# Synthetic analogue approach for the functional domains of copper(II) bleomycins and its DNA cleavage activity

Dhar, Shanta and Nethaji, Munirathinam and Chakravarty, Akhil R (2004) Synthetic analogue approach for the functional domains of copper(II) bleomycins and its DNA cleavage activity. In: Dalton Transactions (24). pp. 4180-4184.

 Preview
PDF
Synthetic_Analogue.pdf

The dicopper(II) complex $[Cu_2(R'SSR)_2(SO_4)_2] (1)$, where R'SSR is a Schiff base, has been prepared from the reaction of $CuSO-4·5H_2O$ with the Schiff base N,N' -1,1'-dithiobis(ethylenesalicylaldimine)$(H_2RSSR)$ and structurally characterized by X-ray crystallography. The crystal structure of 1 shows two ${Cu(R SSR)}^2^+$ units linked by two sulfate ligands each showing a $\eta^3$µ2-binding mode. The Cu... Cu distance is 4.562(2)A with each copper having a square pyramidal (4 + 1) $CuNO_4$ coordination geometry. The monoanionic Schiff base R'SSR has a pendant cationic amine $-SCH_2CH_2NH_3^+$ group which is presumably formed from the hydrolysis of one imine bond of $H_2RSSR$. Complex 1 models the N- and C-terminus domains of bleomycins. The metal centers in 1 are essentially magnetically non-interacting giving a 2J value of $3 cm^-^1$ with the singlet as the ground state. Using complex 1 as a precursor, ternary copper(II) complexes $[Cu(R'SSR)B(SO_4)](2-4)$ are prepared, characterized and their DNA binding and cleavage properties studied (B: kanamycin A,2;2,2'-bipyridine,3;1,10-phenanthroline, 4). IR spectral data suggest a square pyramidal (4 + 1) geometry for the one-electron paramagnetic ternary complexes with the sulfate bound to copper. The complexes are non-conducting in DMF but show conductivity in aqueous medium due to dissociation of the sulfate ligand. They bind to calf thymus DNA in the minor groove giving the relative order: 4 > 2 > 1~3 $(K_a_p_p=5.4*10^5 M^-^1 for 4)$. The precursor complex 1 does not show any apparent chemical nuclease activity when treated with supercoiled (SC) DNA in the presence of 3-mercaptopropionic acid (MPA). The kanamycin A and phen adducts as such or generated under in situ reaction conditions using 1 and the ligand display efficient chemical nuclease activity in the presence of MPA, while the bpy species shows poor cleavage activity. The ternary kanamycin A complex presents the first synthetic model for three functional domains of bleomycins.