Chiral Metal Complexes: Synthesis And The Interaction With DNA

It is important for the research on antitumor drugs to study the specific interactionbetween the small molecules with DNA, due to DNA is one of the main target of antitumordrugs. Since DNA is inherently chiral, its diastereoselective interactions with chiral smallmolecules attract much attention in the field of bioinorganic chemistry. DNA condensation isnot only at the state of high stack naturally, but also the critical process for the DNA behaviorin life. In this article, we study the interaction between the compound of different chirality andstructure with DNA through multiple detection methods.(1) Based on the chiral Schiff base bidentate ligand (L1) and tridentate ligand (L2)condensed by pyridine aldehyde and chiral phenylethylamine, four pairs of Fe(II) and Ni(II)chiral enantiomers (1R-Fe,1S-Fe,1R-Ni,1S-Ni,2R-Fe,2S-Fe,2R-Ni,2S-Ni) weresynthesized and characterized. Furthermore, the results of single crystal X-ray diffractionanalysis indicate that the complexes are mono-nuclear enantiomers with a constrction ofdistorted octahedron due to the coordinates between metal center with N atoms.We study the interaction between the four pairs of enantionmers with ct-DNA throughthe methods of UV-vis spectroscopy, fluorescence spectroscopy, and circular dichroismspectrometry. The results show that all the complexes could bind to ct-DNA with differentbinding affinities. The binding constant of the four pairs of enantionmers ring from4.41×103to1.88×104M-1. The complexes may most likely to bind in the groove of DNA backbonethrough electrostatic interaction. The factors of metal center, structure and chirality of ligandscan influence the DNA binding ability of the complexes. The complexes containing Fe(II)metal center show stronger DNA binding ability with respect to the Ni(II) complexes. Inaddition, the complexes containing tridentate ligand (L2) possess more efficient DNAinteraction than the complexes containing bidentate ligand (L1). Moreover, differentenantiomers exhibit discernible differences in the DNA-binding. The complexes with S-ligandshow stronger DNA binding ability than the respective complexes with R-ligand.(2) Based on the reduced schiff base condensed by asparaginate and salicylaldehyde, apair of heptameric La(III) helical enantiomersM-[La7(S-L)6(CO3)(NO3)6(OCH3)(CH3OH)7]·2CH3OH·5H2O andP-[La7(R-L)6(CO3)(NO3)6(OCH3)(CH3OH)5(H2O)2]·2CH3OH·4H2O (M-La and P-La) weresynthesized and characterized. DNA condensation induced by the enantionmers has beeninvestigated by UV/Vis spectroscopy, fluorescence spectroscopy, circular dichroismspectroscopy, electrophoresis mobility shift assay, right angle light scattering (RALS),dynamic light scattering (DLS), and scanning electron microscopy (SEM) to study thedynamic process of DNA condensation and the morphology and size of DNA condensate. Theenantiomers bind to DNA through electrostatic attraction and hydrogen bond interactions inmajor groove and and rapidly condense free DNA into its compact state at a lowconcentration. DNA condensates possess globular nanoparticles with nearly homogeneoussizes of ca.200-250nm in solid state determined by SEM. DNA decompaction has beenacquired by using ethylenediaminetetraacetic acid (EDTA) disodium salt as disassembly agentor in the surroundings of high salinity. The enantiomers M-La and P-La display discernable discrimination in DNA interaction and DNA condensation, as well as DNA decondensation.In addition, we also study the interaction between the pairs of enantiomers with HTG22through UV/Vis spectroscopy and FRET. The results indicat the complexes can t interact toHTG22effectively. Furthermore, the complexes display the ability of recognition of DNAstructure to some extent.(3) Reduced Schiff base cryptand L was synthesized by the condensation bytris(2-aminoethyl) amine and terephthaladehyde to a containing six amines and characterized.The interaction between compound L with ct-DNA has been investigated by UV/Visspectroscopy, fluorescence spectroscopy, circular dichroism spectroscopy, electrophoresismobility shift assay. After interact with L, the UV absorbance at260nm of DNA decreasedby38.66%, the CD intensity declined72.56%and67.14%for the positive band and negativeband, respectively. Moreover, the DNA electrophoretic band showed darker band compared tothat of free DNA. The results indicate that the compound can interact to ct-DNA effectively,and can induce DNA condensation. The interaction between compound L with G-quadruplexHTG22has been investigated by UV/Vis spectroscopy, circular dichroism spectroscopy andfluorescence resonance energy transfer (FRET). The results suggest the compound induceDNA forming the antiparallel configuration, or make the antiparallel configuration morestable with the melting temperature increasing19.5C according to the result of FRETsuggesting the compound has favourable stabilizing effect on HTG22.