20 ml of water and then washed with 3 x 10 ml of CH 2 Cl 2 The aqueous phase is evaporated The pale yellow residue is dissolved or in 0.5 mL of water and 4 mL of MeOH. L11 (10.0 mg, 68%) is precipitated as a fine pale yellow powder by addition of THF and diethyl ether. IR (ATR cm -1):? 3263 (br); 1567.7 (s); 1538 (s); 1492 (m); 1442 (m); 1396 (s); 1357 (m); 1258 (w); 1231 (w); 1124 (m); 1070 (m); 1008 (w). EXAMPLE 15 SYNTHESIS OF A 5 "COMPOUND A 5" -Et compound was prepared according to US Pat. following reaction scheme: B5006FR 45 Br Br + F --- 'e-F COOEt 35 1 EtOOC 2 "-And COC And Br Br 4" Compound 2 "-And In a Schlenk flask under argon, compound 1 ( 680 mg, 3.5 mmol), compound 35 (1.46 g, 7.7 mmol, obtained according to A. Schmidt, L. Merkel, W.

Eisfeld, Eur. J. Org. Chem. 2005, 2124-2130) and 30 mL of distilled DMF. The solution is cooled to 0 ° C and NaH (60% by weight in oil, 308 mg, 7.7 mmol) is added. The temperature of the mixture is raised to ambient temperature. The mixture is then heated at 40 ° C for 5 hours. After 5 hours of reaction, a white precipitate is formed. The precipitate is separated from the solution by centrifugation.

The addition of water to the mother liquor gives a second isolated precipitate by centrifugation. The entire precipitate is dissolved in 40 ml of a DCMIEau mixture (1: 1). The organic phase is separated and the aqueous phase is washed with 3 x 10 ml of DCM. The organic phases are combined, dried over Na2SO4, filtered and then evaporated to dryness to give the compound 2 "-Et in the form of a white powder (1.75 g, 94%) .1H NMR (CDCl3, 400 MHz): S 8.64 (d, J = 8.5 Hz, 2H), 8.35 (d, J = 8.1 Hz, 2H), 8.31 (s, 2H), 7.56 to 7.45 (m). 4H) 4.62 (q, J = 7.1Hz, 4H) 1.56 (t, J = 7.1Hz, 6H) 13C NMR (CDCl3, 300MHz): δ 14.4; 61.7, 114.7, 115.8, 122.5, 124.8, 125.1, 128.8, 136.5, 139.2, 140.0, 151.9, 162.1, 2935973 and B5006. Compound 4 "(i) Compound 2" -Et (1.7 g, 3.2 mmol) and anhydrous THF (120 ml) are added to a Schlenk flask under argon and the mixture is cooled to -10 ° C. 240 mg, 6.4 mmol) is added in small portions After complete addition of the LiAlH 4, the mixture is stirred at -10 ° C. for 2 hours and then hydrolysed with a minimum of saturated NH 4 Cl solution until the mixture is stirred. This mixture is filtered through Celite and the filtrate is evaporated to dryness to give 1.12 g of a white solid. The solid is introduced into a Schlenk flask under argon, containing distilled DMF (50 mL) and PBr3 (0.6 mL; 6.3 mmol) at room temperature. The mixture is stirred at room temperature for 14 hours. The solvent is evaporated to dryness. The residue obtained is dissolved in 20 ml of DCM and neutralized with 10 ml of a saturated solution of NaHCO 3. The aqueous phase is extracted with dichloromethane (4 × 20 mL), and the combined organic phases are washed with saturated NaCl solution, dried over Na 2 SO 4, filtered and evaporated to dryness. The crude product is purified by chromatography on silica (toluene / petroleum ether (75:25) as eluent) to obtain the compound 4 "(420 mg, 35%), in the form of a pale yellow solid. (CDCl 3, 300 MHz): δ 8.64 (d, J = 8.5 Hz, 2H), 8.04 (s, 2H), 7.92 (d, J = 8.1 Hz, 2H); 7.54-7.37 (m, 4H); 4.90 (s, 4H) .13C NMR (CDCl3, 300MHz): δ 23.2; 113.8; 115.1; 120.7; 4, 124.5, 128.8, 139.1, 140.1, 145.7, 152.3, Compound 5, and 4 "(0.42 g; 73 mmol), iminodiacetic acid ethyl ester (0.29 mL, 1.61 mmol) and K2CO3 (0.40 g, 2.92 mmol) in THF (25 mL) / C'H3CN (50 mL) distilled The reaction mixture is heated at 60 ° C. for 15 h and then filtered The filtrate is concentrated to dryness The resulting oil is dissolved in dichloromethane (20 mL), washed with water water (3 x 10 mL) and saturated NaCl solution The organic phase is dried over Na 2 SO 4, filtered and evaporated at room temperature. The purification by chromatography on silica (CH 2 Cl 2 / MeOH, 100: 00 to 98: 2) of the crude product gives the compound 5 "-Et (322 mg; 56%) as a white solid. 1H NMR (CDCl3, 300 MHz): δ 8.62 (d, J = 8.4 Hz, 2H); 8.18 (d, J = 7.7 Hz, 2H); 7.97 (s, 2H); 7.50-7.26 (m, 4H); 4.40 (s, 4H); 4.19 (q, J = 7.0 Hz, 8H); 3.67 (s, 8H); 1.28 (t, J = 7.0 Hz, 12H). 13C NMR (CDCl3, 300 MHz): 14.2; 50.3; 54.7; 60.5; 112.8; 114.5; 121.7; 122.7; 125.6; 128.3; 135.4; 139.7; 146.8; 152.4; 170.9. IR (ATR, cm-1): 2986 (w), 2905 (w), 1732 (s), 1610 (w), 1586 (w), 1569 (s), 1518 (w), 1438 (s), 1346 (m), 1264 (w), 1236 (w), 1187 (s), 1136 (s), 1070 (s), 1025 (m), 981 (m). EXAMPLE 16 SYNTHESIS OF 5 "COMPOUND A 5" -Bu compound was prepared according to the procedure of Example 15. Br 5 "Bu In a Schlenck flask under argon compound 4 was mixed ( 90 mg, 0.16 mmol), tert-butyl ester of iminodiacetic acid (84.2 mg, 0.34 mmol) and K2CO3 (43 mg, 0.31 mmol) in a THF mixture (5 mL ) / CH3CN (10 mL) distilled. The reaction medium is heated at 80 ° C. for 14 h and then filtered. The filtrate is concentrated to dryness. The resulting oil is dissolved in dichloromethane (50 mL) and washed with water (2 x 25 mL). The organic phase is dried over Na 2 SO 4, filtered and evaporated to dryness. Purification by chromatography on silica (CH 2 Cl 2 / MeOH 100: 00 to 98: 2) of the crude product afforded the compound 5 "-Bu (100 mg, 84%) as a colorless oil. B5006FR

