Enantiomeric pair of copper(II) polypyridyl-alanine complexes: Effect of chirality on their interaction with biomolecules
Chew Hee Ng, Cheang Wei Chan, Jing Wei Lai, Ing Hong Ooi, Kok Vei Chong, Mohd Jamil Maah, Hoi Ling Seng
Journal of Inorganic Biochemistry
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)6and serum albumin.
Circular dichroism, Stereochemistry, Biochemistry, Inorganic chemistry