Synthesis of amino acid esters of the ruthenium naphthalene complex [(C5Me4CH2OH)Ru(C10H8)]+

•Amino acid residues were attached to the cyclopentadienyl ligand of ruthenium complex.•Ruthenium naphthalene complexes inhibit growth of several cancer cell lines.•The structure of alanine ester derivative was established by X-ray diffraction.

Ruthenium naphthalene complex [(C5Me4CH2OH)Ru(C10H8)]+ (2) with hydroxy-substituted cyclopentadienyl ligand reacts with N-Boc-protected alanine, methionine, phenylalanine, and tryptophan in the presence of dicyclohexylcarbodiimide giving organometallic esters of amino acids [(C5Me4CH2OOCCH(CH2R)NHBoc)Ru(C10H8)]+ (3a–d) in 70–86% yields. Irradiation of phenylalanine derivative 3c at 365 nm results in replacement of the naphthalene ligand by the phenyl group giving ansa-complex [(η5-C5Me4)CH2OOCCH(CH2-η6-Ph)NHBoc)Ru]+ (4) in 47% yield. Complexes [3c,d]BF4 containing phenylalanine and tryptophan residues effectively inhibit growth of cancer cell lines B16, MeWo, SCOV3, SKBR3, and A549 (IC50 = 21–96 μM) with activity and selectivity being close to those of the cisplatin. The structure of the alanine derivative [3a]BPh4 was established by X-ray diffraction.

Graphical abstractCyclopentadienyl ruthenium naphthalene complex was functionalized with amino acids. The resulting compounds effectively inhibit growth of several cancer cell lines with activity and selectivity being close to that of the cisplatin.Figure optionsDownload full-size imageDownload as PowerPoint slide