1H NMR (CDCl3, 200 MHz): δ 8.63 (d, J = 8.4 Hz, 2H); 8.21 (d, J = 7.7 Hz, 2H); 7.98 (s, 2H); 7.50 to 7.26 (m, 4H); 4.38 (s, 4H); 3.53 (s, 8H); 1.45 (s, 36H). 13 C NMR (CDCl 3, 200 MHz): δ 28.2; 51.0; 55.7; 81.2; 112.9; 114.6; 122.0; 122.9; 125.9; 128.4; 135.5; 139.8; 147.3; 152.7; 170.4.

EXAMPLE 17 SYNTHESIS OF L12 COMPOUND O) Compound 36 Compound 5 "-Et (90 mg, 0.11 mmol) and hydrochlorinated ethyl 4-aminobutyrate (38 mg, 0.23 mmol) were dissolved in 10 ml. of distilled toluene and 10 ml of triethylamine [Pd (PPh 3) 2 Cl 2] (8 mg, 0.011 mmol) is added The solution is heated at 100 ° C. under a continuous flow of CO at atmospheric pressure for 24 hours. filtered on celite then evaporated to dryness to give a pale yellow oil The residual oil is dissolved in 30 ml of CH 2 Cl 2 and washed with 3 x 15 ml of water, dried over Na 2 SO 4, and evaporated to dryness. mg, 54%) is isolated by column chromatography (SiO2, CH2Cl2 / MeOH, 100/0 to 99.4 / 0.6) as a pale yellow oil.1H NMR (CDCl3, 300MHz): S8 , 64 (d, J = 8.5 Hz, 2H), 8.17 (d, J = 8.1 Hz, 2H), 8.15 (s, 2H), 7.50 to 7.28 (m, 4H), 7.18 (t, J = 5.4 Hz, 11-E), 4.41 (s, 4H), 4.18 (q, J = 7.2 Hz, 10H); s, 8H); 3.62 to 3.55 (m, 2H); 2.47 (t, J = 7.2 Hz, 2H); 2.03; (qt, J = 7.2 Hz, 2H), 1.26 (t, J = 7.2 Hz, 15H). 13C NMR (CDCl3, 300 MHz): S, 14.1; 24.5; 31.9; 39.8; 50.6; 54.8; 60.6; 107.6; 114.5; 121.6; 122.7; 125.6; 128.3; 139.7; 146.5; 146.7; 152.8; 165.2; 171.1; 173.5. COMPOUND L12 Compound 36 (50 mg, 57 mol) is dissolved in 20 ml of methanol / water (1/1). NaOH (14 mg, 0.34 mmol) is added. The mixture is heated at 60 ° C for 4 hours. The solvent is evaporated and the residue is solubilized in 20 ml of water. The aqueous phase is washed with DCM (3 x 10 ml) and then evaporated to dryness to give a pale yellow residue. The residue is dissolved in 0.5 ml of water. Methanol, THF and diethyl ether are added gradually leading to the formation of a precipitate. The mixture is triturated in an ultrasonic bath, the solid is isolated by centrifugation and dried to obtain compound L12 (24 mg, 50%) as a very fine pale brown powder. 1 H NMR (D 2 O, 300 MHz):? 8.35 (s, 2H); 7.95 (s, 2H); 7.80 (s, 2H); 7.50-7.36 (m, 4H); 4.08 (s, 4H); 3.27 (m, 10H); 2.30 (m, 2H); 1.88 (ln, 2H). NMR (D20, 200 MHz): δ 25.7; 35.3; 40.4; 49.3; 58.7; 107.7; 114.4; 121.5; 123.4; 125.7; 129.0; 139.0; 145.8; 146.7; 152.0; 166.9; 179.2; 183.0. IR (cm -1, ATR): v 3390 (s); 1604 (s); 1580 (s); 1555 (w); 1439 (s); 1406 (s); 1328 (w); 1198 (w); 1129 (w); 1069 (w). EXAMPLE 18 SYNTHESIS OF THE COMPOUND The compound in a Schlenk tube is mixed with 5 '- Bu (100 mg. 0.11 mmol), 6-heptynoic acid (17 μL, 0.13 mmol), [Pd (PPh 3) 2 Cl 2] (8.40 mg, 0.01 mmol), distilled THF (10 mL). ) and distilled Et3N (6 mL) This mixture is degassed for 15 min and Cul (3.4 mg, 0.02 mmol) is added to the degassed solution The reaction medium is heated at 40 ° C for 72 minutes. The solvent is 2935973 B5006FR

