Ligand synthesis hydrophilic ligands

Figure 10 Synthesis of axially substituted ruthenium(II) 2,3-naphthalocyanines. Compounds with a variety of hydrophilic axial ligands have been characterized.158...

It is important to keep in mind that hydrophilic prosthetic groups are important for renal rather than hepatobiliary clearance. Wester et al. [62] have demonstrated this with their carbohydrated analogs. Since 18F possesses inherent imaging advantages, the development of a simple and rapid synthesis which will enable 18F-SSTr ligands to be clinically practical is also important. 

They are synthesised at room temperature from an aqueous mixture of tetraethoxysiloxane, isopropanol, hexadecylamine and ammonium hydroxide. Hydrothermal treatment of the spheres in the mother liquor induces the formation of wider pores of 50A and a BET surface area of 350 m /g. The silica spheres possess surface silanol groups which can be used to attach C8 tind C18 ligands, thus converting the surface from a hydrophilic to a hydrophobic one. Subsequent application of these surface modified silica spheres in fast separation HPLC has proven to be successful. The synthesis has been successfully up-scaled (70g) to yield spheres of sizes 0.5, 1,2, 6 and 20 pm. 

A further significant development was the synthesis of a fluorescent form of the hydrophilic P-AR ligand CGP12177 (32). These authors synthesized both a BODIPY and FITC version of CGP12177 and found that the BODIPY form exhibited similar binding characteristics when compared with the native form. Our own work with both these compounds also observed significant photo-bleaching of the FITC form the BODIPY form was far more stable under fluorescence excitation. 

Carboxylate groups were used in many cases to achieve water-solubilization of simple achiral phosphines. With the synthesis of the water-soluble polymer shown in Eq. (2) this methodology was extended into the field of chiral ligands [28a]. Acylation of the diphosphine (2S,4S)-4-diphenylphosphino-2-diphenylphosphinome-thylpyrrolidone (PPM) with poly(acrylic acid) (PPA) yields the hydrophilic macroligand PAA-PMM [28a,b] and PAA-pyrphos [28c]. 

It is established by solubility measurements, that a medium sized ligand should have at least two -CH2OH substituents in order to achieve good aqueous solubility [91], However, through the flexible synthesis of these tertiary phosphines the number and the chain length of the hydroxyalkyl substituents built into the target molecule can be varied easily and this way the balance of hydrophilicity and lipophilidty can be finely tuned. Incorporation of other donor atoms, such as S in 109, and a pendant arm with an other reactive substituent (-COOH in 109) makes these compounds even more versatile. 

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