Ruthenium (ii) polypyridyl complex as a photo-sensitiser in photodynamic therapy, and a procedure for making said ruthenium (ii) polypyridyl complex

A photosensitizer medicament for photodynamic therapy to treat neoplasms comprising a ruthenium (II) coordination compound as a photosensitising agent, wherein said ruthenium (II) coordination compound has the formula:

• wherein n is selected between 0 and 2,
• wherein R is a substituent group selected from the group consisting of:
• hydrogen;
• a methyl group;
• a phenyl group;
• a —CH2NH2 group;
• a —CH2OH group;
• a carboxyl group —COOH;
• an ester group —COOR1,
• where R1 is selected from the group consisting of:
• a linear or branched alkyl group with a number of carbon atoms in the range from 1 to 4;
• an unsubstituted benzyl group;
• a polyethylene glycol methoxy group H(OCH2 CH2)1-4OH;
• an amide group —CONR2R3,
• where
• R2 is hydrogen and R3 is a group selected from the group consisting of:
• a linear or branched alkyl group with a number of carbon atoms comprised in the range from 1 to 4;
• a —(CH2)2NH2 group;
• a phenyl group,
• or
• R2 and R3 are linear or branched alkyl groups with a number of carbon atoms in the range from 1 to 4,
• or
• NR2R3 is a group selected from the group consisting of:
• a cycloalkyl secondary amine with a number of carbon atoms in the range from 4 to 5;
• a heterocycloalkyl secondary amine comprising a heteroatom selected between nitrogen and oxygen,
• wherein said coordination compound is incorporated in liquid-crystalline lamellar and/or non-lamellar lipid nanoparticles.

A process for obtaining a ruthenium (II) coordination compounds having formula:

• where n is selected between 0 and 2,
• where R is a substituent group selected from the group consisting of:
• hydrogen;
• a methyl group;
• a phenyl group;
• a —CH2NH2 group;
• a —CH2OH group;
• a carboxyl group —COOH;
• an ester group —COOR1,
• where R1 is selected from the group consisting of:
• a linear or branched alkyl group with a number of carbon atoms in the range from 1 to 4;
• an unsubstituted benzyl group;
• a polyethylene glycol methoxy group having the formula H(OCH2CH2)1-4OH;
• an amide group —CONR2R3,
• where
• R2 is hydrogen and R3 is a group selected from the group consisting of:
• a linear or branched alkyl group with a number of carbon atoms in the range from 1 to 4;
• a —(CH2)2NH2;
• a phenyl group,
• or
• R2 and R3 are linear or branched alkyl groups with a number of carbon atoms in the range from 1 to 4,
• or
• NR2R3 is a group selected from the group consisting of:
• a cycloalkyl secondary amine with a number of carbon atoms in the range from 4 to 5;
• a heterocycloalkyl secondary amine comprising a heteroatom selected between nitrogen and oxygen,
• said process comprising the sequence of steps of:
• obtaining a reactive polymeric precursor [Ru(CO)2Cl2]m by reaction between ruthenium (Ill) chloride and paraformaldehyde;
• obtaining an intermediate complex trans-Cl[Ru(NN)Cl2(CO)2]:
• where NN is a 2,2′-bipyridine ligand symmetrically functionalised with two equal functional R groups,
• by reaction of said reactive polymer precursor [Ru(CO)2Cl2]m with a predetermined symmetrically functionalized 2,2′-bipyridine group with said two equal R functional groups,
• obtaining said ruthenium (II) coordination compounds by reaction of said intermediate complexes
• with benzo[i]dipyridine[3,2-a:2′,3′-c]phenazine.