Dry concentrate and the resulting residue is dissolved in dichloromethane (50 mL), washed with water (2 x 50 mL). The organic phase is dried over Na 2 SO 4, filtered and evaporated to dryness. Purification by chromatography on silica (CH 2 Cl 2 MeOH, 100: 00 to 98: 5) of the crude product makes it possible to obtain compound 37 (41 mg, 40%), under

5 form of a colorless oil. 1H NMR (CDCl3, 200 MHz): δ 8.65 (d, J = 8.8 Hz, 2H); 8.16 (d, J = 7.7 Hz, 2H); 7.82 (s, 2H); 7.82 to 7.26 (m, 4H); 4.41 (s, 4H); 3.56 (s, 8H); 2.54 to 2.42 (m, 4H); 1.87 to 1.71 (m, 4H); 1.48 (s, 36H). 13C NMR (CDCl3, 200 MHz): S, 8.6; 19.3; 24.5; 27.9; 28.3; 45.0; 50.1; 55.7; 79.3; 81.2; 95.7; 112.3; 114.7; 121.7; 122.5; 125.7; 128.1; 136.4; 139.8; 146.4; 152.3; 170.5. Compound L13 Compound 37 (40mg, 42mol) was dissolved in 3ml CH2Cl2 and 1.5ml TFA. The mixture is stirred for 4 hours at room temperature. The mixture

It is evaporated to dryness and the residue is dissolved in 0.5 ml of methanol. Compound L13 precipitates by addition of diethyl ether. After sonication, centrifugation, washing with diethyl ether and drying under vacuum, the compound L13 (20.8 mg, 52%) is isolated in the form of a beige powder. 1H NMR (CD3OD, 200 MHz): δ 8.47 (d, J = 8.5 Hz, 2H); 8.02 (d, J = 7.9 Hz, 2H); 7.65 (s, 2H); 7.42 to 7.24 (m, 4H); 4.53 (s, 4H); 3.72 (s, 8H); 2.47-2.30 (m, 4H); 1.77-1.63 (m, 4H). 13 C NMR (CDCl 3, 200 MHz): 8.20.0; 25.5; 29.0; 34.5; 47.9; 55.5; 79.5; 98.0; 114.0; 115.9; 121.6; 124.9; 126.8; 130.0; 138.2; 140.8; 141.3; 153.1; 170.0; 177.5. IR (cm-1, ATR): v 3390 (s), 1604 (s), 1580 (s), 1555 (w), 1439 (s), 1406 (s), 1328 (w), 1198 (w) , 1129 (w), 1069 (w).

EXAMPLE 19 Synthesis of Na [TbL21 The ligand L2 (20 mg, 28 mol) and TbC13.6H20 (10.6 mg, 28 μmol) are dissolved in 10 ml of water. The mixture is heated at 60 ° C for 1 hour. The solution is evaporated to dryness and the residue is dissolved in a minimum of water. Methanol, THF and diethyl ether are added gradually leading to the formation of a precipitate which is isolated by centrifugation and dried to obtain Na [TbL2] as a white powder (21.7 mg, 96%). IR (ATR, cm-): v 3390 (br); 3007 (w); 2987 (w); 2921 (w); 2213 (w); 2020 (w); 1602 (s); 1557 (m); 1533 (m); 1470 (w); 1436 (w); 1393 (s); 1213 (w); 1107 (w). ESI / MS (negative mode, McOH / H2O) m / z = 770.4 ([ TbL2] -, 100%) Calculated for C30H25N7O8TbNa.4H2O: C 41.63, H 3.84, N 11.33, C 41.41, H 3.55, N 11.04, EXAMPLE 20 Synthesis of NaFEuL21 The ligand L2 (13.8 mg, 19.6 mol) and EuC13.6H2O (7.2 mg, 19.6 mol) are dissolved in 10 ml of water The mixture is heated at 60 ° C. The solution is evaporated to dryness and the residue is dissolved in a minimum of water, methanol, THF and diethyl ether are gradually added leading to the formation of a precipitate which is isolated by centrifugation and dried for obtain Na [EuL2] (14.1 mg, 91%) as a white powder IR (ATR, cm-1): v 3390 (br), 2992 (w), 2911 (w), 2221 (w); 2018 (w), 1616 (s), 1603 (s), 1553 (m), 1529 (m), 1470 (m), 1432 (m), 1396 (s), 1354 (m), 1258 (w); 20 1228 ( w) 1107 (w) ESI / MS (negative mode, McOH / H2O) m / z = 764.0 ([EuL2] -, 100%), 762.0 ([EuL21-, 80%). Calculations calculated for C30H25N7O8EuNa.2NaCl: C, 39.89; H, 2.79; N, 10.85. Measured C 39.47; H, 2.66; N, 10.60. EXAMPLE 21 Synthesis of Na TEL The ligand L3 (30 mg, 49 mol) and TbCl3.6H2O (18.2 mg, 49 mol) are dissolved in 10 ml of water. The pH of the solution is brought to 8 with a solution of 0.1 M NH 4 OH. The mixture is heated at 60 ° C for 4 hours. The solution is evaporated to dryness and the residue is dissolved in a minimum of water. Methanol, THF and diethyl ether are added gradually leading to the formation of a precipitate which is isolated by centrifugation and dried to obtain Na2 [TbL3] (30 mg, 77%) as a light brown precipitate. R (ATR, cm-1): ν 3243 (br); 2922 (s); 2338 (w); 2117 (w); 1575 (m); 1534 (m); 1474 (s); 1428 (s); 1393 (m); 1356 (s); 1231 (s); 1103 (m); 1066 (m); 1039 (m). ESI / MS (negative mode, McOH / H2O) m / z = 790.0 ([NaTbL3] - 80%); 768.1 ([HTbL3f, 20%). Calculated for C26H22N7O11Tb (NH4) 2.7H2O: C, 33.59; H, 4.77; N 13.56. Measured C 33.45; H, 4.60; N, 13.44. EXAMPLE 22 Synthesis of Na Ezl LL31 The ligand L3 (10 mg, 17 mol) and EuC13.61-12O (6.2 mg, 17 μmol) are dissolved in 10 ml of water. The pH of the solution is brought to 8 with 0.1M NaOH solution. The mixture is heated at 60 ° C for 4 hours. The solution is evaporated to dryness and the residue is dissolved in a minimum of water. Methanol, THF and diethyl ether are added gradually leading to the formation of a precipitate which is isolated by centrifugation and dried to obtain Na2 [EuL3] (12.6 mg, 92%) as a brown powder. IR (ATR, cm-1): ν 3390 (br); 3007 (w); 2990 (w); 2; 161 (w); 2023 (w); 1594 (m); 1533 (s); 1446 (s); 1427 (s); 1393 (m); 1360 (s); 1275 (m); 1260 (m); 1231 (s); 1178 (s); 1101 (s); 1071 (s). ESI / MS (negative mode, McOH / H2O) m / z = 784.0 ([NaEuL3] -, 100%); 782.0 ([NaEuL3] -, 20%); 381.0 ([EuL3] 2 35%); 380.4 ([EuL3] 2 30%). EXAMPLE 23 Synthesis of Na TbL4 Compound L4 (0.06 g, 0.08 mmol) and TbC13.6H2O (33.5 mg, 0.09 mmol) were dissolved in H2O (100 mL). The mixture is stirred for 2 h at 50 ° C. and then filtered while hot. The filtrate is concentrated to a minimum. The addition of THF, MeOH and 2935973 B5006FR

