Enantiomeric pair of copper(II) polypyridyl-alanine complexes: Effect of chirality on their interaction with biomolecules

Like chiral organic drugs, the chemical and biological properties of metal complexes can be dependent on chirality. Two pairs of [Cu(phen)(ala)(H2O)]X·xH2O (phen=1.10-phenanthroline: X=NO3−; ala: l-alanine (l-ala), 1 and d-alanine (d-ala) 2; and (X=Cl−; ala: l-ala, 3 and d-ala, 4) complex salts (x=number of lattice water molecules) have been synthesized and characterized. The crystal structure of 3 has been determined. The same pair of enantiomeric species, viz. [Cu(phen)(l-ala)(H2O)]+ and [Cu(phen)(d-ala)(H2O)]+, have been identified to be present in the aqueous solutions of both 1 and 3, and in those of both 2 and 4 respectively. Both 3 and 4 bind more strongly to ds(AT)6 than ds(CG)6. There is no or insignificant effect of the chirality of 3 and 4 on the production of hydroxyl radicals, binding to deoxyribonucleic acid from calf thymus (CT-DNA), ds(CG)6, G-quadruplex and 17-base pair duplex, and inhibition of both topoisomerase I and proteasome. Among the three proteasome proteolytic sites, the trypsin-like site is inhibited most strongly by these complexes. However, the chirality of 3 and 4 does affect the number of restriction enzymes inhibited, and their binding constants towards ds(AT)6 and serum albumin. Two pairs of [Cu(phen)(ala)(H2O)]X (phen=1.10-phenanthroline; ala=alanine; X=Cl−, NO3−) were synthesized and characterized. Effect of chirality on their interactions with various forms of DNA, binding to bovine serum albumin (BSA), and inhibition of restriction enzymes, topoisomerase I and proteasome are presented and discussed. [Display omitted] •Each [Cu(phen)(ala)(H2O)]+ (phen=phenanthroline; ala=alanine) is square pyramidal.•Chirality of ala has no effect on production of hydroxyl radicals by all enantiomers.•No or minimum effect of chirality on interaction with proteasome and most forms of DNA.•Chirality of ala affects restriction enzyme inhibition, binding to albumin and ds(AT)6.•Complexes exhibit selective inhibition of the proteasome trypsin-like site.