Tetramethyl-phenanthroline copper complexes in the development of drugs to treat cancer: synthesis, characterization and cytotoxicity studies of a series of copper(II)-l-dipeptide-3,4,7,8-tetramethyl-phenanthroline complexes

New Copper(II)-L-Dipeptide-Bathophenanthroline Complexes as Potential Anticancer Agents—Synthesis, Characterization and Cytotoxicity Studies—And Comparative DNA-Binding Study of Related Phen Complexes

“…It presents a pentacoordinate copper(II) center with a N3O equatorial coordination, where 2 N and 1 O atoms come from the dipeptide ligand, whereas the third N atom comes from the batho ligand, which is perpendicular to the plane defined by the dipeptide. The coordination and spatial arrangement are similar to those in the crystal structures of previously reported [Cu(dipeptide)(diimine)] complexes where diimine is: phen [ 18 ], 5-NO 2 -phen [ 19 ], neo [ 20 ] and tmp [ 22 ]. Figure 2 presents the optimized geometry.…”

“…Values of intrinsic binding constants to DNA ( K b ) of the homoleptic and heteroleptic complexes were similar, with values of approximately 1 × 10 3 ( Table S1, Supplementary Materials ). The K b values are approximately ten-fold lower than those of the corresponding [Cu(L-dipeptide)(phen)] [ 18 ] and similar to those of [Cu(L-dipeptide)(tmp)] [ 22 ] complexes, suggesting that phenyl groups impair DNA binding as compared to phen, similarly to methyl groups of tmp.…”

“…The λ max of the visible spectra, calculated according to Prenesti et al [ 28 , 29 ] for the coordination scheme shown in Figure 1 (corresponding to proposed solid-state coordination) is approximately 610–620 nm, similar to the experimental value in DMSO. This suggests that the pentacoordinate heteroleptic complex is the solution’s major species, not excluding others’ existence, as observed for [Cu(L-dipeptide)(phen)], [Cu(L-dipeptide)(neo)], and [Cu(L-dipeptide)(tmp)] complexes [ 18 , 20 , 22 ]. In a DMSO:water (50:50) solution, the same spectral characteristics were observed, with λ max shifted to 620–630 nm.…”

“…All the studied heteroleptic complexes present similar infrared spectra. IR spectra of the obtained complexes were assigned taking into account the calculated IR and interpretation for compound 3 , as well as the previously reported data for related complexes [ 18 , 20 , 22 , 23 , 24 , 25 , 26 ]. The common characteristic bands in the spectra ( Table 2 ), include a broad, very strong peak at approximately 1600 cm −1 corresponding to ν(C=O) + ν(C-N) + ν as (COO), which is characteristic of the coordinated dipeptide moiety.…”

“…Our research group has been working to develop new copper compounds with a cytotoxic activity which may lead to anticancer agents. Different series of [Cu(L-dipeptide)(diimine)] compounds were synthesized and characterized (where diimine: phenanthroline, phen, 5-NO 2 -phenanthroline, 5-NO 2 -phen, neocuproine, neo and 3,4,7,8-tetramethyl-phenanthroline, tmp) [ 18 , 19 , 20 , 21 , 22 ]. In general, they are potent cytotoxic agents, more active than cisplatin, with neo and tmp complexes being the most active of the group.…”