Et2O leads to the formation of a precipitate, which is isolated by centrifugation and then dried in vacuo to give Na2 [TbL4] (0.05 g, 75%), as a white precipitate. IR (cm-1, ATR): ν 2228 (w; vc-c); 1594 (s); 1532 (s); 1478 (w); 1439 (m); 1390 5 (s); 1356 (s).

Calculated for C28H26N7Na2OloTb.2C4H80: C, 44.59; H, 4.37; N, 10.11; measured: C, 44.28; H, 4.61; N, 12.76.

ESI / MS (negative mode, MeOH / H 2 O) m / z: 389.4 ([TbL 5] 2 - 80%).

EXAMPLE 24 Na EuL 4 The L4 ligand (15.0 mg, 19 μmol) in H 2 O (10 mL) is added to EuCl 3 .6H 2 O (8.2 mg, 0.02 mmol) dissolved in H 2 O (5 mL). The mixture is stirred for 2 h at 50 ° C. and then filtered while hot. The filtrate is concentrated to a minimum. The addition of THF, MeOH and Et2O leads to the formation of a precipitate, which

Is isolated by centrifugation and then dried in vacuo to give Na2 [EuL4] (16.7 mg) as a precipitate. IR (cm -1, ATR): v 2160 (w; vc -1); 1603 (s); 1553 (m); 1530 (w); 1434 (w); 1388 (s).

ESI / MS (negative mode, MeOH / H 2 O) m / z: 387.0 ([EuL 4] 2 30%); 386.4 ([EuL4] 2 - 100%), 385.4 ([EuL4] 2 80%).

EXAMPLE 25 Synthesis of EuLS Na The L5 ligand (15.0 mg, 20 mol) in H 2 O (10 mL) is added to EuC13.6H2O (8.0 mg, 0.02 mmol) dissolved in H2O (5 mL). The mixture is agitated

For 2 hours at 50 ° C. and then filtered while hot. The filtrate is concentrated to a minimum. Addition of THF, MeOH and Et2O resulted in the formation of a precipitate, which was isolated by centrifugation and then dried in vacuo to give Na2 [EuL5] (17.3 mg) as a precipitate. 2935973 B5006FR

IR (cml, ATR): v 2161 (w; vc-c); 1587 (s); 1551 (w); 1532 (m); 1384 (s); 1253 (w).

EXAMPLE 26 Synthesis of Naz [EuL61 In a flask containing a solution of L6 ligand (0.03 g, 0.04 mmol) in H 2 O (10 mL) EuCl 3 · 6H 2 O (14.9 mg, 0.04 mmol) was added dissolved in H2O (5 mL). The mixture is stirred for 2 h at 50 ° C. and then filtered while hot. The filtrate is concentrated to a minimum. The addition of THF, MeOH and Et2O leads to the formation of a precipitate, which is isolated by centrifugation and dried under vacuum for

Give Na2 [EuL6] (35.2 mg) as a precipitate. IR (cm -1, ATR): ν 2204 (w; vc -1); 1595 (s); 1509 (w); 1466 (m); 1388 (s); 1248 (m).

EXAMPLE 27 Synthesis of Na L91 L9 L9 ligand (0.03 g, 0.04 mmol) in H2O (20 mL) is added to EuC13.6H2O (17.0 mg, 0.05 mmol) dissolved in H2O (5 mL). The mixture is stirred for 2 h at 50 ° C. and then filtered while hot. The filtrate is concentrated to a minimum. Addition of THF, MeOH and Et2O led to the formation of a precipitate, which was isolated by centrifugation and then dried in vacuo to give Na2 [EuL9] (0.03 g;

92%) as a precipitate. IR (cm-1, ATR): v 2172 (w; vc = c); 1599 (s); 1568 (w); 1532 (m); 1444 (w); 1393 (s); 1358 (w).

ESI / MS (negative mode, MeOH / H2O) m / z: 375.2 ([EuL9] 2-, 100%).

EXAMPLE 28 Synthesis of NaIEuL71 In a flask containing a solution of Ligand 7 (10.2 mg, 0.01 mmol) in H 2 O (10 mL) is added EuCl 3 · 6H 2 O (4.0 mg, 0.01 mmol) dissolved in H2O (5 mL). The mixture is stirred for 2 h at 50 ° C. and then filtered while hot. The filtrate is concentrated to a minimum. Addition of THF, MeOH and Et 2 O leads to the formation of a precipitate, which is isolated by centrifugation and then dried under vacuum to give Na [EuL 7] (7.0 mg, 63%). IR (cm-1, ATR) v 2208 (w; CC); 1596 (s); 1551 (ni); 11531 (m); 1515 (m); 1444 (m); 1390 (s); 1355 (m). ESI / MS (negative mode, MeOH / H2O) m / z: 1009.2 ([NaEuL7 + H] +; 100%); 1008.2 ([NaEuL7] + 65%); 1007.2 ([NaEuL7 + Hr, 80); 1005.2 (80%); 258.5 (20%). EXAMPLE 29 Synthesis of Na TbL9 L9 ligand (0.10 g, 0.14 mmol) in HO (90 mL) is added to TbC13.6H2O (57.5 mg, 0.15 mmol) dissolved in H2O (10 mL). mL). The mixture is stirred for 2 h at 50 ° C. and then filtered while hot. The filtrate is concentrated to a minimum. Addition of THF, MeOH and Et2O resulted in the formation of a precipitate, which was isolated by centrifugation and then dried under vacuum to give Na2 [EuL9] (0.09 g, 81%), as a solution. a pale yellow precipitate. IR (cm-1, ATR):? 1587 (s); 1570 (s); 1535 (s); 1478 (m); 1443 (m); 1389 (s); 1355 (s). Calculated for C24H21ClN8Na2O11Tb.NaCl.H2O: C, 32.80; H, 2.64; N, 12.75; measured: C 32.41; H, 2.34; N, 12.34. ESI / MS (negative mode, MeOH / H2O) m / z: 378.1 ([TbL912-, 80%). EXAMPLE 30 Synthesis of Na 2 TbL 10 1 The L10 ligand (29 mg, 39.1 mol) and TbCl 3 .6H 2 O (14.6 mg, 39.1 mol) are dissolved in 10 ml of water. The mixture is heated at 60 ° C for 1 hour. The solution is evaporated to dryness and the residue is dissolved in a minimum of water. Addition of THF, MeOH and Et2O resulted in the formation of a precipitate, which was isolated by centrifugation and then dried under vacuum to give Na2 [TbL1O] (27.4 mg, 84%) as a powder. white. IR (ATR, v 3355 (br); 2953 (w); 1586 (m); 1'568 (m); 1537 (m); 1392 (m); 1356 (m); 1282 (s); 1259 (s); 1232 (w); 1124 (s); 1060 (s); 1039 (s); 1008 (w). ESI / MS (negative mode, MeOH / H 2 O) m / z = 807.0 ( [NaTbL10] 70%) 392.1 ([TbL10] 2 - 100%) EXAMPLE 31 Synthesis of Na2IEuL10.1 L10 (15mg, 20.2mol) and EuC13.6H2O (7.4mg) 20.2 mol) are dissolved in 10 ml of water The mixture is heated at 60 ° C. for 1 hour The solution is evaporated to dryness and the residue is dissolved in a minimum of water. THF, MeOH and Et2O resulted in the formation of a precipitate, which was isolated by centrifugation and then dried under vacuum to give Nat [EuL10] (13.5 mg, 81%) as a white powder. (ATR, cm "): 3363 (br), 2960 (w), 1587 (m), 1567 (m), 1537 (m), 1391 (m), 1355 (m), 1282 (s), 1257 (s); 1230 (w); 1124 (s); 1067 (s); 1037 (s); 1009 (w). Calculated for C26H25N8Na2O >> Eu6H2O: C 33.52; H 4.00; N 12 , 03. Measured: C 33.28, H 3.7 3, N 11.72, ESI / MS (negative mode, MeOH / H 2 O) m / z: 800.2 ([NaEuL 10] 20%); 801.0 ([NaEuL10] 100%); 388.5 ([EuL10] 2 - 40%) EXAMPLE 32 Synthesis of Na2 [TbL11] L11 (9 mg, 9.6 mol) and TbC13.6H2O (3.9 mg, 9.6 mol) are dissolved in 6 ml of water The mixture is heated at 60 ° C. for 3 hours The solution is evaporated to dryness and the residue is dissolved in a minimum amount of water Methanol, THF and diethyl ether are gradually added and the mixture is triturated to obtain a precipitate which is isolated by centrifugation as a white powder (2.5 mg, 26%) EXAMPLE 33 Synthesis of Na21TbL121 L12 (10 mg, 11.9 mol) and TbCl3 6 H 2 O (4.44 mg, 11.9 mol) are dissolved in 10 ml of water, the mixture is heated at 60 ° C. for 3 hours, the solution is evaporated to dryness and the residue is dissolved in a minimum of The addition of THF, MeOH and Et2O leads to the formation of a precipitate, which is isolated by centrifugation and then dried under vacuum to give Na2 [TbL12] (8.6 mg, 78%) as a precipitate. a white powder.

IR (cm-1, ATR): v 3374 (br), 2937 (w), 1589 (s), 1562 (s), 1532 (m), 1436 (m), 1400 (s), 1342 (m), 1274 (w), 1214 (w), 1196 (w), 1111 (m), 1070 (m), 1012 (w). EXAMPLE 34 Synthesis of NalJEuL12t L12 (7.7 mg, 8.8 mol) and TbC13.6H2O (3.24 mg, 8.8 mol) are dissolved in 10 ml of water. The mixture is heated at 60 ° C for 3 hours. The solution is evaporated to dryness and the residue is dissolved in a minimum of water. Addition of THF, MeOH and Et2O led to the formation of a precipitate, which was isolated by centrifugation and then dried under vacuum to give Na2 [TbL12] (7.9 mg, 97%) as a powder. white.

EXAMPLE 35 Synthesis of Na, JTbL13, L13 (10 mg, 10.5 μmol) is dissolved in 10 ml of water. The solution is made basic (pH = 8) by addition of an aqueous solution of 0.1 M sodium hydroxide. TbC13.6H2O (3.9 mg, 10.5 mol) is added. The mixture is heated at 60 ° C for 3 hours. The solution is evaporated to dryness, the residue is dissolved in a minimum of methanol and THF is added to precipitate the complex. Na3 [EuL13] is isolated by centrifugation as a yellow powder (6.7 mg, 72%). IR (cm-1, ATR): ν 2330 (w; vc-c); 1610 (s); 1435 (m); 1342 (w); 1204 (w); 1106 (m); 1074 (m).

Since the emission spectra of the europium and terbium complexes are very little influenced by the ligand environment in a series or the complexation site is the same, they are very similar from one compound to another. By way of example, the absorption and emission spectra of the TbL4 and EuL6 complexes in water are shown respectively in FIGS. 1 and 2.

In the figures, the left curve represents the absorption spectrum and the right curve represents the emission spectrum. The wavelength is given as abscissa, and the ordinate represents the molar extinction coefficient (E, in M'.cm-1) for the absorption spectrum and the relative intensity of emission (in arbitrary units ) for the

5 emission spectrum. The spectra were carried out on aqueous solutions of the two complexes in buffered medium (TRIS / HCl, 0.01 M, pH = 7.0). The overall absorption and emission properties of the synthesized complexes of europium and terbium are summarized in the following table: Compound Absorption 01120 21120 0D20 TD2o Xmax / nm (s! M "cm-1)% ms % ms Q TbL2 318 (19200) 280 (26000) 3.4 1.3 6.1 2.2 1.3 273 (25500) EuL2 318 (20300) 280 (18300) 15 1.3 32 2.4 0 273 (18500) TbL3 318 (6800) 278 (15400) 19 2.5 22 269 (17500) EuL3 318 (6500) 278 (13600) 4.5 1.4 6.2 2.4 0 269 (15700) TbL4 328 (9030) 277 (20400) 42 2.6 60 3.0 0 265 (39700) EuL4 328 (7450) 277 (18100) 8 1.2 22 2.4 0.2 265 (33200) 314 (23500) EuL5 280 (23600) 1.15 2.3 0.3272 (23800) EuL6 334 (22800) 277 (20600) 14 1.1 30 2.3 0.3267 (22800) 325 (9950) TbL9? 23700) 100 2.5 3.1 0 271 (23300) 328 (8670) EuL9 278 (21200) 8 1.3 12 2.4 0.1 271 (21100) 2935973 B5006EN

59 Compound Absorption (Px20 TE-120 tD2o TD20 Q Xmax / nm (s / M-'.cm- ')% ms% ms TbL10 327 (6900) 279 (16500) 94 2.6 100 3.1 0.2 271 (16000) EuL10 327 (6600) 279 (16300) 12 1.4 32 2.5 0.1 271 (16000) TbL11 - 54 2.4 68 2.9 0 TbL12 309 (12700) 0.746 1, 1 - 360 (11400) EuL12 320 (11400) 16 1.15 34 1.84 0 360 (10700) TbL13 309 (11400) 35 0.9 55 1.35 1.3 360 (8800) The parameters 0x20, (PD2o) , Tx20, zD20 and q respectively represent the quantum luminescence yields in water and in D20, the luminescence lifetime in water and in D20 and the hydration number of the complexes. The absorption of the complexes covers a broad range which extends to the visible for certain compounds (EuL6 and EuL7) .The flexibility of the preparation process makes it possible to modify the electronic delocalization on the ligand and thus to modulate the absorption properties. It is also noted that the spectroscopic properties of some complex They are excellent with near quantum quantum yields (TbL9 and TbL10).

Thus, when compared to related prior art compounds (especially those described in EP-0770610-A1) the complexes of the present invention show a significant improvement in brightness, defined as the product of quantum yield. by the molar extinction coefficient at the absorption maximum (O20x Emax), with values of 9950 and 6490 for a value of 4050 in the best case of the related compounds previously described. It is also noted that the hydration number q, calculated according to the method of Horrocks (Horrocks, WDW Jr, Sudnick, DR Acc Chem Chem Res 1981, 14, 384) is almost constant in the series and close to zero, which means that the complexation site allows a very good protection of the lanthanide ions with respect to the interactions with the water molecules. EXAMPLE 36 LUMINESCENCE BY TWO-PHOTON EXCITATION The two-photon properties of the EuL6 and EuL7 compounds were tested by subjecting an aqueous solution of EuL6 (c = 5x10 -5 M) and an aqueous solution of EuL7 (c = 1xO-4 M). ) at 705 nm laser radiation (Ti: Sapphire laser, Tsunami 3960, Specra Physics, at 80 MHz, UV filter at 630 nm) Figure 3 shows emission spectra after excitation at 705 nm obtained for EuL7 (upper curve) and for EuL6 (lower curve) The abscissa represents the wavelengths X (in nanometers), the ordinate axis represents the emission intensity le (arbitrary units). represents the curves of the intensity emitted (Logle ,, in arbitrary units ua) as a function of the irradiation power (Log P in mW) for the following 15 samples: Curve • solution of fluorescein in water (c = I ., 27x 10-4 M, pH = 11) used as reference; Curve • water Curve ^ solutio Aqueous EuL6 (c = 5x10 -5 M) Curve • EuL7 aqueous solution, (c = 10-4 M) The curves show a perfectly linear relation between the emission intensity and the power of the laser beam with a slope of 2, which demonstrates that the emission phenomenon is due to a two-photon absorption. The calculation of the two-photon absorption cross section at 705 nm, 6705, was performed according to the methods described by Rumi, M, et al., [J. Am. Chem. Soc. 2000, 122, 9500] using fluorescein as reference (x705 = 32.5 GM according to Xu, C Bioimaging 1996, 4, 198-207), and gives 6705 values of 28.6 GM for EuL6 and 27.1 GM for EuL7, which demonstrates the emission efficiency of the complexes after two-photon absorption. EXAMPLE 37 DETERMINATION OF CATIONS IN SOLUTION When a luminescent complex has a recognition site electronically connected to the complexing site, the luminescence properties of the complex can be disturbed by the presence of an analyte which binds on the recognition site. This property has been studied for the Na [EuL7] complex of Example 28. FIG. 5 represents the evolution of the emission intensity of Na [EuL7] in solution in buffered water (TRIS / HC1, 0.01 M, pH 7.0) as a function of the relative amount of copper added to the solution, for a 350 nm Xexc excitation wavelength. The curve shows that the complex which is formed is an adduct con-holding a copper atom by complex Na [EuL7]. The lower curve corresponds to the emission intensity at 585 nm and the upper curve to an emission at 614 nm. Figure 6 shows the evolution of the relative emission intensity of the Na [EuL7] complex as a function of different cations studied and for different values of the added ion concentrations. The relative intensity is represented on the z axis, the y axis corresponds to the four cations studied (Cul +, Zn2 +, Mg2 +, K + and Na + respectively from bottom to top) and the x axis represents the evolution for the quan - added items mentioned in the legends. This figure shows that the complexes of the invention have a very good sensitivity and a selectivity towards copper. With the exception of copper, the addition of metal cations leads only to small variations in emission intensity. In the series of alkaline and alkaline-earth cations, the variations remain small, even when the cation concentrations are very high (up to 100 equivalents of NaCl). Only copper (II) leads to a very strong decrease in luminescence, probably due to an intramolecular charge transfer during the complexation of copper. This example shows the detection selectivity of Na [EuL7] with respect to copper and a high sensitivity of the detection as soon as 1 equivalent is added.

Claims (26)

REVENDICATIONS1. A compound having the formula wherein each of Y 'and Y2 represents an H atom or an alkyl group having from 1 to 4 carbon atoms, or Y 'and Y2 together form a biradical forming an aromatic ring with the two carbon atoms that carry it; A represents -CC-, -CO-NH-, or -CO-O-; X is: * H, NH2, a halogen, * a COOR 'group in which R' is H, an alkaline cation, an N (R3) 4+ quaternary ammonium group in which R3 is H or a linear alkyl chain, a succiimide group -N- (CO-CH2-CH2-CO) -, or a pentafluorophenyl group -C6F5; a biotin function (-CO- (CH 2) 4 - 05H7N 2 OS), a polyheteroaromatic group or a crown ether, n is 0 or 1; E is a linking segment consisting of at least one group selected from -C6H4-, C, oH6-, -CO-NH-, peptide groups containing from 1 to 4 amino acids, and alkylene groups having from 1 to 10 carbon atoms and which optionally comprise at least one heteroatom in the carbon chain, - each of the groups R represents H or an alkali metal or a quaternary ammonium group N (R3) 4+. 2935973 B5006EN 63 2. Compound according to claim 1, characterized in that each of the groups Y 'and Y2 represents H. 3. Compound according to claim 1, characterized in that the group A is a group -C = C-. 5 4. Compound according to claim 1, characterized in that the group A is a group -CO-NH-, 5. Compound according to claim 1, characterized in that the group A is a group -CO-O-; 6. Complex of a lanthanide ion selected from the ions Eu3 +, Tb3 +, Dy3 +, Sm3 +, Er3 +, Yb3 +, Pr3 + and Nd3 + and a ligand chosen from the compounds according to one of claims 1 to 5. The complex of claim 6, wherein the X group of the complex ligand is Br, I, an amine, or a COOR 'group wherein R' is H, Na, a succinimide group -N- (CO-CH 2) CH2-CO) -, or a pentafluorophenyl-C6F5 group; 8. A complex according to claim 6, wherein the X group of the substituent of the ligand is a crown ether or a terpyridine. 9. A complex according to claim 6, wherein the ligand has a group ûA- (E) ä-X wherein A is a group C-C, E comprises a phenyl group and A is a terminal group NaCOO-. The complex of claim 6, wherein the X terminal group of the λA- (E) n-X substituent of the ligand is a biotin group. 11. Process for the preparation of a compound L according to claim 1, characterized in that it comprises: a first stage during which a compound corresponding to the formula 2935973 B5006FR B CO2R 'CO2R' CO2R is reacted; Wherein R 'groups each represents an alkyl group having 1 to 6 carbon atoms, and each of Y1 and Y2 represents an H atom or an alkyl group having 1 to 4 carbon atoms, or Y1 and Y2 together form a biradical forming an aromatic ring with the two carbon atoms that carry it; with a suitable reagent, in the presence of an organometallic catalyst, in an organic solvent, to replace bromine with a group A-Z wherein A is -CC-, -CO-NH-, or -CO-O-; A step in which the R 'groups are replaced by H, an alkali metal or an N (R 3) 4+ quaternary ammonium group in which R 3 is H or a linear alkyl chain; one or more steps for replacing the Z group with a group (E) λ-X, when Z is different from a group (E) n-X in which: X is H; NH2; a halogen; a COOR1 group in which R1 is H, an alkaline cation, an N (R3) 4+ quaternary ammonium group, a N-succinimide group (CO-CH2-CH2-CO) -, or a pentafluorophenyl -C6F5 group; a biotin function (-CO- (CH 2) 4-05H7N 2 OS); a polyheteroaromatic group or a crown ether; E is a linker consisting of at least one group selected from -C6H4-, -C10H6-, -CO-NH-, peptide groups containing from 1 to 4 amino acids, and alkylene groups having from 1 to 10 carbon atoms and which optionally include at least one heteroatom in the carbon chain. 12. Process according to claim 11, characterized in that the step of replacing the linear alkyl groups R 'with an alkali metal cation Na +, K + or Li + is carried out by reaction with NaOH, KOH or LiOH, respectively, in a polar solvent at a temperature between 20 and 100 ° C. 13. Process according to claim 11, characterized in that it comprises a further step of reacting the product obtained with a strong acid in water or with ammonium hydroxide N (R3) 40H to replace the cation. of alkali metal respectively by H or N (R3). 14. Process according to claim 11, characterized in that the step of replacing the R 'groups of the branched alkyl type is carried out by reaction with trifluoroacetic acid (TFA) in an organic solvent. 15. Process according to one of Claims 11 to 13, characterized in that the step of replacing R 'is carried out on a product carrying the final group A- (E) r, -X, or on an intermediate product. obtained at the end of the 1st stage. 16. The process as claimed in claim 11, for the preparation of a compound L in which A is a group -CO-NH- or a group -CO-O-, characterized in that the reagent used during the said step is a amine X- (E) -NH 2, respectively an X- (E) -OH alcohol, in the presence of gaseous carbon monoxide, and that: X is H; NH2; a halogen; a COORI group in which R1 is H, an alkaline cation, a succinimide group -N- (CO-CH2-CH2-CO) -, or a pentafluorophenyl group (-C6F5); a biotin function -CO- (CH 2) 4-05H7N 2 OS; a polyheteroaromatic group or a crown ether, 25 * n is 0 or 1; E is a linking segment consisting of at least one group selected from -C6H4-, C 1 OH6-, -CO-NH-, peptide groups containing from 1 to 4 amino acids, and alkylene groups having from 1 to 10 carbon atoms and which optionally comprise at least one heteroatom in the carbon chain. 2935973 B5006FR 66 17. The process as claimed in claim 11, for the preparation of a compound L in which A is a C = C group, characterized in that the reagent used for the reaction with compound 5 in the first step carries a terminal group HC = C-, and the reaction is carried out in the presence of a complex of Pd and triphenylphosphine. 5 18. Process according to claim 17, characterized in that the compound 5 is reacted with a reagent HC = C- (E) ä-X to obtain the compound 6, according to the reaction scheme Br Y1 I Yi N ^ N The reaction is carried out in the presence of a complex of Pd and triphenyl-10 phosphine in a solvent and the reaction is carried out in the presence of a complex of Pd and triphenyl-10 phosphine in a solvent. organic, at a temperature between 20 and 80 ° C. 19. Process according to claim 17, characterized in that it comprises the steps represented by the following reaction scheme: ## STR1 ## In the first step, the compound 5 is reacted with trimethylsilylacetylene in the presence of an organometallic catalyst in an aprotic organic solvent; The second step of the reaction scheme consists in reacting the compound obtained at the end of the preceding step with a deprotecting agent in an aprotic solvent at a temperature between 0 and 80 ° C. 20. Process according to claim 17, characterized in that: it comprises a step of reacting a compound 8 corresponding to the formula ## STR1 ## wherein R 'represents a group linear or branched alkyl having from 1 to 6 carbon atoms, with a compound F (r) - (E) ,, - X, then a step of replacing the R 'groups with R groups selected from H, the alkaline cations and the quaternary ammonium salts N (R 3) 4+, the group F (r) is H, Cl, Br, I, -O-SO 2 -F-, a boronic acid group (B (OH) 2), a boronic acid ester group (B (O-Alkyl) 2), a trialkyl stannyl group or a trialkyl silyl; X is H; NH2; a halogen; a COOR 'group in which R' is H, an alkaline cation, a succinimide group -N- (CO-CH2-CH2-CO), or a pentafluorophenyl group (-C6F5); a biotin function (-CO- (CH 2) 4 - 05H7N 2 O 5); a polyheteroaromatic group or a crown ether, n is 0 or 1; E is a linking segment consisting of at least one group selected from -C6H4-, -C10H6-, -CO-NH-, peptide groups containing from 1 to 4 amino acids, and alkylene groups having from 1 to to 10 carbon atoms and which optionally comprise at least one heteroatom in the carbon chain. 21. A process for preparing a complex according to one of claims 6 to 10, characterized in that it consists in mixing in equimolar quantities a ligand selected from the compounds according to one of claims 1 to 5 and a salt of lanthanide, heat the mixture, and then neutralize at pH 6-8 after cooling. 22. The method of claim 21, characterized in that the lanthanide salt is selected from nitrates, chlorides, perchlorates and trifluoromethylsulfonates. 23. Use of a complex according to claim 7 for labeling molecules which carry an amine, alcohol, thiol, carboxylic acid or activated ester group. 24. Use of a complex according to claim 8 for the detection of metal cations in solutions. 25. Use of a complex according to claim 9 as a luminescent marker for two-photon absorption 26. Use of a complex according to claim 10 for the recognition of avidin, streptavidin and neuravidin.